Impaired cellular energy metabolism has been widely reported as a key element in dystrophin-deficient muscle degeneration, one of the most significant aspects of Duchenne Muscular Dystrophy (DMD). In a review entitled “Metabogenic and Nutriceutical Approaches to Address Energy Dysregulation and Skeletal Muscle Wasting in Duchenne Muscular Dystrophy,” the authors present and discuss the scientific literature on therapeutic strategies that target energy-producing pathways, specifically nutriceutical and metabogenic supplements. The review was published in Nutrients.
Duchenne muscular dystrophy (DMD), one of nine types of muscular dystrophy, is a chromosome X-linked genetic disorder where a mutation leads to the absence of the cytoskeletal protein dystrophin, resulting in progressive degeneration, muscle weakness and deterioration, and cardiac dysfunction. The chronic and progressive muscle wasting caused by the loss of stability in the muscle components namely during contraction is linked to molecular mechanisms of calcium imbalance, mitochondrial dysfunction and cellular energy perturbations. Muscle metabolic impairments have been attributed to the increased demand for ATP-dependent calcium and muscle repair, but alternatively it has also been suggested as a consequence of the DMD genotype. Several studies have supported the first hypothesis, demonstrating that dystrophin-deficient muscle has an impaired capacity to produce ATP (energy) of up to 50%.
Currently, DMD therapies include corticosteroid treatment, with side-effects such as high blood sugar and bone tissue degradation. A great deal of research has been preformed to find new therapies that reduce the severity and progression of muscle deterioration, namely strategies targeting energy-producing pathways.
Energy-promoting nutriceutical and metabogenic supplements for the treatment of DMD are examples of such compounds. Supplements with therapeutic potential include amino acids and protein isolates, due to their role as building blocks and energy reservoirs. Such molecules include creatine (Cr), taurine, glutamine, arginine and whey protein isolates. Another class of supplements include mitochondrial co-factors and modulators, like the coenzyme Q10, polyphenolic compounds, resveratrol, quercetin and epigallocatechin gallate (EGCG). Finally, the last category of supplements covers adenine nucleotide salvage and de novo synthesis promoters, due to the importance of degradation and re-synthesis of adenine nucleotides in the maintenance of ATP levels in skeletal muscle.
Because of the large amount of clinical information and the availability of most of these products at nutriceutical suppliers, the authors categorized supplements according to their established therapeutic efficacy evidence, although as noted the biggest limiting factor for informed treatment decisions is the lack of efficacy data regarding long-term clinical effect (10 or more years).
Creatine, CoenzymeQ10 and Adenylosuccinic acid were the three supplements included in the “Apparently effective and safe to consume (in human DMD patients)” category. Creatine in a 3–5 g/day dosing range was shown to improve and maintain strength, increase muscle mass and intramuscular energy stores, and attenuate fatigue derived from exercise. On the other hand, coenzymeQ10 improved respiratory functional measures and decrease plasma CK levels, a marker of muscle damage. Finally, adenylosuccinic acid (ASA) also reduced serum CK, enhanced muscle regeneration and increased muscle strength, overall energy and stamina. Additionally, ASA therapy was well tolerated for 10 years, after administration in preclinical DMD (2.5 years).
The researchers conclude that early therapy is important to the clinical efficacy of these compounds and “while promising data has been derived using treatment regimens focused on isolated supplements, we suggest that greater therapeutic value could be gained from administering combined adjuvants in supplement regimens designed to target the various deficits and abnormalities evident in the metabolic milieu that regulates skeletal muscle energy balance and the maintenance of functional muscle mass.”