Omega-3 fatty acid supplementation for distal symmetrical peripheral neuropathy in adults with diabetes mellitus.

Rationale: Diffuse distal symmetrical polyneuropathy (DSPN) is a common complication in people living with diabetes mellitus. There is currently no effective treatment for DSPN. There is a biological rationale that omega-3 polyunsaturated fatty acids (PUFAs) may modify peripheral nerve function in DSPN. However, there is a lack of certainty about the potential benefits and harms of omega-3 PUFAs as a treatment for DSPN.

Objectives: To evaluate the benefits and harms of oral omega-3 PUFA supplements as a treatment for DSPN in adults with diabetes mellitus, compared to placebo or no treatment.

Search methods: We searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two clinical trials registries, together with reference checking, to identify studies eligible for inclusion in the review. The latest search date was 12 June 2024.

Eligibility criteria: We included randomised controlled trials (RCTs) involving adults with type 1 diabetes, type 2 diabetes, or impaired glucose tolerance who had evidence of DSPN, that compared omega-3 PUFA supplements with placebo treatments or no treatment. We excluded studies with an intervention period of less than 180 days.

Outcomes: Our critical outcome was peripheral neuropathy impairment at six months after treatment. Other main outcomes were: symptoms of peripheral neuropathy, pain, quality of life, and adverse events, including any adverse events; adverse events leading to discontinuation of the intervention; and serious adverse events. We recorded outcomes as change from baseline, or the study endpoint measure, if change from baseline data were not reported.

Risk of bias: We used the Cochrane RoB 2 tool to assess bias in the included RCTs.

Synthesis methods: We synthesised results for each outcome using meta-analysis where possible (inverse variance, random-effects model). Where this was not possible due to the nature of the data, we synthesised the results by summarising effect estimates. We used GRADE to assess the certainty of the body of the evidence for each key outcome.

Included studies: This review included two completed RCTs that collectively involved 87 participants.

Synthesis of results: Based on findings from one study (43 participants with type 1 diabetes), oral omega-3 PUFA supplementation for six months may have little to no effect on the short-term risk of developing peripheral neuropathy impairment (RR 0.24, 95% CI 0.03 to 1.94; low-certainty evidence), peripheral neuropathy symptoms (MD -0.17, 95% CI -1.36 to 1.02; low-certainty evidence), or health-related quality of life (MD 0.02, 95% CI -0.06 to 0.10; low-certainty evidence), compared to a placebo treatment. From two studies (pooled estimates from outcomes reported for 78 participants), there may be little or no difference between omega-3 PUFA and placebo supplementation with respect to the risk of developing any adverse event (RR 1.03, 95% CI 0.66 to 1.61; P = 0.88; very low-certainty evidence) or a serious adverse event (RR 0.45, 95% CI 0.11 to 1.85; P = 0.27; very low-certainty evidence), but the evidence is very uncertain. The included studies did not report data on pain outcomes or adverse events leading to discontinuation of the treatment.

Authors' conclusions: There are inadequate data to draw conclusions about the effects of omega-3 PUFA supplementation on peripheral nerve impairment in adults with diabetes mellitus. There may be little to no benefit of oral omega-3 PUFA treatment, compared to placebo or no treatment, for improving peripheral neuropathy symptoms or health-related quality of life. While no harms of omega-3 PUFA treatment are suggested, more data are needed to elucidate any potential risks.

Funding: This review did not have dedicated funding.

Registration: Protocol available via DOI 10.1002/14651858.CD014623.