In last week’s post, I outlined what NAD+ is; how it declines with age and the role that plays in aging; how it can be boosted with healthier lifestyle habits; how it can also be boosted with IV infusions or by taking the oral supplements NMN or NR; and why these supplements have generated tremendous interest in recent years.
But I also explained that, at this point in time, I do not recommend supplementing with NAD+, NMN, or NR. (Needless to say, I do recommend exercise and a healthy diet, both of which have been shown to raise NAD+ levels).
Today I will continue my “FAQ Style” discussion of NAD+, and offer reasons to be very cautious about considering supplementing this molecule.
You explained in your last post that there have been animal studies showing reduced aging when supplementing NAD+/NMN/NR. Are there any human studies that show similar effects? Unfortunately, there are not. At this point there have been at least 20 human trials of these supplements, looking at how boosting NAD+ levels via supplements can affect everything from blood glucose to cholesterol to Parkinson’s disease to long COVID. To date, none of them have shown much of a clear benefit. A few studies that had some methodological flaws did show small benefits, but they were hardly the hoped-for slam dunk that many were anticipating.
I’m surprised to learn that human studies do not show the same promise as animal studies. Can you clarify why that might be? First off, this is not uncommon. Humans are not mice, rats, or monkeys. We have our own unique biology, and it’s unfortunately quite common for a treatment which seems very promising in animal experiments to not pan out in humans. But there is also a darker side to this story, namely that some newer studies in mice (click here for an example) have failed to confirm earlier findings. This also is common in science – a study will show something of interest, but later, when other scientists try to replicate the study, they get a different result. If boosting NAD+ in mice leads to increased longevity in some studies but not in others, it’s probable that the original beneficial findings were not valid, or at least are much weaker than it originally appeared.
OK, researchers haven’t been able to establish a clear benefit to taking NAD+/NMN/NR for longevity purposes, but what about how they make me feel? I have a friend who went on NMN and claims to have much improved energy/gym performance/mental clarity/skin/libido/etc. It’s hard to know what to make of this. Indeed, if you search the internet you will find many testimonials of people who feel that taking NMN or NR have improved their quality of life. One obvious possibility is that this is due to a placebo effect (Placebo effects are shockingly common, with many drug trials finding as many as 40% of people getting significant improvement from an illness when taking a placebo). Another is that people who take supplements to raise NAD+ are probably also engaging in lots of other health promoting behaviors and that these may be behind the improvements they are experiencing. If you follow a Paleo diet, do CrossFit three times per week, walk ten thousand steps a day, regularly sauna, and take an NMN supplement, it’s hard to say that the NMN supplement is the thing helping you to lose weight and feel amazing. Finally, it’s worth acknowledging that raising NAD+ levels with supplements might lead to improvements in quality of life, at least for some people.
I hear what you are saying that NAD+/NMN/NR supplements may not be as great as they are hyped. But maybe I’ll be one of those who feel amazing when taking them. What would be the harm in trying them? If it were clear that these supplements were absolutely harmless, I would agree with this logic. Even if their benefits turned out to be entirely due to placebo, that wouldn’t bother me per se. However, while it’s clear that these supplements are safe in the short-term, there are a few signs that long-term use might be more harmful. For example, a team at the Mayo clinic found that boosting NAD+ levels might ACCELERATE the growth of pancreatic cancer cells. (To be fair, this was a “test tube” study, and hence a fairly weak type of evidence; but so too were the hopeful studies on mice that kicked off the excitement around boosting NAD+. If we are going to get excited when weak lines of evidence show a benefit for boosting NAD+, we should be consistent and take pause when equally weak lines of evidence suggest the possibility of harm).
Perhaps of greater concern is that NMN and NR supplements are closely related to vitamin B3, and once ingested in the body, raise many of the same metabolites that high dose vitamin B3 do. This matters because previous research has established that high dose vitamin B3 can damage blood vessels and lead to an increased risk for cardiovascular disease. So while we don’t know for sure, there are real reasons to be concerned that taking NAD+ boosting supplements may increase the risk for heart attacks and strokes.
Taken in sum, the initial excitement around NAD+ has not panned out so far. There are at least some reasons to think that taking NAD+ boosting supplements might be risky in humans, and there is a lack of clear benefit.
Of course, more research is likely to be done. As that happens, we will learn more about the potential benefits and risks of these supplements, and my opinion may change. But for now, my judgement is that you are best off taking a pass on these supplements for the time being, and focusing instead on the safe way that we know to raise NAD+ levels: namely healthy diet and exercise.
