@article{sakaguchi_nieman_omar_strauch_williams_lila_zhang_2024, title={Influence of 2 Weeks of Mango Ingestion on Inflammation Resolution after Vigorous Exercise}, volume={16}, ISSN={["2072-6643"]}, url={https://www.mdpi.com/2072-6643/16/1/36}, DOI={10.3390/nu16010036}, abstractNote={Mangoes have a unique nutrient profile (carotenoids, polyphenols, sugars, and vitamins) that we hypothesized would mitigate post-exercise inflammation. This study examined the effects of mango ingestion on moderating exercise-induced inflammation in a randomized crossover trial with 22 cyclists. In random order with trials separated by a 2-week washout period, the cyclists ingested 330 g mango/day with 0.5 L water or 0.5 L of water alone for 2 weeks, followed by a 2.25 h cycling bout challenge. Blood and urine samples were collected pre- and post-2 weeks of supplementation, with additional blood samples collected immediately post-exercise and 1.5-h, 3-h, and 24 h post-exercise. Urine samples were analyzed for targeted mango-related metabolites. The blood samples were analyzed for 67 oxylipins, which are upstream regulators of inflammation and other physiological processes. After 2 weeks of mango ingestion, three targeted urine mango-related phenolic metabolites were significantly elevated compared to water alone (interaction effects, p ≤ 0.003). Significant post-exercise increases were measured for 49 oxylipins, but various subgroup analyses showed no differences in the pattern of change between trials (all interaction effects, p > 0.150). The 2.25 h cycling bouts induced significant inflammation, but no countermeasure effect was found after 2 weeks of mango ingestion despite the elevation of mango gut-derived phenolic metabolites.}, number={1}, journal={NUTRIENTS}, author={Sakaguchi, Camila A. and Nieman, David C. and Omar, Ashraf M. and Strauch, Renee C. and Williams, James C. and Lila, Mary Ann and Zhang, Qibin}, year={2024}, month={Jan} }
 @article{nieman_omar_kay_kasote_sakaguchi_lkhagva_weldemariam_zhang_2023, title={Almond intake alters the acute plasma dihydroxy-octadecenoic acid (DiHOME) response to eccentric exercise}, volume={9}, ISSN={["2296-861X"]}, DOI={10.3389/fnut.2022.1042719}, abstractNote={Introduction This investigation determined if 4-weeks ingestion of nutrient-dense almonds mitigated post-exercise inflammation and muscle soreness and damage. Methods An acute 90-min of eccentric exercise (90-EE) was used to induce muscle damage in 64 non-obese adults not engaging in regular resistance training (ages 30–65 years, BMI < 30 kg/m2). Using a parallel group design, participants were randomized to almond (AL) (57 g/d) or cereal bar (CB) (calorie matched) treatment groups for a 4-week period prior to the 90-EE (17 exercises). Blood and 24-h urine samples were collected before and after supplementation, with additional blood samples collected immediately post-90-EE, and then daily during 4 additional days of recovery. Changes in plasma oxylipins, urinary gut-derived phenolics, plasma cytokines, muscle damage biomarkers, mood states, and exercise performance were assessed. Results The 90-EE protocol induced significant muscle damage, delayed onset of muscle soreness (DOMS), inflammation, reduced strength and power performance, and mood disturbance. Interaction effects (2 group × 7 time points) supported that AL vs. CB was associated with reduced post-exercise fatigue and tension (p = 0.051, 0.033, respectively) and higher levels of leg-back strength (p = 0.029). No group differences were found for post-90-EE increases in DOMS and six cytokines. AL was associated with lower levels of serum creatine kinase immediately- and 1-day post-exercise (p = 0.034 and 0.013, respectively). The 90-EE bout increased plasma levels immediately post-exercise for 13 oxylipins. Interaction effects revealed significantly higher levels for AL vs. CB for 12,13-DiHOME (p < 0.001) and lower levels for 9,10-DiHOME (p < 0.001). Urine levels increased in AL vs. CB for seven gut-derived phenolics including 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone that was inversely related to changes in plasma 9,10-DiHOME (r = −0.029, p = 0.021). Discussion These data support some positive effects of almond intake in improving mood state, retaining strength, decreasing muscle damage, increasing the generation of gut-derived phenolic metabolites, and altering the plasma oxylipin DiHOME response to unaccustomed eccentric exercise in untrained adults. The elevated post-exercise plasma levels of 12,13-DiHOME with almond intake support positive metabolic outcomes for adults engaging in unaccustomed eccentric exercise bouts.}, journal={FRONTIERS IN NUTRITION}, author={Nieman, David C. C. and Omar, Ashraf M. M. and Kay, Colin D. D. and Kasote, Deepak M. M. and Sakaguchi, Camila A. A. and Lkhagva, Ankhbayar and Weldemariam, Mehari Muuz and Zhang, Qibin}, year={2023}, month={Jan} }
 @article{nieman_woo_sakaguchi_omar_tang_davis_pecorelli_valacchi_zhang_2023, title={Astaxanthin supplementation counters exercise-induced decreases in immune-related plasma proteins}, volume={10}, ISSN={["2296-861X"]}, DOI={10.3389/fnut.2023.1143385}, abstractNote={Objectives Astaxanthin is a dark red keto-carotenoid found in aquatic animals such as salmon and shrimp, and algae (Haematococcus pluvialis). Astaxanthin has a unique molecular structure that may facilitate anti-oxidative, immunomodulatory, and anti-inflammatory effects during physiological stress. The primary objective of this study was to examine the efficacy of 4-week ingestion of astaxanthin in moderating exercise-induced inflammation and immune dysfunction using a multi-omics approach. Methods This study employed a randomized, double blind, placebo controlled, crossover design with two 4-week supplementation periods and a 2-week washout period. Study participants were randomized to astaxanthin and placebo trials, with supplements ingested daily for 4 weeks prior to running 2.25 h at close to 70%VO2max (including 30 min of 10% downhill running). After the washout period, participants repeated all procedures using the counterbalanced supplement. The astaxanthin capsule contained 8 mg of algae astaxanthin. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5, 3, and 24 h-post-exercise. Plasma aliquots were assayed using untargeted proteomics, and targeted oxylipin and cytokine panels. Results The 2.25 h running bout induced significant muscle soreness, muscle damage, and inflammation. Astaxanthin supplementation had no effect on exercise-induced muscle soreness, muscle damage, and increases in six plasma cytokines and 42 oxylipins. Notably, astaxanthin supplementation countered exercise-induced decreases in 82 plasma proteins (during 24 h recovery). Biological process analysis revealed that most of these proteins were involved in immune-related functions such as defense responses, complement activation, and humoral immune system responses. Twenty plasma immunoglobulins were identified that differed significantly between the astaxanthin and placebo trials. Plasma levels of IgM decreased significantly post-exercise but recovered after the 24 h post-exercise recovery period in the astaxanthin but not the placebo trial. Discussion These data support that 4-week astaxanthin versus placebo supplementation did not counter exercise-induced increases in plasma cytokines and oxylipins but was linked to normalization of post-exercise plasma levels of numerous immune-related proteins including immunoglobulins within 24 h. Short-term astaxanthin supplementation (8 mg/day during a 4-week period) provided immune support for runners engaging in a vigorous 2.25 h running bout and uniquely countered decreases in plasma immunoglobulin levels.}, journal={FRONTIERS IN NUTRITION}, author={Nieman, David C. and Woo, Jongmin and Sakaguchi, Camila A. and Omar, Ashraf M. and Tang, Yang and Davis, Kierstin and Pecorelli, Alessandra and Valacchi, Giuseppe and Zhang, Qibin}, year={2023}, month={Mar} }
 @article{nieman_sakaguchi_omar_davis_shaffner_strauch_lila_zhang_2023, title={Blueberry intake elevates post-exercise anti-inflammatory oxylipins: a randomized trial}, volume={13}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-023-39269-1}, abstractNote={Abstract This study determined if 18 days of supplementation with blueberries (BL) compared to placebo (PL) could mitigate muscle soreness and damage and improve inflammation resolution in untrained adults (n = 49, ages 18–50 years) after engaging in a 90-min bout of “weekend warrior” eccentric exercise. The BL freeze dried supplement provided 1 cup of fresh blueberries per day equivalent with 805 mg/day total phenolics and 280 mg/day anthocyanins. Urine levels of eight BL gut-derived phenolics increased after 14- and 18-days supplementation with 83% higher concentrations in BL vs. PL (p < 0.001). The 90-min exercise bout caused significant muscle soreness and damage during 4d of recovery and a decrease in exercise performance with no significant differences between PL and BL. Plasma oxylipins were identified (n = 76) and grouped by fatty acid substrates and enzyme systems. Linoleic acid (LA) oxylipins generated from cytochrome P450 (CYP) (9,10-, 12,13-dihydroxy-9Z-octadecenoic acids) (diHOMEs) were lower in BL vs. PL (treatment effect, p = 0.051). A compositive variable of 9 plasma hydroxydocosahexaenoic acids (HDoHEs) generated from docosahexaenoic acid (DHA, 22:6) and lipoxygenase (LOX) was significantly higher in BL vs. PL (treatment effect, p = 0.008). The composite variable of plasma 14-HDoHE, 17-HDoHE, and the eicosapentaenoic acid (EPA)-derived oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE) (specialized pro-resolving lipid mediators, SPM, intermediates) was significantly higher in BL vs PL (treatment effect, p = 0.014). Pearson correlations showed positive relationships between post-exercise DHA-LOX HDoHEs and SPM intermediates with urine blueberry gut-derived phenolics (r = 0.324, p = 0.023, and r = 0.349, p = 0.015, respectively). These data indicate that 18d intake of 1 cup/day blueberries compared to PL was linked to a reduction in pro-inflammatory diHOMES and sustained elevations in DHA- and EPA-derived anti-inflammatory oxylipins in response to a 90-min bout of unaccustomed exercise by untrained adults.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Nieman, David C. and Sakaguchi, Camila A. and Omar, Ashraf M. and Davis, Kierstin L. and Shaffner, Cameron E. and Strauch, Renee C. and Lila, Mary Ann and Zhang, Qibin}, year={2023}, month={Jul} }
 @misc{cheatham_nieman_neilson_lila_2022, title={Enhancing the Cognitive Effects of Flavonoids With Physical Activity: Is There a Case for the Gut Microbiome?}, volume={16}, ISSN={["1662-453X"]}, DOI={10.3389/fnins.2022.833202}, abstractNote={Age-related cognitive changes can be the first indication of the progression to dementias, such as Alzheimer’s disease. These changes may be driven by a complex interaction of factors including diet, activity levels, genetics, and environment. Here we review the evidence supporting relationships between flavonoids, physical activity, and brain function. Recent in vivo experiments and human clinical trials have shown that flavonoid-rich foods can inhibit neuroinflammation and enhance cognitive performance. Improved cognition has also been correlated with a physically active lifestyle, and with the functionality and diversity of the gut microbiome. The great majority (+ 90%) of dietary flavonoids are biotransformed into phytoactive phenolic metabolites at the gut microbiome level prior to absorption, and these prebiotic flavonoids modulate microbiota profiles and diversity. Health-relevant outcomes from flavonoid ingestion may only be realized in the presence of a robust microbiome. Moderate-to-vigorous physical activity (MVPA) accelerates the catabolism and uptake of these gut-derived anti-inflammatory and immunomodulatory metabolites into circulation. The gut microbiome exerts a profound influence on cognitive function; moderate exercise and flavonoid intake influence cognitive benefits; and exercise and flavonoid intake influence the microbiome. We conclude that there is a potential for combined impacts of flavonoid intake and physical exertion on cognitive function, as modulated by the gut microbiome, and that the combination of a flavonoid-rich diet and routine aerobic exercise may potentiate cognitive benefits and reduce cognitive decline in an aging population, via mechanisms mediated by the gut microbiome. Mechanistic animal studies and human clinical interventions are needed to further explore this hypothesis.}, journal={FRONTIERS IN NEUROSCIENCE}, author={Cheatham, Carol L. and Nieman, David C. and Neilson, Andrew P. and Lila, Mary Ann}, year={2022}, month={Feb} }
 @article{lawrence_zwetsloot_arthur_sherman_huot_badmaev_grace_lila_nieman_shanely_2021, title={Phytoecdysteroids Do Not Have Anabolic Effects in Skeletal Muscle in Sedentary Aging Mice}, volume={18}, ISSN={["1660-4601"]}, url={https://doi.org/10.3390/ijerph18020370}, DOI={10.3390/ijerph18020370}, abstractNote={Skeletal muscle mass and strength are lost with aging. Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase protein synthesis in C2C12 skeletal muscle cells and muscle strength in young rats. The objective of this study was to determine whether an extract from Ajuga turkestanica (ATE), enriched in phytoecdysteroids, and 20E affect skeletal muscle mass and fiber size, fiber type, activation of the PI3K–Akt signaling pathway, and the mRNA levels of MAFbx, MuRF-1, and myostatin in sedentary aging mice. Aging male C57BL/6 mice (20 months old) received ATE, 20E, or vehicle (CT) once per day for 28 days or a single acute dose. Treatment did not alter body, muscle, or organ mass; fiber cross-sectional area; or fiber type in the triceps brachii or plantaris muscles. Likewise, protein synthesis signaling markers (i.e., phosphorylation of AktSer473 and p70S6kThr389) measured after either 28 days or acutely were unchanged. Neither ATE nor 20E treatment for 28 days affected the mRNA levels of MAFbx, MuRF-1, and myostatin. In conclusion, these data indicate that phytoecdysteroid treatment does not alter muscle mass or fiber type, nor does it activate protein synthesis signaling in the skeletal muscle of sedentary aging mice.}, number={2}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Lawrence, Marcus M. and Zwetsloot, Kevin A. and Arthur, Susan T. and Sherman, Chase A. and Huot, Joshua R. and Badmaev, Vladimir and Grace, Mary and Lila, Mary Ann and Nieman, David C. and Shanely, R. Andrew}, year={2021}, month={Jan} }
 @article{nieman_gillitt_chen_zhang_sha_kay_chandra_kay_lila_2020, title={Blueberry and/or Banana Consumption Mitigate Arachidonic, Cytochrome P450 Oxylipin Generation During Recovery From 75-Km Cycling: A Randomized Trial}, volume={7}, ISSN={["2296-861X"]}, DOI={10.3389/fnut.2020.00121}, abstractNote={Oxylipins are bioactive lipid oxidation products, have vital regulatory roles in numerous physiological processes including inflammation, and can be impacted by diet. This study determined if 2-weeks of blueberry and/or acute banana ingestion influenced generation of n-6 and n-3 PUFA-derived oxylipins during recovery from exercise-induced physiological stress. Cyclists (n = 59, 39 ± 2 years of age) were randomized to freeze-dried blueberry or placebo groups, and ingested 26 grams/d (1 cup/d blueberries equivalent) for 2 weeks. Cyclists reported to the lab in an overnight fasted state and engaged in a 75-km cycling time trial (185.5 ± 5.2 min). Cyclists from each group (blueberry, placebo) were further randomized to ingestion of a water-only control or water with a carbohydrate source (Cavendish bananas, 0.2 g/kg carbohydrate every 15 min) during exercise. Blood samples were collected pre- and post-2-weeks blueberry supplementation, and 0, 1.5, 3, 5, 24, and 48 h-post-exercise. Plasma oxylipins and blueberry and banana metabolites were measured with UPLC–tandem MS/MS. Significant time by treatment effects (eight time points, four groups) were found for 24 blueberry- and seven banana-derived phenolic metabolites in plasma (FDR adjusted p < 0.05). Significant post-exercise increases were observed for 64 of 67 identified plasma oxylipins. When oxylipins were grouped relative to fatty acid substrate [arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA)], and enzyme systems [cytochrome P450 (CYP), lipoxygenase (LOX)], banana and blueberry ingestion were independently associated with significant post-exercise reductions in pro-inflammatory ARA-CYP hydroxy- and dihydroxy-eicosatetraenoic acids (HETEs, DiHETrEs) (treatment effects, FDR adjusted p < 0.05). These trial differences were especially apparent within the first 3 h of recovery. In summary, heavy exertion evoked a transient but robust increase in plasma levels of oxylipins in cyclists, with a strong attenuation effect linked to both chronic blueberry and acute banana intake on pro-inflammatory ARA-CYP oxylipins.}, journal={FRONTIERS IN NUTRITION}, author={Nieman, David C. and Gillitt, Nicholas D. and Chen, Guan-Yuan and Zhang, Qibin and Sha, Wei and Kay, Colin D. and Chandra, Preeti and Kay, Kristine L. and Lila, Mary Ann}, year={2020}, month={Aug} }
 @article{nieman_valacchi_wentz_ferrara_pecorelli_woodby_sakaguchi_simonson_2020, title={Mixed Flavonoid Supplementation Attenuates Postexercise Plasma Levels of 4-Hydroxynonenal and Protein Carbonyls in Endurance Athletes}, volume={30}, ISSN={["1543-2742"]}, DOI={10.1123/ijsnem.2019-0171}, abstractNote={This double-blinded, placebo controlled, randomized crossover trial investigated the influence of 2-week mixed flavonoid versus placebo supplementation on oxinflammation markers after a 75-km cycling time trial in 22 cyclists (42.3 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr post 75-km cycling (176 ± 5.4 min, 73.4 ±2.0% maximal oxygen consumption). The supplement provided 678-mg flavonoids with quercetin (200 mg), green tea catechins (368 mg, 180-mg epigallocatechin gallate), and anthocyanins (128 mg) from bilberry extract, with caffeine, vitamin C, and omega-3 fatty acids added as adjuvants. Blood samples were analyzed for blood leukocyte counts, oxinflammation biomarkers, including 4-hydroxynonenal, protein carbonyls, and peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and glutathione peroxidase. Each of the blood biomarkers was elevated postexercise (time effects, all ps < .01), with lower plasma levels for 4-hydroxynonenal (at 21-hr postexercise) in flavonoid versus placebo (interaction effect, p = .008). Although elevated postexercise, no trial differences for the neutrophil/lymphocyte ratio (p = .539) or peripheral blood mononuclear mRNA expression for cyclooxygenease-2 (p = .322) or glutathione peroxidase (p = .839) were shown. Flavonoid supplementation prior to intensive exercise decreased plasma peroxidation and oxidative damage, as determined by 4-hydroxynonenal. Postexercise increases were similar between the flavonoid and placebo trials for peripheral blood mononuclear mRNA expression for cyclooxygenease-2 and the nuclear factor erythroid 2-related factor 2 related gene glutathione peroxidase (NFE2L2). The data support the strategy of flavonoid supplementation to mitigate postexercise oxidative stress in endurance athletes.}, number={2}, journal={INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM}, author={Nieman, David C. and Valacchi, Giuseppe and Wentz, Laurel M. and Ferrara, Francesca and Pecorelli, Alessandra and Woodby, Brittany and Sakaguchi, Camila A. and Simonson, Andrew}, year={2020}, month={Mar}, pages={112–119} }
 @article{nieman_ferrara_pecorelli_woodby_hoyle_simonson_valacchi_2020, title={Postexercise Inflammasome Activation and IL-1 beta Production Mitigated by Flavonoid Supplementation in Cyclists}, volume={30}, ISSN={["1543-2742"]}, DOI={10.1123/ijsnem.2020-0084}, abstractNote={Inflammasomes are multiprotein signaling platforms of the innate immune system that detect markers of physiological stress and promote the maturation of caspase-1 and interleukin 1 beta (IL-1β), IL-18, and gasdermin D. This randomized, cross-over trial investigated the influence of 2-week mixed flavonoid (FLAV) versus placebo (PL) supplementation on inflammasome activation and IL-1β and IL-18 production after 75-km cycling in 22 cyclists (42 ± 1.7 years). Blood samples were collected before and after the 2-week supplementation, and then 0 hr, 1.5 hr, and 21 hr postexercise (176 ± 5.4 min, 73.4 ± 2.0 %VO2max). The supplement (678 mg FLAVs) included quercetin, green tea catechins, and bilberry anthocyanins. The pattern of change in the plasma levels of the inflammasome adaptor oligomer ASC (apoptosis-associated speck-like protein containing caspase recruitment domain) was different between the FLAV and PL trials, with the FLAV ASC levels 52% lower (Cohen's d = 1.06) than PL immediately following 75-km cycling (interaction effect, p = .012). The plasma IL-1β levels in FLAV were significantly lower than PL (23-42%; Cohen's d = 0.293-0.644) throughout 21 hr of recovery (interaction effect, p = .004). The change in plasma gasdermin D levels were lower immediately postexercise in FLAV versus PL (15% contrast, p = .023; Cohen's d = 0.450). The patterns of change in plasma IL-18 and IL-37 did not differ between the FLAV and PL trials (interaction effects, p = .388, .716, respectively). These data indicate that 2-week FLAV ingestion mitigated inflammasome activation, with a corresponding decrease in IL-1β release in cyclists after a 75-km cycling time trial. The data from this study support the strategy of ingesting high amounts of FLAV to mitigate postexercise inflammation.}, number={6}, journal={INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM}, author={Nieman, David C. and Ferrara, Francesca and Pecorelli, Alessandra and Woodby, Brittany and Hoyle, Andrew T. and Simonson, Andrew and Valacchi, Giuseppe}, year={2020}, month={Nov}, pages={396–404} }
 @article{nieman_lila_gillitt_2019, title={Immunometabolism: A Multi-Omics Approach to Interpreting the Influence of Exercise and Diet on the Immune System}, volume={10}, ISSN={["1941-1421"]}, DOI={10.1146/annurev-food-032818-121316}, abstractNote={ Immunometabolism is an evolving field of scientific endeavor that merges immunology and metabolism and has provided valuable context when evaluating the influence of dietary interventions on exercise-induced immune dysfunction. Metabolomics, lipidomics, and proteomics provide a system-wide view of the metabolic response to exercise by simultaneously measuring and identifying a large number of small-molecule metabolites, lipids, and proteins. Many of these are involved with immune function and regulation and are sensitive to dietary influences, especially acute carbohydrate ingestion from either sugar beverages or fruits such as bananas. Emerging evidence using large multi-omics data sets supports the combined intake of fruit sugars and phytochemicals by athletes during heavy exertion as an effective strategy to improve metabolic recovery, augment viral defense, and counter postexercise inflammation and immune dysfunction at the cell level. Multi-omics methodologies have given investigators new outcome targets to assess the efficacy of various dietary interventions for physiologically stressed athletes. }, journal={ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY, VOL 10}, author={Nieman, David C. and Lila, Mary Ann and Gillitt, Nicholas D.}, year={2019}, pages={341–363} }