NMN Supplementation: Functions and Safety in Health

Table of contents

What is NMN?

Nicotinamide mononucleotide is a biomolecule that naturally occurs in all living organisms. It consists of a ribonucleoside attached to a phosphate group. This molecule is a basic structural unit of RNA. NMN is considered crucial to increase the NAD⁺ levels in the body because it is a direct precursor of NAD⁺.

NAD-nicotinamide adenine dinucleotide is a critically used coenzyme in the normal functioning of cells, it is essential to study how it is synthesized normally from its precursors. The main building blocks used for the synthesis of NAD are tryptophan (an amino acid), nicotinamide (Nam), nicotinic acid (NA) also called niacin, nicotinamide riboside (NR), and NMN. All of these molecules are interestingly different forms of vitamin B3. There are many pathways to produce NAD⁺ in our body. Focusing on NMN, it is made from B vitamins in the body by attaching them to sugar phosphate by the enzyme, NAMPT. Another process is based on NR phosphorylation which also results in the formation of NMN. However, the one with the help of NAMPT is the most crucial step in maintaining the level of NAD⁺ as it is a rate-limiting step. This essentially means that if the concentration of NAMPT is low, it can cause decreased levels of NMN which ultimately results in lower levels of NAD⁺. The levels of NAD⁺ are naturally maintained by calorie restriction as such a state increases the concentration of NAD⁺ in the cells. It is observed that the CR state does not increase the considerable concentration of NAD⁺ inside the cells. In this case, NMN or NAD supplements help a significant deal to retain the balance.

There are different reasons for the drain of NAD⁺ on a cellular level. The major contributing factor of them is the repair process of the damaged DNA. As we age, the metabolic stress increases as a result of which the chromosomes become unstable. To maintain them in an optimized state some special enzymes like sirtuins make use of NAD⁺ as a coenzyme on a large scale. This causes depletion of NAD⁺ in the body. In another important cell organelle- mitochondria, NAD⁺ are used in vital energy generation pathways. That is the reason it is critical to maintain the levels of NAD⁺ in the body. The importance of NMN is that it is more readily absorbed in the body than the NAD itself. This maintains the bioavailability of NMN to be converted into NAD⁺ as the need comes.

In recent years, there has been growing interest in the potential benefits of NMN for human health. Studies show that NMN can improve cognitive function, increase physical performance, and slow the aging process. However, they also note that more research is needed to confirm these findings and to determine the optimal dose and duration of NMN supplementation.

Role of NMN in various Health aspects

Supplements of Nicotinamide mononucleotide (NMN) are instrumental in augmenting metabolic activity and assisting in weight loss by amplifying the NAD+ concentration within our bodies, which tends to decline with advancing age. NAD+ catalyzes metabolic reactions, bolsters energy generation, optimizes mitochondrial operation, and modulates gene expression. NMN aids in the activation of sirtuins, also referred to as the longevity gene, essential for brain functionality, the management of inflammation, and caloric restriction.

Increased weight and a decrease in metabolic rate are frequently interrelated, with inflammation and diminished NAD+ levels interfering with the activity of sirtuins, thus causing obesity. By supplementing NAD+ levels, the function of sirtuins can be enhanced, supporting weight loss without curbing appetite. Rather, it intensifies energy expenditure and oxygen utilization.

In addition to aiding in weight regulation, NMN supplements offer a myriad of other health benefits. They can uphold brain health by restraining the accumulation of beta-amyloid plaques associated with neurological ailments, assist in reproductive health, and foster longevity by alleviating cellular and mitochondrial dysfunction associated with aging.

Improved cognitive function:

Aging causes structural and functional changes in the neurovascular unit, which can lead to vascular cognitive impairment. NAD+ levels decline with age, and this plays a critical role in age-related neurovascular dysfunction. NMN, a key NAD+ intermediate, can restore neurovascular function and improve cognitive function in aged mice. This is likely due to the induction of genes involved in mitochondrial rejuvenation, anti-inflammation, and anti-apoptosis.

In other words, NMN can help to reverse some of the age-related changes in the brain that can lead to cognitive decline.

NMN in Mitochondrial Function

NAD+ is a cofactor for many enzymes that are involved in mitochondrial metabolism. When NAD+ levels are low, these enzymes cannot function properly, which can lead to a decline in mitochondrial function. NAD+ is also a substrate for sirtuins, a family of proteins that play a role in regulating mitochondrial function. When NAD+ levels are low, sirtuins cannot function properly, which can lead to a decline in mitochondrial function.

NAD+ depletion can also lead to an accumulation of damaged mitochondria. Damaged mitochondria can release harmful molecules that can damage other mitochondria, leading to a vicious cycle of mitochondrial dysfunction.

NMN is precursor of NAD+. Hence, it can be replenished through supplementation, which may help to improve mitochondrial function and prevent age-related diseases.

Increased physical performance:

Fatigue is common amongst most people but chronic, severe fatigue is associated with functional impairment and a decreased quality of life.
Nicotinamide mononucleotide (NMN), an intermediate of NAD+ biosynthesis, acts as a source of cellular energy.

Is NMN Safe?

Nicotinamide mononucleotide (NMN) is a supplement that has been shown to increase cellular levels of NAD. NAD is a coenzyme that plays a role in many important cellular processes, including energy production, DNA repair, and cell signaling.

NMN is generally well-tolerated, and both human and animal studies have shown that it has minimal side effects. In fact, research in humans has shown that doses of up to 1,200 mg daily are safe to consume.

NMN Dosage and Side Effects

Dr. David Sinclair consumes 1 gram of nicotinamide mononucleotide (NMN) every morning. Studies have found health benefits with doses as low as 250 mg of NMN per day, up to a maximum of 1,200 mg daily.
There are no side effects of NMN supplements have been found till now.

Is NMN helpful with aging?

Vascular aging is the dysregulation of tiny molecules called microRNAs (miRNAs). These miRNAs play a role in regulating gene expression and have been implicated in the aging process of blood vessels. To investigate the connection between NAD+ depletion and miRNA dysregulation, the researchers conducted a study using aged mice treated with NMN. They compared the miRNA profiles in the blood vessels of these mice with those of young and aged mice that did not receive NMN treatment.

The results of the study showed that the positive effects of NMN treatment on vascular function were associated with changes in miRNA expression in the aged mouse blood vessels. The differentially expressed miRNAs affected by NMN treatment had potential anti-atherogenic effects (protecting against atherosclerosis) and contributed to epigenetic rejuvenation (reversing some age-related changes at the molecular level).

Conclusion

NMN is a safe and well-tolerated supplement that has the potential to offer a variety of health benefits. More research is needed to determine the ideal dose of NMN, but the available data suggest that it is a safe and effective way to increase NAD levels.

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