NAD+ is the most marketed molecule in modern longevity medicine, and one of the most miscommunicated. A thoughtful member has heard of it twenty times before they ask their physician about it. By that point, the claims they have absorbed are too large for the evidence and small enough to miss what the data actually shows, which is genuinely compelling on narrow grounds.
This is an attempt to draw the line that most public writing on NAD+ refuses to draw — between the mechanism, the animal data, the human data, and the claims that are being made on top of the whole stack.
What NAD+ is, precisely
Nicotinamide adenine dinucleotide is a coenzyme present in every cell in the body. In its oxidized form (NAD+), it accepts electrons during glycolysis and the citric acid cycle, becoming NADH. In its reduced form (NADH), it donates electrons to the mitochondrial electron transport chain, where the energy is used to pump protons across the inner membrane and, via ATP synthase, produce the ATP that runs the cell. It is, in short, central to every energy transaction the body makes.
NAD+ is also a substrate for three major enzyme families that matter in aging: sirtuins (a family of deacetylases involved in DNA repair, metabolic regulation, and stress response), PARPs (poly-ADP-ribose polymerases, also involved in DNA damage response), and CD38 (a cell-surface enzyme that consumes NAD+ in immune signaling). These enzymes do not only use NAD+; they degrade it, and the rate of degradation rises with age and chronic inflammation.
The data that made the conversation happen
Shin-ichiro Imai, working at Washington University in St. Louis, and David Sinclair at Harvard are the two researchers most associated with the current wave of interest. Imai’s group demonstrated, across a series of mouse studies, that tissue NAD+ levels decline with age and that supplementation with NAD+ precursors — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) — could partially restore those levels and improve several biomarkers of mitochondrial function, insulin sensitivity, and physical performance. Sinclair’s lab contributed mechanistic work on sirtuin activation and the broader cellular reprogramming thesis that now anchors his public writing.
The mouse data is real. Aged mice on NMN run further, have better glucose tolerance, and show markers of improved mitochondrial biogenesis. The effect sizes are meaningful in rodents. What is less clear is how much of that transfers to healthy human adults.
The most honest summary of the human data, as of late 2025, is that supplementation with NR or NMN reliably raises blood and tissue NAD+ levels (the Martens, Trammell, and Brenner group papers are the cleanest early references), and that in some populations — notably older adults and those with cardiometabolic markers drifting — there are modest improvements in measurable outcomes: reduced blood pressure, improved muscle NAD+ status, small but detectable gains in exercise economy. What does not yet exist in the human literature is a convincing demonstration of lifespan extension, a restoration of youthful biomarkers of aging at scale, or the dramatic functional rejuvenation that the popular writing implies.
The gap between claim and evidence
The gap matters. When a supplement is sold alongside language about “reversing aging” or “restoring cellular youth,” the member walks in expecting something the evidence cannot deliver, and walks out either disappointed or evangelized by placebo. Neither outcome is what a physician-led practice is for.
Our reading of the literature is this: NAD+ precursor supplementation, for members over forty with cardiometabolic drift, is a defensible intervention in the context of a broader plan. It is not a magic bullet. It is a modest, generally well-tolerated input that may contribute to mitochondrial resilience, may support sirtuin-dependent stress response, and has a reasonable safety profile at doses studied (typically 250 to 1000 mg per day of NR or NMN, oral).
What we do not recommend is starting there. Someone who is not sleeping, who is drinking three evenings a week, who has not touched Zone 2 in a year and cannot remember the last time they saw a DEXA scan, does not need NAD+. They need the inputs that matter first, and then the supplement, and not the other way around.
The IV question
Intravenous NAD+ is a separate conversation. The bioavailability case — that IV delivery bypasses first-pass hepatic metabolism and produces higher, more sustained intracellular levels than oral NR or NMN — is plausible on pharmacokinetic grounds and supported by a thin human literature, primarily from Grant and colleagues at Queensland. The therapeutic case — that the higher intracellular levels produce meaningfully better outcomes than oral precursors at reasonable doses — is less established.
Our IV protocol, administered under Dr. Chaudhari’s oversight, is reserved for members with specific indications: post-illness recovery, high-output athletic demands, significant jet lag and shift stress, or biomarker profiles suggesting aggressive cellular stress. It is not a subscription service. It is a clinical tool used when the clinical picture warrants it.
Members who want the wellness-spa version of NAD+ IV should not be our members. The members who are our members understand the difference, and expect the discipline.
What else supports sirtuin-NAD+ signaling, without a prescription
The most durable elevations of tissue NAD+ observed in human studies come not from supplementation but from exercise, caloric restriction, and circadian alignment. Muscle NAD+ rises with training. Hepatic NAD+ rises with fasting windows. Systemic NAD+ oscillates with the light-dark cycle, and chronically shifted sleep — the pattern most executives accept — is associated with blunted oscillation.
The practical reading: members who are already training four times a week, fasting 14 hours overnight, and sleeping on a stable schedule are running endogenous NAD+ elevations that no supplement alone will match. Adding NR or NMN to that baseline is a reasonable topping. Adding it without that baseline is buying a finishing move without the move it is finishing.
Where this lands
You are the kind of person who reads the mechanism before the marketing, and who is rightly tired of the oscillation between miracle claims and dismissive cynicism. NAD+ is neither. It is an interesting molecule with meaningful biology and modest clinical evidence, whose role in a well-built protocol is real but finite. Honesty about the size of the effect is what separates a physician-led practice from a wellness store. We intend to stay on the physician side of that line.
— Published in The Bioneer, Journal. Reviewed by Dr. Swet Chaudhari, MD, Double Board-Certified Medical Director of Wellness Elite Fitness. This piece is informational; it is not medical advice. Consult your physician before beginning any new protocol.