NMN and NAD boosters: what is left of the longevity promise

You heard the word in a podcast. A researcher from Harvard who talks a lot about ageing, a molecule with three letters. NMN. And behind it a sentence that is hard to get out of your head: the cell substance that disappears with age can be topped up again.

Then you search online. And it immediately becomes confusing. One site sells you capsules for eighty euros a month. The next writes that NMN is banned in the US. A third calls it the biggest disappointment of longevity research.

I understand the confusion well. I have spent more evenings reading about this topic than I care to admit.

So here I am trying something unspectacular: to separate the three levels cleanly. What the biochemistry says. What trials in humans have actually measured. And what regulators have decided about it. These three levels do not contradict each other. They simply tell very different parts of the same story.

NAD is not a miracle molecule. It is the currency your cell counts in

Let us start with what is undisputed. Because that is the part the marketing texts get right, only far too loudly.

NAD, written out nicotinamide adenine dinucleotide, sits in every cell of your body. It does essentially three things there, and they hang together.

First, NAD is an electron taxi. In glycolysis and in the respiratory chain, electrons are constantly handed on from one molecule to the next. NAD picks them up, becomes NADH in the process, releases them again in the mitochondria and stands ready once more. Without this shuttling, energy production comes to a halt. That is why NAD appears in every textbook chapter on metabolism.

Second, NAD is consumable material for repair enzymes. When your DNA takes damage, enzymes of the PARP family spring into action. They mark the damaged site so the repair machinery finds it. To make that mark, they take NAD apart. So it is not only used, it is used up.

Third, NAD is a substrate for the sirtuins. That is the enzyme family that gave this topic its longevity reputation. Sirtuins remove chemical tags from proteins and from the packaging of DNA. In doing so they can help decide which genes are being read at any moment. They too need NAD for this, and they consume it.

And now you know why the biochemistry behind this topic is serious, quite independently of what it says on the capsule bottles.

The NAD decline with age: a well documented observation, not a proven cause

Here lies the most important step in thinking in this whole article. It decides how you read everything that follows.

There is data showing that in several tissues the NAD content is lower in older people than in younger ones. This observation is real and has been described more than once.

The jump that advertising then makes is a different one. “NAD falls with age" becomes “the NAD decline causes ageing". And from that comes “whoever tops up NAD slows down ageing". Two of those three sentences are so far not supported.

Here it makes sense to separate clearly what sits on which level of evidence. Well supported is: NAD is a central cofactor, and its concentration is lower with age in several tissues. Mechanistically plausible, but not yet proven in humans, is that this decline is a driving cause of ageing. Clinical tradition without solid endpoint data is the idea that topping up can slow the ageing process.

And now you know why I write “could" so often on this topic. Not out of caution towards the lawyer. But because the data does not give anything stronger.

The whole family: niacin, nicotinamide, NR and NMN

Now it gets practical. Because NMN is not the only route to NAD, and it is by far not the oldest.

Your body builds NAD in three ways. Completely fresh from the amino acid tryptophan, which is laborious. From vitamin B3 in its two classical forms, nicotinic acid and nicotinamide. And, largest by volume, through a recycling route: when sirtuins and PARP take NAD apart, nicotinamide is left over. The enzyme NAMPT feeds it back into production. This route is called the salvage pathway.

NMN sits exactly in this recycling route, one step before the finished NAD. Nicotinamide riboside, NR for short, sits one step before that. That is the whole biochemical difference.

This table contains an uncomfortable punchline. The two oldest and cheapest relatives, nicotinic acid and nicotinamide, are the best studied. The two youngest and most expensive, NR and NMN, are the least studied. And it is precisely for them that the loudest promises are made.

One distinction matters to me here, because it gets mixed up constantly in practice. The NAD infusion is something different from a capsule. It goes through the vein and thereby bypasses the gut. What that means for the effect is likewise barely studied in humans. It is not a supplement but a physician-prepared formulation without a marketing authorisation for this purpose, so it is used outside the authorisation. Like any infusion it can trigger intolerance reactions, nausea, a feeling of tightness in the chest and local irritation. It therefore belongs in a medical conversation with an explanation of benefit, limits and risks, not in a decision made after a blog article. I describe it in a text of its own, without recommending it here.

And now you know why the question “NMN or NAD" is biochemically not a question of competition. They are two points on the same route.

Why the mice look more impressive than we do

Now comes the part where opinions divide. And I deliberately do not want to talk it down, because it genuinely is strong.

The animal data on NMN is good. Not just a little good, but good in a way that rightly makes researchers sit up.

Why does the mouse look so much better than we do? There are at least four sober reasons for that, and none of them is a reproach to the research.

First: the mouse gets the substance over a large part of its life. In trials, people get it over weeks to a few months. Second: the mouse lives in a cage with the same feed, the same light and no stress from tax returns. Third: in the mouse, tissue is examined at the end, in humans mostly only blood. And fourth: a mouse metabolism runs many times faster than yours.

A broad review by a Harvard group collected in 2018 what NAD-raising molecules can do in animal models, from metabolism through cardiovascular function to inflammation. The authors themselves are optimistic about it. They write that safe and effective NAD boosters could raise the body’s resilience against many diseases and extend the healthy human lifespan. This is exactly the point where I am more cautious: a promise is not yet a result. The paper carries the subtitle “The In Vivo Evidence", and in vivo here means animal.

And one more thing belongs to the reading, not only with this paper but with almost every publication in this field: there are close ties between research groups and companies. The declarations of interest sit at the end of every publication. They are worth reading. They do not devalue a paper, they simply belong to the framing.

And now you know why podcast clips about NMN are almost always mouse data, even when the clip no longer says so.

What the human trials actually measured

Now the part you probably came for. And I will give you the result up front, so you do not have to wait until the end.

The NAD level in the blood rises. That is well supported and happens dose-dependently. The clinically relevant endpoints, meaning the things you would notice in everyday life, barely move so far and do so inconsistently.

The best known human trial on NMN appeared in 2021 in the journal Science. A group from St. Louis studied postmenopausal women with prediabetes who were overweight or obese, over ten weeks. Under NMN, insulin-mediated glucose uptake in the muscle rose, measured with the most elaborate method available, the euglycaemic clamp technique. The insulin signalling pathways in muscle tissue also appeared more active.

That is a strong result, and I do not want to make it smaller than it is. At the same time this belongs to it: it was a small trial in a very specific group. A comment in the same journal criticised differences in the baseline situation of the groups, to which the authors replied with a response. And the effect concerned a laboratory parameter, not a symptom that anyone would have felt.

Two further trials are worth mentioning, because they point in different directions. In an American study, 30 overweight or obese adults aged 45 and above received a high dose of a microcrystalline NMN preparation over 28 days. Body weight, diastolic blood pressure as well as total and LDL cholesterol fell more than under placebo. Muscle strength, endurance and insulin sensitivity, by contrast, did not change. This study too was carried out together with the manufacturer of the preparation being tested. In a Japanese trial with 60 older people over twelve weeks, the primary endpoint, a step test, missed significance. Only in the secondary endpoints did a shorter walking time over four metres and better sleep quality in the Pittsburgh questionnaire show up.

This last point is methodologically important. When the pre-specified main endpoint does not respond and secondary endpoints are reported instead, that is a signal to read the results carefully. Not as wrong, but carefully.

And for nicotinamide riboside? There the data is older and in part clearer, but the pattern of results is the same. An eight-week trial showed, at 100, 300 and 1000 mg NR, a rise in whole blood NAD of 22, 51 and 142 percent, without the skin flush known from high niacin doses. A six-week crossover trial in healthy middle-aged and older people confirmed good tolerability and a raised NAD metabolism. The authors then formulated things expressly with restraint: blood pressure and vascular stiffness were questions for future trials, not points already answered.

Two further NR trials are valuable for the framing, because they turned out negative and were published anyway. In 40 obese, insulin-resistant men, 2000 mg NR daily over twelve weeks improved neither insulin sensitivity nor fat metabolism nor body composition. And in a study of twelve older men, NR did raise NAD metabolism in the muscle measurably, but did not change mitochondrial energy yield. Interestingly, inflammatory messengers in the blood fell there, which is being followed up as a signal in its own right.

And now you know why I neither defend nor tear apart NMN. The substance demonstrably does something. What follows from that is so far open.

NMN banned? What sits behind the regulation

If you have searched for “NMN banned", you are not alone. That search happens thousands of times a month, and the answers online are surprisingly poor.

So let us sort it out. It is about two legal areas and two completely different logics.

In the US: since late 2022 the Food and Drug Administration has taken the position that NMN may not be marketed as a dietary supplement. The reason is formal and not toxicological. Under US law a substance falls out of the supplement category if it was previously authorised as a drug candidate for clinical investigation and if corresponding trials were begun and made public. That is exactly what happened with NMN. So it is excluded not because it would be dangerous, but because it is being investigated as a potential medicine.

In the European Union: here novel food law applies. Foods that were not consumed to a significant degree in the EU before May 1997 need a regulatory authorisation before sale. NMN counts as such a novel food. As things stand, no authorisation has been granted. Sale as a food or supplement is therefore not regularly possible in the EU. Offers that are reachable anyway bypass this authorisation, even when they come from third countries.

And now the contrast that makes the matter really interesting: for nicotinamide riboside the situation in Europe is different.

For practice that means something very concrete: with a product without European authorisation, no authority has checked whether label and actual content match, or under what conditions it was produced. Exactly that gap stays open. I deliberately name no sources of supply and no brands here.

And now you know why the answer to “is NMN banned" is neither yes nor no, but: it depends on which legal area you are asking about and which substance you mean.

Homeostasis: why a permanent high dose does not automatically mean more effect

Here comes the thought that is the most important one to me in the whole field of supplements. It holds for zinc, for vitamin D, for iron. And it holds for NAD in particular.

Your body does not regulate nutrients like a water tank that you refill. It regulates them like a thermostat. Whoever turns one screw automatically moves others with it.

For NAD, at least three such feedback loops are known.

First the salvage pathway. The enzyme NAMPT recycles nicotinamide back into NAD. How much it delivers depends not only on supply, but also on how much enzyme the cell is currently providing. More substrate without more enzyme is like more cars without more lanes.

Second the breakdown route through methylation. Surplus nicotinamide is methylated and excreted. In trials, exactly these breakdown products rise markedly at higher doses, among them the compounds abbreviated 2-PY and 4-PY. That suggests the body sheds part of the material taken in through the breakdown route instead of building it into NAD. A clean figure for how large that share is is still missing.

Third the methyl group household. This methylation uses up methyl groups that your body also needs for other tasks, for instance in homocysteine metabolism. In a Scandinavian safety trial with very high NR doses, serum homocysteine rose slightly at the start, while the authors judged the methyl group reserve as intact overall. A small signal, but exactly the kind of signal you want to keep an eye on with long-term use.

The NAD household does not concern one organ, it concerns the whole system. In clinical psychoneuroimmunology we look at such questions through four lenses. With NAD that is particularly worthwhile, because the same molecule plays a part in all four areas.

And now you know why, in the dose-finding trial with 80 people, the highest dose tested did not bring the best performance. It need not be a measurement error. It could come down to exactly these feedback loops. With a single trial that is not yet supported.

Covering a need, high-dose therapy and who is better off keeping their hands off

There is a distinction that is constantly blurred in this whole field, and it is the reason for most misunderstandings.

Covering a need is what you buy online or at the drugstore. Low to moderate doses that fill gaps. No therapeutic effect is to be expected from them, and that is not a shortcoming, it is the purpose.

Orthomolecular medicine or therapeutic high dosing means something else. Clearly higher doses, used in a targeted way, limited in time, under medical supervision and with laboratory follow-up. Only here can a nutrient act like a medicine. And, like a medicine, also develop side effects.

For this topic there is a perfect teaching example, because it comes from the same vitamin family: nicotinic acid, meaning classical niacin, in gram doses.

I am not showing you this example to make you afraid of vitamin B3. But because it shows the principle so clearly: the dose decides whether we are talking about a food or about a therapy. And therapies need an indication, monitoring and an exit plan.

For NMN and NR, exactly this long-term data is still missing in the high-dose range. There are no trials running over years. The longest available studies run a few months.

And now you know why on this topic I do not decide between “take it" and “leave it", but between “with which question" and “under what supervision".

Three levers you can put into practice today

No brands, no sources of supply, no dosing instructions. Just three things that lie in your hands and whose value is independent of how NMN research turns out in the end.

One question remains that I owe you. Why do I today consider targeted topping up more often justified than fifty years ago, when at the same time I write so critically about NMN?

Because the conditions have changed. Soils, varieties, harvest times and storage are different today. For some nutrients, comparative data across decades points to lower contents in fruit and vegetables. A widely cited analysis of American nutrient data from 1950 and 1999 found, across 43 garden crops, a statistically reliable decline for six of thirteen nutrients examined, among them protein, calcium, iron and vitamin C. This data has its limits, and that belongs to the picture: old and new analytical methods are hard to compare methodologically, and part of the effect could simply be that higher-yielding varieties dilute the nutrients more. It is a hint, not a scandal.

Then there is the rest. Highly processed foods deliver a lot of energy with low micronutrient density, and their share of energy intake is high in Western countries. Environmental burdens and chronic stress can raise the need for protective substances such as zinc, selenium and magnesium. How strongly differs a lot between individuals and is hard to quantify. And some medicines can affect the nutrient balance. Most of them are prescription-only and are prescribed for good reasons. For proton pump inhibitors this is described for vitamin B12 and magnesium, for metformin likewise for B12, for diuretics for potassium and magnesium. For hormonal contraception there are indications for B6, B12, folate and zinc, and the data here is more inconsistent. That is no reason to stop a prescribed medicine. It is a reason to raise the topic at your next appointment.

And that is exactly why NMN does not sit at the top of my personal ranking. Not because I consider it nonsense. But because for most people it is the fourth or fifth question, while the first one is still open.

And now you know why the most honest answer to “should I take NMN" starts with a counter-question: what is it that you actually want to change?

Frequent questions about NMN and NAD boosters

How this topic connects with the others

NMN is rarely the first question. These routes lead to the topics that usually come before it.