Clin Nutr. , 2021., https://doi.org/10.1016/j.clnu.2021.02.006.

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

Farley, G Riggs, DW Bhatnagar, A et al.

Abstract

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 VO2 max. 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 cardiovascular fitness are associated with omega-3 PUFAs.

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Key Points

Omega-3 polyunsaturated fatty acids (PUFA), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been shown to have anti-inflammatory properties leading to a lower risk for development of chronic inflammatory diseases. Whether endogenous omega-3 PUFA levels contribute to the health benefits of cardiovascular fitness remains unknown. Here it was postulated that higher intake of omega-3 PUFAs, by facilitating resolution of inflammation, may enhance the salutary effects of exercise. Using data from the National Health and Nutrition Examination Survey (NHANES) to test this hypothesis, the study examined whether plasma levels of omega-3 PUFAs modify the association between cardiovascular fitness and inflammation, sought to determine the role of individual omega-3 PUFAs, and to identify populations most sensitive to the modifying influence of omega-3 PUFAs on cardiovascular fitness. Higher level of omega-3 PUFAs modified the relationship between cardiovascular fitness and inflammation. Individuals who have low circulating levels of omega-3 PUFAs have a reduced inverse association with inflammation and higher levels of cardiovascular fitness. Plasma levels of alpha-linolenic acid and docosahexaenoic acid, but not eicosapentaenoic acid or docosapentaenoic acid, significantly strengthen the negative association between cardiovascular fitness and chronic inflammation. It appears that higher levels of omega-3 PUFA in conjunction with low levels of SFA are important to obtain the anti-inflammatory benefit of exercise. Despite being limited to a small group of individuals with metabolic syndrome, these findings are consistent with the findings of our study showing that omega-3 fatty acids modify the relationship between cardiovascular fitness and inflammation.