Dionysus and Muscular Dystrophy: Clinical Trial Shows the Antioxidant

Muscular dystrophies are inherited disorders characterized by progressive muscle weakness, trouble breathing, or swallowing, and most people who have the condition eventually need a wheelchair. Although therapy, breathing aids, surgery, and some medications like steroids may help maintain muscle fitness and function, the lifespan of muscular dystrophy patients is often shortened since there is no known cure.

Now, recent research on an antioxidant found in grapes and red wine called resveratrol may provide these patients with some hope. A clinical trial run by the Sapporo Medical University School of Medicine found that resveratrol improved motor function and muscle power in the proximal muscles of 11 patients with Duchenne, Becker, or Fukuyama muscular dystrophy. Resveratrol also led to decreased average serum levels of creatine kinase, an enzyme that leaks out of damaged muscle. This clinical study shows that resveratrol administration at early disease stages may afford great benefits to muscular dystrophy patients.

Glucocorticoids: The good, the bad, and the ugly

The conventional and reliable medicine for muscular dystrophy is glucocorticoids, which improve motor function and the quality of life. Although glucocorticoids delay the median age of loss of mobility in Duchenne muscular dystrophy patients by 2.1 to 4.4 years, the medical condition of patients steadily deteriorates under medication. Besides, glucocorticoids have other adverse effects such as cushingoid features, weight gain, behavioral changes, and growth delay. So, there is a medical hole to fill in the treatment of muscular dystrophy patients.

Bringing in the muscle reserves with resveratrol

Resveratrol has been shown to decrease oxidative stress levels in muscles, reduce cardiac and muscular fibrosis, increase the expression levels of proteins critical to muscle function, and inhibit cardiac hypertrophy — the abnormal enlargement, or thickening, of the heart muscle. Moreover, long-term administration of resveratrol improves cardiac and muscular function with a decrease in serum creatine kinase levels to one-third of those in untreated mice modeling muscular dystrophy.

For these reasons, resveratrol could be useful for treating muscular dystrophy patients. But whether these health- and life-span improving effects induced by resveratrol translate to humans is unclear because, to date, there have been no clinical studies investigating this possibility. Since clinical studies show the relatively low toxicity of resveratrol, Kawamura and colleagues planned a pilot phase IIa clinical study in muscular dystrophy patients to investigate its effectiveness in recovering muscle strength and function.

Resveratrol has been shown to reduce cardiac and muscular fibrosis, increase the expression levels of proteins critical to muscle function, and inhibit cardiac hypertrophy.

Small clinical trial confirms resveratrol’s muscle preserving effects

In the present study, the Japanese research team administered resveratrol to patients with Duchenne, Becker, or Fukuyama muscular dystrophy for 24 weeks. Resveratrol was orally administered daily to all participants at an initial dose of 500 mg per day for 8 weeks. The dose was then increased every 8 weeks to 1000 and finally to 1500 mg per day, similar to the dosages of resveratrol administered to healthy subjects and patients with cancer or metabolic diseases.

All patients were then assessed for motor function, muscle strength, and blood examinations. Resveratrol improved motor function and muscle power in the proximal muscles of participants. However, the distal muscles of patients were unaffected. One patient with Becker muscular dystrophy experienced relief from muscle pain during resveratrol administration, which may have contributed to the improvement in motor function

Kawamura and colleagues repetitively measured the motor function and strength of the participants. Despite the advanced medical conditions of the patients, the average muscle function scores increased significantly and a twofold increase was found in the average muscle strength scores of scapula elevation and shoulder abduction after 24 weeks of medication. Also, the average levels of creatine kinase — the enzyme leaked upon muscle damage — decreased considerably by 34%. The only negative effects were that diarrhea and abdominal pain were noted in six and three patients, respectively. These findings show that resveratrol may provide some benefit to muscular dystrophy patients.

Cardiomyopathy and subsequent heart failure is a major cause of death in muscular dystrophy patients. In the present study, Kawamura and colleagues could not detect any improvement in echocardiographic parameters such as the heart’s beat and ability to pump blood or levels of plasma brain natriuretic peptide (BNP), a marker of cardiomyopathy. This may be because all participants showed normal BNP levels, and only 2 patients had a reduced ejection fraction of less than 50%. Longer-term administration of resveratrol may be necessary to reveal the cardiac function of resveratrol in muscular dystrophy patients.

What’s next for treating muscular dystrophy with resveratrol?

A limitation of the present study was that it was not a randomized, double-blind, placebo-controlled trial. The researchers could not analyze an untreated group because the number of patients was limited, and three types of muscular dystrophy patients with various clinical conditions were recruited. Usually, if some possibility concerning the effectiveness of the drug is found in a phase IIa study, a phase IIb clinical study is carried out to identify the effect and dose of the investigational drug by a randomized and double-blind study. Also, an evaluation of the long-term effects of resveratrol on muscular dystrophy patients in a uniform cohort, such as age-matched young Duchenne muscular dystrophy patients, would be beneficial.

If this research translates to humans, soon people with muscular dystrophy could be grape stomping in the vineyards, but until then we'll have to wait by pouring a glass of wine and praying to Dionysus.

Show references

Kawamura K, Fukumura S, Nikaido K, et al. Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study. Sci Rep. 2020;10(1):20585. Published 2020 Nov 25. doi:10.1038/s41598-020-77197-6