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

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 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.

Keywords: CRP; Cardiovascular; Exercise; Inflammation; Omega-3.

Fig. 1.

Predicted mean of CRP and VO₂ max (A), Association between CRP and sums of fatty acid group tertiles (B). Multivariable linear regression models were used to examine the relationship between CRP with VO₂ max and fatty acid group tertiles. CRP was log transformed, and all models were adjusted for age, sex, BMI, and covarying fatty acid group based on Pearson's correlation coefficient (e.g., saturated fatty acids for all groups except saturated fatty acid model, which was adjusted for monounsaturated fatty acids). Beta represents change in log CRP per 1 unit of VO₂ max. Bars represent 95% confidence intervals. * Significantly different than reference (lowest tertile).

Fig. 2.

Association between VO₂ max and CRP stratified by tertiles of fatty acid groups. Results are presented as percent difference and 95% confidence intervals per 10 mL/kg/min of VO₂ max. Solid black line indicates the percent difference between VO₂ max and CRP in the full sample. CRP was log-transformed for normality. Linear regression models were used to test for associations between log-CRP and VO₂ max or fatty acid group tertiles. All models were adjusted for age, sex, BMI, and covarying fatty acid group based on Pearson's correlation coefficient (e.g., saturated fatty acids for all groups except saturated fatty acid model, which was adjusted for monounsaturated fatty acids). * Represents significant interaction between VO₂ max and fatty acid tertile (ref = low).

Fig. 3.

Association between CRP and exploratory factor analysis profiles (tertiles). Results are presented as percent difference and 95% confidence intervals as compared to the lowest tertile. P value for trend are included for each fatty acid profile. CRP was log-transformed for normality. Linear regression models were used to test for associations between log-CRP and factor analysis tertiles. All models were adjusted for age, sex, and BMI. * Significantly different than reference (lowest tertile).

Fig. 4.

Associations between CRP and VO₂ max stratified by factor analysis tertiles. Results are presented as percent difference and 95% confidence intervals per 10 mL/kg/min of VO₂ max. Solid black line indicates the percent difference between VO₂ max and CRP in the full sample. CRP was log-transformed for normality. Linear regression models were used to test for associations between log-CRP and VO₂ max. All models were adjusted for age, sex, race, and BMI.

Fig. 5.

Associations between CRP and VO₂ max stratified by Individual omega-3 PUFA (A) and omega-6 PUFA (B) tertiles. Results are presented as percent difference and 95% confidence intervals per 10 mL/kg/min of VO₂ max. Solid black line indicates the percent difference between VO₂ max and CRP in the full sample. CRP was log-transformed for normality. Linear regression models were used to test for associations between log-CRP and VO₂ max. All models were adjusted for age, sex, and BMI. The alpha-linolenic acid model was additionally adjusted for docosahexaenoic acid. The docosahexaenoic acid model was additionally adjusted for alpha-linoleic acid. * Represents significant interaction between VO₂ max and fatty acid tertile (ref = low).

Fig. 6.

Subgroup analysis of the interactions between omega-3 PUFA tertiles and VO₂ max in predicting CRP. The mean ± S.D. for the sum of omega-3 PUFA levels for each subgroup. Linear regression models were used to test for interactions between VO₂ max and omega-3 PUFA tertiles. All models were adjusted for age, sex, race, and BMI unless they were used as a stratification variable. Results are presented as percent difference and 95% confidence intervals for the interaction term in predicting CRP, using the low omega-3 group as a reference.