Nicotinamide Mononucleotide (NMN) Uses & Dosage

Nicotinamide mononucleotide (NMN) is advertised as the fountain of youth, based on the anti-aging effect observed in preliminary research. However, there’s no clinical evidence to back up these claims. Is it a miracle drug or just another fad? Read on to learn and discover more.

What is Nicotinamide Mononucleotide (NMN)?

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 [1].

The body creates NMN as an intermediate step or “precursor” to NAD. Put simply: higher NMN levels mean higher NAD levels [1].

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 [1].

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 [2].

A small amount of NMN is present in some food sources, including [3, 4]:

• 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 [4].

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 [1].

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 [1].

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 [1].

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 [5].

NMN increased telomere length in mouse liver cells [5].

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 [6].

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 [7, 8].

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, 9].

3) Metabolic Syndrome

In a mouse study, oral NMN improved several health markers, including weight gain, energy metabolism, physical activity, fat profile, and eyesight [10].

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 [10].

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.

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 [6].

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 [11].

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 [11].

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 [12].

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 [13].

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 [14, 15, 16].

NMN also reduced β-amyloid plaque levels in the brains of diseased mice; NR did not [15].

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 [17].

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 [18, 19].

Finally, the higher manufacturing cost of NMN vs NR presents a potential drawback to customers [17].

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 [17, 20].

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 [21, 22].

Completed studies have confirmed that NR is safe and increases NAD+ in humans [23, 24].

More than 20 clinical studies are underway evaluating specific health benefits of NR across a spectrum of health conditions [25].

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 [23, 21].

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 [2].

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.

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 [26].

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 triglycerides [27, 28].

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 [10].

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 [11, 29].

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 [11].

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 [1, 30].

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) [31].

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 [27].

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 [2].

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.

It’s worth mentioning that a one-time purchase of 10 g of NMN from RevGenetics comes with a hefty price-tag of $195.