# NAD+

> Evidence tier A — Controlled human trials · Longevity & Immune · reviewed 2026-11-08
> Source page: https://peptidemeta.com/p/nad-plus/

Also known as: Nicotinamide adenine dinucleotide, NAD, Nadide, Coenzyme I

## Quick answers

**What is NAD+?**

Nicotinamide adenine dinucleotide, a coenzyme central to cellular energy production and sirtuin-mediated DNA repair. NAD+ is a dinucleotide coenzyme (nicotinamide + adenine nucleotides), not a peptide. It is listed here because it is sold and used alongside peptides.

**How strong is the evidence for NAD+?**

Tier A (controlled human trials) on the peptidemeta evidence scale. A randomized placebo-controlled trial of intravenous NAD+ in 180 patients with ischemic heart failure (2025), plus small pilot and pharmacokinetic studies. Most other trials test precursors (NR, NMN), which are different compounds.

**Is NAD+ FDA-approved?**

No. NAD+ is not approved by the FDA for any use. Outside the US: China — NAD+ for injection (“Coenzyme I for injection”), NMPA-registered.

**Is NAD+ banned in sport?**

No. NAD+ is not on the World Anti-Doping Agency Prohibited List.

**How does NAD+ work?**

NAD+ is an essential coenzyme that accepts electrons in glycolysis, the TCA cycle, and beta-oxidation, feeding them into the mitochondrial electron transport chain for ATP production. It also serves as a substrate for sirtuins (SIRT1-7), which deacetylate histones and proteins to regulate DNA repair, mitochondrial biogenesis, and inflammatory responses.

**What is known about the safety of NAD+?**

Endogenous coenzyme with well-characterized biology. IV NAD+ infusions can cause chest tightness, nausea, and cramping during rapid administration (rate-dependent).

## Key facts

- **Evidence tier:** A (Controlled human trials)
- **FDA:** not approved
- **Other approvals:** China — NAD+ for injection (“Coenzyme I for injection”), NMPA-registered
- **WADA:** not on the Prohibited List
- **Peptide:** no
- **Formula:** C21H27N7O14P2
- **Molecular weight:** 663.4 g/mol
- **Routes studied:** Intravenous, Oral, Subcutaneous

## Overview

Nicotinamide adenine dinucleotide, a coenzyme central to cellular energy production and sirtuin-mediated DNA repair. Declining NAD+ levels are a hallmark of biological aging.

## Mechanism

NAD+ is an essential coenzyme that accepts electrons in glycolysis, the TCA cycle, and beta-oxidation, feeding them into the mitochondrial electron transport chain for ATP production. It also serves as a substrate for sirtuins (SIRT1-7), which deacetylate histones and proteins to regulate DNA repair, mitochondrial biogenesis, and inflammatory responses. NAD+ decline with age impairs these pathways.

## Effects reported in research

_Reported outcomes, not promises; see the evidence tier._

- Restored cellular energy metabolism
- Activated sirtuin-mediated DNA repair
- Improved mitochondrial function
- Enhanced mental clarity and reduced fatigue

## Safety & unknowns

Endogenous coenzyme with well-characterized biology. IV NAD+ infusions can cause chest tightness, nausea, and cramping during rapid administration (rate-dependent). NR and NMN oral precursors are generally well-tolerated in clinical trials. Flushing possible with high-dose niacin (a different NAD+ precursor). Widely available as supplements.

## Studies

- Covarrubias AJ, Perrone R, Grozio A, et al. (2021). *NAD+ metabolism and its roles in cellular processes during ageing*. Nature Reviews Molecular Cell Biology. Review. https://pubmed.ncbi.nlm.nih.gov/33353981/
  Review of NAD+ metabolism in ageing, covering its synthesis, consumption by enzymes such as sirtuins and PARPs, and strategies to restore NAD+ levels.
- Martens CR, Denman BA, Mazzo MR, et al. (2018). *Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults*. Nature Communications. Clinical trial. https://pubmed.ncbi.nlm.nih.gov/29599478/
  Randomized, double-blind, placebo-controlled crossover trial (2 × 6 weeks) in which the NAD+ precursor nicotinamide riboside was well tolerated and raised NAD+ metabolism; it tested the precursor, not NAD+ itself.
- Yu X, Xu J, Cao J, et al. (2026). *Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial*. American Journal of Cardiovascular Drugs. Clinical trial. https://pubmed.ncbi.nlm.nih.gov/40954388/
  Single-center RCT in 180 patients with ischemic heart failure: 7 days of IV NAD+ added to standard therapy produced a greater improvement in ejection fraction at 1 month than placebo; differences in clinical events were not statistically significant.

## Status sources

- [Yu et al., Am J Cardiovasc Drugs 2026 — intravenous NAD+ in ischemic cardiomyopathy heart failure, RCT](https://pubmed.ncbi.nlm.nih.gov/40954388/)
- [Grant et al. 2019 — pilot pharmacokinetic study of a 6-hour IV NAD+ infusion](https://pubmed.ncbi.nlm.nih.gov/31572171/)
- [PubChem CID 5892 (NAD)](https://pubchem.ncbi.nlm.nih.gov/compound/5892)
- [NMPA approval-document notice listing Coenzyme I for injection (2026)](https://www.nmpa.gov.cn/directory/web/nmpa/zwfw/sdxx/sdxxyp/yppjfb/20260325152707127.html)
- [WADA 2026 Prohibited List (not named; IV infusions over 100 mL per 12 h are banned under M2.2)](https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf)

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Educational reference only — not medical advice. No dosing information is published. Tiers rate the strength of published evidence, not effectiveness or safety.