Eugene He

NAD (Nicotinamide adenine dinucleotide) is a critical coenzyme that is found in every cell in our body. Coenzymes are ‘helper’ molecules that enzymes need to perform critical processes in our body, such as energy production, DNA repair, and sirtuin activity (regulate cellular health). Without NAD+, life wouldn’t exist. Researchers have linked the process of aging to lower levels of NAD in the body. In fact, Harvard scientist and anti-aging expert Dr. David Sinclair says that by age 50, your NAD levels are about half what they were when you were 20.

Nicotinamide mononucleotide (NMN) and Nicotinamide Riboside (NR) both promote NAD+ production. They are essential for human life, well-being and longevity and there is a lot of exciting research being conducted on these molecules. But what everyone wants to know is which form of NAD+ to consume. So I thought the best way to figure this is letting science speak for itself.

What Science has to say- Which one is Better?

Efficiency

NMN readily and directly converts to NAD+, due to the phosphorus present in NMN, making its conversion to NAD+ possible in a single step. NR, however, lacks phosphorus, therefore the body needs an additional form of compatible phosphorus to transform NR to NAD. When considering NR as a supplement, the lack of phosphorus in NR adds an extra step to the conversion to NAD. NR is first converted to NMN, and thereafter to NAD+, whereas NMN converts to NAD+ in a single step.

This improves the uptake of NMN and leads to faster availability of NAD+ to our body.1

Stability

Studies show that NMN remains intact in drinking water at room temperature for 7–10 days, while another study, looking at the stability of NAD+ and its metabolites, NR showed gradual degradation to NAM (Nicotinamide- a form of Vitamin B3) within one hour, and was unable to reach peripheral tissues, while NMN remained stable in blood.2 Murine models a steep increase of plasma NMN in a mere two and a half minutes, with further increases at 5-10 minutes. In both mice and human studies, NR has been confirmed to be highly unstable and quickly degraded into regular Vitamin B3. As it easily degrades into Vitamin B3, NR is restricted to the rate-limited de novo pathway and cannot increase your NAD+ levels above your baseline.3

In one human study, NR demonstrated a peak only at about 3 hours, at a dosage of 1000 mg. This suggests that NR might need 2-3 hrs to be absorbed by the gut, and some NR gets degraded to nicotinamide before getting converted to NMN.4

While NMN is absorbed through the gut in a few minutes, NR might take upto three hours.

Faster Absorption

It was once thought that NMN must be altered before entering cells but new evidence states that a specific gene, slc12a8 enables NMN to directly enter cells, demonstrating efficient NMN uptake. The slc12a8 gene is very specific to NMN transport only, and not NR. This gene is expressed in many tissues and is rich in the small intestines, enabling NMN to be quickly absorbed in just 2-3 minutes, thus converting to NAD+ in 10-30 min.5

NMN works where NR doesn’t

NMN has quite a few strong advantages of its own. While assessing the efficiency to treat Friedreich’s Ataxia (FRDA), a rare inherited childhood heart disease, NMN was found successful where NR failed.

In the treatment of cognitive impairment in Alzheimer’s disease, for which β-amyloid plaque is thought of as the main culprit, NMN was potent enough to reduce the burden of amyloid β plaque by reducing its production. Though NR was capable of reducing neuroinflammation, reduced hippocampal cell death but it had no impact on the amyloid plaque burden.6

Safety

Whenever an individual starts consuming a supplement, safety is a primary concern. According to studies performed thus far, no safety concerns involve NMN or NR consumption. Both have well established safety studies in humans claiming that NMN and NR entails no safety concerns following their administration.7,8

Conclusion

Current research suggests that NMN has a distinct advantage over NR. NMN is being studied worldwide, and is the compound that the majority of longevity clinical studies are focused on. There is strong potential for the role of NMN in applications and therapeutics beyond anti-aging, such as in diabetes and Alzheimer’s disease.

About Eugene He

Eugene is the founder of Invity, a clinical naturopath and a nutraceutical formulator. He has spent the past twenty years educating and writing about nutrition, phytotherapy and general wellness. His work has been featured in Forbes, Yahoo, Tatler, CEW, Allure and many other publications around the world.

Reference

1. Denu JM. Vitamins and aging: pathways to NAD+ synthesis. Cell. 2007;129(3):453-4.
2. Nikiforov, A et al. Degradation of Extracellular NAD+ Intermediates in Cultures of Human HEK293 Cells. Metabolites 2019, 9, 293.
3. Das A et al. Impairment of an Endothelial NAD-HS Signaling Network Is a Reversible Cause of Vascular Aging. Cell. 2018;173(1):74-89.e20.
4. Airhart, Sophia E et al. “An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.” PloS one vol. 12,12 e0186459. 6 Dec. 2017
5. Grozio A et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nat Metab. 2019;1(1):47-57.
6. Poddar, Saikat Kumar et al. “Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule.” Biomolecules vol. 9,1 34. 21 Jan. 2019.
7. Irie, Junichiro et al. “Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men.” Endocrine journal vol. 67,2 (2020): 153-160.
8. Conze, Dietrich et al. “Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.” Scientific reports vol. 9,1 9772. 5 Jul. 2019.