Treatment with resveratrol (RSV) did not improve exercise capacity or fatty acid oxidation (FAO) in patients with very long chain acyl-CoA dehydrogenase (VLCAD) or carnitine palmitoyltransferase II (CPTII) deficiencies, 2 types of long chain fatty acid oxidation disorder (LCFAOD).
“These results are unexpected as in vitro studies of the effect of RSV on FAO in fibroblasts deficient of VLCAD or CPTII presented evidence of upregulation of the deficient enzyme and thus increased level of FAO,” the study’s authors said.
The randomized, placebo-controlled, double-blind, crossover trial (NCT03728777) was conducted by a multinational team of researchers and included results from 8 patients with genetically verified CPTII or VLCAD deficiencies. The resveratrol regimen was 1000 mg/day for 8 weeks.
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Treatment and placebo groups showed low and similar palmitate oxidation at the end of exercise. Patients’ heart rate and rate of perceived exertion (Borg score) at the end of exercise were also similar between the groups. Also, neither Bouchard diary nor fatigue severity scale showed any statistical difference between groups.
Additional investigations on palmitate turnover showed that its production and utilization increased to the same extent during exercise on both placebo and treatment arms. Moreover, though respiratory exchange rate increased during exercise, suggesting an increase in carbohydrate oxidation, it was similar between the two groups.
Total FAO, plasma palmitate levels, plasma free fatty acid and lactate concentrations, glucose production and utilization, and total carbohydrate oxidation did not alter significantly between groups.
On the other hand, treatment with resveratrol increased plasma glycerol, while decreasing plasma glucose at the end of exercise. However, the authors recognized that this could be a result of a type 1 error in the statistical analysis. “Should the difference on the other hand be true, then the increased plasma levels of glycerol could be the effect of increased lipolysis,” they added.
Storgaard JH, Løkken N, Madsen KL, et al. No effect of resveratrol on fatty acid oxidation or exercise capacity in patients with fatty acid oxidation disorders: a randomized clinical cross‐over trial. J Inherit Metab Dis. Published online January 23, 2022. doi:10.1002/jimd.12479
Resveratrol supplementation in patients with mitochondrial myopathies and skeletal muscle fatty acid oxidation disorders. ClinicalTrials.gov. November 2, 2018. Updated November 27, 2019. Accessed February 1, 2022