The TL;DR
NAD+ is found in every living cell. It has two jobs: (1) It helps turn food into energy (ATP), and (2) It is the fuel for DNA repair enzymes (Sirtuins/PARPs). NAD+ levels drop by ~50% between age 20 and 50. This decline is a primary driver of mitochondrial dysfunction and metabolic aging. Restoring it is a top longevity priority.
Accessibility Level
Level 3 (Advanced): You can measure NAD+ levels (expensive kits), but mostly we focus on boosting it via precursors (NMN/NR) or IV therapy.
The Science of Decline
Why does NAD+ drop with age?
- Decreased Production: The enzyme (NAMPT) that recycles NAD+ gets sluggish.
- Increased Consumption: As we accumulate DNA damage and inflammation (CD38), our bodies chew through NAD+ faster to fix the problems. It’s a supply and demand crisis.
The Consequences
- Low Energy: Mitochondria can’t run the Krebs cycle efficiently = Fatigue.
- DNA Damage: Sirtuins run out of fuel and stop protecting the genome = Mutations.
- Metabolic Disease: Insulin sensitivity drops.
Evidence Matrix
| Source | Verdict | Notes |
|---|---|---|
| Shin-ichiro Imai | Expert | Showed that boosting NAD+ restores communication between the brain and pancreas. |
| David Sinclair | Expert | His lab reversed vascular aging in mice using NMN. |
| Clinical Trials | Emerging | NMN/NR shown to be safe and effective at raising blood NAD+ in humans; efficacy on aging outcomes is still being studied. |
How to Optimize
1. Precursors (Supplements)
You can’t just eat NAD+ (it degrades in the gut). You take the building blocks:
- NMN (Nicotinamide Mononucleotide): One step away from NAD+.
- NR (Nicotinamide Riboside): The other major precursor.
- Niacin (Vitamin B3): The cheap version, but causes flushing and doesn’t activate sirtuins as effectively.
2. Inhibit CD38
CD38 is the enzyme that eats NAD+.
- Apigenin: Found in parsley/chamomile. Inhibits CD38, preserving NAD+.
- Quercetin: Also a CD38 inhibitor.
3. IV Therapy
Direct infusion of NAD+. Expensive ($500+), uncomfortable (nausea), but instantly raises tissue levels.
References
Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metabolism.
Verdin, E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science.
Yoshino, J., et al. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism.