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Two Popular Supplements Boost Anti-aging — Nicotinamide Mononucleotide and Resveratrol


Nicotinamide mononucleotide (NMN) and resveratrol are two anti-aging supplements that have grown in popularity in the longevity field. Together they may slow down cell aging and deliver even more positive effects to the human body. This combination is believed to boost strength, physical endurance, and increase blood flow.

What is NMN?

NMN is one of the main precursors of nicotinamide adenine dinucleotide (NAD+) — an essential enzyme for various critical cell functions, including metabolism, cell growth, and survival. It also plays a key role in boosting energy and stimulating cellular repair.

Studies have shown that NMN could enhance NAD+ biosynthesis and improve disease detection in laboratory mice. For example, in one of the first NMN studies, mice exposed to an NMN supplement experienced increased tissue NMN and NAD+ levels within 15 min in the liver, pancreas, and white adipose tissue. To make long-term NMN administration possible, another group of researchers subjected mice to lower doses. Researchers hope those findings could show positive anti-aging results for humans — by adding it to drinking water.

To determine the effects of long-term NMN administration, scientists conducted a 12-month-long study. Initial findings showed that long-term administration of NMN and dose-dependently significantly suppressed age-associated body weight gain. In addition, mice administered with NMN consumed more food with less weight gain compared to the control group. Interestingly, NMN-administered mice showed enhanced energy metabolism, higher physical activity, and better oxygen consumption.

Furthermore, this study indicated that NMN reverses age-associated gene expression changes, which could induce anti-aging effects at the molecular level. After the conclusion of this research study, researchers performed more than 27 other studies to observe the effects of NMN in mice. These studies confirmed that NMN could:

  • Improve glucose tolerance and insulin secretion
  • Inhibit inflammation, reduce neural cell death
  • Reduce the infarct area after ischemia
  • Restore physical activity
  • Improve learning, memory, and cognitive functions
  • Reduced DNA damage
  • Improve cardiac functions

How powerful is NMN?

Only in the past few years have researchers started to examine the effects of NMN in controlled, randomized trials to see if the effects observed in cells and animal models translate to humans. A Keio University School of Medicine research team conducted the first clinical study. Participants in this study received 100–500 mg of NMN. Results showed that this dosage of NMN was safe and effectively metabolized without causing significant adverse effects.

Previous mouse models had shown that NMN administration might increase NAD+. However, evidence of its effect on humans is still scarce. In one study, healthy volunteers received 250 mg/day of NMN (n = 15) or a placebo (n = 15) for 12 weeks. In addition, NAD+ and its related metabolites in whole blood were examined. Observations showed that NAD+ levels in whole blood increased significantly after NMN administration.

Researchers also tested the anti-aging effects of NMN and its safety in a double-blind, parallel, randomized controlled clinical trial. This study included 66 healthy subjects between the ages of 40 and 65. They took 300 mg of NMN daily after breakfast for 60 days. In the middle of the study (day 30), NAD+ level showed an increase of 11.3%, whereas the placebo group showed no change. Furthermore, by the end of the study, i.e., day 60, the NAD+ level had increased by 38%.

The study proved that a rise in NAD+ in the NMN consuming group was considerably higher than in the placebo group. Increasing the dose or the duration could have more significance. It also did not cause any specific damaging effects in healthy volunteers.

Researchers administered three dosages (300, 600, and 1200 mg/ d) of NMN supplementation to healthy amateur runners during a 6-week exercise training program. The main finding of this study was that NMN supplementation during exercise improved oxygen uptake.

Researchers noticed that combining exercise with NMN supplementation increases oxygen consumption. Additionally, dose-dependent subjects and those with large doses of NMN were better affected, but dosages had no effect on grip strength, the number of push-ups or sit-and-reach reps subjects could complete compared with athletes exercising without supplementation. However, 600 mg/d NMN, not 1200 mg/d NMN, significantly improved single leg stance test results.

The power of Resveratrol

Resveratrol, an antifungal, is a stilbenoid found in grape skins in low amounts. Over 19 model organism-based studies (yeast, nematodes, mice, fruit flies, Mexican fruit flies, and turquoise killifish) revealed that resveratrol could extend lifespan.

A study demonstrated that resveratrol could induce autophagy in human cells in vitro and promote longevity through the Sirt1 gene-dependent induction of autophagy — Sirt1–Sirt7 genes have long been key anti-aging genes. In addition, resveratrol could also promote the activities of nuclear-factor kappa B (NF-κB) and the Sirt1 gene to decrease the levels of inflammatory markers.

The study also showed that resveratrol has protective effects against neurodegenerative diseases by enhancing the secretion of neurotransmitters, increasing the production of new neurons, and decreasing neuroinflammation and oxidative stress. Other studies show that this supplement has a cardioprotective effect by enhancing nitric oxide production, modulating the activity of the renin-angiotensin system, and ameliorating oxidative stress. Many studies have shown that resveratrol is effective in preventing and treating cancers. It does so by significantly inhibiting cancer cell proliferation, migration, and invasion.

Interestingly, researchers found that combining NMN with resveratrol could increase the NAD+ levels in the heart and muscle tissue. Professor David Sinclair, an anti-aging expert, believes that resveratrol works synergistically with NMN. His findings show that resveratrol is needed to activate the sirtuin genes (which protect our DNA and epigenome), while NMN is needed to fuel the sirtuins.

Conclusion

Many studies have shown the positive effects of NMN and resveratrol on our health. However, now science is trying to uncover the biological pathways of these two supplements and to prove how they are important to anti-aging. Several human clinical trials are underway studying how NMN and resveratrol affect the aging process, which should give rise to new, promising results for the longevity field.

Key takeaways

NMN – a pure number one supplement in the longevity field.

NMN increases NAD+ levels in our body (NAD+ is one of the most important molecules in the cell cycle).

Resveratrol – a natural supplement, which is a good antioxidant and also plays an important role in anti-aging.

When taken together, NMN and resveratrol could have synergistic effects and further increase NAD+ levels.

Resources:

Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806.

Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528.

Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021 Jul 8;18(1):54.

Zhou DD, Luo M, Huang SY, Saimaiti A, Shang A, Gan RY, Li HB. Effects and Mechanisms of Resveratrol on Aging and Age-Related Diseases. Oxid Med Cell Longev. 2021 Jul 11;2021:9932218.

https://www.nature.com/articles/d42473-022-00002-7

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