Physical activity lowers the risk for acute respiratory infections: Time for recognition

Physical inactivity is a well-established risk factor for chronic diseases, such as cardiovascular disease, cancer, and diabetes mellitus. There is a growing awareness that physical inactivity should also be regarded as a risk factor for acute respiratory infections (ARIs). ARIs, such as the common cold, influenza, pneumonia, and coronavirus disease 2019 (COVID-19), are among the most pervasive diseases on earth and cause widespread morbidity and mortality. Evidence in support of the linkage between ARIs and physical inactivity has been strengthened during the COVID-19 pandemic because of increased scientific scrutiny. Large-scale studies have consistently reported that the risk for severe COVID-19 outcomes is elevated in cohorts with low physical activity and/or physical fitness, even after adjusting for other risk factors. The lowered risk for severe COVID-19 and other ARIs in physically active groups is attributed to exercise-induced immunoprotective effects, including enhanced surveillance of key immune cells and reduced chronic inflammation. Scientific consensus groups, including those who submitted the Physical Activity Guidelines for Americans, have not yet given this area of research the respect that is due. It is time to add “reduced risk for ARIs” to the “Exercise is Medicine” list of physical activity-related health benefits

Oxylipin Response to Acute and Chronic Exercise: A Systematic Review

Oxylipins are oxidized compounds of polyunsaturated fatty acids that play important roles in the body. Recently, metabololipidomic-based studies using advanced mass spectrometry have measured the oxylipins generated during acute and chronic physical exercise and described the related physiological effects. The objective of this systematic review was to provide a panel of the primary exercise-related oxylipins and their respective functions in healthy individuals. Searches were performed in five databases (Cochrane, PubMed, Science Direct, Scopus and Web of Science) using combinations of the Medical Subject Headings (MeSH) terms: “Humans”, “Exercise”, “Physical Activity”, “Sports”, “Oxylipins”, and “Lipid Mediators”. An adapted scoring system created in a previous study from our group was used to rate the quality of the studies. Nine studies were included after examining 1749 documents. Seven studies focused on the acute effect of physical exercise while two studies determined the effects of exercise training on the oxylipin profile. Numerous oxylipins are mobilized during intensive and prolonged exercise, with most related to the inflammatory process, immune function, tissue repair, cardiovascular and renal functions, and oxidative stress

Healthy lifestyle linked to innate immunity and lipoprotein metabolism: a cross-sectional comparison using untargeted proteomics

Abstract This study used untargeted proteomics to compare blood proteomic profiles in two groups of adults that differed widely in lifestyle habits. A total of 52 subjects in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females) participated in this cross-sectional study. Age, education level, marital status, and height did not differ significantly between LIFE and CON groups. The LIFE and CON groups differed markedly in body composition, physical activity patterns, dietary intake patterns, disease risk factor prevalence, blood measures of inflammation, triglycerides, HDL-cholesterol, glucose, and insulin, weight-adjusted leg/back and handgrip strength, and mood states. The proteomics analysis showed strong group differences for 39 of 725 proteins identified in dried blood spot samples. Of these, 18 were downregulated in the LIFE group and collectively indicated a lower innate immune activation signature. A total of 21 proteins were upregulated in the LIFE group and supported greater lipoprotein metabolism and HDL remodeling. Lifestyle-related habits and biomarkers were probed and the variance (> 50%) in proteomic profiles was best explained by group contrasts in indicators of adiposity. This cross-sectional study established that a relatively small number of proteins are associated with good lifestyle habits

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

Carbohydrate intake attenuates post-exercise plasma levels of cytochrome P450-generated oxylipins.

INTRODUCTION:Oxylipins are bioactive oxidation products derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs) in the linoleic acid and α-linolenic desaturation pathways. PURPOSE:This study determined if carbohydrate intake during prolonged and intensive cycling countered post-exercise increases in n-6 and n-3 PUFA-derived oxylipins. METHODS:The research design utilized a randomized, crossover, counterbalanced approach with cyclists (N = 20, overnight fasted state, 7:00 am start) who engaged in four 75-km time trials while ingesting two types of bananas (Cavendish, Mini-yellow), a 6% sugar beverage, and water only. Carbohydrate intake was set at 0.2 g/kg every 15 minutes, and blood samples were collected pre-exercise and 0 h-, 0.75 h-,1.5 h-, 3 h-, 4.5 h-, 21 h-, 45 h-post-exercise. Oxylipins were measured with a targeted liquid chromatography-multiple reaction monitoring mass spectrometric method. RESULTS:Significant time effects and substantial fold-increases (immediately post-exercise/pre-exercise) were measured for plasma levels of arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 43 of 45 oxylipins. Significant interaction effects (4 trials x 8 time points) were found for plasma ARA (P<0.001) and DHA (P<0.001), but not EPA (P = 0.255), with higher post-exercise values found in the water trial compared to the carbohydrate trials. Significant interaction effects were also measured for 12 of 45 oxylipins. The data supported a strong exercise-induced increase in plasma levels of these oxylipins during the water trial, with carbohydrate ingestion (both bananas types and the sugar beverage) attenuating oxylipin increases, especially those (9 of 12) generated from the cytochrome P-450 (CYP) enzyme system. These trials differences were especially apparent within the first three hours of recovery from the 75-km cycling bout. CONCLUSIONS:Prolonged and intensive exercise evoked a transient but robust increase in plasma levels of oxylipins, with a significant attenuation effect linked to acute carbohydrate ingestion for 28% of these, especially those generated through the CYP enzyme system. TRIAL REGISTRATION:ClinicalTrials.gov, U.S. National Institutes of Health, NCT02994628

Mixed Flavonoid Supplementation Attenuates Post-Exercise 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 &lt; .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

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

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

Image_1_Astaxanthin supplementation counters exercise-induced decreases in immune-related plasma proteins.TIFF

ObjectivesAstaxanthin 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.MethodsThis 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.ResultsThe 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.DiscussionThese 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.</p