Blueberry intake elevates post-exercise anti-inflammatory oxylipins: a randomized trial.

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.

Astaxanthin supplementation counters exercise-induced decreases in immune-related plasma proteins.

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.

Influence of 2 Weeks of Mango Ingestion on Inflammation Resolution after Vigorous Exercise.

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.

Moderate- and High-Intensity Inspiratory Muscle Training Equally Improves Inspiratory Muscle Strength and Endurance-A Double-Blind Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Inspiratory muscle training (IMT) produced outstanding results in the physical performance of active subjects; however, little is known about the best training intensity for this population. The objective was to investigate the impact of an IMT of high intensity, using the critical inspiratory pressure (CIP), on inspiratory muscle strength (IMS), inspiratory muscle endurance (IME), peak power, and oxygen uptake of recreational cyclists; and to compare these results with moderate-intensity IMT (60% of maximal inspiratory pressure [MIP]). METHODS: Thirty apparently healthy male recreational cyclists, 20-40 years old, underwent 11 weeks of IMT (3 times per week; 55 min per session). Participants were randomized into 3 groups: sham group (6 cmH2O; n = 8); 60% MIP (MIP60; n = 10) and CIP (n = 12). All participants performed the IMS test and incremental IME test at the first, fifth, ninth, and 13th weeks of the experimental protocol. Cardiopulmonary exercise testing was performed on an electromagnetic braking cycle ergometer pre-IMT and post-IMT. Data were analyzed using a 2-way repeated measures ANOVA (group and period factors). RESULTS: IMS increased in CIP and MIP60 groups at the ninth and 13th weeks compared with the sham group (P < .001; ß = 0.99). Regarding IME, there was an interaction between the CIP and MIP60 groups in all periods, except in the initial evaluation (P < .001; ß = 1.00). Peak power (in watts) increased after IMT in CIP and MIP60 groups (P = .01; ß = 0.67). Absolute oxygen uptake did not increase after IMT (P = .49; ß = 0.05). Relative oxygen uptake to lean mass values did not change significantly (P = .48; ß = 0.05). CONCLUSION: High-intensity IMT is beneficial on IMS, IME, and peak power, but does not provide additional gain to moderate intensity in recreational cyclists.

Mixed Flavonoid Supplementation Attenuates Postexercise Plasma Levels of 4-Hydroxynonenal and Protein Carbonyls in Endurance Athletes.

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.

Acute Ingestion of a Mixed Flavonoid and Caffeine Supplement Increases Energy Expenditure and Fat Oxidation in Adult Women: A Randomized, Crossover Clinical Trial.

This randomized, double-blinded, crossover study measured the acute effect of ingesting a mixed flavonoid-caffeine (MFC) supplement compared to placebo (PL) on energy expenditure (EE) and fat oxidation (FATox) in a metabolic chamber with premenopausal women (n = 19, mean ± SD, age 30.7 ± 8.0 year, BMI 25.7 ± 3.4 kg/m2). The MFC supplement (658 mg flavonoids, split dose 8:30, 13:00) contained quercetin, green tea catechins, and anthocyanins from bilberry extract, and 214 mg caffeine. Participants were measured twice in a metabolic chamber for a day, four weeks apart, with outcomes including 22 h EE (8:30-6:30), substrate utilization from the respiratory quotient (RQ), plasma caffeine levels (16:00), and genotyping for the single-nucleotide polymorphism (SNP) rs762551. Areas under the curve (AUC) for metabolic data from the MFC and PL trials were calculated using the trapezoid rule, with a mixed linear model (GLM) used to evaluate the overall treatment effect. The 22 h oxygen consumption and EE were significantly higher with MFC than PL (1582 ± 143, 1535 ± 154 kcal/day, respectively, p = 0.003, trial difference of 46.4 ± 57.8 kcal/day). FATox trended higher for MFC when evaluated using GLM (99.2 ± 14.0, 92.4 ± 14.4 g/22 h, p = 0.054). Plasma caffeine levels were significantly higher in the MFC versus PL trial (5031 ± 289, 276 ± 323 ng/mL, respectively, p < 0.001). Trial differences for 22 h EE and plasma caffeine were unrelated after controlling for age and body mass (r = -0.249, p = 0.139), and not different for participants with the homozygous allele 1, A/A, compared to C/A and C/C (p = 0.50 and 0.56, respectively). In conclusion, EE was higher for MFC compared to PL, and similar to effects estimated from previous trials using caffeine alone. A small effect of the MFC on FATox was measured, in contrast to inconsistent findings previously reported for this caffeine dose. The trial variance for 22 h EE was not significantly related to the variance in plasma caffeine levels or CYP1A2*1F allele carriers and non-carriers.

Increased Plasma Levels of Gut-Derived Phenolics Linked to Walking and Running Following Two Weeks of Flavonoid Supplementation.

Using a randomized, double-blinded, placebo-controlled, parallel group design, this investigation determined if the combination of two weeks of flavonoid supplementation (329 mg/day, quercetin, anthocyanins, flavan-3-ols mixture) and a 45-minute walking bout (62.2 ± 0.9% VO2max (maximal oxygen consumption rate)) enhanced the translocation of gut-derived phenolics into circulation in a group of walkers (n = 77). The walkers (flavonoid, placebo groups) were randomized to either sit or walk briskly on treadmills for 45 min (thus, four groups: placebo⁻sit, placebo⁻walk, flavonoid⁻sit, flavonoid⁻walk). A comparator group of runners (n = 19) ingested a double flavonoid dose for two weeks (658 mg/day) and ran for 2.5 h (69.2 ± 1.2% VO2max). Four blood samples were collected (pre- and post-supplementation, immediately post- and 24 h post-exercise/rest). Of the 76 metabolites detected in this targeted analysis, 15 increased after the 2.5 h run, and when grouped were also elevated post-exercise (versus placebo⁻sit) for the placebo⁻ and flavonoid⁻walking groups (p < 0.05). A secondary analysis showed that pre-study plasma concentrations of gut-derived phenolics in the runners were 40% higher compared to walkers (p = 0.031). These data indicate that acute exercise bouts (brisk walking, intensive running) are linked to an increased translocation of gut-derived phenolics into circulation, an effect that is amplified when combined with a two-week period of increased flavonoid intake or chronic training as a runner.