Reviewing Nicotinamide Riboside as a Strategy to Increase NAD Levels
The vitamin B3 derivative nicotinamide riboside is one of the more studied ways to increase nicotinamide adenine dinucleotide (NAD) levels in aged tissues. NAD is important in mitochondrial function, but for incompletely understood reasons becomes less available with advancing age. Delivering precursors to NAD synthesis such as nicotinamide riboside can help to boost NAD levels, but researchers have failed to show that the increase in NAD levels and resulting health benefits of this sort of approach are any better than those produced by regular exercise. Clinical trials of various means of increasing NAD levels have produced mixed to uninspiring results. The open access paper here is in part a review of this history, and in part a pitch for using a different, more stable form of nicotinamide riboside to improve the effect size.
Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage.
Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.