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.


METHODS
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.
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Anja
A
Mähler
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Jochen
J
Steiniger
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Markus
M
Bock
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Lars
L
Klug
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Nadine
N
Parreidt
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Mario
M
Lorenz
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Benno F
BF
Zimmermann
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Alexander
A
Krannich
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Friedemann
F
Paul
From the Experimental & Clinical Research Center-a joint cooperation between Charité-Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany (AM, JS, M Bock, LK, NP, and M Boschmann); NeuroCure Clinical Research Center (AM, M Bock, and FP) and Medical Clinic for Cardiology and Angiology Campus Mitte (ML), Charité-Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany (ML); University of Bonn, Institute of Nutritional and Food Sciences, Bonn, Germany (BFZ); Institute Prof. Dr. Georg Kurz GmbH, Köln, Germany (BFZ); Department of Biostatistics, Clinical Research Unit of Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany (AK); and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany (FP).
Michael
M
Boschmann
D000328:Adult; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002392:Catechin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects; D018592:Cross-Over Studies; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000178:diet therapy* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D019518:Postprandial Period; D012720:Severity of Illness Index; D012727:Sex Characteristics; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism*
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D002392:Catechin; C045651:epigallocatechin gallate
calorimetry; energy metabolism; epigallocatechin-3-gallate; microdialysis; multiple sclerosis; sex difference