What is NAD+?

Scientists have been excited about continuing advances in natural compounds that help stem the aging process.

One of the most well-researched of these is NAD⁺, an important coenzyme that fights aging and disease at the cellular level.¹

Recently, news sources have reported that some celebrities are boosting NAD⁺ as part of their longevity programs.²

However, many Life Extension^® readers are far ahead of this recent trend, as we have been reporting on the potential life-extending benefits of NAD⁺ since 2014.

Potential Anti-Aging Therapy

When it comes to NAD⁺ and longevity, there is a lot to be excited about.

NAD⁺ (nicotinamide adenine dinucleotide) is a coenzyme found abundantly in every living cell.³ It is vital for the functioning of various cells in maintaining healthy aging.⁴

It is critical for hundreds of cellular processes, like DNA repair, energy production, and preventing DNA damage.^4,5

It is also required for the normal function of over 300 enzymes and proteins⁴—one of which belongs to an important group of proteins called sirtuins.⁶

Boosting sirtuin levels is of interest in the fight against aging because low sirtuin activity has been tied to accelerated aging and risk for age-related issues.⁷

NAD⁺ levels are believed to decline with age.⁷ This is likely due to a decrease in synthesis or an increase in degrading enzymes or both. This decline in NAD⁺ levels may contribute to age-related functional decline.8

NAD⁺ precursors are compounds that boost NAD⁺ when taken orally. They are the raw ingredients our body uses to make its own NAD⁺.

Boosting NAD⁺ production with NAD⁺ precursors has gained considerable attention as a potential anti-aging therapy.⁹

In two clinical trials, the NAD⁺ precursor nicotinamide riboside (NR) improved plasma NAD⁺ levels and neuroimaging imaging biomarkers as well as cognitive measures.¹⁰

Indeed, one of the most well-studied NAD⁺ precursors is nicotinamide riboside.¹¹

An open-label non-randomized study in eight healthy individuals found that an ascending dosage supplementation of NR, starting with 250 mg NR/day and building to 2,000 mg/day by the eighth day, raised NAD⁺ levels by two or three times, and was well tolerated.¹²

Extended Lifespan

A potential benefit of replenishing cellular NAD⁺ is to delay some aspects of systemic aging.

For example, preclinical studies have indicated that boosting NAD⁺ with nicotinamide riboside positively impacts physiological functions, aging, and disease. Supplementation has been shown to improve brain, heart, and metabolic health.¹³

Intriguingly, preclinical research has indicated that increasing NAD⁺ levels with nicotinamide riboside can extend lifespan.^14-16

In worms, nicotinamide riboside extended lifespan by 10%.¹⁵

In mice that were the human equivalent of 70 years old, nicotinamide riboside extended median lifespan by about 5%.¹⁶

Given the average American life expectancy of 76 years, this is the equivalent of approximately four additional years of lifespan.¹⁷

Clinical Trials

The benefits of boosting NAD⁺ observed in preclinical studies have intrigued scientists, leading them to investigate whether these benefits translate to humans by supplementation with precursors such as nicotinamide riboside (NR).¹⁸

• In a trial of 30 participants with newly diagnosed Parkinson’s disease, 30 days of supplementation with 1,000 mg of nicotinamide riboside not only significantly increased brain levels of NAD⁺ (measured via magnetic resonance imaging), but it was also associated with decreases in markers of inflammation, as well as mild clinical improvement in symptoms of Parkinson’s disease.¹⁹
• In another trial of 30 clinically stable heart failure patients with reduced ejection fraction, a twice daily dose of 1,000 mg NR doubled the levels of NAD⁺ from baseline and reduced markers of systemic inflammation.²⁰
• A daily dose of 1,000 mg nicotinamide riboside for 21 days in 12 elderly men elevated NAD⁺ levels in the muscles of participants as compared to placebo. A reduction in levels of inflammatory cytokines was also observed in the intervention group.²¹
• In a recent trial of 90 patients with peripheral artery disease (PAD), a condition in which narrowed arteries reduced blood flow to the legs, which can cause severe walking disability, participants were randomized to receive daily for six months:

   

  a. nicotinamide riboside (1,000 mg),

  b. nicotinamide riboside + resveratrol (1,000 mg + 125 mg), or

  c. a placebo.

After six months, supplementation with NR increased the six-minute walking distance by 7 meters (22.9 feet) as compared to a decrease of 10.6 meters (34.7 feet) in the placebo group. In patients with at least 75% adherence to the program, subjects taking NR increased their walking distance by 31 meters (101.7 feet) more than the placebo group, while those receiving NR plus resveratrol had an increase of 26.9 meters (88.2 feet) compared to placebo.²²

Although the NR-alone group showed the greatest numerical improvement in the six-minute walk test, this was not statistically significantly more than the NR + resveratrol group. Poor adherence to taking study medication in the NR + resveratrol group likely contributed to the results. In the NR-alone group 75% were compliant compared to 52% in the NR + resveratrol group. Among participants with ≥75% adherence, both groups had similarly meaningful endurance-enhancing benefits.

Summary

Life Extension has been reporting on anti-aging interventions since 1980. More recently, many of these nutrients are gaining popularity among celebrities and other high-profile individuals interested in longevity.

NAD⁺ is a coenzyme important for energy production, DNA repair, and preventing DNA damage. Boosting levels with the NAD⁺ precursor, nicotinamide riboside, has shown promise to possibly delay some aspects of systemic aging.

A mouse study of NAD⁺ supplementation resulted in a lifespan increase that would be the equivalent of four years if translated to humans.

For those interested in boosting their NAD⁺ levels, one of the most well-documented ways to accomplish this is through oral supplementation with the precursor, nicotinamide riboside, which has been tied to increased lifespan in preclinical studies.

The typical dose for health maintenance is 300 mg of NR daily.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

References

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12. Airhart SE, Shireman LM, Risler LJ, 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. 2017;12(12):e0186459.
13. Mehmel M, Jovanovic N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. 2020 May 31;12(6).
14. Belenky P, Racette FG, Bogan KL, et al. Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD⁺. Cell. 2007 May 4;129(3):473-84.
15. Fang EF, Scheibye-Knudsen M, Brace LE, et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014 May 8;157(4):882-96.
16. Zhang H, Ryu D, Wu Y, et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016 Jun 17;352(6292):1436-43.
17. Available at: https://www.cdc.gov/nchs/fastats/life-expectancy.htm. Accessed Feburary 10, 2025.
18. Freeberg KA, Udovich CC, Martens CR, et al. Dietary Supplementation With NAD⁺-Boosting Compounds in Humans: Current Knowledge and Future Directions. J Gerontol A Biol Sci Med Sci. 2023 Dec 1;78(12):2435-48.
19. Brakedal B, Dolle C, Riemer F, et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metab. 2022 Mar 1;34(3):396-407 e6.
20. Wang DD, Airhart SE, Zhou B, et al. Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2022 Dec;7(12):1183-96.
21. Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019 Aug 13;28(7):1717-28.e6.
22. McDermott MM, Martens CR, Domanchuk KJ, et al. Publisher Correction: Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nat Commun. 2024 Aug 12;15(1):6890.