Omega-3 fatty acid supplementation for diabetic peripheral neuropathy: a Cochrane review

Aims: The objective of this study was to assess the effect of oral omega-3 polyunsaturated fatty acids (omega-3 PUFAs) for distal symmetric polyneuropathy (DSPN).

Methods: This was a systematic review of randomized clinical trials (RCTs) evaluating omega-3 PUFA supplements compared to placebo for the treatment of DSPN in type 1 diabetes (T1D), type 2 diabetes, and impaired glucose tolerance. The critical outcome was peripheral neuropathy impairment at 6 months. Other outcomes included neuropathy symptoms, pain, quality-of-life (QoL) and adverse events. Meta-analysis for each outcome was done where possible; where not possible, effect estimates were summarized.

Results: Two RCTs with a total of 87 participants were included. One 6-month study of (n=43 with T1D) omega-3 PUFA supplements showed no significant effects on peripheral neuropathy impairment (RR 0.24, 95% CI 0.03-1.94), peripheral neuropathy symptoms (MD -0.17, 95% CI -1.36-1.02), or health-related QoL (MD 0.02, 95% CI -0.06-0.10) compared to placebo. Pooled estimates from 78 participants from two studies similarly showed no difference in developing an adverse event (RR 1.03, 95% CI 0.66-1.61; P = 0.88), or serious adverse events (RR 0.45, 95% CI 0.11-1.85; P = 0.27). The evidence for all outcomes was low-certainty to very low-certainty.

Conclusions: There are inadequate data to determine the effects of omega-3 PUFA supplementation on DSPN in adults with diabetes. Larger, well-designed clinical trials are needed to clarify the risks and benefits.

Comments. In this systematic review, the effect of omega-3 PUFA supplementation was evaluated for treatment of DSPN. DSPN is a common and disabling condition and both glycaemic and vascular factors, including dyslipidemia, have been implicated in the pathophysiology (Sloan G et al Nature Reviews Endocrinology 2021;17:400-420). Unfortunately, disease-modifying therapies are limited. Despite theoretical benefits of omega-3 PUFA supplements, this review finds that the current evidence is both limited and weak. The inclusion of only two small RCTs limits the robustness and generalizability of the results. Additionally, the duration of therapy in these RCTs was short, which may be an inadequate amount of time to see any clinically meaningful improvements based on the outcome measures. In summary, while the physiological rationale for omega-3 PUFAs is promising and the intervention is generally considered safe, the current evidence does not support their use as a therapeutic option for DSPN. Future studies with larger sample sizes and more comprehensive outcomes are urgently needed.

Kara Mizokami-Stout

Reference. Britten-Jones AC, Linstrom TA, Makrai E, Singh S, Busija L, MacIsaac RJ, Roberts LJ, Downie LE. Omega-3 fatty acid supplementation for distal symmetrical peripheral neuropathy in adults with diabetes mellitus. Cochrane Database Syst Rev. 2025 Sep 24;9(9):CD014623. doi: 10.1002/14651858.CD014623.pub2. PMID: 40990181; PMCID: PMC12458980.

🔗 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014623.pub2/full