Nicotinamide mononucleotide (NMN) was recently authorized as an ingredient in a new drug application by the US Food and Drug Administration. Due to this authorization, NMN may soon be limited or unavailable for sale in the US, sparking fears that the same may hold for consumers in Europe, as many had to import NMN from the US.
As the global population ages, interest in longevity has spurred the development of many dietary supplements that may counter the effects of aging. The interest in NMN derives from its importance to metabolic health. NMN is promoted to offer anti-aging benefits by supporting mitochondrial function. Studies in rodents and humans found improved insulin sensitivity, and according to several small human studies, it is relatively safe and well tolerated. However, consumers in the EU report that it is difficult to find NMN for sale through European Union companies and that importing the product from the US is difficult and expensive. Alternatives to NMN include nicotinamide riboside (NR), another compound with similar properties.
How do supplements help reverse the aging process?
To carry on biological functions, maintain cognition, and remain physically active, our internal machinery requires a great deal of energy. To produce this energy, we rely on a complex metabolic pathway within each of our cells called cellular respiration. The mitochondria carry out cellular respiration by creating and breaking chemical bonds to store and release energy. In order to do so, electron transport through complex mitochondrial structures is essential for our bodies to meet the needs of our internal energy “grid.”
Two of the most important components of this electron transport are nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide hydride (NADH). It is thought that the level of NAD+ in our cells and tissues declines with age, and this decline may be associated with various age-related conditions and diseases. Thus, the hypothesis that by boosting the precursor molecules needed to manufacture NAD+ and NADH, we may be able to combat some effects of aging was born. Nicotinamide mononucleotide (NMN) is one precursor to nicotinamide adenine dinucleotide (NAD+). Another NAD+ precursor is nicotinamide riboside (NR).
How much do I need to take?
According to the FDA, approximately 16 mg of niacin (vitamin B3), which is a precursor for NAD+, is required daily for adults. The usage of other NAD+ precursor molecules, such as NR and NMN, could boost the rate of NAD+ synthesis, which may contribute to healthy aging. However, NR and NMN are still under research and are yet to receive recommendations on their safety and daily intake doses. NMN and NR are also naturally available in low quantities in foods such as meat, eggs, dairy, certain vegetables, and milk.
Health benefits of NR
As we age, DNA damage and oxidative stress can impair the mitochondrial functions that we rely on to produce energy. In addition, certain diseases, such as obesity, can contribute to chronic systemic inflammation that is associated with elevated oxidative stress. A recent clinical trial of NR vs. placebo among healthy volunteers aged 70–80 found that oral supplementation did decrease levels of circulating inflammatory cytokines, suggesting a possible anti-inflammatory effect. A literature review of the potential benefits of NR includes cardiovascular health, metabolic and neurodegenerative disorders. It is thought that by increasing the intake of NMN or NR, we can provide essential precursors for NAD+ production, which is necessary for the cellular energy "grid". To put it very simply, propping up our cellular energy supply may allow us to carry out these important mitochondrial functions and repair the cellular damage that may be associated with aging.
Is NR available in Europe?
The European Food Safety Authority (EFSA) had already approved nicotinamide riboside chloride (NRC) (a form of nicotinamide riboside (NR)) as a way to supplement niacin (vitamin B3) in foods. In 2020, Chromadex, Inc. requested the EFSA to extend the approval to include selling the product in meal replacements and drink mixes, as well as for special dietary purposes or as a meal replacement for weight loss. In September 2021, NR was only approved as food for special medical populations (FSMP) and as a total diet replacement for weight control (TDRWC).
As such, NR is only available through medical suppliers. The EFSA declined to approve the compound for meal replacement products or nutritional drink mixes. The EFSA panel concluded that nicotinamide riboside chloride, is as safe as pure nicotinamide, for use in FSMP and TDRWC. The maximum use level of 500 mg of NR per day corresponds to a maximum intake of 210 mg nicotinamide per day.
Other secrets to anti-aging at the cellular level
Calorie restriction (but not malnutrition) has a positive impact on health, which may be related to healthy aging. A recent review summarized that calorie restriction reduces body weight and levels of inflammatory markers, blood lipids, and blood pressure. These effects are associated with a lower prevalence of age-related diseases. Furthermore, a review of studies in animals revealed that calorie restriction is associated with autophagy. Autophagy is a process of cell renewal that is diminshed with age. Regarding the benefits, calorie restriction may be a possible strategy for healthy aging.
Calorie restriction may not be a suitable dietary strategy for everyone. We strongly advise consulting with healthcare professionals, especially if you have underlying health conditions, are taking other medications, or have a history of an eating disorder before incorporating calorie restriction into your routine.
Please be aware that from the fall of 2022 NMN is under an investigation as a potential new drug by the FDA. That puts the legality of the product as a dietary supplement in question. It’s a complicated situation that’s not yet solved. However, it is important to note that since we are not a manufacturer or retailer, we do not take any responsibility for the availability of the product as a dietary supplement after having lost its dietary ingredient status.
Nicotinamide mononucleotide (NMN) currently cannot be marketed as a dietary supplement but may be sold in the US. However, NMN is difficult to be purchased in Europe due to legal regulations.
Another molecule — nicotinamide riboside (NR) — with similar properties and effects as NMN is available for sale in Europe and the US.
Good mitochondrial function is important to cellular repair and healthy aging.
Foods such as meat, eggs, vegetables, and milk can also boost NR and NMN.
- Journal of Advanced Research. Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns.
- Cell Metabolism. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice.
- Endocrine Journal. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men.
- Science. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.
- Nutrients. Nicotinamide Riboside—The Current State of Research and Therapeutic Uses.
- EFSA Journal. Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283.
- The Journal of Nutrition. Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk.
- Cell Reports. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.
- Scientific Reports. Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women.
- Advances in Nutrition. Calorie Restriction as a New Treatment of Inflammatory Diseases