What You Should Know About NMN: A Short Guide

Nicotinamide mononucleotide (NMN) is a dietary supplement. As a precursor to other important metabolic compounds, NMN is thought to improve mitochondrial function. Studies in animals have found anti-aging benefits, and several small studies in humans suggest it is safe. If it is so important, why is it banned in the United States? Is it legal to ship to my home?

Key takeaways:
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    The dietary supplement nicotinamide mononucleotide (NMN) is sold as a dietary supplement.
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    NMN is thought to support mitochondrial function and improve longevity.
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    NMN is a precursor to NAD+ and NADH which are important to mitochondrial function.
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    Studies in mice are promising, but human trials have been small.
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    FDA rules on drug testing put the status of NMN as a dietary supplement at risk in the future.

The Food and Drug Administration’s recent ruling precluded NMN (nicotinamide mononucleotide) from being included in the definition of a dietary supplement. This effectively bans NMN from being sold as a dietary supplement. The reason NMN was excluded from the definition of a dietary supplement is that it is now authorized by the FDA for investigation as a new drug.

This ruling has caused concern among both suppliers and consumers. However, some supplement industry experts are uncertain about the actual implications of this ruling on the sale of NMN. The FDA may choose not to expend energy enforcing this ruling yet, and exercise what is called “enforcement discretion.”

What is “enforcement discretion”?

The FDA may choose not to enforce the ruling, exercising the same “enforcement discretion” used with N-acetyl-L-cysteine (NAC). Enforcement discretion means the FDA could decline to enforce rules banning the sale of NMN. This enforcement discretion would be applied to products containing NMN which are legally marketed as dietary supplements.

Is NMN still for sale in the US?

At the moment, NMN supplements are available for purchase in the US through online retailers, with no apparent restrictions on shipping.

Is the FDA ban effective outside the US?

The FDA has no authority over other countries, so the agency’s action in the US has no jurisdiction over sales elsewhere.

Why is the FDA interested in regulating NMN?

In rodent studies, obesity and aging were linked to impaired synthesis (creation) of nicotinamide adenine dinucleotide (NAD+). The role of NMN as a precursor to NAD+ prompted interest in whether supplementation might reverse aging. Studies in rodents found improved insulin sensitivity and other age-related physiologic markers. These findings led to the rapid development of NMN dietary supplements for human use to improve metabolic function.

Laboratory studies have also shown promising results in treating mitochondrial dysfunction. However, dietary supplements cannot make claims about preventing disease without clinical trials in humans. This is why NMN is now authorized for investigation by Metro International Biotech as a new drug.

As explained by HealthNews, Metro International asked the FDA to take seriously its rules about NMN qualifying as a dietary supplement to protect the rights of pharmaceutical companies doing human research on the compound with the intent to seek FDA approval to license it as a drug. Approval as a drug product requires extensive testing in humans and heavy financial investment. Pulling NMN off the supplement shelves would allow profits to be recovered by the pharmaceutical companies developing it as a drug.

Why is NMN important to longevity?

Your cells convert food into energy in the form of ATP (adenosine triphosphate) via the process of cellular respiration in the mitochondria. This process of cellular respiration culminates in the electron transport chain. To start the electron transport chain, NAD+ is converted into NADH (NAD plus hydrogen) and ATP, which stores energy like currency for later use.

ATP is also a nucleotide that holds energy in a molecule composed of sugar (ribose) plus adenine and three phosphates. You may recognize adenine as one of the four nucleotide bases of your DNA (Guanine, Cytosine, Adenine, and Thymine). Nucleotides are the basic building blocks of DNA, RNA, and energy transport — important to life-sustaining cell function and growth.

To keep this process of cellular respiration going to produce ATP, a steady supply of NAD+ must be regulated by the electron transport chain. The importance of NMN as a precursor to NAD+ led to the explosion of research into the metabolic pathways used by the mitochondria because they are the engines that power cellular life.

Interestingly, your body can still make energy even when oxygen is not readily available, such as during an intense workout. This anaerobic cycle is also used during fermentation to make the alcohol you drink. The byproduct of fermentation is ethanol. Regardless of the energy cycle, NADH is an important electron donor which keeps the gears of energy production turning.

Getting energy back out of storage

Recall that a molecule of sugar (glucose) is metabolized through the electron transport chain to produce energy in the form of ATP and water.

For your body to get energy back out of its ATP currency, water is combined with ATP. The process of hydrolysis releases one phosphate, transforming it from adenosine triphosphate (ATP) to adenosine diphosphate (ADP).

When you drink ethanol (wine, beer, etc.) one of the first byproducts of metabolism — acetaldehyde — has toxic effects which cause flushing, headaches, nausea and an increased heart rate. In other words, a hangover.

A second phase of metabolism is required to break down acetaldehyde into an inactive compound (acetic acid). Some people have a mutation on the gene which breaks down acetaldehyde making it less efficient and causing the person to feel the effects of alcohol more strongly.

Have any human trials been conducted?

One study among 10 healthy Japanese men was conducted by researchers affiliated with Keio University School of Medicine in Japan. The 10 men received one dose of NMN at 100, 250, or 500 mg and were then followed for 5 hours to measure blood levels of glucose, insulin, white blood cells, and liver enzymes. Eye function and sleep quality were also measured but no changes were detected. Concentrations of NMN metabolites increased over the observation period but no adverse effects such as flushing, nausea, or liver toxicity were noted. Recall these are the effects of acetaldehyde during the metabolism of alcohol — evidence of the cellular machinery at work generating energy and breaking down harmful substances.

Another study of 25 post-menopausal women with prediabetes was carried out in a randomized trial that assigned 13 women to NMN at 250 mg/day and 12 women to a placebo for 10 weeks. This study used MRI imaging as well as muscle biopsies to evaluate the cellular effects of NMN. No adverse events were noted, and no major changes were found in the bloodwork. Muscle NAD+ values did not change but other metabolite levels in the muscle increased suggesting increased NAD+ turnover. Although skeletal muscle insulin sensitivity and remodeling increased, actual muscle strength, recovery, and fatigue did not seem to be affected by NMN supplementation.

Restoring the energy supply chain

Bringing it all together, the complex process of metabolism — allowing the storage and release of energy — is vital to enjoying life. This process moves electrons around in the mitochondria to create the energy which powers your body.

Scientists think that aging may be related to certain biological supply chain problems, and that supplementing NMN as the precursor molecule for NAD+ may help improve mitochondrial function, insulin sensitivity and cell signaling.

The studies conducted on humans so far have been small and of limited duration. The role of the FDA is to oversee human studies in larger and longer trials to estimate what effect NMN supplementation might have. These studies are also important for identifying safety concerns. Some effects might be detected in the short term, but others — such as causing cancer due to changing growth regulation or cell signaling — have yet to be evaluated.

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