Background:
Greater consumption of omega-3 fatty acids has been associated with lower cardiovascular disease risk. Randomized controlled trials indicate direct, albeit small, beneficial effects of omega-3 fatty acids on plasma triglycerides and blood pressure, yet few studies have tested their impact on insulin resistance and the clustered risk factors comprising the metabolic syndrome.
Hypothesis:
Short-term supplementation with marine omega-3 polyunsaturated fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) will improve aggregated cardiometabolic risk (CMR) in healthy middle-aged adults
Methods:
We conducted a double-blind, placebo-controlled, parallel group clinical trial. Subjects were 30-54 year-old adults free of atherosclerotic disease and diabetes whose intake of EPA and DHA totaled <300 mg/day. Each was randomly assigned to daily fish oil supplements (2g/day containing 1000 mg EPA and 400mg DHA) or matching soybean oil placebo for 18 weeks. Aggregate CMR at baseline and post-intervention was calculated as the standardized sum of standardized distributions of blood pressure, BMI, and fasting serum triglycerides, glucose, and HDL (reverse scored). Missing data due to dropouts (n=17) and outliers (1-6 per variable) were replaced by multivariate imputation. Outcome analyses were conducted with linear regressions of all randomized subjects based on intention-to-treat.
Results:
Participants were 272 healthy adult (57% (154 out of 272) women; 17% (47 out of 272) minority; mean age 42) Pittsburgh-area residents. At baseline, demographics, health parameters, physical activity and EPA and DHA consumption did not differ significantly between treatment groups. No overall treatment effect was found, whereas gender moderated the effects of treatment on CMR risk (gender, p=.001 and gender*treatment interaction term p=.011). In gender-specific analyses, supplementation lowered CMR risk relative to placebo in men(p=.036, effect size=.629, standard error (SE) =.282) but not women (p=.168, effect size .261, SE=.222). Of the individual CMR variables, only HDL-cholesterol in men revealed a significant improvement (p=.012). In men receiving placebo, HDL-cholesterol fell by 1.1 mg/dl, whereas in those receiving fish oil, HDL rose by 1.7 mg/dl. As has been noted in other samples, compared to women men had greater CMR and lower HDL-cholesterol.
Conclusions:
Increased intake of n-3 fatty acids over 4 months reduced CMR in healthy, mid-life men but not women. This finding may be due to poorer baseline CMR and HDL characteristic of men, or to gender differences in fatty acid metabolism. Further study of gender differences in cardiometabolic risk and fatty acid metabolism may lead to gender-tailored preventive interventions.
Omega-3 Fatty Acids Reduce Adipose Tissue Macrophages in Human Subjects With Insulin Resistance