NMN stands for nicotinamide mononucleotide, a compound currently being researched for its potential to reduce or reverse age-related health conditions. Studies conducted on cells and animals have shown that increasing NMN levels stimulates NAD+ metabolism. However, the question remains: can NMN supplements for longevity be effective in humans?
Research on NMN and longevity
What is NMN longevity? NMN, short for nicotinamide mononucleotide, is one of the key precursors of nicotinamide adenine dinucleotide (NAD+), an essential enzyme for many vital cellular functions, including metabolism, DNA repair, cell growth, and survival.
Within the body’s cells, NMN is converted into a molecule called NAD+. The human body requires NAD+ for many metabolic processes and energy production. In simple terms, NMN is the raw material, and NAD+ is the refined version that the body can actually use. The amount of NAD+ produced by the body depends on the amount of NMN stored inside.
At specific doses, NMN supplements have been shown to improve insulin sensitivity and cardiovascular function, while also reducing fatigue with minimal side effects. Researchers at Harvard University, along with longevity expert David Sinclair, are currently studying the promising potential benefits of NMN for various aspects of health, including NMN longevity, diabetes, liver disease, brain health, cardiovascular health, exercise, and sleep improvement.
Research on the effects of NMN longevity supplements is still ongoing and requires further study. Below is some basic information about NMN and existing studies on its potential benefits, optimal dosage, side effects, and safety.
Study 1: Effects of NMN on rodents
According to Dr. Samuel Klein at Washington University School of Medicine in St. Louis, USA, in rodents, NMN reduces the harmful effects of age-related NAD+ depletion and significantly improves some metabolic functions. This has led to the marketing of NMN as a longevity supplement worldwide, despite limited data supporting its benefits in humans.
Study 2: Effects of NMN on cells
NAD+ is abundant in mitochondria, cytoplasm, and cell nuclei. It is essential for adding poly-ADP ribose to proteins and the deacetylation activity of sirtuin enzymes, which are crucial for regulating cell development, energy metabolism, stress resistance, inflammation, circadian rhythms, and neurological function.
NAD+ is synthesized from sources including NMN, tryptophan, nicotinic acid, nicotinamide riboside, and nicotinamide. NAD+ precursors are found in small amounts in natural foods such as cow’s milk, vegetables, and meat. These precursors enter cells in different ways: NMN can be transported across the cell membrane by the Slc12a8 transporter, nicotinamide riboside enters the cell via a specific transporter, and nicotinamide diffuses into the cell due to its small size.
The absorption of NAD+ precursors varies among tissues, but age-related NAD+ decline is observed in many tissues. NAD+ levels in human samples are much lower in adults than in infants.
Reduced NAD+ levels are associated with many signs of aging, from wrinkles to metabolic disorders and neurodegenerative diseases. Furthermore, various metabolic interventions that extend lifespan in rodents, such as exercise, caloric restriction, and regular sleep habits, partly increase NAD+ levels, providing additional evidence that stimulating NAD+ metabolism may help extend human lifespan.
Researchers and drug developers are exploring three main approaches to increase NAD+ levels: supplementing NAD+ precursors (primarily NMN and nicotinamide riboside); activating NAD-synthesizing enzymes; and inhibiting NAD+ degradation. While all three strategies show health benefits in rodent models of human diseases, currently only the supplementation of NAD+ precursors is being explored in humans.
Research on NMN’s effects in humans
Recently, researchers have been conducting studies to determine whether the observed effects of NMN in cells and animal models translate to humans.
In 2016, researchers at Keio University School of Medicine launched the first clinical study in the world to assess the safety of NMN for longevity in humans. They found that in ten healthy Japanese men, a single dose of NMN longevity drink (ranging from 100 to 500 mg) was safe and metabolized effectively without causing any significant side effects. The participants fasted overnight before taking the NMN capsules and then drank only water for the next five hours until they underwent physiological tests.
One study examined the effects of 250 mg of NMN longevity drink daily for 10 weeks in postmenopausal women with prediabetes and overweight or obesity. Those taking NMN longevity drink showed improved insulin sensitivity and signaling.
Another recent study looked at the impact of NMN longevity drink on amateur runners during exercise training. In this study, 48 runners aged 27 to 50 took NMN longevity drink supplements at doses of 300, 600, or 1200 mg per day for 6 weeks or received a placebo.
At the end of the 6 weeks, those who took the NMN longevity drink, in addition to their regular exercise, showed increased aerobic capacity compared to the placebo group, with higher doses showing greater increases. The researchers suggested that this could be related to higher oxygen uptake.
A recent study also examined the impact of NMN longevity drink on sleep quality in Japanese adults aged 65 and older. Participants received either 250 mg of NMN longevity drink or a placebo for 12 weeks.
Although the NMN longevity drink did not appear to improve sleep quality, the researchers observed improvements in general drowsiness and muscle response ability in those taking NMN in the afternoon compared to the placebo group or those taking it in the morning.
Study on NMN’s effects on postmenopausal women
Scientists evaluated the metabolic effects of NMN in women over 55. In this small clinical trial, 13 postmenopausal women with prediabetes and overweight or obesity took 250 mg of NMN longevity drink daily for 10 weeks, while 12 others were given a placebo during the same period. The scientists found that, aside from improving insulin sensitivity in muscles, no other metabolic benefits seen in rodent models were observed in humans.
While NMN longevity drink improved muscle glucose uptake in response to insulin, other expected effects from increased insulin sensitivity, such as lower blood sugar, reduced blood pressure, decreased liver fat, and reduced fatigue, were not observed. However, it is still too early to make any clinical recommendations based on the results from this study. NMN longevity needs to be tested on a larger population and for longer periods to determine whether it has anti-aging effects in humans.
These studies did not report any side effects, but the dose of NMN longevity drink tested in humans (up to 500 mg) is much lower than the doses used in rodents (typically around 300 mg per kilogram; for a 75 kg person, this would equate to 22.5 grams).
Health Benefits of NMN
All the cells in your body use NAD+, and thus need its precursor, NMN, to function properly. NAD+ helps cells regulate several essential functions that keep your cells running smoothly, including energy metabolism, DNA repair, and the cell’s stress response. NAD+ naturally declines with age, and thus its precursor NMN also decreases. This may contribute to some of the health impacts we experience during aging.
Because taking NMN can encourage the body to produce more NAD+, it’s important to consider the research behind the benefits of NAD+. Studies investigating NAD+ have uncovered its potential benefits:
- Increasing Lifespan: Inside cells, NAD+ activates a group of proteins called sirtuins, which help repair DNA. Sirtuin activity is linked to lifespan. On the other hand, low NAD+ levels are associated with age-related diseases.
- Neuroprotective Effects: NAD+ is believed to regulate the production of a protein that helps protect cells against mitochondrial dysfunction and oxidative stress, factors involved in several neurological diseases, including Alzheimer’s disease.
- Reducing Cardiovascular Risk: Studies in rodents have found that high NAD+ levels in the blood can reverse age-related arterial damage, potentially helping protect the body against cardiovascular diseases.
- Cancer Protection: Elevated NAD+ levels may help protect cells against oxidative stress and DNA damage, both of which are involved in cancer development.
- Jet Lag Treatment: Research suggests that NAD+ may help regulate the body’s internal clock, potentially aiding in the treatment of jet lag or other circadian rhythm disorders.
- Improving Muscle Function: Studies in aged rodents have shown that high NAD+ levels improve muscle function, strength, and endurance in older rodents.
It’s important to note that these benefits are found for NAD+, not necessarily for NMN. More research is needed on the benefits of NMN and NAD+.
With the potential health benefits of NMN longevity, some experts believe that NMN supplementation could help reverse the effects of aging. Some even claim that NMN is the “fountain of youth,” at least in animal models. Here, we will look more closely at human studies on NMN supplementation, including potential benefits, safety risks, and available data on the most effective dosages.
How to use NMN for better health and longevity
As NMN and NAD+ levels naturally decline with age, many researchers have suggested that NMN supplementation could help address age-related health issues.
NMN is found in many natural foods. Some NMN-rich food sources include:
- 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 chicken or beef: 0.2 to 0.3 mg per 100 grams
While NMN can be found in foods, there are several reasons why you may want to take NMN supplements instead of relying on a diet. First, NMN content in food is relatively low. To achieve a meaningful amount of NMN in your bloodstream, you would need to eat extremely large quantities of these foods, which may not be realistic or effective. Additionally, the absorption of NMN from food sources is quite low. As a result, supplementing with NMN ensures more efficient absorption and higher quantities available for your cells.
References:
- https://www.nature.com/articles/d42473-022-00002-7
- https://www.nmn.com/news/harvard-scientist-david-sinclair-legitimizes-nmns-life-extending-efficacy
- https://www.sciencedirect.com/science/article/pii/S2090123221001491
- https://www.healthline.com/health/nmn-nicotinamide-mononucleotide-benefits-side-effects-and-dosage
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