You may have heard NAD+ described as a “fountain of youth” molecule. NAD+ (nicotinamide adenine dinucleotide) is essential for energy production, DNA repair, and cellular housekeeping. As we age, NAD+ levels can fall by as much as 10 to 80 percent depending on the tissue. This decline has been linked to problems like insulin resistance, vascular stiffness, and even neurodegenerative disease.
The logic behind supplementation is straightforward: if NAD+ levels drop with age, why not replace them? The challenge is that NAD+ itself is a large, charged molecule that does not cross into cells efficiently. To get around this, researchers have turned to precursors, smaller building blocks that the body can convert into NAD+. The most studied are nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).
Do NR and NMN actually raise NAD+?
Yes. Multiple randomized controlled trials (RCTs) confirm that both NR and NMN increase NAD+ and related metabolites in blood in a dose dependent fashion.
- NR: In a 2018 double blind trial, 500 mg of NR twice daily increased blood NAD+ metabolites by about 60 percent in older adults but did not improve muscle function or energy metabolism over six weeks (Martens et al., Nature Communications, 2018). A 2019 study in older men found no change in muscle NAD+ content or performance, though inflammatory markers like IL-6 decreased.
- NMN: In a 2021 Science trial, postmenopausal women with prediabetes taking 250 mg/day of NMN for 10 weeks improved muscle insulin sensitivity by about 25 percent, while blood NAD+ rose by ~50 percent. Another 2022-2023 series of studies in middle-aged and older adults found NMN increased blood NAD+ by 75-150 percent, but improvements in physical or metabolic outcomes were modest and inconsistent.
The key point: raising NAD+ in blood is consistent, but raising NAD+ inside tissues like muscle or brain is less clear. Some studies see shifts in metabolites that suggest increased turnover rather than actual higher levels in cells.
Do higher NAD+ levels translate into real health benefits?
The results so far are mixed:
- Metabolic health: Some trials show improved insulin sensitivity in specific groups (for example, postmenopausal women with prediabetes), but other studies in healthy or obese adults showed no changes in blood sugar, insulin, or weight.
- Cardiovascular function: A 2018 trial found NR lowered systolic blood pressure and arterial stiffness in older adults with elevated baseline blood pressure, though results were not statistically robust after adjustment. Other studies found no effect.
- Inflammation: Some evidence suggests NR may lower inflammatory markers like IL-6 in older adults, which could be relevant for healthy aging.
- Physical and cognitive function: Trials in healthy adults show minimal changes in exercise capacity or memory. Most of the more dramatic improvements have come from animal models, not people.
- Disease populations: Early studies hint at benefits in Parkinson’s disease (increased brain NAD and modest motor improvements) and ataxia telangiectasia (improved neurological scores).
What about safety?
So far, NMN and NR appear safe and well tolerated in short to medium-term studies (up to about five months at doses up to 2,000 mg/day). Reported side effects are generally mild, like nausea or flushing, and serious adverse events have not been observed.
What remains unclear
- Tissue uptake: We know NAD+ goes up in the blood, but whether that translates into higher NAD+ inside the cells that matter most (muscle, brain, heart) is still debated.
- Consistency: Some people see large boosts in NAD+, while others see much smaller increases.
- Clinical outcomes: Most studies so far are small, short, and focus on surrogate markers (lab values, walking tests). Large, long-term trials are still needed to show whether NAD+ precursors meaningfully reduce disease or extend healthspan.
- Regulation: In late 2022, the U.S. FDA ruled that NMN can no longer be sold as a dietary supplement because it is being investigated as a potential drug, which may affect availability.
Bottom line
NAD+ supplementation is not snake oil, but it is not yet the anti-aging breakthrough that marketing sometimes suggests. NR and NMN reliably raise NAD+ in blood and are safe, but clinical benefits remain modest, inconsistent, and context-dependent. The best signals so far are in people with metabolic impairments or neurodegenerative disease.
For most healthy individuals, lifestyle strategies, regular exercise, resistance training, time-restricted eating, good sleep, and minimizing alcohol, are far more reliable ways to support your body’s NAD+ system and overall longevity. Supplements may hold promise, but we still need larger and longer-term human studies before we can say they truly change the trajectory of aging.
Instalab Research