NMN controversy and exploration
In the field of biomedicine, β-nicotinamide mononucleotide (NMN) has attracted much attention in recent years as a potential anti-aging and energy metabolism compound.
Its accompanying “constant controversy” has also caused widespread concern and discussion.
Faced with this background, we can’t help but ask: Is NMN really trustworthy?
On October 1, 2024, Mianyang Central Hospital, Wuhan University School of Nursing and University of Electronic Science and Technology of China and other institutions jointly published a comprehensive review of NMN (β-nicotinamide mononucleotide) in the journal Frontiers in Pharmacology.
This review integrates domestic and foreign NMN research data up to May 20, 2024, and deeply analyzes the characteristics, metabolic pathways, pharmacological effects and progress of NMN in human clinical trials, drug development and food applications.
Studies have pointed out that NMN has a potential role in anti-aging and promoting energy metabolism, and has shown certain safety and effectiveness in clinical trials.
The application prospect of NMN in the field of medicine and functional food is also concerned.
Overview of NMN features
NMN (β-nicotinamide mononucleotide), as an active isomer of nicotinamide mononucleotide, plays an important role in the field of biochemistry.
There are two isomers of niacinamide mononucleotides, α and β, of which only β is biologically active.
The chemical formula of NMN is accurately expressed as C11H15N2O8P, and its molecular structure is composed of three core parts: nicotinamide base, ribose and phosphate group.
This unique molecular structure gives NMN its unique biochemical properties.
From a physical point of view, NMN presents a white to slightly yellow crystalline powder, and does not have a significant odor.
To ensure its stability, NMN should be stored in a dry, light-free environment and maintained at a low temperature of -20°C.
Its melting point is about 166°C, which provides an important reference for the purification and processing of NMN.
In terms of solubility, NMN shows good solubility to water and can be quickly dissolved in water, but the solubility in acetone is very low.
This characteristic makes it necessary to pay special attention to the choice of solvent during the preparation and application of NMN.
NMN’s pH is typically maintained in the 3.0 to 4.0 range, an acidic environment that helps maintain the stability of its molecules.
It is worth noting that NMN, as a naturally active nucleotide, is an inherent component of the human body and is distributed in a variety of fruits and vegetables.
This discovery not only reveals the widespread existence of NMN in nature, but also provides a broad prospect for its application in the biomedical field.
NMN is involved in metabolism
NMN (β-nicotinamide mononucleotide) is a metabolic intermediate of the key coenzyme NAD+ (nicotinamide adenine dinucleotide) in the body.
As an indispensable coenzyme in the human body, NAD+ is involved in the regulation of thousands of biochemical reactions in the cell and is crucial for sustaining life activities.
As a result of aging and other factors, the level of NAD+ in the body gradually decreases, which can lead to a range of health problems.
The body mainly replenished about 85% of NAD+ through the Salvage Pathway, in which NMN plays a central role.
The in vivo synthesis of NMN also involves the Denovo pathway and the Preiss-Handler pathway, which together ensure a stable supply of NAD+ in vivo to support its diverse and important physiological functions.
It is worth noting that NMN, as a naturally active nucleotide, is an inherent component of the human body and is distributed in a variety of fruits and vegetables.
This discovery not only reveals the widespread existence of NMN in nature, but also provides a broad prospect for its application in the biomedical field.
NMN and health function and effect analysis
Anti-aging effect
Aging is a complex natural process, accompanied by the gradual depletion of NAD+ (nicotinamide adenine dinucleotide), the energy production of organ mitochondria is correspondingly reduced.
NAD+ plays a central role in cellular energy metabolism and repair mechanisms, and decreased levels can weaken mitochondrial function and accelerate the aging process.
Typical signs of aging include mitochondrial dysfunction, cumulative DNA damage, cognitive decline, osteoporosis, and decreased immune function.
NAD+ supplementation is seen as one of the effective strategies to alleviate these aging symptoms.
Studies have shown that NAD+ precursor substances, such as NMN (beta-nicotinamide mononucleotide) and NR (nicotinamide ribose), can maintain the number of melanocyte stem cells and enhance their function, thereby extending lifespan in mouse models, providing a new perspective for anti-aging scientific research.
The research of NMN in the field of anti-aging also faces some limitations and controversies.
The purity and content of different brands of NMN products are significantly different, which leads to the inconsistency between the research results, and there is still a lack of uniform dose standards.
The long-term safety and efficacy of NMN have not been fully validated, especially for the potential risks that may exist when used in large doses.
More importantly, in view of the complexity of the aging process, it is difficult to rely solely on NMN to fully cope with the challenges brought by aging, and it is also necessary to combine healthy diet, moderate physical exercise and good living habits to comprehensively improve the anti-aging effect.
Improve glycolipid metabolism
Type 2 diabetes has become a widespread metabolic health challenge in the world. One of its core features is insulin resistance caused by increased oxidative stress, inflammatory response and lipid metabolism disorder.
When the function of pancreatic beta cells is impaired or insulin secretion is insufficient, insulin deficiency will lead to type 2 diabetes.
Pancreatic beta cells are particularly sensitive to changes in NAD+ (nicotinamide adenine dinucleotide) concentration.
Decreased levels of NAD+ interfere with beta cell metabolism and reduce insulin production, thereby increasing the risk of diabetes.
Studies have shown that NMN (β-nicotinamide mononucleotide) can effectively promote insulin release and improve the sensitivity of peripheral tissues to insulin, and is an effective means to treat diabetes, improve glucose tolerance and insulin sensitivity.
NMN can also regulate fat metabolism, promote fat decomposition and oxidation, and reduce the resistance of fat to insulin.
Long-term intake of NMN can increase NAD+ concentration, optimize mitochondrial energy metabolism, reduce fat accumulation, and help maintain healthy weight.
Improve neurological diseases
The research of NMN in the field of anti-aging also faces some limitations and controversies.
The purity and content of different brands of NMN products are significantly different, which leads to the inconsistency between the research results, and there is still a lack of uniform dose standards.
The long-term safety and efficacy of NMN have not been fully validated, especially for the potential risks that may exist when used in large doses.
More importantly, in view of the complexity of the aging process, it is difficult to rely solely on NMN to fully cope with the challenges brought by aging, and it is also necessary to combine healthy diet, moderate physical exercise and good living habits to comprehensively improve the anti-aging effect.
Alzheimer’s Disease (AD)
In Alzheimer’s disease (AD), amyloid beta (Aβ) is the core pathogenic factor, and the abnormal accumulation of its oligomers in the brain leads to neuronal dysfunction and death, leading to memory loss, cognitive impairment and other symptoms.
Studies have shown that NMN (β-nicotinamide mononucleotide) improves cognitive function and restores NAD+ and ATP levels in AD model rats by enhancing neuron survival, optimizing energy metabolism and reducing reactive oxygen species (ROS) accumulation.
Further studies have shown that NMN can inhibit the production of Aβ in AD mice, reduce amyloid plaque load, synaptic damage and inflammatory response, and thus improve their behavior and cognitive impairment.
These findings reveal the great potential of NMN in the treatment of Alzheimer’s disease.
Parkinson’s Disease (PD)
PD is a chronic neurological disease characterized by motor dysfunction caused by degeneration of dopaminergic neurons in the substantia nigra.
Dopamine synthesis depends on NAD+.
Studies have shown that NMN (β-nicotinamide mononucleotide) can reduce the apoptosis of PD cells, improve energy metabolism, and increase the levels of NAD+ and ATP.
NMN enhanced the activity of NMNAT in PD cells, decreased the content of malondialdehyde and lactate dehydrogenase, and activated SIRT1, providing a new strategy for PD treatment.
Matters needing attention
It is important to note that although NMN is thought to improve neural function by raising NAD+ levels, the exact mechanism is not fully understood.
The efficacy of NMN in neurological diseases reported by different studies varies, which may be related to factors such as study design, sample size, and disease type.
Anti-vascular disease effect
Vascular dysfunction refers to the abnormal function of blood vessels and nerves, which is not caused by organ injury.
Studies have shown that NMN can reduce vascular oxidative stress, improve arteriosclerosis and dysfunction, reduce collagen and increase elastin, and delay arterial aging.
NAD+ is essential for heart energy metabolism, and low levels can cause insufficient energy supply to the heart muscle.
In mice with cardiomyopathy, NMN injection increased the level of NAD+ in cardiac mitochondria, activated SIRT3 enzyme, and improved cardiac function and energy metabolism.
NMN has a positive effect on cerebral hemorrhage, alleviating cerebral edema, cell death and oxidative stress, and improving its symptoms.
Therapeutic effects of visual degenerative diseases
There are many causes of visual impairment, and photoreceptor cell death is a common cause of blindness.
Studies have shown that early NAD+ deficiency in a mouse model of retinal dysfunction affects metabolism and SIRT3 activity, leading to photoreceptor death.
Supplementation of NMN can restore metabolic function, reduce photoreceptor cell death, and significantly improve vision, which is expected to be an effective treatment for retinal degenerative diseases and a therapeutic target for eye diseases.
Acute kidney injury and acute lung injury
Acute kidney injury and lung injury are highly lethal diseases.
SIRT1 and NAD+ levels decrease with age, increasing the risk of acute kidney injury.
NMN preconditioning was effective against kidney injury in cisplatin induced mouse models.
NMN protects the lung injury induced by sepsis in mice, up-regulates the expression of SIRT1, inhibits the acetylation and phosphorylation of NF-κB-p65, and reduces the MPO level in lung tissue by increasing the levels of NAD+ and ATP.
Studies have shown that NMN promotes macrophage polarization through the SIRT1/NF-κB pathway and may be a preventive and therapeutic strategy for acute lung injury induced by sepsis.
Sum up
NMN shows unprecedented potential and value, easily overcoming current limitations and challenges.
Its unique nature has had a profound and significant impact on the pharmaceutical industry.
As research continues to deepen, we have a clearer understanding of the mechanisms and applications of NMN, which makes it highly likely to play a pivotal role in drug development and health management.
The versatility of NMN in treating various diseases and improving overall health will bring unlimited possibilities for scientific research and human healthy life, making our lives better.
