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No effect of resveratrol in patients with mitochondrial myopathy: A cross-over randomized controlled trial
Nicoline Løkken1, Tahmina Khawajazada1, Jesper Helbo Storgaard1
1Copenhagen Neuromuscular Center, Rigshospitalet, University hospital, Copenhagen, Denmark.
Abstract:
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 (VO2 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 VO2 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.
Insights
Resveratrol (RSV) supplementation did not improve exercise capacity in adults with mitochondrial myopathies (MM). This study found no significant differences in heart rate or peak oxygen utilization between RSV and placebo treatments for MM patients.
Area of Science:
- Mitochondrial myopathies
- Nutritional supplements
- Exercise physiology
Background:
- Mitochondrial myopathies (MM) are genetic disorders affecting oxidative phosphorylation, leading to exercise intolerance and fatigue.
- Currently, no specific treatments exist for MM.
- Resveratrol (RSV), a nutritional supplement, has shown potential in preclinical studies to enhance mitochondrial function.
Purpose of the Study:
- To investigate the efficacy of RSV in improving exercise capacity in patients with genetically verified MM.
- To test the hypothesis that RSV supplementation can enhance mitochondrial function and alleviate symptoms in MM patients.
Main Methods:
- A randomized, double-blind, cross-over, placebo-controlled study involving eleven MM patients.
- Participants received 1000 mg/day of RSV or placebo for 8 weeks, followed by a 4-week washout and then the alternative treatment.
- Primary outcomes included changes in heart rate during submaximal exercise and peak oxygen utilization (VO2 max); secondary outcomes assessed perceived exertion, lactate levels, and cellular/tissue biomarkers.
Main Results:
- No significant differences were observed in primary outcomes (heart rate, VO2 max) or secondary outcomes between RSV and placebo treatments.
- Mean heart rate changes were -0.3 bpm with RSV versus 1.8 bpm with placebo (P=0.241).
- Mean VO2 max changes were 0.7 mL/min/kg with RSV versus -0.2 mL/min/kg with placebo (P=0.203).
Conclusions:
- Daily supplementation with 1000 mg of RSV is ineffective in improving exercise capacity in adult patients with mitochondrial myopathies.
- The therapeutic potential of RSV suggested by in vitro studies does not translate into clinically significant benefits for MM patients in vivo.
- Further research may be needed to explore alternative therapeutic strategies for mitochondrial myopathies.
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