TY - JOUR
T1 - (−)-Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy
AU - McDonald, Craig M.
AU - Ramirez-Sanchez, Israel
AU - Oskarsson, Björn
AU - Joyce, Nanette
AU - Aguilar, Candace
AU - Nicorici, Alina
AU - Dayan, Jonathan
AU - Goude, Erica
AU - Abresch, R. Ted
AU - Villarreal, Francisco
AU - Ceballos, Guillermo
AU - Perkins, Guy
AU - Dugar, Sundeep
AU - Schreiner, George
AU - Henricson, Erik K.
N1 - Publisher Copyright:
© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - aerobic exercise, Becker muscular dystrophy, epicatechin, mitochondrial biogenesis follistatin
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U2 - 10.1002/mus.27108
DO - 10.1002/mus.27108
M3 - Article
C2 - 33125736
AN - SCOPUS:85097624997
SN - 0148-639X
VL - 63
SP - 239
EP - 249
JO - Muscle and Nerve
JF - Muscle and Nerve
IS - 2
ER -