NAD+

Overview

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme present in all living cells, not a peptide. It is classified here alongside peptides for user convenience in the anti-aging / metabolic category. NAD+ plays a central role in cellular energy metabolism and redox reactions and is studied for its involvement in mitochondrial function, DNA-damage signaling via sirtuins and PARPs, and age-associated metabolic decline. IV NAD+ is not FDA-approved for any clinical indication; it is administered off-label through compounding pharmacies and functional-medicine clinics with limited rigorous outcome data.

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 is linked to mitochondrial biogenesis, autophagy, and stress-response gene expression, and PARP activity is central to DNA-damage repair. Oral bioavailability of intact NAD+ is poor, which is why clinics market IV infusion; the best human data for raising tissue NAD+ involve oral precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) rather than NAD+ itself.

Research Summary

The strongest human evidence for raising circulating NAD+ comes from oral-precursor trials. A randomized, double-blind, placebo-controlled study of nicotinamide riboside combined with pterostilbene (NRPT) showed sustained dose-dependent increases in whole-blood NAD+ over 8 weeks in healthy adults (Dellinger et al., npj Aging and Mechanisms of Disease, 2017). A Yoshino/Baur/Imai review summarizes the biology and emerging therapeutic potential of NR and NMN, including preclinical healthspan data in aged mice (Cell Metabolism, 2018). Direct IV NAD+ has only small pilot pharmacokinetic data: Grant et al. infused 750 mg over 6 hours in 8 healthy men and documented altered plasma and urine NAD+ metabolome without clinical-outcome endpoints (Frontiers in Aging Neuroscience, 2019). No adequately powered RCTs support IV or SubQ NAD+ for anti-aging, cognition, addiction, or Parkinson's disease; clinic marketing claims outrun the published outcome evidence.

Dosing Information

Reported Side Effects

• Flushing and warmth during IV infusion (rate-dependent)
• Chest tightness or pressure with fast infusion
• Nausea and abdominal cramping
• Anxiety or restlessness during infusion
• Headache and post-infusion fatigue
• Theoretical acute methyl-group depletion with very high-dose repeated IV

Research References

• Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study (2017)
• NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR (2018)
• A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+ (2019)