Nicotinamide mononucleotide (NMN: Vitamin B3) Supplementation Improves Insulin Sensitivity

Vitamin B3 which is nicotinic acid, more commonly referred to as niacin, is a critically important vitamin that serves as the precursor for the cofactors nicotinamide adenine dinucleotide (NAD⁺) and NADP⁺.

Nicotinic acid and niacin represent two different terms for the same chemical form of vitamin B3, whereas nicotinamide represents the modified form containing an NH₂ group. The designation NAD⁺ (and NADP⁺) refers to one of the two oxidation states of the vitamin-derived cofactor, the other being NAD(P)H.

These cofactors are involved in both catabolic (NAD⁺) and anabolic (primarily NADPH) metabolic reactions. In addition, NAD⁺ is a critical component of numerous processes that ultimately control the expression levels of hundreds of different genes.

Please got to the Vitamin B3: Metabolism and Functions page of my website for more details.

I have discussed the the benefits of NAD⁺ many times in my blog:

NAD (VITAMIN B3): BENEFITS AND MEANS OF BOOSTING LEVELS IN THE BODY

IS VITAMIN B3 (NIACIN) THE ANTI-AGING VITAMIN?

The latter post discusses whether or not there is a health benefit to dietary supplementation with vitamin B3. However, it is important to understand several facts about vitamin B3 and dietary supplementation. Not only does the body make NAD⁺ from nicotinic acid/niacin or nicotinamide that are the common food additives or present in vitamin supplements, but is also salvages NAD⁺ from the various reactions that utilize NAD⁺ of NADPH as cofactors. This means that one can supplement one's diet with nicotinic acid/niacin, or nicotinamide (NAM), or nicotinamide riboside (NR), or nicotinate mononucleotide (NAMN), or nicotinamide mononucleotide (NMN). In the context of NAD⁺ synthesis and recycling it appears that NMN is rate limiting factor for overall NAD⁺ production.

Several years ago, as outlined in the second of the two prior posts from my blog linked above, supplementation of rodent chow with NMN resulted in decreases in typical parameters of aging. This manuscript demonstrated that NMN administration in obese mice fed a high-fat diet resulted in increased tissue NAD+ concentrations and improved glucose tolerance, insulin sensitivity, and pancreatic β-cell function (the cells that secrete insulin). In addition, long-term NMN administration in mice fed regular chow mitigated age-associated insulin resistance.

These results led to an explosion in dietary supplements featuring NMN as the active ingredient. However, no long term studies have been carried out to ascertain which form of vitamin B3 is the most beneficial in relationship to health and longevity.

Now, a new study, published in the highly prestigious journal, Science, shows that in humans there is likely to be a significant health benefit to long-term NMN supplementation in the diet.

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

This manuscript reports on the results of a 10-week NMN supplementation in post-menopausal pre-diabetic females. The criteria for inclusion was that the participants were overweight or obese.

At the end of the 10-week trial it was determined that NMN (250 mg per day) treatment improved skeletal muscle insulin sensitivity in the participants, but it did not affect insulin sensitivity in the liver. In addition, the supplementation did not lead to changes in the basal levels of plasma free fatty acids, glucose, or insulin concentrations.

Within the muscles of these participants there was an demonstrable increase in insulin sensitivity as evidenced by increased insulin-stimulated phosphorylation of several key downstream regulators of insulin function such as AKT and mTOR, as well as increased insulin-stimulated uptake of glucose. The level of changes observed with NMN supplementation were equivalent to what has been seen, with respect to insulin sensitivity, in overweight or obese individuals who lose around 10% of their body weight.

IMPORTANT CONSIDERATION: With respect to the form of vitamin B3 used as a supplement it may be that NMN is the best option. This is because several randomized controlled trials conducted in middle-age and older-adult men found that treatment with nicotinamide riboside (NR) did not affect whole-body or muscle insulin sensitivity. Whether other intermediates in the NAD⁺ synthesis and salvage pathways will demonstrate effects equivalent to, or better than, NMN remains to be determined.