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Review
. 2023 Dec 1;78(12):2435-2448.
doi: 10.1093/gerona/glad106.

Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions

Kaitlin A Freeberg  1 , CeAnn C Udovich  1 , Christopher R Martens  2 , Douglas R Seals  1 , Daniel H Craighead  1
Affiliations
Review

Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions

Kaitlin A Freeberg et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance with precursor compounds, such as nicotinamide riboside or nicotinamide mononucleotide, has profound effects on physiological function in models of aging and disease. Translation of these compounds for oral supplementation in humans has been increasingly studied within the last 10 years; however, the clinical evidence that raising NAD+ concentrations can improve physiological function is unclear. The goal of this review was to synthesize the published literature on the effects of chronic oral supplementation with NAD+ precursors on healthy aging and age-related chronic diseases. We identified nicotinamide riboside, nicotinamide riboside co-administered with pterostilbene, and nicotinamide mononucleotide as the most common candidates in investigations of NAD+-boosting compounds for improving physiological function in humans. Studies have been performed in generally healthy midlife and older adults, adults with cardiometabolic disease risk factors such as overweight and obesity, and numerous patient populations. Supplementation with these compounds is safe, tolerable, and can increase the abundance of NAD+ and related metabolites in multiple tissues. Dosing regimens and study durations vary greatly across interventions, and small sample sizes limit data interpretation of physiological outcomes. Limitations are identified and future research directions are suggested to further our understanding of the potential efficacy of NAD+-boosting compounds for improving physiological function and extending human health span.

Keywords: Clinical trials; Nicotinamide riboside; Nutrition; Physiology; Successful aging.

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Conflict of interest statement

The authors have a material transfer agreement with the Chromadex External Research Program to receive the compound nicotinamide riboside for study purposes. The authors declare no commercial or financial relationships that could be viewed as conflicts of interest.

Figures

Figure 1.
Figure 1.
Conceptual display of physiological outcomes assessed in currently published clinical trials investigating chronic supplementation of nicotinamide adenine dinucleotide (NAD+) precursors. Nicotinamide riboside (NR), NR plus pterostilbene (PT), and nicotinamide mononucleotide (NMN) are the main NAD+-boosting compounds that have been tested in clinical trials to date. Studies have been performed in healthy young, midlife, and older populations (middle, far left icon), as well as populations with risk factors such as overweight/obesity (middle, second from left icon), and patient populations (middle, third from left icon). Physiological outcomes assessed include, but are not limited to, (bottom left to right) mitochondrial function, metabolism, inflammation, body composition, vascular function, muscular strength, exercise capacity/physical function, glucose-insulin regulation, and sleep. Designed with resources from flaticon.com.
Figure 2.
Figure 2.
Clinical trials assessing oral supplementation with nicotinamide riboside (NR).
Figure 3.
Figure 3.
Clinical trials assessing oral supplementation with nicotinamide riboside (NR) plus pterostilbene (PT).
Figure 4.
Figure 4.
Clinical trials investigating oral supplementation with nicotinamide mononucleotide (NMN).
Figure 5.
Figure 5.
Current research gaps in the field and suggested future directions. NAD+ = nicotinamide adenine dinucleotide; RCT = randomized controlled trial. Designed with resources from flaticon.com.
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