Metabolic response to epigallocatechin-3-gallate in relapsing-remitting multiple sclerosis: a randomized clinical trial

Background: Muscle weakness and fatigue are common symptoms in multiple sclerosis (MS). Green tea catechins such as (-)epigallocatechin-3-gallate (EGCG) are known to improve energy metabolism at rest and during exercise. Objective: We tested the hypothesis that EGCG improves energy metabolism and substrate utilization in patients with MS. Design: Eighteen patients (8 men) with relapsing-remitting MS (expanded disability status scale score <4.5, all receiving glatiramer acetate) participated in this randomized, double-blind, placebo-controlled, crossover trial at a clinical research center. All patients received EGCG (600 mg/d) and placebo over 12 wk (4-wk washout in between). After each intervention, fasting and postprandial energy expenditure (EE), as well as fat oxidation (FAOx) and carbohydrate oxidation (CHOx) rates, were measured either at rest or during 40 min of exercise (0.5 W/kg). At rest, blood samples and microdialysates from adipose tissue and skeletal muscle were also taken. Results: At rest, postprandial EE and CHOx, as well as adipose tissue perfusion and glucose supply, were significantly lower in men but higher in women receiving EGCG compared with placebo. During exercise, postprandial EE was lower after EGCG than after placebo, indicating an increased working efficiency (men > women). After placebo, exercise EE was mainly fueled by FAOx in both men and women. After EGCG, there was a shift to a higher and more stable CHOx during exercise in men but not in women. Conclusions: Our data indicate that EGCG given to patients with MS over 12 wk improves muscle metabolism during moderate exercise to a greater extent in men than in women, possibly because of sex-specific effects on autonomic and endocrine control. This trial was registered at clinicaltrials.gov as NCT01417312.