A new human clinical trial of NMN supplement

I would like to share a technical information that, you may or may not know. In academia, we call it “Impact Factor.” Impact factor is basically a reference number that shows how important the journal is. That is, the higher the impact factor, the more influential this journal is to the science community.

The journal “Science” has an impact factor of 41.8. That means this level of peer-reviewed journal only accepts cutting-edge results. 

The first clinical trial was published in 2020 in 10 healthy Japanese men (aged 40-60 years old) and the results showed that a single oral administration of NMN was safe and effectively metabolized without causing any adverse effect. It was a “single” dosage of 100, 250, and 500 mg of NMN by capsule. Their urine and blood samples were monitored for 5 hours after taking NMN. However, the data was not supportive of the claims such as NAD+ boosting or any anti-aging effects. Also, in terms of safety, since was just a “single” dose and a small group, we couldn’t conclude that daily NMN supplementation would be safe for the long-term.That’s why I would say this new result represents a vital piece of the big puzzle. Of course, more investigation is needed for a more complete picture of NMN for human use and its effectiveness. 

Now to summarize the clinical trial:

Compared to the first clinical trial, this clinical trial was conducted in 25 postmenopausal women aged 55-72 years old with prediabetes, who were either overweight or obese. 12 were randomized to the placebo group and 13 to the NMN group with a daily dosage of a 250 mg capsule. Then the participants were randomly assigned to 10 weeks of treatment with either the placebo or NMN. Baseline testing was also collected to assess cellular effects of NMN treatment. This approach made the results very reliable.

Now let’s talk about the three breakthrough findings in this clinical trial: 

1. Increasing NAD+ and NMN metabolites (2PY and 4PY) in plasma, peripheral blood mononuclear cells (PBMCs), and skeletal muscle: after 10 weeks treatment of NMN, both plasma concentration of metabolites and NAD+ content in PBMCs increased, but not of placebo (as you can see in figure A and B). As for the skeletal muscle, even though the muscle NAD+ and nicotinamide content did NOT change as you can see in Figure E and F, the muscle metabolites did increase compared to the placebo, indicating that NMN treatment increased muscle NAD+ turnover as you can see in Fig G, H and I.
2. Increasing skeletal muscle insulin sensitivity: After 10 weeks of NMN supplementation, the glucose disposal rate (referring to the “muscle insulin sensitivity”) was 25% ± 7% greater than before. This improvement is comparable with two other clinical results observed after ~10% WEIGHT LOSS and after 12 weeks of treatment with the insulin sensitizing drug TROGLITAZONE in people with obesity.
3. Increasing skeletal muscle insulin signaling in the NMN group but not in the placebo group as you can in Figure B and C by evaluating insulin-stimulated phosphorylated AKT and mTOR, which are key components of insulin signaling pathway involved in regulating glucose uptake and muscle remodeling. The observations were consistent with studies in rodent models.

What did NOT change after 10 weeks of placebo or NMN treatment?

• Body composition: such as fat mass, fat-free mass, intrahepatic fat content.
• Metabolic variables: such as blood pressure, blood glucose, free fatty acid, insulin, lipids and so on. 
• Muscle mitochondrial oxidative capacity
• Muscle physical function 

However, no effect doesn’t mean NO GOOD. 

The fact that NMN specifically affected the insulin sensitivity in muscle and did NOT affect other important variables associated with insulin resistance, indicates that NMN has SELECTIVE BENEFITIAL effects on ONLY insulin-mediated glucose metabolism in muscle.

The take-home message here is:

1. Is it safe to take 250mg per day NMN for 10 weeks?  YES
2. Does NMN really boost the NAD+ in human?  YES
3. Does NMN increase the skeletal muscle insulin sensitivity and signaling? YES

Currently, there are three more clinical trials at the recruiting stage for evaluating anti-aging, organ system biology, muscle recovery and physical capacity using oral NMN supplementation. 

Again, Stay healthy and Live Longer.