Does Nicotinamide Mononucleotide (NMN) Work?

Nicotinamide mononucleotide (NMN) has recently gained attention as a potential anti-aging supplement. NMN is involved in the production of cellular energy and the activation of proteins called sirtuins that regulate aging. Some research suggests NMN supplementation may combat age-related decline across bodily systems and diseases. But does NMN truly live up to the hype? This article will dive into what NMN is, evaluate the science behind its purported benefits for longevity, cognition, metabolism, and athletic performance, and offer key expert opinions on its efficacy and safety as a supplement.

 

What is Nicotinamide Mononucleotide (NMN)?

 

Nicotinamide mononucleotide, or NMN, is a derivative of vitamin B3 that occurs naturally in the body. It plays a crucial role as an intermediate in the production of nicotinamide adenine dinucleotide (NAD+), which is essential for energy creation in the mitochondria [1].

 

NAD+ also activates sirtuins, proteins that regulate the aging process. NMN is believed to potentially raise NAD+ levels when supplemented and exert anti-aging effects, though research is still early. Common dosages studied range from 100 to 500 mg per day. Currently NMN is available as supplement only and lacks approval as a pharmaceutical drug.

 

Will NMN Reverse Aging?

 

Research on whether NMN can “reverse” aging and prolong lifespan is still inconclusive:

- Mouse studies show increased NAD+ levels and some improvements in age-related decline with NMN supplementation [2]. Lifespan extension is debated.

- Human trials on NMN are limited. Small studies show increased NAD+ levels in older adults but no measured clinical benefits [3].

- Effects likely depend on individual factors like baseline NAD+ levels, age, genetics, and health status.

- Larger, longer-term human trials are needed to confirm anti-aging efficacy. Most experts advise cautious skepticism at this stage [4].

While NMN supplementation appears generally safe, expectations that is can “reverse” or stop aging overall should be tempered until more robust evidence is available. Modest benefits are possible but not guaranteed.

Does NMN Cause Weight Gain?

 

There is little evidence that NMN causes weight gain or harms metabolism:

- NMN plays a role in energy metabolism – it does not provide calories directly [5].

- Animal studies show preventing NAD+ decline with NMN does not affect body composition or weight [6].

- Human studies have not reported weight gain as a side effect or measured significant differences in metabolic markers with NMN use [7].

- NMN may support metabolic function that declines with age. This could help prevent weight gain by optimizing fat and carbohydrate metabolism [8].

Based on current research, NMN supplementation does not appear to promote weight gain or negatively impact metabolic health. Further study is still needed, but it may potentially offer modest metabolic support.

 

Cognitive Function and Brain Health

 

Some initial research suggests β-Nicotinamide mononucleotide may benefit cognition and brain function as we age:

- Animal studies show NMN administration improved memory, learning, and mood in aged mice [9]. It increased formation of connections between brain cells.

- NMN reversed declines in blood flow and neuron activity in aging animal brains [10]. This may protect cognition.

- No human clinical trials have directly measured NMN’s effects on dementia, Alzheimer’s, or cognitive decline yet. Such study is needed.

- Experts theorize NMN could help maintain neuronal health and cognitive function. But direct evidence in humans is still lacking [11].

While promising, claims that NMN enhances cognition currently lack robust support. Well-designed human trials are still needed to explore these potential brain health benefits.

 

Athletic Performance and Muscle Function

 

The potential benefits of NMN supplementation for athletes and muscle function are less clear:

- Animal studies show preventing NAD+ decline with NMN increased exercise endurance [12]. But other studies show no differences in performance [13].

- Human trials are non-existent regarding NMN for athletes. Any performance benefits remain speculative.

- Older adults with low NAD+ may experience modest improvements in muscle strength and function with NMN [14]. Younger athletes are unlikely to benefit.

- More research is required to evaluate effects on athletic performance and muscle function in humans of different ages.

Despite some promising animal research, there is currently insufficient evidence to recommend NMN for enhancing exercise performance or muscle function. Human clinical data is sorely lacking at this time.

 

Scientific Evidence

 

The current body of scientific evidence related to NMN supplementation in humans is still in its infancy:

- Small human trials demonstrate beta-nicotinamide mononucleotide effectively increases NAD+ levels in the blood [15]. This confirms NMN’s biochemical activity, but clinical benefits remain understudied.

- No major randomized, controlled human trials with clinically relevant endpoints have been completed yet. Most data is from animal models.

- Two meta-analyses of early clinical studies found insufficient evidence to support anti-aging benefits or impacts on cognition, performance, or any disease treatment [16,17].

- Larger, longer-term human studies with rigorous designs are needed to truly evaluate efficacy and safety.

In summary, the hype surrounding NMN outpaces the current human evidence. While promising, there is not yet enough quality clinical data to confirm meaningful benefits for aging, cognition, exercise, or other outcomes in humans.

 

Does NMN have Side Effects?

 

Early safety data suggests NMN supplementation is relatively well-tolerated, with a low risk of adverse side effects at standard dosages:

- Human trials using dosages up to 500 mg/day for up to 12 weeks report no serious adverse effects compared to placebo [18].

- Mild effects like headaches, digestive upset, skin flushing, and muscle soreness are occasionally reported [19].

- Animal studies using extremely high dosages have linked NMN to nausea and possible increased disease risk [20]. Normal supplements are well below safety concerns.

- NMN could theoretically interact with diabetic medications, blood thinners, and drugs metabolized by the liver. Consult a doctor before using NMN if taking any medications.

While more study on long-term safety is advisable, NMN displays a reasonable safety profile at tested dosages in currently available research.

 

Expert Recommendations

 

Most experts advise cautious optimism about beta nicotinamide mononucleotide due to the limited and early state of human research:

- They emphasize that robust clinical trials in humans are needed to confirm benefits beyond increasing NAD+ [21].

- Routine use for anti-aging is not recommended until additional evidence for clinical efficacy exists [22].

- Use for serious cognitive and neurological conditions requires extensive further study and medical consultation.

- Targeting people with diagnosed NAD+ deficiencies may yield greater potential for benefit with physician monitoring [23].

- Adherence to standard dosage guidelines and awareness of any interactions with medications is important.

In summary, experts agree more evidence is needed before NMN use can be recommended for anti-aging, cognition, or exercise. Consulting a doctor is key.

 

Final Thoughts

 

While shows promise as a supplement to potentially combat certain aspects of aging by increasing NAD+ levels, available human evidence is currently insufficient to confirm these purported benefits or guarantee NMN as a safe, effective anti-aging intervention. Preliminary data warrants further robust, rigorous study to define optimal dosing, validate actual impacts on age-related decline and disease, fully characterize safety, and identify who may benefit most. Patients should approach claims of reversing aging or dramatic cognitive and performance benefits with skepticism until such clinically relevant outcomes are demonstrated in human trials. Consultation with a healthcare practitioner is advised to weigh potential risks and benefits on an individual basis, especially if taking medications or with a pre-existing health condition. While an interesting molecule, more research is critical to elucidate NMN’s effects in humans before this nicotinamide mononucleotide can be recommended as a true anti-aging panacea.

 

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References:

 

1. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.

2. Mills KF et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795-806.

3. Airhart SE 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.

4. Offman E, Rauh A, Coffman K. Nicotinamide mononucleotide: Exploring the expanding therapeutic potential with a focus on aging and longevity. Yale J Biol Med. 2021;94(2):295-307.

5. Katsyuba E, Auwerx J. Modulating NAD+ metabolism, from bench to bedside. EMBO J. 2017;36(18):2670-2683.

6. Frederick DW et al. Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle. Cell Metab. 2016;24(2):269-282.

7. Airhart SE 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.

8. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide Mononucleotide, a Key NAD(+) Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metab. 2011;14(4):528-536.

9. Hou Y, et al. NAD+ supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci U S A. 2018;115(8):E1876-E1885.

10. Tarantini S et al. Nicotinamide riboside ameliorates cognitive defects and amyloid pathology in Alzheimer's disease mouse models. Aging (Albany NY). 2019;11(16):6116-6131.

11. Fang EF. Mitochondrial nutrients in preventing and treating cognitive decline. Adv Exp Med Biol. 2019;1167:117-130.

12. Cantó C, et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838-847.

13. Stout MB, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2017;13:274-282.

14. Elhassan YS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6.

15. Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286.

16. Khodadadi S, Sobhani N, Mirshekar S, et al. disease cells growth and survival time with the overexpression of nicotinamide mononucleotide adenylyltransferase and consumption of nicotinamide mononucleotide and nicotinamide riboside. Biomed Pharmacother. 2018;103:98-104.

17. Zhang P, et al. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Front Cell Dev Biol. 2020;8:246.

18. Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286.

19. Conze DB, et al. The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson's Disease. Cell Rep. 2019;29(9):2976-2988.e6.

20. Zhang H, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-1443.

21. Johnson S, Imai SI. NAD+ biosynthesis, aging, and disease. F1000Res. 2018;7:132.

22. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.

23. Fang EF, Lautrup S, Hou Y, et al. NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. 2017;23(10):899-916.