Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

Summary

Comprehensive review covering the in vivo preclinical and emerging clinical evidence for NAD+-boosting interventions — NR, NMN, nicotinic acid, nicotinamide, PARP inhibitors, and CD38 inhibitors. Rajman, Chwalek, and Sinclair systematically summarize rodent evidence across aging, metabolic disease, neurodegeneration, cardiovascular disease, and inflammatory conditions, and compare mechanistic coverage (sirtuins, PARPs, CD38, cADPR signaling). The paper distinguishes what is firmly established (tissue NAD+ decline with age, precursor supplementation raises NAD+ in most tissues, SIRT1/SIRT3 activation rescues multiple hallmarks in mice) from what remains speculative (lifespan extension in mammals, human clinical efficacy, tissue-selective delivery). It provides a structured framework for evaluating NAD+ claims by intervention class and organ system and remains one of the most-cited single entry points into the field for clinicians and translational researchers. Published at the inflection point between early mouse data and the first wave of human RCTs, the review set expectations for what subsequent trials would need to demonstrate.

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