Study summary · research use only
Regulation of and challenges in targeting NAD(+) metabolism
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses regulation of nicotinamide adenine dinucleotide (NAD+/NADH) metabolism, noting that NAD+ levels fall in response to stress and can be replenished through supplementation. The authors describe limitations of, assumptions about, and unappreciated factors affecting NAD+ supplementation, including ongoing controversies, the role of the microbiome in modulating availability of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), distinct cellular compartments with separate NAD+ and NADH pools, and non-canonical NAD+ and NADH degradation pathways. The review concludes that further investment in understanding the fundamental biology, detection, and metabolites of NAD+ in specific cells and compartments is needed to support translational efforts to raise NAD+ levels in humans.
Abstract
Nicotinamide adenine dinucleotide, in its oxidized (NAD+) and reduced (NADH) forms, is a reduction-oxidation (redox) co-factor and substrate for signalling enzymes that have essential roles in metabolism. The recognition that NAD+ levels fall in response to stress and can be readily replenished through supplementation has fostered great interest in the potential benefits of increasing or restoring NAD+ levels in humans to prevent or delay diseases and degenerative processes. However, much about the biology of NAD+ and related molecules remains poorly understood. In this Review, we discuss the current knowledge of NAD+ metabolism, including limitations of, assumptions about and unappreciated factors that might influence the success or contribute to risks of NAD+ supplementation. We highlight several ongoing controversies in the field, and discuss the role of the microbiome in modulating the availability of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments that have distinct pools of NAD+ and NADH, and non-canonical NAD+ and NADH degradation pathways. We conclude that a substantial investment in understanding the fundamental biology of NAD+, its detection and its metabolites in specific cells and cellular compartments is needed to support current translational efforts to safely boost NAD+ levels in humans.
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