NMN US market update

The US Food and Drug Administration (FDA) has issued a new attitude towards the regulation of NMN, announcing that it will not restrict the sale of NMN for the time being, and will issue an updated ruling on the petition of the NPA (Natural Products Association) by July 31, 2025.

The Natural Products Association (NPA) argues that it should continue to be legally marketed as a dietary supplement.

This news tentatively confirms that NMN can continue to be sold in the US market without direct intervention by the FDA, which will be positive news for manufacturers, retailers and consumers worldwide.

The outcome of the NPA lawsuit is not only about the future of NMN as a dietary supplement, it could also have far-reaching implications for the entire pharmaceutical and natural products industry.

What is NMN?

NMN, full name: β-nicotinamide mononucleotide, is a naturally occurring bioactive nucleotide.

Nicotinamide adenine dinucleotide (NAD+) is a key intracellular cofactor, widely involved in regulating important biological processes such as energy metabolism, oxidative damage and inflammatory response. NAD+ levels in vivo gradually decrease with the increase of age, and NAD+ levels are closely related to many problems related to aging.

As a precursor of NAD+, NMN can effectively increase the level of NAD+ in the body, and help to slow down the aging process and reduce the risk of various diseases related to aging, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases.

The efficacy of NMN

1. anti-aging

Senescence is the process by which cells irreversibly stop dividing and enter a permanent state of growth arrest without undergoing cell death, while unrepaired DNA damage or other cellular stress can induce senescence.

FIG. | 12 features of aging: loss of genomic stability, telomere depletion, epigenetic changes, loss of protein homeostasis, dysfunction of macroautophagy, dystrophic sensitivity, mitochondrial dysfunction, cellular senescence, stem cell depletion, altered intercellular communication, chronic inflammation, and dysbiosis.

With the increase of age, the level of NAD+ in the body will continue to decline, and at the same time, the DNA in the cell and the energy factory mitochondria will gradually accumulate damage, and the accumulation of DNA damage will also lead to the decline of the synthesis ability of NAD+ in the body, resulting in a series of age-related diseases.

Previous studies have shown that supplementation of NAD+ preforms, such as niacin (NA), niacinamide mononucleotide (NMN) and niacinamide riboside (NR), can significantly improve the level of NAD+ in vivo, of which NMN has the highest conversion efficiency.

2. Anti-cardiovascular disease

Cardiovascular diseases are the leading causes of death worldwide and include: coronary heart disease, cerebrovascular disease, peripheral artery disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis and pulmonary embolism.

The cardiovascular system is made up of the heart and blood vessels and is essential for sustaining life.

The cardiovascular system circulates blood throughout the body, delivering oxygen and nutrients to tissues while removing waste products.

The heart is a muscular organ that pumps blood through a vast network of arteries, veins and capillaries.

Previous studies have shown that NMN supplementation is beneficial for cardiovascular health.

Increasing NAD+ levels improves endothelial function, reduces oxidative stress, and enhances overall vascular health.

Increasing NAD+ levels can lead to better blood pressure management and reduce the risk of atherosclerosis, improving endothelial function and reducing oxidative stress are essential for maintaining a healthy cardiovascular system.

3. Improve glycolipid metabolism

Diabetes, hyperlipidemia, fatty liver…… In modern life, many people suffer from diseases related to glucose and lipid metabolism.

The reason is that the body’s sugar and lipid metabolism disorders.

Obesity is likely to cause multi-organ insulin resistance and chronic inflammation. Obesity and its related metabolic disorders are closely related to the occurrence of diseases such as type 2 diabetes mellitus, non-alcoholic fatty liver disease and atherosclerosis.

A number of studies have reported that exogenous NMN supplementation can improve the metabolic function of the body and improve the symptoms of obesity and related metabolic disorders.

Metabolic processes of NMN, NRK: nicotinamide ribokinase; NMNAT: nicotinamide mononucleotide adenosine transferase; NAMPT: Nicotinamide phosphoribosyl transferase

4. Improve neurological diseases

In recent years, with the increasing burden of aging of the global population, the occurrence of neurological diseases has gradually intensified, and the neurological diseases such as Alzheimer’s disease (AD), multiple sclerosis, spinal cord injury and Parkinson’s disease (PD) have not yet found specific drugs.

As an important precursor of NAD+, NMN promotes the hydrogen transfer effect of NAD+ in biological processes by increasing the level of NAD+ in the body, thus promoting the synthesis of proteins and polysaccharides, improving the efficiency of substance transport and regulation, and improving metabolic function, especially in nervous system diseases. NMN can play a neuroprotective role through antioxidant, anti-inflammatory, mitochondrial protection, and prevention of neuronal and axonal degeneration.

5. Improve vision

As we age, the function of the retina begins to decline. When the function of the retina deteriorates, a range of eye diseases can occur.

Vision impairment can seriously affect quality of life, causing depression and anxiety, difficulty walking, and an increased risk of falls and fractures.

NMN has been shown to protect the eye from retinal damage caused by light.

High IOP can cause retinal ischemia/reperfusion injury (I/R injury), and NMN can improve the I/R injury and protect the health of the retina.

Who is suitable for NMN supplementation?

1. Middle-aged and elderly people:

As people age, the level of NAD+ in the body gradually decreases, leading to a decline in cell function and aging.

As a precursor of NAD+, NMN can increase the level of NAD+, thus activating longevity protein Sirtuins, improving mitochondrial function and delaying aging.

2. Patients with neurodegenerative diseases:

Diseases such as Parkinson’s disease and Alzheimer’s disease are often accompanied by brain cell death and increased oxidative stress.

NMN has the function of repairing DNA and protecting the nervous system, and can reduce brain cell death and oxidative stress, thus improving cognitive impairment and restoring cognitive ability.

3. Sub-healthy population:

With the fast pace of modern life and high pressure, many people are in a sub-health state, manifested as chronic fatigue, poor sleep, and decreased vision.

NMN can improve mitochondrial function, increase energy metabolism level, and help to alleviate sub-health symptoms and improve physical fitness.

4. Obese people:

Obesity not only affects the appearance, but also may lead to a variety of diseases, such as cardiovascular disease, diabetes and so on.

NMN can improve insulin sensitivity, help control blood sugar levels, and improve weight and health in obese people.

5. Athletes or people who regularly engage in high intensity exercise:

NMN may help relieve muscle damage and fatigue and promote post-exercise recovery.

At the same time, pregnant women and nursing mothers, people with serious diseases such as heart disease, liver disease, tumors, kidney disease, etc., younger people (especially under the age of 25), are taking prescription drugs or other herbal medicines, and other people are not appropriate to take NMN.

Sum up

In 2013, a team of scientists from Harvard Medical School discovered NMN and published it in the journal Cell and confirmed that NAD+ precursor NMN can reverse aging and prolong life, thus opening the situation of NMN in the field of aging intervention and prevention and treatment of age-related diseases.

Up to now, hundreds of NMN and NAD+ related research reports have been published in authoritative international journals such as Nature, Science and Cell, confirming the significant effects of NMN in the fields of delaying aging, repairing DNA damage, regulating metabolism and protecting the heart.

The change in the regulatory attitude of the US FDA to NMN (will not limit the sale of NMN for the time being) is bound to drive the vigorous development of NMN in medical health and usher in a new wave of development.

References:

[1] Hallmarks of aging: An expanding universe https://www.sciencedirect.com/science/article/pii/S0092867422013770
[2] Liu Youshuo, Zhan Junkun, Wang Jianye, et al. Consensus of Chinese geriatrics experts on anti-aging drug Intervention (2024) [J]. Chinese Journal of Geriatrics, 2024, 43(2) : 148-161. (in Chinese) DOI: 10.3760/cma.j.issn.0254-9026.2024.02.002.
[3]The versatile multi-functional substance NMN: its unique characteristics, metabolic properties, pharmacodynamic effects, clinical trials, and diverse applications
[4]Effect of NMN on obesity and its related metabolic disorders
[5] Zhang C J, Li Y, Yu Y, et al. Research progress on the role of niacinamide mononucleotide in central nervous system diseases [J]. Chinese Journal of Neuromedicine, 2023, 22(9) : 947-952. DOI: 10.3760/cma.j.cn115354-20230210-00067.
[6]Lee, D., Tomita, Y., Miwa, Y., Shinojima, A., Ban, N., Yamaguchi, S., … & Kurihara, T. (2022). Nicotinamide Mononucleotide Prevents Retinal Dysfunction in a Mouse Model of Retinal Ischemia/Reperfusion Injury. International Journal of Molecular Sciences, 23(19), 11228.