(P11-036-23) Mean Baseline NAD+ in Human Biofluids and Tissues: An Evaluation of the Clinical Evidence

Objectives: Depletion of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for cellular function, is linked to tissue dysfunction and disease. Unlike urinary vitamin B3 metabolites, it is unclear whether NAD+ levels are valid indicators of NAD+ status. While NAD+ levels can be increased through supplementation, defining low, normal, and optimal NAD+ levels remain unclear without an established baseline. The objective of this analysis was to determine mean baseline NAD+ levels in human biofluids, tissue, and by health status.

Methods: Unpublished and published, peer-reviewed clinical studies measuring mean baseline NAD+ were analyzed. Where possible, values were standardized to µM or pmol/mg for each tissue. Study participants were divided based on health status into healthy or diagnosed health condition (DHC).

Results: 52 clinical studies met the inclusion criteria: 32 intervention studies; 20 cross-sectional studies. Mean baseline NAD+ was measured in various biofluids and tissues, with whole blood being the most prevalent (30). Mean baseline NAD+ for whole blood, blood plasma, serum, and neuronal extracellular vesicles (NEV) was 23.9, 0.10, 0.0012, and 0.0017 µM, respectively. Heart and liver tissue NAD+ was 590 and 274 pmol/mg, respectively. Skin tissue, peripheral blood mononuclear cells (PBMC), muscle, and brain tissue NAD+ were reported as 283.4, 23.7, 300.9, and 298.3 pmol/mg, as well as 3.1, 10.5, 836.6, and 152.9 µM, respectively. There was substantial heterogeneity in baseline NAD+, suggesting levels are dependent upon the tissue type and biofluid. NAD+ values were assessed by health status for the following biofluids/tissues: whole blood (healthy: 24.8 µM, DHC: 20.3 µM); muscle (healthy: 499.8 pmol/mg; 907 µM, DHC: 22.3 pmol/mg; 766 µM); liver (healthy: 616 µM, DHC: 512 µM), and PBMC (healthy: 10.1 pmol/mg, DHC: 30.5 pmol/mg).

Conclusions: There is no consensus for normal, low, or optimum NAD+ levels and whether these are indicators of NAD+ status. Limitations include small sample size, heterogeneity in biofluid or tissue analyzed, method of NAD+ analysis, and unit measurements for NAD+. Standardized methods of NAD+ analysis and unit measurements are needed, in addition to epidemiological data of NAD+ in multiple biofluids and tissues, and large, diverse populations.

Funding Sources: None