Optimizing NAD Status: Establishing Recommended Intakes for the Novel NAD Precursor, Nicotinamide Riboside

Abstract

ObjectivesNicotinamide adenine dinucleotide (NAD) is the central catalyst in cells’ energy production and regulates enzymes involved in DNA repair, innate immunity and cell senescence. Metabolic stresses such as poor diet, infection and certain diseases are linked to depletion of cells’ NAD pool, suggesting a role for optimal NAD status in health. However, current dietary recommendations for NAD are based on niacin and avoidance of pellagra, while the tolerable upper intake level (UL) is based on skin flushing, both outdated endpoints. Supplementation with the NAD precursor, nicotinamide riboside (NR), safely raises NAD levels in in humans in a dose-dependent manner suggesting that NR could be a candidate for dietary recommendations to optimize NAD status. The objective was to evaluate the published and ongoing clinical trials with NR to identify data in support of and research gaps related to dietary recommendations. MethodsUtilizing a database of NR research maintained by the authors, published clinical studies were evaluated for safety, demonstration of clinical benefit, demonstration of an increase in cell/tissue NAD, biomarkers of intake and benefit, study population characteristics and study limitations. Ongoing registered clinical trials were also analyzed to assess potential future relevant outcomes. Results12 published clinical studies showed NR supplementation to be safe, with no flushing effect, at a maximum dose of 2000 mg/day for up to 12 weeks; 9 studies demonstrated an elevation in NAD+, however, variation in sampling and testing methods affect the consistency of study results. In addition to elevation of NAD+, muscle acetylcarnitine was identified as a potential biomarker of intake. To date, NR has been evaluated in adults, with variations in gender and race. Ongoing registered and results from published clinical trials suggest NR may benefit inflammation, blood pressure, muscle function, body composition and cognition. Research gaps include the need for a validated biomarker of NAD status and consistent findings on clinical endpoints in different populations. ConclusionsThough there is early support for dietary recommendations for NR, research gaps, including a validated biomarker of NAD status and a causal link to relevant health outcomes need to be filled to revise the current recommendations. Funding SourcesNone.