Acute Effects of Combined Metabolic Activators and NAD+ Precursors on NAD+ Metabolites: Clinical Findings

Objectives

To investigate the safety and acute effects of six different combined metabolic activators (CMA) formulations, each containing 1000 mg of one of the following NAD+ precursors: nicotinamide riboside (NR), niacin, nicotinamide mononucleotide (NMN), nicotinamide (NAM), or flush-free niacin (FF-N).

Journal

Free Radical Biology and Medicine

Key Outcomes

• CMAs combined with NAM, NMN, or NR were the most effective at increasing NAD+ levels, whereas FF-N had little impact on NAD+ metabolites.
• CMAs with niacin caused widespread flushing and led to the most extensive metabolomic disruption, indicating it may be less suitable for supplementation.
• CMAs with NR and NMN effectively enhanced NAD+ metabolism while causing minimal changes in overall plasma metabolites. Notably, CMA with NR also slightly reduced plasma glucose, though levels remained within the normal range.
• Several CMA combinations were associated with improvements in glutathione-related metabolites, suggesting potential benefits for redox balance and antioxidant support.

Duration

24 hours

Dose

1000 mg*

*Combined metabolic activator supplement consisting of 12.35 g L-serine, 2.55 g N-acetyl-L-cysteine, and 3.73 g L-carnitine tartrate with or without 1000 mg NR, niacin, NMN, NAM, or FF-N.

Study Design

Randomized, double-blind, placebo-controlled study in 70 healthy subjects