Nicotinamide Riboside Boosts Skeletal Muscle Mass

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By the time someone reaches their 80s, they can experience up to a 50 percent loss of skeletal muscle mass and strength. It’s called sarcopenia, and it affects 5–13 percent of people aged 60–70 and 11–50 percent of those 80+. One promising therapy for preserving skeletal muscle mass and reducing the effects of sarcopenia is supplementation with Nicotinamide Riboside (NR). This is according to a placebo-controlled, randomized, double-blind, and crossover study in Cell Reports.

Researchers sought to determine whether NR supplements could help increase skeletal muscle NAD+ metabolome, which declines with age. They also wanted to know if NR might impact muscle mitochondrial bioenergetics. For the study, 12 marginally overweight men with a median age of 75  were given 1 gram of oral NR per day for 21 days. The results? 

“Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR,” say study authors.

Additional Details

Subjects were given 250 mg capsules of NR chloride (Niagen) and instructed to take two pills in the morning and two in the evening. NR was shown to be well-tolerated and safe. In fact, four men reported an increase in their libido while taking NR. “The protocol design included muscle biopsy, fasting blood analyses, glucose tolerance test, muscle arteriovenous difference technique, venous occlusive plethysmography, and indirect calorimetry analysis,” say study authors.

Conclusion

“We report that oral NR augments the aged human skeletal muscle NAD+ metabolome while inducing a transcriptional signature without affecting mitochondrial function or systemic cardiometabolic parameters. The targeted NAD+ metabolome analysis suggests pre-existing NAD+ sufficiency, despite hand-grip strength consistent with muscle aging. Our data may suggest that chronological age per se may not be a major factor in altering muscle and brain NAD+ metabolism, unlike aged laboratory mice. A limitation of this trial may be the number of participants or the duration of NR administration; however, the sample size was sufficient to detect NR-driven changes in the NAD+ metabolome, muscle transcriptional signature, and inflammatory profile. The transcriptional downregulation of mitochondrial gene sets also argues against the lack of a bioenergetic NR effect being due to the sample size. Further studies are needed to conceptualize some of the NR-mediated changes in this experimental medicine study. 

Overall, these studies support that oral NR is available to human skeletal muscle, and they reveal anti-inflammatory NR properties, both of which may be beneficial in the context of aging, muscle, or inflammatory disease groups.”

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