What Are the Proven Benefits of NMN?

NAD+ (nicotinamide adenine dinucleotide) is an essential molecule for human life—but its levels decline with age due, in part, to an accumulation of DNA damage and cellular or metabolic requirements. With a reduction in NAD+ activity comes accelerations in aging, including cellular, tissue, and organ dysfunction that leads to disease.

Research has found that NAD+ levels can drop by as much as 50% between the ages of 40 and 60, with an additional decline upon reaching older age. Low NAD+ levels have been linked to every hallmark of aging, including cellular senescence, telomere attrition, epigenetic alterations, mitochondrial dysfunction, and more.

So, what does NMN have to do with NAD+? In a process known as the “NAD salvage pathway,” our bodies can produce NAD+ from unused forms of nicotinamide, including NMN. As an NAD+ precursor, NMN is thought to maintain healthy NAD+ levels with age. Unlike other NAD+ precursors, NMN can be directly converted into NAD+ without requiring additional steps. For this reason, longevity researchers have been studying the effects of NMN on various aspects of aging—let’s see what they’ve discovered so far. 

Proven Benefits of NMN: A Look at Human Studies 

While there have been many studies looking at the effects of NMN in animals, yeast, or cell-based cultures (which are informative and can tell us a lot about what NMN does mechanistically), human clinical trials are obviously more relevant and helpful in determining how NMN affects us as walking and talking people.

Improved Markers of Biological Age

In a study of middle-aged healthy adults, those who took NMN (at doses of 300, 600, or 900mg) for 60 days had unchanged markers of biological age. Although this doesn’t sound like a good thing, the placebo group had increased biological age, suggesting that NMN can slow this internal aging process. 

NMN has also been found to increase telomere length—the “endcaps” to our chromosomes that protect them from damage and shorten with age. In this study, researchers looked at telomere length in PBMCs (peripheral blood mononuclear cells) from middle-aged humans (in addition to mice) after supplementing with 300mg NMN for 40 days. They found that PBMC telomere length was significantly increased after NMN supplementation in both humans and mice. However, this study was not placebo-controlled and only studied 10 men, so larger and more controlled trials are needed to verify that NMN lengthens telomeres. 

Metabolic Markers and Glucose Metabolism

In April 2021, a clinical trial published in Science showed that NMN supported several markers of skeletal muscle glucose metabolism that are commonly dysregulated in people with metabolic disorders. In this study, obese and metabolically dysregulated postmenopausal women received a placebo or NMN (250 mg/day) for ten weeks. No adverse events were observed, and the NMN group had improvements in skeletal muscle insulin sensitivity, insulin signaling, and muscle remodeling, suggesting better metabolic health.

A small study with metabolically healthy postmenopausal women also found that supplementing with 300mg of NMN for eight weeks led to significant reductions in hemoglobin A1C—a measure of glycated hemoglobin that is a proxy for blood sugar control. 

Improved Athletic Performance

In 2021, a clinical study of amateur runners compared three doses of NMN—300, 600, and 1200 mg—for six weeks. While there were no changes to body composition (like body fat or BMI), there was a dose-dependent increase in skeletal muscle oxygen utilization in the 600mg and 1200mg groups, indicating enhanced aerobic capacity. This suggests that skeletal muscle is sensitive to NMN, and moderately high doses of NMN may be able to support endurance in amateur athletes. 

Another study with 80 middle-aged healthy adults looked at the effects of various doses of NMN (300, 600, and 900mg) for 60 days. The research team found that all three NMN doses led to significant increases in walking distance during a six-minute walking test, with the longest walking distances coming from the 600 and 900mg groups. The adults taking the higher doses of NMN (600 and 900mg) also had improvements on the “SF-36” questionnaire, which measures physical functioning, bodily pain, general health, vitality, and emotional and mental health.   

Reductions in Fatigue  

A January 2022 study published in the journal Nutrients looked at the effects of taking 250 mg of NMN in the morning or afternoon on older adults’ sleep quality, fatigue, and physical performance. They found that adults taking NMN in the afternoon had the greatest reductions in drowsiness, suggesting an improvement in daytime energy levels. 

Muscle Health

In the previously mentioned January 2022 study published in Nutrients, the older adults taking NMN (250 mg) in the afternoon also had significant improvements in lower limb function, as measured by a “5-times sit-to-stand” test. 

Plus, a study with older men also found beneficial results for muscle health. In this research, men with an average age of 71 who took 250mg of NMN for six weeks had significant improvements in performance in the left grip test and gait speed, a marker of both leg strength and aerobic capacity. However, NMN did not increase the skeletal muscle mass of the men in this study. Both gait speed and grip strength are vital markers of age-related muscle health and functional capacity and can predict future mortality. For example, a study of over 10,000 American adults found that those with the slowest walking speeds are at a 42% increased risk of mortality compared to speedier walkers. 

Cardiovascular Health 

In a small study from 2023, healthy middle-aged adults who took 250mg of NMN per day for 12 weeks experienced reductions in arterial stiffness—a marker of cardiovascular health and function. 

Another small study showed that postmenopausal women who supplemented with 300mg of NMN for eight weeks had significant increases in HDL cholesterol, which is a beneficial type of cholesterol linked to improved heart health. 

Skin Health

The same small study has also suggested that supplemental NMN can improve markers of aging skin. In this research with postmenopausal women, six out of seven items on a subjective visual scale were improved after supplementing with 300mg of NMN for eight weeks: skin moisture, flakiness (dry skin), blemishes, elasticity, make-up application, and rough skin, with the only marker not improved being skin eruptions (breakouts). Supplemental NMN also significantly reduced advanced glycation products in the skin, indicating improvements in markers of skin aging.

Key Takeaways: 

NMN is a precursor to NAD+, which is a necessary coenzyme in all cells of the body that decreases with age and is responsible for many age-related conditions. The main benefits of supplemental NMN discovered in human clinical trials thus far include supporting markers of biological age, metabolic health, blood glucose metabolism, athletic performance, physical health, and cardiovascular function. 

While the results are promising, longer and larger human trials are still needed to determine the best and safest NMN dosages and frequencies needed to support health and longevity. As most of the mentioned studies are small, short in duration, and low in diversity, we need additional trials to verify these results. 

References: 

Igarashi M, Nakagawa-Nagahama Y, Miura M, et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging. 2022;8(1):5. Published 2022 May 1. doi:10.1038/s41514-022-00084-z

Katayoshi T, Uehata S, Nakashima N, et al. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Sci Rep. 2023;13(1):2786. Published 2023 Feb 16. doi:10.1038/s41598-023-29787-3

Kim M, Seol J, Sato T, Fukamizu Y, Sakurai T, Okura T. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Nutrients. 2022;14(4):755. Published 2022 Feb 11. doi:10.3390/nu14040755

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;18(1):54. Published 2021 Jul 8. doi:10.1186/s12970-021-00442-4

Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. Epub 2012 Jul 27. PMID: 22848760; PMCID: PMC3407129.

McGrath BM, Johnson PJ, McGrath R, Cawthon PM, Klawitter L, Choi BJ. A Matched Cohort Analysis for Examining the Association Between Slow Gait Speed and Shortened Longevity in Older Americans. J Appl Gerontol. 2022;41(8):1905-1913. doi:10.1177/07334648221092399

Niu KM, Bao T, Gao L, et al. The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase. Front Nutr. 2021;8:756243. Published 2021 Nov 29. doi:10.3389/fnut.2021.756243

Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Adv Nutr. 2023;14(6):1416-1435. doi:10.1016/j.advnut.2023.08.008

Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023;45(1):29-43. doi:10.1007/s11357-022-00705-1

Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;eabe9985. doi:10.1126/science.abe9985