Highlights: 

  • Stanfield says that much of the expectations involving NMN surround early mouse studies showing improvements in muscle performance and metabolic health. 
  • Based on his analysis, Stanfield says that human studies have not yet met these expectations. 
  • Stanfield’s takeaways may be premature, and more studies that include more participants are needed. 

New Zealand’s Dr. Stanfield is a practicing physician who, in a recent video, divulged his thoughts on human studies involving NMN. To him, excitement for NMN accelerated after Harvard’s Dr. David Sinclair appeared on the Joe Rogan Experience about five years ago. At the time, there were no NMN human clinical trials, and much of the excitement behind NMN was based on a 2016 mouse study, says Stanfield. 

In the 2016 study, NMN was shown to mitigate age-associated physiological decline in mice. For this reason, Stanfield says many individuals started taking NMN in the hopes of improving muscle performance, being more resilient against illness and infection, boosting energy levels, and improving measures of metabolic health. Were these hopes fulfilled? Based on his readings of the first 18 NMN human studies, Stanfield provides his four takeaways. 

Takeaway One 

Stanfield’s first takeaway is that NMN appears to be safe over a short duration. He says that all 18 studies, which lasted less than three months, showed NMN was safe. With that being said, the fourth takeaway concerns the long-term safety of NMN.

Continuing, Stanfield excludes four studies from his analysis that are not randomized trials. He only includes randomized trials, where individuals are randomly selected to participate in either a treatment (e.g. NMN) or placebo group, which helps control for the placebo effect. 

To illustrate the importance of randomized placebo-controlled trials, Stanfield points to the multitude of social media influencers touting NMN’s benefits. However, he emphasizes that the positive reviews for NMN could be a result of the placebo effect — effects achieved via perception rather than a treatment. Hence, the purpose of NMN randomized trials is to determine if NMN has any significant effects beyond the placebo effect. 

Takeaway Two 

While NMN boosts NAD+ levels in the blood when measured, it does not appear to raise NAD+ in muscle tissue. This is according to one study of prediabetic women, which is the only study wherein muscle NAD+ was measured. Stanfield also notes that another NAD+ precursor NR does not increase muscle NAD+ levels in humans. He then wonders whether NMN can improve muscle performance without raising muscle NAD+ levels.

He goes on to cite a study suggesting that exercise raises muscle NAD+ levels. The study showed that older adults who engaged in endurance exercise for 3 hours per week have similar muscle NAD+ levels to younger adults who did not undergo structured exercise routines, while sedentary older adults have low NAD+ levels. Based on this study, Stanfield says it is likely that we can support our muscle NAD+ levels with diet and exercise. Still, Stanfield acknowledges that it may be possible for NMN to improve muscle performance without raising muscle NAD+ levels.

To Stanfeild’s estimation, 16 different measures of fitness and muscle performance were assessed across the NMN studies. Of the 16, three showed a benefit, twelve showed no improvements beyond a placebo, and one was incredibly controversial, according to Stanfield. The controversy came from a study done in India, where the walking speeds of middle-aged individuals was very slow and more similar to that of 80-year-olds. As such, Stanfield says that these results were dismissed by other scientists. 

Overall, Stanfield says that since most measures of fitness and muscle performance showed no improvement, his second key takeaway is that NMN likely does not improve muscle performance. 

Takeaway Three 

One of the hopes from the early mouse studies was that NMN could improve metabolic health, according to Stanfield. He says there were 28 measures of metabolic health, including metabolic markers like body composition, LDL cholesterol, insulin, and glucose. Of the 28 measures, he says, twenty-three showed no effect, one showed worsening insulin, and four showed a benefit. 

Furthermore, one of these benefits is difficult to interpret, Stanfield explains. The data under question came from a study done in China showing that insulin sensitivity was improved by NMN. However, the insulin sensitivity of the NMN-treated group did not change. Instead, the insulin sensitivity of the placebo group worsened. He goes on to say that it is difficult to understand how a group of people could worsen their insulin sensitivity in such a short duration of time.

Stanfield concludes that it is not overly convincing that NMN improves metabolic health, which is his third key takeaway. 

Takeaway Four 

Before revealing his fourth takeaway, Stanfield subtly plugs his own brand of multivitamin, which contains 50 mg of vitamin B3. He explains that he does not take more than 50 mg of vitamin B3 because a study showed that taking high doses (1-3g/day) of niacin, a form of vitamin B3, increased death rates by 10%. Additionally, a recent study suggested that niacin metabolites trigger inflammation, which may explain niacin’s association with increased cardiovascular disease risk. 

Since NMN is a form of vitamin B3, which may be converted to niacin in the gut, Stanfield believes there are long-term safety concerns with NMN — his fourth takeaway. 

Is Stanfield Right?

Clearly, Stanfield’s first takeaway is correct, and NMN is safe if taken for about 60 days. His concerns over long-term safety are justified in that there have not been long-term NMN human studies. However, whether NMN has the same effects as niacin is up for debate. For example, while niacin is known to cause flushing of the skin, NMN does not. Thus, human studies are needed to determine how NMN is metabolized and how this affects inflammation. 

When it comes to Stanfield’s assessments of physical performance and metabolic health, he does not lay out his criteria. Thus, simply saying that 4 out of 28 measures of metabolic health showed benefits is not very meaningful without defining what constitutes a “measure of metabolic health.” According to the NMN human studies, there are clearly more than four benefits, including improved insulin sensitivity, an increase in HDL cholesterol and decrease in HabA1c glucose, and a decrease in body weight, blood pressure, and LDL cholesterol. 

Additionally, Stanfield did not address the author’s reasoning behind the slower walking speed of the participants in the study conducted in India. In the study’s discussion, the authors state,

“The results of our six-minute walking test are right within the published range of 294-691 m of healthy Indian adults considering all our trial participants are Indian ethnicity.”

The authors say this because of findings showing that the walking speed of Western populations does not necessarily apply to Indian subjects.

Overall, while Stanfield may be right about some things, it is still too early to make definitive conclusions on NMN’s benefits. Most of the studies so far have been small exploratory studies with the primary objective of determining NMNs safety and if it increases blood NAD+ levels. Longer studies with more participants will help to confirm or deny Stanfield’s takeaways.