DHA-rich fish oil and regular moderate exercise: a combined intervention to improve cardiovascular, metabolic and inflammatory biomarkers in obesity.

The current obesity epidemic has intensified research on lifestyle interventions aimed at combating obesity and associated cardiovascular (CV) and metabolic risk. This clustering of risk factors with obesity is known as the “Metabolic Syndrome” (MS). There is now a large body of evidence detailing the ability of omega-3 fatty acids (n-3 FA) and regular moderate exercise to independently ameliorate several CV risk factors; however the combination of these interventions may be a more effective strategy in reducing CV risk than either treatment alone. This thesis describes the independent and combined effects of supplementation with docosahexaenoic acid (DHA) rich fish oil, and regular moderate exercise, on CV, metabolic and inflammatory biomarkers. Sedentary, overweight volunteers (BMI > 25kg/m2) with mild hypertension (140/90 – 160/100mmHg), elevated plasma triglycerides (TAG) (>1.6mmol/L) or elevated total cholesterol (TC) (>5.5mmol/L) were recruited in three cohorts for a 12-week intervention trial. Subjects were randomised to one of the following interventions: fish oil, fish oil and exercise, sunflower oil (placebo), sunflower oil and exercise. Subjects consumed 6 g/day of DHA-rich fish oil (26% DHA, 6% EPA; ~1.9g n-3 FA) or sunflower oil. The exercise groups walked 3 days/wk for 45 min, at 75% age-predicted maximal heart rate (HR). Outcome measures were assessed and compared across each intervention group at Weeks 0, 6 and 12, with the exception of body composition, heart rate variability (HRV) and immune functions, which were assessed at Weeks 0 and 12 only. Apart from the consumption of allocated capsules, all subjects were instructed to maintain their normal diet during the study. If not asked to exercise as part of the intervention subjects were also instructed to maintain their normal level of physical activity. Supplementation with DHA rich fish oil resulted in substantial increases in total long chain n-3 FA and DHA levels in erythrocyte membranes, accompanied by reduction of TAG, increase of high-density lipoprotein (HDL) cholesterol and reduction of superoxide production by stimulated neutrophils. Both the increase in HDL and the decrease in superoxide production were correlated with the change in erythrocyte DHA. Endothelium dependent arterial vasodilation (assessed by flow-mediated dilatation, FMD), HRV and HR response to exercise were also improved in subjects supplemented with the DHA-rich fish oil. Regular moderate intensity exercise, either alone or in addition to the DHA-rich fish oil supplementation, had no effect on these parameters, although it improved the compliance of small resistance arteries. Interestingly, however, both DHA-rich fish oil and regular exercise reduced body fat and these effects were additive when the interventions were combined. The change in fat mass was accompanied by an increase in fat oxidation during exercise, as measured by the respiratory exchange ratio. For the population as a whole, reductions in total and abdominal fat mass were associated with reductions in blood pressure. In summary, this study is the first to evaluate the metabolic and CV benefits that can be achieved by combining n-3 FA supplementation from fish oil and regular aerobic exercise in overweight/obese adults. While this combination did not produce any synergistic effects, several independent benefits were attained. The high compliance rate (>85%) within this study indicates that this intervention is well tolerated and may therefore be sustainable in the longer term. Future research should evaluate the mechanisms underlying the n-3 FA - mediated improvements in body composition.Thesis (PhD) -- School of Molecular and Biomedical Science, 200