Omega-3 polyunsaturated fatty acids modify the inverse association between systemic inflammation and cardiovascular fitness.

BACKGROUND AND OBJECTIVE: Exercise increases quality of life and lowers all-cause mortality, likely by preventing cardiovascular disease. Although the beneficial effects of exercise are linked with reductions in chronic inflammation, individual responses vary and factors that contribute to the anti-inflammatory effects of cardiovascular fitness remain largely undefined. We sought to investigate the role of fatty acids in the inverse relationship between inflammation and cardiovascular fitness. APPROACH AND RESULTS: In this cross-sectional study using data from 435 participants in NHANES and linear regression models with CRP as the outcome, we observed significant negative interactions between VO2max and omega-3 polyunsaturated fatty acids (PUFAs) but not saturated, monounsaturated, or omega-6 PUFAs. When stratified by omega-3 PUFA tertiles, participants in the medium tertile, but not low tertile, show an enhanced negative association between VO2max and CRP, with a -32.0% difference (95% CI: -44.95, -15.9%) per 10 mL/kg/min of VO2max. Exploratory factor analysis identified five unique dietary fatty acid (FA) profiles. The FA profile consisting predominantly of omega-3 PUFA had the strongest negative association for VO2max and CRP, with a -28.2% difference in CRP (95% CI: -43.4, -8.9) per 10 mL/kg/min of VO2max. We also found that alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) enhanced the negative association between VO2max and CRP, suggesting that the anti-inflammatory response to VO2max capacity is associated with ALA and DHA levels. Males, Whites, and individuals with lower BMI were more sensitive to the effects of omega-3 PUFAs, while having high SFA levels attenuated the benefit. CONCLUSIONS: This study suggests that omega-3 PUFAs are effect modifiers for VO2max and CRP and that the anti-inflammatory benefits of increasing cardiovascular fitness are associated with omega-3 PUFAs.

Space Flight Diet-Induced Deficiency and Response to Gravity-Free Resistive Exercise.

Immune system dysregulation is among the many adverse effects incurred by astronauts during space flights. Omega-3 fatty acids, ß-alanine, and carnosine are among the many nutrients that contribute to immune system health. For space flight, crewmembers are prescribed a diet with a macronutrient composition of 55% carbohydrate, 30% fat, and 15% protein. To quantify omega-3 fatty acid, ß-alanine and carnosine intakes from such a diet, and to examine each nutrient's impact on exercise performance, 21 participants adhered to the aforementioned macronutrient ratio for 14 days which was immediately followed by a workout performed on gravity-independent resistive exercise hardware. Results included daily omega-3 fatty acid intakes below the suggested dietary intake. Daily omega-3 fatty acid, ß-alanine and carnosine intakes each correlated with non-significant amounts of variance from the workout's volume of work. Given the nutritional requirements to maintain immune system function and the demands of in-flight exercise countermeasures for missions of increasingly longer durations current results, in combination with previously published works, imply in-flight supplementation may be a prudent approach to help address the physiological and mental challenges incurred by astronauts on future space flights.

Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial).

BACKGROUND: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD. METHODS AND RESULTS: Eighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: -34±46 mg/dL, P<0.001; placebo -10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group. CONCLUSIONS: High-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids-derived products and mediators in patients with PAD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270.