Boosting NAD+ improves muscle disease

Abstract

NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open.

Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively.

Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%.

Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.

SOURCE: Cell Metabolism

EDITOR’S NOTE: Increased blood levels of NAD+ were achieved here with a readily available supplement, niacin (vitamin B3).


Niacin

Abstract

Nicotinic acid and nicotinamide, collectively referred to as niacin, are nutritional precursors of the bioactive molecules nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are important cofactors for most cellular redox reactions, and as such are essential to maintain cellular metabolism and respiration.

NAD also serves as a cosubstrate for a large number of ADP-ribosylation enzymes with varied functions. Among the NAD-consuming enzymes identified to date are important genetic and epigenetic regulators, e.g., poly(ADP-ribose)polymerases and sirtuins.

There is rapidly growing knowledge of the close connection between dietary niacin intake, NAD(P) availability, and the activity of NAD(P)-dependent epigenetic regulator enzymes. It points to an exciting role of dietary niacin intake as a central regulator of physiological processes, e.g., maintenance of genetic stability, and of epigenetic control mechanisms modulating metabolism and aging.

Insight into the role of niacin and various NAD-related diseases ranging from cancer, aging, and metabolic diseases to cardiovascular problems has shifted our view of niacin as a vitamin to current views that explore its potential as a therapeutic.

FULL TEXT: Adv Food Nutr Res