Omega-3 fats have little or no effect on type 2 diabetes — meta-analysis

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Omega3Type 2 diabetes is a leading cause of illness and death, with annual costs estimated at over $800bn worldwide. The rise in type 2 diabetes is mainly due to increased body fatness and inactivity so diet and body weight are key in treating, preventing, and delaying its onset.

Previous studies have suggested that polyunsaturated fatty acids (PUFAs) derived from oily fish (long-chain omega-3) and from plants (alpha-linolenic acid and omega-6) may have beneficial effects on the body that could help protect against type 2 diabetes but results are inconclusive. Many countries also recommend a diet high in polyunsaturated fats for a range of conditions, including diabetes.

To explore this further, researchers at the University of East Anglia analysed the results of 83 randomised controlled trials involving 121,070 people with and without diabetes, all of at least six months duration. Trials assessed the effects of increasing long-chain omega-3, alpha-linolenic acid, omega-6 or total PUFAs on new diabetes diagnoses or measures of glucose metabolism (how well the body processes sugars) taken either as supplements or via enriched or naturally rich foods. The quality of evidence for each trial was also measured.

The researchers found that increasing long-chain omega-3 fats (LCn3, from fish oils, by 2g per day LCn3 over a mean trial duration of 33 months) had little or no effect on likelihood of diabetes diagnosis or on glucose metabolism, and this did not change with longer duration.

Effects of alpha-linolenic acid (or ALA, another type of omega-3), omega-6 and total PUFAs on diabetes diagnosis were unclear (as the evidence was of very low-quality). Meta-analysis (combining the results of the trials) suggested little or no effect of these fats on measures of glucose metabolism.

There was a suggestion that high doses of long-chain omega-3 fats (more than 4.4g per day) may have negative effects on diabetes risk and glucose metabolism, but the researchers stress that this finding should be interpreted with caution.

The researchers point to some weaknesses, including missing data and risk of bias in some trials. Nevertheless, when they restricted their analyses to only include the highest quality trials (those at lowest risk of bias) there was still no effect on diabetes risk or glucose metabolism.

The researchers say this is the most extensive review to date assessing the effects of polyunsaturated fats on diabetes and glucose metabolism in long-term randomised controlled trials.

As such, they say “there is no convincing evidence to suggest that altering our LCn3, ALA, omega-6 or total PUFA intakes alters glucose metabolism or risk of diabetes.” And they suggest that supplements “should not be encouraged for diabetes prevention or treatment.

Larger, high quality trials of at least 12 months duration looking at the effects of ALA, omega-6, oily fish and total PUFA on diabetes diagnosis and measures of glucose metabolism would be helpful, they conclude.

Abstract
Objective: To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism.
Design: Systematic review and meta-analyses.
Data sources: Medline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews.
Eligibility criteria: Randomised controlled trials of at least 24 weeks’ duration assessing effects of increasing α-linolenic acid, long chain omega-3, omega-6, or total PUFA, which collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA1c), and/or homoeostatic model assessment for insulin resistance (HOMA-IR).
Data synthesis: Statistical analysis included random effects meta-analyses using relative risk and mean difference, and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline risk of diabetes and use of antidiabetes drugs, trial duration, and dose. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE.
Results: 83 randomised controlled trials (mainly assessing effects of supplementary long chain omega-3) were included; 10 were at low summary risk of bias. Long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes (relative risk 1.00, 95% confidence interval 0.85 to 1.17; 58 643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA1c mean difference −0.02%, 95% confidence interval −0.07% to 0.04%; plasma glucose 0.04, 0.02 to 0.07, mmol/L; fasting insulin 1.02, −4.34 to 6.37, pmol/L; HOMA-IR 0.06, −0.21 to 0.33). A suggestion of negative outcomes was observed when dose of supplemental long chain omega-3 was above 4.4 g/d. Effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), but little or no effect on measures of glucose metabolism was seen, except that increasing α-linolenic acid may increase fasting insulin (by about 7%). No evidence was found that the omega-3/omega-6 ratio is important for diabetes or glucose metabolism.
Conclusions: This is the most extensive systematic review of trials to date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors. Evidence suggests that increasing omega-3, omega-6, or total PUFA has little or no effect on prevention and treatment of type 2 diabetes mellitus.

Authors
Tracey J Brown, Julii Brainard, Fujian Song, Xia Wang, Asmaa Abdelhamid, Lee Hooper

BMJ material
BMJ abstract


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