New Review of Marine-Derived Omega-3 Supplementation on Cardiovascular Disease Risk Factors in Diabetics
Hartweg J et al., Curr. Opin. Lipidol., 20 :30-38, 2009.
Division of Public Health and Primary Healthcare, Oxford Centre for Diabetes, School of Primary Care Research, University of Oxford, Oxford, UK
The present publication from this group at the University of Oxford in the UK presents a systematic review of combined results from numerous randomized controlled trials as published up to the fall of 2008 which have researched the potential effects of supplementation with EPA/DHA combined at varying doses and durations on numerous risk factors for cardiovascular disease in individuals with type 2 diabetes. This systematic review (and meta-analysis) provides a pooled summation of results from 24 individual trials conducted between 1996-2008 involving 1533 participants.
The average daily dose of omega-3 fatty acids was 2.4 grams (2400 mg per day) over an average time period of 24 weeks. Compared to the participants in the various trials given a placebo (control) supplement, omega-3 supplementation significantly reduced fasting blood triglyceride levels (by 7%), fibrinogen by 10%, and platelet aggregation to ADP and to collagen by 22 and 21%, respectively. A small but significant increase of 3% in circulating LDL-cholesterol was noted after omega-3 supplementation. These results are of considerable interest since the aforementioned risk factors are all of importance for cardiovascular disease and corresponding cardiac events in individuals with type 2 diabetes. It is noted that fibrinogen is associated with the so-called ‘coagulation cascade’ in the blood which can lead to thrombosis and that higher levels of circulating fibrinogen in the blood are associated with cardiovascular disease. Thrombosis refers to the formation of a blood clot or ‘thrombus’ within a blood vessel which can significantly restrict or obstruct blood flow through the circulatory system. Reductions in the tendency for circulating blood platelets to form aggregates (aggregation) have been associated with a reduced risk of thrombosis.
In their analyses of the numerous clinical trials as evaluated, the present authors did not find any overall effect of omega-3 supplementation on circulating levels of glycated hemoglobin as compared with controls; furthermore, omega-3 supplementation was not associated with a significant change in fasting insulin levels and had no overall consistent effect on fasting blood glucose concentrations. No consistent and significant effect of omega-3 supplementation was found on HDL-cholesterol levels, LDL particle size, various inflammatory biomarkers, and blood pressures. The authors pointed out that the small but statistically significant increase in LDL-cholesterol levels with omega-3 supplementation are currently unclear with respect to clinical significance and should be placed in the context of other favourable effects of omega-3 polyunsaturates including blood triglyceride-lowering. They also noted the considerable variability in triglyceride-lowering in the various trials with higher doses of omega-3 supplementation having greater triglyceride-lowering effects.
In conclusion, the authors state that their findings ‘support the current American Heart Association anti-arrhythmic guidelines that recommend 1 g/day EPA and DHA for individuals with established CVD disease and 4 g/day for those with hypertriglyceridemia’.
Dr. Holub's Comments:
It is noteworthy that one of the contributing factors to the small but statistically significant rise in LDL-cholesterol levels as noted by the authors in their current review may arise from the indirect method used in numerous health-care systems for estimating LDL-cholesterol levels by way of the so-called ‘Friedwald equation’. This equation indirectly calculates the LDL-cholesterol level by subtracting the levels of HDL-cholesterol and a portion of the fasting triglyceride levels from the total cholesterol concentration such that dietary strategies which lower triglyceride levels can result in a calculated elevation in LDL-cholesterol levels. The present review did not analyze for the effect of omega-3 supplementation as EPA/DHA and clinical cardiovascular events or related death since none of the trials which they examined with respect to risk factor measurements reported upon cardiovascular disease-related endpoints. It is noted that there are major clinical outcome trials in progress or recently completed wherein the potential effect of omega-3 supplementation in patients with type 2 diabetes on ‘hard’ cardio events are being measured but no published results from such studies are yet available. With respect to the AFORRD randomized controlled trial, which is evaluating statin treatment in factorial with omega-3 supplementation with respect to risk reduction in people with type 2 diabetes but without known cardiovascular disease, the longer-duration results with omega-3 (past 4 months treatment) have not yet been published (Holman et al., Diabetologia, 52:50-59 (2009)).