@article{debelo_fiecke_terekhov_reuhs_hamaker_ferruzzi_2023, title={Compositional analysis of phytochemicals and polysaccharides from Senegalese plant ingredients: Adansonia digitata (baobab), Moringa oleifera (moringa) and Hibsicus sabdariffa (hibiscus)}, volume={32}, ISSN={["2352-3646"]}, DOI={10.1016/j.nfs.2023.100144}, abstractNote={Certain indigenous African plant materials, including Adansonia digitata (baobab), Moringa oleifera (moringa), and Hibiscus sabdariffa (hibiscus) could be leveraged in food-to-food fortification strategies due to their high content of nutrients, dietary fiber, and phenolic compounds. However, more studies are needed to understand the nutritional composition of commercially available food ingredients. The objective of this study was to examine the phytochemical and polysaccharide compositions of commercially available baobab, moringa, and hibiscus ingredients from Senegal. Characterization of carotenoids, tocopherols, phenolic compounds, monosaccharide composition, and glycosyl linkage was carried out. We observed that moringa contained the greatest content of carotenoids and tocopherols. Moringa also contained significant amounts of the flavonols quercetin 3-glucoside and quercetin 3-rutinoside, while baobab had greater concentrations of flavan-3-ols. Substantial content of anthocyanins was observed for hibiscus, but not moringa or baobab. The predominant monosaccharide in baobab was xylose, while hibiscus was a combination of xylose, galactose, and glucose. The primary monosaccharides in moringa were galactose and glucose. Based on our glycosyl linkage analysis, (1 → 2)- and (1 → 2,4)-linked rhamnose were attributed to rhamnogalacturonan-I, while (1 → 4)-linked glucose and (Terminal →)-linked xylose were attributed to xyloglucans. The phytochemical and polysaccharide characterization of baobab, moringa, and hibiscus suggested that delivery of micronutrients, such as iron and carotenoids, could be impacted when applied as functional food ingredients.}, journal={NFS JOURNAL}, author={Debelo, Hawi and Fiecke, Chelsey and Terekhov, Anton and Reuhs, Bradley and Hamaker, Bruce and Ferruzzi, Mario G.}, year={2023}, month={Aug} }
 @article{weaver_ferruzzi_maiz_cladis_nakatsu_mccabe_lila_2023, title={Crop, Host, and Gut Microbiome Variation Influence Precision Nutrition: An Example of Blueberries}, volume={12}, ISSN={["2076-3921"]}, url={https://doi.org/10.3390/antiox12051136}, DOI={10.3390/antiox12051136}, abstractNote={Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition.}, number={5}, journal={ANTIOXIDANTS}, author={Weaver, Connie M. and Ferruzzi, Mario G. and Maiz, Maria and Cladis, Dennis P. and Nakatsu, Cindy H. and McCabe, George P. and Lila, Mary Ann}, year={2023}, month={May} }
 @article{schmidt_ozturk_young_bugusu_li_claddis_mohamedshah_ferruzzi_hamaker_2023, title={Formation of cereal protein disulfide-linked stable matrices by apigeninidin, a 3-deoxyanthocyanidin}, volume={404}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2022.134611}, abstractNote={The food matrix is a factor affecting digestion rate of macronutrients, like starch. Sorghum protein networks surrounding starch have been associated with its comparatively low starch digestibility, though their formation mechanism is unclear. Since sorghums contain 3-deoxyanthocyanidins with redox property that could promote sulfhydryl-disulfide interchanges, we hypothesized that added apigeninidin (a 3-deoxyanthocyanidin) will form matrices in a non-matrix-forming cereal (corn). A model system using ovalbumin determined apigeninidin as a polymerizing agent. Starch digestion and microstructure of cereal porridges from yellow corn with and without added apigeninidin, commercial blue corn, and white sorghum were examined. Apigeninidin addition promoted protein matrices in yellow corn and attenuated initial starch digestion rate that was related to matrix formation rather than α-amylase inhibition. Blue corn with 3-deoxyanthocyanidins formed protein matrices with similar lower overall starch digestibility as sorghum. Promoting matrix formation in cereal-based foods with 3-deoxyanthocyanidins may be a strategy to modulate starch digestion rate.}, journal={FOOD CHEMISTRY}, author={Schmidt, Leigh C. R. and Ozturk, Oguz K. and Young, Jennifer and Bugusu, Betty and Li, Min and Claddis, Dennis and Mohamedshah, Zulfiqar and Ferruzzi, Mario and Hamaker, Bruce R.}, year={2023}, month={Mar} }
 @article{iglesias-carres_racine_chadwick_nunn_kalambur_neilson_ferruzzi_2023, title={Mechanism of off-color formation in potato chips fried in oil systems containing ascorbic acid as a stabilizer}, volume={179}, ISSN={["1096-1127"]}, DOI={10.1016/j.lwt.2023.114682}, abstractNote={The use of alternative, green antioxidant (AOX) systems is demanded by consumers. Natural AOX systems pose significant challenges. For example, in frying applications, these AOX can negatively alter potato chip color, one of the most important traits in consumer selection. We evaluated the role of natural AOX systems containing ascorbic acid, tocopherols, and other antioxidants in amino acid-related undesirable color formation in fried potato chips. Results indicated that both oil phase AOX and potato factors are critical to generation of off-color formation in fried potato chips through Maillard type reactions. Ascorbic acid solubilization in oil and migration to the chip surface play key roles in observed off-color formation. However, multiple complex reactions may be responsible for color development, which may involve food matrix components. Contributions of AOX other than ascorbic acid appear minimal. Nevertheless, some browning can occur regardless of the presence of ascorbic acid. Color formation through glutamine occurred in the absence of ascorbic acid, but its presence greatly exacerbates color generation, while color generation via asparagine is barely modulated by ascorbic acid. AOX and free amino acid concentrations, temperature, and moisture are critical factors for controlling undesirable color formation during frying with natural oil AOX systems.}, journal={LWT-FOOD SCIENCE AND TECHNOLOGY}, author={Iglesias-Carres, Lisard and Racine, Kathryn C. and Chadwick, Sydney and Nunn, Candace and Kalambur, Sathya B. and Neilson, Andrew P. and Ferruzzi, Mario G.}, year={2023}, month={Apr} }
 @article{solverson_albaugh_debelo_ferruzzi_baer_novotny_2023, title={Mixed Berry Juice and Cellulose Fiber Have Differential Effects on Peripheral Blood Mononuclear Cell Respiration in Overweight Adults}, volume={15}, ISSN={["2072-6643"]}, DOI={10.3390/nu15071709}, abstractNote={Berries and other anthocyanin-rich foods have demonstrated anti-obesity effects in rodents and humans. However, the bioactive components of these foods and their mechanisms of action are unclear. We conducted an intervention study with overweight and obese adults to isolate the effects of different berry components on bioenergetics. Subjects consumed whole mixed berries (high anthocyanin, high fiber), pressed berry juice (high anthocyanin, low fiber), berry-flavored gelatin (low anthocyanin, low fiber), or fiber-enriched gelatin (low anthocyanin, high fiber) for one week prior to a meal challenge with the same treatment food as the pre-feed period. Peripheral blood mononuclear cells were collected 2 h after the meal challenge, and cellular respiration was assessed via high-resolution respirometry. The high-anthocyanin, low-fiber treatment (berry juice) and the low-anthocyanin, high-fiber treatment (fiber-enriched gelatin) had opposite effects on cellular respiration. In the fasted state, berry juice resulted in the highest oxygen-consumption rate (OCR), while fiber-enriched gelatin resulted in the highest OCR in the fed state. Differences were observed in multiple respiration states (basal, state 3, state 4, uncoupled), with the greatest differences being between the pressed berry juice and the fiber-enriched gelatin. Different components of berries, specifically anthocyanins/flavonoids and fiber, appear to have differential effects on cellular respiration.}, number={7}, journal={NUTRIENTS}, author={Solverson, Patrick and Albaugh, George P. and Debelo, Hawi A. and Ferruzzi, Mario G. and Baer, David J. and Novotny, Janet A.}, year={2023}, month={Apr} }
 @article{hodges_maiz_cao_lachcik_peacock_mccabe_mccabe_cladis_jackson_ferruzzi_et al._2023, title={Moderate consumption of freeze-dried blueberry powder increased net bone calcium retention compared with no treatment in healthy postmenopausal women: a randomized crossover trial}, volume={118}, ISSN={["1938-3207"]}, DOI={10.1016/j.ajcnut.2023.05.033}, abstractNote={Preclinical studies suggest that blueberry consumption is associated with improved bone health.We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment.OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance.In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions.Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02630797.}, number={2}, journal={AMERICAN JOURNAL OF CLINICAL NUTRITION}, author={Hodges, Joanna K. and Maiz, Maria and Cao, Sisi and Lachcik, Pamela J. and Peacock, Munro and McCabe, George P. and McCabe, Linda D. and Cladis, Dennis P. and Jackson, George S. and Ferruzzi, Mario G. and et al.}, year={2023}, month={Aug}, pages={382–390} }
 @article{tambe_jacquet_strathearn_hensel_colon_chandran_yousef_grace_ferruzzi_wu_et al._2023, title={Protective Effects of Polyphenol-Rich Extracts against Neurotoxicity Elicited by Paraquat or Rotenone in Cellular Models of Parkinson's Disease}, volume={12}, ISSN={["2076-3921"]}, url={https://www.mdpi.com/2076-3921/12/7/1463}, DOI={10.3390/antiox12071463}, abstractNote={Parkinson’s disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O2 consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction.}, number={7}, journal={ANTIOXIDANTS}, author={Tambe, Mitali A. and Jacquet, Aurelie de Rus and Strathearn, Katherine E. and Hensel, Jennifer A. and Colon, Bryce D. and Chandran, Aswathy and Yousef, Gad G. and Grace, Mary H. and Ferruzzi, Mario G. and Wu, Qingli and et al.}, year={2023}, month={Jul} }
 @article{dzakovich_debelo_albertsen_che_jones_simon_zhao_glassman_ferruzzi_2023, title={Trait stacking simultaneously enhances provitamin A carotenoid and mineral bioaccessibility in biofortified Sorghum bicolor}, ISSN={["2042-650X"]}, DOI={10.1039/d2fo03606a}, abstractNote={Vitamin A, iron, and zinc deficiencies are prevalent in sub-Saharan Africa. Biofortified sorghum varieties evaluated here could potentially address these deficiencies simultaneously.}, journal={FOOD & FUNCTION}, author={Dzakovich, Michael P. and Debelo, Hawi and Albertsen, Marc C. and Che, Ping and Jones, Todd J. and Simon, Marissa K. and Zhao, Zuo-Yu and Glassman, Kimberly and Ferruzzi, Mario G.}, year={2023}, month={Jul} }
 @article{hayes_mohamedshah_chadwick-corbin_hoskin_iorizzo_lila_neilson_ferruzzi_2022, title={Bioaccessibility and intestinal cell uptake of carotenoids and chlorophylls differ in powdered spinach by the ingredient form as measured using in vitro gastrointestinal digestion and anaerobic fecal fermentation models}, volume={13}, ISSN={["2042-650X"]}, url={https://doi.org/10.1039/D2FO00051B}, DOI={10.1039/d2fo00051b}, abstractNote={Insights into food matrix factors impacting bioavailability of bioactive carotenoids and chlorophylls from fruits and vegetable ingredients are essential to understanding their ability to promote health. The stability and bioaccessibility of carotenoids and chlorophylls were assessed from dehydrated, spray-dried, freeze-dried and fresh spinach ingredient forms using in vitro models simulating upper gastrointestinal (GI) digestion and lower GI anaerobic fecal fermentation. Intestinal transport of bioaccessible bioactives from both upper and lower GI compartments was assessed using the Caco-2 human intestinal cell model. Differences in carotenoid and chlorophyll contents were observed between ingredient forms and these influenced bioaccessibility. Lower carotenoid and chlorophyll contents in spray dried spinach resulted in the lowest total bioaccessible content among all spinach treatments (5.8 ± 0.2 μmoles per g DW carotenoid and chlorophyll). The total bioaccessible content was statistically similar between freeze-dried (12.5 ± 0.6 μmoles per g DW), dehydrated (12.5 ± 3.2 μmoles per g DW), and fresh spinach (14.2 ± 1.2 μmoles per g DW). Post anaerobic fermentation, cellular accumulation of carotenoids was higher (17.57-19.52 vs. 5.11-8.56%), while that of chlorophylls was lower (3.05-5.27 vs. 5.25-6.44%), compared to those observed following upper GI digestion. Collectively, these data suggest that spinach forms created by various drying technologies deliver similar levels of bioaccessible spinach bioactives and that the lower GI tract may serve as a site for significant absorption fostered by interactions with gut microbial communities that liberate additional bioactives from the spinach matrix.}, number={7}, journal={FOOD & FUNCTION}, publisher={Royal Society of Chemistry (RSC)}, author={Hayes, Micaela and Mohamedshah, Zulfiqar and Chadwick-Corbin, Sydney and Hoskin, Roberta and Iorizzo, Massimo and Lila, Mary Ann and Neilson, Andrew P. and Ferruzzi, Mario G.}, year={2022}, month={Mar} }
 @article{mohamedshah_hayes_chadwick-corbin_neilson_ferruzzi_2022, title={Bioaccessibility, gut microbial metabolism and intestinal transport of phenolics from 100% Concord grape juice and whole grapes are similar in a simulated digestion and fecal fermentation model}, volume={3}, ISSN={["2042-650X"]}, DOI={10.1039/d1fo04226b}, abstractNote={Phenolic rich 100% grape juice has been associated with many health benefits, but its place in dietary guidance is controversial relative to whole fruit. Direct comparisons of phenolic profiles and bioavailability between these food forms are needed. Phenolic bioaccessibility and metabolism from Concord (CG) and Niagara (NG) grapes and corresponding 100% juices were investigated using an in vitro digestion coupled with anaerobic gut fermentation model. Intestinal transport of resulting bioaccessible phenolics and microbial metabolites was estimated using a Caco-2 cell model. Total bioaccessible phenolics from both upper and lower digestion were similar (P > 0.05) between NG (400.9 ± 26.3 μmol per 100 g) and NGJ (349.5 ± 8.3 μmol per 100 g) and significantly different (P < 0.05) between CG (417.2 ± 24.4 μmol per 100 g) and CGJ (294.3 ± 45.4 μmol per 100 g) total cellular transport of phenolics was similar (P > 0.05) between whole grapes (89.4 ± 5.3 μmol per 100 g for CG, and 71.8 ± 2.4 μmol per 100 g for NG) and 100% juices (88.0 ± 5.6 μmol per 100 g for CGJ, and 85.3 ± 9.4 μmol per 100 g for NGJ). Differences were observed between the location of phenolic metabolism, bioaccessibility and subsequent cellular transport of individual phenolics between grapes and juice matrices. Specifically, greater amounts of phenolics were transported from grape juices than whole grapes from the upper tract. However, cumulative bioaccessibility and transport from upper and lower GI digestion/fermentation together indicates that the absorbable phenolics from 100% grape juice is similar to that of whole grapes, suggesting that phenolic-mediated health benefits from consumption of whole fruit and juice may be similar.}, journal={FOOD & FUNCTION}, author={Mohamedshah, Zulfiqar and Hayes, Micaela and Chadwick-Corbin, Sydney and Neilson, Andrew P. and Ferruzzi, Mario G.}, year={2022}, month={Mar} }
 @article{lila_hoskin_grace_xiong_strauch_ferruzzi_iorizzo_kay_2022, title={Boosting the Bioaccessibility of Dietary Bioactives by Delivery as Protein-Polyphenol Aggregate Particles}, volume={4}, ISSN={["1520-5118"]}, url={https://doi.org/10.1021/acs.jafc.2c00398}, DOI={10.1021/acs.jafc.2c00398}, abstractNote={Protein-polyphenol aggregate particles concurrently fortify a functional food product with healthy dietary proteins and concentrated polyphenols. However, what impact does ingestion of aggregate particles have on ultimate health relevance of either the polyphenolic molecules in the matrix or the protein molecules? Because human health benefits are contingent on bioavailability after ingestion, the fate of these molecules during transit in the gastrointestinal tract (GIT) will dictate their utility as functional food ingredients. This brief review explores diverse applications of protein-polyphenol particles in the food industry and the bioaccessibility of both bioactive polyphenolic compounds and edible proteins. Evidence to date suggests that complexation of phytoactive polyphenolics effectively enhances their health-relevant impacts, specifically because the phytoactives are protected in the protein matrix during transit in the GIT, allowing intact, non-degraded molecules to reach the colon for catabolism at the gut microbiome level, a prerequisite to realize the health benefits of these active compounds.}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Lila, Mary Ann and Hoskin, Roberta Targino and Grace, Mary H. and Xiong, Jia and Strauch, Renee and Ferruzzi, Mario and Iorizzo, Massimo and Kay, Colin}, year={2022}, month={Apr} }
 @article{racine_iglesias-carres_herring_ferruzzi_kay_tessem_neilson_2022, title={Cocoa extract exerts sex-specific anti-diabetic effects in an aggressive type-2 diabetes model: A pilot study}, volume={626}, ISSN={["1090-2104"]}, DOI={10.1016/j.bbrc.2022.08.018}, abstractNote={Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ (ob/ob) and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Acute cocoa reduced fasting hyperglycemia in females, but not males, after 2 weeks. Chronic cocoa supplementation (6-10 weeks) ameliorated hyperinsulinemia in males and worsened hyperlipidemia and hyperinsulinemia in females, yet also preserved and enhanced beta cell survival in females. The underlying mechanisms of these differences warrant further study. If sex differences are apparent in subsequent preclinical studies, clinical studies will be warranted to establish whether these differences are relevant in humans. Sex differences may need to be considered when designing human dietary interventions for T2D.}, journal={BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS}, author={Racine, Kathryn C. and Iglesias-Carres, Lisard and Herring, Jacob A. and Ferruzzi, Mario G. and Kay, Colin D. and Tessem, Jeffery S. and Neilson, Andrew P.}, year={2022}, month={Oct}, pages={205–210} }
 @article{mengist_grace_mackey_munoz_pucker_bassil_luby_ferruzzi_lila_iorizzo_2022, title={Dissecting the genetic basis of bioactive metabolites and fruit quality traits in blueberries (Vaccinium corymbosum L.)}, volume={13}, ISSN={["1664-462X"]}, DOI={10.3389/fpls.2022.964656}, abstractNote={Blueberry is well-recognized as a healthy fruit with functionality derived largely from anthocyanin and chlorogenic acid. Despite their importance, no study to date has evaluated the genetic basis of these bioactives in blueberries and their relationship with fruit quality traits. Hence, to fill this gap, a mapping population including 196 F1 individuals was phenotyped for anthocyanin and chlorogenic acid concentration and fruit quality traits (titratable acidity, pH, and total soluble solids) over 3 years and data were used for QTL mapping and correlation analysis. Total soluble solids and chlorogenic acid were positively correlated with glycosylated anthocyanin and total anthocyanin, respectively, indicating that parallel selection for these traits is possible. Across all the traits, a total of 188 QTLs were identified on chromosomes 1, 2, 4, 8, 9, 11 and 12. Notably, four major regions with overlapping major-effect QTLs were identified on chromosomes 1, 2, 4 and 8, and were responsible for acylation and glycosylation of anthocyanins in a substrate and sugar donor specific manner. Through comparative transcriptome analysis, multiple candidate genes were identified for these QTLs, including glucosyltransferases and acyltransferases. Overall, the study provides the first insights into the genetic basis controlling anthocyanins accumulation and composition, chlorogenic acid and fruit quality traits, and establishes a framework to advance genetic studies and molecular breeding for anthocyanins in blueberry.}, journal={FRONTIERS IN PLANT SCIENCE}, author={Mengist, Molla Fentie and Grace, Mary H. and Mackey, Ted and Munoz, Bryan and Pucker, Boas and Bassil, Nahla and Luby, Claire and Ferruzzi, Mario and Lila, Mary Ann and Iorizzo, Massimo}, year={2022}, month={Sep} }
 @article{bechoff_shee_mvumi_ngwenyama_debelo_ferruzzi_nyanga_mayanja_tomlins_2022, title={Estimation of nutritional postharvest losses along food value chains: A case study of three key food security commodities in sub-Saharan Africa}, ISSN={["1876-4525"]}, DOI={10.1007/s12571-021-01238-9}, abstractNote={Abstract Postharvest losses (PHLs) amplify food insecurity and reduce the amount of nutrients available to vulnerable populations, especially in the world's Low and Middle Income Countries (LMICs). However, little is known about nutrient loss at the various postharvest stages. The objective of our study was to develop a methodology and a tool to estimate nutritional postharvest losses (NPHLs) along food value chains for three distinct food commodities in sub-Saharan Africa. The study used a combination of literature, laboratory and field data to investigate NPHLs caused by both changes in quantity and quality of food material (quantitative and qualitative NPHLs, respectively). The method can be expanded to various other food value chains. A user-friendly predictive tool was developed for case studies involving maize and cowpea in Zimbabwe, and for sweet potato in Uganda. Quantitative and qualitative NPHLs were combined and converted into predicted nutrient loss and nutritional requirement lost due to postharvest losses. The number of people who may not meet their daily nutritional needs, as a result of the food and nutrient losses at country level, was estimated. The estimates consider nutritionally vulnerable groups such as children under five years and pregnant women. The nutrient density of the harvested food material, the level of food production, the postharvest stages along the food value chain, the levels of pest damage along the value chain, and the susceptibility of the nutrients to degradation e.g. during storage, are all important factors that affect NPHLs. Our modelling work suggests that reducing PHLs along food value chains could significantly improve access to nutritious food for populations in LMICs.}, journal={FOOD SECURITY}, author={Bechoff, Aurelie and Shee, Apurba and Mvumi, Brighton M. and Ngwenyama, Patrick and Debelo, Hawi and Ferruzzi, Mario G. and Nyanga, Loveness K. and Mayanja, Sarah and Tomlins, Keith I.}, year={2022}, month={Feb} }
 @article{adetola_kruger_ferruzzi_hamaker_taylor_2022, title={Potential of moringa leaf and baobab fruit food-to-food fortification of wholegrain maize porridge to improve iron and zinc bioaccessibility}, volume={73}, ISSN={["1465-3478"]}, DOI={10.1080/09637486.2021.1911962}, abstractNote={Food-to-food fortification (FtFF) with moringa leaf (iron source) and/or baobab fruit (citric acid and ascorbic acid source) (each 13-15 g/100 g porridge dry basis (db)) was studied to improve iron and zinc nutritive quality in African-type wholegrain maize-based porridges using in vitro dialysability assay. Moringa FtFF decreased percentage and total bioaccessible iron and zinc, by up to 84% and 45%, respectively. Moringa was very high in calcium, approximately 3% db and calcium-iron-phytate complexes inhibit iron bioavailability. Baobab FtFF increased percentage and total bioaccessible iron and zinc, especially in porridges containing carrot + mango (β-carotene source) and conventionally fortified with FeSO4, by up to 111% and 60%, respectively. The effects were similar to those when ascorbic and citric acids were added as mineral absorption enhancers. While moringa FtFF could be inhibitory to iron and zinc bioavailability in cereal-based porridges, baobab fruit FtFF could improve their bioavailability, especially in combination with conventional iron fortification.}, number={1}, journal={INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION}, author={Adetola, Oluyimika Y. and Kruger, Johanita and Ferruzzi, Mario G. and Hamaker, Bruce R. and Taylor, John R. N.}, year={2022}, month={Jan}, pages={15–27} }
 @article{simpson_de souza_damani_rogers_williams_weaver_ferruzzi_chadwick-corbin_nakatsu_2022, title={Prune supplementation for 12 months alters the gut microbiome in postmenopausal women}, volume={11}, ISSN={["2042-650X"]}, DOI={10.1039/d2fo02273g}, abstractNote={Prunes have health benefits, particularly in postmenopausal women. It is likely that the gut microbiome mediates some of these effects, but its exact role remains to be elucidated. This study aims to characterize the effect of prune supplementation on the gut microbiome of postmenopausal women. The fecal microbiome of 143 postmenopausal women ages 55-75 who met the compliance criteria in a randomized controlled trial of a 12-month dietary intervention in one of three treatment groups - no prunes (n = 52), 50 g prunes per day (n = 54), or 100 g prunes per day (n = 37) - was characterized at baseline and at the 12-month endpoint using 16S rRNA gene sequencing and QIIME2. Additional outcomes included assessment of select urinary phenolic metabolites and inflammatory markers. After 12 months, microbiomes of women consuming 50 g prunes had decreased evenness in bacteria taxa (Pielou's Evenness, Kruskal-Wallis p = 0.026). Beta diversity comparisons indicated significant differences in microbiomes among prune treatments (Bray-Curtis PERMANOVA, p = 0.005), and the effect was different at each prune dose (p = 0.057). Prunes enriched some bacterial taxa such as the family Lachnospiraceae (LEfSe LDA = 4.5). Some taxa correlated with urinary phenolic metabolites and inflammatory markers. Blautia negatively correlated with total urinary phenolics (r = -0.25, p = 0.035) and Lachnospiraceae UCG-001 negatively correlated with plasma concentrations of IL-1β (r = -0.29, p = 0.002). Differing gut microbiomes and correlation of some taxa with select phenolic metabolites and inflammatory markers, particularly Lachnospiraceae, after prune consumption suggest a potential mechanism mediating health effects. The microbiome differences at each dose may have implications for the use of prunes as a non-pharmacological whole food intervention for gut health.}, journal={FOOD & FUNCTION}, author={Simpson, Abigayle M. R. and De Souza, Mary Jane and Damani, Janhavi and Rogers, Connie and Williams, Nancy I. and Weaver, Connie and Ferruzzi, Mario G. and Chadwick-Corbin, Sydney and Nakatsu, Cindy H.}, year={2022}, month={Nov} }
 @article{grace_hoskin_hayes_iorizzo_kay_ferruzzi_lila_2022, title={Spray-dried and freeze-dried protein-spinach particles; effect of drying technique and protein type on the bioaccessibility of carotenoids, chlorophylls, and phenolics}, volume={388}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2022.133017}, abstractNote={The effects of protein carrier and drying technique on the concentration and bioaccessibility of lipophilic compounds (lutein, β-carotene, chlorophylls a and b) and hydrophilic flavonoids in freeze-dried (FD) or spray-dried (SD) spinach juice and protein-spinach particles were investigated. Carotenoid and chlorophyll contents were highest in FD spinach juice without protein (147 and 1355 mg/100 g, respectively). For both SD and FD protein-spinach particles, SPI best protected carotenoids and chlorophylls (123 and 1160 mg/g, respectively), although the bioaccessibility of lipophilic compounds in WPI particles was higher than SPI particles (p < 0.05). For flavonoids, the drying technique was more important than the type of carrier, since FD particles had higher total flavonoids than SD. However, SD particles had higher bioaccessibility for most flavonoids (40-90 %) compared to FD (<20 %). The drying method and protein carrier can be designed to produce protein-spinach ingredients with desired concentration of compounds and bioaccessibility.}, journal={FOOD CHEMISTRY}, author={Grace, Mary H. and Hoskin, Roberta T. and Hayes, Micaela and Iorizzo, Massimo and Kay, Colin and Ferruzzi, Mario G. and Lila, Mary Ann}, year={2022}, month={Sep} }
 @article{lim_ferruzzi_hamaker_2022, title={Structural requirements of flavonoids for the selective inhibition of alpha-amylase versus alpha-glucosidase}, volume={370}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2021.130981}, abstractNote={In the present study, 14 structurally unique flavonoids were screened to systematically investigate structural requirements for selectively inhibiting human α-amylase versus α-glucosidase to obtain a slow but complete starch digestion for health benefit. The selective inhibition property of three flavonoids chosen against the two classes of starch digestive enzymes was confirmed through various analytical techniques - in vitro inhibition assay, fluorescence quenching, kinetic study, and molecular modeling. Considering the chemical structure of flavonoids, the double bond between C2 and C3 and OH groups at A5 and B3 are critical for the inhibition of α-amylase allowing flavonoids to lie parallel on the α-amylase catalytic active site, whereas the OH groups at B3 and C3 are important for α-glucosidase inhibition causing B-ring specific entry into the catalytic active site of α-glucosidase. Our findings provide insights into how to apply flavonoids to effectively control digestion rate for improving physiological responses.}, journal={FOOD CHEMISTRY}, author={Lim, Jongbin and Ferruzzi, Mario G. and Hamaker, Bruce R.}, year={2022}, month={Feb} }
 @article{cladis_weaver_ferruzzi_2021, title={(Poly)phenol toxicity in vivo following oral administration: A targeted narrative review of (poly)phenols from green tea, grape, and anthocyanin-rich extracts}, ISSN={["1099-1573"]}, DOI={10.1002/ptr.7323}, abstractNote={Fruit- and vegetable-derived (poly)phenols are secondary plant metabolites that may have beneficial effects on human health when consumed regularly. Recent years have seen rapid growth in both consumer demand for and research interest in (poly)phenol-rich dietary supplements, natural colorants, and functional foods. As these products continue to enter the marketplace and (poly)phenol intake patterns change from traditional food products to these sources, attention must be paid to the potential for toxicity from consuming elevated doses of (poly)phenols. To date, much remains unknown regarding the safety of high doses of (poly)phenols, especially in vivo. In this targeted narrative review, we summarize evidence from in vivo investigations of (poly)phenol toxicity after oral administration of green tea extracts, grape-derived phenolics, and anthocyanin-rich extracts. There is limited evidence of overt toxicity from oral ingestion of these (poly)phenol-rich sources, though more research on the safety of high doses-as well as defining what constitutes a "high" dose of both individual and complex mixtures of (poly)phenols-is needed before these observations can be used to create dietary guidance for consumers.}, journal={PHYTOTHERAPY RESEARCH}, author={Cladis, Dennis P. and Weaver, Connie M. and Ferruzzi, Mario G.}, year={2021}, month={Nov} }
 @article{geocze_barbosa_lima_ferruzzi_fidencio_sant'ana_silverio_2021, title={Caryocar brasiliense Camb. fruits from the Brazilian Cerrado as a rich source of carotenoids with pro-vitamin A activity}, volume={101}, ISSN={["1096-0481"]}, DOI={10.1016/j.jfca.2021.103943}, abstractNote={Caryocar brasiliense Camb. is the best-known fruit of the Brazilian Cerrado. This fruit has yellow pulp containing several carotenoids and has a strong and exotic flavor; however, its composition may vary due to factors such as genotypic differences, seasonality, cultivation forms, climatic and soil characteristics, maturation stage, type of storage and processing. Therefore, the present study aimed to determine the chemical composition of carotenoids with pro-vitamin A activity of C. brasiliense fruits from 18 Brazilian municipalities. The vitamin A value expressed as μg Retinol Activity Equivalent (RAE) in the fresh fruit and carotenoid profile were determined by high-performance liquid chromatography coupled to a diode array detector (HPLC- DAD). The main carotenoids found were β-cryptoxanthin and β-carotene. High variation in vitamin A values were observed, especially among the fruits from Gato-Preto-MA with (1.4 μg RAE/100 g fresh fruit) and Januária-MG (719 μg RAE/100 g fresh fruit). PC1 and PC2 explored about 98.80% of the data variance in the multivariate analysis, Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) and organized the C. brasiliense fruits in three clusters by decreasing vitamin A values. The fruits from the municipalities of Januária, Japonvar, Arinos, Salinas and Montes Claros showed higher carotenoid content.}, journal={JOURNAL OF FOOD COMPOSITION AND ANALYSIS}, author={Geocze, Katalin C. and Barbosa, Luiz C. A. and Lima, Claudio F. and Ferruzzi, Mario G. and Fidencio, Paulo H. and Sant'ana, Helena M. P. and Silverio, Flaviano O.}, year={2021}, month={Aug} }
 @article{lyu_rodriguez_ferruzzi_pasinetti_murrough_simon_wu_2021, title={Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles}, volume={8}, ISSN={["2296-861X"]}, DOI={10.3389/fnut.2021.780226}, abstractNote={Bioactive dietary polyphenols in grape (Vitis vinifera) have been used in Dietary Supplements (DSs) with the aim to prevent numerous diseases, including cardiovascular and neurodegenerative diseases, and to reduce depression and anxiety. Given prior recognition that DSs can be quality challenged from the purity, authentication, adulteration, and actual concentration of targeted bioactives, to ensure consumer health protection as well as the quality and safety of grape polyphenol-based DSs, the present investigation was aimed at establishing a comprehensive quality control (QC) approach for grape polyphenol-based DSs in support of a human clinical study. In this study, the manufactured grape seed polyphenol extract (GSPE) and trans-resveratrol (RSV) capsules and Concord Grape Juice (CGJ) along with the corresponding original drug materials were analyzed using the developed different liquid chromatography/UV-visible spectroscopy/mass spectrometry (LC/UV-Vis/MS) methods. The weight variation of GSPE and RSV capsules was also evaluated according to the US Pharmacopeia (USP) tests. The results indicate that the total identified polyphenol content in each grape seed extract (GSE) capsule/CGJ is very similar and all GSE/RSV capsules pass the content/weight uniformity test. Given the complexity of these and many botanical products from the issues of purity, quality, adulteration, consistency, and their coupling to the complex chemistry in each grape-derived botanical, quality assurance and the steps needed to ensure grape-derived DSs being well homogeneous and stable and containing the known and expected bioactives at specific concentration ranges are fundamental to any research study and in particular to a clinical trial. Each of these issues is essential to provide a solid foundation upon which clinical trials with botanicals can be conducted with the goal of realizing measurable mental health outcomes such as reducing depression and anxiety as well as understanding of their underlying biological mechanisms.}, journal={FRONTIERS IN NUTRITION}, author={Lyu, Weiting and Rodriguez, David and Ferruzzi, Mario G. and Pasinetti, Giulio M. and Murrough, James W. and Simon, James E. and Wu, Qingli}, year={2021}, month={Dec} }
 @article{xu_debelo_roman_guo_ferruzzi_martinez_2021, title={Co-extruded wheat/okra composite blends result in soft, cohesive and resilient crumbs rich in health-promoting compounds}, volume={364}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2021.130395}, abstractNote={This work investigates the partial solubilization of cell wall polysaccharides in okra flours and the changes in the profile of free and bound phenolics through twin-screw extrusion. The comparison between extruded wheat flour-native okra flour (EWF-OF) and extruded wheat flour-extruded okra flour (EWF-EOF) composite blends revealed that extrusion led to an increase of soluble dietary fiber from 7.76 to 10.02 g/100 g. Extrusion of okra also resulted in a significant increase of free and bound phenolic acids, the latter consisting mostly of ferulic acid, as well as the thermal degradation of free epigallocatechin, and the binding of a small portion of quercetin-3-O-glucoside likely to a carbohydrate fraction. Bread crumbs from EWF-EOF (at 15% replacement level) exhibited a significantly lower hardness and higher elasticity, cohesiveness and resilience (from 28.28 N, 0.94, 0.49 and 0.17 to 7.54 N, 0.99, 0.70 and 0.35, respectively), which closely resembled the textural attributes of wheat bread.}, journal={FOOD CHEMISTRY}, author={Xu, Kang and Debelo, Hawi and Roman, Laura and Guo, Mengmeng and Ferruzzi, Mario G. and Martinez, Mario M.}, year={2021}, month={Dec} }
 @article{lewandowski_zhang_hayes_ferruzzi_paton_2021, title={Design and Nutrient Analysis of a Carotenoid-Rich Food Product to Address Vitamin A and Protein Deficiency}, volume={10}, ISSN={["2304-8158"]}, DOI={10.3390/foods10051019}, abstractNote={Worldwide undernutrition affects over 820 million individuals and is the underlying cause of over 50% of all childhood deaths. Sweet potatoes have been promoted to address vitamin A (vitA) deficiency, with a single, orange-fleshed sweet potato (OFSP) providing enough vitA, as β-carotene, to meet daily needs. However, the bioavailability of β-carotene is dependent on the presence of dietary fat, which is not provided by OFSP, and it lacks some essential amino acids. Therefore, in an attempt to create a food product that meets daily vitA requirements with adequate bioavailability and complete protein, we designed and assessed a sweet potato, peanut paste, and legume product. The final food product formulation, developed through computer modeling, resulted in a 65/5/35 (w/w/w) formulation in a 250 g serving and ~330 kcal. We then confirmed the nutrient content of macronutrients, and essential amino acids, zinc, and iron contents. Total β-carotene was assessed by HPLC and was lower than predicted through computer modeling, likely due to losses through thermal processing and/or degradation from storage. The results of this project indicate that the three ingredients can be combined into a single 250 g food product to provide >300 kcal energy, complete protein, and micronutrients in a more bioavailable form.}, number={5}, journal={FOODS}, author={Lewandowski, Kristina and Zhang, Xiaoyu and Hayes, Micala and Ferruzzi, Mario G. and Paton, Chad M.}, year={2021}, month={May} }
 @article{lim_ferruzzi_hamaker_2021, title={Dietary starch is weight reducing when distally digested in the small intestine}, volume={273}, ISSN={["1879-1344"]}, DOI={10.1016/j.carbpol.2021.118599}, abstractNote={Nowadays, carbohydrate-based foods have a negative consumer connotation and low carb diets have become a popular way to lose weight. Here, we show how digestible starch and flavonoids can be used as a dietary approach to manage food intake and weight gain through elevation of glucagon-like peptide-1 (GLP-1) secretion for gut-brain axis communication. This was achieved by extending the digestion of cooked starch to the distal small intestine using luteolin or quercetin as α-amylase-specific inhibitors with competitive inhibition mechanism. In a mouse model, extended and complete digestion produced a signature blunted glycemic profile that induced elevation of GLP-1 and positive regulation of hypothalamic neuropeptides with significantly reduced food intake and weight gain (p < 0.05). These findings represent a shift in paradigm of dietary carbohydrates from weight increasing to reducing, and have implications for industry and public health related to the design of carbohydrate-based foods/ingredients for managing obesity and diabetes.}, journal={CARBOHYDRATE POLYMERS}, author={Lim, Jongbin and Ferruzzi, Mario G. and Hamaker, Bruce R.}, year={2021}, month={Dec} }
 @article{lyu_omar_patel_rodriguez_ferruzzi_pasinetti_murrough_muzzio_simon_wu_2021, title={Dissolution Study on Grape Polyphenol Hard Gelatin Capsule Dietary Supplements}, volume={8}, ISSN={["2296-861X"]}, DOI={10.3389/fnut.2021.780260}, abstractNote={Methods for a dissolution study by ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC-QqQ/MS) analysis of grape polyphenol dietary supplements, namely, grape seed extract (GSE) and resveratrol (RSV) capsules, were developed following the guidance of United States Pharmacopeia (USP) <2040>. Two dissolution media, 0.1 N hydrochloric acid (pH 1.2) and 0.05 M acetate buffer (pH 4.6), were evaluated with dissolution apparatus (USP 1), 100 rpm rotation speed, and 900 ml dissolution medium volume. Dissolution profiling was performed over 120 min. Major phenolic compounds of gallic acid, catechin, epicatechin, and procyanidin B2 were quantitated to obtain the dissolution profile of GSE capsules, and trans-RSV was used for RSV capsules. Results indicated that the released trans-RSV for RSV capsules in both of the dissolution media meets the USP standards, and that for the GSE capsules, all the four marker compounds passed the dissolution test in the HCl medium but did not reach a 75% release within 60 min in the acetate buffer. These promising results suggest that the general USP dissolution protocols are adequate for the successful release of RSV capsules in HCl medium and acetate buffer and GSE capsules (in HCl medium), but may be inadequate for GSE capsules in acetate buffer. These results showed that under a low pH of 1.2 (simulated stomach environment), bioactive compounds were released on time from the GSE capsules and met the USP guidelines; however, under a higher pH of 4.6 (simulated duodenum environment), the same biomarkers failed, suggesting the need to further improve the dissolution of GSE over a wider range of pH environments to enhance bioavailability and efficacy.}, journal={FRONTIERS IN NUTRITION}, author={Lyu, Weiting and Omar, Thamer and Patel, Harna and Rodriguez, David and Ferruzzi, Mario G. and Pasinetti, Giulio M. and Murrough, James W. and Muzzio, Fernando J. and Simon, James E. and Wu, Qingli}, year={2021}, month={Nov} }
 @article{coelho_alfenas_debelo_wightman_ferruzzi_mattes_2021, title={Effects of Concord grape juice flavor intensity and phenolic compound content on glycemia, appetite and cognitive function in adults with excess body weight: a randomized double-blind crossover trial}, ISSN={["2042-650X"]}, DOI={10.1039/d1fo02049h}, abstractNote={Background & aims: Concord grape (Vitis lambrusca) juice (CGJ) contains a unique combination of polyphenolic compounds with diverse effects on human health. It also has an intense sensory profile that may modify food choice. Daily consumption of CGJ over 8 weeks reduced fasting blood glucose. However, the impact on 24h-postprandial glucose response from CGJ is still not clear. The purpose of this study was to assess the effect of CGJ flavor intensity and phenolic content on 24 h postprandial glucose concentrations, appetitive sensations, and cognitive function in adults with excess body weight when consumed alone or with a meal. Methods: In a randomized, double-blind, crossover design study, participants consumed three types of beverages: 100% CGJ, a polyphenol-free grape flavored drink with the same flavor essence (LP) or a polyphenol-free grape flavored drink with reduced flavor essence (LPF) either without (trial I) or with (trial II) a meal. 24 h glucose was measured through continuous glucose monitoring. Phenolic metabolite excretion was assessed in 24 h urine samples. Appetite (hunger, thirst, fullness, desire to eat, and prospective consumption) and cognitive function (alertness, energetic, strength, calmness, and relaxation) were assessed hourly through visual analog scales. Results: Thirty-four adults completed trial I and 34 adults completed trial II. When consumed with a meal, beverages with customary flavor essence (CGJ and LP) reduced hunger, desire to eat, and prospective consumption and consumption of the polyphenol-free reduced flavor essence beverage was associated with higher 24 h glucose tAUC. No consistent effects were observed for cognitive outcomes. When consumed alone, CGJ was related to lower glycemic responses by those excreting a higher concentration of the phenolic metabolite iso/ferulic-3'-O-glucuronide, but in beverages without CG phenolics and reduced flavor essence, glycemia was higher among those excreting higher concentrations of caffeic acid-O-sulfate. Conclusions: Both natural phenolics and flavor essence of CGJ may help to moderate appetite and glycemia. Clinical Trials registered at http://www.clinicaltrials.gov: NCT03409484 (trial I) and NCT03409497 (trial II).}, journal={FOOD & FUNCTION}, author={Coelho, Olivia G. L. and Alfenas, Rita de Cassia G. and Debelo, Hawi and Wightman, JoLynne D. and Ferruzzi, Mario G. and Mattes, Richard D.}, year={2021}, month={Oct} }
 @article{mengist_bostan_young_kay_gillitt_ballington_kay_ferruzzi_ashrafi_lila_et al._2021, title={High-density linkage map construction and identification of loci regulating fruit quality traits in blueberry}, volume={8}, ISSN={["2052-7276"]}, url={https://doi.org/10.1038/s41438-021-00605-z}, DOI={10.1038/s41438-021-00605-z}, abstractNote={Abstract Fruit quality traits play a significant role in consumer preferences and consumption in blueberry ( Vaccinium corymbosum L). The objectives of this study were to construct a high-density linkage map and to identify the underlying genetic basis of fruit quality traits in blueberry. A total of 287 F 1 individuals derived from a cross between two southern highbush blueberry cultivars, ‘Reveille’ and ‘Arlen’, were phenotyped over three years (2016–2018) for fruit quality-related traits, including titratable acidity, pH, total soluble solids, and fruit weight. A high-density linkage map was constructed using 17k single nucleotide polymorphisms markers. The linkage map spanned a total of 1397 cM with an average inter-loci distance of 0.08 cM. The quantitative trait loci interval mapping based on the hidden Markov model identified 18 loci for fruit quality traits, including seven loci for fruit weight, three loci for titratable acidity, five loci for pH, and three loci for total soluble solids. Ten of these loci were detected in more than one year. These loci explained phenotypic variance ranging from 7 to 28% for titratable acidity and total soluble solid, and 8–13% for pH. However, the loci identified for fruit weight did not explain more than 10% of the phenotypic variance. We also reported the association between fruit quality traits and metabolites detected by Proton nuclear magnetic resonance analysis directly responsible for these fruit quality traits. Organic acids, citric acid, and quinic acid were significantly ( P < 0.05) and positively correlated with titratable acidity. Sugar molecules showed a strong and positive correlation with total soluble solids. Overall, the study dissected the genetic basis of fruit quality traits and established an association between these fruit quality traits and metabolites.}, number={1}, journal={HORTICULTURE RESEARCH}, author={Mengist, Molla F. and Bostan, Hamed and Young, Elisheba and Kay, Kristine L. and Gillitt, Nicholas and Ballington, James and Kay, Colin D. and Ferruzzi, Mario G. and Ashrafi, Hamid and Lila, Mary Ann and et al.}, year={2021}, month={Dec} }
 @article{hayes_corbin_nunn_pottorff_kay_lila_iorrizo_ferruzzi_2021, title={Influence of simulated food and oral processing on carotenoid and chlorophyll in vitro bioaccessibility among six spinach genotypes}, volume={5}, ISSN={["2042-650X"]}, url={https://doi.org/10.1039/D1FO00600B}, DOI={10.1039/d1fo00600b}, abstractNote={Increasing the density of micronutrients and phytochemicals in vegetable foods through plant breeding and processing is of value for consumers. However, the extent to which interactions between genetics and processing (G × P) can be leveraged for green leafy vegetables to improve the delivery of such compounds is unknown. Using spinach as a model, a three-phase in vitro digestion method with and without simulated oral processing (mastication) and coupling to a Caco-2 human intestinal cell culture model was used to determine whether bioaccessibility and intestinal uptake of carotenoids and chlorophylls can be modified from six spinach genotypes, fresh or processed as blanched, sterilized, and juiced products. Carotenoid and chlorophyll bioaccessibility varied significantly with the genotype (p < 0.001) and processing treatment (p < 0.001), with processing having a more profound influence on the bioaccessibility, decreasing micellarization of phytochemicals from juiced (25.8-29.3%), to fresh (19.5-27.9%), to blanched (14.9-20.5%), and sterilized spinach (10.4-13.0%). Oral mastication had a significant influence on the carotenoid bioaccessible content of sterilized spinach (0.3-0.5 μmoles per g DW) as compared to fresh spinach (0.1-0.3 μmoles per g DW), most likely due to the additive effect of thermal processing and mastication on facilitating digestive breakdown of the spinach matrix. Caco-2 accumulation of carotenoid and chlorophyll was modestly but significantly (<0.001) lower in fresh spinach (2.4%) compared to other treatment samples (3.7-4.8%). These results suggest that the genotype, processing treatment, and genotype × processing (G × P) interaction may affect carotenoid and chlorophyll bioaccessibility in spinach and that food processing remains a dominant factor in modulating the bioavailability of these phytochemicals.}, journal={FOOD & FUNCTION}, publisher={Royal Society of Chemistry (RSC)}, author={Hayes, Micaela and Corbin, Sydney and Nunn, Candace and Pottorff, Marti and Kay, Colin D. and Lila, Mary Ann and Iorrizo, Massimo and Ferruzzi, Mario G.}, year={2021}, month={May} }
 @article{de groote_munyua_traore_taylor_ferruzzi_ndiaye_onyeoziri_hamaker_2021, title={Measuring consumer acceptance of instant fortified millet products using affective tests and auctions in Dakar, Senegal}, volume={24}, ISSN={["1559-2448"]}, DOI={10.22434/IFAMR2020.0068}, abstractNote={Small-scale affordable extruders create new opportunities for small enterprise food processors to manufacture nutritionally enhanced products. Still, consumer interest in these products needs to be assessed first. Affective tests with 296 consumers in Dakar, Senegal, evaluated five pearl millet flours: (a) conventional, compared to four instant-porridge flour products; (b) sifted; (c) wholegrain; (d) sifted with premix; (e) wholegrain with micronutrient premix and food-to-food fortified (FtFF). Willingness-to-pay (WTP) was elicited through experimental auctions under two treatments: firstly without information, then with information. Consumers liked FtFF (taste, aroma, appearance) but were indifferent to instant. They did not appreciate wholegrain flour (appearance) or premix (appearance, aroma and taste). Without information, consumers showed no differences in WTP. With information, consumers paid premiums for FtFF (27-30%) (both treatments), and premix (17%), instant (9%), and wholegrain (-10%) (one treatment). Costs of instant, wholegrain and premix products were lower than consumers’ WTP, indicating potential profits, but not those of FtFF. There is a market for instant cereals in Senegal. Consumers require product information in order to compromise on some attributes to benefit from instant, fortified and wholegrain pearl millet products. Manufacture would be cost-effective, but FtFF costs need to be reduced.}, number={3}, journal={INTERNATIONAL FOOD AND AGRIBUSINESS MANAGEMENT REVIEW}, author={De Groote, Hugo and Munyua, Bernard and Traore, Djibril and Taylor, John R. N. and Ferruzzi, Mario and Ndiaye, Cheikh and Onyeoziri, Isiguzoro O. and Hamaker, Bruce R.}, year={2021}, pages={499–522} }
 @article{sato_pellegrini_cregor_mcandrews_choi_maiz_johnson_mccabe_mccabe_ferruzzi_et al._2021, title={Skeletal Protection and Promotion of Microbiome Diversity by Dietary Boosting of the Endogenous Antioxidant Response}, volume={36}, ISSN={["1523-4681"]}, DOI={10.1002/jbmr.4231}, abstractNote={There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen-induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (α-diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (β-diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex. © 2020 American Society for Bone and Mineral Research (ASBMR).}, number={4}, journal={JOURNAL OF BONE AND MINERAL RESEARCH}, author={Sato, Amy Y. and Pellegrini, Gretel G. and Cregor, Meloney and McAndrews, Kevin and Choi, Roy B. and Maiz, Maria and Johnson, Olivia and McCabe, Linda D. and McCabe, George P. and Ferruzzi, Mario G. and et al.}, year={2021}, month={Apr}, pages={768–778} }
 @article{nkhata_liceaga_rocheford_hamaker_ferruzzi_2021, title={Storage of biofortified maize in Purdue Improved Crop Storage (PICS) bags reduces disulfide linkage-driven decrease in porridge viscosity}, volume={136}, ISSN={["1096-1127"]}, DOI={10.1016/j.lwt.2020.110262}, abstractNote={Abstract Assessing rheological properties of biofortified maize through post-harvest storage is critical for its successful translation to consumer foods. Changes in flour rheology were assessed following post-harvest storage in Purdue Improved Crop Storage (PICS) of a white and two biofortified orange maize genotypes (OPVI and OPVII). Whole grains were stored in PICS bags with (PICS-oxy) or without (PICS-noxy) oxygen scavenger and compared to storage in traditional polypropylene woven bags. Flour pasting profiles were assessed over 8 months of storage. Initial porridge viscosities from biofortified maize were lower than from white maize. After 8 months, higher viscosities (p}, journal={LWT-FOOD SCIENCE AND TECHNOLOGY}, author={Nkhata, Smith G. and Liceaga, Andrea M. and Rocheford, Torbert and Hamaker, Bruce R. and Ferruzzi, Mario G.}, year={2021}, month={Jan} }
 @article{nino_reddivari_ferruzzi_liceaga_2021, title={Targeted Phenolic Characterization and Antioxidant Bioactivity of Extracts from Edible Acheta domesticus}, volume={10}, ISSN={["2304-8158"]}, DOI={10.3390/foods10102295}, abstractNote={With entomophagy gaining popularity in the Western hemisphere as a solution for future food insecurity, research on alternative protein sources, such as edible insects, has become relevant. Most of the research performed on insects has been on their nutritional qualities; however, little is known regarding bioactive compounds, such as polyphenols, that, if present in the insect, could provide additional benefits when the insect is consumed. In this study, methanolic extracts of Acheta domesticus from two farms and their corresponding feeds were obtained using a microwave-assisted extraction. Targeted phenolic characterization was accomplished through LC-MS/MS leading to the identification of 4-hydroxybenzoic acid, p-coumaric acid, ferulic acid, and syringic acid as major phenolic compounds in both A. domesticus extracts. Furthermore, the in vitro antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical cation (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical assays demonstrating the superior quenching activity of the A. domesticus extracts compared to the feeds. The discovery of phenolic compounds in A. domesticus implies the ability of this insect species to sequester and absorb dietary phenolics leading to possible added health benefits when consumed.}, number={10}, journal={FOODS}, author={Nino, Maria Catalina and Reddivari, Lavanya and Ferruzzi, Mario G. and Liceaga, Andrea M.}, year={2021}, month={Oct} }
 @article{debelo_ndiaye_kruger_hamaker_ferruzzi_2020, title={African Adansonia digitata fruit pulp (baobab) modifies provitamin A carotenoid bioaccessibility from composite pearl millet porridges}, volume={57}, ISSN={["0975-8402"]}, DOI={10.1007/s13197-019-04173-y}, abstractNote={Food-to-food fortification of staple cereal products using nutrient-dense plants shows promise to address multiple micronutrient deficiencies including vitamin A, iron and zinc in Sub-Saharan Africa. However, there is limited information on the potential interaction effects that such food-to-food fortified strategies may have on individual micronutrient bioavailability. The main objective of the current study was to investigate the impact of incorporating Adansonia digitata (baobab fruit pulp), a mineral-rich plant material, on the delivery of carotenoids from a composite cereal porridge. Formulations of native fruit/vegetable-cereal composites were screened for interactions which could influence both bioaccessibility and subsequent intestinal uptake of provitamin A carotenoids. Proportions of pearl millet flour and plant materials were dry blended to provide composite cereal porridges with total provitamin A carotenoid concentrations ranging from 3590.7 ± 23.4 to 3698.5 ± 26.5 μg/100 g (fw) and baobab concentrations ranging from 0 to 25% (dw).While there were no significant differences in provitamin A carotenoid bioaccessibility from porridge formulations containing 5 or 15% baobab, inclusion of 25% baobab resulted in a significant (p < 0.05) decrease in bioaccessibility (13.3%) as compared to the control (23.8%). Despite the reduced bioaccessibility, 6 h uptake efficiency of provitamin A carotenoids by Caco-2 human intestinal cells was not significantly altered by 25% baobab inclusion. These findings suggest that the inhibitory effects on carotenoid micellarization (bioaccessibility) observed with increased baobab addition may not ultimately limit the bioavailability of carotenoids.}, number={4}, journal={JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE}, author={Debelo, Hawi and Ndiaye, Cheikh and Kruger, Johanita and Hamaker, Bruce R. and Ferruzzi, Mario G.}, year={2020}, month={Apr}, pages={1382–1392} }
 @misc{iorizzo_curaba_pottorff_ferruzzi_simon_cavagnaro_2020, title={Carrot Anthocyanins Genetics and Genomics: Status and Perspectives to Improve Its Application for the Food Colorant Industry}, volume={11}, ISSN={["2073-4425"]}, DOI={10.3390/genes11080906}, abstractNote={Purple or black carrots (Daucus carota ssp. sativus var. atrorubens Alef) are characterized by their dark purple- to black-colored roots, owing their appearance to high anthocyanin concentrations. In recent years, there has been increasing interest in the use of black carrot anthocyanins as natural food dyes. Black carrot roots contain large quantities of mono-acylated anthocyanins, which impart a measure of heat-, light- and pH-stability, enhancing the color-stability of food products over their shelf-life. The genetic pathway controlling anthocyanin biosynthesis appears well conserved among land plants; however, different variants of anthocyanin-related genes between cultivars results in tissue-specific accumulations of purple pigments. Thus, broad genetic variations of anthocyanin profile, and tissue-specific distributions in carrot tissues and organs, can be observed, and the ratio of acylated to non-acylated anthocyanins varies significantly in the purple carrot germplasm. Additionally, anthocyanins synthesis can also be influenced by a wide range of external factors, such as abiotic stressors and/or chemical elicitors, directly affecting the anthocyanin yield and stability potential in food and beverage applications. In this study, we critically review and discuss the current knowledge on anthocyanin diversity, genetics and the molecular mechanisms controlling anthocyanin accumulation in carrots. We also provide a view of the current knowledge gaps and advancement needs as regards developing and applying innovative molecular tools to improve the yield, product performance and stability of carrot anthocyanin for use as a natural food colorant.}, number={8}, journal={GENES}, author={Iorizzo, Massimo and Curaba, Julien and Pottorff, Marti and Ferruzzi, Mario G. and Simon, Philipp and Cavagnaro, Pablo F.}, year={2020}, month={Aug} }
 @article{mohamedshah_chadwick-corbin_wightman_ferruzzi_2020, title={Comparative assessment of phenolic bioaccessibility from 100% grape juice and whole grapes}, volume={11}, ISSN={["2042-650X"]}, url={https://doi.org/10.1039/D0FO00792G}, DOI={10.1039/d0fo00792g}, abstractNote={Concord and Niagara grape juice have comparable or greater absolute bioaccessibility of major classes of phenolic compounds compared to masticated whole grapes.}, number={7}, journal={FOOD & FUNCTION}, publisher={Royal Society of Chemistry (RSC)}, author={Mohamedshah, Zulfiqar and Chadwick-Corbin, Sydney and Wightman, JoLynne D. and Ferruzzi, Mario G.}, year={2020}, month={Jul}, pages={6433–6445} }
 @article{de groote_mugalavai_ferruzzi_onkware_ayua_duodu_ndegwa_hamaker_2020, title={Consumer Acceptance and Willingness to Pay for Instant Cereal Products With Food-to-Food Fortification in Eldoret, Kenya}, volume={41}, ISSN={["1564-8265"]}, DOI={10.1177/0379572119876848}, abstractNote={Background: Maize is the major food staple in East and Southern Africa, where food-processing industries are emerging fast. New low-cost extrusion cookers allow small enterprises to enter the market for processed cereals, including instant, fortified, and flavored products. Objective: Assess consumers’ interest and preferences for the new products. Methods: Consumers (n = 220) in Eldoret, Kenya, were invited to evaluate 4 new cereal products: (1) sifted maize flour mixed with sorghum, (2) instant sifted mixed flour, (3) instant whole flour, and (4) instant whole flour fortified with natural ingredients and to compare them to conventional sifted maize flour, using 2 preparations: stiff porridge ( ugali) and soft porridge ( uji). These were followed by economic experiments to estimate consumers’ willingness to pay (WTP) for the new products and traits. Results: For ugali, consumers preferred conventional sifted maize flour, while for uji, they appreciated the new products, especially sifted mixed flour (with sorghum) and instant whole mixed flour. Fortification with food-to-food sources was not appreciated, especially for ugali. Comparing WTP for the traits with their production cost showed that mixed, whole, and instant flours were economical, but not fortification. Maize/sorghum mixtures realized a benefit of 24% over conventional maize flour, whole meal 11%, and instant mixtures 5%. Conclusions: There is a potential market for improved cereal products in Kenya, but more for uji than for ugali, especially with instant, mixed, and whole flour. Acceptable and affordable products, fortified with other foods that are locally available, however, still need to be developed, especially for ugali.}, number={2}, journal={FOOD AND NUTRITION BULLETIN}, author={De Groote, Hugo and Mugalavai, Violet and Ferruzzi, Mario and Onkware, Augustino and Ayua, Emmanuel and Duodu, Kwaku G. and Ndegwa, Michael and Hamaker, Bruce R.}, year={2020}, month={Jun}, pages={224–243} }
 @article{mengist_burtch_debelo_pottorff_bostan_nunn_corbin_kay_bassil_hummer_et al._2020, title={Development of a genetic framework to improve the efficiency of bioactive delivery from blueberry}, volume={10}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC7560831}, DOI={10.1038/s41598-020-74280-w}, abstractNote={Abstract In the present study, we applied a novel high-throughput in vitro gastrointestinal digestion model to phenotype bioaccessibility of phenolics in a diverse germplasm collection representing cultivated highbush blueberries. Results revealed significant ( P < 0.05) differences between accessions, years, and accession by year interaction for relative and absolute bioaccessibility of flavonoids and phenolic acids. Broad sense heritability estimates revealed low to moderate inheritances of relative and absolute bioaccessibility, suggesting that besides environmental variables, genetics factors could control bioaccessibility of phenolics. Acylated anthocyanins had significantly higher relative bioaccessibility than non-acylated anthocyanins. Correlation analysis indicated that relative bioaccessibility did not show significant association with fruit quality or raw concentration of metabolites. The study also identified accessions that have high relative and absolute bioaccessibility values. Overall, combining the bioaccessibility of phenolics with genetic and genomic approaches will enable the identification of genotypes and genetic factors influencing these traits in blueberry.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Mengist, Molla F. and Burtch, Haley and Debelo, Hawi and Pottorff, Marti and Bostan, Hamed and Nunn, Candace and Corbin, Sydney and Kay, Colin D. and Bassil, Nahla and Hummer, Kim and et al.}, year={2020}, month={Oct} }
 @misc{chung_zhao_wang_shams-white_karlsen_cassidy_ferruzzi_jacques_johnson_wallace_2020, title={Dose-Response Relation between Tea Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Population-Based Studies}, volume={11}, ISSN={["2156-5376"]}, DOI={10.1093/advances/nmaa010}, abstractNote={Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL) increase in daily tea consumption (estimated 280 mg and 338 mg total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I2 = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I2 = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.}, number={4}, journal={ADVANCES IN NUTRITION}, author={Chung, Mei and Zhao, Naisi and Wang, Deena and Shams-White, Marissa and Karlsen, Micaela and Cassidy, Aedin and Ferruzzi, Mario and Jacques, Paul F. and Johnson, Elizabeth J. and Wallace, Taylor C.}, year={2020}, month={Jul}, pages={790–814} }
 @article{ndiaye_martinez_hamaker_campanella_ferruzzi_2020, title={Effect of edible plant materials on provitamin A stability and bioaccessibility from extruded whole pearl millet (P. typhoides) composite blends}, volume={123}, ISSN={["1096-1127"]}, DOI={10.1016/j.lwt.2020.109109}, abstractNote={Blends of cereals and nutrient dense plant materials are increasingly being explored as a strategy for food-to-food fortification in areas of Sub-Saharan Africa, where processing is often applied to enhance product attributes, shelf life and safety. However, little is known regarding the potential impact of these strategies on micronutrient retention and bioaccessibility. In this study whole grain pearl millet (WGM) was blended with carrot powder (source of provitamin A) and Adansonia digitata (Baobab) and Moringa oleifera (Moringa) leaf powders (source of iron) to provide formulations with 25% of the recommended daily allowance (RDA) for Vitamin A. These blends were extruded to produce instant cereal porridges appropriate for consumer markets. Recovery of provitamin A carotenoid ranged from 60.0 to 90.3% after extrusion with higher recoveries in formulations including Moringa and Baobab. Extrusion had a significant negative (p < 0.05) impact on β-carotene bioaccessibility compared to corresponding dry blends (52% versus 47%; P < 0.05). However, the presence of Baobab in the formulation did enhance provitamin A carotenoid bioaccessibility. These results suggest that extruded blends of native plant materials with whole grain millet has potential to deliver products with stable and bioaccessible provitamin A.}, journal={LWT-FOOD SCIENCE AND TECHNOLOGY}, author={Ndiaye, Cheikh and Martinez, Mario M. and Hamaker, Bruce R. and Campanella, Osvaldo H. and Ferruzzi, Mario G.}, year={2020}, month={Apr} }
 @article{armah_ferruzzi_gletsu-miller_2020, title={Feasibility of Mass-Spectrometry to Lower Cost and Blood Volume Requirements for Assessment of B Vitamins in Patients Undergoing Bariatric Surgery}, volume={10}, ISSN={["2218-1989"]}, DOI={10.3390/metabo10060240}, abstractNote={Bariatric surgery induces deficiencies in a combination of B vitamins. However, high costs and a large blood volume requirement are barriers to routine screening. We adapted and validated a method coupling tandem mass spectrometry (MS/MS) with high-performance liquid chromatography (HPLC) to facilitate cost-effective analysis for simultaneous detection of B vitamins in low volumes of plasma. Based on existing methods, pooled plasma was extracted using hexane and acetonitrile and seven B vitamin analytes were separated using HPLC. Detection was performed with an Agilent 6460 triple quadrupole tandem mass spectrometer (MS/MS) using electrospray ionization in the positive ion mode. We evaluated linearity, recovery, precision, and limit of detection, as well as costs of the assay. We evaluated seven B vitamins from plasma; five (riboflavin, nicotinamide, pantothenic acid, pyridoxine, and biotin) were detected and quantified with precision and linearity. Recovery ranged from 63 to 81% for each of the vitamins, except for nicotinamide—the recovery of which was suppressed to 40%, due to plasma matrix effects. We demonstrated the feasibility of the HPLC–MS/MS method for use in patients who undergo bariatric surgery by analyzing pooled plasma from patients with a lower cost and blood volume than had we sent the samples to a commercial laboratory. It is advantageous and feasible, in terms of low cost and blood volume requirement, to simultaneously measure plasma concentrations of B vitamins using HPLC–MS/MS. With further improvements, the method may enable personalized nutritional assessment for the nutritionally compromised, bariatric surgery population.}, number={6}, journal={METABOLITES}, author={Armah, Seth and Ferruzzi, Mario G. and Gletsu-Miller, Nana}, year={2020}, month={Jun} }
 @article{moser_shin_kasturi_hamaker_ferruzzi_bordenave_2020, title={Formulation of Orange Juice with Dietary Fibers Enhances Bioaccessibility of Orange Flavonoids in Juice but Limits Their Ability to Inhibit In Vitro Glucose Transport}, volume={68}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.0c03334}, abstractNote={The effect of formulating orange juice (OJ) with dietary fibers (DFs) on in vitro bioaccessibility of flavonoids and their ability to inhibit glucose transport in Caco-2 cells were investigated on Valencia orange fruit (OF), OJ, and OJ formulated with 1 and 2.8% DFs. DFs were either orange pomace (P) or commercial pulverized citrus pulp fiber (CF). Juice extraction and formulation with CF led to minimal loss of flavonoids compared to formulation with P (474 μmol/100 g for OF vs 315–368 μmol/100 g for OJ and OJ with CF, and 266–280 μmol/100 g for OJ with P). Addition of DFs led to similar or improved flavonoid bioaccessibility compared to OJ (9.5% in OJ vs 7.9–33.4% with DFs) but higher glucose transport in Caco-2 cells (0.45 μmol/min in OJ alone vs 0.64–0.94 μmol/min with DFs). This paradoxical effect was attributed to potential complexation of flavonoids and DFs, preventing flavonoids from interfering with glucose transport.}, number={35}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Moser, Sydney E. and Shin, Jin-E and Kasturi, Prabhakar and Hamaker, Bruce R. and Ferruzzi, Mario G. and Bordenave, Nicolas}, year={2020}, month={Sep}, pages={9387–9397} }
 @article{sorkin_kuszak_bloss_fukagawa_hoffman_jafari_barrett_brown_bushman_casper_et al._2020, title={Improving natural product research translation: From source to clinical trial}, volume={34}, ISSN={["1530-6860"]}, DOI={10.1096/fj.201902143R}, abstractNote={While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.}, number={1}, journal={FASEB JOURNAL}, author={Sorkin, Barbara C. and Kuszak, Adam J. and Bloss, Gregory and Fukagawa, Naomi K. and Hoffman, Freddie Ann and Jafari, Mahtab and Barrett, Bruce and Brown, Paula N. and Bushman, Frederic D. and Casper, Steven J. and et al.}, year={2020}, month={Jan}, pages={41–65} }
 @article{hayes_pottorff_kay_van deynze_osorio-marin_lila_iorrizo_ferruzzi_2020, title={In Vitro Bioaccessibility of Carotenoids and Chlorophylls in a Diverse Collection of Spinach Accessions and Commercial Cultivars}, volume={68}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.0c00158}, abstractNote={Spinach, a nutrient-dense, green-leafy vegetable, is a rich source of carotenoid and chlorophyll bioactives. While the content of bioactives is known to vary with the genotype, variation in bioaccessibility is unknown. Bioaccessibility was explored in 71 greenhouse-grown spinach genotypes in fall and spring 2018/2019. Spinach was phenotyped for its greenness, leaf texture, leaf shape, and SPAD chlorophyll content. Postharvest, spinach was washed, blanched, and homogenized prior to assessment of bioactive bioaccessibility using a novel high-throughput in vitro digestion model followed by high-performance liquid chromatography with a photodiode array detector analysis. There was a significant variation in the bioaccessible content for all bioactives (p < 0.05), except for chlorophyll b (p = 0.063) in spring-grown spinach. The correlation coefficients of bioaccessible contents between seasons reveal that lutein (r = 0.52) and β-carotene (r = 0.55) were correlated to a greater extent than chlorophyll a (r = 0.38) and chlorophyll b (r = 0.19). The results suggest that carotenoid and chlorophyll bioaccessible contents may vary based on spinach genotypes and may be stable across seasons.}, number={11}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Hayes, Micaela and Pottorff, Marti and Kay, Colin and Van Deynze, Allen and Osorio-Marin, Juliana and Lila, Mary Ann and Iorrizo, Massimo and Ferruzzi, Mario G.}, year={2020}, month={Mar}, pages={3495–3505} }
 @article{cladis_debelo_lachcik_ferruzzi_weaver_2020, title={Increasing Doses of Blueberry Polyphenols Alters Colonic Metabolism and Calcium Absorption in Ovariectomized Rats}, volume={64}, ISSN={["1613-4133"]}, DOI={10.1002/mnfr.202000031}, abstractNote={Scope Blueberries are rich sources of bioactive polyphenols that may provide health benefits when consumed regularly, leading to their increased marketing as dietary supplements. However, the metabolic changes associated with consuming concentrated doses of purified polyphenols, as may be present in dietary supplements, are unknown, especially when considering the colonic metabolites formed. This study aimed to evaluate the pharmacokinetics of high doses of purified blueberry polyphenols. Methods and results 5-month old, ovariectomized Sprague-Dawley rats are acutely dosed with purified blueberry polyphenols (0, 75, 350, and 1000 mg total polyphenols per kg body weight (bw)) and 45Ca to measure calcium absorption. Blood and urine are collected for 48 h after dosing and phenolic metabolites measured via ultra high-pressure liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The most prominent metabolites are colonically generated cinnamic and hippuric acids. Smaller amounts of other phenolic acids, flavonols, and anthocyanins are also detected. Most metabolites follow a dose–response relationship, though several show saturated absorption. Maximal metabolite concentrations are reached within 12 h for a majority of compounds measured, while some (e.g., hippuric acid) peaked up to 24 h post-dosing. Calcium absorption is significantly increased in the highest dose group (p = 0.03). Conclusion These results indicate that increased doses of blueberry polyphenols induce changes in intestinal phenolic metabolism and increase calcium absorption.}, number={12}, journal={MOLECULAR NUTRITION & FOOD RESEARCH}, author={Cladis, Dennis P. and Debelo, Hawi and Lachcik, Pamela J. and Ferruzzi, Mario G. and Weaver, Connie M.}, year={2020}, month={Jun} }
 @misc{ferruzzi_kruger_mohamedshah_debelo_taylor_2020, title={Insights from in vitro exploration of factors influencing iron, zinc and provitamin A carotenoid bioaccessibility and intestinal absorption from cereals}, volume={96}, ISSN={["1095-9963"]}, DOI={10.1016/j.jcs.2020.103126}, abstractNote={Developments in genetics, agronomics and processing has positioned staple cereals as important sources of iron, zinc and provitamin A (pVA) carotenoids for nutritionally vulnerable populations. Significant effort has been placed on understanding the bioavailability of these micronutrients from cereal foods, including the exploration of underlying mechanisms by which their bioavailability can be modified. While micronutrient bioavailability is preferably assessed in clinical trials, relevant in vitro digestion and intestinal cell culture models have been applied to study effects of genetic, agronomic, post-harvest and food processing on micronutrient bioavailability. This review (1) critically assesses the application of in vitro models in the exploration of mechanisms associated with iron, zinc and provitamin A carotenoid bioaccessibility and intestinal absorption from cereal foods, and (2) identifies remaining gaps in order to frame future strategies to improve the nutritional impact of cereal foods.}, journal={JOURNAL OF CEREAL SCIENCE}, author={Ferruzzi, Mario G. and Kruger, Johanita and Mohamedshah, Zulfiqar and Debelo, Hawi and Taylor, John R. N.}, year={2020}, month={Nov} }
 @article{li_griffin_corbin_neilson_ferruzzi_2020, title={Modulating Phenolic Bioaccessibility and Glycemic Response of Starch-Based Foods in Wistar Rats by Physical Complexation between Starch and Phenolic Acid}, volume={68}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.0c01387}, abstractNote={This study assessed the impact of caffeic and ferulic acid complexation with maize amylopectin or potato starch on glycemic parameters. In comparison to starch–phenolic mixtures, starch–phenolic complexes resulted in significant modification of phenolic bioaccessibility and cellular uptake (p < 0.05). In addition, glucose release from in vitro digestion of starch was modestly reduced in the complexes compared to native starch alone (21.2–26.8 versus 29.8–30.5 mM). Furthermore, intestinal glucose transport, assessed in Caco-2 cell monolayers, was not affected by the presence of complexes (82.4–124 versus 100% at 90 min). However, a reduced glycemic response was evident in a Wistar rat model, with significant reduction in 240 min of blood glucose area under the curve following oral administration of the potato starch–ferulic acid complex compared to native potato starch (26 170 ± 556 versus 28 951 ± 486 mg min dL–1; p < 0.001). These alterations were attributed to complexation-induced resistant starch formation and phenolic entrapment, providing an alternative mechanistic approach to modulate glycemic properties of starch-based foods.}, number={46}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Li, Min and Griffin, Laura E. and Corbin, Sydney and Neilson, Andrew P. and Ferruzzi, Mario G.}, year={2020}, month={Nov}, pages={13257–13266} }
 @article{ferruzzi_hamaker_bordenave_2020, title={Phenolic compounds are less degraded in presence of starch than in presence of proteins through processing in model porridges}, volume={309}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2019.125769}, abstractNote={Phenolic compounds are known to bind non-covalently with starch, but the impact of this interaction on the stability of the phenolic compounds through processing and digestion has received little attention. In this study, we examined the recovery of intact phenolic compounds (gallic acid-GA, catechin-CAT and epigallocatechin gallate-EGCG) from processed and digested porridges with different formulations (starch or starch/protein). We observed that phenolics were less degraded in presence of starch only than in presence of starch + proteins. This protection seemed to be linked to the ability of the phenolic compounds to form V-type inclusion complexes with starch, with GA, CAT and EGCG in decreasing order of protection. This work could influence formulation of functional cereal-based foods containing phenolic compounds in order to maximize their retention.}, journal={FOOD CHEMISTRY}, author={Ferruzzi, Mario G. and Hamaker, Bruce R. and Bordenave, Nicolas}, year={2020}, month={Mar} }
 @misc{ho_ferruzzi_wightman_2020, title={Potential health benefits of (poly)phenols derived from fruit and 100% fruit juice}, volume={78}, ISSN={["1753-4887"]}, DOI={10.1093/nutrit/nuz041}, abstractNote={Abstract (Poly)phenol-rich diets have been associated with reduced risk of various diseases. Coffee and tea are typically identified as dietary sources of chlorogenic acid and flavan-3-ols; however, 100% fruit juice greatly contributes to anthocyanin, flavonol, flavan-3-ols, and flavanone intake, making them complementary sources of dietary (poly)phenols. Thus, the aim of this narrative review was to provide an overview of fruit (poly)phenols and their potential health benefits. Fruit (poly)phenols have been associated with several health benefits (eg, reduced risk of cardiovascular disease and neurocognitive benefits). Although perspectives on 100% fruit juice consumption are controversial due to the perception of sugar content, growing evidence supports the role of fruit in whole and 100% juice forms to provide consumer benefits in alignment with dietary guidance. However, differences in (poly)phenol profiles and bioavailability likely exist between whole fruit and 100% fruit juice due to processing and the presence/absence of fiber. Ongoing studies are better defining similarities and differences between whole fruit and 100% fruit juice to elucidate protective mechanisms and align with processing and consumer products.}, number={2}, journal={NUTRITION REVIEWS}, author={Ho, Kacie K. H. Y. and Ferruzzi, Mario G. and Wightman, JoLynne D.}, year={2020}, month={Feb}, pages={145–174} }
 @article{debelo_li_ferruzzi_2020, title={Processing influences on food polyphenol profiles and biological activity}, volume={32}, ISSN={["2214-8000"]}, DOI={10.1016/j.cofs.2020.03.001}, abstractNote={Increasing evidence supports the role of polyphenols in human health and has driven interest in translation of polyphenol rich ingredients to human foods. Food processing is a critical tool in development of consumer products aligned with clinical benefits. It is critical to consider how food processing may alter stability, bioavailability and ultimate biological activity of polyphenols. This review highlights processing parameters documented to impact polyphenol stability and provides examples of how select food processes impact polyphenols. Recent studies on whole grains, tea and fruit beverages document process induced losses as well as modification of bioavailability. However, characterization of processes-derived polyphenol degradation products is limited. Furthermore, bioactivity alterations remain mostly based on in vitro/preclinical systems. Growing evidence that polyphenol–macronutrient interactions can impact polyphenol profiles, bioavailability and bioactivities, including interactions with microbiota, suggest that consideration of the broader food matrix is critical in translation of experimental concepts to human foods.}, journal={CURRENT OPINION IN FOOD SCIENCE}, author={Debelo, Hawi and Li, Min and Ferruzzi, Mario G.}, year={2020}, month={Apr}, pages={90–102} }
 @misc{igho-osagie_cara_wang_yao_penkert_cassidy_ferruzzi_jacques_johnson_chung_et al._2020, title={Short-Term Tea Consumption Is Not Associated with a Reduction in Blood Lipids or Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials}, volume={150}, ISSN={["1541-6100"]}, DOI={10.1093/jn/nxaa295}, abstractNote={A recent systematic review of epidemiological evidence suggests that higher amounts of tea intake are associated with lower risks of cardiovascular disease (CVD) incidence and mortality.Our study objective was to assess mechanisms by which tea consumption may influence CVD risks.A systematic review and meta-analysis was conducted to investigate the effects of green and/or black tea consumption (≥4 wk) on systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride (TG) in healthy populations and among at-risk adults (analyzed separately) with metabolic syndrome, prediabetes, and hypercholesterolemia. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the strength of evidence (SoE).A total of 14 unique RCTs which randomly assigned 798 participants to either green tea, black tea, or placebo controls were included in our analyses. Intervention durations ranged from 4 to 24 wk (mean: 7.4 wk). Individual studies were judged as moderate to high quality based on risk of bias assessments. SoE was low to moderate owing to low sample sizes and insufficient power for most included studies to observe changes in the measured CVD biomarkers. Meta-analyses showed no significant effects of tea consumption on SBP, DBP, total cholesterol, LDL cholesterol, HDL cholesterol, and TG in healthy and at-risk adults (i.e., adults with obesity, prediabetes, borderline hypercholesterolemia, and metabolic syndrome).Short-term (4-24 wk) tea consumption does not appear to significantly affect blood pressure or lipids in healthy or at-risk adults, although the evidence is limited by insufficient power to detect changes in these CVD biomarkers. High-quality RCTs with longer durations and sufficient sample sizes are needed to fully elucidate the effects of tea. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020134513.}, number={12}, journal={JOURNAL OF NUTRITION}, author={Igho-Osagie, Ebuwa and Cara, Kelly and Wang, Deena and Yao, Qisi and Penkert, Laura P. and Cassidy, Aedin and Ferruzzi, Mario and Jacques, Paul F. and Johnson, Elizabeth J. and Chung, Mei and et al.}, year={2020}, month={Dec}, pages={3269–3279} }
 @article{li_ndiaye_corbin_foegeding_ferruzzi_2020, title={Starch-phenolic complexes are built on physical CH-pi interactions and can persist after hydrothermal treatments altering hydrodynamic radius and digestibility of model starch-based foods}, volume={308}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2019.125577}, abstractNote={Leveraging phenolic complexation to optimize starch functionality and digestibility is restrained by the obscurity of their physicochemical nature and molecular basis. To define starch-phenolic complexes under hydrothermal treatments, maize amylopectin and potato starch were complexed with caffeic acid, ferulic acid and gallic acid. Starch hydrothermal stability and digestibility were measured by differential scanning calorimeter and Englyst's method, respectively. While monosaccharide compositions and glycosidic linkages were analyzed by GC-MS, hydrodynamic radius and proton magnetic resonance of gelatinized complexes were measured by dynamic light scattering and NMR respectively. Compared with native starches, starch-phenolic complexes were not chemically modified and had modestly lower estimated glycemic indexes and significantly lower gelatinization temperatures (p < 0.05). Starch-phenolic complexes also had significantly lower levels of phenolic proton intensities and hydrodynamic radii relative to the control starch-phenolic mixtures (p < 0.05). These results suggested that phenolics may complex with starch through non-covalent CH-π bonds along α-(1 → 4) glycosidic chains.}, journal={FOOD CHEMISTRY}, author={Li, Min and Ndiaye, Cheikh and Corbin, Sydney and Foegeding, E. Allen and Ferruzzi, Mario G.}, year={2020}, month={Mar} }
 @article{wang_cassidy_ferruzzi_jacques_johnson_zhao_shams-white_karlsen_wallace_chung_2020, title={Tea Flavonoids and Risk of Cardiovascular and All-Cause Mortality: A Systematic Review and Meta-Analysis}, volume={79}, ISSN={["1475-2719"]}, DOI={10.1017/S0029665120001573}, abstractNote={Abstract There is increasing evidence that both black and green tea are beneficial for prevention of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes.Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥ 4 studies were performed. 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, eachcup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87- 1.00) with large heterogeneity (I 2 = 81.4%; p = 0.005). Current evidence indicates that increased tea consumption may reduce cardiovascular and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO.}, number={OCE2}, journal={PROCEEDINGS OF THE NUTRITION SOCIETY}, author={Wang, Ding Ding and Cassidy, Aedin and Ferruzzi, Mario G. and Jacques, Paul and Johnson, Elizabeth and Zhao, Naisi and Shams-White, Marissa and Karlsen, Micaela and Wallace, Taylor C. and Chung, Mei}, year={2020}, pages={E209–E209} }
 @misc{hayes_ferruzzi_2020, title={Update on the bioavailability and chemopreventative mechanisms of dietary chlorophyll derivatives}, volume={81}, ISSN={["0271-5317"]}, DOI={10.1016/j.nutres.2020.06.010}, abstractNote={Chlorophyll, a phytochemical responsible for the green pigmentation in plants, has been studied for almost 100 years for its biological activities in humans. Over the past 30 years, the potential chemopreventative activities of both natural chlorophylls and their processed induced derivatives as well as the semisynthetic forms, such as sodium copper chlorophyllin, have been the focus of many research efforts. Established as potential chemopreventative agents with little to no bioavailability themselves, the activities of chlorophyll derivatives were generally ascribed to their ability to modulate mutagen/carcinogen bioavailability, their metabolism, and ultimately their ability to decrease the “exposure” to these carcinogens for humans at risk. More recently, systemic activities of chlorophyll derivatives have been reported to include modulation of oxidative stress and regulation of xenobiotic metabolizing systems and gene expression of systems critical to prevention of initiation and/or progression of cancer including NFE2-related factor 2, nuclear factor kappa B, TGF-β, and β-catenin pathways. With this in mind, the goals of this review are to provide an update to the comprehensive review of Ferruzzi and Blakeslee (2007) to include new insights into the behavior of chlorophyll derivatives in the gut as well as evidence of the systemic bioavailability of chlorophyll derivatives and their metabolites in support of potential impacts in prevention of cancer throughout the body.}, journal={NUTRITION RESEARCH}, author={Hayes, Micaela and Ferruzzi, Mario G.}, year={2020}, month={Sep}, pages={19–37} }
 @misc{kruger_taylor_ferruzzi_debelo_2020, title={What is food-to-food fortification? A working definition and framework for evaluation of efficiency and implementation of best practices}, volume={19}, ISSN={["1541-4337"]}, DOI={10.1111/1541-4337.12624}, abstractNote={Food-to-food fortification (FtFF) is an emerging food-based strategy that can complement current strategies in the ongoing fight against micronutrient deficiencies, but it has not been defined or characterized. This review has proposed a working definition of FtFF. Comparison with other main food-based strategies clearly differentiates FtFF as an emerging strategy with the potential to address multiple micronutrient deficiencies simultaneously, with little dietary change required by consumers. A review of literature revealed that despite the limited number of studies (in vitro and in vivo), the diversity of food-based fortificants investigated and some contradictory data, there are promising fortificants, which have the potential to improve the amount of bioavailable iron, zinc, and provitamin A from starchy staple foods. These fortificants are typically fruits and vegetables, with high mineral as well as ascorbic acid and β-carotene contents. However, as the observed improvements in micronutrient bioavailability and status are relatively small, measuring the positive outcomes is more likely to be impactful only if the FtFF products are consumed as regular staples. Considering best practices in implementation of FtFF, raw material authentication and ingredient documentation are critical, especially as the contents of target micronutrients and bioavailability modulators as well as the microbiological quality of the plant-based fortificants can vary substantially. Also, as there are only few developed supply chains for plant-based fortificants, procurement of consistent materials may be problematic. This, however, provides the opportunity for value chain development, which can contribute towards the economic growth of communities, or hybrid approaches that leverage traditional premixes to standardize product micronutrient content.}, number={6}, journal={COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY}, author={Kruger, Johanita and Taylor, John R. N. and Ferruzzi, Mario G. and Debelo, Hawi}, year={2020}, month={Nov}, pages={3618–3658} }
 @article{solverson_henderson_debelo_ferruzzi_baer_novotny_2019, title={An Anthocyanin-Rich Mixed-Berry Intervention May Improve Insulin Sensitivity in a Randomized Trial of Overweight and Obese Adults}, volume={11}, ISSN={["2072-6643"]}, DOI={10.3390/nu11122876}, abstractNote={Evidence supports the beneficial effects of berries on glucoregulation, possibly related to flavonoid content, fiber content, or both. The purpose of this study was to assess the potential of mixed berries to improve insulin sensitivity and to identify the potential role of flavonoids and fiber. In a randomized cross-over trial with four treatment periods, overweight/obese men and women were fed a controlled 45% fat diet for one week prior to a meal-based glucose tolerance test. The same base diet was provided during each feeding period with the addition of one of four treatments: whole mixed berries, sugar matched mixed berry juice, sugar matched gelatin, and sugar/fiber matched gelatin. Subjects then completed a meal-based oral glucose tolerance test. Serum glucose, insulin and non-esterified fatty acids were not different between individual treatments. However, in a secondary analysis, the combined berry preparations resulted in a lower serum insulin area under the curve (difference of 0.15 ± 0.066 ln pmol min/mL, mean ± SE, p = 0.0228), compared to the combined gelatin treatments, while the difference for serum glucose did not quite meet statistical significance (difference of 0.17 ± 0.093 ln mg·min/dL, mean ± SE, p = 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.}, number={12}, journal={NUTRIENTS}, author={Solverson, Patrick M. and Henderson, Theresa R. and Debelo, Hawi and Ferruzzi, Mario G. and Baer, David J. and Novotny, Janet A.}, year={2019}, month={Dec} }
 @article{nkhata_ortiz_baributsa_hamaker_rocheford_ferruzzi_2019, title={Assessment of oxygen sequestration on effectiveness of Purdue Improved Crop Storage (PICS) bags in reducing carotenoid degradation during post-harvest storage of two biofortified orange maize genotypes}, volume={87}, ISSN={["1095-9963"]}, DOI={10.1016/j.jcs.2019.02.007}, abstractNote={Increasing adoption of biofortified orange maize in developing countries requires economical storage methods to manage product quality and carotenoid retention. This study assessed the utility of the Purdue Improved Crop Storage (PICS) bags with a specific focus on retention of provitamin A and other carotenoids in two biofortified maize genotypes (OPVI and OPVII). Grain was stored at ambient conditions for eight months in PICS bags with and without an O2 scavenger, (PICS-oxy) and (PICS-noxy), respectively, or in common polypropylene woven bags. After 4 months of storage carotenoid content was significantly higher (p < 0.05) in grain stored in PICS-oxy compared to PICS-noxy or woven bags demonstrating the importance of entrapped oxygen on maize carotenoid degradation. Differences were observed in stability between the two mize genotypes. After 8 months, carotenoid stability remained dependent on storage bag and genotype with retention being greater in PICS-oxy and PICS-noxy compared to woven bags and OPVI maintained a higher carotenoid retention than OPVII maize. Oxygen content and genotype were determining factors in the effectiveness of PICS to mitigate carotenoid degradation during post-harvest storage.}, journal={JOURNAL OF CEREAL SCIENCE}, author={Nkhata, Smith G. and Ortiz, Darwin and Baributsa, Dieudonne and Hamaker, Bruce and Rocheford, Torbert and Ferruzzi, Mario G.}, year={2019}, month={May}, pages={68–77} }
 @article{pico_corbin_ferruzzi_martinez_2019, title={Banana flour phenolics inhibit trans-epithelial glucose transport from wheat cakes in a coupled in vitro digestion/Caco-2 cell intestinal model}, volume={10}, ISSN={["2042-650X"]}, DOI={10.1039/c9fo01679a}, abstractNote={A 10% replacement of wheat flour with banana flour subjected to different processing conditions resulted in from 45.0 to 54.5% higher glucose transport inhibition.}, number={10}, journal={FOOD & FUNCTION}, author={Pico, Joana and Corbin, Sydney and Ferruzzi, Mario G. and Martinez, Mario M.}, year={2019}, month={Oct}, pages={6300–6311} }
 @article{cheng_ferruzzi_jones_2019, title={Fate of lutein-containing zein nanoparticles following simulated gastric and intestinal digestion}, volume={87}, ISSN={0268-005X}, url={http://dx.doi.org/10.1016/J.FOODHYD.2018.08.013}, DOI={10.1016/J.FOODHYD.2018.08.013}, abstractNote={Abstract Zein nanoparticles (ZNPs) were prepared to encapsulate lutein via solvent-induced nanoprecipitation, and the stability of the zein nanoparticles with encapsulated lutein (ZLNPs) was determined following in vitro gastric and intestinal simulation. Stability was assessed by dynamic light scattering, gel electrophoresis, tendency towards sedimentation, and both atomic force and light microscopy. ZNPs possessed a hydrodynamic radius of ∼75 nm, which was not altered with incorporation of lutein. Gastric digestion conditions induced significant aggregation and sedimentation of ZLNPs, which were not fully digested by gastric enzymes and were found adhered to lipid droplets in light micrographs. Aggregation was decreased and digestion was promoted during gastric digestion if salt was omitted, indicating that a high ion concentration increased ZLNP aggregation and limited enzymatic digestion. ZLNPs were redispersed in intestinal conditions and completely digested into peptides. In comparison to aqueous lutein dispersions, incorporation within ZNPs increased lutein's digestive stability by ∼58% but reduced its micellarization efficiency by ∼42%. These findings indicated that ZNPs provided a degree of physical protection to encapsulated carotenoids in gastric conditions yet might partially interfere with certain pathways for carotenoid bioaccessibility.}, journal={Food Hydrocolloids}, publisher={Elsevier BV}, author={Cheng, Christopher J. and Ferruzzi, Mario and Jones, Owen G.}, year={2019}, month={Feb}, pages={229–236} }
 @article{merwe_kruger_ferruzzi_duodu_taylor_2019, title={Improving iron and zinc bioaccessibility through food-to-food fortification of pearl millet with tropical plant foodstuffs (moringa leaf powder, roselle calyces and baobab fruit pulp)}, volume={56}, ISSN={["0975-8402"]}, DOI={10.1007/s13197-019-03711-y}, abstractNote={Essential mineral (iron and zinc) deficiencies are still prevalent in the Semi-arid Tropics, where many people consume monotonous, predominantly cereal-based diets. This study aimed to evaluate the potential of including tropical plant foodstuffs high in iron and zinc (moringa leaves and roselle calyces) or mineral availability enhancers (baobab fruit pulp) in a pearl millet-based food containing a plant food-based provitamin A source, with the aim of preventing iron and zinc deficiencies in the Semi-arid Tropics. Mineral bioaccessibility was assessed by dialysability assay. Moringa, roselle and baobab considerably increased iron and zinc bioaccessibility when added at 10 parts:100 parts pearl millet (dry basis). These foodstuffs, increased the contribution to the absolute iron requirements of women of reproductive age by 2.5, 2.1 and 2.3 times for moringa, roselle and baobab, respectively and to their absolute zinc requirements by 2.4, 2.1 and 2.7 times, respectively. Combining these plant foodstuffs could contribute up to 28% and 41% of the women’s absolute iron and zinc requirements, respectively, from a single meal. Moringa, despite having the highest iron content, when added at a very high level (30 parts:100 parts pearl millet) decreased bioaccessible iron and zinc, most probably primarily due to its high calcium content. Food-to-food fortification of staple cereal foods with moringa leaves, roselle calyces or baobab fruit pulp plus a provitamin A source can potentially sustainably improve iron and zinc bioavailability in the diets of at-risk communities in the Semi-arid Tropics.}, number={4}, journal={JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE}, author={Merwe, Renee and Kruger, Johanita and Ferruzzi, Mario G. and Duodu, Kwaku G. and Taylor, John R. N.}, year={2019}, month={Apr}, pages={2244–2256} }
 @article{pico_xu_guo_mohamedshah_ferruzzi_martinez_2019, title={Manufacturing the ultimate green banana flour: Impact of drying and extrusion on phenolic profile and starch bioaccessibility}, volume={297}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2019.124990}, abstractNote={Use of banana flours as functional ingredients is growing due to their nutritional benefits derived from phenolics and dietary fiber. However, the effect oven-drying, freeze-drying and extrusion on the phenolic compounds or starch digestibility is not understood. In this work, phenolic acids (gallic acid, caffeic acid), flavan-3-ols (epicatechin, catechin) and flavonols (quercetin-3-O-glucoside and myricetin) were quantified in banana flour processed by different methods. Epicatechin, the most abundant phenolic in all flours (up to 1.93 mg/100 g), was significantly reduced during thermal processing (oven-drying and extrusion). Meanwhile, phenolic acids and flavonols were found to be more thermally stable. Thus, oven-drying and extrusion generally improved the extractability of phenolic acids and flavonols. Freeze-drying resulted in native flours with significantly higher insoluble dietary fiber (up to 43.3%), although the digestible starch fraction was digested more rapidly than the oven-dried counterpart.}, journal={FOOD CHEMISTRY}, author={Pico, Joana and Xu, Kang and Guo, Mengmeng and Mohamedshah, Zulfiqar and Ferruzzi, Mario G. and Martinez, Mario M.}, year={2019}, month={Nov} }
 @article{li_george_hunter_hamaker_mattes_ferruzzi_2019, title={Potato product form impacts in vitro starch digestibility and glucose transport but only modestly impacts 24 h blood glucose response in humans}, volume={10}, ISSN={["2042-650X"]}, DOI={10.1039/c8fo02530d}, abstractNote={Potatoes are rich in phenolic compounds which have been reported to impact starch digestion and intestinal glucose transport in model systems through phenolic–starch interactions.}, number={4}, journal={FOOD & FUNCTION}, author={Li, Min and George, Judy and Hunter, Stephanie and Hamaker, Bruce and Mattes, Richard and Ferruzzi, Mario G.}, year={2019}, month={Apr}, pages={1846–1855} }
 @article{lim_zhang_ferruzzi_hamaker_2019, title={Starch digested product analysis by HPAEC reveals structural specificity of flavonoids in the inhibition of mammalian alpha-amylase and alpha-glucosidases}, volume={288}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2019.02.117}, abstractNote={An accurate high-performance anion-exchange chromatography (HPAEC) method is presented to measure the inhibition property of flavonoids against mammalian starch digestive enzymes, because flavonoids interfere with commonly used 3,5-dinitrosalicylic acid (DNS) and glucose oxidase/peroxidase (GOPOD) methods. Eriodictyol, luteolin, and quercetin increased absorbance values (without substrate) in the DNS assay and, with substrate, either overestimated or underestimated values in the DNS and GOPOD assays. Using a direct HPAEC measurement method, flavonoids showed different inhibition properties against α-amylase and α-glucosidases, showing different inhibition constants (Ki) and mechanisms. The double bond between C2 and C3 on the C-ring of flavonoids appeared particularly important to inhibit α-amylase, while the hydroxyl group (OH) at C3 of the C-ring was related to inhibition of α-glucosidases. This study shows that direct measurement of starch digestion products by HPAEC should be used in inhibition studies, and provides insights into structure-function aspects of polyphenols in controlling starch digestion rate.}, journal={FOOD CHEMISTRY}, author={Lim, Jongbin and Zhang, Xiaowei and Ferruzzi, Mario G. and Hamaker, Bruce R.}, year={2019}, month={Aug}, pages={413–421} }
 @article{ortiz_nkhata_rocheford_ferruzzi_2019, title={Steeping of Biofortified Orange Maize Genotypes for Ogi Production Modifies Pasting Properties and Carotenoid Stability}, volume={9}, ISSN={["2073-4395"]}, DOI={10.3390/agronomy9110771}, abstractNote={Biofortified orange maize open-pollinated varieties and hybrids with higher provitamin A carotenoids (pVACs) have been released in sub-Saharan Africa and will be introduced throughout the local food systems. This study assessed the impact of steeping, a traditional processing method, on retention of carotenoids and starch pasting properties of porridges made from select biofortified maize genotypes. Steeping had a modest effect (<9% loss) on total carotenoid stability during relatively shorter steeping periods (<72 h). However, more extended steeping periods (up to 120 h) had a detrimental effect on total carotenoid recovery (61% loss). Xanthophylls showed greater stability (82% retention) compared to carotenes (30% retention) during subsequent wet cooking of fermented flours. Interestingly, steeping of maize did modify pasting properties, with peak viscosities increasing from 24–72 h of steeping potentially impacting cooking stability. These results suggest that steeping can impact carotenoid retention and potentially optimal steeping times would be 24–72 h for acceptable carotenoid retention.}, number={11}, journal={AGRONOMY-BASEL}, author={Ortiz, Darwin and Nkhata, Smith G. and Rocheford, Torbert and Ferruzzi, Mario G.}, year={2019}, month={Nov} }
 @article{li_ho_hayes_ferruzzi_2019, title={The Roles of Food Processing in Translation of Dietary Guidance for Whole Grains, Fruits, and Vegetables}, volume={10}, ISSN={["1941-1421"]}, DOI={10.1146/annurev-food-032818-121330}, abstractNote={The Dietary Guidelines for Americans (DGA) recommend the consumption of whole grains, fruits, and vegetables as part of a healthy diet. However, current consumption patterns suggest that most Americans are not meeting these recommendations. The challenge remains to align the DGA guidance with the food environment and consumers’ expectations for product quality, availability, and affordability. Currently, processed foods play an increasingly important role in American diets. Often characterized as unhealthy, processed foods are contributors to both food and nutritional security. When the alignment of processing strategies with DGA principles exists, achieving DGA goals is more likely, regardless of processing level. In this review, select processing strategies for whole grains, fruits, and vegetables are described to show how DGA principles can guide processing efforts to create healthier products. Although whole grains, supported by industry-wide innovation and guidance, have had some success with consumers, improving intake of fruit and vegetable products remains a challenge. Closing consumption gaps requires new innovations and products aligned with consumer preferences and DGA principles.}, journal={ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY, VOL 10}, author={Li, Min and Ho, Kacie K. H. Y. and Hayes, Micaela and Ferruzzi, Mario G.}, year={2019}, pages={569–596} }
 @article{ho_cheng_wang_simon_wu_zhao_carry_ferruzzi_faith_valcarcel_et al._2018, title={A Comprehensive Database and Analysis Framework To Incorporate Multiscale Data Types and Enable Integrated Analysis of Bioactive Polyphenols}, volume={15}, ISSN={["1543-8384"]}, DOI={10.1021/acs.molpharmaceut.7b00412}, abstractNote={The development of a given botanical preparation for eventual clinical application requires extensive, detailed characterizations of the chemical composition, as well as the biological availability, biological activity, and safety profiles of the botanical. These issues are typically addressed using diverse experimental protocols and model systems. Based on this consideration, in this study we established a comprehensive database and analysis framework for the collection, collation, and integrative analysis of diverse, multiscale data sets. Using this framework, we conducted an integrative analysis of heterogeneous data from in vivo and in vitro investigation of a complex bioactive dietary polyphenol-rich preparation (BDPP) and built an integrated network linking data sets generated from this multitude of diverse experimental paradigms. We established a comprehensive database and analysis framework as well as a systematic and logical means to catalogue and collate the diverse array of information gathered, which is securely stored and added to in a standardized manner to enable fast query. We demonstrated the utility of the database in (1) a statistical ranking scheme to prioritize response to treatments and (2) in depth reconstruction of functionality studies. By examination of these data sets, the system allows analytical querying of heterogeneous data and the access of information related to interactions, mechanism of actions, functions, etc., which ultimately provide a global overview of complex biological responses. Collectively, we present an integrative analysis framework that leads to novel insights on the biological activities of a complex botanical such as BDPP that is based on data-driven characterizations of interactions between BDPP-derived phenolic metabolites and their mechanisms of action, as well as synergism and/or potential cancellation of biological functions. Out integrative analytical approach provides novel means for a systematic integrative analysis of heterogeneous data types in the development of complex botanicals such as polyphenols for eventual clinical and translational applications.}, number={3}, journal={MOLECULAR PHARMACEUTICS}, author={Ho, Lap and Cheng, Haoxiang and Wang, Jun and Simon, James E. and Wu, Qingli and Zhao, Danyue and Carry, Eileen and Ferruzzi, Mario G. and Faith, Jeremiah and Valcarcel, Breanna and et al.}, year={2018}, month={Mar}, pages={840–850} }
 @article{ortiz_ponrajan_pablo bonnet_rocheford_ferruzzi_2018, title={Carotenoid Stability during Dry Milling, Storage, and Extrusion Processing of Biofortified Maize Genotypes}, volume={66}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.7b05706}, abstractNote={Translation of the breeding efforts designed to biofortify maize (Z. mays) genotypes with higher levels of provitamin A carotenoid (pVAC) content for sub-Saharan Africa is dependent in part on the stability of carotenoids during postharvest through industrial and in-home food processing operations. The purpose of this study was to simulate production of commercial milled products by determining the impact of dry milling and extrusion processing on carotenoid stability in three higher pVAC maize genotypes (C17xDE3, Orange ISO, Hi27xCML328). Pericarp and germ removal of biofortified maize kernels resulted in ∼10% loss of total carotenoids. Separating out the maize flour fraction (<212 μm) resulted in an additional ∼15% loss of total carotenoids. Carotenoid degradation was similar across milled maize fractions. Dry-milled products of Orange ISO and Hi27xCML328 genotypes showed ∼28% pVAC loss after 90-days storage. Genotype C17xDE3, with highest levels of all-trans-β-carotene, showed a 68% pVAC loss after 90-day storage. Extrusion processing conditions were optimal at 35% extrusion moisture, producing fully cooked instant maize flours with high pVAC retention (70–93%). These results support the notion that postharvest losses in maize milled fractions may be dependent, in part, on genotype and that extrusion processing may provide an option for preserving biofortified maize products.}, number={18}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Ortiz, Darwin and Ponrajan, Amudhan and Pablo Bonnet, Juan and Rocheford, Torbert and Ferruzzi, Mario G.}, year={2018}, month={May}, pages={4683–4691} }
 @article{li_pernell_ferruzzi_2018, title={Complexation with phenolic acids affect rheological properties and digestibility of potato starch and maize amylopectin}, volume={77}, ISSN={["1873-7137"]}, DOI={10.1016/j.foodhyd.2017.11.028}, abstractNote={Abstract As well-documented inhibitors of starch digestive enzymes, dietary phenolics are less known for the ability to modify starch structures and functionality. This study aimed to characterize changes in starch structures by complexing individual phenolic acids with maize amylopectin and potato starch respectively, and to determine pasting properties and digestibility of the resulting complexes. FTIR-ATR results confirmed (995/1022 and 1047/1022 cm−1/cm−1) reduced crystallinity in short-range order of both starches, which were likely caused by a decrease in moisture content and/or by attenuation of molecular interactions in both crystalline and amorphous lamellas. Measurements of apparent amylose content and amylose leaching discovered formation of amylose-like structures in amylopectin and V-type amylose in potato starch. These structural changes were negatively associated with pasting temperature, peak viscosity, hot paste viscosity and cold paste viscosity. Digestibility was modestly lower for starch-phenolic acid complexes than for native starch and starch-phenolic acids mixtures. More interestingly, a small fraction of phenolic acids remained bound to starch molecules after pasting of starch-phenolic acid complexes, suggesting bound phenolic acids as a potential factor inhibiting starch hydrolysis.}, journal={FOOD HYDROCOLLOIDS}, author={Li, Min and Pernell, Chris and Ferruzzi, Mario G.}, year={2018}, month={Apr}, pages={843–852} }
 @article{ahmad_rich_koch_croft_ferruzzi_kay_hodgson_ward_2018, title={Effect of adding milk to black tea on vascular function in healthy men and women: a randomised controlled crossover trial}, volume={9}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C8FO01019F}, DOI={10.1039/C8FO01019F}, abstractNote={Tea consumption may improve endothelial function and blood pressure via increased bioavailability and bioactivity of nitric oxide. However, questions remain as to the impact of the common practice of adding milk.To investigate the effect of regular consumption of black tea, with and without milk, on vascular function and blood pressure in healthy volunteers.A randomised, controlled, crossover study was performed in 17 healthy volunteers; 7 men and 10 women, mean age 22.4 ± 3.0 years. Participants received each of the following treatments in random order for 4 weeks, with no washout period in between, (i) hot water, (ii) black tea and (iii) black tea with milk. Vascular function was assessed using flow-mediated dilatation (FMD) of the brachial artery at the end of each treatment period. In addition, participants monitored their home blood pressure for the last 7 days of each treatment period. A blood and urine sample was also collected at the end of each treatment period.Black tea increased FMD compared to the hot water control group (1.00 ± 0.18%, P < 0.0001). Black tea with milk decreased FMD compared to both the hot water control (-0.64 ± 0.19%, P = 0.001) and black tea (-1.64 ± 0.19%, P < 0.0001). Compared with hot water, black tea did not alter blood pressure, while black tea with milk increased systolic (1.1 ± 0.5 mmHg, P = 0.03) and diastolic blood pressure (2.0 ± 0.5 mmHg, P < 0.0001). Black tea (-1.8 ± 0.5 bpm, P < 0.001) and black tea with milk (-1.8 ± 0.6 bpm, P < 0.001) lowered heart rate compared to hot water. No significant difference for plasma nitrate or nitrite was observed between treatment groups.The addition of milk to black tea alters the acute/short-term impact of regular tea consumption on vascular function and blood pressure in young healthy men and women. The exact mechanism for this affect remains unknown and longer-term trials to establish this effect in a range of populations are warranted.}, number={12}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Ahmad, Adilah F. and Rich, Lisa and Koch, Henrietta and Croft, Kevin D. and Ferruzzi, Mario G. and Kay, Colin D. and Hodgson, Jonathan M. and Ward, Natalie C.}, year={2018}, pages={6307–6314} }
 @article{fenton_owens_lipka_ortiz_tiede_mateos-hernandez_ferruzzi_rocheford_2018, title={High-density linkage mapping of vitamin E content in maize grain}, volume={38}, ISSN={1380-3743 1572-9788}, url={http://dx.doi.org/10.1007/S11032-018-0780-7}, DOI={10.1007/S11032-018-0780-7}, number={3}, journal={Molecular Breeding}, publisher={Springer Science and Business Media LLC}, author={Fenton, Megan E. and Owens, Brenda F. and Lipka, Alexander E. and Ortiz, Darwin and Tiede, Tyler and Mateos-Hernandez, Maria and Ferruzzi, Mario G. and Rocheford, Torbert}, year={2018}, month={Feb} }
 @article{furrer_chegeni_ferruzzi_2018, title={Impact of potato processing on nutrients, phytochemicals, and human health}, volume={58}, ISSN={1040-8398 1549-7852}, url={http://dx.doi.org/10.1080/10408398.2016.1139542}, DOI={10.1080/10408398.2016.1139542}, abstractNote={Potatoes (Solanum tuberosum) are an important global crop that can be transformed into many products impacting several health dimensions ranging from undernutrition, food security and disease prevention to issues of overnutrition including obesity, diabetes, heart disease. Processed potato products are typically categorized as high fat and sodium foods, as well as being classified as a significant source of carbohydrate, in the form of starch. Conversely, potato products are less known for their contribution of key micronutrients (vitamin C, potassium, magnesium), fiber, and phytochemicals (phenolics and carotenoids). More recent insight into the nutritional value of potatoes and the potential of potato phytochemicals to modulate oxidative and inflammatory stress as well as the potential to alter glycemic response has resulted in increased interest in strategies to improve and leverage the nutritional quality of processed potatoes. This review summarizes critical information on nutritional profiles of potatoes and their processed products and describes the state of the science relative to the influence of in-home and common commercial processing on nutritional quality and potential impacts on human health.}, number={1}, journal={Critical Reviews in Food Science and Nutrition}, publisher={Informa UK Limited}, author={Furrer, Amber N. and Chegeni, Mohammad and Ferruzzi, Mario G.}, year={2018}, month={Jan}, pages={146–168} }
 @article{elegbede_li_jones_campanella_ferruzzi_2018, title={Interactions Between Flavonoid-Rich Extracts and Sodium Caseinate Modulate Protein Functionality and Flavonoid Bioaccessibility in Model Food Systems}, volume={83}, ISSN={["1750-3841"]}, DOI={10.1111/1750-3841.14132}, abstractNote={Abstract With growing interest in formulating new food products with added protein and flavonoid‐rich ingredients for health benefits, direct interactions between these ingredient classes becomes critical in so much as they may impact protein functionality, product quality, and flavonoids bioavailability. In this study, sodium caseinate (SCN)‐based model products (foams and emulsions) were formulated with grape seed extract (GSE, rich in galloylated flavonoids) and green tea extract (GTE, rich in nongalloylated flavonoids), respectively, to assess changes in functional properties of SCN and impacts on flavonoid bioaccessibility. Experiments with pure flavonoids suggested that galloylated flavonoids reduced air‐water interfacial tension of 0.01% SCN dispersions more significantly than nongalloylated flavonoids at high concentrations (>50 μg/mL). This observation was supported by changes in stability of 5% SCN foam, which showed that foam stability was increased at high levels of GSE (≥50 μg/mL, P < 0.05) but was not affected by GTE. However, flavonoid extracts had modest effects on SCN emulsion. In addition, galloylated flavonoids had higher bioaccessibility in both SCN foam and emulsion. These results suggest that SCN‐flavonoid binding interactions can modulate protein functionality leading to difference in performance and flavonoid bioaccessibility of protein‐based products. Practical Application As information on the beneficial health effects of flavonoids expands, it is likely that usage of these ingredients in consumer foods will increase. However, the necessary levels to provide such benefits may exceed those that begin to impact functionality of the macronutrients such as proteins. Flavonoid inclusion within protein matrices may modulate protein functionality in a food system and modify critical consumer traits or delivery of these beneficial plant‐derived components. The product matrices utilized in this study offer relevant model systems to evaluate how fortification with flavonoid‐rich extracts allows for differing effects on formability and stability of the protein‐based systems, and on bioaccessibility of fortified flavonoid extracts.}, number={5}, journal={JOURNAL OF FOOD SCIENCE}, author={Elegbede, Jennifer L. and Li, Min and Jones, Owen G. and Campanella, Osvaldo H. and Ferruzzi, Mario G.}, year={2018}, month={May}, pages={1229–1236} }
 @article{de groote_kariuki_traore_taylor_ferruzzi_hamaker_2018, title={Measuring consumers' interest in instant fortified pearl millet products: a field experiment in Touba, Senegal}, volume={98}, ISSN={0022-5142}, url={http://dx.doi.org/10.1002/JSFA.8722}, DOI={10.1002/JSFA.8722}, abstractNote={Abstract BACKGROUND In Africa, food‐processing industries are emerging fast, especially for cereals. New low‐cost extrusion cookers give small enterprises an opportunity to enter the market for processed cereal products, in particular instant, fortified and flavoured mixes. Before engaging in the marketing of these products, consumers' interest needs to be assessed. This study used a combination of affective tests and experimental auctions with 200 consumers in Touba, Senegal, to evaluate four new products with conventional pearl millet flour as the control: instant pearl millet flour, instant pearl millet flour with added dry mango and carrot powder (naturally fortified), and the previous products with added conventional chemical micronutrient fortificants. RESULTS During affective tests, consumers made little distinction between the five products in appearance, aroma, taste and overall appreciation. The experimental auctions showed that, without providing additional information on the products, there was no difference in ‘willingness to pay’ (WTP) between them. However, after that information is provided, consumers were willing to pay a modest premium for instant flour, and a large premium for added mango and carrot extract and for added micronutrients, but were not willing to pay a premium if those micronutrients came from natural sources. Income increased overall WTP, while education increased WTP for instant flour. CONCLUSION There is a potential market in low‐income African countries for instant and fortified cereal food products, but likely in the higher income and education groups. The increased cost needs to be compared to the premiums consumers are willing to pay. In the next step, the new and promising products could be tested in pilot markets, with target consumers. © 2017 Society of Chemical Industry}, number={6}, journal={Journal of the Science of Food and Agriculture}, publisher={Wiley}, author={De Groote, Hugo and Kariuki, Sarah W and Traore, Djibril and Taylor, John RN and Ferruzzi, Mario G and Hamaker, Bruce R}, year={2018}, month={Apr}, pages={2320–2331} }
 @article{moser_aragon_furrer_van klinken_kaczmarczyk_lee_george_hamaker_mattes_ferruzzi_2018, title={Potato phenolics impact starch digestion and glucose transport in model systems but translation to phenolic rich potato chips results in only modest modification of glycemic response in humans}, volume={52}, ISSN={["0271-5317"]}, DOI={10.1016/j.nutres.2018.02.001}, abstractNote={Beneficial effects of some phenolic compounds in modulation of carbohydrate digestion and glycemic response have been reported, however effects of phenolics from processed potato products on these endpoints are not well known. The aims of this study were to characterize phenolic profiles of fresh potatoes (purple, red, or white fleshed; 2 varieties each) and chips, and to examine the potential for potato phenolic extracts (PPE) to modulate starch digestion and intestinal glucose transport in model systems. Following in vitro assessment, a pilot clinical study (n=11) assessed differences in glycemic response and gastric emptying between chips from pigmented and white potatoes. We hypothesized that phenolics from pigmented potato chips would be recovered through processing and result in a reduced acute glycemic response in humans relative to chips made from white potatoes. PPEs were rich in anthocyanins (~98, 11 and ND mg/100 g dw) and chlorogenic acids (~519, 425 and 157 mg/100 g dw) for purple, red and white varieties respectively. While no significant effects were observed on starch digestion by α-amylase and the α-glucosidases, PPEs significantly (p<0.05) decreased the rate of glucose transport, measured following transport of 1,2,3,4,5,6,6-d7 -glucose (d7-glu) across Caco-2 human intestinal cell monolayers, by 4.5-83.9%. Consistent with in vitro results, consumption of purple potato chips modestly but significantly (p<0.05) decreased blood glucose at 30 and 60 minutes post consumption compared to white chips without impacting gastric emptying. These results suggest that potato phenolics may play a modest role in modulation of glycemic response and these effects may result in subtle differences between consumer products.}, journal={NUTRITION RESEARCH}, author={Moser, Sydney and Aragon, Ingrid and Furrer, Amber and Van Klinken, Jan-Willem and Kaczmarczyk, Melissa and Lee, Byung-Hoo and George, Judy and Hamaker, Bruce R. and Mattes, Richard and Ferruzzi, Mario G.}, year={2018}, month={Apr}, pages={57–70} }
 @article{aragón_ceballos_dufour_ferruzzi_2018, title={Pro-vitamin A carotenoids stability and bioaccessibility from elite selection of biofortified cassava roots (Manihot esculenta, Crantz) processed to traditional flours and porridges}, volume={9}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C8FO01276H}, DOI={10.1039/C8FO01276H}, abstractNote={The effects of fermentation and thermal processing on the stability and bioaccessibility of pVAC from elite selections of biofortified cassava roots were assessed to determine the potential for genotype x processing effects.}, number={9}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Aragón, Ingrid J. and Ceballos, Hernán and Dufour, Dominique and Ferruzzi, Mario G.}, year={2018}, pages={4822–4835} }
 @article{redan_albaugh_charron_novotny_ferruzzi_2017, title={Adaptation in Caco-2 Human Intestinal Cell Differentiation and Phenolic Transport with Chronic Exposure to Blackberry (Rubus sp.) Extract}, volume={65}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.7b00027}, abstractNote={As evidence mounts for a health-protective role of dietary phenolics, the importance of understanding factors influencing bioavailability increases. Recent evidence has suggested chronic exposure to phenolics may impact their absorption and metabolism. To explore alterations occurring from chronic dietary exposure to phenolics, Caco-2 cell monolayers were differentiated on Transwell inserts with 0–10 μM blackberry (Rubus sp.) total phenolics extracts rich in anthocyanins, flavonols, and phenolic acids. Following differentiation, apical to basolateral transport of phenolics was assessed from an acute treatment of 100 μM blackberry phenolics from 0 to 4 h. Additionally, differences in gene expression of transport and phase II metabolizing systems including ABC transporters, organic anion transporters (OATs), and uridine 5'-diphospho (UDP) glucuronosyltransferases (UGTs) were probed. After 4 h, 1 μM pretreated monolayers showed a significant (P < 0.05) decrease in the percentage of cumulative transport including less epicatechin (42.1 ± 0.53), kaempferol glucoside (23.5 ± 0.29), and dicaffeoylquinic acid (31.9 ± 0.20) compared to control. Finally, significant (P < 0.05) alterations in mRNA expression of key phase II metabolizing enzymes and transport proteins were observed with treatment. Therefore, adaptation to blackberry extract exposure may impact intestinal transport and metabolism of phenolics.}, number={13}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Redan, Benjamin W. and Albaugh, George P. and Charron, Craig S. and Novotny, Janet A. and Ferruzzi, Mario G.}, year={2017}, month={Apr}, pages={2694–2701} }
 @article{furrer_cladis_kurilich_manoharan_ferruzzi_2017, title={Changes in phenolic content of commercial potato varieties through industrial processing and fresh preparation}, volume={218}, ISSN={["1873-7072"]}, DOI={10.1016/j.foodchem.2016.08.126}, abstractNote={Reported content and process stability of phenolics in potato products is inconsistent. Changes in phenolic content of select varieties through fresh and industrial preparation/reconstitution were assessed. Total chlorogenic acids (CQAs) ranged from 43 to 953 mg/100 g dw and were more concentrated in pigmented compared to white/yellow-fleshed potatoes. Anthocyanin (ANC) content ranged from 18.6 to 22.9 mg/100 g dw and were mainly present in the flesh of pigmented potatoes. Retention of phenolics through commercial processing ranged from 49 to 85% for pigmented varieties and 32–55% for white/yellow. CQA levels were reduced through processing but to a greater extent in white relative to pigmented potatoes. ANCs were well retained through industrial processing of pigmented potatoes (79–129%). Levels of CQA were significantly (p < 0.05) lower in some industrially versus freshly processed products but not for all products. While some differences exist, overall, industrially processed potato products compare favorably to fresh preparation in levels and recovery of phenolics.}, journal={FOOD CHEMISTRY}, author={Furrer, Amber and Cladis, Dennis P. and Kurilich, Anne and Manoharan, Ramesh and Ferruzzi, Mario G.}, year={2017}, month={Mar}, pages={47–55} }
 @article{redan_chegeni_ferruzzi_2017, title={Differentiated Caco-2 cell monolayers exhibit adaptation in the transport and metabolism of flavan-3-ols with chronic exposure to both isolated flavan-3-ols and enriched extracts}, volume={8}, ISSN={["2042-650X"]}, DOI={10.1039/c6fo01289b}, abstractNote={The relatively low oral bioavailability of flavan-3-ols from acute doses is commonly highlighted as a limitation when considering the biological significance of these compounds. However, evidence suggests that the absorption of flavan-3-ols may be enhanced during periods of repeated exposure which is more representative of dietary patterns. To explore changes occurring in the upper small intestine from repeated exposure to dietary flavan-3-ols, Caco-2 human intestinal cells were cultured and differentiated in the presence of isolated flavan-3-ols epigallocatechin gallate (EGCG) and epicatechin (EC) or flavan-3-ol-rich green tea and grape seed extracts. Following differentiation, cellular accumulation, Phase II metabolism, and transcellular transport were assessed from a final acute dose of the respective pretreated compound or extract. 10 μM EGCG pretreatment significantly (P < 0.05) decreased the appearance rate of both sulfated and methyl sulfate EGCG metabolites compared to the control. In contrast, 10 μM EC pretreatment resulted in a significantly greater appearance of methylated EC from acute treatment. After 4 h, 10 μM green tea extract pretreatment resulted in a significant (P < 0.05) 38% greater cumulative transport of EC, in addition to 44-60% increased transport of EGCG and epicatechin gallate (ECG) at 60 min compared to the control. For monolayers pretreated with 10 μM grape seed extract, there was a significant (P < 0.05) 17-56% greater cumulative transport of C and EC after 4 h. Assessment of the mRNA expression of select xenobiotic and metabolizing genes revealed that pretreatment with green tea and grape seed extracts significantly (P < 0.05) increased the expression of COMT, ABCC2 and ABCB1. Overall, these results suggest that intestinal adaptation to both isolated flavan-3-ols and extracts rich in these compounds alters their intestinal transport and metabolism.}, number={1}, journal={FOOD & FUNCTION}, author={Redan, Benjamin W. and Chegeni, Mohammad and Ferruzzi, Mario G.}, year={2017}, month={Jan}, pages={111–121} }
 @misc{simon_decker_ferruzzi_giusti_mejia_goldschmidt_talcott_2017, title={Establishing Standards on Colors from Natural Sources}, volume={82}, ISSN={["1750-3841"]}, DOI={10.1111/1750-3841.13927}, abstractNote={Abstract Color additives are applied to many food, drug, and cosmetic products. With up to 85% of consumer buying decisions potentially influenced by color, appropriate application of color additives and their safety is critical. Color additives are defined by the U.S. Federal Food, Drug, and Cosmetic Act (FD&C Act) as any dye, pigment, or substance that can impart color to a food, drug, or cosmetic or to the human body. Under current U.S. Food and Drug Administration (FDA) regulations, colors fall into 2 categories as those subject to an FDA certification process and those that are exempt from certification often referred to as “natural” colors by consumers because they are sourced from plants, minerals, and animals. Certified colors have been used for decades in food and beverage products, but consumer interest in natural colors is leading market applications. However, the popularity of natural colors has also opened a door for both unintentional and intentional economic adulteration. Whereas FDA certifications for synthetic dyes and lakes involve strict quality control, natural colors are not evaluated by the FDA and often lack clear definitions and industry accepted quality and safety specifications. A significant risk of adulteration of natural colors exists, ranging from simple misbranding or misuse of the term “natural” on a product label to potentially serious cases of physical, chemical, and/or microbial contamination from raw material sources, improper processing methods, or intentional postproduction adulteration. Consistent industry‐wide safety standards are needed to address the manufacturing, processing, application, and international trade of colors from natural sources to ensure quality and safety throughout the supply chain.}, number={11}, journal={JOURNAL OF FOOD SCIENCE}, author={Simon, James E. and Decker, Eric A. and Ferruzzi, Mario G. and Giusti, M. Monica and Mejia, Carla D. and Goldschmidt, Mark and Talcott, Stephen T.}, year={2017}, month={Nov}, pages={2539–2553} }
 @article{venado_owens_ortiz_lawson_mateos-hernandez_ferruzzi_rocheford_2017, title={Genetic analysis of provitamin A carotenoid β-cryptoxanthin concentration and relationship with other carotenoids in maize grain (Zea mays L.)}, volume={37}, ISSN={1380-3743 1572-9788}, url={http://dx.doi.org/10.1007/S11032-017-0723-8}, DOI={10.1007/S11032-017-0723-8}, number={10}, journal={Molecular Breeding}, publisher={Springer Science and Business Media LLC}, author={Venado, Rafael E. and Owens, Brenda F. and Ortiz, Darwin and Lawson, Tyler and Mateos-Hernandez, Maria and Ferruzzi, Mario G. and Rocheford, Torbert R.}, year={2017}, month={Sep} }
 @article{chen_ferruzzi_wu_simon_talcott_wang_ho_todd_cooper_pasinetti_et al._2017, title={Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat}, volume={61}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/MNFR.201700111}, DOI={10.1002/MNFR.201700111}, abstractNote={The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model.(ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8-h pharmacokinetic study was performed. After 24 h, a second dose of SGP was administered and 1 h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished Cmax for all catechin, epicatechin, quercetin and resveratrol conjugated metabolites. Bioavailability was significantly lower in ZDF rats for methylated flavan-3-ol, RES, and quercetin metabolites. Significantly lower levels of metabolites of RES, quercetin, and flavan-3-ols were found in brains of ZDF rats. There was no significant difference between ZDF and LN in anthocyanins in plasma and no anthocyanins were detectable in brain extracts. ZDF rats showed significantly higher urinary excretion for all polyphenols.Diabetes may alter the overall bioavailability of some polyphenols in plasma and brain in part due to higher urinary clearance.}, number={10}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Chen, Tzu-Ying and Ferruzzi, Mario G. and Wu, Qing-Li and Simon, James E. and Talcott, Stephen T. and Wang, Jun and Ho, Lap and Todd, George and Cooper, Bruce and Pasinetti, Giulio M. and et al.}, year={2017}, month={Aug}, pages={1700111} }
 @misc{santeramo_barbieri_2017, title={On the demand for agritourism: a cursory review of methodologies and practice}, volume={14}, ISSN={["2156-8324"]}, url={http://dx.doi.org/10.1080/21568316.2015.1137968}, DOI={10.1080/21568316.2015.1137968}, abstractNote={During the last decades agritourism has expanded tremendously worldwide given visitors’ increased interest to appreciate the life in the countryside and farmers’ need to enhance their revenues from different economic activities. Despite such enlarged agritourism development, scant information is available on the state of its demand at both national and international levels. Given such a need, we cursorily reviewed the range of econometric methods employed to evaluate the demand of agritourism, summarizing the salient findings in their application. Our assessment shows that current studies provide a limited characterization of the agritourism demand, especially in terms of methods utilized and information compiled. We suggest that a broader set of economic approaches are needed to control for existing bias and model flaws, and to isolate the features and amenities pulling visitors to agritourism destinations. We also suggest expanding economic studies to fully capture the impact of increased agritourism demand in surrounding communities.}, number={1}, journal={TOURISM PLANNING & DEVELOPMENT}, author={Santeramo, Fabio Gaetano and Barbieri, Carla}, year={2017}, pages={139–148} }
 @article{li_koecher_hansen_ferruzzi_2017, title={Phenolics from Whole Grain Oat Products as Modifiers of Starch Digestion and Intestinal Glucose Transport}, volume={65}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.7b02171}, abstractNote={Four oat varieties and three product forms (porridge, cereal, and snack bar) were assessed to determine the impact of oat phenolics on starch digestibility and intestinal glucose transport. α-Amylase activity was enhanced by 20 GAE μM (gallic acid equivalent) of phenolics extracted from oat (96.7–118%, p < 0.05), while it was modestly inhibited at 500 GAE μM (83.0–95.4%). Maltose hydrolysis was reduced (49.6–82.4%, p < 0.05), albeit with high IC50 values (500–940 GAE μM). Free and bound oat phenolic extracts dose-dependently attenuated transport of d-glucose-1,2,3,4,5,6,6-d7 by Caco-2 monolayers over 60 min. Oat foods were then subjected to a coupled in vitro digestion/Caco-2 intestinal cell model to determine relevance to whole food systems. Digestive release of glucose was similar among products; however, glucose transport was significantly reduced from digesta of GMI 423 porridge and puffed cereal by 34% ± 12% and 20% ± 10% (p < 0.05) at 60 min. Results suggest phenolics might be a factor modulating glycemic response of oat products.}, number={32}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Li, Min and Koecher, Katie and Hansen, Laura and Ferruzzi, Mario G.}, year={2017}, month={Aug}, pages={6831–6839} }
 @misc{byrd-bredbenner_ferruzzi_fulgoni_murray_pivonka_wallace_2017, title={Satisfying America's Fruit Gap: Summary of an Expert Roundtable on the Role of 100% Fruit Juice}, volume={82}, ISSN={["1750-3841"]}, DOI={10.1111/1750-3841.13754}, abstractNote={Abstract The 2015 to 2020 Dietary Guidelines for Americans (DGAs) recognize the role of 100% fruit juice in health and in helping people meet daily fruit recommendations and state that 100% fruit juice is a nutrient‐dense beverage that should be a primary choice, along with water and low‐fat/fat‐free milk. The DGAs note that children are consuming 100% fruit juice within recommendations (that is, 120 to 180 mL/d for children aged 1 to 6 y and 236 to 355 mL/d for children aged 7 to 18 y). Evidence shows that compared to nonconsumers, those who consume 100% fruit juice come closer to meeting daily fruit needs and have better diet quality. In children, 100% fruit juice is associated with increased intakes of nutrients such as vitamin C, folate, and potassium. When consumed within the DGA recommendations, 100% fruit juice is not associated with overweight/obesity or childhood dental caries and does not compromise fiber intake. Preliminary data suggest that polyphenols in some 100% fruit juices may inhibit absorption of naturally occurring sugars. Given its role in promoting health and in helping people meet fruit needs, experts participating in a roundtable discussion agreed that there is no science‐based reason to restrict access to 100% fruit juice in public health nutrition policy and programs such as the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Reducing or eliminating 100% fruit juice could lead to unintended consequences such as reduced daily fruit intake and increased consumption of less nutritious beverages (for example, sugar‐sweetened beverages).}, number={7}, journal={JOURNAL OF FOOD SCIENCE}, author={Byrd-Bredbenner, Carol and Ferruzzi, Mario G. and Fulgoni, Victor L., III and Murray, Robert and Pivonka, Elizabeth and Wallace, Taylor C.}, year={2017}, month={Jul}, pages={1523–1534} }
 @article{novotny_chen_terekhov_gebauer_baer_ho_pasinetti_ferruzzi_2017, title={The effect of obesity and repeated exposure on pharmacokinetic response to grape polyphenols in humans}, volume={61}, ISSN={["1613-4133"]}, DOI={10.1002/mnfr.201700043}, abstractNote={Scope Evidence suggests that dietary pattern may affect polyphenol absorption and/or metabolism. Further, obesity is associated with lower circulating nutrients, though the reason is unclear. We investigated the pharmacokinetic (PK) response of polyphenols in obese/overweight versus lean individuals before and after repeated dosing of grape polyphenols. Methods and results A pilot study was conducted in which PK challenges were administered before and after 10 days of repeated dosing with polyphenols. Volunteers (6 lean, 6 overweight/obese) consumed resveratrol, grape seed extract, and grape juice (2125 mg total polyphenols) daily. On days 1 and 11, blood samples were collected for 6 h after the polyphenol dose and analyzed for deconjugated catechin, epicatechin, resveratrol, and quercetin. Area under the plasma polyphenol mass by time curves (AUCs) were greater for catechin, epicatechin, and quercetin on day 11 versus day 1 for low BMI individuals (p = 0.039) but not high BMI individuals. Further, AUCs were greater for epicatechin and resveratrol for low versus high BMI individuals (p = 0.041), with a similar trend for catechin (p = 0.065), on day 11 but not day 1. Conclusion These results suggest that that obesity and repeated exposure may modify polyphenol absorption and/or metabolism in humans.}, number={11}, journal={MOLECULAR NUTRITION & FOOD RESEARCH}, author={Novotny, Janet A. and Chen, Tzu-Ying and Terekhov, Anton I. and Gebauer, Sarah K. and Baer, David J. and Ho, Lap and Pasinetti, Giulio M. and Ferruzzi, Mario G.}, year={2017}, month={Nov} }
 @article{debelo_novotny_ferruzzi_2017, title={Vitamin A}, volume={8}, ISSN={["2156-5376"]}, DOI={10.3945/an.116.014720}, number={6}, journal={ADVANCES IN NUTRITION}, author={Debelo, Hawi and Novotny, Janet A. and Ferruzzi, Mario G.}, year={2017}, month={Nov}, pages={992–994} }
 @article{shahnazari_turner_iwaniec_wronski_li_ferruzzi_nissenson_halloran_2016, title={Dietary dried plum increases bone mass, suppresses proinflammatory cytokines and promotes attainment of peak bone mass in male mice}, volume={34}, ISSN={0955-2863}, url={http://dx.doi.org/10.1016/J.JNUTBIO.2016.04.007}, DOI={10.1016/J.JNUTBIO.2016.04.007}, abstractNote={Nutrition is an important determinant of bone health and attainment of peak bone mass. Diets containing dried plum (DP) have been shown to increase bone volume and strength. These effects may be linked to the immune system and DP-specific polyphenols. To better understand these relationships, we studied DP in skeletally mature (6-month-old) and growing (1- and 2-month-old) C57Bl/6 male mice. In adult mice, DP rapidly (<2 weeks) increased bone volume (+32%) and trabecular thickness (+24%). These changes were associated with decreased osteoclast surface (Oc.S/BS) and decreased serum CTX, a marker of bone resorption. The reduction in Oc.S/BS was associated with a reduction in the osteoclast precursor pool. Osteoblast surface (Ob.S/BS) and bone formation rate were also decreased suggesting that the gain in bone in adult mice is a consequence of diminished bone resorption and formation, but resorption is reduced more than formation. The effects of DP on bone were accompanied by a decline in interleukins, TNF and MCP-1, suggesting that DP is acting in part through the immune system to suppress inflammatory activity and reduce the size of the osteoclast precursor pool. Feeding DP was accompanied by an increase in plasma phenolics, some of which have been shown to stimulate bone accrual. In growing and young adult mice DP at levels as low as 5% of diet (w/w) increased bone volume. At higher levels (DP 25%), bone volume was increased by as much as 94%. These data demonstrate that DP feeding dramatically increases peak bone mass during growth.}, journal={The Journal of Nutritional Biochemistry}, publisher={Elsevier BV}, author={Shahnazari, Mohammad and Turner, Russell T. and Iwaniec, Urszula T. and Wronski, Thomas J. and Li, Min and Ferruzzi, Mario G. and Nissenson, Robert A. and Halloran, Bernard P.}, year={2016}, month={Aug}, pages={73–82} }
 @article{ortiz_rocheford_ferruzzi_2016, title={Influence of Temperature and Humidity on the Stability of Carotenoids in Biofortified Maize (Zea maysL.) Genotypes during Controlled Postharvest Storage}, volume={64}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/ACS.JAFC.5B05698}, DOI={10.1021/ACS.JAFC.5B05698}, abstractNote={Maize is a staple crop that has been the subject of biofortification efforts to increase the natural content of provitamin A carotenoids. Although significant progress toward increasing provitamin A carotenoid content in maize varieties has been made, postharvest handling factors that influence carotenoid stability during storage have not been fully established. The objectives of this study were to determine carotenoid profiles of six selected provitamin A biofortified maize genotypes at various developmental stages and assess the stability of carotenoids in maize kernels during controlled storage conditions (12 month period), including elevated temperature and relative humidity. There were no significant changes in the content of individual carotenoids within genotypes during kernel development from 45 days after pollination through the time of harvest. Carotenoid losses through traditional grain drying were also minimal (<9%). However, the stability of carotenoids in maize kernels over storage time after harvest was found to be dependent on both temperature and humidity, with variation observed among genotypes. Different forms of provitamin A carotenoids follow similar degradation rates. The genotype C17xDE3 had a degradation rate 2 times faster than those of the other genotypes evaluated (P < 0.001). These differences in carotenoid stability under controlled storage were attributed, in part, to observed differences in the physical properties of the kernels (surface area and porosity). These results support the notion that effective control of moisture content and temperature of the kernels during storage conditions is essential to reduce the speed of degradative reactions.}, number={13}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Ortiz, Darwin and Rocheford, Torbert and Ferruzzi, Mario G.}, year={2016}, month={Mar}, pages={2727–2736} }
 @article{lipkie_ferruzzi_weaver_2016, title={Low bioaccessibility of vitamin D2from yeast-fortified bread compared to crystalline D2bread and D3from fluid milks}, volume={7}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C6FO00935B}, DOI={10.1039/C6FO00935B}, abstractNote={The assessment of the efficacy of dietary and supplemental vitamin D tends to be confounded by differences in the serum 25-hydroxyvitamin D response between vitamin D2 and vitamin D3. Serum response differences from these vitamers may be due to differences in bioavailability. To address this specifically, the bioaccessibility was assessed for vitamin D2 from breads fortified with UV-treated yeast, and a benchmark against staple vitamin D3 fortified foods including bovine milks and infant formula, as well as crystalline vitamin D2 fortified bread. Fortified foods were subjected to a three-stage static in vitro digestion model, and vitamin D was analyzed by HPLC-MS. Vitamin D bioaccessibility was significantly greater from bovine milks and infant formula (71-85%) than from yeast-fortified sandwich breads (6-7%). Bioaccessibility was not different between whole wheat and white wheat bread (p > 0.05), but was ∼4× lower from yeast-fortified bread than from crystalline vitamin D2 fortified bread (p < 0.05). Intact yeast cells were observed in the digesta of yeast fortified bread. These results indicate that the low bioavailability of yeast D2 in comparison to other vitamin D2 sources is likely due to entrapment within a less digestible yeast matrix and not only to metabolic differences between vitamins D2 and D3.}, number={11}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Lipkie, Tristan E. and Ferruzzi, Mario G. and Weaver, Connie M.}, year={2016}, pages={4589–4596} }
 @article{dzakovich_ferruzzi_mitchell_2016, title={Manipulating Sensory and Phytochemical Profiles of Greenhouse Tomatoes Using Environmentally Relevant Doses of Ultraviolet Radiation}, volume={64}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/ACS.JAFC.6B02983}, DOI={10.1021/ACS.JAFC.6B02983}, abstractNote={Fruits harvested from off-season, greenhouse-grown tomato plants have a poor reputation compared to their in-season, garden-grown counterparts. Presently, there is a gap in knowledge with regard to the role of UV-B radiation (280–315 nm) in determining greenhouse tomato quality. Knowing that UV-B is a powerful elicitor of secondary metabolism and not transmitted through greenhouse glass and some greenhouse plastics, we tested the hypothesis that supplemental UV-B radiation in the greenhouse will impart quality attributes typically associated with garden-grown tomatoes. Environmentally relevant doses of supplemental UV-B radiation did not strongly affect antioxidant compounds of fruits, although the flavonol quercetin-3-O-rutinoside (rutin) significantly increased in response to UV-B. Physicochemical metrics of fruit quality attributes and consumer sensory panels were used to determine if any such differences altered consumer perception of tomato quality. Supplemental UV-A radiation (315–400 nm) pre-harvest treatments enhanced sensory perception of aroma, acidity, and overall approval, suggesting a compelling opportunity to environmentally enhance the flavor of greenhouse-grown tomatoes. The expression of the genes COP1 and HY5 were indicative of adaptation to UV radiation, which explains the lack of marked effects reported in these studies. To our knowledge, these studies represent the first reported use of environmentally relevant doses of UV radiation throughout the reproductive portion of the tomato plant life cycle to positively enhance the sensory and chemical properties of fruits.}, number={36}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Dzakovich, Michael P. and Ferruzzi, Mario G. and Mitchell, Cary A.}, year={2016}, month={Aug}, pages={6801–6808} }
 @article{li_koecher_hansen_ferruzzi_2016, title={Phenolic recovery and bioaccessibility from milled and finished whole grain oat products}, volume={7}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C6FO00760K}, DOI={10.1039/C6FO00760K}, abstractNote={Phenolics naturally present in whole grain oats are recovered well through traditional grain processing, milling and food processing.}, number={8}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Li, Min and Koecher, Katie and Hansen, Laura and Ferruzzi, Mario G.}, year={2016}, pages={3370–3381} }
 @article{camelo-méndez_ferruzzi_gonzález-aguilar_bello-pérez_2015, title={Carbohydrate and Phytochemical Digestibility in Pasta}, volume={8}, ISSN={1866-7910 1866-7929}, url={http://dx.doi.org/10.1007/S12393-015-9117-Z}, DOI={10.1007/S12393-015-9117-Z}, number={1}, journal={Food Engineering Reviews}, publisher={Springer Science and Business Media LLC}, author={Camelo-Méndez, Gustavo A. and Ferruzzi, Mario G. and González-Aguilar, Gustavo A. and Bello-Pérez, Luis A.}, year={2015}, month={Mar}, pages={76–89} }
 @article{villani_reichert_ferruzzi_pasinetti_simon_wu_2015, title={Chemical investigation of commercial grape seed derived products to assess quality and detect adulteration}, volume={170}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/J.FOODCHEM.2014.08.084}, DOI={10.1016/J.FOODCHEM.2014.08.084}, abstractNote={Fundamental concerns in quality control arise due to increasing use of grape seed extract (GSE) and the complex chemical composition of GSE. Proanthocyanidin monomers and oligomers are the major bioactive compounds in GSE. Given no standardized criteria for quality, large variation exists in the composition of commercial GSE supplements. Using HPLC/UV/MS, 21 commercial GSE containing products were purchased and chemically profiled, major compounds quantitated, and compared against authenticated grape seed extract, peanut skin extract, and pine bark extract. The antioxidant capacity and total polyphenol content for each sample was also determined and compared using standard techniques. Nine products were adulterated, found to contain peanut skin extract. A wide degree of variability in chemical composition was detected in commercial products, demonstrating the need for development of quality control standards for GSE. A TLC method was developed to allow for rapid and inexpensive detection of adulteration in GSE by peanut skin.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Villani, Tom S. and Reichert, William and Ferruzzi, Mario G. and Pasinetti, Giulio M. and Simon, James E. and Wu, Qingli}, year={2015}, month={Mar}, pages={271–280} }
 @article{xu_simon_welch_wightman_ferruzzi_ho_pasinetti_wu_2015, title={Correction to Survey of Polyphenol Constituents in Grapes and Grape-Derived Products}, volume={63}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/ACS.JAFC.5B01552}, DOI={10.1021/ACS.JAFC.5B01552}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to Survey of Polyphenol Constituents in Grapes and Grape-Derived ProductsYanping Xu, James E. Simon, Cara Welch, JoLynne D. Wightman, Mario G. Ferruzzi, Lap Ho, Giulio M. Pasinetti, and Qingli Wu*Cite this: J. Agric. Food Chem. 2015, 63, 14, 3804Publication Date (Web):April 6, 2015Publication History Published online6 April 2015Published inissue 15 April 2015https://doi.org/10.1021/acs.jafc.5b01552Copyright © 2015 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views468Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (110 KB) Get e-Alertsclose Get e-Alerts}, number={14}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Xu, Yanping and Simon, James E. and Welch, Cara and Wightman, JoLynne D. and Ferruzzi, Mario G. and Ho, Lap and Pasinetti, Giulio M. and Wu, Qingli}, year={2015}, month={Apr}, pages={3804–3804} }
 @article{blount_ferruzzi_raftery_pasinetti_dixon_2015, title={Corrigendum to “Enzymatic synthesis of substituted epicatechins for bioactivity studies in neurological disorders” [Biochem. Biophys. Res. Commun. 417 (1) (6 January 2012) 457–461]}, volume={460}, ISSN={0006-291X}, url={http://dx.doi.org/10.1016/J.BBRC.2015.02.142}, DOI={10.1016/J.BBRC.2015.02.142}, number={2}, journal={Biochemical and Biophysical Research Communications}, publisher={Elsevier BV}, author={Blount, Jack W. and Ferruzzi, Mario and Raftery, Dan and Pasinetti, Giulio M. and Dixon, Richard A.}, year={2015}, month={May}, pages={489} }
 @article{simsek_quezada-calvillo_ferruzzi_nichols_hamaker_2015, title={Dietary Phenolic Compounds Selectively Inhibit the Individual Subunits of Maltase-Glucoamylase and Sucrase-Isomaltase with the Potential of Modulating Glucose Release}, volume={63}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/JF505425D}, DOI={10.1021/JF505425D}, abstractNote={In this study, it was hypothesized that dietary phenolic compounds selectively inhibit the individual C- and N-terminal (Ct, Nt) subunits of the two small intestinal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), for a modulated glycemic carbohydrate digestion. The inhibition by chlorogenic acid, caffeic acid, gallic acid, (+)-catechin, and (-)-epigallocatechin gallate (EGCG) on individual recombinant human Nt-MGAM and Nt-SI and on mouse Ct-MGAM and Ct-SI was assayed using maltose as the substrate. Inhibition constants, inhibition mechanisms, and IC50 values for each combination of phenolic compound and enzymatic subunit were determined. EGCG and chlorogenic acid were found to be more potent inhibitors for selectively inhibiting the two subunits with highest activity, Ct-MGAM and Ct-SI. All compounds displayed noncompetitive type inhibition. Inhibition of fast-digesting Ct-MGAM and Ct-SI by EGCG and chlorogenic acid could lead to a slow, but complete, digestion of starch for improved glycemic response of starchy foods with potential health benefit.}, number={15}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Simsek, Meric and Quezada-Calvillo, Roberto and Ferruzzi, Mario G. and Nichols, Buford L. and Hamaker, Bruce R.}, year={2015}, month={Apr}, pages={3873–3879} }
 @article{malaypally_liceaga_kim_ferruzzi_martin_goforth_2015, title={Influence of molecular weight on intracellular antioxidant activity of invasive silver carp ( Hypophthalmichthys molitrix ) protein hydrolysates}, volume={18}, ISSN={1756-4646}, url={http://dx.doi.org/10.1016/J.JFF.2014.06.011}, DOI={10.1016/J.JFF.2014.06.011}, abstractNote={Protein hydrolysates from underutilized silver carp (SPH) were prepared using Flavourzyme (F-15 to F-60) and Alcalase (A-15 to A-60) at 15, 30, 45 and 60 min, respectively. SPH F-30 and A-60 showed promising chemical-based antioxidant activity and were further fractionated according to size to evaluate caco-2 cell based antioxidant activity. F-30 and A-60 peptide fractions with <3 kDa (F-30 < 3, A-60 < 3) showed higher cell-based antioxidant activity under stressed and non-stressed conditions. Further, IC50 values of F-30 < 3 (1–3 mg/mL) was lower than A-60 < 3 fractions (4 to 12 mg/mL), indicating higher cellular antioxidant activity of F-30 < 3 compared to A-60 < 3 under all conditions. The presence of active peptides with desired amino acid sequence in F-30 < 3 compared to A-60 < 3 may have contributed to its higher cellular antioxidant activity. Overall, SPH exhibited antioxidant capacity, hence using an underutilized, invasive fish for environmental and economic gain in the form of promising functional ingredients.}, journal={Journal of Functional Foods}, publisher={Elsevier BV}, author={Malaypally, Sravanthi P. and Liceaga, Andrea M. and Kim, Kee-Hong and Ferruzzi, Mario and Martin, Fernanda San and Goforth, Reuben R.}, year={2015}, month={Oct}, pages={1158–1166} }
 @article{ho_ferruzzi_liceaga_san martín-gonzález_2015, title={Microwave-assisted extraction of lycopene in tomato peels: Effect of extraction conditions on all-trans and cis-isomer yields}, volume={62}, ISSN={0023-6438}, url={http://dx.doi.org/10.1016/J.LWT.2014.12.061}, DOI={10.1016/J.LWT.2014.12.061}, abstractNote={Lycopene is the primary carotenoid in tomato peels, a processing byproduct, and can be used as a natural color or bioactive ingredient. Unfortunately, extractions are inefficient as lycopene is extremely nonpolar and susceptible to degradation. As a rapid technique, microwave-assisted extraction (MAE) potentially offers efficient lycopene recovery. Thus, the objectives of this research were to: 1) optimize MAE of lycopene from tomato peels and 2) evaluate the effect of treatment on all-trans and isomer yields. Response surface methodology (RSM) was employed to optimize lycopene extraction with solvent ratio solid–liquid ratios, microwave power, and delivered energy equivalents as factors. High performance liquid chromatography with a diode array detector (HPLC-DAD) was used for isomer separation and quantification. Optimum MAE conditions were determined as: 0:10 solvent ratio at 400 W with a yield of 13.592 mg/100 g of extracted all-trans-lycopene. RSM suggested that ethyl acetate was a better MAE solvent for lycopene recovery as compared to hexane, which overall extracted less lycopene. HPLC-DAD indicated that MAE significantly improved all-trans and total lycopene yields, while conventional extraction demonstrated higher proportions of cis-isomer yields. Additionally, electron micrographs showed that significant structural disruption occurred in MAE-treated samples, possibly allowing for the improved lycopene extraction.}, number={1}, journal={LWT - Food Science and Technology}, publisher={Elsevier BV}, author={Ho, K.K.H.Y. and Ferruzzi, M.G. and Liceaga, A.M. and San Martín-González, M.F.}, year={2015}, month={Jun}, pages={160–168} }
 @article{zhao_wang_bi_ferruzzi_yemul_freire_mazzola_ho_dubner_pasinetti_2015, title={Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction}, volume={89}, ISSN={0197-0186}, url={http://dx.doi.org/10.1016/J.NEUINT.2015.07.023}, DOI={10.1016/J.NEUINT.2015.07.023}, abstractNote={Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.}, journal={Neurochemistry International}, publisher={Elsevier BV}, author={Zhao, Wei and Wang, Jun and Bi, Weina and Ferruzzi, Mario and Yemul, Shrishailam and Freire, Daniel and Mazzola, Paolo and Ho, Lap and Dubner, Lauren and Pasinetti, Giulio Maria}, year={2015}, month={Oct}, pages={191–197} }
 @article{chen_kritchevsky_hargett_feller_klobusnik_song_cooper_jouni_ferruzzi_janle_2015, title={Plasma bioavailability and regional brain distribution of polyphenols from apple/grape seed and bilberry extracts in a young swine model}, volume={59}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/MNFR.201500224}, DOI={10.1002/MNFR.201500224}, abstractNote={Scope The pharmacokinetics, bioavailability, and regional brain distribution of polyphenols from apple-grape seed extract (AGSE) mixture and bilberry extract were studied after 3 weeks of dosing in weanling pigs. Materials and methods Weanling piglets were treated for 3 weeks with extracts of (AGSE) or bilberry extracts, using a physiological (27.5 mg/kg) or supplement (82.5 mg/kg) dose. A 24-h pharmacokinetic study was conducted and brain tissue was harvested. Major flavan-3-ol and flavonol metabolites including catechin-O-β-glucuronide, epicatechin-O-β-glucuronide, 3′O-methyl-catechin-O-β-glucuronide, 3′O-methyl-epicatechin-O-β-glucuronide, quercetin-O-β-glucuronide, and O-methyl-quercetin-O-β-glucuronide were analyzed in plasma, urine, and regional brain extracts from AGSE groups. Anthocyanidin-O-galactosides and O-glucosides of delphinidin (Del), cyanidin (Cyn), petunidin (Pet), peonidin (Peo), and malvidin (Mal) were analyzed in plasma, urine, and brain extracts from bilberry groups. Conclusion Significant plasma dose-dependence was observed in flavan-3-ol metabolites of the AGSE group and in Mal, Del and Cyn galactosides and Pet, Peo, and Cyn glucosides of the bilberry groups. In the brain, a significant dose dependence was found in the cerebellum and frontal cortex in all major flavan-3-ol metabolites. All anthocyanidin glycosides, except for delphinidin, showed a dose-dependent increase in the cerebellum.}, number={12}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Chen, Tzu-Ying and Kritchevsky, Janice and Hargett, Katherine and Feller, Kathryn and Klobusnik, Ryan and Song, Brian J. and Cooper, Bruce and Jouni, Zeina and Ferruzzi, Mario G. and Janle, Elsa M.}, year={2015}, month={Oct}, pages={2432–2447} }
 @article{wang_ho_faith_ono_janle_lachcik_cooper_jannasch_d'arcy_williams_et al._2015, title={Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease β-amyloid oligomerization}, volume={59}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/MNFR.201400544}, DOI={10.1002/MNFR.201400544}, abstractNote={Scope Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age‐related neurodegenerative disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE‐derived phenolic acid in the brain. Methods and results We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3‐hydroxybenzoic acid and 3‐(3´‐hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3‐hydroxybenzoic acid and 3‐(3´‐hydroxyphenyl)propionic acid potently interfere with the assembly of β‐amyloid peptides into neurotoxic β‐amyloid aggregates that play key roles in AD pathogenesis. Conclusion Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.}, number={6}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Wang, Dongjie and Ho, Lap and Faith, Jeremiah and Ono, Kenjiro and Janle, Elsa M. and Lachcik, Pamela J. and Cooper, Bruce R. and Jannasch, Amber H. and D'Arcy, Bruce R. and Williams, Barbara A. and et al.}, year={2015}, month={Apr}, pages={1025–1040} }
 @article{blount_redan_ferruzzi_reuhs_cooper_harwood_shulaev_pasinetti_dixon_2015, title={Synthesis and Quantitative Analysis of Plasma-Targeted Metabolites of Catechin and Epicatechin}, volume={63}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/JF505922B}, DOI={10.1021/JF505922B}, abstractNote={Grape seed polyphenolic extract (GSPE) rich in the flavan-3-ols (+)-catechin and (-)-epicatechin beneficially modulates Alzheimer's Disease phenotypes in animal models. The parent molecules in the extract are converted to a series of methylated and glucuronidated derivatives. To fully characterize these metabolites and establish a robust quantitative assay of their levels in biological fluids, we have implemented a partial synthetic approach utilizing chemical methylation followed by enzymatic glucuronidation. Liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to assign unequivocal structures to the compounds. An analytical method using solid-phase extraction and LC-MS/MS in selective reaction monitoring mode (SRM) was validated for their quantitation in plasma. These studies provide a basis for improvements in future work on the bioavailability, metabolism, and mechanism of action of metabolites derived from dietary flavan-3-ols in a range of interventions.}, number={8}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Blount, Jack W. and Redan, Benjamin W. and Ferruzzi, Mario G. and Reuhs, Bradley L. and Cooper, Bruce R. and Harwood, John S. and Shulaev, Vladimir and Pasinetti, Giulio and Dixon, Richard A.}, year={2015}, month={Feb}, pages={2233–2240} }
 @article{song_manganais_ferruzzi_2015, title={Thermal degradation of green tea flavan-3-ols and formation of hetero- and homocatechin dimers in model dairy beverages}, volume={173}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/J.FOODCHEM.2014.10.026}, DOI={10.1016/J.FOODCHEM.2014.10.026}, abstractNote={Interactions between polyphenols and macromolecules may impact polyphenol stability and bioavailability from foods. The impact of milk on tea flavan-3-ol stability to thermal treatment was investigated. Single strength (36.2 protein per L), quarter strength (9.0 g protein per L) milk, and control model beverages were incubated with epigallocatechin gallate and green tea extract at 62 or 37 °C for 180 min. Intact flavan-3-ols and select auto-oxidation products [theasinesins (THSNs) and P-2 dimers] were quantified by LC-MS. Generally, greater polyphenol to protein ratios increased first order degradation rates, consequently decreasing formation of oxidation products. The presence of galloyl and hydroxy moieties was associated with higher stability of monomeric flavan-3-ols with increasing protein concentrations suggesting potential for protein affinity to stabilise flavan-3-ols to thermal treatment. Absence of these moieties led to no observable improvements in stability. These results suggest that protein interactions may be useful in stabilising flavan-3-ols through thermal processing.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Song, Brian J. and Manganais, Chris and Ferruzzi, Mario G.}, year={2015}, month={Apr}, pages={305–312} }
 @article{lipkie_banavara_shah_morrow_mcmahon_jouni_ferruzzi_2014, title={Caco-2 accumulation of lutein is greater from human milk than from infant formula despite similar bioaccessibility}, volume={58}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/MNFR.201400126}, DOI={10.1002/MNFR.201400126}, abstractNote={Scope Clinical evidence suggests that the bioavailability of lutein is lower from infant formula than from human milk. The purpose of this study was to assess characteristics of human milk and lutein‐fortified infant formula that may impact carotenoid delivery. Methods and results Carotenoid bioaccessibility and intestinal absorption were modeled by in vitro digestion coupled with Caco‐2 human intestinal cell culture. Twelve human milk samples were assessed from 1–6 months postpartum, and 10 lutein‐fortified infant formula samples from three lutein sources in both ready‐to‐use and reconstituted powder forms. The relative bioaccessibility of lutein was not different ( p > 0.05) between human milk (29 ± 2%) and infant formula (36 ± 4%). However, lutein delivery was 4.5 times greater from human milk than infant formula when including Caco‐2 accumulation efficiency. Caco‐2 accumulation of lutein was increasingly efficient with decreasing concentration of lutein from milk. Carotenoid bioaccessibility and Caco‐2 accumulation were not affected by lactation stage, total lipid content, lutein source, or form of infant formula (powder vs. liquid). Conclusion These data suggest that the bioavailability of carotenoids is greater from human milk than infant formula primarily due to intestinal absorptive processes, and that absorption of lutein is potentiated by factors from human milk especially at low lutein concentration.}, number={10}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Lipkie, Tristan E. and Banavara, Dattatreya and Shah, Bhavini and Morrow, Ardythe L. and McMahon, Robert J. and Jouni, Zeina E. and Ferruzzi, Mario G.}, year={2014}, month={Jul}, pages={2014–2022} }
 @article{xu_simon_welch_wightman_ferruzzi_ho_pasinetti_wu_2014, title={Correction to Survey of Polyphenol Constituents in Grapes and Grape-Derived Products}, volume={62}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/JF5012819}, DOI={10.1021/JF5012819}, number={13}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Xu, Yanping and Simon, James E. and Welch, Cara and Wightman, JoLynne D. and Ferruzzi, Mario G. and Ho, Lap and Pasinetti, Giulio M. and Wu, Qingli}, year={2014}, month={Mar}, pages={3010–3010} }
 @article{sharma_joy_boushey_ferruzzi_leonov_mccrory_2014, title={Effects of Para-Aminobenzoic Acid (PABA) Form and Administration Mode on PABA Recovery in 24-Hour Urine Collections}, volume={114}, ISSN={2212-2672}, url={http://dx.doi.org/10.1016/J.JAND.2013.07.045}, DOI={10.1016/J.JAND.2013.07.045}, abstractNote={Para-aminobenzoic acid (PABA) has long been used as an objective measure to assess completeness of 24-hour urine collections. However, pharmaceutical-grade PABA for human ingestion is not available in the United States. An alternative, the potassium salt of PABA, aminobenzoate potassium, can be obtained for clinical use, although it has not yet been validated in this role. Both PABA and aminobenzoate potassium can be directly ingested in their tablet or capsule forms or added to food before consumption. Our aim was to investigate the effect of form (PABA vs aminobenzoate potassium) and administration mode (directly ingested as a tablet/capsule vs added to food) on urinary PABA recovery levels. Twenty healthy participants underwent 3 test days separated by two 24-hour wash-out periods. Three test conditions, one on each test day, were investigated in randomized order: PABA tablet, aminobenzoate potassium capsule, and PABA or aminobenzoate potassium in food. Ingestion of each dose was supervised and participants performed the 24-hour urine collections while free-living. The 24-hour urine collections were analyzed for PABA recovery (%R) levels using a colorimetric assay. Recoveries 85% to 110% were deemed complete and those >110% were reanalyzed by high pressure liquid chromatography and mass spectrometry. Only complete collections (>85%R) were included in analyses. The recovery for the PABA tablet, aminobenzoate potassium capsule, and PABA/aminobenzoate potassium in food were similar at 98.8%R±2.0%R, 95.1%R±2.3%R, and 93.2%R±2.1%R, respectively, and did not differ significantly. These results suggest that aminobenzoate potassium may be used as an alternative to PABA for assessing the completeness of 24-hour urine collections and to track compliance with consuming provided diets in community-dwelling studies.}, number={3}, journal={Journal of the Academy of Nutrition and Dietetics}, publisher={Elsevier BV}, author={Sharma, Rashmi S. and Joy, Raechel C. and Boushey, Carol J. and Ferruzzi, Mario G. and Leonov, Alexei P. and McCrory, Megan A.}, year={2014}, month={Mar}, pages={457–463} }
 @article{bordenave_hamaker_ferruzzi_2014, title={Nature and consequences of non-covalent interactions between flavonoids and macronutrients in foods}, volume={5}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C3FO60263J}, DOI={10.1039/C3FO60263J}, abstractNote={Many of the potential health benefits of flavonoids have been associated with their specific chemical and biological properties including their ability to interact and bind non-covalently to macronutrients in foods. While flavonoid-protein interactions and binding have been the subject of intensive study, significantly less is understood about non-covalent interactions with carbohydrates and lipids. These interactions with macronutrients are likely to impact both the flavonoid properties in foods, such as their radical scavenging activity, and the food or beverage matrix itself, including their taste, texture and other sensorial properties. Overall, non-covalent binding of flavonoids with macronutrients is primarily driven by van der Waals interactions. From the flavonoid perspective, these interactions are modulated by characteristics such as degree of polymerization, molecular flexibility, number of external hydroxyl groups, or number of terminal galloyl groups. From the macronutrient standpoint, electrostatic and ionic interactions are generally predominant with carbohydrates, while hydrophobic interactions are generally predominant with lipids and mainly limited to interactions with flavonols. All of these interactions are involved in flavonoid-protein interactions. While primarily associated with undesirable characteristics in foods and beverages, such as astringency, negative impact on macronutrient digestibility and hazing, more recent efforts have attempted to leverage these interactions to develop controlled delivery systems or strategies to enhance flavonoids bioavailability. This paper aims at reviewing the fundamental bases for non-covalent interactions, their occurrence in food and beverage systems and their impact on the physico-chemical, organoleptic and some nutritional properties of food.}, number={1}, journal={Food Funct.}, publisher={Royal Society of Chemistry (RSC)}, author={Bordenave, Nicolas and Hamaker, Bruce R. and Ferruzzi, Mario G.}, year={2014}, pages={18–34} }
 @article{strathearn_yousef_grace_roy_tambe_ferruzzi_wu_simon_lila_rochet_et al._2014, title={Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson׳s disease}, volume={1555}, ISSN={0006-8993}, url={http://dx.doi.org/10.1016/J.BRAINRES.2014.01.047}, DOI={10.1016/J.BRAINRES.2014.01.047}, abstractNote={Neuropathological evidence indicates that dopaminergic cell death in Parkinson׳s disease (PD) involves impairment of mitochondrial complex I, oxidative stress, microglial activation, and the formation of Lewy bodies. Epidemiological findings suggest that the consumption of berries rich in anthocyanins and proanthocyanidins may reduce PD risk. In this study, we investigated whether extracts rich in anthocyanins, proanthocyanidins, or other polyphenols suppress the neurotoxic effects of rotenone in a primary cell culture model of PD. Dopaminergic cell death elicited by rotenone was suppressed by extracts prepared from blueberries, grape seed, hibiscus, blackcurrant, and Chinese mulberry. Extracts rich in anthocyanins and proanthocyanidins exhibited greater neuroprotective activity than extracts rich in other polyphenols, and a number of individual anthocyanins interfered with rotenone neurotoxicity. The blueberry and grape seed extracts rescued rotenone-induced defects in mitochondrial respiration in a dopaminergic cell line, and a purple basal extract attenuated nitrite release from microglial cells stimulated by lipopolysaccharide. These findings suggest that anthocyanin- and proanthocyanidin-rich botanical extracts may alleviate neurodegeneration in PD via enhancement of mitochondrial function.}, journal={Brain Research}, publisher={Elsevier BV}, author={Strathearn, K.E. and Yousef, G.G. and Grace, M.H. and Roy, S.L. and Tambe, M.A. and Ferruzzi, M.G. and Wu, Q.-L. and Simon, J.E. and Lila, M.A. and Rochet, J.-C. and et al.}, year={2014}, month={Mar}, pages={60–77} }
 @article{pawlowski_martin_mccabe_ferruzzi_weaver_2014, title={Plum and Soy Aglycon Extracts Superior at Increasing Bone Calcium Retention in Ovariectomized Sprague Dawley Rats}, volume={62}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/JF403310Q}, DOI={10.1021/JF403310Q}, abstractNote={Plant-derived polyphenols have been shown to influence bone turnover and bone properties in the estrogen-depleted state. We used a crossover design in ovariectomized rats (n = 16 rats for each diet) to investigate the effect of supplementation of two doses each of blueberry, plum, grape, grape seed extract, and resveratrol on bone. We tested the aglycon and glucoside forms of genistein to quantify differences in efficacy on bone calcium retention. Rats were given an intravenous dose of 45Ca to prelabel bone, and bone calcium retention was assessed by urinary excretion of 45Ca:Ca ratio during an intervention period compared with nonintervention. Genistein aglycon increased bone calcium retention significantly (p < 0.05) more than the glucoside (22% vs 13%, respectively). Plum extract (0.45% w/w total dietary polyphenols) and resveratrol (0.2% w/w total dietary polyphenols) were also effective, increasing bone calcium retention by 20% (p = 0.0153) and 14% (p = 0.0012), respectively. Several polyphenolic-rich diets improved bone calcium retention.}, number={26}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Pawlowski, Jessica W. and Martin, Berdine R. and McCabe, George P. and Ferruzzi, Mario G. and Weaver, Connie M.}, year={2014}, month={Jun}, pages={6108–6117} }
 @article{d'imperio_cardinali_d'antuono_linsalata_minervini_redan_ferruzzi_2014, title={Stability–activity of verbascoside, a known antioxidant compound, at different pH conditions}, volume={66}, ISSN={0963-9969}, url={http://dx.doi.org/10.1016/J.FOODRES.2014.09.037}, DOI={10.1016/J.FOODRES.2014.09.037}, abstractNote={Verbascoside (VB) is a phenolic antioxidant present in different plants, but, as reported for other polyphenols, could be unstable at different pH conditions. The aim of this work was to assess how chemical modification of VB, occurring during incubation at pH values similar to gastric (pH 3) and intestinal (pH 7) conditions, may impact antioxidant activity in two human intestinal cells lines. Quali-quantitative approaches were performed in order to evaluate the specific interactions between VB and its derivatives. HPLC analysis was performed to assess possible VB transformation into derivative products. The antioxidant activity of a mixture of VB, isoverbascoside (IsoVB) and oxidized products (obtained after incubation at pH 7), or purified VB and IsoVB, was assessed in two human intestinal cell lines (HT-29 and Caco-2) using a DCFH-DA probe. VB was stable at pH 3 with a recovery of ~ 100% after 24 h. In contrast, VB was unstable at pH 7, with a loss of 62.4%, transforming into IsoVB and other oxidative products. Cellular antioxidant assays found that the mixture of oxidized VB products resulted less active (EC50 ranging from 2.7 to 3.4 μM) than VB (EC50 ranging from 0.24 to 0.29 μM), IsoVB (EC50 ranging from 0.85 to 1.4 μM), and VB + IsoVB (EC50 ranging from 0.12 to 0.21 μM). Cellular uptake of IsoVB was found to differ between cell lines, with higher uptake by Caco-2 compared to HT-29. Both graphical and mathematical methods identified different interactions between VB and IsoVB on the two cell lines. In conclusion, the antioxidant activity of VB can be modified by the conditions present in intestinal environment.}, journal={Food Research International}, publisher={Elsevier BV}, author={D'Imperio, M. and Cardinali, A. and D'Antuono, I. and Linsalata, V. and Minervini, F. and Redan, B.W. and Ferruzzi, M.G.}, year={2014}, month={Dec}, pages={373–378} }
 @article{moser_chegeni_jones_liceaga_ferruzzi_2014, title={The effect of milk proteins on the bioaccessibility of green tea flavan-3-ols}, volume={66}, ISSN={0963-9969}, url={http://dx.doi.org/10.1016/J.FOODRES.2014.09.018}, DOI={10.1016/J.FOODRES.2014.09.018}, abstractNote={Abstract While the impact of interactions between flavan-3-ol and protein on food quality has been reported, the ability of these interactions to modify flavan-3-ol bioavailability remains unclear. The objectives of this study were to characterize the influence of milk proteins and mineral components of the milk matrix on in vitro bioaccessibility of green tea flavan-3-ols and to assess the relative impact of protein digestibility in the GI tract on protein-flavan-3-ol binding. Protein solutions containing sodium-caseinate (S-CSN, 35.6 mg/mL), α-lactalbumin (α-LA, 1 mg/mL), β-lactoglobulin (β-LG, 3.5 mg/mL), or non-fat dry milk (NFDM) were prepared in Jenness Koops (JK) buffer containing milk salts and formulated at 10–40% (v/v) into green tea beverages containing 0.6 mg/mL total flavan-3-ols. Samples were subjected to a three-stage in vitro digestion to assess flavan-3-ol digestive release and stability (bioaccessibility). Milk protein, most notably S-CSN, significantly decreased (p}, journal={Food Research International}, publisher={Elsevier BV}, author={Moser, Sydney and Chegeni, Mohammad and Jones, Owen G. and Liceaga, Andrea and Ferruzzi, Mario G.}, year={2014}, month={Dec}, pages={297–305} }
 @article{failla_chitchumronchokchai_ferruzzi_goltz_campbell_2014, title={Unsaturated fatty acids promote bioaccessibility and basolateral secretion of carotenoids and α-tocopherol by Caco-2 cells}, volume={5}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C3FO60599J}, DOI={10.1039/C3FO60599J}, abstractNote={Bioavailability of carotenoids and tocopherols from foods is determined by the efficiency of transfer from food/meal to mixed micelles during digestion, incorporation into chylomicrons for trans-epithelial transport to lymphatic/blood system, and distribution to target tissues.}, number={6}, journal={Food Funct.}, publisher={Royal Society of Chemistry (RSC)}, author={Failla, Mark L. and Chitchumronchokchai, Chureeporn and Ferruzzi, Mario G. and Goltz, Shellen R. and Campbell, Wayne W.}, year={2014}, pages={1101–1112} }
 @article{song_jouni_ferruzzi_2013, title={Assessment of phytochemical content in human milk during different stages of lactation}, volume={29}, ISSN={0899-9007}, url={http://dx.doi.org/10.1016/j.nut.2012.07.015}, DOI={10.1016/j.nut.2012.07.015}, abstractNote={The present study reports the presence of several carotenoids and flavonoids in human milk samples.Samples were collected from 17 women who delivered healthy term babies (≥ 37 wk of gestation) at 1-, 4-, and 13-wk postpartum intervals.Epicatechin (63.7-828.5 nmol/L), epicatechin gallate (55.7-645.6 nmol/L), epigallocatechin gallate (215.1-2364.7 nmol/L), naringenin (64.1-722.0 nmol/L), kaempferol (7.8-71.4 nmol/L), hesperetin (74.8-1603.1 nmol/L), and quercetin (32.5-108.6 nmol/L) were present in human milk samples with high inter-/intraindividual variability. With the exception of kaempferol, the mean flavonoid content in human milk was not statistically different among lactation stages. In contrast, carotenoids α-carotene (59.0-23.2 nmol/L), β-carotene (164.3-88.0 nmol/L), α-cryptoxanthin (30.6-13.5 nmol/L), β-cryptoxanthin (57.4-24.8 nmol/L), zeaxanthin (46.3-21.4 nmol/L), lutein (121.2-56.4 nmol/L), and lycopene (119.9-49.5 nmol/L) significantly decreased from weeks 1 to 13 of lactation.The observed differences in the relative concentrations of the two phytochemical classes in human milk may be a result of several factors, including dietary exposure, stability in the milk matrix, efficiency of absorption/metabolism, and transfer from plasma to human milk. These data support the notion that flavonoids, as with carotenoids, are dietary phytochemicals present in human milk and potentially available to breast-fed infants.}, number={1}, journal={Nutrition}, publisher={Elsevier BV}, author={Song, Brian J. and Jouni, Zeina E. and Ferruzzi, Mario G.}, year={2013}, month={Jan}, pages={195–202} }
 @article{serrano-niño_cavazos-garduño_hernandez-mendoza_applegate_ferruzzi_san martin-gonzález_garcía_2013, title={Assessment of probiotic strains ability to reduce the bioaccessibility of aflatoxin M1 in artificially contaminated milk using an in vitro digestive model}, volume={31}, ISSN={0956-7135}, url={http://dx.doi.org/10.1016/j.foodcont.2012.09.023}, DOI={10.1016/j.foodcont.2012.09.023}, abstractNote={Abstract Aflatoxin M 1 (AFM 1 ) is a highly toxic compound, stable during milk processing, cheese ripening and storage. Hence, it may be found as contaminant in milk and dairy products with hazardous effects for human beings. Different efforts have been made to detoxify toxin-contaminated food, or to decrease its absorption at intestinal level. In this regard, several in vitro and in vivo studies have demonstrated the potential of probiotic bacteria to remove aflatoxins from model systems. Therefore, the aims of this study were to assess the ability of five probiotic strains to bind AFM 1 in PBS, and to reduce its bioaccessibility in artificially contaminated milk using an in vitro digestive model. All assessed strains exhibited different degrees of aflatoxin binding in PBS, ranging from 19.95 to 25.43%. Moreover, AFM 1 's bioaccessibility in the in vitro digestive model was reduced from 22.72 to 45.17%, depending on assessed probiotic strain. The results of this work suggest that the probiotic strains tested could help to reduce harmful effects of AFM 1 to humans exposed to the aflatoxin through consumption of contaminated milk and/or dairy products.}, number={1}, journal={Food Control}, publisher={Elsevier BV}, author={Serrano-Niño, J.C. and Cavazos-Garduño, A. and Hernandez-Mendoza, A. and Applegate, B. and Ferruzzi, M.G. and San Martin-González, M.F. and García, H.S.}, year={2013}, month={May}, pages={202–207} }
 @article{cardinali_rotondo_minervini_linsalata_d'antuono_debellis_ferruzzi_2013, title={Assessment of verbascoside absorption in human colonic tissues using the Ussing chamber model}, volume={54}, ISSN={0963-9969}, url={http://dx.doi.org/10.1016/J.FOODRES.2013.06.017}, DOI={10.1016/J.FOODRES.2013.06.017}, abstractNote={The intestinal absorption of verbascoside (VB), a phenylpropanoid glycoside, extracted and purified from olive mill waste water (OMWW), was investigated using viable and healthy human colonic tissues, mounted in an Ussing chamber. Additionally, VB absorption and transport through the intestinal mucosa were quantified using permeability coefficients. VB absorption was time-dependent and varied in relation to the specific colonic segments considered. In particular, major uptake/absorption (0.50 μg/cm2) occurred between 5 and 15 min in the proximal tract of the colon, followed by descending colon (0.38 μg/cm2) between 30 and 60 min, and sigmoid–rectum colon (0.34 μg/cm2) at 60 min. Overall, VB was absorbed rapidly, with an average uptake of 0.29 μg VB per cm2, corresponding to a total accumulation efficiency of ~ 0.12%. Moreover, the presence of the VB in the basolateral side supported the hypothesis of its bioavailability in the extent of 0.1%. In addition, the permeability coefficient calculation has contributed in a deeper understanding of VB absorption and transport across the human intestinal barrier and could be utilized for other polyphenols present in food and in dietary supplements.}, number={1}, journal={Food Research International}, publisher={Elsevier BV}, author={Cardinali, Angela and Rotondo, Floriana and Minervini, Fiorenza and Linsalata, Vito and D'Antuono, Isabella and Debellis, Lucantonio and Ferruzzi, Mario G.}, year={2013}, month={Nov}, pages={132–138} }
 @article{lipkie_de moura_zhao_albertsen_che_glassman_ferruzzi_2013, title={Bioaccessibility of Carotenoids from Transgenic Provitamin A Biofortified Sorghum}, volume={61}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/JF305361S}, DOI={10.1021/JF305361S}, abstractNote={Biofortified sorghum (Sorghum bicolor (L.) Moench) lines are being developed to target vitamin A deficiency in Sub-Saharan Africa, but the delivery of provitamin A carotenoids from such diverse germplasms has not been evaluated. The purpose of this study was to screen vectors and independent transgenic events for the bioaccessibility of provitamin A carotenoids using an in vitro digestion model. The germplasm background and transgenic sorghum contained 1.0-1.5 and 3.3-14.0 μg/g β-carotene equivalents on a dry weight basis (DW), respectively. Test porridges made from milled transgenic sorghum contained up to 250 μg of β-carotene equivalents per 100 g of porridge on a fresh weight basis (FW). Micellarization efficiency of all-trans-β-carotene was lower (p < 0.05) from transgenic sorghum (1-5%) than from null/nontransgenic sorghum (6-11%) but not different between vector constructs. Carotenoid bioaccessibility was significantly improved (p < 0.05) by increasing the amount of coformulated lipid in test porridges from 5% w/w to 10% w/w. Transgenic sorghum event Homo188-A contained the greatest bioaccessible β-carotene content, with a 4-8-fold increase from null/nontransgenic sorghum. While the bioavailability and bioconversion of provitamin A carotenoids from these grains must be confirmed in vivo, these data support the notion that biofortification of sorghum can enhance total and bioaccessible provitamin A carotenoid levels.}, number={24}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Lipkie, Tristan E. and De Moura, Fabiana F. and Zhao, Zuo-Yu and Albertsen, Marc C. and Che, Ping and Glassman, Kimberly and Ferruzzi, Mario G.}, year={2013}, month={Jun}, pages={5764–5771} }
 @article{goltz_sapper_failla_campbell_ferruzzi_2013, title={Carotenoid bioavailability from raw vegetables and a moderate amount of oil in human subjects is greatest when the majority of daily vegetables are consumed at one meal}, volume={33}, ISSN={0271-5317}, url={http://dx.doi.org/10.1016/J.NUTRES.2013.02.010}, DOI={10.1016/J.NUTRES.2013.02.010}, abstractNote={While the impact of food composition and processing on carotenoid bioavailability has been the subject of several investigations, the effect of meal patterning remains unknown. The aim of this pilot study was to assess the impact of select consumption patterns on the bioavailability of carotenoids from vegetables. On three randomized testing days, subjects consumed raw salad vegetables and 8 g canola oil over a two meal period in three meal patterns. Meal patterns included consumption of 100% of vegetables and oil in the first meal and 0% in the second, 75% in the first meal and 25% in the second, and 50% in the first meal and 50% in the second. Additional protein-rich "chef's salad" ingredients were distributed equally between meals. We hypothesized that carotenoid absorption would be highest when 50% of vegetables and oil were consumed at each meal and lowest when 100% were consumed at once. Blood was collected 0 to 12 hours postprandially and triacylglycerol-rich lipoprotein fractions (TRL) were isolated by ultracentrifugation. TRL carotenoid concentrations were analyzed by high performance liquid chromatography-diode array detector. Considering all carotenoids, absorption expressed as area under the curve was greatest when ≥75% of vegetables were consumed in a single meal (P < .05). Absorption of carotenes also followed this trend (P < .05 for α- and β-carotene). For xanthophylls, consuming all vegetables in one meal increased absorption compared to intake of 50% at each meal (P < .05). These data suggest that carotenoid absorption may be the greatest when daily recommended vegetables are consumed in one meal compared to smaller doses over multiple meals.}, number={5}, journal={Nutrition Research}, publisher={Elsevier BV}, author={Goltz, Shellen R. and Sapper, Teryn N. and Failla, Mark L. and Campbell, Wayne W. and Ferruzzi, Mario G.}, year={2013}, month={May}, pages={358–366} }
 @article{li_taylor_ferruzzi_mauer_2013, title={Color and chemical stability of tea polyphenol (−)-epigallocatechin-3-gallate in solution and solid states}, volume={53}, ISSN={0963-9969}, url={http://dx.doi.org/10.1016/j.foodres.2012.11.019}, DOI={10.1016/j.foodres.2012.11.019}, abstractNote={Abstract (−)-Epigallocatechin-3-gallate (EGCG), the main component with the highest biological activity in green tea, has been extensively studied for its activities and degradation behaviors in infusions and solutions. However, neither the characterization of its degradation products in solutions, nor its color degradation and stability in the solid state are well documented. Therefore, in this present study, the color and chemical stability of EGCG in solutions with various concentrations ranging from 0.05 mg/mL to 30 mg/mL and in the solid state following storage at 0% and 85% relative humidity (RH), 80 °C were investigated. Color parameters were monitored over time, and the chemical stability was determined using high performance liquid chromatography (HPLC)–diode array detection (DAD) analysis and HPLC–mass spectrometry (MS). Mathematical models for color degradation of EGCG in both solution and solid states were established. The chemical stability of EGCG was found to be affected by its physical state, concentration of reactants, oxygen levels, pH, and RH conditions. Epimerization and oxidation were found to be the two major reactions causing the degradation of EGCG in the solution and solid state, respectively. Major degradation products, catechin monomers and oxidation dimers, were identified. Cleavage products, gallic acid and catechin monomers, were also found. These results further elaborated the degradation mechanisms of EGCG in solutions of varying concentrations and revealed the chemical changes resulting in color degradation of EGCG in the solid state.}, number={2}, journal={Food Research International}, publisher={Elsevier BV}, author={Li, Na and Taylor, Lynne S. and Ferruzzi, Mario G. and Mauer, Lisa J.}, year={2013}, month={Oct}, pages={909–921} }
 @article{guo_mah_davis_jalili_ferruzzi_chun_bruno_2013, title={Dietary fat increases quercetin bioavailability in overweight adults}, volume={57}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/mnfr.201200619}, DOI={10.1002/mnfr.201200619}, abstractNote={Scope Epidemiologic evidence supports that dietary quercetin reduces cardiovascular disease (CVD) risk, but its oral bioavailability is paradoxically low. The aim of this study was to determine whether dietary fat would improve quercetin bioavailability in adults at high risk for CVD and to assess lipid-mediated micellarization of quercetin in vitro. Methods and results In a randomized, cross-over study, overweight/obese men and postmenopausal women (n = 4 M/5 F; 55.9 ± 2.1 years; 30.8 ± 1.4 kg/m2) ingested 1095 mg of quercetin aglycone with a standardized breakfast that was fat-free (<0.5 g), low-fat (4.0 g), or high-fat (15.4 g). Plasma was obtained at timed intervals for 24 h to measure quercetin and its methylated metabolites isorhamnetin and tamarixetin. Compared to the fat-free trial, plasma quercetin maximum concentration (Cmax), and area under curve (AUC0–24 h) increased (p < 0.05) by 45 and 32%, respectively, during the high-fat trial. During the high-fat trial, isorhamnetin Cmax and AUC0–24 h also increased by 40 and 19%, respectively, whereas Cmax and AUC0–24 h of tamarixetin increased by 46 and 43%, respectively. Dietary fat dose-dependently increased micellarization efficiency of quercetin aglycone in vitro. Conclusion Dietary fat improves quercetin bioavailability by increasing its absorption, likely by enhancing its micellarization at the small intestine.}, number={5}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Guo, Yi and Mah, Eunice and Davis, Catherine G. and Jalili, Thunder and Ferruzzi, Mario G. and Chun, Ock K. and Bruno, Richard S.}, year={2013}, month={Jan}, pages={896–905} }
 @article{wang_williams_ferruzzi_d’arcy_2013, title={Microbial metabolites, but not other phenolics derived from grape seed phenolic extract, are transported through differentiated Caco-2 cell monolayers}, volume={138}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2012.09.103}, DOI={10.1016/j.foodchem.2012.09.103}, abstractNote={Grape seed phenolic extract (GSE) is predicted to have health benefits, even though its bioavailability, including digestibility, permeability and ultimate metabolism, are still poorly understood. In vitro gastric and pancreatic digestion and in vitro ileal and faecal fermentation were combined with Caco-2 cell permeability studies for GSE samples. Qualitatively, there was no change in type/number of GSE compounds following gastric and pancreatic digestion and LC–MS analysis. However, the monomers were significantly (P < 0.05) increased after gastric digestion, along with a significant (P < 0.05) decrease in polymers. In addition, all forms of phenolic compounds decreased following pancreatic digestion. However, none of the original GSE phenolic compounds passed the Caco-2 cell monolayer, since all were recovered in the apical compartment. In contrast, the two intestinal microbiota metabolites with deprotonated molecular weights of [M–H]-165/121 and 193/175, that were found both in the ileal and faecal fermented samples, passed the Caco-2 cell monolayer.}, number={2-3}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Wang, Dongjie and Williams, Barbara A. and Ferruzzi, Mario G. and D’Arcy, Bruce R.}, year={2013}, month={Jun}, pages={1564–1573} }
 @article{song_sapper_burtch_brimmer_goldschmidt_ferruzzi_2013, title={Photo- and Thermodegradation of Anthocyanins from Grape and Purple Sweet Potato in Model Beverage Systems}, volume={61}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf3044007}, DOI={10.1021/jf3044007}, abstractNote={Recently, interest in the application of natural pigments to replace synthetic dyes in beverages has grown. The present study investigates the stability of anthocyanin-rich grape and purple sweet potato (PSP) extracts to photo- and thermostresses in ready-to-drink (RTD) beverage models including hot fill beverages with various concentrations of ascorbic acid, a preserved beverage, and a vitamin-enriched water beverage. Thermo- and photostresses were induced at 40, 60, and 80 °C and 250, 500, and 750 W/m2, respectively. Qualitative and quantitative data on anthocyanin content were collected by pH differential assay and LC-MS. Increasing concentration of ascorbic acid caused more rapid degradation through thermostress, but had a protective effect through photostress. Additionally, PSP was significantly less stable than grape extract in the vitamin-enriched water model beverage through photostress. Furthermore, photostress caused the formation of monoacylated peonidins from diacylated peonidins.}, number={6}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Song, Brian J. and Sapper, Teryn N. and Burtch, Claire E. and Brimmer, Karen and Goldschmidt, Mark and Ferruzzi, Mario G.}, year={2013}, month={Feb}, pages={1364–1372} }
 @article{lipkie_janasch_cooper_hohman_weaver_ferruzzi_2013, title={Quantification of vitamin D and 25-hydroxyvitamin D in soft tissues by liquid chromatography–tandem mass spectrometry}, volume={932}, ISSN={1570-0232}, url={http://dx.doi.org/10.1016/J.JCHROMB.2013.05.029}, DOI={10.1016/J.JCHROMB.2013.05.029}, abstractNote={Inadequate data on tissue distribution of vitamin D and its metabolites remains a barrier to defining health outcomes of vitamin D intake and 25-hydroxyvitamin D (25(OH)D) status. The purpose of this study was to develop a method for the analysis of vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), 25(OH)D2, and 25(OH)D3 in soft tissues, and determine distribution in select tissues from a dose-response study of vitamin D2 and vitamin D3 in rats. Liver, gastrocnemius muscle, and epididymal fat homogenates were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization following liquid-liquid extraction, solid-phase extraction, and derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). A dose-response was observed in most tissues for vitamin D and 25(OH)D from both vitamers. Vitamin D concentration was greater in epididymal fat than gastrocnemius muscle and liver, but 25(OH)D concentration was not significantly different between tissues. Soft tissues of rats fed crystalline vitamin D3 had higher concentrations of total vitamin D than those of rats fed yeast-derived vitamin D2, while total 25(OH)D concentrations were similar between vitamin D sources. This method is well suited to more complete studies of vitamin D bioavailability and metabolite tissue distribution.}, journal={Journal of Chromatography B}, publisher={Elsevier BV}, author={Lipkie, Tristan E. and Janasch, Amber and Cooper, Bruce R. and Hohman, Emily E. and Weaver, Connie M. and Ferruzzi, Mario G.}, year={2013}, month={Aug}, pages={6–11} }
 @article{wang_tang_ferruzzi_gong_song_janle_chen_cooper_varghese_cheng_et al._2013, title={Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model}, volume={57}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/MNFR.201300230}, DOI={10.1002/MNFR.201300230}, abstractNote={Scope Metabolic syndrome has become an epidemic and poses tremendous burden on the health system. People with metabolic syndrome are more likely to experience cognitive decline. As obesity and sedentary lifestyles become more common, the development of early prevention strategies is critical. In this study, we explore the potential beneficial effects of a combinatory polyphenol preparation composed of grape seed extract, Concord purple grape juice extract, and resveratrol, referred to as standardized grape polyphenol preparation (SGP), on peripheral as well as brain dysfunction induced by metabolic syndrome. Methods and results We found dietary fat content had minimal effect on absorption of metabolites of major polyphenols derived from SGP. Using a diet-induced animal model of metabolic syndrome (DIM), we found that brain functional connectivity and synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only prevented peripheral metabolic abnormality but also improved brain synaptic plasticity. Conclusion Our study demonstrated that SGP, comprised of multiple bioavailable and bioactive components targeting a wide range of metabolic syndrome related pathological features, provides greater global protection against peripheral and central nervous system dysfunctions and can be potentially developed as a novel prevention/treatment for improving brain connectivity and synaptic plasticity important for learning and memory.}, number={12}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Wang, Jun and Tang, Cheuk and Ferruzzi, Mario G. and Gong, Bing and Song, Brian J. and Janle, Elsa M. and Chen, Tzu-Ying and Cooper, Bruce and Varghese, Merina and Cheng, Alice and et al.}, year={2013}, month={Aug}, pages={2091–2102} }
 @article{wang_williams_ferruzzi_d'arcy_2012, title={Different concentrations of grape seed extract affectin vitrostarch fermentation by porcine small and large intestinal inocula}, volume={93}, ISSN={0022-5142}, url={http://dx.doi.org/10.1002/jsfa.5753}, DOI={10.1002/jsfa.5753}, abstractNote={BACKGROUND: Grape seed extract (GSE) phenolics have potential health-promoting properties, either from compounds present within the extract, or metabolites resulting from gastrointestinal tract (GIT) fermentation of these compounds. This study describes how GSE affected the kinetics and end-products of starch fermentation in vitro using pig intestinal and fecal inocula. Six GSE concentrations (0, 60, 125, 250, 500, and 750 µg ml−1 were fermented in vitro by porcine ileal and fecal microbiota using starch as the energy source. Cumulative gas production, and end-point short chain fatty acids and ammonia were measured. RESULTS: GSE phenolics altered the pattern (gas kinetics, and end-products such as SCFA and NH) of starch fermentation by both inocula, at concentrations above 250 µg ml−1. Below this level, neither inoculum showed any significant (P > 0.05) effect of the GSE. CONCLUSION: The results show that GSE phenolics at a concentration over 250 µg ml−1 can have measurable effects on microbial activity in an in vitro fermentation system, as evidenced by the changes in kinetics and end-products from starch fermentation. This suggests that fermentation patterns could be conceivably shifted in the actual GIT, though further evidence will be required from in vivo studies. Copyright © 2012 Society of Chemical Industry}, number={2}, journal={Journal of the Science of Food and Agriculture}, publisher={Wiley}, author={Wang, Dongjie and Williams, Barbara A and Ferruzzi, Mario G and D'Arcy, Bruce R}, year={2012}, month={Jul}, pages={276–283} }
 @article{ferruzzi_bordenave_hamaker_2012, title={Does flavor impact function? Potential consequences of polyphenol–protein interactions in delivery and bioactivity of flavan-3-ols from foods}, volume={107}, ISSN={0031-9384}, url={http://dx.doi.org/10.1016/j.physbeh.2012.02.020}, DOI={10.1016/j.physbeh.2012.02.020}, abstractNote={Astringency is a component of the overall flavor experienced when consuming polyphenol rich foods and beverages such as tea, wine, cocoa and select fruits. Following consumption, the astringent sensation results from the well documented ability of polyphenols to bind to salivary proline rich proteins (PRP) and facilitate their precipitation in the oral cavity. In a similar fashion, polyphenols are also known to non-specifically bind food and other biological proteins. While much is known regarding the polyphenol-protein interactions leading to astringency, significantly less information is available regarding the impact of these polyphenol-protein interactions with food or other biological proteins on relevant physiological outcomes. This paper focuses on the interactions between flavan-3-ols, one of the most abundant dietary polyphenol forms, with proteins in food, salivary PRP and other physiological proteins. The physiological implications of these interactions in food and through the gut will be discussed in relation to manipulation of flavan-3-ol bioavailability, metabolism and biological activities including inhibition of digestive enzymes in the gut.}, number={4}, journal={Physiology & Behavior}, publisher={Elsevier BV}, author={Ferruzzi, Mario G. and Bordenave, Nicolas and Hamaker, Bruce R.}, year={2012}, month={Nov}, pages={591–597} }
 @article{paranjpe_ferruzzi_morgan_2012, title={Effect of a flash vacuum expansion process on grape juice yield and quality}, volume={48}, ISSN={0023-6438}, url={http://dx.doi.org/10.1016/J.LWT.2012.02.021}, DOI={10.1016/J.LWT.2012.02.021}, abstractNote={Flash vacuum expansion is a process where a heated product is rapidly exposed to low pressure, or vacuum, causing interstitial water in the product to rapidly flash and rupture a portion of the tissue. This process has potential to aid juice expression and improve extraction of potentially healthy components from fruits and vegetables. In this study, the yield and quality of juice extracted from grapes treated by flash vacuum expansion, heat and enzymes, heat only, and no treatment were compared. The flash expansion process was first studied using Thompson seedless grapes. Lower chamber pressures and higher fruit temperatures were found to improve juice yield and phytochemical composition. While the process could improve polyphenol content and extraction over traditional methods, juice yield was lower than enzyme processing. Tissue damage on grape skins, measured via electrical impedance, was highest after flash vacuum expansion and resulted in higher polyphenol extraction. Juice pressed from concord grapes treated with flash vacuum expansion was compared with heat and enzyme processing, heat treatment only, and cold pressing. Flash vacuum expansion provided juice yields similar to enzyme processing and higher than heat treatment or cold pressing. The process also improved juice anthocyanins over enzyme processing, heat processing, and cold pressing. This investigation provides a comparison of the flash vacuum expansion process and more traditional grape processing methods. It also provides insight into the role of key operating conditions on juice yield and quality.}, number={2}, journal={LWT - Food Science and Technology}, publisher={Elsevier BV}, author={Paranjpe, Shriram S. and Ferruzzi, Mario and Morgan, Mark T.}, year={2012}, month={Oct}, pages={147–155} }
 @article{blount_ferruzzi_raftery_pasinetti_dixon_2012, title={Enzymatic synthesis of substituted epicatechins for bioactivity studies in neurological disorders}, volume={417}, ISSN={0006-291X}, url={http://dx.doi.org/10.1016/j.bbrc.2011.11.139}, DOI={10.1016/j.bbrc.2011.11.139}, abstractNote={Glucuronidated and/or methylated metabolites of the proanthocyanidin (PA) monomer (-)-epicatechin are detected in both blood and brain following feeding of rodents with a monomeric grape seed PA extract shown to reduce symptoms in a mouse model of Alzheimer's disease. To generate metabolites for future mechanistic studies, we investigated the ability of recombinant human glucuronosyl transferases of the UGT1A and UGT2B families to glucuronidate epicatechin or 3'-O-methyl epicatechin in vitro. Of twelve enzymes tested, UGT1A9 was the most efficient, producing epicatechin 3'-O-glucuronide as the major product. Incubation of UGT1A9 with 3'-O-methyl-epicatechin resulted in two major products, one of which was identified as 3'-O-methyl-epicatechin 5-O-glucuronide, a major metabolite found in blood plasma and brain tissue of the rodents following feeding with a grape seed extract. We also investigated in vitro methylation of epicatechin and epicatechin glucuronides by human catechol O-methyltransferase. Enzymatic production of 3'-O-methyl-epicatechin 5-O-glucuronide was optimized to 50% overall yield. These studies form a basis for generation of mg quantities of pure epicatechin (methyl) glucuronides of biological significance, and provide clarification of structure of previously identified epicatechin metabolites.}, number={1}, journal={Biochemical and Biophysical Research Communications}, publisher={Elsevier BV}, author={Blount, Jack W. and Ferruzzi, Mario and Raftery, Dan and Pasinetti, Giulio M. and Dixon, Richard A.}, year={2012}, month={Jan}, pages={457–461} }
 @article{li_taylor_ferruzzi_mauer_2012, title={Kinetic Study of Catechin Stability: Effects of pH, Concentration, and Temperature}, volume={60}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf304116s}, DOI={10.1021/jf304116s}, abstractNote={The degradation behaviors of catechins in dilute aqueous systems, including tea beverages and catechin solutions, have been documented; however, their reaction kinetics in green tea concentrated solutions, and impacts of pH, concentration, and temperature thereon, have not yet been established. In this study, reactions were conducted at pH levels ranging from 1.5 to 7, concentrations ranging from 1 to 1666.7 mg/mL, and temperatures ranging from 25 to 120 °C. Catechin contents were determined using high-performance liquid chromatography. Catechins were found to be more stable at high concentrations around pH 4. An empirical model for catechin content was established as a function of pH and temperature and showed good correlation between green tea concentrated solutions and previous reports of catechin stability in powder systems. These results provide useful approaches for shelf life calculations and catechin loss predictions at given temperature and pH conditions in green tea concentrates.}, number={51}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Li, Na and Taylor, Lynne S. and Ferruzzi, Mario G. and Mauer, Lisa J.}, year={2012}, month={Dec}, pages={12531–12539} }
 @article{goltz_campbell_chitchumroonchokchai_failla_ferruzzi_2012, title={Meal triacylglycerol profile modulates postprandial absorption of carotenoids in humans}, volume={56}, ISSN={1613-4125}, url={http://dx.doi.org/10.1002/mnfr.201100687}, DOI={10.1002/mnfr.201100687}, abstractNote={Dietary lipids are considered to be primary potentiators of carotenoid absorption, yet the amount and source required to optimize bioavailability has not been systematically evaluated. The objective of this study was to examine the impact of both amount and source of triacylglycerols on postprandial absorption of carotenoids from vegetable salads.Healthy subjects (n = 29) were randomized using a Latin square design (3 × 3) and consumed three identical salads with 3, 8, or 20 g of canola oil, soybean oil, or butter. Blood was collected from 0-10 h and triacylglycerol-rich fractions (TRLs) were isolated by ultracentrifugation. Carotenoid contents of TRL fractions were analyzed by HPLC-DAD. Considering all lipid sources, 20 g of lipid promoted higher absorption compared to 3 and 8 g for all carotenoid species (p < 0.05), except for α-carotene (p = 0.07). The source of lipid had less impact on the absorption of carotenoids than amount of lipid. Pooling results from all lipid amounts, monounsaturated fatty acid rich canola oil trended toward enhancing absorption of lutein and α-carotene compared to saturated fatty acid rich butter (p = 0.06 and p = 0.08, respectively).While both amount and source of co-consumed lipid affect carotenoid bioavailability from vegetables, amount appears to exert a stronger effect.}, number={6}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Goltz, Shellen R. and Campbell, Wayne W. and Chitchumroonchokchai, Chureeporn and Failla, Mark L. and Ferruzzi, Mario G.}, year={2012}, month={Jun}, pages={866–877} }
 @article{knable_vempati_freire_ferruzzi_pasinetti_2012, title={P3-342: Intranasal delivery of bioactive polyphenol metabolites to prevent and/or treat Alzheimer's disease and other forms of dementia}, volume={8}, ISSN={1552-5260}, url={http://dx.doi.org/10.1016/j.jalz.2012.05.1566}, DOI={10.1016/j.jalz.2012.05.1566}, abstractNote={While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity and limited knowledge regarding their bioavailability, metabolism and bioactivity in the brain. We recently demonstrated that dietary supplementation with a grape-derived polyphenolic preparation, namely a monomeric-enriched catechin and epicatechin fraction (Mo), significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). We also found that Mo treatment resulted in the accumulation of proanthocyanidin metabolites in the brain at a concentration of ∼400 nM. One of the metabolites identified in the brain following Mo treatment, Metaphenol-A1, was shown to promote basal synaptic transmission and long-term potentiation (LTP) at physiologically relevant concentrations in hippocampal slices through mechanisms associated with cAMP-response-element-binding-protein signaling. C57BL/6 mice were treated with Metaphenol-A1 (7.5 μM) by intranasal route. Brain sections were then harvested at 5, 10, 15, and 60 minutes. Pharmacokinetics and neuronal molecular changes were assessed in the samples collected. The same delivery approach will be applied to the Tg2576 mouse model of AD to assess its effect on cognitive function. We are currently evaluating the pharmacokinetics and brain bioavailability of Metaphenol-A1 delivered via a novel, non-invasive intranasal delivery apparatus. We will also asses the effects of Metaphenol-A1 delivered in this manner on LTP and cognitive function in AD mice. Our study will provide insights into developing a novel, safe approach to directly deliver a bioactive therapeutic agent to the central nervous system for AD prevention/treatment.}, number={4S_Part_16}, journal={Alzheimer's & Dementia}, publisher={Wiley}, author={Knable, Lindsay and Vempati, Prashant and Freire, Daniel and Ferruzzi, Mario and Pasinetti, Giulio}, year={2012}, month={Jul}, pages={P577–P577} }
 @article{xu_simon_ferruzzi_ho_pasinetti_wu_2012, title={Quantification of anthocyanidins in the grapes and grape juice products with acid assisted hydrolysis using LC/MS}, volume={4}, ISSN={1756-4646}, url={http://dx.doi.org/10.1016/j.jff.2012.04.010}, DOI={10.1016/j.jff.2012.04.010}, abstractNote={A simple and precise acid-assisted hydrolysis method was established for the quantification of anthocyanidins in 15 grape juice samples, four grape berries and four grape skins using LC/MS. Under optimized conditions, five major anthocyanidins including delphinidin, cyanidin, petunidin, peonidin and malvidin in the hydrolyzed grape extracts were successfully separated within 25 min and quantified individually. The results revealed that the total concentration of anthocyanidins was not symmetrically distributed in the different grape juice products. While quantitative distribution of anthocyanidins in grape berries and skins are quite similar, anthocyanidin concentration in grape skins was found to be four to eight times higher than their corresponding berries. The precision of this method was validated by recovery percentages of five anthocyanidins, ranging from 98.59% to 103.20% with the relative standard deviation (RSD) less than 5.03%. This quantitative method provides a rapid and accurate tool to quantitatively study individual anthocyanidins in grapes or grape juice samples for quality control and to facilitate the evaluation and comparison of new commercial grapes or grape juices products in the market.}, number={4}, journal={Journal of Functional Foods}, publisher={Elsevier BV}, author={Xu, Yanping and Simon, James E. and Ferruzzi, Mario G. and Ho, Lap and Pasinetti, Giulio Maria and Wu, Qingli}, year={2012}, month={Oct}, pages={710–717} }
 @article{houchins_burgess_campbell_daniel_ferruzzi_mccabe_mattes_2011, title={Beverage vs. Solid Fruits and Vegetables: Effects on Energy Intake and Body Weight}, volume={20}, ISSN={1930-7381 1930-739X}, url={http://dx.doi.org/10.1038/oby.2011.192}, DOI={10.1038/oby.2011.192}, abstractNote={Beverage consumption has been implicated in weight gain, but questions remain about the veracity of the association, whether the relationship is causal and what property of beverages is responsible. It was hypothesized that food form is the most salient attribute. Thus, a randomized controlled trial of food form was conducted. Energy-matched beverage or solid forms of fruits and vegetables were provided to 34, lean or overweight/obese adults for two 8-week periods with a 3-week washout interspersed. Dietary compensation was incomplete (beverage 53%; solid 78%) and body weight increased after the beverage (1.95 ± 0.33 kg) (77% fat mass) and solid (1.36 ± 0.30 kg) (85% fat mass) treatments (both P < 0.0005). Differences between food forms were not significant. The lean group had the highest dietary compensation (119%) and no significant weight change (0.84 ± 0.53 kg) after consuming the solid fruits and vegetables whereas the overweight/obese group had lower compensation and significant weight gain during the solid arm (46%, 1.77 ± 0.32 kg, P < 0.0001). In contrast, incomplete dietary compensation and weight gain occurred in both the lean (43%, 1.61 ± 0.44 kg, P = 0.003) and overweight/obese (61%, 2.22 ± 0.47 kg, P < 0.0005) groups during the beverage arm. Secondary analyses revealed the obese group gained more weight than the lean and overweight groups during the beverage intervention (P = 0.024). These data demonstrate energy consumed as beverages may be especially problematic for weight gain. They also indicate that advice to increase fruit and vegetable consumption should emphasize total energy intake because the additional energy contributed may promote weight gain, especially among overweight and obese individuals.}, number={9}, journal={Obesity}, publisher={Wiley}, author={Houchins, Jenny A. and Burgess, John R. and Campbell, Wayne W. and Daniel, James R. and Ferruzzi, Mario G. and McCabe, George P. and Mattes, Richard D.}, year={2011}, month={Jun}, pages={1844–1850} }
 @article{kean_bordenave_ejeta_hamaker_ferruzzi_2011, title={Carotenoid bioaccessibility from whole grain and decorticated yellow endosperm sorghum porridge}, volume={54}, ISSN={0733-5210}, url={http://dx.doi.org/10.1016/j.jcs.2011.08.010}, DOI={10.1016/j.jcs.2011.08.010}, abstractNote={Sorghum is a staple crop and a potential dietary source of carotenoids in semi-arid regions of Africa, but information on the bioavailability of these pigments is limited. This study aimed at exploring the effects of agronomic manipulation on sorghum carotenoid contents at selected stages of kernel development and maturation and assessing carotenoid bioaccessibility from matured yellow-endosperm sorghum varieties (P88 and P1222), by comparing porridge made from sorghum whole and decorticated milled grains. Carotenoid content of sorghum milled fractions ranged from 2.90 to 7.22 mg/kg in P88 unbagged decorticated flour, at 50 and 30 days after half bloom (DAHB) respectively, to 9.87–13.69 mg/kg in bagged decorticated bran fractions in P88, at 50 and 30 DAHB respectively. Maize milled fractions were significantly (P < 0.05) higher in carotenoid content than all sorghum products. Bagging increased sorghum carotenoid content by 8–184% vs. unbagged panicles. Carotenoid bioaccessibility was generally higher from sorghum (63–81%) compared to maize (45–47%). Micellarization of xanthophylls (75%) was more efficient than carotenes (52%) in sorghum, while they were similar in maize (40–49%). These results suggest that the higher bioaccessibility of sorghum carotenoids combined with efforts to enhance sorghum carotenoid content may allow for sorghum to provide similar levels of bioaccessible carotenoid pigments as common yellow maize.}, number={3}, journal={Journal of Cereal Science}, publisher={Elsevier BV}, author={Kean, Ellie G. and Bordenave, Nicolas and Ejeta, Gebisa and Hamaker, Bruce R. and Ferruzzi, Mario G.}, year={2011}, month={Nov}, pages={450–459} }
 @article{hiatt_ferruzzi_taylor_mauer_2011, title={Deliquescence Behavior and Chemical Stability of Vitamin C Forms (Ascorbic Acid, Sodium Ascorbate, and Calcium Ascorbate) and Blends}, volume={14}, ISSN={1094-2912 1532-2386}, url={http://dx.doi.org/10.1080/10942911003650338}, DOI={10.1080/10942911003650338}, abstractNote={The stability and type of vitamin C added to foods is important for enhancing product quality, label claims, and shelf-life. To improve understanding of stability, the effects of deliquescence, storage relative humidity (RH) formulation, and addition of ascorbyl palmitate and dehydroascorbic acid on degradation of vitamin C at 25°C were studied. Individual vitamin C forms (ascorbic acid, sodium, and calcium ascorbate) and mixtures were stored below, near, and above their deliquescence RH for up to 12 weeks. Vitamin C stability was significantly affected by RH and vitamin form (p < 0.0001). Formulation affected deliquescence and chemical stability: mixtures were significantly less stable above RH0mix than below (p < 0.0001). Ascorbyl palmitate-enhanced degradation rates of more soluble vitamin C forms, and the presence of dehydroascorbic acid reduced vitamin blend stability. It is important that vitamin C products be stored below the deliquescence RH to avoid enhanced vitamin losses.}, number={6}, journal={International Journal of Food Properties}, publisher={Informa UK Limited}, author={Hiatt, Ashley N. and Ferruzzi, Mario G. and Taylor, Lynne S. and Mauer, Lisa J.}, year={2011}, month={Nov}, pages={1330–1348} }
 @article{kim_bordenave_ferruzzi_safavy_kim_2011, title={Modification of Curcumin with Polyethylene Glycol Enhances the Delivery of Curcumin in Preadipocytes and Its Antiadipogenic Property}, volume={59}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf103873k}, DOI={10.1021/jf103873k}, abstractNote={Conjugation of curcumin (CCM) by polyethylene glycol (PEG) has been previously developed to improve water solubility of the natural form of CCM and its antiproliferative role in some human cancer cell lines. This study examined the cellular uptake kinetics of the natural form of CCM and CCM−PEG. Their cytotoxic effect in proliferating preadipocytes and antiadipogenic property in differentiating preadipocytes had also been investigated. CCM and CCM−PEG were found to be differently absorbed in 3T3-L1 preadipocytes and adipocytes with a limited amount of CCM−PEG absorption in the cell. The improved water solubility of CCM−PEG was correlated with increased cellular retention of CCM in 3T3-L1 cells, particularly in preadipocytes. Consequently, CCM−PEG treatment sensitized proliferating preadipocytes to CCM-induced cell toxicity. Furthermore, incubation of differentiating 3T3-L1 cells with CCM−PEG resulted in improvement of the inhibitory role of CCM in adipocyte differentiation with no toxic effect. These results suggest that pegylation-improved water solubility and cellular retention of CCM may be uniquely useful for improving the delivery of CCM in preadipocytes and its antiadipogenic ability.}, number={3}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Kim, Choon Young and Bordenave, Nicolas and Ferruzzi, Mario G. and Safavy, Ahmad and Kim, Kee-Hong}, year={2011}, month={Feb}, pages={1012–1019} }
 @article{pasinetti_wang_marambaud_ferruzzi_gregor_knable_ho_2011, title={Neuroprotective and metabolic effects of resveratrol: Therapeutic implications for Huntington's disease and other neurodegenerative disorders}, volume={232}, ISSN={0014-4886}, url={http://dx.doi.org/10.1016/j.expneurol.2011.08.014}, DOI={10.1016/j.expneurol.2011.08.014}, abstractNote={Resveratrol is a naturally occurring polyphenolic compound associated with beneficial effects on aging, metabolic disorders, inflammation and cancer in animal models and resveratrol is currently being tested in numerous clinical trials. Resveratrol may exert these effects by targeting several key metabolic sensor/effector proteins, such as AMPK, SIRT1, and PGC-1α. Resveratrol has also received considerable attention recently for its potential neuroprotective effects in neurodegenerative disorders where AMPK, SIRT1 or PGC-1α may represent promising therapeutic targets. A recent study published in Experimental Neurology (Ho et al., 2010) examined the therapeutic potential of a micronised proprietary resveratrol formulation, SRT501 in the N171-82Q transgenic mouse model of Huntington's disease (HD). HD is a progressive and devastating genetic neurodegenerative disorder that is associated with downregulation of PGC-1α activity. The Ho et al. study found that SRT501 treatment did not lead to significant improvement in weight loss, motor performance, survival and striatal atrophy. However, other studies have reported neuroprotective effects of resveratrol and a distantly related polyphenol, fisetin, in HD models. HD has been associated with diabetes mellitus. Interestingly, evidence from the Ho et al. study suggests a resveratrol formulation induced beneficial anti-diabetic effect in N171-82Q mice. This commentary summarizes the pertinent outcomes from the Ho et al. study and discusses the further prospects of resveratrol and other polyphenols, including novel grape-derived polyphenols, in the treatment of HD and other neurodegenerative disorders.}, number={1}, journal={Experimental Neurology}, publisher={Elsevier BV}, author={Pasinetti, Giulio Maria and Wang, Jun and Marambaud, Philippe and Ferruzzi, Mario and Gregor, Paul and Knable, Lindsay Alexis and Ho, Lap}, year={2011}, month={Nov}, pages={1–6} }
 @article{xu_simon_welch_wightman_ferruzzi_ho_passinetti_wu_2011, title={Survey of Polyphenol Constituents in Grapes and Grape-Derived Products}, volume={59}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf202438d}, DOI={10.1021/jf202438d}, abstractNote={A rapid and comprehensive qualitative method has been developed to characterize the different classes of polyphenols, such as anthocyanins, flavonols, phenolic acids, and flavanols/proanthocyanidins, in grape products. The detection was achieved by two runs with the same LC gradient in different MS ionization modes and mobile phase modifiers (positive ionization mode and 0.4% trifluoroacetic acid for anthocyanins and flavonols; negative ionization mode and 0.1% formic acid for phenolic acids and flavanols). From an analysis of the MS and UV data and in comparison with the authenticated standards, a total of 53 compounds were identified, including 33 anthocyanins, 12 flavonols, 4 phenolic acids, and 4 flavanols/proanthocyanidins. With the method developed, a survey was then conducted to qualitatively assess the composition of polyphenols among 29 different grape products including original grape, grape juice, grape wine, and grape-derived dietary supplements, and their chemical profiles were systematically compared. This method provided a comprehensive qualitative insight into the composition of polyphenols in grape-derived products.}, number={19}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Xu, Yanping and Simon, James E. and Welch, Cara and Wightman, JoLynne D. and Ferruzzi, Mario G. and Ho, Lap and Passinetti, Guilio M. and Wu, Qingli}, year={2011}, month={Oct}, pages={10586–10593} }
 @article{vingtdeux_giliberto_zhao_chandakkar_wu_simon_janle_lobo_ferruzzi_davies_et al._2010, title={AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism}, volume={285}, ISSN={0021-9258 1083-351X}, url={http://dx.doi.org/10.1074/jbc.M109.060061}, DOI={10.1074/jbc.M109.060061}, abstractNote={Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease. Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease. IntroductionAlzheimer disease (AD) 2The abbreviations used are: ADAlzheimer diseaseAβamyloid-βAPPamyloid-β precursor proteinAMPKAMP-activated protein kinaseCaMKKβcalcium/calmodulin-dependent protein kinase kinase-βACCacetyl-CoA carboxylaseAICAR5-aminoimidazole-4-carboxamide-1-β-ribosideCAconstitutively activeDNdominant negativeHPLChigh performance liquid chromatographyLC3light chain 3CREBcAMP-response element-binding proteinELISAenzyme-linked immunosorbent assayWBWestern blotLCliquid chromatographyMSmass spectrometryERendoplasmic reticulum. is a progressive neurodegenerative disorder and the first cause of dementia. Amyloid-β (Aβ) peptides have a central role in the pathogenesis of the disease and represent the core components of the senile plaques, the lesions invariably found in the neocortex and hippocampus of the AD brains (1.Selkoe D.J. Physiol. Rev. 2001; 81: 741-766Crossref PubMed Scopus (5121) Google Scholar, 2.Wilquet V. De Strooper B. Curr. Opin. Neurobiol. 2004; 14: 582-588Crossref PubMed Scopus (202) Google Scholar). In the amyloidogenic pathway, the amyloid-β precursor protein (APP) is sequentially cleaved by the aspartic protease β-secretase/BACE1 and by the γ-secretase proteolytic complex to produce various Aβ peptides, including the most abundant isoforms Aβ1–40 and Aβ1–42 (3.Haass C. EMBO J. 2004; 23: 483-488Crossref PubMed Scopus (479) Google Scholar, 4.Marambaud P. Robakis N.K. Genes Brain Behav. 2005; 4: 134-146Crossref PubMed Scopus (60) Google Scholar).Epidemiological data suggest that moderate consumption of red wine is associated with a lower incidence of dementia and AD (5.Luchsinger J.A. Mayeux R. Lancet Neurol. 2004; 3: 579-587Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar). The naturally occurring polyphenol resveratrol (trans-3,4′,5-trihydroxystilbene), which is found in abundance in red wine, has antioxidant and neuroprotective properties in vitro and could explain, in part, the beneficial effects of wine consumption in AD (6.Ramassamy C. Eur. J. Pharmacol. 2006; 545: 51-64Crossref PubMed Scopus (587) Google Scholar, 7.Vingtdeux V. Dreses-Werringloer U. Zhao H. Davies P. Marambaud P. BMC Neurosci. 2008; 9: S6Crossref PubMed Scopus (192) Google Scholar). Importantly, resveratrol controls Aβ levels by facilitating its proteolytic clearance in cultured cell lines (8.Marambaud P. Zhao H. Davies P. J. Biol. Chem. 2005; 280: 37377-37382Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar). However, the exact molecular mechanism by which resveratrol controls Aβ metabolism is currently unknown. Furthermore, evidence is missing to support the notion that orally administered resveratrol is bioavailable and bioactive in the brain.A growing body of literature has demonstrated the beneficial effect of resveratrol on age-related metabolic deterioration and its protective role in metabolic diseases, such as type 2 diabetes and obesity. Resveratrol mimics caloric restriction by extending the lifespan of different small organisms, including Saccharomyces cerevisiae and Caenorhabditis elegans (9.Baur J.A. Sinclair D.A. Nat. Rev. Drug Discov. 2006; 5: 493-506Crossref PubMed Scopus (3163) Google Scholar, 10.Greer E.L. Brunet A. Aging Cell. 2009; 8: 113-127Crossref PubMed Scopus (419) Google Scholar), and by delaying several aging phenotypes in mice (11.Pearson K.J. Baur J.A. Lewis K.N. Peshkin L. Price N.L. Labinskyy N. Swindell W.R. Kamara D. Minor R.K. Perez E. Jamieson H.A. Zhang Y. Dunn S.R. Sharma K. Pleshko N. Woollett L.A. Csiszar A. Ikeno Y. Le Couteur D. Elliott P.J. Becker K.G. Navas P. Ingram D.K. Wolf N.S. Ungvari Z. Sinclair D.A. de Cabo R. Cell Metab. 2008; 8: 157-168Abstract Full Text Full Text PDF PubMed Scopus (957) Google Scholar). Resveratrol also appears to be protective against the deregulation of energy homeostasis observed in mouse models for metabolic syndromes via the activation of key metabolic sensor proteins, such as the AMP-activated protein kinase (AMPK) and the deacetylase from the sirtuin family SIRT1 (12.Cantó C. Auwerx J. Curr. Opin. Lipidol. 2009; 20: 98-105Crossref PubMed Scopus (1057) Google Scholar, 13.Um, J. H., Park, S. J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., Chung, J. H. (2009) Diabetes, in pressGoogle Scholar).AMPK is a Ser/Thr protein kinase formed by a heterotrimeric complex comprising a catalytic α subunit and regulatory β and γ subunits. AMPK is activated by different upstream kinases via phosphorylation within its activation loop at Thr-172 (14.Carling D. Sanders M.J. Woods A. Int. J. Obes. 2008; 32: S55-S59Crossref PubMed Scopus (221) Google Scholar, 15.Hardie D.G. Nat. Rev. Mol. Cell Biol. 2007; 8: 774-785Crossref PubMed Scopus (1730) Google Scholar). The main AMPK-activating kinase is LKB1, a protein expressed ubiquitously and recruited for AMPK phosphorylation after an elevation of the AMP/ATP ratio. The calcium/calmodulin-dependent protein kinase kinase-β (CaMKKβ), a kinase with a more restricted expression in neural tissue, also activates AMPK. AMPK phosphorylation at Thr-172 by CaMKKβ is triggered by an increase in cytosolic calcium levels. AMPK targets several proteins involved in cellular energy balance, including a regulator of fatty acid biosynthesis, acetyl-CoA carboxylase (ACC). The calcium/CaMKKβ/AMPK signaling pathway also controls mechanisms relevant to protein degradation by controlling mTOR (mammalian target of rapamycin) signaling and autophagy (16.H⊘yer-Hansen M. Bastholm L. Szyniarowski P. Campanella M. Szabadkai G. Farkas T. Bianchi K. Fehrenbacher N. Elling F. Rizzuto R. Mathiasen I.S. Jäättelä M. Mol. Cell. 2007; 25: 193-205Abstract Full Text Full Text PDF PubMed Scopus (875) Google Scholar). Indeed, mTOR is a potent repressor of autophagy and is negatively controlled by AMPK (14.Carling D. Sanders M.J. Woods A. Int. J. Obes. 2008; 32: S55-S59Crossref PubMed Scopus (221) Google Scholar, 15.Hardie D.G. Nat. Rev. Mol. Cell Biol. 2007; 8: 774-785Crossref PubMed Scopus (1730) Google Scholar).In recent years, several studies have focused on the potential relationship between AD and metabolic diseases. Obesity and diabetes significantly increase cognitive decline and AD risk (17.Craft S. Arch. Neurol. 2009; 66: 300-305Crossref PubMed Scopus (414) Google Scholar), supporting the notion that molecular mechanisms of cellular energy homeostasis are linked to AD pathogenesis. Here we identify the mechanism involved in the anti-amyloidogenic effect of resveratrol by showing that this polyphenol lowered Aβ accumulation via activation of the metabolic sensor AMPK in different cell lines and in mouse primary neurons. Resveratrol activated AMPK by increasing intracellular calcium levels and by promoting AMPK phosphorylation at Thr-172 by CaMKKβ. Activation of AMPK by resveratrol resulted in mTOR inhibition and initiation of autophagy and lysosomal clearance of Aβ. Importantly, we also demonstrate that resveratrol, orally administered in mice, reached the brain where it activated AMPK and significantly reduced Aβ levels and deposition in the cerebral cortex, showing that resveratrol is both bioavailable and bioactive in the brain after oral dosing.RESULTSOur previous studies demonstrated that a 24-h incubation with resveratrol significantly reduced extracellular Aβ levels in APP-transfected cells (8.Marambaud P. Zhao H. Davies P. J. Biol. Chem. 2005; 280: 37377-37382Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar). Both secreted Aβ1–40 and Aβ1–42 were similarly diminished by resveratrol treatments, with a comparable apparent IC50 of about 30 μm (see Ref. 8.Marambaud P. Zhao H. Davies P. J. Biol. Chem. 2005; 280: 37377-37382Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar and supplemental Fig. S1). At the same concentrations, resveratrol did not noticeably affect the steady state levels of full-length APP or APP C-terminal fragments (Ref. 8.Marambaud P. Zhao H. Davies P. J. Biol. Chem. 2005; 280: 37377-37382Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar and supplemental Fig. S1), showing that resveratrol reduced Aβ levels without affecting APP processing.In this study we sought to identify the signaling pathway implicated in the control of Aβ levels by resveratrol. Using a kinase screen analyzing 28 major phosphoproteins, we determined that phosphorylation at Thr-172 on AMPK α2 subunit was the most robust effect of resveratrol in HEK293 cells (Fig. 1, A–C). Consistent with an activation of AMPK, resveratrol treatment also resulted in a significant elevation of AMPK α1 subunit phosphorylation (Fig. 1, A–C). Additional positive hits were identified, including the AMPK target CREB (24.Kim E.K. Miller I. Aja S. Landree L.E. Pinn M. McFadden J. Kuhajda F.P. Moran T.H. Ronnett G.V. J. Biol. Chem. 2004; 279: 19970-19976Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar, 25.Thomson D.M. Herway S.T. Fillmore N. Kim H. Brown J.D. Barrow J.R. Winder W.W. J. Appl. Physiol. 2008; 104: 429-438Crossref PubMed Scopus (144) Google Scholar) and the previously reported target of resveratrol, the checkpoint kinase Chk2 (26.Tyagi A. Singh R.P. Agarwal C. Siriwardana S. Sclafani R.A. Agarwal R. Carcinogenesis. 2005; 26: 1978-1987Crossref PubMed Scopus (135) Google Scholar) (Fig. 1, A–C). The effect of resveratrol on AMPK and CREB phosphorylation was confirmed by WB analyses. Resveratrol increased the phosphorylation of AMPK and its target ACC in a dose-dependent manner and at concentrations consistent with the effect of this polyphenol on Aβ levels (Fig. 1, D and E). In the same concentration range, resveratrol also strongly increased dose-dependently the phosphorylation of CREB and ATF1, another CREB/ATF family member (Fig. 1, D and E). Notably, resveratrol treatment resulted in a robust increase in c-Fos protein levels (Fig. 1D). c-Fos gene promoter contains cyclic AMP response elements, and CREB is a strong regulator of the transcription of this gene (27.Marambaud P. Wen P.H. Dutt A. Shioi J. Takashima A. Siman R. Robakis N.K. Cell. 2003; 114: 635-645Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar, 28.Ahn S. Olive M. Aggarwal S. Krylov D. Ginty D.D. Vinson C. Mol. Cell. Biol. 1998; 18: 967-977Crossref PubMed Scopus (445) Google Scholar), suggesting that resveratrol not only increased CREB phosphorylation but also activated its transcriptional activity. Together, these results indicate that one of the primary effects of resveratrol is to target AMPK to increase its phosphorylation at Thr-172 and to promote its activation, as demonstrated by the increased phosphorylation of ACC and CREB upon resveratrol treatment.Like resveratrol, (+)-catechin is a powerful plant-derived antioxidant (29.Yilmaz Y. Toledo R.T. J. Agric. Food Chem. 2004; 52: 255-260Crossref PubMed Scopus (564) Google Scholar). Although catechin has some structural similarities with resveratrol, it is ineffective at reducing Aβ levels in cultured cells at concentrations as high as 40 μm (see Fig. 1, F and G, and Ref. 8.Marambaud P. Zhao H. Davies P. J. Biol. Chem. 2005; 280: 37377-37382Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar). We found that catechin had no effect on AMPK phosphorylation (Fig. 1G), suggesting that the effect on Aβ levels and AMPK activation is relatively specific to resveratrol and independent of its antioxidant properties.The activating phosphorylation of AMPK at Thr-172 is primarily controlled by two kinases, LKB1 and CaMKKβ. LKB1 activation is tightly controlled by ATP levels via changes in the AMP/ATP ratio (14.Carling D. Sanders M.J. Woods A. Int. J. Obes. 2008; 32: S55-S59Crossref PubMed Scopus (221) Google Scholar, 15.Hardie D.G. Nat. Rev. Mol. Cell Biol. 2007; 8: 774-785Crossref PubMed Scopus (1730) Google Scholar). Because resveratrol was proposed to influence cellular ATP levels (30.Zheng J. Ramirez V.D. Br. J. Pharmacol. 2000; 130: 1115-1123Crossref PubMed Scopus (381) Google Scholar), we examined whether resveratrol affects ATP levels upon conditions inhibiting Aβ accumulation in HEK293 cells. We found no effect of 20 or 40 μm resveratrol on ATP levels (Fig. 2A). Furthermore, resveratrol treatment was still able to promote AMPK phosphorylation in the LKB1-deficient HeLa cells (Fig. 2B), indicating that LKB1 activation is not required for the effect of resveratrol on AMPK phosphorylation. We then asked whether resveratrol modulates cytosolic calcium levels in treated cells. Measurements of intracellular calcium levels were conducted under resting conditions in the presence of physiological levels of extracellular calcium. To reveal possible changes in the rate of calcium entry in treated cells, measurements were also performed under extracellular calcium add-back conditions, as previously described (21.Dreses-Werringloer U. Lambert J.C. Vingtdeux V. Zhao H. Vais H. Siebert A. Jain A. Koppel J. Rovelet-Lecrux A. Hannequin D. Pasquier F. Galimberti D. Scarpini E. Mann D. Lendon C. Campion D. Amouyel P. Davies P. Foskett J.K. Campagne F. Marambaud P. Cell. 2008; 133: 1149-1161Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar). These conditions are obtained after a transient external calcium depletion to generate a driving force for calcium entry into the cells. Using the calcium fluorescent dye Fluo-4, we found that resveratrol significantly increased cytosolic calcium levels both at resting conditions and after calcium add-back (Fig. 2, C and D). Because cytosolic calcium levels are also controlled by release of the ion from intracellular stores, such as the endoplasmic reticulum (ER), we also evaluated the effect of resveratrol treatment on ER calcium levels. Measurements of ER calcium levels were performed by blocking the sarco/endoplasmic reticulum calcium-ATPase (SERCA), a manipulation that generates a passive leak of calcium from the ER to the cytosol. In Fluo-4-loaded cells, in the absence of extracellular calcium, and in the presence of the SERCA inhibitor thapsigargin, resveratrol dose-dependently reduced the levels of ER calcium (Fig. 2E). Together these results show that resveratrol impaired intracellular calcium homeostasis by significantly increasing cytosolic calcium levels and by facilitating both calcium entry and ER calcium depletion. Because CaMKKβ is activated by an increase in cytosolic calcium, we then asked whether CaMKKβ is involved in the activation of AMPK by resveratrol. We found that the CaMKKβ inhibitor STO-609 effectively reduced the effect of resveratrol on the phosphorylation of both AMPK and ACC (Fig. 2F), indicating that resveratrol increased cytosolic calcium to promote CaMKKβ-dependent phosphorylation and activation of AMPK.FIGURE 2Resveratrol increases intracellular calcium levels and promotes CaMKKβ-dependent phosphorylation of AMPK. A, shown are intracellular ATP levels in APP-HEK293 cells treated for 1 or 24 h with the indicated concentrations of resveratrol (RSV) or with 2-deoxy-d-glucose + antimycin A (2DG/AM; used as control for ATP production inhibition). B, shown are WB analyses of pAMPK, AMPK, actin, and LKB1 levels in HEK293 (lane 1) and HeLa (lanes 2–6) cells treated with the indicated concentrations of resveratrol. C, shown are cytosolic calcium measurements with Fluo-4 loading and calcium add-back conditions in APP-HEK293 cells treated for 24 h with the indicated concentrations of RSV. Cells were incubated in calcium-free buffer (0 CaCl2) and then challenged with physiological extracellular calcium concentrations (1.4 mm CaCl2) to monitor the progressive restoration of basal cytoplasmic calcium levels. Traces illustrate the mean relative fluorescence units (RFU) ± S.D. (shaded area) of three independent experiments. CTRL, control. D, peak and steady state of cytosolic calcium measurements are as in C, expressed in ΔF/F0. Histograms show the mean ± S.D. of three independent experiments. *, p < 0.001 (Student's t test). E, shown are cytosolic calcium measurements in cells treated with RSV as in C and incubated with 2 μm thapsigargin in calcium-free buffer. F, shown are WB analyses of pAMPK, pACC, and actin levels in APP-HEK293 cells incubated for 24 h with the indicated concentrations of STO-609 and in the absence (−) or presence (+) of 40 μm RSV.View Large Image Figure ViewerDownload Hi-res image Download (PPT)We then sought to determine whether direct activation of AMPK controls Aβ metabolism. Pharmacological activation of AMPK by the use of the AMP analog AICAR strongly and significantly lowered extracellular Aβ levels in HEK293 and N2a cells (Fig. 3, A–D). AICAR treatments at concentrations reducing Aβ resulted in a robust increase in the phosphorylation of AMPK and ACC (Fig. 3, A and B), confirming the activation of AMPK in these conditions. In addition, genetic activation of AMPK by transfection of a constitutively active form of AMPK α1 subunit (31.Stein S.C. Woods A. Jones N.A. Davison M.D. Carling D. Biochem. J. 2000; 345: 437-443Crossref PubMed Scopus (484) Google Scholar) led to a robust increase of ACC phosphorylation and to a significant reduction of Aβ levels (Fig. 3, E–G). Thus, AMPK activation in cell lines lowered extracellular Aβ accumulation, including Aβ1–40 and Aβ1–42. Furthermore, expression of a dominant-negative form of AMPK (31.Stein S.C. Woods A. Jones N.A. Davison M.D. Carling D. Biochem. J. 2000; 345: 437-443Crossref PubMed Scopus (484) Google Scholar) significantly inhibited the effect of resveratrol on ACC phosphorylation (Fig. 3, H and I) and on the levels of secreted Aβ (Fig. 3H), including Aβ1–40 and Aβ1–42 (Fig. 3J). Together these data show that resveratrol lowered Aβ levels by activating AMPK.FIGURE 3Resveratrol lowers Aβ levels by activating AMPK. A, APP-HEK293 cells were treated for 24 h with the indicated concentrations of AICAR. Secreted Aβ and cellular pAMPK, AMPK, pACC, ACC, and actin levels were analyzed by WB. B, shown are densitometric analysis and quantification of the pACC/ACC ratio in cells treated as in A. a.u., arbitrary units. C and D, shown are ELISA measurements of secreted Aβ1–40 and Aβ1–42 levels from APP-HEK293 (C) or APP-N2a (D) cells treated with AICAR as in A. E, APP-HEK293 cells were transfected for 24 h with control vector (Vector) or with a Myc-tagged constitutively active form of AMPK (CA-AMPK). Myc-AMPK, pACC, ACC, actin, and secreted Aβ levels were analyzed by WB. F, shown are densitometric analysis and quantification of the pACC/ACC ratio in cells treated as in E. G, shown are ELISA measurements of secreted Aβ1–40 and Aβ1–42 levels from cells treated as in E. H, APP-HEK293 cells were transfected with control vector (V) or with a Myc-tagged dominant negative form of AMPK (DN). 24 h post-transfection, cells were treated for 24 h with DMSO (CTRL) or 40 μm resveratrol (RSV). Myc-AMPK, pACC, ACC, actin, and secreted Aβ levels were analyzed by WB. I, shown are densitometric analysis and quantification of the pACC/ACC ratio in cells treated as in H. J, shown are ELISA measurements of secreted Aβ1–40 and Aβ1–42 levels from cells treated as in H. Histograms in B–D, F, G, I, and J show the mean ± S.D. of 3–4 independent experiments. *, p < 0.05; **, p < 0.01; ***, p < 0.001 (Student's t test).View Large Image Figure ViewerDownload Hi-res image Download (PPT)AMPK is expressed in many cell types and tissues. In the adult brain, all AMPK isoforms predominantly localize in neurons (32.Turnley A.M. Stapleton D. Mann R.J. Witters L.A. Kemp B.E. Bartlett P.F. J. Neurochem. 1999; 72: 1707-1716Crossref PubMed Scopus (230) Google Scholar, 33.Culmsee C. Monnig J. Kemp B.E. Mattson M.P. J. Mol. Neurosci. 2001; 17: 45-58Crossref PubMed Scopus (294) Google Scholar). A more restricted expression of some AMPK subunits was also found in hippocampal astrocytes (32.Turnley A.M. Stapleton D. Mann R.J. Witters L.A. Kemp B.E. Bartlett P.F. J. Neurochem. 1999; 72: 1707-1716Crossref PubMed Scopus (230) Google Scholar). Although AMPK activation has been extensively studied in hypothalamic neurons for its role in food intake (34.Claret M. Smith M.A. Batterham R.L. Selman C. Choudhury A.I. Fryer L.G. Clements M. Al-Qassab H. Heffron H. Xu A.W. Speakman J.R. Barsh G.S. Viollet B. Vaulont S. Ashford M.L. Carling D. Withers D.J. J. Clin. Invest. 2007; 117: 2325-2336Crossref PubMed Scopus (401) Google Scholar, 35.Minokoshi Y. Alquier T. Furukawa N. Kim Y.B. Lee A. Xue B. Mu J. Foufelle F. Ferré P. Birnbaum M.J. Stuck B.J. Kahn B.B. Nature. 2004; 428: 569-574Crossref PubMed Scopus (1318) Google Scholar), little is known about the constitutive levels of activation of AMPK in neurons or in glial cells in other brain regions, such as the hippocampus and cortex. By immunofluorescence in adult mouse brain, we found that activated AMPK is present in most cortical and hippocampal neurons, as shown by the strong colocalization between phosphorylated AMPK and the neuronal marker NeuN (Fig. 4A, panels a–f). No significant staining for phosphorylated AMPK was found in hippocampal astrocytes (Fig. 4A, panels g–i), indicating that under constitutive conditions in the brain, AMPK is mostly active in neurons. Using immunocytochemistry, we confirmed that activated AMPK is present in primary neuronal cultures (Fig. 4B).FIGURE 4Resveratrol lowers Aβ levels by activating AMPK in primary neurons. A, shown is pAMPK (panels a, d, and g), NeuN (panels b and e), GFAP (panel h), and merged (panels c, f, and i) staining of sagittal brain sections of an adult mouse. Hippocampus (panels a–c and g–i) and cerebral cortex (panels d–f) are shown. B, shown is phase contrast (PC), 4′,6-diamidino-2-phenylindole (DAPI), NeuN, pAMPK, and merged staining of 15 days in vitro primary neuronal cultures from J20 APP transgenic mice. C–H, WB analyses of pAMPK, AMPK, pACC, ACC, APP, and actin (C, E, and G) and ELISA measurements of secreted Aβ1-x levels (D, F, and H) in 15 days in vitro J20 mouse primary neurons treated for 24 h with the indicated concentrations of resveratrol (RSV, C and D) or AICAR (E and F). Primary neurons in G and H were treated for 24 h with 80 μm resveratrol or its vehicle (DMSO, control (CTRL)) in the absence or presence of compound C (CC, 20 μm). **, p < 0.01; ns, not significant (Student's t test).View Large Image Figure ViewerDownload Hi-res image Download (PPT)In this context and to confirm our findings in a more physiologically relevant system, we assessed the effect of resveratrol on AMPK activation and Aβ levels in primary neurons. We found that resveratrol significantly and in a dose-dependent manner reduced secreted Aβ levels in primary neurons isolated from APP transgenic mouse forebrain (Fig. 4D), whereas full-length APP levels remained unchanged (Fig. 4C). At concentrations reducing Aβ, resveratrol led to an increase in phosphorylated AMPK and ACC (Fig. 4C), showing that resveratrol can activate AMPK in forebrain neurons. Direct activation of AMPK with AICAR also resulted in a significant decrease in neuronal Aβ levels (Fig. 4, E and F). Importantly, pretreatment with the AMPK inhibitor, compound C, significantly prevented the effect of resveratrol on neuronal Aβ levels (Fig. 4, G and H). Together, these results show that in neurons resveratrol reduced secreted Aβ accumulation by activating AMPK.To gain insight into the mechanism by which resveratrol promotes a reduction of Aβ levels, we asked whether the polyphenol facilitates intracellular degradation of Aβ. Our previous work has shown that resveratrol does not significantly affect APP processing and Aβ production but instead facilitates intracellular Aβ clearance (8.Marambaud P. Zhao H. Davies P. J. Biol. Chem. 2005; 280: 37377-37382Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar). AMPK is a key regulator of autophagy (or macroautophagy), an evolutionary conserved lysosomal pathway involved in protein and organelle turnover via the formation of vacuoles known as autophagosomes (36.Maiuri M.C. Zalckvar E. Kimchi A. Kroemer G. Nat. Rev. Mol. Cell Biol. 2007; 8: 741-752Crossref PubMed Scopus (2761) Google Scholar). Autophagy is deregulated in AD brain and participates in intracellular Aβ degradation in vitro and in vivo (37.Jaeger P.A. Wyss-Coray T. Mol. Neurodegener. 2009; 4: 16Crossref PubMed Scopus (138) Google Scholar, 38.Nixon R.A. J. Cell Sci. 2007; 120: 4081-4091Crossref PubMed Scopus (549) Google Scholar). AMPK activation promotes autophagy by repressing the Ser/Thr protein kinase mTOR, which represents a key blocker of autophagosome formation (39.Meijer A.J. Codogno P. Autophagy. 2007; 3: 238-240Crossref PubMed Scopus (129) Google Scholar). Interestingly, resveratrol was found to induce autophagy in cancer cell lines (40.Opipari Jr., A.W. Tan L. Boitano A.E. Sorenson D.R. Aurora A. Liu J.R. Cancer Res. 2004; 64: 696-703Crossref PubMed Scopus (342) Google Scholar). In this context we asked whether resveratrol (i) inhibits mTOR activity, (ii) promotes autophagy, and (iii) leads to intracellular degradation of Aβ by the lysosomal system.We observed that treatments of HEK293 cells with resveratrol resulted in a dose-dependent inhibition of the phosphorylation of p70-S6 kinase, eIF4B (eukaryotic initiation factor 4B), and S6 ribosomal protein, three proteins downstream from mTOR activation (Fig. 5, A and B). Importantly, resveratrol treatments also led to a strong and dose-dependent conversion of the light chain 3 (LC3) protein from LC3-I to LC3-II, which represents a marker for autophagy induction (Fig. 5, C–E). Furthermore, formation of autophagosomes immunoreactive for LC3 was observed in the presence of resveratrol (Fig. 5F). Finally, treatment with the lysosomotropic drugs bafilomycin A1 and chloroquine, which neutralize lysosomal degradation, resulted in a significant increase of intracellular Aβ accumulation in the presence of resveratrol (Fig. 5, G and H). In summary, these data show that resveratrol inhibited mTOR to induce autophagy and intracellular degradation of Aβ by the lysosomal system.FIGURE 5Resveratrol induces autophagy and lysosomal degradation of Aβ. A–D, APP-HEK293 cells were treated for 24 h with the indicated concentrations of resveratrol (RSV). Cell extracts were then analyzed by WB for phospho-p70S6K (p-p70S6K), p70S6K, phospho-eIF4B (peIF4B), phospho-S6 (pS6), and actin (A) and for LC3 (C). Densitometric analysis and quantification of the p-p70S6K/p70S6K (B) and LC3-II/LC3-I (D) ratios are shown. a.u., arbitrary units. E, WB analyses of LC3 and actin in APP-HEK293 cells treated for the indicated times}, number={12}, journal={Journal of Biological Chemistry}, publisher={American Society for Biochemistry & Molecular Biology (ASBMB)}, author={Vingtdeux, Valérie and Giliberto, Luca and Zhao, Haitian and Chandakkar, Pallavi and Wu, Qingli and Simon, James E. and Janle, Elsa M. and Lobo, Jessica and Ferruzzi, Mario G. and Davies, Peter and et al.}, year={2010}, month={Jan}, pages={9100–9113} }
 @article{neilson_sapper_janle_rudolph_matusheski_ferruzzi_2010, title={Chocolate Matrix Factors Modulate the Pharmacokinetic Behavior of Cocoa Flavan-3-ol Phase II Metabolites Following Oral Consumption by Sprague−Dawley Rats}, volume={58}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf1005353}, DOI={10.1021/jf1005353}, abstractNote={The impact of carbohydrates and milk on the bioavailability of catechin (C) and epicatechin (EC) from chocolate has been previously studied. However, little data exist regarding potential modulation of the phase II metabolism by these chocolate matrix factors. The objectives of this study were to assess the impact of matrix composition on qualitative and quantitative profiles of circulating catechins and their metabolites following administration of commercially relevant chocolate confections. Sprague−Dawley rats were administered 1.5 g of a confection (reference dark, high sucrose, or milk chocolate) by intragastric gavage, and plasma samples were collected over 8 h. High-performance liquid chromatography−mass spectrometry analysis was performed to quantify C, EC, and their metabolites. The predominant metabolites were O-glucuronides (two metabolites) and O-Me-O-glucuronides (three metabolites). Plasma concentrations of metabolites were generally the highest for high sucrose treatment and lowest for milk treatment, while the reference dark treatment generally resulted in intermediate concentrations. The O-Me-(±)-C/EC-O-β-glucuronide (peak 4) was significantly higher for the high sucrose treatment (2325 nM h) versus the milk treatment (1300 nM h). Additionally, CMAX values for (±)-C/EC-O-β-glucuronide (peak 3) and two O-Me-(±)-C/EC-O-β-glucuronides (peaks 4 and 6) were significantly higher for the high sucrose treatment (4012, 518, and 2518 nM, respectively) versus the milk treatment (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate both metabolism and plasma pharmacokinetics and, to a lesser extent, the overall bioavailability of catechins from chocolate confections.}, number={11}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Neilson, Andrew P. and Sapper, Teryn N. and Janle, Elsa M. and Rudolph, Ralf and Matusheski, Nathan V. and Ferruzzi, Mario G.}, year={2010}, month={Jun}, pages={6685–6691} }
 @article{adamec_jannasch_huang_hohman_fleet_peacock_ferruzzi_martin_weaver_2010, title={Development and optimization of an LC-MS/MS-based method for simultaneous quantification of vitamin D2, vitamin D3, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3}, volume={34}, ISSN={1615-9306}, url={http://dx.doi.org/10.1002/jssc.201000410}, DOI={10.1002/jssc.201000410}, abstractNote={Abstract Simultaneous and accurate measurement of vitamin D and 25‐hydroxyvitamin D in biological samples is a barrier limiting our ability to define “optimal” vitamin D status. Thus, our goal was to optimize conditions and evaluate an LC‐MS method for simultaneous detection and quantification of vitamin D 2 , vitamin D 3 , 25‐hydroxyvitamin D 2 and 25‐hydroxyvitamin D 3 in serum. Extraction and separation of vitamin D forms were achieved using acetone liquid–liquid extraction and by a reversed phase C8 column, respectively. Detection was performed on a triple quadrupole tandem mass spectrometer (QQQ‐MS/MS) equipped with atmospheric pressure photo ionization source. The LOQs for all analytes tested were 1 ng/mL for hydroxylated molecules and 2 ng/mL for the parent vitamin Ds. RSD at lower LOQ (2 ng/mL) and in medium (80 ng/mL) and high (200 ng/mL) quality control samples did not exceed 20 and 15% CV, respectively. Accuracy of the method for determination of hydroxylated molecules was also validated using National Institutes of Standards and Technology standard samples and found to be in the range of 90.9–111.2%. In summary, a sensitive and reproducible method is reported for simultaneous quantification of vitamin D 2 , vitamin D 3 , 25‐hydroxyvitamin D 2 and 25‐hydroxyvitamin D 3 molecules in biological samples.}, number={1}, journal={Journal of Separation Science}, publisher={Wiley}, author={Adamec, Jiri and Jannasch, Amber and Huang, Jianjie and Hohman, Emily and Fleet, James C. and Peacock, Munro and Ferruzzi, Mario G. and Martin, Berdine and Weaver, Connie M.}, year={2010}, month={Nov}, pages={11–20} }
 @article{peters_green_janle_ferruzzi_2010, title={Formulation with ascorbic acid and sucrose modulates catechin bioavailability from green tea}, volume={43}, ISSN={0963-9969}, url={http://dx.doi.org/10.1016/j.foodres.2009.08.016}, DOI={10.1016/j.foodres.2009.08.016}, abstractNote={In order to investigate the impact of common food ingredients on catechin absorption, green tea (GT) extract (50 mg) was formulated plain, with sucrose (GT + S), with ascorbic acid (GT + AA) and with sucrose and ascorbic acid (GT + S + AA). Bioavailability and bioaccessibility were assessed in Sprague Dawley rats and an in vitro digestion/Caco-2 cell model respectively. Absorption of epigallocatechin (EGC) and epigallocatechin gallate (EGCG) was significantly (P < 0.05) enhanced in GT + S + AA formulations (AUC0–6 h = 3237.0 and 181.8 pmol h/L plasma respectively) relative to GT control (AUC0–6 h = 1304.1 and 61.0 pmol h/L plasma respectively). In vitro digestive recovery was higher for EGC and epicatechin (EC) (∼51–53%) relative to EGCG and epicatechin gallate (ECG) (<20%) and was modestly enhanced in GT + S and GT + S + AA formulations. Accumulation of EGC, EGCG and ECG by Caco-2 cells was significantly (P < 0.05) higher from GT + S + AA compared to other formulations while retention of catechins was enhanced in presence of ascorbic acid. These data suggest that formulation with sucrose and ascorbic acid may improve catechin bioavailability by enhancing bioaccessibility and intestinal uptake from tea.}, number={1}, journal={Food Research International}, publisher={Elsevier BV}, author={Peters, Catrina M. and Green, Rodney J. and Janle, Elsa M. and Ferruzzi, Mario G.}, year={2010}, month={Jan}, pages={95–102} }
 @article{gutierrez-orozco_stephens_neilson_green_ferruzzi_bomser_2010, title={Green and Black Tea Inhibit Cytokine-Induced Il-8 Production and Secretion in AGS Gastric Cancer Cells via Inhibition of NF-κB Activity}, volume={76}, ISSN={0032-0943 1439-0221}, url={http://dx.doi.org/10.1055/s-0030-1249975}, DOI={10.1055/s-0030-1249975}, abstractNote={Corrected by: Erratum for: Green and Black Tea Inhibit Cytokine-Induced Il-8 Production and Secretion in AGS Gastric Cancer Cells via Inhibition of NF-κB ActivityPlanta Med 2010; 76(15): E7-E7DOI: 10.1055/s-0030-1250052}, number={15}, journal={Planta Medica}, publisher={Georg Thieme Verlag KG}, author={Gutierrez-Orozco, Fabiola and Stephens, Brian and Neilson, Andrew and Green, Rodney and Ferruzzi, Mario and Bomser, Joshua}, year={2010}, month={May}, pages={1659–1665} }
 @article{marambaud_vingtdeux_giliberto_zhao_chandakkar_wu_simon_janle_lobo_ferruzzi_et al._2010, title={P2-317: Resveratrol lowers beta-amyloid accumulation and deposition in vivo
 by controlling AMPK signaling}, volume={6}, ISSN={1552-5260}, url={http://dx.doi.org/10.1016/j.jalz.2010.05.1368}, DOI={10.1016/j.jalz.2010.05.1368}, abstractNote={Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the deposition of Abeta peptides into cerebral senile plaques. A growing body of literature has demonstrated the beneficial effect of the natural polyphenol resveratrol on age-related metabolic deterioration and its protective role in metabolic diseases, such as diabetes. Recently, several studies have focused on the potential relationship between AD and metabolic diseases. Diabetes and obesity significantly increase cognitive decline and AD risk, supporting the notion that molecular mechanisms of cellular energy homeostasis are linked to AD pathogenesis. Resveratrol appears to be protective against the deregulation of energy homeostasis observed in mouse models for metabolic syndromes via the activation of key metabolic sensor proteins, such as the AMP-activated protein kinase (AMPK). Resveratrol also lowers Abeta levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Here we sought to determine whether the anti-amyloidogenic effect of resveratrol is linked to mechanisms involved in cellular energy homeostasis. Cell lines and APP-transgenic mice were employed to identify the mechanism by which resveratrol promotes Abeta clearance in vitro and in vivo. We found that resveratrol lowered Abeta accumulation via activation of AMPK. AMPK is a Ser/Thr protein kinase activated by CaMKKbeta, which controls mechanisms relevant to protein degradation by regulating mTOR signaling and autophagy. Our results show that resveratrol activated AMPK via CaMKKbeta. Activation of AMPK by resveratrol resulted in mTOR inhibition and initiation of autophagy and lysosomal clearance of Abeta. Importantly, we also demonstrate that resveratrol, orally administered in mice, reached the brain where it activated AMPK and significantly reduced Abeta levels and deposition in the cerebral cortex, indicating that resveratrol is both bioavailable and bioactive in the brain after oral dosing. This study identifies AMPK as a key neuroprotective kinase against Abeta accumulation in cell lines and in vivo in mice. This work provides a rationale for exploring the therapeutic potential of resveratrol and AMPK activation in AD.}, journal={Alzheimer's & Dementia}, publisher={Wiley}, author={Marambaud, Philippe and Vingtdeux, Valérie and Giliberto, Luca and Zhao, Haitian and Chandakkar, Pallavi and Wu, Qingli and Simon, James E. and Janle, Elsa M. and Lobo, Jessica and Ferruzzi, Mario G. and et al.}, year={2010}, month={Jul}, pages={S406–S406} }
 @article{neilson_song_sapper_bomser_ferruzzi_2010, title={Tea catechin auto-oxidation dimers are accumulated and retained by Caco-2 human intestinal cells}, volume={30}, ISSN={0271-5317}, url={http://dx.doi.org/10.1016/j.nutres.2010.05.006}, DOI={10.1016/j.nutres.2010.05.006}, abstractNote={Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers (theasinensins [THSNs] and P-2 analogs) were quantified in commercial teas by high-performance liquid chromatography-mass spectrometry. (-)-Epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) homodimers were present at 10 to 43 and 0 to 62 mumol/g leaf, respectively. The EGC-EGCG heterodimers were present at 0 to 79 mumol/g. The potential intestinal absorption of these dimers was assessed using Caco-2 intestinal cells. Catechin monomers and dimers were detected in cells exposed to media containing monomers and preformed dimers. Accumulation of dimers was significantly greater than monomers from test media. Three-hour accumulation of EGC and EGCG was 0.19% to 0.55% and 1.24% to 1.35%, respectively. Comparatively, 3-hour accumulation of the EGC P-2 analog and THSNs C/E was 0.89% +/- 0.28% and 1.53% +/- 0.36%, respectively. Accumulation of P-2 and THSNs A/D was 6.93% +/- 2.1% and 10.1% +/- 3.6%, respectively. The EGCG-EGC heterodimer P-2 analog and THSN B 3-hour accumulation was 4.87% +/- 2.2% and 4.65% +/- 2.8%, respectively. One-hour retention of P-2 and THSNs A/D was 171% +/- 22% and 29.6% +/- 9.3% of accumulated amount, respectively, suggesting intracellular oxidative conversion of THSNs to P-2. These data suggest that catechin dimers present in the gut lumen may be readily absorbed by intestinal epithelium.}, number={5}, journal={Nutrition Research}, publisher={Elsevier BV}, author={Neilson, Andrew P. and Song, Brian J. and Sapper, Teryn N. and Bomser, Joshua A. and Ferruzzi, Mario G.}, year={2010}, month={May}, pages={327–340} }
 @article{ferruzzi_2010, title={The influence of beverage composition on delivery of phenolic compounds from coffee and tea}, volume={100}, ISSN={0031-9384}, url={http://dx.doi.org/10.1016/j.physbeh.2010.01.035}, DOI={10.1016/j.physbeh.2010.01.035}, abstractNote={Epidemiological data suggest that consumption of coffee and tea is associated with a reduced risk of several chronic and degenerative diseases including cardiovascular disorders, diabetes, obesity and neurodegenerative disorders. Both coffee and tea are a rich source of phenolic compounds including chlorogenic acids in coffee; and flavan-3-ols as well as complex theaflavins and thearubigens in tea. Coffee and tea are two of the most commonly consumed beverages in the world and thus represent a significant opportunity to positively affect disease risk and outcomes globally. Central to this opportunity is a need to better understand factors that may affect the bioavailability of specific phenolic components from coffee and tea based beverages. An overview of the phenolic composition of coffee and tea is discussed in the context of how processing and composition might influence phenolic profiles and bioavailability of individual phenolic components. Specifically, the impact of beverage formulation, the extent and type of processing and the influence of digestion on stability, bioavailability and metabolism of bioactive phenolics from tea and coffee are discussed. The impact of co-formulation with ascorbic acid and other phytochemicals are discussed as strategies to improve absorption of these health promoting phytochemicals. A better understanding of how the beverage composition impacts phenolic profiles and their bioavailability is critical to development of beverage products designed to deliver specific health benefits.}, number={1}, journal={Physiology & Behavior}, publisher={Elsevier BV}, author={Ferruzzi, Mario G.}, year={2010}, month={Apr}, pages={33–41} }
 @article{vingtdeux_zhao_chandakkar_wu_simon_janle_lobo_ferruzzi_davies_marambaud_2009, title={C1 Régulation des taux cérébraux de peptide Aß par l’AMP kinase}, volume={165}, ISSN={0035-3787}, url={http://dx.doi.org/10.1016/S0035-3787(09)72554-8}, DOI={10.1016/S0035-3787(09)72554-8}, abstractNote={Introduction Le resveratrol (trans-3,4’,5-trihydroxystilbene) est un polyphenol naturel capable d’induire la degradation du peptide beta-amyloide (Abeta), le constituant majeur des plaques seniles formees au cours de la maladie d’Alzheimer. En plus de ses activites anti-oxydantes et anti-inflammatoires, des etudes ont demontrees que le resveratrol mimait l’effet de la restriction calorique sur l’allongement de la duree de vie chez differents organismes. Entre outre, l’administration reguliere de resveratrol augmente l’esperance de vie des souris soumises a un regime hypercalorique. Comme cela a ete demontre pour la restriction calorique, les effets benefiques du resveratrol sur la longevite passent par l’activation de la proteine kinase activee par l’AMP (AMPK). L’AMPK joue un role cle dans la regulation du metabolisme energetique en ciblant des proteines impliquees par exemple dans la synthese et l’oxydation des acides gras, ou encore en regulant la degradation proteique via l’inhibition du represseur de l’autophagie : mTOR. Ces donnees suggerent que l’effet du resveretrol sur le metabolisme de l’Abeta pourrait egalement passer par l’activation de l’AMPK. Materiel et methodes/Resultats Nous avons confirme l’effet du resveratrol sur la diminution du peptide Abeta in vitro dans les cellules HEK293 et N2a qui surexpriment APP. Grâce a l’utilisation d’une methode de criblage de kinases, nous avons identifie l’AMPK comme etant l’une des cibles principales du resveratrol. Nous avons determine que l’activation de l’AMPK par le resveratrol resulte d’une augmentation des niveaux intracellulaires de calcium et de l’activation de CaMKKbeta. De plus, l’activation pharmacologique de l’AMPK ou l’expression par transfection d’une forme constitutivement active de la kinase entraine une diminution de l’Abeta. Inversement, l’utilisation d’un dominant negatif de l’AMPK inhibe l’effet du resveratrol sur Abeta, suggerant que le resveratrol diminue Abeta en activant AMPK. L’activation d’AMPK par le resveratrol entraine l’inhibition de mTOR, augmentant ainsi l’autophagie et la degradation intracellulaire de l’Abeta. Finalement, l’administration de resveratrol a des souris transgeniques APP/ PS1 entraine une activation de l’AMPK dans le cerveau et une diminution signficative de l’Abeta et des depots amyloides dans le cortex. Conclusion Nos resultats indiquent que l’activation de la voie CaMKKbeta/AMPK/mTOR par le resveratrol entraine la degradation intracellulaire de l’Abeta par un mecanisme d’autophagie.}, number={10}, journal={Revue Neurologique}, publisher={Elsevier BV}, author={Vingtdeux, V. and Zhao, H. and Chandakkar, P. and Wu, Q. and Simon, J. and Janle, E. and Lobo, J. and Ferruzzi, M. and Davies, P. and Marambaud, P.}, year={2009}, month={Oct}, pages={19} }
 @article{shim_ferruzzi_kim_janle_santerre_2009, title={Impact of phytochemical-rich foods on bioaccessibility of mercury from fish}, volume={112}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2008.05.030}, DOI={10.1016/j.foodchem.2008.05.030}, abstractNote={The effects of phytochemical-rich foods on bioaccessibility of mercury in fish tissue (the amount of mercury that is released from fish into gastrointestinal tract fluid following a simulated digestion) were investigated using an in vitro digestion. Total mercury in the aqueous phase following a simulated digestion of fish with added food treatments was used to measure mercury bioaccessibility. Green tea extract (31–2000 mg), black tea extract (31–2000 mg), and soy protein (50–100 mg) significantly reduced mercury bioaccessibility by 82–92%, 88–91%, and 44–87%, respectively. Grapefruit juice (0.5–10 ml) did not reduce mercury in the aqueous phase. Wheat bran (50–1000 mg) decreased mercury bioaccessibility (84%); oat bran and psyllium reduced bioaccessibility (by 59–75%, 15–31%, respectively) at amounts greater than 500 mg. We therefore suggest that co-consumption of foods containing phytochemicals at the same time as fish that contains mercury may potentially reduce mercury absorption compared to eating fish alone.}, number={1}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Shim, Soon-Mi and Ferruzzi, Mario G. and Kim, Young-Cheul and Janle, Elsa M. and Santerre, Charles R.}, year={2009}, month={Jan}, pages={46–50} }
 @article{neilson_george_janle_mattes_rudolph_matusheski_ferruzzi_2009, title={Influence of Chocolate Matrix Composition on Cocoa Flavan-3-ol Bioaccessibility In Vitro and Bioavailability in Humans}, volume={57}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf902919k}, DOI={10.1021/jf902919k}, abstractNote={Conflicting data exist regarding the influence of chocolate matrices on the bioavailability of epicatechin (EC) from cocoa. The objective of this study was to assess the bioavailability of EC from matrices varying in macronutrient composition and physical form. EC bioavailability was assessed from chocolate confections [reference dark chocolate (CDK), high sucrose (CHS), high milk protein (CMP)] and cocoa beverages [sucrose milk protein (BSMP), non-nutritive sweetener milk protein (BNMP)], in humans and in vitro. Six subjects consumed each product in a randomized crossover design, with serum EC concentrations monitored over 6 h post consumption. Areas under the serum concentration−time curve (AUC) were similar among chocolate matrices. However, AUCs were significantly increased for BSMP and BNMP (132 and 143 nM h) versus CMP (101 nM h). Peak serum concentrations (CMAX) were also increased for BSMP and BNMP (43 and 42 nM) compared to CDK and CMP (32 and 25 nM). Mean TMAX values were lower, although not statistically different, for beverages (0.9−1.1h) versus confections (1.8−2.3h), reflecting distinct shapes of the pharmacokinetic curves for beverages and confections. In vitro bioaccessibility and Caco-2 accumulation did not differ between treatments. These data suggest that bioavailability of cocoa flavan-3-ols is likely similar from typical commercial cocoa based foods and beverages, but that the physical form and sucrose content may influence TMAX and CMAX.}, number={20}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Neilson, Andrew P. and George, Judy C. and Janle, Elsa M. and Mattes, Richard D. and Rudolph, Ralf and Matusheski, Nathan V. and Ferruzzi, Mario G.}, year={2009}, month={Oct}, pages={9418–9426} }
 @article{weaver_barnes_wyss_kim_morré_morré_simon_lila_janle_ferruzzi_2009, title={Research highlights from the Purdue-UAB Botanicals Research Center for Age Related Diseases}, volume={47}, ISSN={1388-0209 1744-5116}, url={http://dx.doi.org/10.1080/13880200902988603}, DOI={10.1080/13880200902988603}, abstractNote={The Purdue-UAB Botanicals Research Center for Age Related Disease uses multidisciplinary and innovative technologies to investigate the bioavailability of bioactive polyphenolic constituents from botanicals and their relationship to human health. Many age-related diseases are associated with oxidative stress and tissue damage. One of the research goals of the Purdue-UAB Center is to investigate the bioavailability of bioactive natural compounds from a complex botanical mixture to the organ affected by the disease, determine the uptake and metabolism of these compounds and relate these data to a protective mechanism. Equally important is to screen commercially available botanicals for their safety and efficacy. The central aims of the Center include the investigation of botanicals and their relationship to bone antiresorptive capacity, cognitive function, vascular effects, and cancer prevention.}, number={8}, journal={Pharmaceutical Biology}, publisher={Informa UK Limited}, author={Weaver, Connie M. and Barnes, Stephen and Wyss, J. Michael and Kim, Helen and Morré, Dorothy M. and Morré, D. James and Simon, James E. and Lila, Mary Ann and Janle, Elsa M. and Ferruzzi, Mario G.}, year={2009}, month={Jul}, pages={768–773} }
 @article{kean_hamaker_ferruzzi_2008, title={Carotenoid Bioaccessibility from Whole Grain and Degermed Maize Meal Products}, volume={56}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf8018613}, DOI={10.1021/jf8018613}, abstractNote={Although yellow maize (Zea mays) fractions and products are a source of dietary carotenoids, only limited information is available on the bioavailability of these pigments from maize-based foods. To better understand the distribution and bioavailability of carotenoid pigments from yellow maize (Z. mays) products, commercial milled maize fractions were screened for carotenoid content as were model foods including extruded puff, bread, and wet cooked porridge. Carotenoid content of maize fractions ranged from a low of 1.77−6.50 mg/kg in yellow maize bran (YCB) to 12.04−17.94 mg/kg in yellow corn meal (YCM). Lutein and zeaxanthin were major carotenoid species in maize milled fractions, accounting for ∼70% of total carotenoid content. Following screening, carotenoid bioaccessibility was assessed from model foods using a simulated three-stage in vitro digestion process designed to measure transfer of carotenoids from the food matrix to bile salt lipid micelles (micellarization). Micellarization efficiency of xanthophylls was similar from YCM extruded puff and bread (63 and 69%), but lower from YCM porridge (48%). Xanthophyll micellarization from whole yellow corn meal (WYCM) products was highest in bread (85%) and similar in extruded puff and porridge (46 and 47%). For extruded puffs and breads, β-carotene micellarization was 10−23%, but higher in porridge (40−63%), indicating that wet cooking may positively influence bioaccessibility of apolar carotenes. The results suggest that maize-based food products are good dietary sources of bioaccessible carotenoids and that specific food preparation methods may influence the relative bioaccessibility of individual carotenoid species.}, number={21}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Kean, Ellie G. and Hamaker, Bruce R. and Ferruzzi, Mario G.}, year={2008}, month={Nov}, pages={9918–9926} }
 @article{albrecht_clubbs_ferruzzi_bomser_2008, title={Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation}, volume={171}, ISSN={0009-2797}, url={http://dx.doi.org/10.1016/j.cbi.2007.09.001}, DOI={10.1016/j.cbi.2007.09.001}, abstractNote={Epigallocatechin-3-gallate (EGCG), a tea polyphenol, inhibits the proliferation of many cancer cell lines; however, the antiproliferative mechanism(s) are not well-characterized. The objective of this study is to identify the cellular signaling mechanism(s) responsible for the antiproliferative effects of EGCG in the PC-3 prostate cancer cell line. EGCG inhibited PC-3 cell proliferation in a concentration-dependent manner with an IC50 value of 39.0 μM, but had no effect on the proliferation of a nontumorigenic prostate epithelial cell line (RWPE-1). Treatment of PC-3 cells with EGCG (0–50 μM) resulted in time and concentration-dependent activation of the extracellular signal-regulated kinase (ERK1/2) pathway. EGCG treatment did not induce ERK1/2 activity in RWPE-1 cells. The activation of ERK1/2 by EGCG was not inhibited using PD98059, a potent inhibitor of mitogen-activated protein kinase kinase (MEK), the immediate upstream kinase responsible for ERK1/2 activation; suggesting a MEK-independent signaling mechanism. Pretreatment of PC-3 cells with a phosphoinositide-3 kinase (PI3K) inhibitor partially reduced both EGCG-induced ERK1/2 activation and the antiproliferative effects of this polyphenol. These results suggest that ERK1/2 activation via a MEK-independent, PI3-K-dependent signaling pathway is partially responsible for the antiproliferative effects of EGCG in PC-3 cells.}, number={1}, journal={Chemico-Biological Interactions}, publisher={Elsevier BV}, author={Albrecht, Daniel S. and Clubbs, Elizabeth A. and Ferruzzi, Mario and Bomser, Joshua A.}, year={2008}, month={Jan}, pages={89–95} }
 @article{hiatt_ferruzzi_taylor_mauer_2008, title={Impact of Deliquescence on the Chemical Stability of Vitamins B1, B6, and C in Powder Blends}, volume={56}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf800709f}, DOI={10.1021/jf800709f}, abstractNote={Single vitamin ingredients and blends in premixes are widely used in the food and supplement industries and are predominantly in powder form. To meet label claims and/or determine appropriate overages, it is important to characterize the stability of these ingredients. Although moisture is a known promoter of instability in powder blends, the combined effects of storage relative humidity (RH), formulation, and deliquescence on the stability of these systems are not well-characterized. The objective of this study was to determine the effect of deliquescence on the stability of vitamins B1, B6, and C and their mixtures. Deliquescence points (RH0s) for all formulations were determined by moisture sorption analysis. Single, binary, ternary, and quaternary mixtures of thiamin HCl, pyridoxine HCl, sodium ascorbate, and fructose were stored in RH-controlled environmental chambers between 43 and 98% RH at 22 °C for up to 12 weeks. Vitamin stability was determined by high-performance liquid chromatography (HPLC). Formulation and storage RH significantly affected vitamin stability. Thiamin and ascorbate degradation were significantly promoted above the RH0, while pyridoxine was least affected by storage RH. The deliquescence lowering phenomenon enhanced moisture sorption of blends at RHs below the RH0s. Ascorbate enhanced thiamin degradation. Therefore, formulation, storage conditions, and the relation of these to deliquescence points may affect the shelf life, quality, and functionality of vitamin blends and should be considered in product development, processing, storage, and use.}, number={15}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Hiatt, Ashley N. and Ferruzzi, Mario G. and Taylor, Lynne S. and Mauer, Lisa J.}, year={2008}, month={Aug}, pages={6471–6479} }
 @article{machado_ferruzzi_nielsen_2008, title={Impact of the Hard-to-Cook Phenomenon on Phenolic Antioxidants in Dry Beans (Phaseolus vulgaris)}, volume={56}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf072861y}, DOI={10.1021/jf072861y}, abstractNote={Epidemiological studies have established a link between consumption of dry beans and lower incidence of degenerative diseases. This relationship is attributed in part to properties of natural antioxidants present in beans. The objective of this study was to determine if the hard-to-cook (HTC) phenomenon in beans had a negative effect on the content of free and bound phenolic antioxidants and antioxidant capacity. Folin−Ciocalteu, Trolox equivalent antioxidant capacity, and HPLC methods were used to quantify the content of phenolic acids and antioxidant capacity. Results showed that the HTC phenomenon did not equally affect the content and antioxidant capacity of phenolic acids in different bean cultivars. Black beans were most affected, the contents of free and acid hydrolyzable phenolic acids being reduced by 35 and 36%, respectively, and the antioxidant activity by 18 and 25%, respectively. This study showed that the HTC phenomenon affected a potential nutritive characteristic of dry beans.}, number={9}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Machado, Cynthia M. and Ferruzzi, Mario G. and Nielsen, S. Suzanne}, year={2008}, month={May}, pages={3102–3110} }
 @article{ortiz_ferruzzi_taylor_mauer_2008, title={Interaction of Environmental Moisture with Powdered Green Tea Formulations: Effect on Catechin Chemical Stability}, volume={56}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf800246s}, DOI={10.1021/jf800246s}, abstractNote={Green tea and tea catechins must be stable in finished products to deliver health benefits; however, they may be adversely affected by tea processing/storage conditions and the presence of other components. The objective of this study was to determine the effects of storage relative humidity (RH) and addition of other ingredients on catechin stability in simulated dry beverage mixtures. Samples of green tea powder alone and mixed with sucrose, citric acid, and/or ascorbic acid were prepared and stored in desiccators at 22 degrees C and 0-85% RH for up to 3 months. Epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate were determined by high-performance liquid chromatography (HPLC). Formulation and the interaction of formulation and RH significantly promoted catechin degradation ( P < 0.0001). The chemical degradation of total and individual catechins in green tea powder formulations was significantly increased ( P < 0.0001) by exposure to increasing RH, and the degradation was exacerbated at > or = 58% RH by the presence of powdered citric acid and at > or = 75% RH by the presence of ascorbic acid. Catechins degraded the most in formulations containing both acids. Although catechin chemical stability was maintained at < or = 43% RH in all samples stored at 22 degrees C for 3 months, caking was observed in samples at these relative humidities. These results are the first to demonstrate that addition of other dry components to tea powders may affect catechin stability in finished dry blends and highlight the importance of considering the complex interplay between a multicomponent system and its environment for developing stable products.}, number={11}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Ortiz, J. and Ferruzzi, M. G. and Taylor, L. S. and Mauer, L. J.}, year={2008}, month={Jun}, pages={4068–4077} }
 @article{neilson_hopf_cooper_pereira_bomser_ferruzzi_2007, title={Catechin Degradation with Concurrent Formation of Homo- and Heterocatechin Dimers duringin VitroDigestion}, volume={55}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf071645m}, DOI={10.1021/jf071645m}, abstractNote={Catechins were subjected to in vitro gastric and small intestinal digestion. EGCG, EGC, and ECG were significantly degraded at all concentrations tested, with losses of 71–91, 72–100, and 60–61%, respectively. EC and C were comparatively stable, with losses of 8–11 and 7–8%, respectively. HLPC-ESI-MS/MS indicated that EGCG degradation under simulated digestion resulted in production of theasinensins (THSNs) A and D (m/z 913) and P-2 (m/z 883), its autoxidation homodimers. EGC dimerization produced the homodimers THSN C and E (m/z 609) and homodimers analogous to P-2 (m/z 579). ECG homodimers were not observed. EGCG and EGC formed heterodimers analogous to the THSNs (m/z 761) and P-2 (m/z 731). EGCG and ECG formed homodimers analogous to the THSNs (m/z 897). This study provides an expanded profile of catechin dimers of digestive origin that may potentially form following consumption of catechins. These data provide a logical basis for initial screening to detect catechin digestive products in vivo.}, number={22}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Neilson, Andrew P. and Hopf, Amber S. and Cooper, Bruce R. and Pereira, Michael A. and Bomser, Joshua A. and Ferruzzi, Mario G.}, year={2007}, month={Oct}, pages={8941–8949} }
 @article{kean_ejeta_hamaker_ferruzzi_2007, title={Characterization of Carotenoid Pigments in Mature and Developing Kernels of Selected Yellow-Endosperm Sorghum Varieties}, volume={55}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf062939v}, DOI={10.1021/jf062939v}, abstractNote={Sorghum is a critical source of food in the semiarid regions of sub-Saharan Africa and India and a potential source of dietary phytochemicals including carotenoids. The objective of this study was to determine the carotenoid profiles of sorghum cultivars, selected on the basis of their yellow-endosperm kernels, at various developmental stages. Following extraction from sorghum flours, carotenoids were separated by high-performance liquid chromatography (HPLC) with diode array detection. Total carotenoid content in fully matured yellow-endosperm sorghum kernels (0.112−0.315 mg/kg) was significantly lower (p < 0.05) than that in yellow maize (1.152 mg/kg) at physiological maturity. Variation in total carotenoids and within individual carotenoid species was observed in fully mature sorghum cultivars. For developing kernels, large increases in carotenoid content occurred between 10 and 30 days after half bloom (DAHB), resulting in a peak accumulation between 6.06 and 28.53 μg of total carotenoids per thousand kernels (TK). A significant (p < 0.05) decline was noted from 30 to 50 DAHB, resulting in a final carotenoid content of 2.62−15.02 μg/TK total carotenoids. (all-E)-Zeaxanthin was the most abundant carotenoid, ranging from 2.22 to 13.29 μg/TK at 30 DAHB. (all-E)-β-Carotene was present in modest amounts (0.15−3.83 μg/TK). These data suggest the presence of genetic variation among sorghum cultivars for carotenoid accumulation in developing and mature kernels. Keywords: Carotenoids; lutein; zeaxanthin; provitamin A; sorghum; maize; HPLC; cereals; development}, number={7}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Kean, Ellie G. and Ejeta, Gebisa and Hamaker, Bruce R. and Ferruzzi, Mario G.}, year={2007}, month={Apr}, pages={2619–2626} }
 @article{green_murphy_schulz_watkins_ferruzzi_2007, title={Common tea formulations modulatein vitro digestive recovery of green tea catechins}, volume={51}, ISSN={1613-4125 1613-4133}, url={http://dx.doi.org/10.1002/mnfr.200700086}, DOI={10.1002/mnfr.200700086}, abstractNote={Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with < 20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with ⪇ 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p < 0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81–98%), EGCG (56–76%), EC (86–95%), and ECG (30–55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.}, number={9}, journal={Molecular Nutrition & Food Research}, publisher={Wiley}, author={Green, Rodney J. and Murphy, Angus S. and Schulz, Burkhard and Watkins, Bruce A. and Ferruzzi, Mario G.}, year={2007}, month={Sep}, pages={1152–1162} }
 @article{watkins_hannon_ferruzzi_li_2007, title={Dietary PUFA and flavonoids as deterrents for environmental pollutants}, volume={18}, ISSN={0955-2863}, url={http://dx.doi.org/10.1016/j.jnutbio.2006.12.002}, DOI={10.1016/j.jnutbio.2006.12.002}, abstractNote={Various nutrients and plant-derived phytochemicals are associated with a reduced risk of many diet-related chronic diseases including cardiovascular disease, cancer, diabetes, arthritis and osteoporosis. A common theme that links many chronic diseases is uncontrolled inflammation. The long-chain (LC) omega-3 polyunsaturated fatty acids (PUFA) and flavonoids are known to possess anti-inflammatory actions in cell cultures, animal models and humans. Minimizing the condition of persistent inflammation has been a primary aim for drug development, but understanding how food components attenuate this process is at the nexus for improving the human condition. The prevalence of environmental toxins such as heavy metals and organics that contribute to diminished levels of antioxidants likely aggravates inflammatory states when intakes of omega-3 PUFA and flavonoids are marginal. Scientists at Purdue University have formed a collaboration to better understand the metabolism and physiology of flavonoids. This new effort is focused on determining how candidate flavonoids and their metabolites affect gene targets of inflammation in cell culture and animal models. The challenge of this research is to understand how LC omega-3 PUFA and flavonoids affect the biology of inflammation. The goal is to determine how nutrients and phytochemicals attenuate chronic inflammation associated with a number of diet-related diseases that occur throughout the life cycle. The experimental approach involves molecular, biochemical and physiological endpoints of aging, cancer, obesity and musculoskeletal diseases. Examples include investigations on the combined effects of PUFA and cyanidins on inflammatory markers in cultures of human cancer cells. The actions of catechins and PUFA on muscle loss and osteopenia are being studied in a rodent model of disuse atrophy to explain how muscle and bone communicate to prevent tissue loss associated with injury, disease and aging. The purpose of this review is to introduce the concept for studying food components that influence inflammation and how LC omega-3 PUFA and flavonoids could be used therapeutically against inflammation that is mediated by environmental pollutants.}, number={3}, journal={The Journal of Nutritional Biochemistry}, publisher={Elsevier BV}, author={Watkins, B and Hannon, K and Ferruzzi, M and Li, Y}, year={2007}, month={Mar}, pages={196–205} }
 @article{ferruzzi_blakeslee_2007, title={Digestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives}, volume={27}, ISSN={0271-5317}, url={http://dx.doi.org/10.1016/j.nutres.2006.12.003}, DOI={10.1016/j.nutres.2006.12.003}, abstractNote={The growing body of epidemiological and experimental evidence associating diets rich in fruits and vegetables with prevention of chronic diseases such as cancer has stimulated interest in plant food phytochemicals as physiologically active dietary components. Chlorophyll and its various derivatives are believed to be among the family of phytochemical compounds that are potentially responsible for such associations. Dietary chlorophyll is predominantly composed of lipophilic derivatives including chlorophyll a and b (fresh fruits and vegetables), metal-free pheophytins and pyropheophytins (thermally processed fruits and vegetables), as well as Zn-pheophytins and Zn-pyropheophytins (thermally processed green vegetables). Water-soluble derivatives including chlorophyllides, pheophorbides, as well as a commercial-grade derivative known as sodium copper chlorophyllin (SCC) also contribute to the diversity of dietary chlorophyll derivatives. Although the use of chlorophyll derivatives, especially SCC, in traditional medical applications is well documented, it is perhaps the potential of chlorophyll as a cancer preventative agent that has drawn significant attention recently. Biological activities attributed to chlorophyll derivatives consistent with cancer prevention include antioxidant and antimutagenic activity, mutagen trapping, modulation of xenobiotic metabolism, and induction of apoptosis. Although most research has focused on commercial-grade SCC, the extent to which natural chlorophyll derivatives modulate biomarkers of cancer risk is also being explored. Recent research efforts have also included investigation of the impact of digestive factors on chlorophyll structure and bioaccessibility as a means to better understand the extent to which these pigments may be bioavailable in humans and therefore have more systemic impact in the prevention of cancer.}, number={1}, journal={Nutrition Research}, publisher={Elsevier BV}, author={Ferruzzi, Mario G. and Blakeslee, Joshua}, year={2007}, month={Jan}, pages={1–12} }
 @article{rudelle_ferruzzi_cristiani_moulin_macé_acheson_tappy_2007, title={Effect of a Thermogenic Beverage on 24-Hour Energy Metabolism in Humans*}, volume={15}, ISSN={1930-7381 1930-739X}, url={http://dx.doi.org/10.1038/oby.2007.529}, DOI={10.1038/oby.2007.529}, abstractNote={To test whether consumption of a beverage containing active ingredients will increase 24-hour energy metabolism in healthy, young, lean individuals.Thirty-one male and female subjects consumed 3 x 250-mL servings of a beverage containing green tea catechins, caffeine, and calcium for 3 days in a single-center, double-blind, placebo-controlled, cross-over design study. On the 3rd day, 23-hour energy metabolism, extrapolated to 24-hour, was measured in a calorimeter chamber. Blood pressure and heart rate were measured, and total day and night urines were analyzed for urea and catecholamine excretion.Twenty-four-hour energy expenditure (EE) and 24-hour fat oxidation were lower in women than in men (p < 0.0001 and p < 0.015, respectively). Although there were no treatment or treatment/gender effects on substrate oxidation, treatment increased 24-hour EE by 106 +/- 31 kcal/24 hours (p = 0.002), equivalent to 4.7 +/- 1.6 kcal/h (day; p = 0.005) and 3.3 +/- 1.5 kcal/h (night; p = 0.04). No significant differences were observed in hemodynamic parameters.The present study provides evidence that consumption of a beverage containing green tea catechins, caffeine, and calcium increases 24-hour EE by 4.6%, but the contribution of the individual ingredients cannot be distinguished. Although this increase is modest, the results are discussed in relation to proposed public health goals, indicating that such modifications are sufficient to prevent weight gain. When consumed regularly as part of a healthy diet and exercise regime, such a beverage may provide benefits for weight control.}, number={2}, journal={Obesity}, publisher={Wiley}, author={Rudelle, Servane and Ferruzzi, Mario G. and Cristiani, Isabelle and Moulin, Julie and Macé, Katherine and Acheson, Kevin J. and Tappy, Luc}, year={2007}, month={Feb}, pages={349–355} }
 @article{huo_ferruzzi_schwartz_failla_2007, title={Impact of Fatty Acyl Composition and Quantity of Triglycerides on Bioaccessibility of Dietary Carotenoids}, volume={55}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf071687a}, DOI={10.1021/jf071687a}, abstractNote={A carotenoid-rich salad meal with varying amounts and types of triglycerides (TG) was digested using simulated gastric and small intestinal conditions. Xanthophylls (lutein and zeaxanthin) and carotenes (α-carotene, β-carotene, and lycopene) in chyme and micelle fraction were quantified to determine digestive stability and efficiency of micellarization (bioaccessibility). Micellarization of lutein (+zeaxanthin) exceeded that of α- and β-carotenes, which was greater than that of lycopene for all test conditions. Micellarization of carotenes, but not lutein (+zeaxanthin), was enhanced (P < 0.05) by addition of TG (2.5% v/w) to the meal and was dependent on fatty acyl chain length in structured TG (c18:1 > c8:0 > c4:0). The degree of unsaturation of c18 fatty acyl chains in TG added to the salad purée did not significantly alter the efficiency of micellarization of carotenoids. Relatively low amounts of triolein and canola oil (0.5–1%) were required for maximum micellarization of carotenes, but more oil (∼2.5%) was required when TG with medium chain saturated fatty acyl groups (e.g., trioctanoin and coconut oil) was added to the salad. Uptake of lutein and β-carotene by Caco-2 cells also was examined by exposing cells to micelles generated during the simulated digestion of salad purée with either triolein or trioctanoin. Cell accumulation of β-carotene was independent of fatty acyl composition of micelles, whereas lutein uptake was slightly, but significantly, increased from samples with digested triolein compared to trioctanoin. The results show that the in vitro transfer of α-carotene, β-carotene, and lycopene from chyme to mixed micelles during digestion requires minimal (0.5–1%) lipid content in the meal and is affected by the length of fatty acyl chains but not the degree of unsaturation in TG. In contrast, fatty acyl chain length has limited if any impact on carotenoid uptake by small intestinal epithelial cells. These data suggest that the amount of TG in a typical meal does not limit the bioaccessibility of carotenoids.}, number={22}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Huo, Tianyao and Ferruzzi, Mario G. and Schwartz, Steven J. and Failla, Mark L.}, year={2007}, month={Oct}, pages={8950–8957} }
 @article{oonsivilai_cheng_bomser_ferruzzi_ningsanond_2007, title={Phytochemical profiling and phase II enzyme-inducing properties of Thunbergia laurifolia Lindl. (RC) extracts}, volume={114}, ISSN={0378-8741}, url={http://dx.doi.org/10.1016/j.jep.2007.08.015}, DOI={10.1016/j.jep.2007.08.015}, abstractNote={Thunbergia laurifolia Lindl. (Acanthaceae) or Rang Chuet (RC) is described in traditional medicine for protection against dietary and environmental toxicants. This work, therefore, investigated RC's phytochemical profile, antimutagenic activity, and xenobiotic detoxification potential in its extracts. RC extracts were prepared by infusion with water, ethanol, acetone and subsequently assayed for major phytochemical constituents. Total phenolic content was 24.33, 5.65, and 1.42microg gallic acid equivalent (GAE) per mL for water, ethanol and acetone extract, respectively. HPLC analysis identified caffeic acid and apigenin as primary constituents of water extracts. Acetone and ethanol extracts contained primarily chlorophyll a and b, pheophorbide a, pheophytin a, and lutein. Treatment of Hepa 1C1C7 cells with standardized RC extracts resulted in a dose-dependent increase in QR specific activity for all extracts. Acetone extract (92microg GAE/mL) increased QR activity 2.8-fold, while ethanol (120microg GAE/mL) and water (1000microg GAE/mL) extracts increased QR activity by 1.35- and 1.56-fold, respectively. The RC extracts were subsequently assayed for mutagen and antimutagenic activity by bacterial reverse mutagenesis assay. All three RC extracts exhibited strong dose-dependent antimutagenic activity inhibiting 2-aminoanthracene induced mutagenesis up to 87% in Salmonella typhimurium TA 98. These results support the traditional medicinal use of RC for detoxification and suggest the potential role of both phenolic acids and natural chlorophyll constituents in modulating these effects.}, number={3}, journal={Journal of Ethnopharmacology}, publisher={Elsevier BV}, author={Oonsivilai, Ratchadaporn and Cheng, Crystal and Bomser, Joshua and Ferruzzi, Mario G. and Ningsanond, Suwayd}, year={2007}, month={Dec}, pages={300–306} }
 @article{ferruzzi_green_2006, title={Analysis of catechins from milk–tea beverages by enzyme assisted extraction followed by high performance liquid chromatography}, volume={99}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2005.08.010}, DOI={10.1016/j.foodchem.2005.08.010}, abstractNote={Extraction and analysis of physiologically significant tea catechins from complex food matrices is complicated by strong association of tea catechins with macronutrients such as proteins. Dependable extraction methods are required to accurately assess and validate levels of bioactive tea catechins in new products. The objective of this work was to investigate recovery of tea catechins from dairy matrices and evaluate pepsin treatment as an enzymatic step to enhance catechin recovery from milk and other protein rich formulations. Brewed green tea was combined with skim milk to produce test solutions ranging from 10% to 50% milk. Samples were treated by either acid (0.1 N HCl), methanol, or by pepsin (40.0 mg/mL). Following treatments, samples were centrifuged and supernatants analyzed for tea catechins by reversed phase C18 HPLC with photodiode array detection. Recovery of total catechins was highest for pepsin treated samples (89–102%), followed by methanol deproteination (78–87%) and acid precipitation (20–74%) with values decreasing with increased milk content. Individual recovery of gallated catechins, namely epigallocatechin-gallate (EGCG) and epicatechin-gallate (ECG), was most affected by the presence and level of milk. The usefulness of pepsin treatment for enhancing recovery of tea catechins was further demonstrated in analysis of commercial soy and milk–tea beverages.}, number={3}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Ferruzzi, Mario G. and Green, Rodney J.}, year={2006}, pages={484–491} }
 @article{ferruzzi_lumpkin_schwartz_failla_2006, title={Digestive Stability, Micellarization, and Uptake of β-Carotene Isomers by Caco-2 Human Intestinal Cells}, volume={54}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf0530603}, DOI={10.1021/jf0530603}, abstractNote={While isomeric profiles of carotenoids found in food often differ from those in body fluids and tissues, insights about the basis for these differences remain limited. We investigated the digestive stability, relative efficiency of micellarization, and cellular accumulation of trans and cis isomers of β-carotene (BC) using an in vitro digestion procedure coupled with human intestinal (Caco-2) cells. A meal containing applesauce, corn oil, and either water-soluble beadlets (WSB) or Dunaliella salina (DS) as a BC source was subjected to simulated gastric and small intestinal digestion. BC isomers were stable during digestion, and the efficiency of micellarization of cis-BC isomers exceeded that of all-trans-BC isomers. The cellular profile of carotenoids generally reflected that in micelles generated during digestion, and intracellular isomerization was minimal. These data suggest that cis isomers of BC are preferentially micellarized during digestion and transferred across the brush-border surface of the enterocyte from mixed micelles with similar efficiency as all-trans-BC at the concentrations of the carotenoids utilized in this study. Keywords: β-carotene; carotenoids; cis isomers; in vitro digestion; Caco-2 intestinal cells; HPLC; electrochemical detection}, number={7}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Ferruzzi, Mario G. and Lumpkin, John L. and Schwartz, Steven J. and Failla, Mark}, year={2006}, month={Apr}, pages={2780–2785} }
 @article{neilson_green_wood_ferruzzi_2006, title={High-throughput analysis of catechins and theaflavins by high performance liquid chromatography with diode array detection}, volume={1132}, ISSN={0021-9673}, url={http://dx.doi.org/10.1016/j.chroma.2006.07.059}, DOI={10.1016/j.chroma.2006.07.059}, abstractNote={Increased interest in potential health-protective activities of flavonoid-rich tea has created the need to take advantage of HPLC column and system advances in order to optimize methodologies for flavonoid analysis. Two new RP-C18 methods for HPLC-DAD analysis of tea flavonoids were developed to facilitate separation of catechins within 5 min and separation of catechins and theaflavins within 10 min total analysis time. Calibration results indicate that these methods have on-column limits of detection on the order of 1-10 pmol for most tea catechins, and method replication generally resulted in intraday and interday peak area variation of <5% for catechins and <9% for theaflavins in green and black tea infusions. These new methods are therefore sensitive, reproducible, and represent a 2-4-fold reduction in HPLC analysis time from existing analytical methods. These improvements are readily achievable with commonly used HPLC equipment, thus facilitating increased sample throughput and efficiency across a broad range of experimental applications.}, number={1-2}, journal={Journal of Chromatography A}, publisher={Elsevier BV}, author={Neilson, Andrew P. and Green, Rodney J. and Wood, Karl V. and Ferruzzi, Mario G.}, year={2006}, month={Nov}, pages={132–140} }
 @article{ferruzzi_schwartz_2005, title={Thermal Degradation of Commercial Grade Sodium Copper Chlorophyllin}, volume={53}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf051010s}, DOI={10.1021/jf051010s}, abstractNote={Sodium copper chlorophyllin (SCC), a water-soluble commercial derivative of chlorophyll, has gained importance as a food colorant and dietary supplement with apparent chemopreventive activities. The thermal stability of SCC was studied to assess the potential application of this chlorophyll derivative for use in thermally processed foods and supplements. Thermal degradation of an aqueous 500 ppm SCC solution was monitored between 25 and 100 °C by a loss of absorbance at 627 nm. Decomposition was also followed by reversed phase C18 HPLC with photodiode array detection to monitor the loss of Cu(II)Chlorin e4, the major component of commercial grade SCC. The rate of thermal degradation of SCC was found to follow first-order reaction kinetics. HPLC analysis confirmed the ultraviolet and visible absorbance data and also demonstrated loss of the major SCC component, Cu(II)Chlorin e4, at a rate faster than that of overall SCC. The activation energy was estimated using the Arrhenius equation and found to be 13.3 ± 0.8 and 16.0 ± 2.1 kcal/mol for the thermal degradation of SCC and Cu(II)Chlorin e4, respectively. The observed temperature sensitivity of SCC was determined to be similar to that of natural chlorophyll and raises the possibility of color deterioration when used in food products where mild to severe thermal treatment is applied. Furthermore, the implication of rapid loss of Cu(II)Chlorin e4, a reported bioactive component of SCC, upon heating may result in alteration of potential dietary benefits such as antimutagenic and antioxidant activity. Keywords: Sodium copper chlorophyllin; Cu(II)Chlorin e4; thermal degradation; UV−vis spectrophotometry; HPLC}, number={18}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Ferruzzi, Mario G. and Schwartz, Steven J.}, year={2005}, month={Sep}, pages={7098–7102} }