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NMN belongs to the family of nucleotides, organic molecules found in most of the foods we eat.
As with all nucleotides, NMN is composed of 3 parts: a nitrogenous base, a sugar, and a phosphate group.
While most nucleotides are used to build DNA, NMN is used to make nicotinamide adenine dinucleotide (NAD) and fine-tune energy balance.
The body creates NMN as an intermediate step or “precursor” to NAD. Put simply: higher NMN levels mean higher NAD levels.
NAD increases the body’s main energy currency (ATP), balances the circadian rhythm, and enables hundreds of enzymatic reactions – many of which delay aging. Levels of NAD, especially its NAD+ form, naturally decrease with age in many tissues.
Snapshot
Proponents:
- • Slows aging in animals
- • May improve diabetes & metabolic syndrome
- • May support kidney and heart health
- • More stable than nicotinamide riboside (NR)
- • No observed side effects
Skeptics:
- • Not studied in humans
- • Expensive
- • Oral form may not be bioavailable
- • Long-term safety unknown
Food Sources
Because most human cells cannot directly import NAD, they have to create it from the inside. NMN, on the other hand, can quickly enter cells in the small intestine, liver, pancreas, and fatty tissue. Mice absorb NMN from the small intestine into the bloodstream within 3-5 minutes. Within 15 minutes, NMN is distributed to tissues and converted to NAD.
A small amount of NMN is present in some food sources, including:
- • Edamame (immature soybeans)
- • Broccoli
- • Cucumbers
- • Cabbage
- • Avocados
- • Tomatoes
While NMN can be found in trace amounts in these vegetables, it would be difficult to eat enough of them to effectively boost NAD levels. Our bodies use NMN to make NAD, one of the major drivers of energy metabolism. NMN can be absorbed in the gut, but we get only trace amounts from food.
Potential Benefits of NMN
NAD levels naturally decline with aging; as they do, cells and organs start to function less efficiently. Low NAD levels have been associated with multiple age-related diseases. That said, the research behind the health effects of NMN, in particular, is scarce.
So, is NMN the fountain of youth or just another anti-aging fad?
Animal and Cellular Research (Lacking Evidence)
No clinical evidence supports the use of NMN for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
1) Anti-Aging
Harvard geneticist David Sinclair proposed that increasing NAD will slow down aging and delay age-related disease in humans. Sinclair’s group leads NMN research under the assumption that it can boost NAD levels.
Sinclair even patented an NAD booster, which is currently marketed by Elysium Health. The company was founded in 2014 by Sinclair’s former mentor, MIT biologist Leonard Guarente. They sell products claimed to boost NAD levels.
The figure below depicts the mechanisms by which Sinclair believes NAD levels can be increased in the human body alongside corresponding health benefits.
Telomere Length
Telomeres are long “tails” of repeating DNA code at the ends of chromosomes. Every time a chromosome duplicates itself, it loses some of its telomere; thus, as an organism ages, telomeres shorten, eventually leading to cell death. NMN increased telomere length in mouse liver cells.
Sirtuins
In mice, NMN increases the activity of a family of molecules called the sirtuins, which are involved in a complex anti-aging mechanism that scientists are only beginning to understand. NMN specifically increases SIRT1 (sirtuin 1) gene activity.
Sirtuins combat oxidative stress, DNA damage, and cellular aging. Low sirtuins levels have been linked to aging and aging-related diseases, while high sirtuins enhance fertility in women. NMN might, in theory, slow the aging process by extending telomeres and activating sirtuins. However, to date, this has only been demonstrated in mouse and cellular studies.
2) Diabetes
NMN oral supplementation in mice helped with age- and diet-related diabetes. After a single dose of NMN, mice had increased insulin secretion in response to glucose as well as increased sensitivity to insulin.
3) Metabolic Syndrome
In a mouse study, oral NMN improved several health markers, including weight gain, energy metabolism, physical activity, fat profile, and eyesight.
This was a long-term study: lab mice typically only live for 2 years, and the mice were followed for 1 year. At a high NMN dose (300 mg per kg of body weight per day) mice lost 18% of their body weight with no added exercise.
Interestingly, younger mice did not benefit; older mice were simply restored to a “younger” health profile, which might support the claims about the anti-aging effects of NMN. Mice consuming NMN for about half their lifespan had lower weight and better energy metabolism, fat profile, and eyesight.
4) Kidney Damage
In another study, oral NMN improved kidney function and prevented kidney damage in aging mice. These effects are probably due to increased NAD and SIRT1, which activate anti-aging and anti-inflammatory pathways.
5) Heart Health
In elderly mice, oral NMN restored the elasticity of capillary walls and reversed blood vessel damage caused by age (through SIRT1). These mice had improved blood flow and capillary repair compared to mice that did not receive NMN.
New blood vessels actually sprouted within the elderly mice’s skeletal muscles. After the experiment, their vascular system and endurance were similar to that of young mice.
In a similar and more recent study, elderly mice that received NMN had drastically improved blood flow to their brains. Given that blood flow to the brain is impaired in hypertension, Alzheimer’s disease, and stroke, this result bodes well for NMN’s impact on these diseases.
Friedreich’s Ataxia
One study investigated a mouse model of Friedreich’s Ataxia, a rare genetic heart disease that emerges during childhood. High dose NMN (500 mg per kg of body weight) twice a week for six weeks improved heart muscle strength and function compared to controls]. In mice, NMN improves blood flow to the muscles and brain by promoting the growth of new capillaries and repairing existing ones.
6) Alzheimer’s Disease
NAD levels are decreased in Alzheimer’s Disease. In two mouse studies of Alzheimer’s Disease, both NMN and nicotinamide riboside (NR) decreased neuroinflammation and improved memory, learning, and motor control. SIRT3 gene activity, the loss of which may be correlated with brain tissue degeneration, also increased.
NMN also reduced β-amyloid plaque levels in the brains of diseased mice; NR did not.
The superior performance of NMN may be due to its ability to cross the blood-brain barrier. Note, however, that NMN was injected under the skin, whereas NR was administered by mouth. In mice with Alzheimer’s disease, NMN can cross the blood-brain-barrier, improve memory, and reduce β-amyloid plaques.
Limitations and Caveats
Regardless of Dr. Sinclair’s claims and the general hype around anti-aging supplements, current NMN research is limited to animal studies.
Sinclair’s motives are also questionable: his research helped spur the resveratrol anti-aging fad of the early 2000’s, and he has financial interests in over two dozen companies. In 2004, Sinclair founded a company called Sirtris Pharmaceuticals to promote resveratrol supplements. Four years later, Sirtris was sold to GlaxoSmithKline for $720 million dollars. However, in 2010, Glaxo halted the research on resveratrol (SRT501) after discouraging results and even some side effects in humans.
Finally, the higher manufacturing cost of NMN vs NR presents a potential drawback to customers.
Nicotinamide Riboside vs. Nicotinamide Mononucleotide
Nicotinamide riboside (NR) is another intermediate in the biosynthesis of NAD. Unlike NAD, NR is highly available in diet, predominantly in cow’s milk, and is more readily taken up by cells than NMN.
Chemically, NR is an NMN molecule lacking a phosphate group.
Clinical Studies & Known Effects in Humans
In contrast to NMN, human studies have been completed on NR. NR is currently marketed as a supplement by various companies including Elysium Health, alone or in combination with the antioxidant pterostilbene, a polyphenol found in blueberries. Pterostilbene is closely related to resveratrol, though it is more bioavailable.
Completed studies have confirmed that NR is safe and increases NAD+ in humans.
More than 20 clinical studies are underway evaluating specific health benefits of NR across a spectrum of health conditions.
Tissue & Cell Penetration
NR is not stable in the bloodstream – that is, it breaks down quickly into other compounds – and is not detected in blood plasma in either mice or humans, even after very high doses. NR alone or in combination with pterostilbene increases NAD in the blood, however.
NMN is absorbed and detected in the blood in animals for a short time; it then penetrates into cells and tissues. As such, it might be distributed throughout the body more effectively than NR.
Which One is Better?
It is difficult to determine whether NMN or NR is more effective: they have overlapping roles in boosting NAD and activating sirtuins, but human studies for NMN are lacking. However, several mouse studies have shown clear advantages of NMN over NR. NMN may be absorbed and transported throughout the body more effectively than its close relative, nicotinamide riboside (NR). However, human studies are lacking.
Safety & Side Effects
Keep in mind that the safety profile of NMN is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is not a definite one, and you should consult your doctor about other potential side effects, based on your health condition and possible drug or supplement interactions.
Safety
NR is generally recognized as safe by the FDA. NMN hasn’t been evaluated yet, although it is already on the market.
Several studies are underway to determine the safety of NMN as a nutraceutical in humans. The first Phase I study began in 2016 to assess the safety of NMN and its and time course in the blood. Another large study is evaluating the supplement in a group of 50 older women with high blood glucose, BMI, and blood.
In a long-term study in mice, oral NMN was administered for 1 year at 100 and 300 mg per kg of body weight per day – much higher than the dosage advertised for humans. There were no adverse effects or signs of toxicity.
Cancer Risks
One concern is that, because NMN promotes the growth of new blood vessels, it could also promote angiogenesis and increase blood flow to tumors. In theory, this could cause tumors to grow and resist treatment.
Additionally, certain brain cancers depend on NAD to grow. Therefore, increasing NAD through NMN supplementation could be dangerous in people at risk of these cancers.
However, in Sinclair’s study, NMN’s effect on angiogenesis – the growth of new blood vessels – only restored the elderly mice’s vascular health to that of normal young mice. There were no signs of increased cancer risk in this or other long-term NMN animal studies. More studies should look into its effects on cancer risk, though.
Side Effects
NR and NMN have fewer unfavorable side effects than other NAD precursors. For example, niacin (vitamin B3), the most widely used NAD precursor, causes an array of side effects including niacin flush when taken at high doses. The safety of NMN in humans is unknown. According to animal studies, it causes no adverse effects, even at high doses over a long time.
Dosage & Supplement Forms
Dosage
Because NMN is not approved by the FDA for any condition, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error. Discuss with your doctor if NMN may be useful as a complementary approach in your case and which dose you should take.
In mouse studies, NMN was given through a feeding tube or added directly to the animals’ water at dosages of several hundred mg per kg of body weight per day. This dosage would be impractical for humans: using a common conversion factor, a corresponding dose in a 60 kg adult would easily be greater than 2 grams per day (2,000 mg per day).
Doses in human supplements vary around a few hundred mg per day. For example, in a study of 50 women, the dosage being tested is 125 mg NMN twice daily over 8 weeks.
David Sinclair, who publicly attributes his own youthfulness and good health to the benefits of NMN, reportedly takes 1 gram of NMN daily in combination with 0.5 grams of resveratrol, but his claims should be taken with a grain of salt.
Supplement Forms
NMN supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.
NMN is currently marketed as a pill and in powder form.
Companies selling NMN as a supplement claim that taking it orally is effective in boosting NAD. This claim is based on the discovery of Slc12a8, the protein which helps absorb NMN in the gut.
The company ALIVE BY NATURE markets a sublingual (under the tongue) formulation of NMN that they claim is more likely to be absorbed into the bloodstream.
Untitled Document
Because NMN is not approved by the FDA for any condition, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error. Discuss with your doctor if NMN may be useful as a complementary approach in your case and which dose you should take.
In mouse studies, NMN was given through a feeding tube or added directly to the animals’ water at dosages of several hundred mg per kg of body weight per day. This dosage would be impractical for humans: using a common conversion factor, a corresponding dose in a 60 kg adult would easily be greater than 2 grams per day (2,000 mg per day).
Doses in human supplements vary around a few hundred mg per day. For example, in a study of 50 women, the dosage being tested is 125 mg NMN twice daily over 8 weeks.
David Sinclair, who publicly attributes his own youthfulness and good health to the benefits of NMN, reportedly takes 1 gram of NMN daily in combination with 0.5 grams of resveratrol, but his claims should be taken with a grain of salt. *
How Much NMN Do I Need To Take For It To Be Effective?
Most rodent studies showing NMN’s effectiveness in preventing age-related ailments use dosages of about 300 mg/kg. So, for a 75 kg (about 165 pounds) person, this would equate to 22,500 mg (22.5 g). Given the cost of NMN, this would likely cost over $100 per dose and, if taken once daily, over $35000 per year.
But larger organisms like humans don’t need such high doses to be effective. There is a scientific concept called “volume of distribution” that says rodents like mice need higher substance doses by a factor of 12.3 compared to humans. So, a 300 mg/kg dose in mice would equal a 24.39 mg/kg dose in humans with a 75 kg person needing about 1.829 grams for the same effect. Keep in mind that the 300 mg/kg dose in mice is considered a “huge” dose and that it probably provides more than enough NMN for effectiveness. The question then becomes, “How much NMN does a person need to take for it to have a significant effect?”
A study in mice showed that 100 mg/kg per day mitigated most age-related physiological decline. Based on that dosage, for an average adult weighing 62 kg (about 137 pounds), an optimal dosage would be about 500 mg per day. This calculation is based on dividing the human dosage by a factor of 12.3 to match the rodent “volume of distribution.” In the same manner, larger adults weighing 90 kg should take about 750 mg per day.
What NMN Doses Have Been Used in Human Studies?
A research team from Japan ran a human clinical study testing the safety of oral doses of NMN up to 500 mg and found no alterations in physiological measurements like heart rate or blood pressure. Results from this study support that one NMN dose of up to 500 mg is safe and well-tolerated.
A study from scientists at the Washington University School of Medicine in St. Louis showed that oral 250 mg doses per day of NMN for 10 weeks improves older women’s muscle insulin sensitivity and structure. These findings show that more affordable NMN doses of 250 mg per day can be safe and effective in improving muscle insulin sensitivity.
Another study from the University of Tokyo has shown that 250 mg per day oral doses of NMN for 12 weeks improves muscle function in men over age 65. NMN supplementation improved walking speed, the ability to rise from a chair, and grip strength in the aged men.
In addition, ongoing clinical trials are measuring NMN’s safety with long-term administration for up to 24 weeks with doses ranging from 200 to 300 mg/day. NMN’s efficacy in improving cardiometabolic function, glucose metabolism, and other health parameters are also being tested in middle-aged and elderly people with age-related diseases like high blood pressure, diabetes, obesity, and malnutrition.
How Much Should I Take?
Taking the human and animal studies of efficacy and safety into consideration and calculating optimal NMN doses, the recommended dose that adults between 30 and 60 years old take is 500 mg per day. People over age 65 can safely take 750 mg per day to maximize NMN’s benefits.
How Much NMN Would a Scientist Take?
Harvard professor David Sinclair who studies aging has talked about taking NMN to stay healthy and prevent aging. Dr. Sinclair has said that he takes 1 gram of NMN daily, along with resveratrol, metformin, and aspirin with no adverse effects. *
Note 1: Safety Evaluation for Restorin® NMN, a NAD+ Precursor
Note 2: Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Note 3: Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration
Note 4: Safety evaluation after acute and sub-chronic oral administration of high purity Nicotinamide mononucleotide (NMN-C®) in Sprague-Dawley rats
Note 8: Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects
Note 10: Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women
Note 11: 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
Note 13: Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration
Note 15: Toxicology study profile of Nicotinamide mononucleotide after acute and 90-day sub chronic dosing in Wistar rats and mutagenicity tests