What are the effects of Nicotinamide riboside supplementation on humans?

Introduction of Nicotinamide riboside

Nicotinamide riboside(NR) is a precursor to the important cofactor nicotinamide adenine dinucleotide(NAD⁺) and has elicited metabolic benefits in multiple preclinical studies. Until now, NR has only been available to humans as an oral supplement. People have used NR for anti-aging, high cholesterol, high blood pressure, Alzheimer's disease, obesity, etc., but there is no good scientific evidence to support these uses.

Benefitis of Nicotinamide riboside

The general finding in human NR trials, especially those concerned with metabolism, is that NR supplementation has very few clinically relevant effects. That said, it bears mentioning that only ~7 years have passed since the first report of an exploratory human NR trial was published, and since then, many of the conducted studies have been focused on safety, used small sample sizes, had generally healthy, albeit in some cases elderly or obese, participants, or all of the above. The single somewhat reproducible beneficial effect of NR in these trials has been a reduction of inflammatory markers in whole blood or immune cells.

In addition, oral NR supplementation has been shown multiple times to increase NAD⁺ and a range of its related metabolites in whole blood and, occasionally, PBMCs. Data on the NAD-boosting effect of NR in other tissues than blood is unfortunately limited to muscle and brain at this time, and while the report regarding the brain is highly encouraging for further study, there is no indication that oral NR increases muscle NAD⁺ levels.

It is notable that despite this, oral NA treatment of patients with mitochondrial myopathy and NAD⁺ deficiency has been demonstrated to rescue muscle NAD⁺ levels and improve muscle strength, mitochondrial function, and exercise performance. Similarly, multiple preclinical investigations of NR have led to improved mitochondrial function in muscle, but as detailed previously, human studies of NR supplementation have failed to replicate this finding. The use of relatively healthy individuals for these NR studies could potentially explain the discrepancy, so future human trials may benefit from identifying a population with NAD⁺deficiency.

It is clear that oral treatment with NR in humans has not been fully explored. NR has shown some promise in the reduction of inflammatory markers in blood, as well as in the treatment of diverse severe diseases and, potentially, hypertension. These findings all deserve rigorous follow-up studies. Likewise, NRPT may be beneficial for patients with acute kidney injury or amytrophic lateral sclerosis, although further studies are needed to ascertain this, as well as to delineate the individual effects of these two compounds.

References:

[1] MADS V DAMGAARD; Jonas T T. What is really known about the effects of nicotinamide riboside supplementation in humans.[J]. Science Advances, 2023, 9 29: eadi4862. DOI:10.1126/sciadv.adi4862.

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