Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes

Abstract

Aims/hypothesis To determine the effects of marine-derived n-3 polyunsaturated fatty acids (PUFA) on established and emerging lipid and lipoprotein cardiovascular risk markers in patients with type 2 diabetes. Materials and methods We performed a systematic review and meta-analysis of randomised controlled trials comparing dietary or non-dietary intake of n-3 PUFA with placebo in patients with type 2 diabetes by searching databases from 1966 to December 2006. Changes in the following variables were recorded triacylglycerol; total cholesterol; HDL, LDL and VLDL and their subfractions; lipid ratios; apolipoproteins; and cholesterol particle sizes. Results There were 23 trials on non-dietary supplementation, involving 1,075 subjects with a mean treatment duration of 8.9 weeks, with sufficient data to permit pooling. Compared with placebo, n-3 PUFA had a statistically significant effect on four outcomes, reducing levels of (1) triacylglycerol (18 trials, 969 subjects) by 25% (mean 0.45 mmol/l; 95% CI −0.58 to −0.32; p<0.00001); (2) VLDL-cholesterol (7 trials, 238 subjects) by 36% (0.07 mmol/l; 95% CI −0.13 to 0.00; p=0.04); and (3) VLDL-triacylglycerol (6 trials, 178 subjects) by 39.7% (0.44 mmol/l; 95% CI −0.83 to −0.05; p= 0.03); while slightly increasing LDL (16 trials, 565 subjects) by 5.7% (0.11 mmol/l; 95% CI 0.00 to 0.22; p=0.05). There were no significant effects on total cholesterol, apolipoproteins, lipid subfractions or ratios. Conclusions/interpretation In addition to recognised triacylglycerol-lowering effects, n-3 PUFA supplementation decreases VLDL-cholesterol and VLDL-triacylglycerol, but may have an adverse effect on LDL-cholesterol. Larger and longer term clinical trials are required to conclusively establish the effect of n-3 PUFA on cardiovascular risk markers and outcomes in type 2 diabetic patients.

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

“…These include anti-arrhythmic, haemostatic and anti-inflammatory effects and blood-pressure lowering [45]. AFORRD showed no change in systolic or diastolic blood pressure, but in our meta-analysis, omega-3 PUFA supplementation decreased diastolic blood pressure by 1.8 mmHg in patients with diabetes, with no effect on systolic blood pressure [18]. Blood-pressure reduction with omega-3 PUFA appears to be dose-dependent [46] and again the omega-3 EE90 2 g/day dose used in AFORRD may have been too small.…”

“…Fibrate therapy can improve both of these, but there are concerns about combining them with statins because of adverse events [14] and the failure of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial to demonstrate CVD-risk reduction with fenofibrate [15]. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) are an alternative triacylglycerol-lowering therapy; there is strong epidemiological evidence suggesting favourable outcomes in people with type 2 diabetes with high omega-3 PUFA intake [16] and improvements in CVD-risk-factor profiles [17,18]. Studies involving wider populations have been less supportive [19], and a prospective primary-care trial is required to establish whether omega-3 PUFA, alone or with a statin, can improve risk-factor levels and reduce estimated CVD risk as a prelude to cardiovascular-outcome studies.…”

Systematic review of omega-3 enriched foods and health

“…The dosages used in studies with health benefits are consistent with findings made in a LC3PUFA supplementation meta-analysis by Hartweg et al (2007), who concluded that LC3PUFA offer cholesterol lowering effects and that high doses (>2g/d) may offer greater benefits in this area.…”

“…For example, studies have shown consistently good evidence linking LC3PUFA consumption to a host of health benefits, including improved cardiovascular (CV) health, kidney health, mental health, reduction of triglyceride levels and certain cancer forms (Geelen et al, 2007 ;Hartweg et al, 2007 ;Miller et al, 2009 ;Carayol et al, 2010 ;MusaVeloso et al, 2011). Current n-3 clinical treatment areas include CV disease, cancer, type 2 diabetes, depression and stress, inflammatory diseases and Alzheimer's disease (Gogus and Smith 2010).…”

Parenteral nutrition-associated cholestasis and triglyceridemia in surgical term and near-term neonates: A pilot randomized controlled trial of two mixed intravenous lipid emulsions

“…In animal models, addition of fish oil triglycerides to IVLE was found to increase blood clearance of large size emulsion particles, probably due to increased particle uptake by extra-hepatic tissues [40,41]. In adults with hypertriglyceridemia, fish oils were effective in reducing triacylglycerol and particularly VLDL triacylglycerol levels [42]. Finally, the influence of the type of IVLE container on fat globule size is controversial.…”