Investigating the Neuroprotective Effect of Oral Omega-3 Fatty Acid Supplementation in Type 1 Diabetes (nPROOFS1): A Randomized Placebo-Controlled Trial
What this study found
Compared with placebo, six-month n-3 PUFA supplementation increased CNFL by 2.70 mm/mm2 (95% CI 1.64–3.75; P<0.001). CNFD increased by 4.98 nerves/mm2 (95% CI 2.51–7.44; P=0.004) and CNBD by 11.23 branches/mm2 (95% CI 7.01–15.45; P=0.002). Omega-3 Index increased by 3.3 percentage points (95% CI 2.4–4.2). Corneal sensitivity and most peripheral nerve function measures showed no between-group differences; adverse events were similar. Tear break-up time favored n-3 PUFA. Authors conclude that long-chain omega-3 PUFA supplementation induces corneal neuroregeneration and may modulate peripheral…
- Study & population
- Design: single-center, double-masked, randomized, two-arm parallel-group, superiority, placebo-controlled trial.
- Intervention
- Active: oral long-chain omega-3 PUFA supplements totaling 1,800 mg/day (1,080 mg EPA + 720 mg DHA), taken as two capsules daily for 180 ± 24 days.
- Key limitation
- Small sample size and single-center design; not powered for most functional neuropathy endpoints; primary endpoint CNFL is a surrogate marker; baseline CNFL and age imbalances; six-month duration may be insufficient to detect changes in traditional neuropathy measures; multiplicity not fully controlled for secondary…
View source
Open PDFOriginal 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 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/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.