Vitamin B3 revitalises energy metabolism in muscle disease

By Nikki Hancocks

- Last updated on GMT

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Getty | halfpoint

Related tags vitamin B3 Niacin Research muscle disease

Niacin, a vitamin B3 form improves NAD+ levels and improves muscle strength and performance in patients with the progressive muscle disease, mitochondrial myopathy, according to an international team of scientists.

NAD+ metabolite and its derivatives are fundamental orchestrators of daily homeostasis in our tissues while Vitamin B3 forms have been found to be potent boosters of energy metabolism in rodents as they are a precursors for NAD+.

As fasting has been shown to promote health and longevity in mice, a variety of "NAD boosters" are being developed. However, whether actual NAD+ deficiency exists in human disease, and whether NAD+ boosters could have curative effects in patients with degenerative diseases, has remained elusive.

Human study

In the current publication, a collaborative team of investigators led by Professor at University of Helsinki Anu Suomalainen-Wartiovaara and academy research fellow Eija Pirinen, studied five mitochondrial myopathy patients plus two sex- and age-matched healthy controls for each patient.

The team found that NAD+ levels are lower in both the blood and muscle of mitochondrial myopathy patients.

"The disease is characterised by progressive muscle weakness, exercise intolerance and cramps. Currently, no treatments that would slow down disease progression exist"​, says Suomalainen-Wartiovaara.

An increasing dose of NAD+-booster niacin (from 250 mg/day up to 750 or 1,000 mg/day) for patients and their matched controls for 10 or 4 months, respectively. 

These doses have been reported previously to elevate high-density lipoprotein (HDL) cholesterol in patients with hypercholesterolemia​. 

Pirinen and colleagues report that niacin treatment efficiently increased blood NAD+ both in patients and healthy subjects up to 8-fold. Niacin restored NAD+ in the muscle of the patients to the normal level and improved strength of large muscles and mitochondrial oxidative capacity. Overall metabolism shifted towards that of normal subjects.

Known niacin side effects (hot flushes and tingling sensation of extremities​) were experienced by all study subjects when the dose exceeded 500 mg/day. These symptoms were, however, ameliorated upon continued use. The subjects also reported flatulence, gastrointestinal irritation, and skin drying. One male patient reported transiently enhanced signs of gout. Two control subjects discontinued the study after two months due to gastrointestinal irritation; the remaining participants tolerated niacin well.

The authors conclude that the results of this open pilot study revealed that niacin is a promising treatment option for mitochondrial myopathy. The authors emphasise, however, that niacin and NAD+ are efficient metabolic modifiers and niacin treatment should be cautiously applied only when NAD deficiency is detected.

"Our results are a proof-of-principle that NAD+ deficiency exists in humans and that NAD+ boosters can delay progression of mitochondrial muscle disease"​, Suomalainen-Wartiovaara comments.

"The study is a significant leap in the development of targeted therapy options for energy metabolic diseases"​, Suomalainen-Wartiovaara continues.

Source: Cell Metabolism

Suomalainen. A., et al

"Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy"

http://dx.doi.org/10.1016/j.cmet.2020.04.008

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