Longevity and NMN Levels
From Ponce de Leon and the Fountain of Youth to “miracle cures” for aging, the search for immortality is as old as humanity. As scientists delve deeper into our genetic code, more information has been revealed about cellular aging and death. While immortality is not possible, we have more ways than ever to delay the impact of aging. Nicotinamide mononucleotide (NMN) may be another key to prolonging life.
If you’re interested in aging and longevity innovations, you may have heard of NMN, which stands for nicotinamide mononucleotide. It’s a molecule your body makes naturally, but some people also take it as a supplement. Scientists, such as Harvard University professor and longevity expert David Sinclair, are currently looking into its promising potential benefits for many different areas of health.
The role of NMN in the body
Nicotinamide mononucleotide (NMN) is a substance made by our bodies that are converted into nicotinamide adenine dinucleotide (NAD+). NAD+ is required by all cells to provide energy and regulate critical survival functions. NAD+ cannot be readily absorbed into the body but must be synthesized from precursors like NMN, tryptophan, and nicotinamide. Unfortunately, over time, NMN and, subsequently, NAD+ levels decline as part of the aging process. People in their mid 40’s often have half the amount of NAD+, than in their 20’s.
NMN supplements, which is a derivative of vitamin B3 (niacin), assist several functions in the body. It is responsible for energy production and metabolism, cell growth, regulation of inflammation and response to oxidative stress, DNA repair, and gene expression.
With age, NMN is not produced at the same capacity as during youth. This age-related decrease in NMN occurs in all organ systems. There are several factors that may contribute to the decline in NMN with aging:
To produce NMN, our body requires an enzyme called nicotinamide phosphoribosyltransferase (NAMPT), which levels and function decline as we age.
Dietary intake of niacin may decrease with age, which may limit the availability of NMN precursors. Though NMN is naturally found in small amounts in fruits and vegetables such as avocados, broccoli, cabbage, edamame, and cucumbers. It is unlikely to be able to boost NAD+ to optimum levels via diet alone, supplementation of NMN is often need. To give you an example, you would need to consume approx. 100 kg of broccoli, just to obtain 250 mg of NMN daily.
UV damage can trigger the enzyme poly ADP-ribose polymerase to repair DNA damage, which consumes large amounts of NAD+ and NMN. UV light is the number one cause of premature skin aging. NMN is a powerful antioxidant that may scavenge up free radicals. Studies suggest that NMN may help reduce free radicals produced by the sun that attack our cells and destroy our collagen and elastin. Collagen and elastin destruction leads to wrinkles and sagging skin.
Luckily, exercise and other lifestyle factors such as calorie restriction can boost the activity of NAMPT and consequently the production of NMN and NAD+ counteracting their age-related decline. Along with direct NMN supplementation, bio wellness and longevity are realistically obtainable.
“NMN, which is a derivative of vitamin B3 (niacin), boosts NAD+ levels within the body, assist several functions in the body. It is responsible for energy production and metabolism, cell growth, regulation of inflammation and response to oxidative stress, DNA repair, and gene expression”
Benefits of increased NAD+ levels
Since taking NMN may help your body produce more NAD+, it’s also important to consider the research behind the benefits of NAD+. Studies investigating NAD+ shed light on its potential benefits:
Increased longevity. In your cells, NAD+ activates a group of proteins called sirtuins, which help repair your DNA. The activity of sirtuins is linked to longevity. NMN increased NAD+ levels may help support cellular repair mechanisms, reduce age-related decline, and promote overall well-being.
Energy Production. Energy decline is a common complaint as we age. NMN may help boost energy levels by stimulating mitochondrial function and promoting efficient energy production, ultimately combating fatigue and increasing vitality.
Protective effects on the brain. NAD+ is thought to modulate the production of a protein that helps guard cells against impairment of mitochondrial function and oxidative stress. These cellular stressors are related to some neurological diseases, including Alzheimer’s disease. NAD+ is crucial to brain function, the brain uses a tremendous amount of energy and low levels of NAD+ affect the brain’s ability to function optimally.
Help reduce heart disease risk. Studies have found that high NAD+ levels in the blood reversed age-related arterial damage, which may help guard against heart disease. Also increased NAD+ has been found to promote the production of nitric oxide, a molecule that plays a crucial role in maintaining blood vessel health. Nitric oxide helps dilate blood vessels, improve blood flow, and reduce the risk of blood clots. By increasing nitric oxide production, may help support cardiovascular health and reduce the risk of other related conditions.
Sleep support. NAD+ plays a vital role in the regulation of the sleep-wake cycle. A healthy circadian rhythm is closely associated with sirtuins, a group of proteins that support cellular health and play a key role in regulating cellular homeostasis. However, sirtuins can only work properly when sufficient amounts of NAD+ are present in the cell.
Support muscles. Research has shown that high blood NAD+ levels helped improve muscle function, strength, and endurance. Oral NMN supplementation can be an efficient NAD+ booster for preventing aging-related muscle dysfunctions in humans.
Insulin sensitivity. NMN increases NAD+ levels that assist with muscle insulin sensitivity, insulin signalling, and remodelling in people with prediabetes, along with assisting insulin resistance.
It may protect against cancer cells. Elevated NAD+ levels may help protect cells against oxidative stress and DNA damage, which are associated with cancer development.
“NMN increased NAD+ levels help to support cellular repair mechanisms, reduce age-related decline, and promote overall well-being. Including energy production, insulin sensitivity, brain & heart support, along with improved muscle function”
But does NMN supplementation actually work?
Research on the effects of NMN supplementation in people is relatively new, but there is a growing number of clinical trials (the gold standard for demonstrating a clinical benefit) that now have been published.
Here we’ll take a look at the clinical human trials, along with the research study links.
A 2023 human trial confirmed that Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects, assisting with insulin resistance and sensitivity. Healthy volunteers received 250 mg of NMN once a day in the morning for 12 weeks, and the plasma concentrations of NMN and NAD+ were measured monthly. Physiological and laboratory tests were performed within 2 h after lunch (at 2 pm) before and during NMN administration.
https://pubmed.ncbi.nlm.nih.gov/37344088/
2023 randomized, double-blind, placebo-controlled trial. Found that NMN reduced arterial stiffness after long-term nicotinamide mononucleotide supplementation. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group.
https://pubmed.ncbi.nlm.nih.gov/36797393/
2023 clinical trial of thirty overweight or obese adults, aged 45 years +/-, supplemented with tablets each containing 500 mg of nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics. Finding found that middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.
https://pubmed.ncbi.nlm.nih.gov/36740954/
A 2022 multi-centre, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Measured the efficacy and safety of NMN supplementation in healthy middle-aged adults, involving daily doses of 300mg, 600mg and 900mg. All 80 participants completed the trial without trial protocol violation. Blood NAD+ concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline. Blood NAD+ concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events, laboratory and clinical measures, were found, and NMN supplementation was well tolerated.
https://pubmed.ncbi.nlm.nih.gov/36482258/
2022 clinical trial regarding if Nicotinamide Mononucleotide is safely metabolized and significantly reduces Blood Triglyceride levels in healthy individuals. This human study showed that a 300mg NMN administration significantly increased blood NAD+ levels without damaging blood cells and significantly reduced blood triglyceride (TG) levels. These findings imply that administration of NMN may lead to the prevention and treatment of diseases associated with increased TG levels, such as fatty liver and diabetes.
https://pubmed.ncbi.nlm.nih.gov/36225528/
A 2022 clinical human study. NMN supplementation elevates blood NAD+ levels and alters muscle function in healthy older men. Participants were administered 250 mg NMN per day for 6 or 12 weeks in a placebo-controlled, randomized, double-blind, parallel-group trial. NMN supplementation was well tolerated and caused no significant deleterious effect. Metabolomic analysis of whole blood samples demonstrated that oral NMN supplementation significantly increased the NAD + and NAD + metabolite concentrations. There were nominally significant improvements in gait speed and performance in the left grip test. Oral NMN supplementation can be an efficient NAD + booster for preventing aging-related muscle dysfunctions in humans.
https://pubmed.ncbi.nlm.nih.gov/35927255/
A 2022 Safety evaluation study of β-nicotinamide mononucleotide (NMN) oral administration in healthy adult men and women. a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of 1250 mg of NMN administered orally once daily for up to 4 weeks in 31 healthy adult men and women aged 20-65 years. Oral administration of NMN did not result in changes exceeding physiological variations in multiple clinical trials, including anthropometry, hematological, biochemical, urine, and body composition analyses. Moreover, no severe adverse events were observed during the study period. Our results indicate that NMN is safe and well-tolerated in healthy adult men and women an oral dose of 1250 mg once daily for up to 4 weeks.
https://pubmed.ncbi.nlm.nih.gov/36002548/
2022 clinical trail showing that Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. A 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signalling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodelling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signalling, and remodelling in women with prediabetes who are overweight or obese.
https://pubmed.ncbi.nlm.nih.gov/33888596/
Another recent 2022 clinical trail, examined the effects of taking NMN on sleep quality in Japanese adults 65 years old or older. Participants in this study received either 250 mg of NMN or a placebo control for 12 weeks. Although taking NMN supplements did not appear to improve sleep quality, the researchers did see improvements in overall drowsiness and muscle responsiveness in the people who received NMN in the afternoon compared with the placebo group or those who took it in the morning.
https://pubmed.ncbi.nlm.nih.gov/35215405/
A 2022 prospective, placebo-controlled, double-blind study. Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance. 14 male participants with diabetes and impaired physical performance, aged 80 years +/-, supplemented with 250mg NMN daily for 24 weeks. Found improved prevalence of frailty and changes in central retinal thickness. NMN was tolerable without any severe adverse events.
https://pubmed.ncbi.nlm.nih.gov/36443648/
A 2021 randomized, double-blind study of Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners. nalysis of covariance of the change from baseline over the 6 week treatment showed that the oxygen uptake (VO2), percentages of maximum oxygen uptake (VO2max), power at first ventilatory threshold, and power at second ventilatory threshold increased to a higher degree in the medium and high dosage groups compared with the control group. NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle.
https://pubmed.ncbi.nlm.nih.gov/34238308/
A 2020 study regarding the effect of oral administration of NMN on clinical parameters and nicotinamide metabolite levels. Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.
https://pubmed.ncbi.nlm.nih.gov/31685720/
For further information, we recommend reading up on Dr David Sinclair, an Australian-American biologist and professor for the Department of Genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biological Mechanisms of Aging. Dr Sinclair is particularly well-known for his work on genes and molecules involved in regulating lifespan and longevity, including the SIRT1 gene and its associated proteins, which regulate cellular processes such as DNA repair, metabolism, and gene expression.
“As you can see, the frequency of human trials in the past year has greatly increased due to public interest and potential therapeutic applications. Along with this, there is a huge resourse of other scientific studies and research papers regarding NAD+ levels, NMN and anti-ageing.”
How can I increase my NMN naturally?
NMN is found naturally in a variety of foods. Some NMN-rich dietary sources.
avocados — 0.36 to 1.60 mg per 100 grams
broccoli — 0.25 to 1.12 mg per 100 grams
cabbage — up to 0.9 mg per 100 grams
tomatoes — 0.26 to 0.30 mg per 100 grams
raw beef — 0.06 to 0.42 mg per 100 grams
Small amounts of NMN are also found in cow’s milk, cucumbers, and edamame. Dietary levels will not compare with those of NMN supplements, but there’s nothing wrong with getting a natural dose from what we eat.
Is NMN safe, and does it have side effects?
NMN is an ideal supplement to increase cellular levels of NAD because it’s well-tolerated, and both human and animal studies have observed it had minimal side effects.
Research in humans has shown that doses of up to 1,200 mg daily are safe to consume.
