Understanding NMN Side Effects: What You Should Know Before Taking It

Few longevity supplements today get people talking quite like nicotinamide mononucleotide (NMN). It has been talked up and talked about not just by researchers and longevity experts but also by big names in the field who have been quick to embrace it. Now, NMN is a staple in all those podcasts discussing healthy aging, where it is repeatedly cited as the next must-have supplement for various health benefits.

But for all the excitement, some things tend to get brushed aside, which is exactly what I will be looking into — the downsides. This is not the side of NMN supplements you often hear from those same people talking it up. And so, I will be laying out the current findings that we have on NMN supplements today to give you an evidence-based view of where things really stand with this compound.

What is NMN, and how does it work?

To understand NMN, we first need to define what it is. I will start by breaking down what NMN does, how and to what extent it works in the body, and what that tells us about its potential role in health and longevity.

NMN and its role in the body

Now, with all the talk around NMN and its supposed longevity benefits — the idea that taking this compound could help you live longer — you might assume it is some artificially created lab product. However, NMN is actually a naturally occurring molecule in the human body and can also be found in certain fruits and vegetables, albeit in small amounts. So, think of NMN as a molecule that is essential for many functions of your body and one that plays a central role in cellular processes such as mitochondrial function, energy metabolism, and energy production.

What really catapulted NMN as a potential longevity compound, particularly among anti-aging advocates and biohackers, were early animal studies. These studies suggested a potential connection between NMN and increased lifespan in model organisms, which sparked the widespread interest in NMN supplements we see today.

As for how NMN works, researchers have put forward several hypotheses about its potential mechanisms. Based on current data, the primary role of NMN is to act as a precursor to nicotinamide adenine dinucleotide (NAD+), which is a molecule involved in processes like mitochondrial function, energy metabolism, and DNA repair. It’s theorized that as we age, NAD+ levels start to drop, and with that drop, age-associated physiological decline and certain age-related diseases may emerge.

But again, the exact way NMN works remains a rather complex question, and researchers are still trying to figure it out. While the hypotheses show promise, there is no consensus agreement on its exact mechanism of action yet. Much of the evidence is still in the early stages, and more longitudinal human studies are needed to fully understand how NMN supplementation impacts our biology.

NMN supplementation: potential benefits

From reversing aging and supporting cellular energy metabolism and energy production to improving brain and heart health, NMN is getting quite the reputation. But, with research on this supplement still being a work in progress, many of the claims on the effects of NMN don’t quite match the current evidence. So, let's see what the science actually has to say about some of the benefits that are associated with NMN supplements.

Anti-aging effects

Perhaps the biggest talking point around NMN supplements is their potential anti-aging effects, though this remains largely unproven. As we just covered, NMN’s primary role is believed to be increasing NAD+ levels, which explains its strong link to longevity. So far, around 18 clinical studies have been published on NMN, with 13 of them examining its impact on NAD+ levels in the body.

The findings from these 13 studies have been mixed. For instance, a 60-day study with 66 healthy adults found that NMN supplementation increased NAD+ levels by 38% compared to the beginning of the study. The authors also noted that the difference between the increase of NAD+ levels wasn’t statistically significant among NMN and placebo groups.

Another study with 80 participants found a dose-dependent increase in NAD+ levels with NMN supplementation, though these increases didn’t appear to correlate with the measures of biological or chronological age nor with other health markers.

Beyond NAD+ levels, several studies have looked at NMN’s effects on common physical age-associated changes. In one, 250 mg of NMN supplementation daily for 12 weeks improved lower limb function in older adults. However, a separate study using NMN in the form of MIB-626 found no significant improvements in muscle strength, fatigue resistance, or aerobic capacity.

Another trial reported a statistically significant reduction in blood biological age with NMN supplementation, but not all findings have been positive. For example, a study in older adults with diabetes and impaired physical performance found no significant improvements in grip strength or walking speed after taking NMN for 24 weeks. Similarly, another study found no differences in performance between the NMN and placebo groups in a stepping test at either four or 12 weeks.

From these studies, we can see that NMN shows potential in supporting certain aspects of cellular processes related to aging, but it’s unlikely to reverse age-related changes or aging itself on a broad scale. While early studies are promising, more long-term clinical trials with larger groups of human participants are needed to fully define the extent to which NMN may induce anti-aging effects, if any.

Insulin sensitivity and insulin resistance

Another area where NMN has shown promise is metabolic disorders. Research on how it might influence insulin function in humans is still unfolding, but the initial findings are certainly intriguing.

In a 10-week trial, 250 mg of NMN per day was administered to 25 postmenopausal women with prediabetes and overweight or obesity to assess its effects on body composition, skeletal muscle insulin sensitivity, insulin signaling, muscle NAD+ content, and specific gene expression. The results revealed increased skeletal muscle insulin sensitivity and improved skeletal muscle insulin signaling.

In a study involving 66 healthy adults aged 40 to 65, NMN supplementation appeared to prevent the worsening of insulin resistance. This was measured by HOMA — a parameter used to assess insulin sensitivity, with higher HOMA index values indicating a greater risk of insulin resistance.

The study found that while there was no significant change in HOMA scores for the NMN group, the placebo group saw a notable rise, implying an increase in insulin resistance, which essentially means a decline in insulin sensitivity. As greater insulin sensitivity is what has been linked to anti-aging, the fact that the parameters worsened in the placebo group but showed only a marginal change with NMN suggests NMN may hold potential anti-aging metabolic effects.

These studies hint that NMN supplementation may potentially improve insulin sensitivity in very specific populations. However, the reality is that they are the only two human studies on the subject, and there is simply not enough data to say for certain how NMN supplements impact metabolic health in the long run. So, while we see the potential, the evidence, on the other hand, still leaves a lot to be determined.

Cardiovascular health

Another area of interest for NMN research is its potential effects on cardiovascular health. Although much of the evidence is still just emerging, both animal and human studies have begun to explore whether NMN supplementation might offer benefits for heart health.

A couple of small human studies have hinted at some potentially favorable cardiovascular effects of NMN. In a 12-week trial of 36 healthy middle-aged participants who took daily NMN supplements, the authors observed some potential for NMN in alleviating arterial stiffness, though no significant difference was found compared to the placebo.

Another study involving 30 middle-aged and older adults with overweight or obesity found that taking 500 mg of NMN twice daily for 28 days resulted in significant decreases in diastolic blood pressure, as well as total LDL and non-HDL cholesterol levels.

In animal studies, however, the improvements are more pronounced:

Looking at these findings, it’s clear that the potential of NMN supplements for cardiovascular health is there, but the current evidence, which is mostly based on a couple of human studies with specific populations, is not enough to form final conclusions. We have animal studies suggesting a promising benefit for heart health, but existing research is still in the hypothesis-generating stage. In order to truly confirm whether NMN can improve or support cardiovascular health in humans, we will need more large-scale clinical trials.

Side effects and risks of NMN supplementation

Side effects and risks of NMN supplements — this is the side of the popular compound that tends to get less attention. But before jumping into studies and what effects have or have not been observed, it’s important for me to note that, in general, NMN has shown a favorable safety profile thus far. However, as I have mentioned throughout, the research is still very fresh, meaning both the potential benefits and side effects are not yet fully clear or well-established.

From what has been studied in humans so far, a 2020 study on 10 healthy men observed that oral administration of NMN at doses up to 500 mg per day did not trigger any notable symptoms or changes in vital signs like heart rate, blood pressure, oxygen saturation, or body temperature. Laboratory results showed only minor fluctuations in some blood markers, including serum bilirubin, creatinine, chloride, and blood glucose levels — but nothing outside the normal range.

A little more recently, in 2022, a safety evaluation study on 31 healthy adults aged 20 to 65 examined a higher daily dose of 1,250 mg of NMN over four weeks and reported no severe adverse events. Clinical assessments, including anthropometry, laboratory tests, and body composition, showed no significant deviations beyond normal variation. As for liver and kidney function, the study also found no notable changes in biochemical markers, even at this high dose.

So, based on the available human data, NMN appears to be safe and well-tolerated for healthy adults at doses up to 1,250 mg per day, which is the highest dosage examined so far, for at least up to four weeks.

That said, the data we have today comes only from preliminary human studies and animal research. And while NMN shows a generally favorable profile, rare side effects or unforeseen reactions could still emerge, so it’s important not to overlook those possibilities as well.

Are there any long-term effects and concerns?

Let me start by saying that there’s still much to learn about the effects of NMN in this regard. The available evidence on its long-term effects, whether positive or negative, is far from sufficient — there are very few studies available to form any clear conclusions.

However, despite the lack of research, some theories have been presented. There have been suggestions, particularly from animal studies, that NAD+ precursors like NMN or nicotinamide riboside (NR) could, in theory, promote the growth of existing cancer cells. However, this remains speculative, with no human evidence indicating that NMN poses a cancer risk.

In fact, some preclinical studies have even explored its potential anti-cancer properties. But, these findings are still far from final and need more investigation in large-scale human trials before any conclusions can be drawn.

Are there any recommendations on dosage and administration?

As of today, there are no official medical recommendations on how much NMN one should take. The available data comes from a handful of clinical trials in humans, and that's all we have so far. While this can offer a rough indication of what may be generally well-tolerated and safe for certain populations, it cannot be considered an official guideline or recommendation for appropriate dosage.

Daily NMN dosage in human studies

Clinical trials involving NMN have tested daily doses ranging from as low as 100 mg to as high as 1,250 mg over the course of four weeks. All 18 human studies we reviewed have reported that NMN is generally well-tolerated. In the market today, NMN supplements typically fall within the 125 mg to 900 mg range, which aligns with the available indications of what may be considered safe.

What’s also interesting is that some research suggests that the effects of NMN may actually plateau at higher doses. This indicates to us that more shouldn’t always be regarded as better with this compound. And while higher doses have shown greater improvements in exercise performance, for example, those studies that have evaluated multiple doses of NMN have also revealed that people’s responses can really vary.

But again, the reality is that the findings we have today are still too limited. Without more extensive clinical trials, we cannot form definitive recommendations on the nicotinamide mononucleotide supplementation dosage.

Forms of NMN administration

You will find NMN supplements in different forms, such as powder, capsule, or tablet. But as of now, no research points to one being the most effective or considered a gold standard. The general idea is that the form in which NMN is taken could affect how well your body absorbs it, but there are still no studies providing conclusive proof of which form that may be.

Another thing that you should also be aware of is that while searching for an NMN supplement, you might come across brands that pitch what are called liposomal formulas, which are intended to improve bioavailability. However, don’t be too quick to buy into these claims, as many of these formulas haven’t been proven effective through human clinical trials or pre-clinical studies.

For some expert advice on what to look for when picking the right NMN supplement, I previously spoke with Dominyka Sitavičiūtė, an in-house researcher at Wellnesspulse, and here's what she had to say:

Choose reputable brands, look for third-party testing and certificates of analysis, and always remember that no supplement can replace a healthy lifestyle and balanced diet. It’s important to keep realistic expectations in mind — while NMN supplements may actually offer potential health benefits, they are not a guaranteed shortcut to significantly extended longevity. After all, they are just supplements.

Dominyka Sitavičiūtė

Who should avoid NMN supplements

Given that NMN, the compound, and specific NMN formulations available on the market lack robust research regarding concrete benefits, safety profiles, and recommended dosages, it’s probably best to keep a cautious approach if you are thinking about trying NMN supplements.

People in higher-risk groups — such as children, pregnant or breastfeeding individuals, adults with chronic conditions or extensive medical history, or those taking multiple medications — should be especially cautious. Due to the current state of research, we don’t fully know how NMN interacts with other compounds or how it might affect people in these groups, raising concerns for many. So, it’s recommended that these individuals hold off on taking NMN until there’s more clarity and, as always, consult with a healthcare provider before making any decisions.

Conclusion

At the end of the day, while there’s a lot of talk around NMN — much of which might be justified given the growing interest and expanding research in longevity — it’s still a relatively new compound, as I have mentioned throughout. The effects on the aging process and the long-term administration safety of NMN are not fully set in stone yet. And while NMN seems to have a generally favorable safety profile, it’s important that you keep expectations in check and not just jump on the trend because you saw it on social media or heard it from a biohacker. The benefits observed so far don’t conclusively suggest that NMN will reverse aging on a broad scale.

There's no denying that NMN continues to turn heads, especially in the anti-aging circles, with plenty of potential discussed here. But the science is still in its infancy, and it’s essential we don’t get too carried away. It’s all about staying realistic and sticking to what we know about NMN today. But that doesn't mean that we should close ourselves off to the possibility of new discoveries. It’s imperative that we remain open to the evolving research and adjust our view of NMN accordingly, whether the findings turn out to be positive or negative.