The Effect of Short-Term NAD3® Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 Years

Abstract

Objective This study aimed to assess the impact of acute and short-term supplementation with NAD3^®, a theacrine-containing supplement, on circulating adult stem cell numbers in a healthy male and female population aged 40-70 years. Methods This was a double-blind, placebo-controlled crossover study with 12 participants randomized to receive either NAD3® or a placebo for seven days. Blood samples were collected after an overnight fast, before and after the seven-day supplementation period, and one and two hours after the final supplement dose. Using flow cytometry, circulating stem cells, including lymphocytoid CD34⁺ stem cells (CD45^dimCD34⁺), stem cells associated with vascular maintenance and repair (CD45^dimCD34⁺CD309⁺), CD34⁺ stem cells linked to a progenitor phenotype (CD45^dimCD34⁺CD309^neg), circulating endothelial stem cells (CD45^negCD31⁺CD309⁺), and mesenchymal stem cells (CD45^negCD90⁺) were quantified. Results Acute NAD3^® supplementation did not result in the mobilization of stem cells from the bone marrow. However, seven days of daily NAD3^® supplementation resulted in selective changes in circulating stem cell numbers. A significant time*treatment interaction was observed for CD45^dimCD34⁺ cells (p=0.04) and CD45^dimCD34⁺CD309^neg cells (p=0.04), indicating a decrease in cell numbers with supplementation. There was also a trend toward an increase in circulating endothelial cells (p=0.08) with seven days of NAD3^®supplementation. Conclusion Short-term NAD3® supplementation demonstrated an effect on the quantity of bone marrow-derived stem cells in circulation. The study suggests that this theacrine-containing supplement may play a role in modulating adult stem cell populations, emphasizing the potential impact of NAD3® on regenerative processes. Further research with extended supplementation periods and larger sample sizes is warranted to elucidate the functional consequences of these changes and explore the therapeutic implications for age-related declines in stem cell function.

Keywords: aging; circulating stem cells; nicotinamide adenine dinucleotide (nad+); supplement; theacrine.