Nutritional therapy improves function and complements corticosteroid intervention in mdx mice

Abstract

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, ␣-lipoic acid, and ␤-hydroxy-␤-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 Ͻ 0.05), decreased grip strength fatigue (P Ͻ 0.05), decreased number of internalized myonuclei (P Ͻ 0.01), and smaller retroperitoneal fat pad stores (P Ͻ 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.

An Omega-3 Fatty Acid-Enriched Diet Prevents Skeletal Muscle Lesions in a Hamster Model of Dystrophy

“…In this context, protocols based on different drugs, genes, and cells have been proposed to counteract muscle derangement, [2][3][4] and nutritional supplements have been considered in the attempt to increase muscle strength and prevent myocyte catabolism [5][6][7] or to decrease corticosteroid side effects. 8 3 and 6 polyunsaturated fatty acids (PUFAs) are metabolically and functionally distinct and often have opposing physiological effects. Mammals depend on dietary intake of 3 fatty acids through vegetable sources or fish oil because their cells lack enzymes necessary to synthesize the 18-C precursor of 3 fatty acids and to introduce a double bond at the 3 and 6 position.…”

Therapeutics in Duchenne muscular dystrophy

“…56 Finally, a combination of creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid and betahydroxy-beta-methylbutyrate (HMB) improved strength and decreased fatigue in the mdx mouse. 57 This combination was better than any individual supplement alone as well as prednisone alone, although all had some benefit. The combination with prednisone provided the best results.…”

Review of Phase II and Phase III clinical trials for Duchenne muscular dystrophy

“…Other supplements (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) when given in combinations, were found to improve strength in the mdx mouse, with greatest efficacy in combination with prednisone [83]. Oral creatine supplementation alone showed efficacy in trials in mdx mice but demonstrated no beneficial effects on strength and function in patients with DMD [84][85][86].…”