Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials

The BMJ

Aug 2019

DOI: 10.1136/bmj.l4697

Citations:249

Influential Citations:13

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomised controlled trials in adults aged ≥18 years at risk of diabetes (healthy individuals and those with diagnosed diabetes), not pregnant or acutely ill; long-term trials (≥24 weeks) comparing higher versus lower intake of omega-3, omega-6, or total PUFA; conducted in community settings.

Intervention

Long-chain PUFA intake for at least 24 weeks via oral supplementation; long-chain omega-3 (EPA+DHA) given as oils or capsules at varying doses, including high-dose regimens (>4.4 g/day); regimens also included alpha-linolenic acid (ALA), omega-6, and total PUFA delivered by supplements or diet (including oily fish).

Results

Long-chain omega-3 supplementation probably has little or no effect on diabetes diagnosis or glucose metabolism. Diabetes incidence risk: RR 1.00 (0.85–1.17). HbA1c: −0.02% (−0.07 to 0.04). Fasting glucose: +0.04 mmol/L (0.02–0.07). Fasting insulin: +1.02 pmol/L (−4.34 to 6.37). HOMA-IR: +0.06 (−0.21 to 0.33). At higher doses (>4.4 g/d), results suggested possible negative effects. α-linolenic acid (ALA) may increase fasting insulin by ~7% (low-quality evidence). Effects of omega-6 and total PUFA on diabetes risk and glucose metabolism are unclear or minimal; no evidence that omega-3/omega-6 ratio matters. Conclusion: increasing omega-3, omega-6, or total PUFA probably has little or no effect on prevention or treatment of type 2 diabetes; if long-chain omega-3 is used to lower triglycerides or by people at risk for diabetes, doses below 4.4 g/d should be encouraged; more robust trials are needed.

Limitations

Many trials had risk of bias; only 10 of 83 trials were at low summary risk of bias; substantial missing data across trials (data could not be analyzed or were unreported); heterogeneity in PUFA types, doses, delivery matrices (supplements vs foods); limited data and low-quality evidence for ALA, omega-6, and total PUFA; potential publication bias; results largely based on supplementation trials, with limited oily-fish data; generalizability mainly to industrialized countries.

Abstract

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. Systematic review registration PROSPERO CRD42017064110. show less