A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women-A Randomized Controlled Trial.

Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40-70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women.

Extracts of Fruits and Vegetables Activate the Antioxidant Response Element in IMR-32 Cells.

BACKGROUND: The biological effects of antioxidant nutrients are mediated in part by activation of antioxidant response elements (AREs) on genes for enzymes involved in endogenous pathways that prevent free radical damage. Traditional approaches for identifying antioxidant molecules in foods, such as total phenolic compound (TP) content or oxygen radical absorption capacity (ORAC), do not measure capacity to activate AREs. OBJECTIVES: The goal of this study was to develop an assay to assess the ARE activation capacity of fruit and vegetable extracts and determine whether such capacity was predicted by TP content and/or ORAC activity. METHODS: Fruits and vegetables were homogenized, extracted with acidified ethanol, lyophilized, and resuspended in growth medium. Human IMR-32 neuroblastoma cells, transfected with an ARE-firefly luciferase reporter, were exposed to extracts for 5 h. Firefly luciferase was normalized to constitutively expressed Renilla luciferase with tertiary butylhydroquinone (tBHQ) as a positive control. TP content and ORAC activity were measured for each extract. Relations between TPs and ORAC and ARE activity were determined. RESULTS: A total of 107 of 134 extracts tested significantly activated the ARE-luciferase reporter from 1.2- to 58-fold above that of the solvent control (P < 0.05) in human IMR-32 cells. ARE activity, TP content, and ORAC ranked higher in peels than in associated flesh. Despite this relation, ARE activity did not correlate with TP content (Spearman ρ = 0.05, P = 0.57) and only modestly but negatively correlated with ORAC (Spearman ρ = -0.24, P < 0.01). Many extracts activated the ARE more than predicted by the TP content or ORAC. CONCLUSIONS: The ARE reporter assay identified many active fruit and vegetable extracts in human IMR-32 cells. There are components of fruits and vegetables that activate the ARE but are not phenolic compounds and are low in ORAC. The ARE-luciferase reporter assay is likely a better predictor of the antioxidant benefits of fruits and vegetables than TP or ORAC.

Influence of vitamin D mushroom powder supplementation on exercise-induced muscle damage in vitamin D insufficient high school athletes.

Incidence of vitamin D deficiency is increasing worldwide. The purpose of this study was to determine if supplementation with vitamin D2 from Portobello mushroom powder would enhance skeletal muscle function and attenuate exercise-induced muscle damage in low vitamin D status high school athletes. Participants were randomised to Portobello mushroom powder (600 IU/d vitamin D2) or placebo for 6 weeks. Participants then completed a 1.5-h exercise session designed to induce skeletal muscle damage. Blood samples and measures of skeletal muscle function were taken pre-supplementation, post-supplementation/pre-exercise and post-exercise. Six weeks supplementation with vitamin D2 increased serum 25(OH)D2 by 9.9-fold and decreased serum 25(OH)D3 by 28%. Changes in skeletal muscle function and circulating markers of skeletal muscle damage did not differ between groups. In conclusion, 600 IU/d vitamin D2 increased 25(OH)D2 with a concomitant decrease in 25(OD)D3, with no effect on muscular function or exercise-induced muscle damage in high school athletes.

Influence of a polyphenol-enriched protein powder on exercise-induced inflammation and oxidative stress in athletes: a randomized trial using a metabolomics approach.

OBJECTIVES: Polyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training. METHODS: Water soluble polyphenols from blueberry and green tea extracts were captured onto a polyphenol soy protein complex (PSPC). Subjects were recruited, and included 38 long-distance runners ages 19-45 years who regularly competed in road races. Runners successfully completing orientation and baseline testing (N = 35) were randomized to 40 g/d PSPC (N = 17) (2,136 mg/d gallic acid equivalents) or placebo (N = 18) for 17 d using double-blinded methods and a parallel group design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO2max). Blood samples were collected pre- and post-14 d supplementation, and immediately and 14 h after the third day of running in subjects completing all aspects of the study (N = 16 PSPC, N = 15 placebo), and analyzed using a metabolomics platform with GC-MS and LC-MS. RESULTS: Metabolites characteristic of gut bacteria metabolism of polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4-hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively, P<0.05), an effect which persisted for 14-h post-exercise. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14-h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05). Established biomarkers for inflammation (CRP, cytokines) and oxidative stress (protein carbonyls) did not differ between groups. CONCLUSIONS: PSPC supplementation over a 17-d period did not alter established biomarkers for inflammation and oxidative stress but was linked to an enhanced gut-derived phenolic signature and ketogenesis in runners during recovery from 3-d heavy exertion. TRIAL REGISTRATION: ClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT01775384.

Chia seed supplementation and disease risk factors in overweight women: a metabolomics investigation.

OBJECTIVE/SETTING: This study assessed the effectiveness of milled and whole chia seed in altering disease risk factors in overweight, postmenopausal women using a metabolomics approach. DESIGN/INTERVENTION: Subjects were randomized to chia seed (whole or milled) and placebo (poppy seed) groups, and under double-blinded procedures ingested 25 g chia seed or placebo supplements each day for 10 weeks. SUBJECTS: Subjects included 62 overweight (body-mass index 25 kg/m(2) and higher), nondiseased, nonsmoking, postmenopausal women, ages 49-75 years, with analysis based on the 56 subjects who completed all phases of the study. OUTCOME MEASURES: Pre- and poststudy measures included body mass and composition, blood pressure and augmentation index, serum lipid profile, inflammation markers from fasting blood samples, plasma fatty acids, and metabolic profiling using gas chromatography-mass spectrometry with multivariate statistical methods including principal component analysis and partial least-square discriminant analysis (PLS-DA). RESULTS: Plasma α-linolenic acid (N=ALA) increased 58% (interaction effect, p=0.002) and eicosapentaenoic acid (EPA) 39% (p=0.016) in the milled chia seed group (N=14) compared to nonsignificant changes in the whole chia seed (N=16) and placebo (N=26) groups. Pre-to-post measures of body composition, inflammation, blood pressure, augmentation index, and lipoproteins did not differ between chia seed (whole or milled) and placebo groups (all interaction effects, p>0.05). Global metabolic difference scores for each group calculated through PLS-DA models were nonsignificant (Q(2)Y<0.40), and fold-changes for 28 targeted metabolites associated with inflammation and disease risk factors did not differ between groups. CONCLUSIONS: Ingestion of 25 g/day milled chia seed compared to whole chia seed or placebo for 10 weeks by overweight women increased plasma ALA and EPA, but had no influence on inflammation or disease risk factors using both traditional and metabolomics-based measures.

Bananas as an energy source during exercise: a metabolomics approach.

This study compared the acute effect of ingesting bananas (BAN) versus a 6% carbohydrate drink (CHO) on 75-km cycling performance and post-exercise inflammation, oxidative stress, and innate immune function using traditional and metabolomics-based profiling. Trained cyclists (N = 14) completed two 75-km cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass spectrometry. Blood glucose levels and performance did not differ between BAN and CHO (2.41±0.22, 2.36±0.19 h, P = 0.258). F2-isoprostanes, FRAP, IL-10, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG increased with exercise, with no trial differences except for higher levels during BAN for IL-10, IL-8, and FRAP (interaction effects, P = 0.003, 0.004, and 0.012). Of 103 metabolites detected, 56 had exercise time effects, and only one (dopamine) had a pattern of change that differed between BAN and CHO. Plots from the PLS-DA model visualized a distinct separation in global metabolic scores between time points [R²Y(cum) = 0.869, Q²(cum) = 0.766]. Of the top 15 metabolites, five were related to liver glutathione production, eight to carbohydrate, lipid, and amino acid metabolism, and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during 75-km cycling resulted in similar performance, blood glucose, inflammation, oxidative stress, and innate immune levels. Aside from higher dopamine in BAN, shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a similar pattern of heightened production of glutathione and utilization of fuel substrates in several pathways.

Supplementation of milled chia seeds increases plasma ALA and EPA in postmenopausal women.

Ten postmenopausal women (age 55.6 ± 0.8 years, BMI 24.6 ± 1.1 kg/m²) ingested 25 g/day milled chia seed during a 7-week period, with six plasma samples collected for measurement of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Subjects operated as their own controls with overnight fasted blood samples taken at baseline (average of two samples), and then after 1, 2, 3, 5, and 7 weeks supplementation. Plasma ALA increased significantly after one week supplementation and was 138 % above baseline levels by the end of the study (overall time effect, P < 0.001). EPA increased 30 % above baseline (overall time effect, P = 0.019) and was correlated across time with ALA (r = 0.84, P = 0.02). No significant change in plasma DPA levels was measured (overall time effect, P = 0.067). Plasma DHA decreased slightly by the end of the study (overall time effect, P = 0.030) and was not correlated with change in ALA. In conclusion, ingestion of 25 g/day milled chia seeds for seven weeks by postmenopausal women resulted in significant increases in plasma ALA and EPA but not DPA and DHA.

Combined fruit and vegetable intake is correlated with improved inflammatory and oxidant status from a cross-sectional study in a community setting.

Previous studies have examined the relationship between specific nutrient and food intakes with limited markers of either inflammation or oxidant status. The objective of this study was to determine if an increase in combined self-reported fruit and vegetable (F&V) intake in a community setting was associated with improved multiple markers of inflammatory and oxidant status. A community group (N = 1000, age 18-85 years, 61% female) gave two fasted blood samples separated by 12 weeks. Blood inflammatory biomarkers included total leukocytes (WBC), plasma C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1, and granulocyte colony stimulating factor. Measured oxidant status markers were ferric reducing ability of plasma (FRAP), oxygen radical absorbance capacity (ORAC) and plasma F2-isoprostanes. The relation of markers across categories of F&V intake was examined. In analyses controlling for other important dietary and lifestyle factors, IL-6 and TNF-α were significantly lower across categories of increasing F&V intakes (p < 0.008). FRAP and ORAC were significantly higher (p < 0.0001 and p = 0.047 respectively) while F(2)-isoprostanes was significantly lower (p < 0.0001) across F&V categories. In a community study, several markers of both inflammation and oxidant status were associated in a putatively salutary direction by higher intake of combined F&V, supporting current guidelines suggesting increased F&V consumption for the prevention of chronic diseases.

Effect of mixed flavonoids, n-3 fatty acids, and vitamin C on oxidative stress and antioxidant capacity before and after intense cycling.

Consumption of plant flavonoids, antioxidants, and n-3 fatty acids is proposed to have many potential health benefits derived primarily through antioxidant and anti-inflammatory activities. This study examined the effects of 1,000 mg quercetin + 1,000 mg vitamin C (QC); 1,000 mg quercetin, 1,000 mg vitamin C, 400 mg isoquercetin, 30 mg epigallocatechin gallate, and 400 mg n-3 fatty acids (QFO); or placebo (P), taken each day for 2 wk before and during 3 d of cycling at 57% W(max) for 3 hr, on plasma antioxidant capacity (ferricreducing ability of plasma [FRAP], oxygen-radical absorbance capacity [ORAC]), plasma oxidative stress (F(2)-isoprostanes), and plasma quercetin and vitamin C levels. Thirty-nine athletes were recruited and randomized to QC, QFO, or P. Blood was collected at baseline, after 2 wk supplementation, immediately postexercise, and 14 hr postexercise. Statistical design used a 3 (groups) × 4 (times) repeated-measures ANOVA with post hoc analyses. Plasma quercetin was significantly elevated in QC and QFO compared with P. Plasma F(2)-isoprostanes, FRAP, and vitamin C were significantly elevated and ORAC significantly decreased immediately postexercise, but no difference was noted in the overall pattern of change. Post hoc analyses revealed that the QC and QFO groups did not exhibit a significant increase in F(2)-isoprostanes from baseline to immediately postexercise compared with P. This study indicates that combining flavonoids and antioxidants with n-3 fatty acids is effective in reducing the immediate postexercise increase in F(2)-isoprostanes. Moreover, this effect occurs independently of changes in plasma antioxidant capacity.

The acute effect of ingesting a quercetin-based supplement on exercise-induced inflammation and immune changes in runners.

This study tested the acute anti-inflammatory and immune-modulating influence of a quercetin-based supplement consumed by endurance athletes 15 min before an intense 2-hr run. In this randomized, crossover study, 20 runners (11 men, 9 women, age 38.4 ± 2.1 yr) completed two 2-hr treadmill runs at 70% VO(2max) (3 wk apart). Subjects ingested either 4 quercetin-based chews (Q-chew) or placebo chews (PL) 15 min before the runs. The 4 Q-chews provided 1,000 mg quercetin, 120 mg epigallocatechin 3-gallate, 400 mg isoquercetin, 400 mg each eicosapentaenoic acid and docosahexaenoic acid, 1,000 mg vitamin C, and 40 mg niacinamide. Subjects provided blood samples 30 min before, immediately after, and 1 hr postexercise and were analyzed for plasma quercetin, total blood leukocytes (WBC), C-reactive protein (CRP), 9 cytokines (IL-6, TNFα, GM-CSF, IFNγ, IL-1ß, IL-2, IL-8, IL-10, and IL-12p70), granulocyte (GR) and monocyte (MO) phagocytosis (PHAG), and oxidative-burst activity (OBA). Plasma quercetin increased from 80.0 ± 26.0 µg/L to 6,337 ± 414 µg/L immediately postexercise and 4,324 ± 310 µg/L 1 hr postexercise after ingestion of Q-chews, compared with no change in PL (p < .001). Exercise caused significant increases in, CRP, GM-CSF, IL-10, IL-1ß, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG and decreases in GR-OBA and MO-OBA, but no differences in the pattern of change were measured between Q-chew and PL trials. Acute ingestion of Q-chews 15 min before heavy exertion caused a strong increase in plasma quercetin levels but did not counter postexercise inflammation or immune changes relative to placebo.

Quercetin with vitamin C and niacin does not affect body mass or composition.

In vitro and animal data suggest that quercetin affects adipogenesis and basal metabolism; however, whether this metabolic effect translates to reductions in body mass or improvement in body composition in humans is unknown. This study investigated 12-week supplementation of 2 different doses of quercetin, combined with vitamin C and niacin, on body mass and composition in a large, heterogeneous group of adults (n = 941; 60% female, 40% male; 18-85 years of age; 45% normal body mass index, 30% overweight, 25% obese). Subjects were randomized into 3 groups, with supplements administered in double-blind fashion: Q500 = 500 mg quercetin·day(-1), Q1000 = 1000 mg quercetin·day(-1), and placebo. Quercetin supplements were consumed twice daily over a 12-week period, and pre- and poststudy body mass and composition measurements were taken in an overnight fasted state. A general linear model was used to predict change in body mass and composition across groups with adjustment for demographic and lifestyle factors. Plasma quercetin increased in a dose-responsive manner in both Q500 and Q1000 groups relative to placebo. After adjustment for confounders, no significant differences in body mass (males interaction p value = 0.721, females p = 0.366) or body composition (males p = 0.650, females p = 0.639) were found between Q500 or Q1000 groups compared with placebo. No group differences in body mass or body composition were found in a subgroup of overweight and obese subjects. High-dose quercetin supplementation (500 and 1000 mg·day(-1)) for 12 weeks in a large, heterogeneous group of adults did not affect body mass or composition.

Influence of quercetin supplementation on disease risk factors in community-dwelling adults.

BACKGROUND: In vitro data indicate quercetin has antioxidative and anti-inflammatory functions with the potential to lower disease risk factors, but data in human beings are limited. OBJECTIVE: The objective of this study was to investigate the effect of quercetin, vitamin C, and niacin supplements (500 mg quercetin, 125 mg vitamin C, and 5 mg niacin [Q-500]; 1,000 mg quercetin, 250 mg vitamin C, and 10 mg niacin [Q-1,000]), on disease risk factors in a large group of community adults (n=1,002, 60% women) varying widely in age and body mass index. DESIGN: Subjects were randomized into one of three groups (placebo, Q-500, or Q-1,000) and ingested supplements for 12 weeks. Blood samples were taken pre- and postsupplementation, and plasma quercetin, inflammatory markers (ie, C-reactive protein and five cytokines), diagnostic blood chemistries, blood pressure, and blood lipid profiles were measured. RESULTS: Plasma quercetin increased in the Q-500 and Q-1,000 groups. No differences in blood chemistries were found except for a small decrease in serum creatinine and increase in glomerular filtration rate in Q-500 and Q-1,000 groups. A small decrease in mean arterial blood pressure was measured for Q-500 and Q-1,000 groups compared to placebo. A difference in serum total cholesterol was measured between Q-500 and placebo groups, and there was small decrease in high-density lipoprotein cholesterol levels in the Q-1,000 group. Change in inflammatory measures did not differ between groups except for a slight decrease in interleukin-6 for the Q-1,000 group. CONCLUSIONS: Q-500 or Q-1,000 supplementation for 12 weeks had a negligible influence on disease risk factors.

A 45-minute vigorous exercise bout increases metabolic rate for 14 hours.

INTRODUCTION: The magnitude and duration of the elevation in resting energy expenditure after vigorous exercise have not been measured in a metabolic chamber. This study investigated the effects of inserting a 45-min vigorous cycling bout into the daily schedule versus a controlled resting day on 24-h energy expenditure in a metabolic chamber. METHODS: Ten male subjects (age = 22-33 yr) completed two separate 24-h chamber visits (one rest and one exercise day), and energy balance was maintained for each visit condition. On the exercise day, subjects completed 45 min of cycling at 57% Wmax (mean ± SD = 72.8% ± 5.8% VO(2)max) starting at 11:00 a.m. Activities of daily living were tightly controlled to ensure uniformity on both rest and exercise days. The area under the energy expenditure curve for exercise and rest days was calculated using the trapezoid rule in the EXPAND procedure in the SAS and then contrasted. RESULTS: The 45-min exercise bout resulted in a net energy expenditure of 519 ± 60.9 kcal (P < 0.001). For 14 h after exercise, energy expenditure was increased 190 ± 71.4 kcal compared with the rest day (P < 0.001). CONCLUSIONS: In young male subjects, vigorous exercise for 45 min resulted in a significant elevation in postexercise energy expenditure that persisted for 14 h. The 190 kcal expended after exercise above resting levels represented an additional 37% to the net energy expended during the 45-min cycling bout. The magnitude and duration of increased energy expenditure after a 45-min bout of vigorous exercise may have implications for weight loss and management.

A 12-week supplementation with quercetin does not affect natural killer cell activity, granulocyte oxidative burst activity or granulocyte phagocytosis in female human subjects.

Quercetin, a flavonoid found in fruits and vegetables, is a strong antioxidant with anti-inflammatory, antimicrobial and immune-modulating properties. The purpose of the present study was to investigate the effects of long-term quercetin supplementation on innate immune function and inflammation in human subjects. Female subjects (n 120; aged 30-79 years) were recruited from the community and randomised to one of three groups, with supplements administered using double-blinded procedures: 500 mg quercetin/d (n 38), 1000 mg quercetin/d (n 40) or placebo (n 42). Subjects ingested two soft chew supplements twice daily during the 12-week study period. Fasting blood samples were obtained pre- and post-study and were analysed for plasma quercetin, IL-6, TNF-alpha and leucocyte subset cell counts. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed in a subset of seventy-four subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed in sixty-four subjects. Eighteen subjects had overlapping data. Quercetin supplementation at two doses compared with placebo increased plasma quercetin (interaction effect; P < 0.001) but had no significant influence on blood leucocyte subsets, plasma IL-6 or TNF-alpha concentration, NKCA, GOBA or phagocytosis. NKCA was inversely correlated with BMI (r - 0.25; P = 0.035) and body fat percentage (r - 0.38; P = 0.001), and positively correlated with self-reported physical fitness level (r 0.24; P = 0.032). In summary, results from the present double-blinded, placebo-controlled, randomised trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 weeks significantly increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females.

Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial.

Quercetin in culture with target cells and pathogens exerts anti-pathogenic activities against a wide variety of viruses and bacteria. A few small-scale human quercetin supplementation studies have produced conflicting results regarding quercetin's effects on upper respiratory tract infection rates, and little is known regarding the appropriate human dose. The purpose of this randomized, double-blinded, placebo-controlled trial was to measure the influence of two quercetin doses (500 and 1000 mg/day) compared to placebo on upper respiratory tract infection (URTI) rates in a large community group (N=1002) of subjects varying widely in age (18-85 years). Subjects ingested supplements for 12 weeks and logged URTI symptoms on a daily basis using the Wisconsin Upper Respiratory Symptom Survey (WURSS). No significant group differences were measured for URTI outcomes for all subjects combined, or when analyzing separately by gender, body mass index, and age categories. Regression analysis revealed that the strongest interaction effect with group status was self-reported fitness level. A separate analysis of subjects 40 years of age and older rating themselves in the top half of the entire group for fitness level (N=325) showed lower URTI severity (36% reduction, P=0.020) and URTI total sick days (31% reduction, P=0.048) for the Q-1000 group compared to placebo. In summary, for all subjects combined, quercetin supplementation over 12 weeks had no significant influence on URTI rates or symptomatology compared to placebo. A reduction in URTI total sick days and severity was noted in middle aged and older subjects ingesting 1000 mg quercetin/day for 12 weeks who rated themselves as physically fit.

Effect of n-3 fatty acids and antioxidants on oxidative stress after exercise.

PURPOSE: n-3 fatty acids are known to exert multiple beneficial effects including anti-inflammatory actions that may diminish oxidative stress. Supplementation with antioxidant vitamins has been proposed to counteract oxidative stress and improve antioxidant status. Therefore, this project investigated the effects of daily supplementation in 48 trained cyclists over 6 wk and during 3 d of continuous exercise on F2-isoprostanes (oxidative stress), plasma n-3 fatty acids, and antioxidant status (oxygen radical absorption capacity and ferric-reducing antioxidant potential). METHODS: Cyclists were randomized into n-3 fatty acids (N3) (n = 11) (2000 mg of eicosapentaenoic acid and 400 mg of docosahexaenoic acid), a vitamin-mineral (VM) complex (n = 12) emphasizing vitamins C (2000 mg), E (800 IU), A (3000 IU), and selenium (200 microg), a VM and n-3 fatty acid combination (VN3) (n = 13), or placebo (P) (n = 12). Blood was collected at baseline and preexercise and postexercise. A 4 x 3 repeated-measures ANOVA was performed to test main effects. RESULTS: After exercise, F2-isoprostanes were higher in N3 (treatment effect P = 0.014). Eicosapentaenoic acid and docosahexaenoic acid plasma values were higher after supplementation (interaction effect P = 0.001 and 0.006, respectively) in both n-3 supplemented groups. Oxygen radical absorption capacity declined similarly among all groups after exercise. Ferric-reducing antioxidant potential exhibited significant interaction (P = 0.045) and significantly increased after exercise in VN3 and VM (P < 0.01). CONCLUSIONS: This study indicates that supplementation with n-3 fatty acids alone significantly increases F2-isoprostanes after exhaustive exercise. Lastly, antioxidant supplementation augments plasma antioxidant status and modestly attenuates but does not prevent the significant n-3 fatty acid associated increase in F2-isoprostanes postexercise.

Quercetin supplementation does not alter antioxidant status in humans.

This study measured the influence of ingesting quercetin on plasma measures for oxidative stress and antioxidant capacity. Male and female subjects (n = 1002) varying in age (18-85 years) and body mass index (BMI) (16.7-52.7 kg/m(2)) were studied. Subjects were randomized to one of three groups using double-blinded methods: placebo, 500 mg or 1000 mg quercetin/day with 125 mg or 250 mg vitamin C/day, respectively. Pre- and post-study fasting blood samples show that plasma quercetin increased in a dose-responsive manner. The pattern of change in plasma F(2)-isoprostanes, oxidized low density lipoprotein, reduced glutathione, ferric reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) did not differ between supplementation groups or after adjustment for gender, age, BMI and disease status. In summary, quercetin supplementation over 12 weeks in doses of 500 mg or 1000 mg/day significantly increased plasma quercetin levels, but had no influence on several measures of oxidative stress and antioxidant capacity.

Quercetin's influence on exercise performance and muscle mitochondrial biogenesis.

PURPOSE: To determine the influence of 2 wk of quercetin (Q; 1000 mg x d(-1)) compared with placebo (P) supplementation on exercise performance and skeletal muscle mitochondrial biogenesis in untrained, young adult males (N = 26, age = 20.2 +/- 0.4 yr, VO2max = 46.3 +/- 1.2 mL x kg(-1) x min(-1)). METHODS: Using a randomized, crossover design with a 2-wk washout period, subjects provided blood and muscle biopsy samples presupplementation and postsupplementation periods and were given 12-min time trials on 15% graded treadmills after 60 min of moderate exercise preloads at 60% VO2max. RESULTS: Plasma Q levels rose significantly in Q versus P during the 2-wk supplementation period (interaction P value <0.001). During the 12-min trial, the net change in distance achieved was significantly greater during Q (2.9%) compared with P (-1.2%; 29.5 +/- 11.5 vs -11.9 +/- 16.0 m, respectively, P = 0.038). Skeletal muscle messenger RNA expression tended to increase (range = 16-25%) during Q versus P for sirtuin 1 (interaction effect, P = 0.152), peroxisome proliferator-activated receptor gamma coactivator-1alpha (P = 0.192), cytochrome c oxidase (P = 0.081), and citrate synthase (P = 0.166). Muscle mitochondrial DNA (relative copy number per diploid nuclear genome) increased 140 +/- 154 (4.1%) with Q compared with -225 +/- 157 (6.0% decrease) with P (P = 0.098). CONCLUSIONS: In summary, 1000 mg x d(-1) Q versus P for 2 wk by untrained males was associated with a small but significant improvement in 12-min treadmill time trial performance and modest but insignificant increases in the relative copy number of mitochondrial DNA and messenger RNA levels of four genes related to mitochondrial biogenesis.

n-3 polyunsaturated fatty acids do not alter immune and inflammation measures in endurance athletes.

The purpose of this study was to test the influence of 2.4 g/d fish oil n-3 polyunsaturated fatty acids (n-3 PUFA) over 6 wk on exercise performance, inflammation, and immune measures in 23 trained cyclists before and after a 3-d period of intense exercise. Participants were randomized to n-3 PUFA (n = 11; 2,000 mg eicosapentaenoic acid [EPA], 400 mg docosahexaenoic acid [DHA]) or placebo (n = 12) groups. They ingested supplements under double-blind methods for 6 wk before and during a 3-d period in which they cycled for 3 hr/d at ~57% W(max) with 10-km time trials inserted during the final 15 min of each 3-hr bout. Blood and saliva samples were collected before and after the 6-wk supplementation period, immediately after the 3-hr exercise bout on the third day, and 14 hr postexercise and analyzed for various immune-function and inflammation parameters. Supplementation with n-3 PUFA resulted in a significant increase in plasma EPA and DHA but had no effect on 10-km time-trial performance; preexercise outcome measures; exercise-induced increases in plasma cytokines, myeloperoxidase, blood total leukocytes, serum C-reactive protein, and creatine kinase; or the decrease in the salivary IgA:protein ratio. In conclusion, 6 wk supplementation with a large daily dose of n-3 PUFAs increased plasma EPA and DHA but had no effect on exercise performance or in countering measures of inflammation and immunity before or after a 3-d period of 9 hr of heavy exertion.

Chia seed does not promote weight loss or alter disease risk factors in overweight adults.

The objective of this study was to assess the effectiveness of chia seed (Salvia hispanica L) in promoting weight loss and altering disease risk factors in overweight adults. The hypothesis was that the high dietary fiber and alpha-linolenic (ALA) contents of chia seed would induce a small but significant decrease in body weight and fat and improve disease risk factors. Subjects were randomized to chia seed (CS) and placebo (P) groups, and under single-blinded procedures, ingested 25 g CS or P supplements mixed in 0.25 L water twice daily before the first and last meal for 12 weeks. Ninety nondiseased, overweight/obese men and women between the ages of 20 and 70 years were recruited into the study, with 76 subjects (n = 39 CS, n = 37 P) completing all phases of the study. Pre- and poststudy measures included body mass and composition (dual energy x-ray absorptiometry), inflammation markers from fasting blood samples (C-reactive protein, interleukin 6, monocyte chemoattractant protein 1, and tumor necrosis factor alpha), oxidative stress markers (trolox equivalent antioxidant capacity and plasma nitrite), blood pressure, and a serum lipid profile. Plasma ALA increased 24.4% compared to a 2.8% decrease in CS and P, respectively (interaction effect, P = .012). No group differences were measured for changes in plasma eicosapentaenoic acid and docosahexaenoic acid (interaction effects, P = .420 and .980, respectively). Pre-to-post measures of body composition, inflammation, oxidative stress, blood pressure, and lipoproteins did not differ between CS and P for both sexes. In conclusion, ingestion of 50 g/d CS vs P for 12 weeks by overweight/obese men and women had no influence on body mass or composition, or various disease risk factor measures.