Enhance Trial: Effects of NAD3® on Hallmarks of Aging and Clinical Endpoints of Health in Middle Aged Adults: A Subset Analysis Focused on Blood Cell NAD+ Concentrations and Lipid Metabolism

Abstract

Limited pre-clinical and clinical data suggest theacrine or theacrine-based supplements modulate biological processes associated with lipid metabolism and aging. Herein, we sought to examine if 12 weeks of daily supplementation with a theacrine-based supplement (termed NAD3®; 312 mg of combined Wasabia japonica freeze-dried rhizome standardized for isothicyantes, theacrine, and copper (I)niacin chelate) altered serum lipids as well as select nicotinamide adenine dinucleotide (NAD+)-associated metabolites in peripheral blood mononuclear cells (PBMCs). Twenty-eight participants (12 males, 16 females) were randomly assigned to receive either NAD3 (n = 13; age: 52 ± 7 years old, body mass index: 29.0 ± 5.0 kg/m2) or a cellulose placebo (n = 15; age: 51 ± 5 years old, body mass index: 28.3 ± 3.9 kg/m2). Blood samples were obtained in mornings following overnight fasts prior to supplementation (Pre) and following the 12-week intervention (Post). PBMCs were freshly isolated and prepared for targeted NAD+ metabolomics, and serum as well as whole blood was assayed for blood lipids and other safety markers through a commercial laboratory. Significant interactions (p < 0.05) were observed for total cholesterol, LDL cholesterol, and LDL: HDL ratio and post hoc analyses indicated these biomarkers significantly decreased with NAD3 supplementation (Pre-to-Post percent decreases were 11.1, 15.2, and −18.9%, respectively). A significant interaction was also observed for PBMC NAD+: NADH values, where levels trended downward from Pre to Post in the CTL group (p = 0.081) and values at Post were greater in NAD3 versus CTL (p = 0.023). No interactions were observed for systolic/diastolic blood pressure, body mass, or blood markers indicative of clinical safety. Although participant numbers were limited, these first-in-human data demonstrate a theacrine-based NAD3 supplement can favorably alter biomarkers of lipid metabolism and cellular NAD+ status. However, the latter data are limited to targeted NAD+ metabolites, and the effects of supplementation on other cellular metabolites or mechanisms related to the observed outcomes need to be further explored.