Will you live to 120? · The Hunger Switch

A measured word on metformin

And here is why that history matters so much: the same logic, and several of the same people, drove the next and current wave — NAD⁺ precursors. Since you can’t easily get NAD⁺ itself into cells, the strategy shifted to feeding the body molecules it converts into NAD⁺: nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). These are the supplements at the center of today’s longevity marketplace, and they are the chapter’s titular oversold molecules. To evaluate them honestly, separate cleanly what is established from what is not:

What is solid. NAD⁺ really does decline with age in many tissues. And supplementing NMN or NR really does raise NAD⁺ levels in the blood and tissues of human beings — this part is well-replicated and not in dispute. In mice, NMN and NR show a range of benefits across many studies — metabolic, vascular, and others. The biology is real.

What is not. There is, as of now, no convincing evidence that raising NAD⁺ in humans produces meaningful functional benefits — that it slows aging, extends healthy lifespan, or prevents disease. The human trials are mostly small, short, and focused on biomarkers; where they look at actual function — insulin sensitivity, physical performance, strength — the results are mixed and, at best, modest. No human study has shown a lifespan or robust healthspan benefit from any NAD⁺ precursor. This is precisely the trap from Chapters 1 and 2, returning in chemical form: NAD⁺ is a biomarker you can reliably move, and moving a biomarker is not the same as moving aging. “It raises your NAD⁺” is a thermometer claim, not a thermostat claim.

There is even a live scientific dispute about whether oral NMN does what the bottle implies. Charles Brenner — the biochemist who identified NR as an NAD⁺ precursor in the first place, and a pointed critic of NAD⁺ overclaiming — argues that NMN is not efficiently taken up intact into cells, and that swallowed NMN likely has to be converted to NR before it can get in, making the choice of NMN over NR partly a marketing distinction. The claim is contested; what matters for you is that even the mechanism by which the most popular version is supposed to work is unsettled among the experts.

A word on the conflicts of interest, because they are the most important media-literacy lesson in this chapter: they run in every direction. The most prominent NMN champion has co-founded companies built on it. Brenner, the NMN skeptic, has commercial ties to NR. The studies, the supplements, the podcasts, and the patents are tangled together so thoroughly that almost no prominent voice in NAD⁺ biology is financially neutral. This does not mean everyone is lying — most of the underlying science is sincere. It means that when you read “new study shows NAD⁺ booster reverses aging,” your first question should always be who benefits if I believe this, and your second should be what was the actual outcome measured — and the honest answer to the second is almost always “a biomarker, in a small study, for a short time.”

The tangle even reached the regulators. NMN was sold for years as a dietary supplement, until in 2022 the U.S. FDA reversed itself and concluded that NMN could no longer be marketed as a supplement — because it was simultaneously being developed as an investigational drug (a company co-founded by the field’s most famous NMN advocate had begun the formal drug-development process for it). Under U.S. law, a molecule being investigated as a drug can be barred from sale as a supplement. The result has been a regulatory muddle, inconsistently enforced, with NMN still widely sold. But sit with the picture: the same molecule, framed in two incompatible ways at once — a harmless natural supplement you can buy by the jar, and a patented investigational pharmaceutical — depending on which framing serves the seller. There is no sharper illustration in this book of how commercial incentives shape what reaches you and how it is described.

So, the honest bottom line on the NAD⁺ story, holding both halves: this is serious biology — NAD⁺ matters, it declines with age, precursors reliably restore it, and the mouse data are real and interesting. And the human evidence does not remotely support the claims made for these molecules, the mechanism of the most popular one is disputed, the entire field is saturated with financial conflict, and the gap between the marketing and the data is the widest in all of longevity science. NMN may yet prove useful; the point is that right now, nobody knows that it does, and a great many people are paid to tell you they do.

Deeper Water — what it would actually take to believe a NAD⁺ booster. It is worth spelling out exactly what evidence would move a NAD⁺ precursor from “moves a biomarker” to “slows aging,” because the same template applies to every supplement in this book. First, you would need a large, randomized, placebo-controlled trial — not nine people, not an open-label study where everyone knows what they’re taking, but enough subjects, randomized, with a real placebo, to rule out chance and wishful thinking. Second, the outcome measured would have to be something that matters — not NAD⁺ levels, not even a clock reading (recall from Chapter 2 that clocks are unvalidated surrogates), but a hard endpoint: fewer diseases, better physical function sustained over years, or longer life. Third, and most demanding, you’d want the result replicated by independent groups with no financial stake — because the resveratrol collapse taught us that a single lab’s positive result, especially a commercially interested one, can be an artifact. By that standard, rapamycin (multi-lab, placebo-controlled animal data, started late in life, now being tested in dogs and humans) is years ahead of NMN, and the difference is not subtle. The reason to insist on this standard is not pedantry. It is that the history of this exact field — antioxidants in the next chapter, resveratrol in this one — is a graveyard of compounds that moved a biomarker, generated excitement and revenue, and then failed the only test that counted.

A measured word on metformin

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