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What is NAD⁺? The coenzyme, the claims, and what the trials actually show

NAD⁺ is a coenzyme every one of your cells already uses, and its levels fall with age. That much is settled. What raising it back up actually does for you is a very different question — and the answer explains why the cheapest form has the best evidence.

Julian Roth7 min read
NAD⁺ availability falls with ageAge →Illustrative shape, not trial data — see the references for measured outcomes.

NAD⁺ — nicotinamide adenine dinucleotide — is a coenzyme found in every living cell you have. It is not a drug, not a hormone, and not something exotic: it is a molecule your metabolism already runs on, and has since long before anyone thought to sell it to you.

Its main job is moving electrons around. Cells extract energy from food through a chain of reactions that need something to carry electrons between steps, and NAD⁺ is the primary carrier. It also acts as fuel for a family of enzymes — sirtuins and PARPs — involved in DNA repair and in regulating how genes are switched on and off. When people talk about NAD⁺ and aging, those enzymes are usually what they mean.

Why anyone is selling it

NAD⁺ availability declines with age. That observation is the foundation the entire NAD⁺ industry is built on, and the reasoning that follows from it is genuinely appealing: if levels fall as you get older, and the enzymes that repair your DNA run on it, then restoring levels ought to push something back in the right direction.

Ought to. The gap between that premise and demonstrated results is where almost everything interesting about this category lives — and it is the gap most of the marketing steps neatly over.

What has actually been shown

Two claims need separating, because the industry consistently blurs them.

Claim one: you can raise NAD⁺ levels. This is well supported. Oral precursors — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) — reliably raise NAD⁺ in human studies. In older adults, NR raised the skeletal muscle NAD⁺ metabolome[1]. Oral NR raised NAD⁺ in plasma extracellular vesicles in a randomized trial [2]. In a randomized, double-blind, placebo-controlled trial of 80 healthy middle-aged adults (n = 80), randomized for 60 days to placebo or 300 mg, 600 mg or 900 mg of NMN once daily, blood NAD concentration rose significantly in every NMN group at both day 30 and day 60, against placebo and against baseline (all p ≤ 0.001)[3]. A separate placebo-controlled trial in older adults reported the same direction of effect[4]. Whatever else is uncertain, the chemistry works.

Claim two: raising NAD⁺ makes you better. This is where the evidence thins dramatically. Individual trials have found specific, narrow effects. In a 10-week randomized, placebo-controlled, double-blind trial in postmenopausal women with prediabetes who were overweight or obese, insulin-stimulated glucose disposal — measured by hyperinsulinemic-euglycemic clamp, the reference method — increased after NMN and did not change on placebo [5]. The same dose-ranging trial that measured blood NAD also found six-minute walking distance significantly higher than placebo in the 300 mg, 600 mg and 900 mg groups at days 30 and 60 (all p < 0.01) [3]. NR has been tested in Parkinson’s disease [6] and in older adults with mild cognitive impairment [7]. These are real studies in specific populations with specific endpoints, and several are small. None establishes that NAD⁺ supplementation makes a healthy person more energetic, sharper, or slower to age, which is what it is overwhelmingly sold for. An effect on a clamp measurement in prediabetic women is a genuine finding; it is not the claim on the bottle.

A trial in overweight and older adults set out to test exactly that kind of broad physiological benefit and is worth reading if you want to see how modest the results in this field tend to be [8].

The part that matters when you go to buy some

Almost everything above comes from trials of oral precursors. That is not an accident of what researchers find interesting — it is where the human research exists. The injections, IV drips, nasal sprays and patches sold as NAD⁺ therapy have no controlled outcome trials supporting the benefits they advertise.

So the category has an unusual shape, and it is the single most useful thing to understand before spending money on it: the evidence ranking runs almost exactly opposite to the price ranking. The cheapest form — a capsule — has the most human data behind it. The most expensive form — an IV drip that can run into four figures a month — has the least.

There is also a regulatory point that gets buried. Injectable, IV and nasal NAD⁺ sold through telehealth in the United States is compounded, which means it is not FDA-approved and the FDA has not reviewed it for safety, efficacy or quality before it reaches you. That is not a scandal about one seller; it is how the whole category works, and you should know it going in.

So should you take it?

That is a question for you and a clinician, not for a website. What we can tell you is how to avoid the expensive mistake: if you want to try NAD⁺, the honest starting point is an oral precursor, because it costs the least and has the most evidence behind it. If you later decide you want an injection, you will at least be choosing it knowing what the extra money does and does not buy.

And treat “reverses aging” as a marketing claim wherever you meet it, including on pages that earn a commission. Nobody has shown that, in any format, at any price.

Frequently asked

What does NAD⁺ do in the body?
It is a coenzyme that carries electrons through the reactions cells use to extract energy from food, and it fuels enzymes involved in DNA repair and gene regulation — sirtuins and PARPs. Every cell you have uses it, continuously.
Does NAD⁺ decline with age?
Yes, NAD⁺ availability falls as people get older, and that observation is the premise the entire NAD⁺ supplement and therapy industry rests on. The premise is sound; what is unproven is that pushing levels back up produces the benefits it is marketed for.
Do NAD⁺ supplements actually raise NAD⁺ levels?
Oral precursors do. Nicotinamide riboside and NMN have both been shown in randomized human studies to raise measured NAD⁺ levels. That is the part of the claim that is well supported. Whether raised levels translate into more energy, sharper cognition or slower aging in healthy people has not been established in controlled outcome trials.
Which form of NAD⁺ is best?
On the weight of human evidence, oral precursors — and they are also the cheapest. Injections, IV drips, nasal sprays and patches cost more and have no controlled outcome trials behind them for wellness uses. The evidence ranking in this category runs roughly opposite to the price ranking.
Is NAD⁺ therapy FDA-approved?
No. Injectable, IV and nasal NAD⁺ sold through US telehealth is compounded, which means it is not FDA-approved and the FDA has not reviewed it for safety, efficacy or quality before it is dispensed. Oral precursors are sold as dietary supplements, a category the FDA also does not review before sale.

Sources

  1. [1] Elhassan YS, Kluckova K, Fletcher RS, et al. (2019). Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures Cell Reports. PMID 31412242
  2. [2] Vreones M, Mustapic M, Moaddel R, et al. (2023). Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin Aging Cell. PMID 36515353
  3. [3] Yi L, Maier AB, Tao R, et al. (2023). The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial GeroScience. PMID 36482258
  4. [4] Morifuji M, Higashi S, Ebihara S, et al. (2024). Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind, randomized, placebo-controlled study GeroScience. PMID 38789831
  5. [5] Yoshino M, Yoshino J, Kayser BD, et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women Science. PMID 33888596
  6. [6] Brakedal B, Dölle C, Riemer F, et al. (2022). The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease Cell Metabolism. PMID 35235774
  7. [7] Orr ME, Kotkowski E, Ramirez P, et al. (2024). A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment GeroScience. PMID 37994989
  8. [8] Pencina KM, Valderrabano R, Wipper B, et al. (2023). Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study The Journal of Clinical Endocrinology & Metabolism. PMID 36740954

Where to get it

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