title: Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200 μg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVCQ and TlimQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Passerieux
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France and Department of Clinical Physiology, University Hospital, Montpellier, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Hayot
authors.affiliation: Department of Biostatistics and Epidemiology, University Hospital of Montpellier, Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Jaussent
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Carnac
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France and Department of Clinical Physiology, University Hospital, Montpellier, France.
authors.forename: Fares
authors.initials: F
authors.lastname: Gouzi
authors.affiliation: Department of Respiratory Exploration and Department of Sports Medicine, Larrey University Hospital, Toulouse CEDEX, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Pillard
authors.affiliation: Department of Biostatistics and Epidemiology, University Hospital, Montpellier, France and CIC 1001-INSERM.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Picot
authors.affiliation: Alan Turing Institute Almere, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Böcker
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hugon
authors.affiliation: Department of cardiovascular Surgery and Department of CREDEC, University Hospital of Liege, Belgium.
authors.forename: Joel
authors.initials: J
authors.lastname: Pincemail
authors.affiliation: Department of cardiovascular Surgery and Department of CREDEC, University Hospital of Liege, Belgium.
authors.forename: Jean O
authors.initials: JO
authors.lastname: Defraigne
authors.affiliation: Utrecht University, Department of Biology, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Verrips
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France and Department of Clinical Physiology, University Hospital, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.affiliation: University of Montpellier 1 and 2, INSERM Unit 1046, Montpellier, France and Department of Clinical Physiology, University Hospital, Montpellier, France. Electronic address: dalila.laoudj-chenivesse@inserm.fr.
authors.forename: Dalila
authors.initials: D
authors.lastname: Laoudj-Chenivesse
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005684:Gait / Q000187:drug effects; D005942:Gluconates / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D010807:Physical Endurance / Q000187:drug effects; D010865:Pilot Projects; D012645:Selenomethionine / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage*; D016138:Walking
chemical_list: D005942:Gluconates; D014810:Vitamin E; D012645:Selenomethionine; D001205:Ascorbic Acid; C030691:gluconic acid
keywords: Antioxidants; Facioscapulohumeral muscular dystrophy (FSHD); Oxidative stress; Physical performance; Radical oxygen species