NAD+ Side Effects: What the Research Actually Shows

NAD+ has become one of the most talked-about molecules in longevity research, and with that popularity has come one of the most common questions people search for: does it have side effects? The answers online range from “none at all, it is natural” to worrying claims about cancer. Neither extreme matches the published research. The real picture is more interesting, and more honest: NAD+ and its precursors have been studied in a growing number of human trials, most of which report that they are well tolerated in the short term, while several important questions remain open.

This guide sets out what the research has actually found about the safety and tolerability of NAD+ and the molecules used to raise it, what kinds of effects have been reported, what the theoretical concerns are, and what is still unknown, citing the studies throughout. It is an educational overview of research findings, not medical advice. Crown Peptides supplies NAD+ for laboratory research use only.

The Short Answer

Short-term human studies of NAD+ precursors, mainly nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have generally reported that they were well tolerated, with no serious safety problems identified over the weeks to months studied. Intravenous NAD+ has been studied in only a very small number of people. There are no long-term human safety data. Researchers have also raised theoretical questions, particularly about the role of NAD+ in rapidly dividing cells, that have not been answered.

First, What NAD+ Is

NAD+, nicotinamide adenine dinucleotide, is a coenzyme found in every living cell. It carries electrons in energy production, fuels the sirtuin enzymes that regulate metabolism and stress responses, and is consumed by PARP enzymes that repair DNA. Research indicates its levels decline with age in several tissues. Because it is so central to cellular life, it is natural to ask whether raising it could have unwanted effects as well as intended ones. Our NAD+ guide covers its biology, and NAD+ vs NMN explains how its precursors fit in.

The different forms being studied

When people ask about “NAD+ side effects”, they may mean several quite different things: NAD+ itself, given intravenously or in other forms; its precursors NMN and NR, usually taken by mouth in studies; or older forms of vitamin B3, such as nicotinic acid, which have their own well-known effects. The safety evidence differs for each, so it is important to be clear which is being discussed.

A Short History: Vitamin B3, Pellagra and NAD+

The story of NAD+ safety begins with a disease caused by having too little of it. Pellagra, caused by deficiency of vitamin B3, the raw material for NAD+, was once common in parts of Europe and the American South where diets relied heavily on maize. It causes inflamed skin, diarrhoea, confusion and, if untreated, death. In 1937, Conrad Elvehjem at the University of Wisconsin showed that nicotinic acid cured a similar condition in dogs, and vitamin B3 soon eradicated pellagra wherever it was added to diets. That history is a vivid reminder of how essential NAD+ is.

From the 1950s, high amounts of nicotinic acid were used medically to lower cholesterol and alter blood fats, giving researchers decades of experience with its side effects, particularly flushing. The newer precursors, NR and NMN, came to prominence in the 2000s and 2010s as researchers looked for ways to raise NAD+ without those effects, and their human safety studies are therefore much more recent.

Side Effects by Form: A Comparison

Nicotinic acid (niacin)

The most studied form at high amounts, with decades of clinical use. Flushing is very common. Effects on the liver and blood sugar have been reported at high amounts over long periods.

Nicotinamide

Does not cause flushing. At very high amounts, some studies have linked it to effects on the liver. It can also inhibit sirtuins at high concentrations in the laboratory, which is one reason researchers explored other precursors.

Nicotinamide riboside (NR)

Studied in several small randomised human trials, generally well tolerated over weeks to months.

Nicotinamide mononucleotide (NMN)

Studied in several small human trials, including single-dose safety studies and trials lasting weeks to months, generally well tolerated within those periods.

NAD+ itself

Given intravenously, studied in very few people; given by other routes, even less well studied. Much of what happens to NAD+ outside cells involves breakdown into smaller precursors, which means its effects may overlap with theirs.

What Human Studies of NAD+ Precursors Found

Nicotinamide riboside

In a 2018 randomised, placebo-controlled crossover trial published in Nature Communications, Martens, Seals and colleagues gave healthy middle-aged and older adults NR or placebo for six weeks (PMID: 29599478, PMC5876407). NR was well tolerated and increased NAD+ metabolism in blood cells, and no serious adverse events were attributed to it.

Nicotinamide mononucleotide

In a 2020 study in Endocrine Journal, Irie and colleagues at Keio University gave healthy Japanese men single oral amounts of NMN and monitored them closely (PMID: 31685720). They found no significant changes in heart rate, blood pressure, oxygen saturation or body temperature, and laboratory tests showed only small changes that stayed within normal ranges. Levels of NMN breakdown products in the blood rose as expected. The study was designed as an early safety assessment.

A 2021 randomised, placebo-controlled trial in Science gave NMN or placebo to postmenopausal women with prediabetes for 10 weeks, finding improved muscle insulin sensitivity without reported safety problems (PMID: 33888596, PMC8550608). A 2024 study in the same journal examined longer-term NMN supplementation in a small group of healthy middle-aged Japanese men, adding to the tolerability data (PMID: 38191197).

What the precursor trials have in common

These trials were small, lasted weeks to a few months, and mostly enrolled relatively healthy people. Within those limits, they consistently reported good tolerability. That is genuinely reassuring about short-term use in the settings studied, but it does not tell us about long-term effects, rare effects or effects in people with health conditions.

What Is Known About Intravenous NAD+

Intravenous NAD+ has been promoted widely, but the published research is very limited. In a 2019 pilot study in Frontiers in Aging Neuroscience, Grant and colleagues in Australia infused NAD+ over six hours in a small group of healthy men and measured NAD+ and its metabolites in blood and urine (PMID: 31572171, PMC6751327). They found that plasma NAD+ and its metabolites did not rise until after two hours, suggesting the body rapidly takes up and breaks down infused NAD+, and they detected increased urinary excretion of NAD+ and methylnicotinamide by six hours. The study was designed to track metabolism rather than to establish safety, and it involved very few participants. Beyond small studies like this, controlled data on intravenous NAD+ are scarce.

Effects Reported With Older Forms of Vitamin B3

Much of what is known about the side effects of raising NAD+ precursors comes from nicotinic acid, or niacin, which has been used for decades at high amounts to alter blood fats. Niacin commonly causes flushing, a warm, red, sometimes itchy feeling in the skin caused by blood vessel widening. At high amounts over long periods, it has been associated with effects on the liver and on blood sugar in some people. NR and NMN were attractive to researchers partly because they raise NAD+ through different routes that do not produce the typical niacin flush. Nicotinamide, another form of vitamin B3, does not cause flushing but at very high amounts has been linked in some studies to effects on the liver.

Who Has Not Been Studied

The human trials so far have mostly involved healthy adults or specific groups, such as women with prediabetes or middle-aged men. That leaves large gaps. There are essentially no data on pregnancy or breastfeeding, children, people with cancer or a history of cancer, people with liver or kidney disease, or people taking multiple medicines. Researchers are careful to note that results from healthy volunteers cannot simply be applied to these groups.

The Theoretical Concerns Researchers Raise

Rapidly dividing cells

NAD+ supports energy production and DNA repair in all cells, including cells that divide rapidly. Many cancer cells rely heavily on NAD+ and on NAMPT, the enzyme that recycles it, and NAMPT inhibitors have even been investigated as cancer treatments. That has led researchers to ask whether raising NAD+ could, in some circumstances, support the growth of existing tumours. There is no evidence that NAD+ precursors cause cancer, and some research points in the opposite direction, but the question has not been resolved by long-term human data.

Methylation load

When the body clears excess nicotinamide, one route is methylation by the enzyme NNMT, which uses up methyl groups from the donor molecule SAM. Researchers have raised the theoretical question of whether large, sustained amounts of NAD+ precursors could affect the body’s methylation balance. The Keio study found that the methylated breakdown products of nicotinamide rose with NMN, as expected.

Senescent cells and inflammation

Some research suggests that NAD+ could influence the inflammatory signals released by senescent cells, old cells that have stopped dividing. How this plays out in people over the long term is not known.

Interactions

Interactions between NAD+ precursors and medicines have not been studied systematically.

NAD+ and the Liver

The liver is where much of the body’s NAD+ is made from tryptophan and where excess nicotinamide is cleared. It is also the organ most often linked to side effects of high-dose vitamin B3, particularly nicotinic acid over long periods. For that reason, liver markers are among the most important safety measures in NAD+ research, and they were monitored in the precursor trials, which did not report problems within the periods and amounts studied. Long-term effects on the liver of sustained high intake of newer precursors have not been established.

NAD+ and Blood Sugar

High-dose nicotinic acid has been associated with rises in blood sugar in some people, which is one reason its effects on metabolism were watched closely. The newer precursors appear to behave differently: the 2021 NMN trial actually found improved muscle insulin sensitivity in women with prediabetes, and the Keio safety study found only small changes in blood glucose within the normal range. Because NAD+ sits at the heart of energy metabolism, blood sugar and insulin measures remain important in any study of these compounds.

How NAD+ Evidence Compares With Other Research Compounds

Compared with many research peptides, NAD+ precursors have a relatively strong human safety record, with several randomised, placebo-controlled trials. That contrasts with compounds such as BPC-157, whose human data are extremely limited, as explained in BPC-157 side effects. But compared with licensed medicines, which are tested in thousands of people over long periods, the NAD+ evidence is still modest. It sits in the middle of the evidence ladder: more human data than most research compounds, far less than approved drugs.

Why “Natural” Does Not Settle the Question

NAD+ is a natural molecule, and the body makes and recycles it constantly. That is a reasonable basis for expecting it to be well tolerated in modest amounts, and the short-term trials support that expectation. But natural molecules can still have effects at levels or in contexts the body does not normally encounter, and NAD+ sits at the centre of so many processes that changing its levels could, in principle, have wide-ranging effects. The honest answer is that the short-term evidence is reassuring and the long-term evidence does not yet exist.

How Long-Term Safety Would Be Established

Answering the long-term questions would require larger randomised trials lasting a year or more, in more varied populations, with systematic recording of all adverse events and careful monitoring of the areas of theoretical concern, including markers of cell growth, methylation and liver function. Some such trials are under way. Until they report, the long-term safety profile of NAD+ and its precursors remains an open question rather than a settled one.

Reading NAD+ Safety Claims Online

Claims about NAD+ safety online tend to fall into two camps. Some say it is completely safe because it is natural and present in every cell. Others suggest it is dangerous because it may feed cancer. Both overstate the evidence. The first ignores the fact that the long-term effects of raising NAD+ above its natural levels have not been studied; the second presents a theoretical question as if it were an established finding. The most reliable approach is to look at what controlled studies have actually measured, in whom and for how long, which is what this guide tries to do.

Why Product Quality Matters

NAD+ is sensitive to heat, light and moisture. Degraded material contains breakdown products, such as nicotinamide and ADP-ribose, that have their own biological effects. Products from unregulated sources may also contain much less of the stated compound than claimed. Studies of falsified products sold online have found very low purity and contamination (PMID: 30029448). For research, verified material is the first safeguard. Our guide how to tell if peptides are real explains how verification works.

What Trial Participants Were Monitored For

It helps to know what the precursor trials actually looked for, because a finding of “no significant side effects” is only as meaningful as the monitoring behind it. The Keio NMN safety study tracked heart rate, blood pressure, oxygen saturation, body temperature, a wide range of blood tests, eye examinations and sleep quality, as well as the levels of NMN breakdown products. The NR trial monitored blood tests and recorded adverse events against placebo. These are thorough measures for short studies. What they cannot capture are effects that appear only after months or years, or that occur in only a small fraction of people, which is why larger and longer trials are the next step.

Why Short-Term Tolerability Matters Anyway

It would be wrong to dismiss short-term tolerability data as meaningless. For many research compounds, even this level of human evidence does not exist. Knowing that NAD+ precursors did not cause obvious problems in controlled studies of weeks to months, with careful monitoring, gives researchers a sound basis for designing longer studies, and suggests that any long-term effects, if they exist, are unlikely to be dramatic in the short term. It is a meaningful first step, just not the last one.

How NAD+ Safety Is Studied

Safety monitoring

Well-designed studies record vital signs, blood tests of liver, kidney and blood sugar function, and every symptom reported, comparing everything with a placebo group.

Metabolite tracking

Because NAD+ is broken down into many metabolites, studies increasingly measure the whole NAD+ network, including methylated breakdown products, to understand where the extra material goes.

Longer follow-up

The biggest gap is duration. Studies lasting a year or more, in larger and more varied groups, are needed to answer the long-term questions.

Safety Readouts in Laboratory Research

For researchers working with NAD+ in cells and animals, measuring potential unwanted effects alongside intended ones strengthens any study. Useful readouts include cell proliferation markers, measures of DNA damage and repair, the balance of NAD+ to NADH, methylated nicotinamide metabolites, markers of liver and kidney function in animals, and inflammatory markers. Including these measures gives a much fuller picture of how raising NAD+ affects a biological system, and helps address the theoretical questions described above.

The Technical Breakdown: Where Extra NAD+ Goes

Uptake and breakdown

NAD+ outside cells is broken down by enzymes such as CD38 and CD73 into smaller molecules, including NMN and NR, which cells can take up and rebuild into NAD+. The Australian infusion study’s finding that plasma NAD+ rose only after two hours is consistent with rapid uptake and breakdown.

Clearance

Excess nicotinamide is methylated by NNMT to form methylnicotinamide and then further broken down into pyridone compounds that are excreted in urine. Those are the metabolites that rose in the Keio NMN study and the infusion study.

Why flushing happens with niacin but not NR or NMN

Nicotinic acid activates a receptor called HCA2 on skin immune cells, triggering release of prostaglandins that widen blood vessels. NR and NMN do not act on that receptor, which is why they do not typically cause flushing.

The NAMPT question

NAMPT, the rate-limiting enzyme of NAD+ recycling, is often highly active in tumours. Precursors such as NMN bypass NAMPT, which is part of why researchers want long-term data on how bypassing that control step behaves over time.

NAD+ and Other Molecules in the Same Network

NAD+ does not act alone, and raising it can affect related molecules. NADP+ and its reduced form NADPH, made from NAD+, power antioxidant defences, including the recycling of glutathione, and the synthesis of fats and cholesterol. NADH, the reduced form of NAD+, carries electrons to the mitochondria. Changing NAD+ levels can shift the balance between these forms, with knock-on effects on metabolism and oxidative stress. That is why researchers increasingly measure the whole network rather than NAD+ alone, and why effects that are not obvious from NAD+ levels may still appear. Compounds such as Methylene Blue, which interacts with the electron transport chain, and L-Carnitine, which feeds fat into the mitochondria, act on the same energy system from other directions.

What Would Change the Picture

Several kinds of new evidence would change what can be said about NAD+ safety. Long-term randomised trials in larger and more varied groups would reveal any slow-developing or uncommon effects. Studies in people with specific conditions, carefully designed and monitored, would show whether the short-term tolerability seen in healthy volunteers holds more widely. Research specifically testing the theoretical concerns, such as effects on cell growth markers and methylation over time, would either reassure or raise flags. Until that evidence arrives, the fair position is cautious optimism grounded in the short-term data.

Related Reading and Compounds

Read NAD+ levels by age, are peptides safe, Epitalon vs NAD+ and NAD+ vs MOTS-c. Related compounds include 5-Amino-1MQ, which inhibits NNMT, MOTS-c, SS-31 and Glutathione. Browse the ageing and cellular research peptides category.

NAD+ Side Effects: Questions, Answered

Does NAD+ have side effects?

Short-term human studies of NAD+ precursors have generally reported good tolerability. Long-term effects are not known, and intravenous NAD+ has been studied in very few people.

Does NMN cause any side effects?

Small human trials, including a safety study in healthy Japanese men and a 10-week trial in women with prediabetes, reported no significant safety problems within the periods studied.

Why does niacin cause skin flushing?

Because nicotinic acid activates a receptor on skin immune cells that triggers blood vessel widening. NR and NMN do not act on this receptor.

Can NAD+ cause cancer?

There is no evidence that it does. Because cancer cells rely heavily on NAD+, researchers have raised the theoretical question of whether raising it could support existing tumours, which long-term studies have not yet addressed.

Is NR or NMN better tolerated?

Both have generally been well tolerated in small, short human trials. There are no large head-to-head safety comparisons.

Why is NAD+ important?

It is essential for energy production, DNA repair and the sirtuin enzymes that regulate metabolism. Severe deficiency of its building blocks causes pellagra.

Is NAD+ safe to research in the laboratory?

NAD+ is a standard laboratory reagent. As with any research compound, it should be handled with normal laboratory precautions and stored cold, dry and away from light to prevent degradation.

What were NMN trial participants monitored for?

In the Keio safety study, heart rate, blood pressure, oxygen saturation, temperature, blood tests, eye examinations and sleep quality, alongside NMN breakdown products.

Where can I read the studies mentioned here?

Every study is linked to its PubMed record, where the abstract and often the full paper can be read.

Does NAD+ affect the liver?

Liver effects have been reported with high-dose nicotinic acid over long periods. Short-term trials of NR and NMN monitored liver markers and did not report problems, but long-term data are lacking.

Does NAD+ affect blood sugar?

High-dose nicotinic acid can raise blood sugar in some people. By contrast, a 2021 NMN trial found improved muscle insulin sensitivity in women with prediabetes.

Has NAD+ been studied in pregnancy?

No. There are essentially no human data on NAD+ precursors in pregnancy, breastfeeding or children.

Is intravenous NAD+ well studied?

No. Published data come from very small studies designed mainly to track metabolism.

Reassuring So Far, Unfinished Overall

The research on NAD+ and its precursors is more encouraging than many research compounds: several randomised human trials, consistent reports of short-term tolerability and a clear understanding of how the body handles these molecules. But the trials have been small and short, intravenous use is barely studied, and the long-term questions, especially around rapidly dividing cells, remain open. The honest summary is that the short-term evidence is reassuring, the theoretical questions deserve serious study, and the long-term story is still being written.

For laboratory research, start with verified material. Explore NAD+ from Crown Peptides, every batch HPLC and mass spectrometry verified and dispatched from the UK.