Effect of a multicomponent nutritional supplement on functional outcomes for Duchenne muscular dystrophy: A randomized controlled trial.

BACKGROUND & AIMS: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular condition causing progressive muscle weakness and premature death. Whilst effective treatments such as gene therapy are developed, families often seek complementary therapies such as nutrition supplements to help their son maintain function; however, there is limited evidence supporting the use of nutritional supplements in DMD. This study aimed to compare the effect of a Standard nutritional supplement with an Enhanced nutritional supplement combining three nutriceuticals on functional outcomes in ambulatory boys with Duchenne muscular dystrophy (DMD). DESIGN: A 50-week double blinded, randomized, controlled crossover trial was conducted in four Australian neuromuscular centres. Primary outcome measures were 6-min walk distance (6MWD) and community ambulation (StepWatch™ Activity Monitoring). Secondary outcome measures included body composition and quality of life. Serum 25-hydroxyvitamin D was measured. RESULTS: Twenty-seven boys completed the intervention. Traditional crossover analysis demonstrated the Enhanced supplement compared to the Standard supplement was associated with a difference of +12 (95% CI: -16, 40) metres in 6MWD, +0.5 (95% CI: -53, 54) inactive minutes per day and -95 (95% CI: -887, 696) steps per day. A mixed effect model indicated a potentially clinically important effect of the Enhanced supplement on the 6MWD of +31 (95% CI: -19, 81) metres. Mean serum 25 hydroxyvitamin D levels at week 50 was 94 (95% CI: 84, 104) nmol/L. There was no observable effect of either supplement regime on body composition or quality of life. CONCLUSIONS: Whilst a positive effect of the Enhanced supplement on functional outcomes was observed, this finding was inconclusive due to the small sample size. The results do not support the use of combined nutritional supplements to improve body composition or quality of life in DMD. A dose of 2000 IU vitamin D was an adequate dose to raise serum 25-hydroxyvitamin D over 50 weeks. CLINICAL TRIAL REGISTRY: Registry #: ACTRN12610000462088, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12610000462088.

Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited nerve disorder. CMT1A is characterised by peripheral nerve demyelination, weakness, and impaired motor function and is caused by the duplication of PMP22, the gene that encodes peripheral myelin protein 22. High-dose ascorbic acid has been shown to have remyelinating potential and to correct the phenotype of a transgenic mouse model of CMT1A by decreasing expression of PMP22. We tested the efficacy and safety of ascorbic acid supplementation in children with CMT1A. METHODS: This 12-month, randomised, double-blind, placebo-controlled trial undertaken between June, 2007, and December, 2008, assessed high-dose oral ascorbic acid (about 30 mg/kg/day) in 81 children with CMT1A (2-16 years). Randomisation was done on a 1:1 ratio by a computer-generated algorithm. All investigators and participants were blinded to treatment allocation with the exception of the trial pharmacist. The primary efficacy outcome was median nerve motor conduction velocity (m/s) at 12 months. Secondary outcomes were foot and hand strength, motor function, walking ability, and quality of life. Compliance was measured by plasma ascorbic acid concentration, pill count, and medication diary entries. Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, Number 12606000481572. FINDINGS: 81 children were randomly assigned to receive high-dose ascorbic acid (n=42) or placebo (n=39). 80 children completed 12 months of treatment. The ascorbic acid group had a small, non-significant increase in median nerve motor conduction velocity compared with the placebo group (adjusted mean difference 1.7 m/s, 95% CI -0.1 to 3.4; p=0.06). There was no measurable effect of ascorbic acid on neurophysiological, strength, function, or quality of life outcomes. Two children in the ascorbic acid group and four children in the placebo group reported gastrointestinal symptoms. There were no serious adverse events. INTERPRETATION: 12 months of treatment with high-dose ascorbic acid was safe and well tolerated but none of the expected efficacy endpoints were reached.

Dietary L-tyrosine supplementation in nemaline myopathy.

Nemaline myopathy is defined by the presence of nemaline bodies, or rods, on muscle biopsy. Facial and bulbar weakness in nemaline myopathy cause chewing and swallowing difficulties, recurrent aspiration, and poor control of oral secretions. This article discusses 5 patients (4 infants and 1 adolescent) with nemaline myopathy who received dietary supplementation with L-tyrosine (250 to 3000 mg/day). All 4 infants were reported to have an initial decrease in sialorrhoea and an increase in energy levels. The adolescent showed improved strength and exercise tolerance. No adverse effects of treatment were observed. Dietary tyrosine supplementation may improve bulbar function, activity levels, and exercise tolerance in nemaline myopathy.