(−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy

Abstract

Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods Seven participants received (−)‐epicatechin 50 mg twice per day for 8 weeks. Pre‐ and postprocedures included biceps brachii biopsy to assess muscle structure and growth‐relevant endpoints by western blotting, mitochondria volume measurement, and cristae abundance by electron microscopy, graded exercise testing, and muscle strength and function tests. Results Western blotting showed significantly increased levels of enzymes modulating cellular bioenergetics (liver kinase B1 and 5′‐adenosine monophosphate–activated protein kinase). Peroxisome proliferator‐activated receptor gamma coactivator‐1alpha, a transcriptional coactivator of genes involved in mitochondrial biogenesis and cristae‐associated mitofilin levels, increased as did cristae abundance. Muscle and plasma follistatin increased significantly while myostatin decreased. Markers of skeletal muscle regeneration myogenin, myogenic regulatory factor‐5, myoblast determination protein 1, myocyte enhancer factor‐2, and structure‐associated proteins, including dysferlin, utrophin, and intracellular creatine kinase, also increased. Exercise testing demonstrated decreased heart rate, maximal oxygen consumption per kilogram, and plasma lactate levels at defined workloads. Tissue saturation index improved in resting and postexercise states. Discussion (−)‐Epicatechin, an exercise mimetic, appears to have short‐term positive effects on tissue biomarkers indicative of mitochondrial biogenesis and muscle regeneration, and produced improvements in graded exercise testing parameters in patients with BMD.

Polyphenols and Their Effects on Muscle Atrophy and Muscle Health

“…In the Becker muscular dystrophic muscle, EC increased muscle regeneration by upregulating Myf5, MyoD, myogenin, MEF2a, and follistatin and downregulating myostatin. It acted as mitochondrial bioenergetics by promoting mitochondrial biogenesis through PGC1-α [ 56 ]. In C2C12 cells, EC treatment enhanced myotube growth and mitochondrial biogenesis by activating the transcription factors Nrf2, TFAM, and citrate synthase through G-protein-coupled estrogen receptor (GPER) activation [ 57 ].…”

Restorative Effects of (-)-Epicatechin in a Rat Model of Gulf War Illness Muscle Atrophy and Fatigue

“…Improvements were also accompanied by decreased plasma levels of markers of OS and in ammation (13). In patients with peripheral artery disease, high avanol cocoa supplementation for 3 months led to a signi cant increase in the 6-minute walk test while increasing calf perfusion and capillarity (25) and in Becker muscular dystrophy patients, treatment with Epi (50 mg BID for 2 months) led to increases in quadriceps and plasma follistatin levels while myostatin decreased (14). Markers of SkM regeneration and structure-associated proteins also increased with Epi and exercise testing demonstrated decreased heart rate, maximal oxygen consumption/kilogram and plasma lactate levels.…”

“…In an aged female rat model of early stage heart failure, Epi signi cantly reduces the plasma levels of multiple cytokines and protein carbonyls an effect, replicated in older human subjects provided high avanol cocoa (13). In a pilot study in patients with Becker muscular dystrophy, multiple serum markers of SkM improved with 8 weeks of 100 mg/day of Epi treatment (14). However, no studies have examined the potential of Epi to reverse GWI associated detrimental changes in SkM and modulators of in ammation.…”

Regulation of Cytochrome c Oxidase by Natural Compounds Resveratrol, (–)-Epicatechin, and Betaine

“…EPI treatment of isolated rat heart mitochondria stimulated mitochondrial state 2 respiration in a dose-dependent manner and suppressed cytochrome c release, indicating stabilized integrity of mitochondrial membranes [142]. Its positive effect on membranes was further supported by an increase in cristae formation in skeletal muscle of patients with type 2 diabetes and heart failure [140] and with Becker muscular dystrophy [143], and in mouse heart and muscle [132].…”