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

Abstract

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 dia-betes. 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 out-comes included change in other corneal nerve parame-ters, 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 reti-nopathy grade and adverse events. Between July 2017 and September 2019, 43 participants received n-3 (n 5 21) or placebo (n 5 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/mm2 (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.