P.58No effect of resveratrol supplementation in patients with mitochondrial myopathy - a randomized, double-blind, placebo-controlled, cross-over study

Abstract

Mitochondrial myopathies (MM) are caused by mutations that affect proteins involved in oxidative phosphorylation. Main symptoms are exercise intolerance and fatigue. Currently, there is no specific treatment for MM. Resveratrol (RSV) is a well-known nutritional supplement that may target several mitochondrial metabolic pathways. It has been shown to enhance oxidative capacity and have antioxidant and anti-inflammatory properties in cells and animal models. The study is the first to asses if RSV can improve mitochondrial function and thereby improve exercise capacity in patients with MM. The study design was randomized, double-blind, crossover and placebo-controlled. Ten patients with genetically verified MM were randomized to receive either 1000 mg/day RSV or placebo (P) for 8 weeks followed by 8 weeks with the opposite treatment separated by a 4-week washout. Primary outcomes were changes in heart rate (HR) during submaximal cycling exercise, and peak oxygen utilization (VO2max) during maximal exercise. Secondary outcomes included reduction in perceived exertion (Borg scale), changes in lactate production, and self-rated function (SF-36) and fatigue scores (FSS). Values are presented as mean change from baseline to end-treatments ±SD. The paired non-parametric Wilcoxon test was used to compare treatment effects with ≤0.05 as level of significance. The results show no changes in primary or secondary outcomes between treatments. Mean HR changes were -0.3±4.2 (RSV) vs 1.8±4.9 bpm (P), p= 0.241. Delta VO2max were 54±90 (RSV) vs -50±209 l/min (P), p=0.203. Delta lactate concentrations and perceived exertion during submaximal exercise, and SF-36 and FSS did not change (p>0.05). This study provides evidence that RSV 1000 mg daily is ineffective in improving exercise capacity in adults with MM. These findings indicate that previous in vitro studies suggesting a therapeutic potential for RSV in MM do not translate into clinically meaningful effects in vivo.