NAD+ in Humans: The Review That Cuts Through the Hype (Nature Metabolism, 2025)

NAD+ is one of the most popular supplements in the longevity world. It’s also one of the most oversold. A review published in Nature Metabolism (October 2025, PMID 41083806) is, to date, one of the most rigorous analyses of what the clinical evidence in humans actually says.

Spoiler: less than most longevity clinics will admit.

What the review says (the facts)

The authors (Vinten et al., 2025) evaluated the clinical literature on NAD+ precursor supplementation (NMN, NR, niacin) in older adults. Key conclusions:

The age-related decline in NAD+ in humans has been consistently observed in only a limited number of studies — it’s not as robust as commonly advertised.
Human clinical trials show limited efficacy, with heterogeneous results across studies.
Extrapolation from rodent data is problematic: what works in animal models doesn’t always replicate in humans.
The lack of data on NAD+ metabolism in specific tissues remains a major obstacle to defining real therapeutic value.

The three precursors and their distinct profiles

A nuance routinely lost in longevity marketing is that “supplementing NAD+” is not a single thing. The review analyzes three precursors with very different characteristics:

Nicotinamide riboside (NR). The most studied precursor in humans. Multiple trials have confirmed it raises blood NAD+ levels in a dose-dependent manner. However, the translation of that elevation into functional clinical benefits — muscle strength, cognitive function, insulin resistance — has been inconsistent across studies. Oral bioavailability is reasonable, but a significant portion is metabolized to nicotinamide before reaching target tissues.

Nicotinamide mononucleotide (NMN). It has fewer published clinical trials than NR, although commercial interest has grown exponentially. Available data suggest NMN also raises blood NAD+, but evidence of functional benefits is even more preliminary. An additional complication is that NMN regulation varies across jurisdictions: in the U.S., its status as a dietary supplement has been disputed by the FDA.

Niacin (vitamin B3). The oldest and cheapest precursor. It has decades of clinical use for dyslipidemia, with a well-documented efficacy and safety profile in that indication. As a strategy for raising NAD+, it’s effective but causes flushing (cutaneous vasodilation) at relevant doses, which limits adherence. The review notes that niacin is rarely included in the “premium” protocols of longevity clinics, possibly because its low price doesn’t fit the market positioning.

The gap between blood and tissues

One of the review’s most relevant findings — and the most uncomfortable for clinics — is the distinction between raising NAD+ in blood and raising NAD+ in the tissues where it actually matters (muscle, brain, liver). Most trials measure NAD+ in whole blood or in peripheral blood mononuclear cells. But metabolic compartments are not communicating vessels: the fact that NAD+ rises in blood does not guarantee it rises in the skeletal muscle of a 65-year-old patient or in the neurons of a patient with early cognitive decline.

This limitation has direct implications for commercial claims. When a clinic shows “before and after” blood NAD+ levels following an IV infusion, it’s measuring something real — but not necessarily something clinically significant.

Why this matters for clinics

NAD+ IV is one of the most widely offered services at longevity clinics. The price can range from €300 to €1,500 per session. With that information, and this review on the table, a responsible clinic should at minimum:

Inform the patient about the real state of the evidence (limited in humans, not “proven”).
Not use NAD+ as a marketing anchor (“rejuvenate your cells”).
Offer the treatment — if offered — within a framework of “experimental intervention with follow-up”, not as established therapy.

The pricing question is especially relevant: if niacin at €0.10 per dose raises NAD+ comparably to a €1,000 IV infusion, the added value of the premium format needs clinical justification that, according to this review, doesn’t yet exist. Clinics that take seriously the distinction between evidence and experimentation should incorporate these nuances into their patient communications.

The practical question for any clinic

If you sell NAD+ IV, what do you measure before and after? What do you expect to change? How do you inform the patient about the evidence threshold?

If you don’t have clear answers to those three questions, it’s not precision medicine: it’s marketing with a syringe.

Primary source: Nature Metabolism / PubMed (Source: Nature Metabolism, 2025).