NAD+ 101: What It Is, Potential Benefits, Risks & the 2025 NMN Update
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme every cell uses for energy production, DNA repair, and cell signaling. Interest has surged around supporting NAD+ levels with lifestyle strategies and precursors like NR or NMN. Here’s what the science actually shows, what’s still emerging, and what changed with NMN’s status in 2025.
What is NAD+ and why does it matter?
NAD+ shuttles electrons (redox reactions) and serves as fuel for enzymes involved in DNA repair and cellular stress responses (e.g., sirtuins and PARPs). Adequate NAD+ is linked to mitochondrial function, metabolic homeostasis, and healthy aging biology. 1, 5, 10, 15
Do NAD+ levels change with age?
Multiple reviews report age-related declines in NAD+ and related pathways (e.g., SIRT1/NAMPT). While cause-and-effect in humans is complex, this decline is a major rationale behind NAD+ “boosting” strategies. 5, 12, 13
Ways to support NAD+: lifestyle first
- Exercise: Human studies and reviews show training can upregulate NAMPT and pathways tied to NAD+ and mitochondrial biogenesis. 4, 17, 6
- Sleep & circadian rhythm: The circadian clock and NAD+/sirtuin system are intertwined; consistent sleep/wake timing supports these networks. 3, 12, 5
Supplements & therapies: what the evidence shows
Niacinamide/Niacin (vitamin B3) & precursors
NR (nicotinamide riboside): In a 6-week trial of middle-aged/older adults, NR was well-tolerated and significantly increased blood NAD+ levels; downstream clinical outcomes were exploratory. 2, 6
NMN (nicotinamide mononucleotide): A placebo-controlled study in overweight/obese women with prediabetes found improved muscle insulin sensitivity with NMN vs. placebo, while other trials/meta-analyses show consistent NAD+ increases but mixed clinical outcomes overall. 7, 14, 12
IV NAD+ & IV NR
Claims for IV NAD+ are ahead of the data. A 2024 pilot of intravenous NR reported acceptable short-term safety, but controlled evidence for clinical benefits of IV NAD-related infusions remains limited. 9
Safety & who should avoid NAD+ boosters
- General tolerance: NR and NMN have shown favorable short-term safety in trials and reviews, though long-term outcomes are still being studied. 4, 14
- Niacinamide/niacin: High-dose niacin can cause flushing; very high doses of niacinamide have been linked to liver enzyme elevations — stay within clinician-guided ranges.
- Pregnancy/breastfeeding & active cancer care: Always consult your oncology/OB team before starting any NAD+-modulating regimen.
2025 regulatory update: is NMN legal as a supplement?
Yes — as of Sept 29, 2025, FDA letters responding to citizen petitions state that NMN is not excluded from the definition of a dietary supplement because it was marketed as a supplement in the U.S. prior to drug investigations. (This reverses the agency’s 2022 position.) 8, 16
Note that this decision addressed status, not efficacy claims. Standard supplement rules still apply (no disease-treatment claims, good-manufacturing practices, etc.).
How Mint Med can help
- Personalized guidance: We review your goals, meds, and labs to decide if NAD+ support fits — and if so, how (lifestyle, nutrition, or precursors).
- Evidence-aligned approach: We set realistic expectations, track outcomes, and prioritize safety.
Medical disclaimer: This article is educational and not medical advice. Supplements are not intended to diagnose, treat, cure, or prevent any disease. Always consult a licensed clinician about your specific situation.
References
- Yusri K, et al. The role of NAD+ metabolism and its modulation. Nature (2025).
- Martens CR, et al. Chronic nicotinamide riboside is well-tolerated and elevates NAD+ in humans. Nat Commun (2018).
- Cuenoud B, et al. Circadian rhythm and NAD metabolites. Front Nutr (2023).
- Radenkovic D, et al. Clinical evidence for targeting NAD therapeutically. Mech Ageing Dev (2020).
- Poljšak B, et al. Central role of NAD+ in aging. Oxid Med Cell Longev (2023).
- Martens CR, et al. NR elevates blood NAD+ in older adults. PubMed (2018).
- Yoshino M, et al. NMN increases muscle insulin sensitivity in women with prediabetes. Science (2021).
- FDA → NPA citizen-petition response (PDF): NMN not excluded from dietary supplement definition. Regulations.gov (Sept 29, 2025).
- Pilot study of intravenous NR safety. medRxiv (2024).
- Chini CCS, et al. NAD metabolism & aging. Mech Ageing Dev (2023).
- Juan CG, et al. SIRT1/NAMPT/NAD+ meta-analysis. Sci Rep (2023).
- Imai S, et al. NAD+ & sirtuins in aging/longevity. NPJ Aging Mech Dis (2016).
- Freeberg KA, et al. Dietary NAD+ boosters: human data summary. Nutrients (2023).
- Burtscher J, et al. NAD & hypoxic stress; SIRT1/PARP context. Mitochondrion (2024).
- Koh JH, et al. Exercise, NAMPT and NAD+ pool. Int J Mol Sci (2021).
- NutraIngredients-USA. FDA declares NMN lawful in dietary supplements. News summary (Sept 30, 2025).
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