Nicotinamide mononucleotide (NMN) is a derivative of vitamin B3 (also called niacin or nicotinic acid). Structurally, NMN consists of a nicotinamide base attached to a ribose sugar and phosphate group. NMN is found throughout the body, including in fluids and tissues, and can be found in a variety of food sources such as fruits, vegetables, and meats.
NMN levels have been linked to a variety of disorders including cancer and cognitive decline.
NMN is one of the main precursors of nicotinamide adenine dinucleotide (NAD+), an important metabolic redox co-enzyme that is also involved in cellular processes including neuroinflammation, DNA repair, and gene expression.
Over 400 enzymes in the body required NAD+ and adequate levels of NAD+ support health benefits throughout the body including the central nervous system and vascular system. NAD+ participates in energy metabolism at nearly every step and is also important for cell survival, regulation of gene transcription, and calcium homeostasis.
NAD+ is consumed by a variety of enzymes, making it necessary to promote synthesis in order to maintain the cellular pool of NAD+.
In addition to the effects of NAD+, the ratio of NAD+ to its reduced form NADH is important for maintaining metabolic homeostasis as it is critical in the synthesis of carbohydrates, proteins, lipids, and nucleotides.
The ratio of NAD+ to NADH is also involved in immune cell function, metabolic pathways, DNA repair, and maintenance, and may be involved in the development of several diseases. Similarly, nicotinamide adenine dinucleotide phosphate (NADPH) helps balance the redox state of cells and tissues by reducing glutathione and reducing reactive oxygen species (ROS).
NMN is Safe and Effective:
Studies are ongoing to determine the optimal dose, efficacy, and safety of NMN. Preclinical studies in animal models indicate that NMN is a safe option for increasing NAD+ levels, and for humans, it may be a safer, more effective option than other niacin derivatives.6-10 NMN is able to increase NAD+ synthesis without unwanted side effects that occur with direct NAD+ administration including fatigue and anxiety.
In healthy adult men and women, a daily oral dose of 1250 mg was safe and well-tolerated for up to 4 weeks. Preclinical models have demonstrated that more is not better when it comes to NMN supplementation.
Consequently, NMN supplementation needs to be targeted to a specific range in order to yield the beneficial effects of supplementation but avoid the detrimental effects that can occur with high-dose supplementation. In a human trial, supplementation at 250mg/day for 10 weeks did not result in any adverse effects but did lead to beneficial changes in body composition, gene expression, and metabolic benefits. Potential side effects of NMN supplementation can include nausea, stomach discomfort, and headaches.
NMN Influence Hallmarks of Aging:
NAD+ levels decline with age throughout the body, which likely contributes to many of the adverse effects of aging and age-associated conditions. Mechanistically, NMN restores NAD+ synthesis, raising levels that allow it to carry out important cellular functions including activating SIRT1 and regulating genes involved in inflammation, oxidative stress, and circadian rhythm. SIRT1 is a member of the Sirtuin family, an important regulator of cellular function, longevity, and age-associated physiological changes. Aging is also marked by DNA damage, however, NAD+ is able to activate an enzyme involved in repairing DNA damage. The ability of NMN to alleviate oxidative stress also helps mitigate some of the natural effects of aging related to oxidative stress.
Maintaining adequate levels of NAD+ is critical to mitochondrial health, an important target for anti-aging interventions. Aging is marked by a decline in energy production in mitochondria throughout the tissues in the body and causes a reduction in the function of mitochondria throughout the body. However, NMN is able to restore NAD+ levels which can reverse these detrimental effects of aging. Furthermore, when communication is interrupted between the mitochondria and nucleus, mitochondrial function quickly declines which contributes to age-associated diseases. NMN is able to restore communication and therefore mitochondrial function, alleviating disturbances that lead to age-related issues.
Much of the existing research on the effectiveness of NMN stems from preclinical models, but the results are promising. NMN can improve neuron function in the brain, boost cognition and memory in animal models of cognitive decline, and prevent age-associated loss of neural stem cells. NMN can also assist in DNA repair, an important pathway to prevent a cell from entering a senescent state, which can contribute to low-grade, chronic inflammation (inflamed aging). It can also improve blood vessel health and integrity and improve mitochondria function in the heart, as well as exert vasoprotective effects including improving endothelium-dependent vasodilation, decreasing oxidative stress, and reducing age-related changes in gene expression. The ability of NMN to reverse age-related vascular changes is likely mediated through its ability to activate sirtuin proteins and microRNAs.
Aging affects many systems in the body, including the reproductive system. The quality of oocytes, the egg before it matures, declines as humans age which limits human fertility. In a preclinical model, increasing NAD+ levels through NMN administration restored the quality of oocytes and improved embryo development and functional fertility in aged mice. The decline in oocyte quality has been attributed to genome instability, reduced mitochondrial bioenergetics, and increased reactive oxygen species – three pathways that NMN is able to target.
Similarly, NMN may be a potential therapeutic treatment for polycystic ovary syndrome (PCOS). PCOS is an endocrine disorder that is closely related to metabolic disturbances such as insulin resistance and obesity. In an animal model, NMN was able to restore NAD+ levels, reduce lipid deposition, and improve other metabolic measures in mice including insulin sensitivity. The ability of NMN to reduce metabolic disturbances may benefit individuals with PCOS by restoring metabolic health and NAD+ levels.
NAD+ is also important for male fertility, although studies are primarily in the pre-clinical stage. Male fertility and sperm quality can be negatively impacted by aging as well as metabolic conditions. Because NMN is able to restore reduced NAD+ levels and promote DNA repair, it may have beneficial effects on sperm quality and count. Additionally, SIRT1 which can be activated by NAD+, is involved in maintaining redox balance in the testes and regulating testosterone production.
NAD+ is critical to healthy energy metabolism. Because NMN can increase NAD+ synthesis, it was tested to determine if the cellular-level benefits extend all the way up to the entire body. So far, clinical studies have confirmed the beneficial effects of NMN on physical activity that were previously found in animal models. A six-week, randomized, double-blind, placebo-controlled study in amateur runners demonstrated that supplementation with NMN resulted in an increase in measures of aerobic capacity including VO2, VO2max, and exercise intensity tolerance in individuals receiving 600mg/day. NMN was able to increase aerobic capacity, possibly by increasing oxygen utilization in skeletal muscle and improving mitochondrial function.
Support Overall Health:
The ability of NMN supplementation to restore NAD+ levels makes it an attractive option for the general population. Additionally, the diverse roles of NAD+ make it crucial to overall health and wellness, making it critical to maintain adequate levels of NAD+. NMN supplementation can lead to increased insulin sensitivity and restore gene expression for genes involved in inflammation, oxidative stress, and circadian rhythm. These three pathways affect thousands of processes throughout the body and can promote health when they are balanced and working properly. Additionally, metabolic disturbances are often due, at least in part, to an increase in oxidative stress, inflammation, and/or impaired lipid metabolism, but NAD+ is able to target all three pathways.
The main pathways through which NMN works include activating SIRT1, reducing oxidative stress, and enhancing cellular energetics and mitochondrial function. NMN functions at the cellular level but its effects are vital to the healthy functioning of organs throughout the body, supporting overall health. Supplementation with NMN has been found to influence some of the pathways involved in aging and metabolic syndrome, and also enhance physical activity.
NMN is available in our office for your convenience, or we can ship it to your home. Retail pricing is $250 for a bottle of 60 vegecaps, 320mg each, a 30-day supply. You take 1 capsule by mouth twice daily for a month. Take a break for a month, then repeat for a month. This anti-aging, mitochondrial-boosting health supplement may help you find your “Fountain of Youth”.
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