NMN / NR
NAD+ boosters
NAD+ Precursor Supplements
Evidence Level: Limited Evidence
Mostly animal data or anecdotal reports, theoretical basis
Regulatory Status: NMN: FDA declared it cannot be sold as a dietary supplement (Nov 2022), though enforcement is limited and sales continue. NR: Available as a dietary supplement (Niagen/Tru Niagen).
NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are precursors to NAD+, a coenzyme essential for cellular energy production and hundreds of metabolic processes. NAD+ levels decline significantly with age—by some estimates, 50% by middle age—leading researchers to theorize that boosting NAD+ might slow aging. The excitement is understandable: NAD+ activates sirtuins (proteins linked to longevity), supports DNA repair, and maintains mitochondrial function. Animal studies have shown promising results. David Sinclair's research on NMN in mice sparked mainstream interest. But here's the reality check: human data is limited and mixed. Studies show NMN and NR successfully raise blood NAD+ levels. What's less clear is whether that translates to meaningful health benefits. Short-term trials (none longer than 3 months) have shown modest improvements in some metabolic markers, but no study has demonstrated lifespan extension in humans.
How It Works
The NAD+ Decline Problem
NAD+ levels decline with age across tissues—skin, blood, liver, muscle, and brain. This decline is associated with reduced cellular function and increased susceptibility to age-related diseases. According to the "NAD World" hypothesis from research in npj Aging, this decline is a key driver of the aging process.
How NMN and NR Boost NAD+
Both are precursors that get converted into NAD+ through different pathways:
- NMN (nicotinamide mononucleotide) is one step away from NAD+ and can be transported directly into cells via the Slc12a8 transporter
- NR (nicotinamide riboside) requires two conversion steps but is efficiently absorbed and has strong uptake into tissues
Human trials confirm both successfully elevate blood NAD+ levels. The question is what happens next.
Sirtuins: The Supposed Target
Sirtuins (SIRT1-7) are a family of proteins that regulate metabolism, stress resistance, and aging. They require NAD+ as a cofactor. The theory is that by boosting NAD+, you enhance sirtuin activity, which promotes:
- DNA repair
- Mitochondrial function
- Reduced inflammation
- Improved metabolism
This is the basis for NAD+ supplements' anti-aging claims. But while the biochemistry is sound, whether oral supplementation provides meaningful sirtuin activation is debated.
The Bioavailability Question
A significant concern is whether oral NMN/NR actually reaches the tissues that matter. While blood levels rise, we have limited data on tissue-specific NAD+ increases in humans. Some researchers argue much of the supplement is metabolized before reaching target tissues.
Potential Benefits
- Successfully raises blood NAD+ levels in human trials—that part is proven
- NMN improved aerobic capacity in amateur runners in one study
- Some studies show improved insulin sensitivity, particularly in prediabetic women
- Subjective improvements in sleep quality reported in older adults
- Generally well-tolerated—no major side effects in trials up to 12 weeks
- NR showed improved redox homeostasis and exercise performance in elderly in a crossover study
- No serious adverse effects reported at doses up to 1200mg/day for 6 weeks
Risks & Considerations
- Lack of long-term human data—no trials beyond 3 months exist
- Not proven to extend lifespan or delay aging in humans
- A recent clinical trial showed no improvement in physical performance parameters
- Theoretical cancer concern: elevated NAD+ may support tumor growth, particularly in cancers with upregulated NAMPT
- Quality control issues: studies found up to 28% discrepancy between labeled and actual NMN content in supplements
- NMN regulatory status is uncertain—FDA ruled it cannot be sold as a supplement (though sales continue)
- Expensive relative to unproven benefits—$30-100+/month for quality products
- May not reach target tissues effectively despite raising blood levels
Dosing Information
Human trials have used NMN at doses ranging from 250mg to 1200mg daily, typically 250-500mg for general use. NR has been studied at 300-1000mg daily. There's no established optimal dose for longevity purposes. One interesting finding: a study found that only participants who took NMN in the evening (after 18:00) showed significant improvement in physical well-being and decreased sleepiness—suggesting timing may matter.
- •Common supplement doses are 250-500mg NMN daily, or 300mg NR (Tru Niagen standard dose)
- •Evening dosing may be more effective based on one study's findings
- •Sublingual forms may improve bioavailability by bypassing first-pass liver metabolism
- •Look for third-party tested products given quality control concerns in the supplement industry
- •NR is available as Tru Niagen (ChromaDex) with more quality assurance than most NMN products
- •Some practitioners recommend cycling (5 days on, 2 off) though there's no evidence this is necessary
Practical Tips
- 1Be skeptical of bold anti-aging claims—the evidence doesn't support them yet
- 2If you try NMN/NR, buy from reputable sources with third-party testing (quality varies wildly)
- 3Consider NR (Tru Niagen) if you want more regulatory certainty and quality control
- 4Don't expect dramatic results—any effects are likely subtle and gradual
- 5People with active cancer or high cancer risk should avoid NAD+ precursors as a precaution
- 6Keep expectations realistic: raising NAD+ levels is proven, but downstream benefits are not
- 7Save your money for interventions with stronger evidence: exercise, sleep, nutrition
- 8If cost is a concern, niacin (vitamin B3) raises NAD+ at a fraction of the cost, though with flushing side effects
Key Research
Safety and Antiaging Effects of NMN in Human Clinical Trials: An Update
Advances in Nutrition / PMC, 2023
Comprehensive review of NMN human trials. NMN is safe up to 1200mg/day and successfully raises blood NAD+ levels. Some studies show improved aerobic capacity, insulin sensitivity, and sleep quality. But no trials exceed 3 months, limiting conclusions about long-term anti-aging effects.
View StudyNAD+ metabolism and arterial stiffness after NMN supplementation
Scientific Reports (Nature), 2023
Randomized, double-blind, placebo-controlled trial showing NMN safely elevated NAD+ metabolism and showed potential for alleviating arterial stiffness in healthy middle-aged adults.
View StudyNMN and NR Comparison Review
Food Frontiers (Wiley), 2025
Updated comparison of NMN and NR mechanisms, preclinical evidence, and clinical trials. Notes both successfully raise NAD+ but calls for more rigorous human studies to establish therapeutic benefits.
View StudySafety evaluation of NMN in healthy adults
Scientific Reports (Nature), 2022
NMN at doses up to 1200mg/day for 6 weeks was physiologically safe in humans. No serious adverse events reported. Confirmed NMN increases blood NAD+ levels.
View StudyNAD World 3.0: NMN Transporter and eNAMPT in Aging
npj Aging, 2025
Updates the NAD World hypothesis with new understanding of NMN transport (Slc12a8) and extracellular NAMPT (eNAMPT). Suggests these pathways are critical for mammalian aging and longevity control.
View StudyRelated Treatments
Disclaimer: This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider before starting any treatment. Evidence levels and regulatory status can change—this content was last updated December 2024.