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MD NAD+ · The medical file

NAD+ benefits in human and animal experiments

A muscle experiment, a walking test, mouse eyes and a tumour model ask very different questions. Some of the most interesting findings resist a broad anti-ageing headline.

Muscle insulin sensitivity

The 2021 NMN trial in prediabetic, postmenopausal women administered 250 mg/day for 10 weeks. Muscle insulin sensitivity improved, along with insulin signalling. HbA1c and body composition did not change.

Insulin sensitivity describes how readily tissue responds to insulin. A muscle test can detect a change that a broader blood-sugar measure does not pick up. That makes this a useful physiological finding, and it also makes the population essential to the result: these were women with prediabetes after menopause.

The muscle response is the NMN lead I take seriously. Calling the result a general metabolic upgrade would erase the boundaries that make it interesting. A repeat with the same kind of participants and a longer follow-up would be much more informative than another sweeping claim about vitality.

Walking distance

In the 2023 multicenter trial in healthy middle-aged adults, participants received NMN at 300, 600 or 900 mg/day for 60 days, or placebo. Blood NAD+ was higher in every NMN group on days 30 and 60. The researchers also reported improved walking distance and quality-of-life scores, with no safety issues at the amounts tested.

The authors selected 600 mg/day as optimal within that experiment. That wording needs its setting attached: it describes their judgement about their trial, and does not establish a personal amount or prove that this group beat every other group for walking.

Walking is a welcome change of subject after so many blood measurements. I want this line of research to become sturdier, because a change in physical performance is closer to the reason people become interested in NAD+ in the first place.

A technician arranging a chair in a long green-floored corridor
An imagined walking-test setting, illustrated for this page; no participant or study location is depicted.

Blood pressure and the NR trial

Healthy middle-aged and older adults received NR at 1000 mg/day for six weeks in the Martens crossover trial. Whole-blood NAD+ rose about 60%, and no serious adverse events were reported. The study also found trends toward lower systolic blood pressure and less aortic stiffness.

Those cardiovascular observations tempt a larger story. I would give them another trial before granting them that role. The blood rise was the firmer result; the pressure and stiffness signals remain leads worth following.

Mouse eyes and ears

In glaucoma-prone mice given nicotinamide, retinal NAD+ declined with age. At the highest amount tested, 93% of eyes did not develop glaucoma. This was an animal experiment using a vitamin precursor, and its striking figure describes those mouse eyes.

Another mouse study of noise-induced hearing loss gave NR before noise exposure. It preserved more of the connections between cochlear hair cells and nerves and aided hearing recovery. The timing and the animal model are central to that result.

I understand the fascination with mouse sight and hearing. They offer unusually tangible outcomes: sight and hearing. Human benefit needs human testing of those outcomes, with the relevant ingredient and route, before these findings can become a treatment claim.

Melanoma cells and the supply problem

The work on drug-resistant melanoma cells complicates the cheerful version of NAD+ biology. Resistant cells increased NAMPT, an enzyme involved in making NAD+. Blocking it depleted NAD+ and ATP, the cell's usable energy supply. Mice carrying those tumours survived longer after inhibition.

This was cell-line and mouse-xenograft research. It raises a theoretical concern about supporting the metabolism of an existing cancer; it does not establish that NAD+ supplementation causes cancer in people. The biology depends on context, including which cells receive the extra supply.

Because of that melanoma experiment, I distrust “more” as a complete health argument. A molecule can be essential and still participate in processes that a treatment is trying to restrain.

The human evidence in 2025

The Nature Metabolism review of NAD+ precursor supplementation concluded that human efficacy remained limited. Consistent age-related NAD+ decline had been observed in only a limited number of human studies, and tissue-specific data were sparse.

That assessment leaves room for the muscle and walking findings. It also demands a more careful account of ageing than the familiar story of an empty tank being topped up. My interest now rests on a functional result that connects a tissue measurement with a durable change people can use.

The trial amounts collect the study parameters. For the distinct risks of intravenous delivery, there is a separate infusion file.