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No effect of resveratrol in patients with mitochondrial myopathy: A cross‐over randomized controlled trial
Author(s) -
Løkken Nicoline,
Khawajazada Tahmina,
Storgaard Jesper Helbo,
RaaschouPedersen Daniel,
Christensen Maja Elling,
Hornsyld Tessa Munkeboe,
Krag Thomas,
Ørngreen Mette C.,
Vissing John
Publication year - 2021
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12393
Subject(s) - medicine , placebo , exercise intolerance , randomized controlled trial , heart rate , crossover study , myopathy , vo2 max , resveratrol , cardiology , endocrinology , gastroenterology , heart failure , pharmacology , blood pressure , pathology , alternative medicine
Mitochondrial myopathies (MM) are caused by mutations that typically affect genes involved in oxidative phosphorylation. Main symptoms are exercise intolerance and fatigue. Currently, there is no specific treatment for MM. Resveratrol (RSV) is a nutritional supplement that in preclinical studies has been shown to stimulate mitochondrial function. We hypothesized that RSV could improve exercise capacity in patients with MM. The study design was randomized, double‐blind, cross‐over and placebo‐controlled. Eleven patients with genetically verified MM were randomized to receive either 1000 mg/day RSV or placebo (P) for 8 weeks followed by a 4‐week washout and then the opposite treatment. Primary outcomes were changes in heart rate (HR) during submaximal cycling exercise and peak oxygen utilization (VO 2 max) during maximal exercise. Secondary outcomes included reduction in perceived exertion, changes in lactate concentrations, self‐rated function (SF‐36) and fatigue scores (FSS), activities of electron transport chain complexes I and IV in mononuclear cells and mitochondrial biomarkers in muscle tissue among others. There were no significant differences in primary and secondary outcomes between treatments. Mean HR changes were −0.3 ± 4.3 (RSV) vs 1.8 ± 5.0 bpm (P), P = .241. Mean VO 2 max changes were 0.7 ± 1.4 (RSV) vs −0.2 ± 2.3 mL/min/kg (P), P = .203. The study provides evidence that 1000 mg RSV 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 .