Investigating the Neuroprotective Effect of Oral Omega-3 Fatty Acid Supplementation in Type 1 Diabetes (nPROOFS1): A Randomized Placebo-Controlled Trial

This randomized, double-masked, placebo-controlled trial evaluated the effects of oral omega-3 (n-3) fatty acid supplementation on peripheral nerves in type 1 diabetes. Participants with type 1 diabetes were assigned (1:1) to n-3 (1,800 mg/day fish oil) or placebo (600 mg/day olive oil) supplements for 180 days. The primary outcome was change from baseline in central corneal nerve fiber length (CNFL) at day 180. Secondary outcomes included change in other corneal nerve parameters, corneal sensitivity, peripheral small and large nerve fiber function, and ocular surface measures. Efficacy was analyzed according to the intention-to-treat principle. Safety assessments included diabetic retinopathy grade and adverse events. Between July 2017 and September 2019, 43 participants received n-3 (n = 21) or placebo (n = 22) supplements. All participants, except for two assigned to placebo, completed the trial. At day 180, the estimated increase in CNFL in the n-3 group, compared with placebo, was 2.70 mm/mm(2) (95% CI 1.64, 3.75). The Omega-3 Index increased relative to placebo (3.3% [95% CI 2.4, 4.2]). There were no differences in most small or large nerve fiber functional parameters. Adverse events were similar between groups. In conclusion, we found in this randomized controlled trial that long-chain n-3 supplements impart corneal neuroregenerative effects in type 1 diabetes, indicating a role in modulating peripheral nerve health.