Background/Aims: Regular fish consumption is associated with low cardiovascular disease risk. However, randomised control trials (RCT) of fish oil supplements produce variable results, recently interpreted to no longer support beneficial effects of long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) EPA and DHA in treating or preventing cardiovascular disease (Nestel P et al., Heart Lung Circ 2015;24:769-779).
Methods: This review considers issues key to understanding the contradiction.
Results: 1) Most RCT report no exclusion criteria for fish eaters and fewer analyse n-3 PUFA status. Even in RCT with exclusions overlap of tissue n-3 PUFA status remain between control and treated groups. 2) Cardiac effects (sudden death, heart failure) derive from myocardial membrane incorporation of DHA. The LCn-3PUFA intake in cohort studies derives from seafood, providing more DHA than EPA, whereas most RCT use supplements rich in EPA, low in DHA. 3) Nutritional and therapeutic effects of LCn-3PUFA derive from direct and indirect mechanisms. Effects on heart rate, heart failure and sudden death occur at lower intakes than influence classical coronary artery disease risk factors such as hyper- triglyceridaemia. RCT designs combining cardiac and arterial disease populations and composite endpoints propose a common substrate and assume common mechanisms of action.
Conclusions: Many fish oil RCT included in systematic reviews are methodologically unsound, failing to consider background diet and multiple mechanisms of LCn-3PUFA or clinical disease Mechanisms of action must be better understood and RCT design and analysis improved to resolve apparent contradictory effects of LC n-3 PUFA supplements and eating fish.
Funding source(s): N/A