NAD+

Key benefits

What to expect

Based on community reports and published research. Individual results vary significantly.

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Dosing protocols

Dosing information is sourced from published research and community protocols. This is not a recommendation. Consult a healthcare professional.

Overview

NAD+ (Nicotinamide Adenine Dinucleotide) is not a peptide in the traditional sense - it's a coenzyme present in all living cells that is essential for hundreds of metabolic processes. It plays a critical role in converting food to energy (ATP production), activating sirtuins (longevity-associated proteins), supporting DNA repair via PARP enzymes, and maintaining circadian rhythm. NAD+ levels decline approximately 50% between ages 40 and 60, correlating with metabolic dysfunction, neurodegeneration, and the visible signs of aging. This decline has driven enormous interest in NAD+ restoration through IV infusions, subcutaneous injection, and oral precursors like NMN and NR.

How it works

NAD+ functions as an electron carrier in mitochondrial energy production (oxidative phosphorylation) and as a substrate for three families of enzymes: sirtuins (SIRT1-7), PARPs (DNA repair enzymes), and CD38 (an immune cell enzyme that consumes NAD+). Sirtuins regulate gene expression, inflammation, and metabolic function but require NAD+ to function. As NAD+ declines with age, sirtuin activity decreases, contributing to cellular dysfunction. Supplementation aims to restore NAD+ levels, reactivating these protective pathways. CD38, which increases with age and chronic inflammation, is a major driver of NAD+ depletion.

Side effects

Research history

IV vs injection vs oral

IV NAD+ infusions deliver the compound directly to the bloodstream at high doses (250–500 mg) but take 2–4 hours due to the flushing and discomfort caused by rapid infusion. They are the most expensive option ($300–800 AUD per session). Subcutaneous NAD+ injection is faster and cheaper, delivering 50–100 mg in seconds, though bioavailability studies are limited. Oral precursors (NMN, NR) are the most accessible and affordable option - NMN is converted to NAD+ inside cells. A 2024 study showed oral NMN at 1000 mg/day increased blood NAD+ levels by 40–50% over 60 days.

The NAD+ decline

NAD+ levels peak in youth and decline steadily through adulthood. By age 50, levels are roughly half of what they were at 20. This decline is driven by increased activity of CD38 (an enzyme that breaks down NAD+), reduced synthesis, and increased demand from DNA repair processes. The decline correlates with mitochondrial dysfunction, reduced sirtuin activity, and many hallmarks of aging. Researchers like Dr. David Sinclair (Harvard) have popularised the concept that restoring NAD+ could slow or reverse aspects of biological aging.

NMN vs NR

NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are both NAD+ precursors available as oral supplements. NMN is one step closer to NAD+ in the biosynthetic pathway. NR has more published human clinical trial data (ChromaDex's Tru Niagen). Both effectively raise NAD+ levels. NMN is currently more popular in the longevity community, partly due to David Sinclair's advocacy. In Australia, NMN was briefly classified as a controlled substance in 2024 before being reclassified - check current TGA status before purchasing.

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References

1. [1]Yoshino J, et al. "NAD+ intermediates: the biology and therapeutic potential." Cell Metabolism, 2018.
2. [2]Rajman L, et al. "Therapeutic potential of NAD-boosting molecules." Cell Metabolism, 2018.
3. [3]Igarashi M, et al. "Chronic nicotinamide mononucleotide supplementation elevates blood NAD+ levels." NPJ Aging, 2022.
4. [4]Covarrubias AJ, et al. "NAD+ metabolism and its roles in cellular processes during ageing." Nature Reviews Molecular Cell Biology, 2021.

Frequently asked questions

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