The Perennial Journal · The Science
What the science actually says about NAD⁺
NAD⁺ is one of the most essential molecules in your body — and the research on it is genuinely fascinating. It's also frequently overstated. Here's the honest version: what's proven, what's still emerging, and what we won't pretend to know.
Our rule: every strong claim on this page describes what NAD⁺ does in the body — established biology — not a promise about what a capsule does to you.
Start here
What NAD⁺ actually is
NAD⁺ (nicotinamide adenine dinucleotide) is a coenzyme found in every living cell. Without it, cells can't turn food into usable energy. It does two distinct jobs.
Job one
An energy carrier
It shuttles electrons through the reactions that convert food into ATP — the fuel your cells run on. In this role it's recycled continuously, cycling between NAD⁺ and NADH.
Job two
A cellular currency
It's also consumed as a raw material by repair and signaling enzymes (sirtuins, PARPs, CD38). Every time they work, they spend NAD⁺ — so the body must keep remaking it.
Reviewed in Covarrubias et al., Nature Reviews Molecular Cell Biology, 2021.1
Four established roles
What NAD⁺ is required for
Energy metabolism
The central electron carrier in glycolysis, the TCA cycle and oxidative phosphorylation — the pathways that produce ATP.2
DNA repair
The substrate that PARP enzymes consume to detect and help repair damaged DNA.3
Cellular stress response
Sirtuins — enzymes tied to stress resistance and healthy aging — are NAD⁺-dependent and cannot function without it.4
Cellular signaling
Enzymes like CD38 use NAD⁺ to generate calcium-signaling messengers that regulate immune and metabolic function.5
Each role is established cell biology — that NAD⁺ is required for these processes is not in dispute.
The age problem
NAD⁺ falls as we age
Across many human tissues, NAD⁺ levels decline with age — and NAD⁺ is consumed and remade every day, so the body depends on a steady supply of raw material to keep up.
NAD⁺ correlates strongly and negatively with age in human tissue — Massudi et al., PLOS ONE, 2012.6
The bridge
Why NMN — and what it's proven to do
You can't absorb NAD⁺ directly — the molecule is too large. So the body uses precursors: smaller building blocks it converts into NAD⁺. NMN is the NAD⁺ precursor used in the leading human trials, including a 2021 Science study in postmenopausal women.
Perennial uses NMN — the form studied at a verified 500 mg dose.
The proven part: in multiple randomized controlled trials, oral NMN significantly raised blood NAD⁺ levels — dose-dependently, with the increase leveling off around 600 mg per day.7
Dose-ranging RCT: Yi et al., GeroScience, 2023.7 In a small trial of postmenopausal women, NMN also improved skeletal-muscle insulin sensitivity — Yoshino et al., Science, 2021.8
Tolerability
Well tolerated in the trials so far
Across human trials to date, oral NMN has been well tolerated, with no serious adverse events reported.
250–1250
mg per day studied
up to 12
weeks in trials
0
serious adverse events
Safety at 1250 mg/day — Fukamizu et al., Scientific Reports, 2022.9 Trials to date are short (weeks, not years); long-term safety is not yet established.
Where the research is going
The science is still being written
NAD⁺ is one of the most actively studied molecules in longevity science. Dozens of registered human trials are underway right now — a measure of how seriously the field is investigating it, and a reminder that the story is still unfolding.
40+
registered human trials
20+
completed to date
Phase 2
studies underway at leading universities
Registered trials span metabolic health, cardiovascular function, neurological conditions and healthy aging — at institutions including Harvard-affiliated Brigham & Women's Hospital and Washington University. Source: ClinicalTrials.gov.12 These studies are ongoing; registration is not evidence of benefit, and we'll update this page as results are published.
Radical honesty
What we will — and won't — claim
Most of this category oversells. We'd rather tell you exactly where the evidence stands.
Proven in humans
- NAD⁺ is essential for energy, DNA repair and cellular stress responses
- NAD⁺ declines with age in human tissue
- Oral NMN raises blood NAD⁺
- NMN is well tolerated short-term
Emerging / early
- Muscle insulin sensitivity (one small RCT in postmenopausal women)
- Cellular mechanisms shown mainly in mouse studies10
- Most human outcome trials are small, short and industry-funded
We won't claim
- That it reverses aging
- That it treats or prevents any disease
- Proven weight or performance benefits
- A specific "% NAD⁺ boost"
References
- Covarrubias AJ, et al. NAD⁺ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021. link
- Cantó C, et al. NAD⁺ metabolism and the control of energy homeostasis. Cell Metab. 2015. link
- Gupte R, et al. PARPs and ADP-ribosylation. Genes Dev. 2017. link
- Katsyuba E, et al. NAD⁺ homeostasis in health and disease. Nat Metab. 2020. link
- Hogan KA, et al. The multi-faceted ecto-enzyme CD38. Front Immunol. 2019. link
- Massudi H, et al. Age-associated changes in oxidative stress and NAD⁺ metabolism in human tissue. PLOS ONE. 2012. link
- Yi L, et al. The effect of NMN supplementation on NAD⁺ (dose-ranging RCT). GeroScience. 2023. link
- Yoshino M, et al. NMN increases muscle insulin sensitivity in prediabetic women. Science. 2021. link
- Fukamizu Y, et al. Safety evaluation of β-NMN at 1250 mg/day. Sci Rep. 2022. link
- Gomes AP, et al. Cell. 2013; Das A, et al. Cell. 2018 — mechanistic studies in mice.
- Vinten J, et al. NAD⁺ precursor supplementation in human ageing: clinical evidence and challenges. Nat Metab. 2025. link
- ClinicalTrials.gov — U.S. National Library of Medicine registry of clinical studies (search: nicotinamide mononucleotide), accessed 2026. link
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. NAD⁺ biology described on this page is general scientific information, not a claim about outcomes from taking this product. Consult your healthcare provider before starting any new supplement.