Nutritional Support and Metabolic Management in Duchenne and Other Muscular Dystrophies: From Clinical Practice to Molecular Mechanisms

Duchenne muscular dystrophy (DMD) and related muscular dystrophies impose an enormous and growing clinical burden, not only through progressive muscle wasting and loss of motor function, but also through a constellation of systemic metabolic and nutritional complications that are under-recognised, under-studied, and under-treated. Advances in standard of care, most notably the widespread use of glucocorticoids and improved respiratory support, have substantially extended survival; yet this very success has exposed a generation of patients to long-term metabolic sequelae for which clinical guidance remains thin and nutritional intervention strategies largely undefined. Moreover, the advent of molecular therapies in the clinical setting has given rise to unprecedented challenges with respect to the provision of dynamic and personalized supportive treatment. This Research Topic brings together clinicians, nutritionists, and basic scientists to establish a rigorous evidence base for nutritional and metabolic management across the full spectrum of muscular dystrophies.

A central challenge in the field is the accurate characterisation of body composition. Body mass index, the default metric in general clinical practice, is profoundly misleading in patients with progressive muscle replacement by fat and connective tissue: individuals with advanced DMD may be severely obese by adiposity criteria yet appear within normal BMI range, while those on long-term glucocorticoids develop frank Cushingoid features and accelerated fat deposition that BMI alone cannot capture. Dual-energy X-ray absorptiometry (DEXA) provides a far more informative window into lean mass, fat mass, and bone mineral density, yet its systematic use in this population, and the interpretation norms appropriate to it, remain underdeveloped. Similarly, resting energy expenditure (REE) in muscular dystrophy has received surprisingly little attention: the progressive loss of metabolically active muscle tissue, combined with immobility and pharmacological interventions, is expected to profoundly alter caloric requirements across the disease trajectory, yet current dietary recommendations are largely extrapolated from healthy populations or from anecdotal clinical experience.

The metabolic complications of long-term glucocorticoid therapy deserve particular focus. Common metabolic concerns of obesity, fatty liver, metabolic syndrome, T2DM, and dyslipidaemias seen in the older general adult population are a concern for the young adult DMD patients on long term glucocorticoid therapy. Obesity, growth retardation, and iatrogenic Cushing syndrome are well-recognised side effects in DMD, but their nutritional determinants and the degree to which dietary intervention can mitigate them remain poorly characterised. Closely linked is the increasing recognition of insulin resistance and glucose intolerance in this population, driven by glucocorticoid use, physical inactivity, and altered body composition.

Bone health represents another critical and underserved domain: chronic glucocorticoid exposure, inadequate weight-bearing activity, impaired vitamin D metabolism, and low calcium intake conspire to produce rates of low bone mineral density and fracture that are clinically significant yet rarely addressed with structured nutritional protocols.

Beyond the musculoskeletal axis, this Research Topic emphasises metabolic complications affecting organ systems not traditionally considered primary targets in muscular dystrophy care. Cardiac metabolism is an emerging frontier: dystrophin deficiency in cardiomyocytes drives a distinctive pattern of mitochondrial dysfunction, energetic insufficiency, and membrane fragility that underlies the cardiomyopathy affecting the majority of DMD patients as they enter the second decade of life. Whether specific dietary patterns, fatty acid profiles, micronutrient supplementation, or metabolic modulators can support cardiac energetics in this context is an open and clinically urgent question. Renal and urological complications, notably nephrolithiasis secondary to hypercalciuria driven by immobility, glucocorticoids, and vitamin D supplementation, receive insufficient attention in nutritional care planning. Chronic kidney disease (CKD) from cardiorenal syndrome in adult patients with late-stage cardiomyopathy and severe left ventricular dysfunction is an emerging medical problem with longer survival of patients with DMD. Electrolyte disturbances, including hypokalaemia and hypomagnesaemia in the context of diuretic use or poor dietary intake, similarly lack evidence-based management guidelines in this setting.

Gastrointestinal dysfunction, and gastroparesis and constipation in particular, deserve emphasis disproportionate to its apparent mundanity. GI dysmotility in muscular dystrophies is a direct consequence of smooth muscle involvement. Physical inactivity, opioid and anticholinergic medications, and inadequate fibre and fluid intake predispose to severe constipation in this population. This carries life-threatening risks: intestinal pseudo-obstruction, acute gastric dilation, and aspiration have been reported as proximate causes of avoidable death in otherwise stable patients. Dietary fibre optimisation, hydration strategies, and the evidence base for laxative regimens in neuromuscular disease require urgent systematic attention.

The basic science dimension of this Research Topic is anchored in the recognition that muscular dystrophies are, at their core, inflammatory diseases. The sterile inflammatory cascade initiated by membrane fragility and muscle fibre necrosis, driven in part by innate immune receptor signalling and sustained by the release of damage-associated molecular patterns. creates a metabolic microenvironment profoundly unfavourable to muscle regeneration. Mitochondrial dysfunction, both a cause and a consequence of this chronic inflammatory state, impairs oxidative phosphorylation, increases reactive oxygen species production, and accelerates muscle fibre loss. These pathways create a strong biological rationale for antioxidant and anti-inflammatory nutritional strategies: compounds including coenzyme Q10, resveratrol, taurine, N-acetylcysteine, omega-3 fatty acids, and curcumin have been studied in preclinical models and, to a lesser extent, in early clinical studies. We welcome mechanistic studies, translational work, and clinical trials addressing these agents. We also invite critical appraisal of the evidence for supplements self-administered by patients and families. The unadvised, unsupervised intake of such compounds is a significant and growing safety concern: interactions with disease-modifying therapies, supraphysiological dosing of fat-soluble vitamins, and commercially promoted products with no rigorous evidence of benefit and real potential for harm represent a clinical challenge this Research Topic aims to address directly.

This Research Topic welcomes original research articles, systematic reviews, meta-analyses, narrative reviews, clinical trials, observational studies, and translational/mechanistic studies covering, but not limited to:

• Body composition assessment: DEXA vs. BMI and alternative metrics; reference standards for neuromuscular disease populations.
• Resting energy expenditure: caloric requirement modelling across disease stages and functional levels.
• Obesity and iatrogenic Cushing syndrome: nutritional determinants and dietary intervention strategies.
• Insulin resistance and glucose metabolism in muscular dystrophies.
• Bone health: vitamin D and calcium status, fracture risk, supplementation strategies, bone mineral density monitoring.
• Cardiac metabolism and nutritional support in dystrophin-deficient cardiomyopathy.
• Cardiorenal syndrome; trajectory of renal function in DMD.
• Nephrolithiasis prevention: fluid intake, dietary calcium and oxalate management, urine chemistry in immobile patients.
• Electrolyte disturbances: prevalence, causes, and clinical management.
• Gastrointestinal dysmotility, gastroparesis and constipation: dietary fibre, hydration, laxative protocols; prevention of life-threatening complications.
• Inflammatory and immune pathways: role of nutritional status and dietary pattern in disease modulation.
• Mitochondrial dysfunction and bioenergetics: nutritional modulators and metabolic support strategies.
• Antioxidant and anti-inflammatory supplementation: mechanistic studies, preclinical models, and clinical evidence.
• Safety and evidence review of commonly self-administered nutritional supplements in muscular dystrophy.