NMN (β-Nicotinamide Mononucleotide) is a precursor of NAD⁺ (Nicotinamide Adenine Dinucleotide).
Chemical structure diagram of NMN (β-Nicotinamide Mononucleotide).
So, what exactly is NAD⁺?
NAD⁺ is widely distributed in all human cells and is an essential coenzyme for the body.
NAD⁺ participates in various biological reactions in the human body.
As shown in the diagram, NAD⁺ is involved in metabolism, redox reactions, DNA maintenance and repair, genomic stability, and epigenetic regulation, all of which are critical for maintaining overall health and physiological balance.
Because of its vital role, our body requires a large and constant supply of NAD⁺. Within cells, NAD⁺ is continuously synthesized, broken down, and recycled to maintain stable cellular NAD⁺ levels. However, during the aging process, the balance between NAD⁺ synthesis and breakdown is disrupted—consumption outpaces production, leading to a natural decline in NAD⁺ levels.
Studies have shown that NAD⁺ levels can decline by up to 50% between the ages of 40 and 60, and low NAD⁺ levels are closely associated with many age-related health issues, such as muscle degeneration, cognitive decline, hyperpigmentation, and hair loss—symptoms collectively known as degenerative signs of aging.
Mechanism of Action of NMN
NMN exerts its anti-aging effects by increasing the levels of NAD⁺ in the body.
Studies have shown that supplementing with NMN can effectively elevate NAD⁺ levels, thereby improving cellular energy metabolism and repair capabilities, which are crucial for maintaining cell health and proper function.
At this point, a natural question arises: Since NMN works by boosting NAD⁺ levels to fight aging, why not just directly supplement NAD⁺ instead?
Reasons for Not Supplementing NAD⁺ Directly
-
Large Molecule Size and Low Absorption Efficiency
NAD⁺ is a relatively large molecule, making its absorption efficiency in the intestines quite low when directly supplemented. In contrast, NMN has a smaller molecular size, allowing it to be more easily absorbed through the intestinal epithelial cells and enter the bloodstream efficiently. -
Low Cellular Transport Efficiency
NAD⁺ struggles to cross cell membranes directly and enter the cell interior. Conversely, NMN is transported into cells more effectively, where it is rapidly converted into NAD⁺. This is facilitated by specific transport proteins, such as Slc12a8, which actively transport NMN into cells, thereby boosting intracellular NAD⁺ levels more efficiently. -
Low Stability and High Degradation Rate
NAD⁺ is unstable in the digestive tract and easily degraded before reaching systemic circulation. NMN, however, is relatively more stable and can remain in the body longer, where it is efficiently converted into NAD⁺.
As a result, directly ingesting NAD⁺ may lead to significant breakdown before it enters the bloodstream, greatly reducing its effectiveness.
Effects of NMN
1. Anti-Aging
In 2016, a research team led by Professor Shinichiro Imai from the Washington University School of Medicine conducted a long-term study on mice with oral NMN supplementation. After 12 months of oral NMN administration, the mice were compared to normally aging mice without NMN supplementation. The results showed that orally administered NMN was rapidly converted into NAD⁺ in tissues and effectively eliminated various age-related physiological declines. Moreover, NMN exhibited no toxicity or side effects.
Supplementing with NMN also improves mitochondrial function, increases cellular energy supply, and delays age-related functional decline.
2. Enhanced Metabolism
In 2019, Professor Nina Klimova and her team at the University of Maryland School of Medicine found that intraperitoneal injection of NMN significantly increased mitochondrial NAD⁺ levels in the hippocampus of experimental mice. This led to a rise in ATP levels in brain tissue, thereby enhancing bioenergetic metabolism in the body.
Additionally, NMN supplementation was shown to increase the activity of antioxidant enzymes in mitochondria and reduce the production of reactive oxygen species (ROS), further supporting cellular health and metabolic efficiency.
3. DNA Damage Repair
PARPs (Poly ADP-Ribose Polymerases) are DNA repair enzymes located in the cell nucleus. Under stress conditions, they catalyze DNA repair, and NMN serves as a crucial substrate for PARPs in biological cells.
In 2017, Professor David Sinclair and his team at Harvard Medical School discovered the mechanism by which NAD⁺ participates in DNA damage repair. With aging, NAD⁺ levels gradually decline, and the DNA repair enzyme PARP1 increasingly binds to DBC1 (Deleted in Breast Cancer 1), forming the PARP1-DBC1 complex. This complex hinders PARP1’s ability to repair damaged DNA. By elevating NAD⁺ levels, the formation of the PARP1-DBC1 complex is disrupted, thereby restoring PARP1’s DNA repair activity.
4. Enhancing Vascular Vitality
In 2018, Professor David Sinclair’s team at Harvard Medical School found that aged mice (18 months old) given oral NMN for two months experienced a restoration of capillary number and density to levels seen in young mice. Additionally, their muscle blood perfusion and dissolved oxygen content increased during rest, and the exercise endurance of the aged mice improved by 58% to 80%, with reduced blood lactate levels after exercise.
These findings indicate that NMN can improve vascular function, lower blood pressure, and reduce the risk of cardiovascular diseases.
5. Weight Control
In 2017, Professor Margaret J. Morris and her team at the University of New South Wales Medical School conducted a series of studies on NMN’s role in weight management. They found that in mice with genetic obesity, both NMN supplementation and exercise effectively reduced obesity and improved glucose tolerance and mitochondrial function. However, NMN showed stronger effects than exercise on regulating liver fat metabolism, specifically in enhancing lipolysis (via Hadh) and lipogenesis (via Fasn). NMN injections increased NAD⁺ levels, thereby activating Sirtuins proteins, which further promoted both the breakdown and synthesis of liver fat, contributing to improved metabolic balance.
6. Promoting Brain Health
Risk factors such as diabetes, midlife hypertension, obesity, physical inactivity, and smoking are closely associated with vascular dementia and Alzheimer’s disease. Maintaining neurovascular function is crucial for preventing neurodegenerative diseases.
In 2019, Dr. Tarantini S and his team at the University of Oklahoma Health Sciences Center found that intraperitoneal injection of NMN had a significant protective effect on the brain microvasculature of aging mice. NMN reduced oxidative stress in brain microvascular endothelial cells, improved endothelial function, and restored neurovascular coupling (NVC) responses in the cortices of aging mice, ultimately contributing to better cortical function and potentially lowering the risk of cognitive decline.
7. Improving Insulin Resistance and Preventing Diabetes
Insulin resistance (IR) refers to the decreased sensitivity of target organs to insulin, meaning that normal insulin levels produce lower-than-expected biological effects. Insulin sensitivity is used to describe the severity of insulin resistance—the lower the sensitivity, the less effective each unit of insulin is at regulating glucose metabolism.
Two main causes of type 2 diabetes are:
-
Insufficient insulin secretion.
-
Low insulin sensitivity (high insulin resistance).
In 2016, Dr. Kelly L. Stromsdorfer and colleagues at the Washington University School of Medicine discovered that NAD⁺ levels decline in the adipose tissue of obese and aging mice, which is closely linked to severe insulin resistance in multiple organs. When NMN was added to the drinking water of mice with insulin resistance caused by specific enzyme deficiencies, it reversed insulin resistance and reduced plasma free fatty acid concentrations, suggesting NMN’s significant potential in improving insulin sensitivity and preventing diabetes.
