NMN for Weight Loss: What's the Science Behind It?

NMN (nicotinamide mononucleotide) is a naturally occurring molecule that acts as NAD+ (nicotinamide adenine dinucleotide) precursor. NAD+ is required in cellular energy production, DNA repair, and cell survival. Depleted NAD+ levels are linked to various health disorders; as such, NMN supplementation gained increasing popularity. It's noteworthy that NMN is no longer sold as a supplement in the U.S., following the FDA's permission to investigate NMN as a potential new drug. This suggests promising developments in its potential use beyond mere supplementation.

Additionally, while NMN is recognized for its role in longevity and anti-aging, recent research suggests it may also aid in weight loss and combating obesity. Let's delve into the science behind NMN's potential for weight management.

Can NMN help with weight loss?

Several experimental studies support the benefits of taking NMN for weight loss.

For instance, one study evaluated long-term (12-month) administration of NMN in mice during their normal aging. The study reported that NMN may enhance mitochondrial metabolism, improve energy metabolism and physical activity, improve insulin sensitivity, and suppress age-associated weight gain.

More recently, the group of Dr. David Sinclair — an expert in NMN, longevity, and aging — tested the effects of NMN in the offspring of obese mice. Offspring of obese mothers usually have impaired metabolism, which makes them prone to obesity and metabolic disorders. In this study, they found that under a high-fat diet, the offspring of obese mothers exhibited better metabolic responses when given NMN: improved glucose tolerance, reduced fat buildup, and enhanced fat breakdown.

Nonetheless, these pieces of evidence are from animal studies and may not necessarily translate to humans.

Human studies and clinical evidence

Human clinical evidence directly evaluating the effects of NMN supplementation on weight loss is lacking.

In 2023, Harvard scientists studied the various health effects of NMN supplementation in 30 middle-aged and older adults with overweight or obesity. After receiving 2,000 mg β-NMN daily for 28 days, participants had increased NAD+ levels, decreased diastolic blood pressure, reduced cholesterol levels, and significant reductions in body weight, offering clinical benefits that warrant larger clinical trials in the future.

In a study involving 25 postmenopausal women with pre-diabetes and overweight or obesity, no significant differences were observed in body composition (body weight, fat mass, fat-free mass, intra-abdominal adipose tissue volume, and intrahepatic triglyceride content), following a 10-week supplementation of 250 mg/day NMN.

Similarly, in a study of 42 healthy older men, there was no observed change in visceral fat and fat mass parameters following 6–12 weeks of 250 mg/day NMN supplementation.

These are minimal clinical studies that do not yet provide a strong conclusion. The differences in dosages, duration, number of participants, end-point parameters, and the study populations' health status or comorbidities played a role in outcome differences. Hence, a large-scale, well-designed clinical trial directly evaluating weight loss potential is needed.

NMN mechanisms of action

While research on NMN's potential health benefits on weight management is ongoing, it is proposed to play a role in weight loss through several mechanisms.

• SIRT1 activation. NAD+ boosts the activity of certain proteins in our cells called sirtuins. These proteins are involved in various cellular processes including metabolism, DNA repair, stress response, and aging. SIRT1, a type of sirtuin, is involved in the regulation of metabolism and plays a role in management of fat storage and use in our bodies. Taking NMN supplements is proposed to help activate SIRT1.
• AMPK activation. Collective research findings point out that the enzyme AMPK is involved in cellular energy homeostasis. It is proposed that NMN may increase AMPK activity, which may result in increased energy usage and the burning of fat, potentially aiding weight loss and supporting efforts against obesity.
• May support lipolysis (fat breakdown). NMN has the ability to boost the activity of the enzyme ATGL, which plays a key role in breaking down triglycerides, the main type of fat stored in our bodies. As a result, NMN may support weight loss by increasing the expression of this enzyme, thus promoting the breakdown of stored triglyceride fats, potentially aiding in achieving a healthier weight.

Overall, considering that there are multiple different mechanisms that have been proposed of NMN-induced NAD+ enhancement, some of which may have an impact on specific mechanisms involving fat metabolism, NMN may emerge as another weight loss strategy. However, well-designed clinical trials are still needed to conclusively support this claim.

What are the other potential benefits of NMN?

Various potential health benefits are tied to NMN supplementation. Some areas have more evidence backed by larger clinical trials, while NMN’s benefits in other areas are still in their early stages. However, most of these effects were reported in animal studies, which warrants further investigation if the same is true in humans.

Here are some of the science-backed health benefits of NMN:

• Anti-aging. Since NMN boosts circulating levels of NAD+, and NAD+ is involved in multiple cellular homeostasis and repair processes, boosting NAD+ levels via NMN supplementation has been widely investigated. In animal studies, NMN supplementation is associated with improvements in lifespan, health status, and age-related decline in several tissues.
• Energy levels. NMN supplementation may increase NAD+ levels that fuel mitochondrial functions and energy production. Mouse models also show increased energy expenditure and higher physical activity.
• Insulin action. NMN’s positive effect on insulin sensitivity and glucose metabolism has also been reported both in animal models of obesity and human trials.
• Cardiovascular health. Mice studies of NMN supplementation in the cardiovascular field are also growing. For example, research in mutant mice shows that by preserving the mitochondrial homeostasis in the heart, NMN may even protect against heart failure.
• Neuroprotection. The neuroprotective properties of NMN have also been investigated in several neurological disease models, including neuroinflammation during traumatic brain injury, neurodegeneration, intracerebral hemorrhage, and learning and memory impairment, however more research is necessary.

Final words

The science behind NMN for weight loss shows some promise. However, much of it has been conducted in animal models or in vitro studies. Human clinical trials directly evaluating the effects of NMN on weight loss with larger sample sizes are needed to validate the effects and determine the optimal dosage, safety, and long-term implications for weight management. Additionally, individual responses to NMN may vary as other factors may also be at play.