Without one little energy molecule called ATP, life as we know it would not exist, and without NAD, there would be no ATP. New scientific studies indicate NMN may extend a person’s healthspan, the period of life spent in good health. Is this really a miracle drug? 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, specifically, its NAD+ form, naturally decrease with age in many tissues. And so, NAD earned its reputation as a fountain of youth [1].

nicotinamide mononucleotide
Fig. Source https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515

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; it is then 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].

Our bodies use NMN to make NAD, one of the major drivers of energy metabolism. NMN readily crosses from the gut to the blood, but we get only trace amounts of it from food.

Snapshot

PROs

  • Slows aging in animals
  • May improve diabetes & metabolic syndrome
  • May support kidney health
  • May improve blood flow
  • More stable than nicotinamide riboside (NR)
  • No observed side effects

CONs

  • Not well studied in humans
  • Very expensive
  • Oral form may not be bioavailable
  • May promote tumor growth

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. So, is NMN the fountain of youth or an anti-aging fad [1]?

1) May Slow the Aging Process

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].

nicotinamide mononucleosis
Fig. Source https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/

Telomere Length

Telomeres are long “tails” of repeating DNA code at the ends of chromosomes. They act as a protective buffer that allows chromosomes to divide without damage or loss of information.

Every time a chromosome duplicates itself, it loses some of its telomere; thus, as an organism ages, telomeres shorten. Eventually, with telomere loss, cell division stops altogether, leading to cell death [5].

NMN increases telomere length in mouse liver cells. If this result can be reproduced in animal and human studies, then NMN will have proven itself a true anti-aging supplement [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 are present in almost all species on Earth, from yeast to humans, which speaks to their importance for sustaining life. They 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].

NMN may slow the aging process by extending telomeres and activating sirtuins. However, to date, this has only been demonstrated only in mouse and cellular studies.

2) May Improve Diabetes

NMN oral supplementation in mice effectively treats age- and diet-related diabetes in mice. 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) May Improve 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. Interestingly, younger mice did not benefit; older mice were simply restored to a “younger” health profile [10].

Mice consuming NMN for about half their lifespan had lower weight and better energy metabolism, fat profile, and eyesight.

4) May Support Kidney Health

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) May Improve Cardiovascular 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].

In mice, NMN improves blood flow to the muscles and brain by promoting the growth of new capillaries and helps repair existing ones.

6) May Prevent 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].

However, 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].

In mice with Alzheimer’s disease, NMN can cross the blood-brain-barrier, improve memory, and reduce β-amyloid plaques.

Nicotinamide Riboside vs. Nicotinamide Mononucleotide

Nicotinamide riboside (NR) is another intermediate in the biosynthesis of NAD. Unlike NAD, NR is highly available in the diet, predominantly in cow’s milk, and is more readily taken up by cells than NMN [17, 18].

Chemically, NR is an NMN molecule lacking a phosphate group.

NR and NMN
NR(left) and NMN (right) from Wikimedia Commons

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 [19, 20].

Completed studies have confirmed that NR is safe and increases NAD+ in humans [21, 22].

More than 20 clinical studies are underway evaluating specific health benefits of NR across a spectrum of health conditions [23].

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 [21, 19].

NAD is needed most inside the cells and tissues. Because NR is physically smaller, it may also enter cells more easily than NMN… but it doesn’t enter them more specifically.

Unlike NR, NMN docks to a special protein on the cell surface to cross the membrane. This protein, known as Slc12a8, is expressed on the surface of cells in the small intestine and pancreas. It is like an exclusive access door for NMN to gain entry to cells [2].

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, and human studies are lacking, especially for NMN. 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

Safety

NR is generally recognized as safe by the FDA. NMN hasn’t been evaluated yet, although it is already on the market [24].

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 [25, 26].

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. Since laboratory mice only live for about 2 years, this is equivalent to giving a drug to a person for half of their life [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. Meanwhile, 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, 27].

However, in Sinclair’s study, NMN’s effect on angiogenesis – the birth 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, 28].

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.

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. And despite promising results, no studies to date of the efficacy of NMN have been completed in humans.

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 [29, 30].

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

Dosage & Supplement Forms

Dosage

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 and studies are only on the order of 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 [25].

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 gram of resveratrol mixed with his morning yogurt.

Supplement Forms

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.

NMN is present in some fruits and vegetables but only in trace amounts: less than 2 mg/kg [32].

User Reviews

Due to the recent introduction of commercially-available NMN supplements, there are not yet many independent reviews of its efficacy.

As mentioned earlier, David Sinclair (who has a vested interest in promoting the supplements) vouches for their benefits towards his own good health. Sinclair, who is 49, has been taking 1 g of NMN per day for 3 years and boasts to have the lung capacity, cholesterol, and blood pressure of a “young adult” and the “heart rate of an athlete.”

There is a cost, however: a one-time purchase of 10 g of NMN from RevGenetics comes with a hefty price-tag of $195 USD. Sinclair’s habit would cost the average consumer $19.50 per day, plus tax.

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Takeaway

Nicotinamide mononucleotide (NMN) is a precursor to NAD with reported anti-aging effects. It may combat oxidative stress and cell damage by activating the sirtuins and extending telomeres. In turn, NMN may improve a host of aging-related brain, heart, and metabolic diseases.

NMN is very similar to nicotinamide riboside (NR), but lacking clinical trials. It can be taken orally as a pill/powder or under the tongue. Clinical studies currently underway are using around 250 mg per day.

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