Nutritional therapy improves function and complements corticosteroid intervention in mdx mice.
Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.
Payne
Eric T
ET
Department of Pediatrics, McMaster University Medical Center, 1200 Main Street W, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Yasuda
Nobuo
N
Bourgeois
Jacqueline M
JM
Devries
Michaela C
MC
Rodriguez
M Christine
MC
Yousuf
Junaid
J
Tarnopolsky
Mark A
MA
D000818:Animals; D001835:Body Weight; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D019787:Linoleic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000178:diet therapy* / Q000188:drug therapy; D010809:Physical Fitness; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D045442:Rotarod Performance Test; D008063:Thioctic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014631:Valerates / Q000008:administration & dosage / Q000627:therapeutic use
D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D008063:Thioctic Acid; D019787:Linoleic Acid; D011239:Prednisolone; D003404:Creatinine; D003402:Creatine Kinase