NAD+

Overview

NAD+ (Nicotinamide Adenine Dinucleotide) is a coenzyme present in all living cells that plays a central role in cellular energy metabolism and redox reactions. Researchers study NAD+ for its involvement in mitochondrial function, DNA repair signaling via sirtuins and PARPs, and age-associated metabolic decline.

Mechanism of Action

NAD+ functions as a primary electron carrier in glycolysis, the TCA cycle, and oxidative phosphorylation. Beyond its redox role, NAD+ serves as a consumable substrate for sirtuin deacetylases (SIRT1-7), poly(ADP-ribose) polymerases (PARPs), and CD38/CD157 ectoenzymes. Sirtuin activation promotes mitochondrial biogenesis, autophagy, and stress resistance gene expression, while PARP activity is critical for DNA damage repair.

Research Summary

Preclinical studies in aged murine models have demonstrated that NAD+ repletion restores tissue NAD+ levels, improves mitochondrial function, and extends healthspan markers (Yoshino et al., Cell Metabolism, 2018). A Phase I clinical trial of IV NAD+ in healthy volunteers established safety and pharmacokinetics (Grant et al., Antioxidants & Redox Signaling, 2019). The CHROME trial showed sustained increases in whole-blood NAD+ levels over 8 weeks with oral NR supplementation (Dellinger et al., Nature Communications, 2017).

Dosing Information

Reported Side Effects

• Flushing during IV infusion
• Nausea and gastrointestinal discomfort
• Headache
• Fatigue or malaise following infusion
• Mild elevations in LDL cholesterol observed with NR/PT combination

Research References

• NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR (2018)
• Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably (2017)
• Cellular Compartmentation and the Redox/Nonredox Functions of NAD+ (2019)