Meta-analysis of the effects of n-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes

Hartweg, Janine; Farmer, Andrew; Holman, Rury R.; Neil, H. A. W.

doi:10.1007/s00125-006-0486-y

Cited by 52 publications

(25 citation statements)

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“…The lack of effect of omega-3 EE90 2 g/day on total cholesterol, HDL-C and LDL-C is consistent with the results of our recent meta-analysis examining the effect of non-dietary supplementation with omega-3 PUFA on lipids and lipoproteins in 18 trials involving a total of up to 999 patients with type 2 diabetes [17]. However, the small but statistically significant reduction in triacylglycerol of 0.09 mmol/l (5.6%) in AFORRD was substantially less than the 0.46 mmol/l (95% CI 0.33-0.59) reduction shown in the meta-analysis.…”

Section: Discussionsupporting

confidence: 89%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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Aims/hypothesis The aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 (omega-3 EE90; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids) on estimated cardiovascular disease (CVD) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy. Methods A central computer randomised 800 patients in 59 UK general practices to atorvastatin (n=401, 20 mg/day) or placebo (n=399) and omega-3 EE90 (n=397, 2 g/day) or placebo (n=403) in a concealed factorial manner. Participants with LDL-cholesterol <2.6 mmol/l, triacylglycerol <1.5 mmol/l and estimated 10-year CVD risk <20% were compared at 4 months.Results Mean (SD) age was 63.5 (11.7) years, HbA 1c 6.9 (1.1) % and known diabetes duration (median [interquartile range]) was 4 (2-8) years. Fifty-seven per cent were men, 90% white and 74% had an estimated 10-year CVD risk ≥20%. Of 732 patients with 4-month data, more allocated atorvastatin (n=371) compared with placebo (n=361) achieved LDLcholesterol <2.6 mmol/l (91% vs 24%, p<0.001) and had estimated 10-year CVD risks <20% (38% vs 26%, p<0.001). No differences were seen between those allocated omega-3 EE90 (n=371) compared with placebo (n=361) for participants achieving triacylglycerol <1.5 mmol/l (65% vs 60%, p=0.18) or estimated 10-year CVD risks <20% (34% vs 30%, p=0.18). There were no side effects of note. Conclusions/interpretation Many community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies. The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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“…However, studies generally show no significant effect of n-3 LCP on haemostatic factors levels or activities in healthy subjects (177)(178)(179) , with similar findings for algal DHA (180) . In type 2 diabetics, fish oil supplementation decreased fibrinogen levels by 10 % (162) , and increased factor VII by 25% (181) , based on meta-analysis of three trials (159 participants) and two trials (116 participants), respectively. More studies are needed to clarify the independent effects of EPA and DHA on haemostatic factors.…”

Section: Effects Of Epa and Dha On Thrombosis And Haemostasismentioning

confidence: 99%

The differential effects of EPA and DHA on cardiovascular risk factors

2011

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Compelling evidence exists for the cardioprotective benefits resulting from consumption of fatty acids from fish oils, EPA (20 :5n-3) and DHA (22 :6n-3). EPA and DHA alter membrane fluidity, interact with transcription factors such as PPAR and sterol regulatory element binding protein, and are substrates for enzymes including cyclooxygenase, lipoxygenase and cytochrome P450. As a result, fish oils may improve cardiovascular health by altering lipid metabolism, inducing haemodynamic changes, decreasing arrhythmias, modulating platelet function, improving endothelial function and inhibiting inflammatory pathways. The independent effects of EPA and DHA are poorly understood. While both EPA and DHA decrease TAG levels, only DHA appears to increase HDL and LDL particle size. Evidence to date suggests that DHA is more efficient in decreasing blood pressure, heart rate and platelet aggregation compared to EPA. Fish oil consumption appears to improve arterial compliance and endothelial function; it is not yet clear as to whether differences exist between EPA and DHA in their vascular effects. In contrast, the beneficial effect of fish oils on inflammation and insulin sensitivity observed in vitro and in animal studies has not been confirmed in human subjects. Further investigation to clarify the relative effects of consuming EPA and DHA at a range of doses would enable elaboration of current understanding regarding cardioprotective effects of consuming oily fish and algal sources of long chain n-3 PUFA, and provide clearer evidence for the clinical therapeutic potential of consuming either EPA or DHA-rich oils.

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“…In a previous systematic review, we considered the effects of n-3 PUFA supplementation on thrombogenic and other emerging markers for cardiovascular disease [17]. Here we examine the effects of marine-derived n-3 PUFA supplementation on emerging and established lipid risk markers in patients with type 2 diabetes in randomised placebo-controlled clinical trials, deriving, where possible, pooled estimates of effect size.…”

mentioning

confidence: 99%

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

et al. 2007

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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.

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Meta-analysis of the effects of n-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes

Cited by 52 publications

References 68 publications

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

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

The differential effects of EPA and DHA on cardiovascular risk factors

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

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