The Ultimate Guide to NMN Supplements in 2024: the Science about NMN

 Table of Contents:

 

1. What is NMN?

2. What are the sources of NMN?

3. What are the roles of NMN?

• Activation of DNA repair pathways PARPs

• Synthesis of NADP+ against oxidative damage

• Activation of histone deacetylases sirtuins

• Reversal of vascular aging

• Hepatorenal protective effect

• Skeletal muscle anti-aging

• Protecting the damaged heart

 

4. Health benefits of NAD+ precursors

• Regulates the biological clock and slows down biological aging

• Protecting the central nervous system

• Improvement of metabolic syndrome

• Reversal of vascular aging

• Hepatorenal protective effect

• Skeletal muscle anti-aging

• Protecting the damaged heart

5. BalanceGenics PURE NMN

 

 

1. What is NMN?

NMN full name is nicotinamide mononucleotide, or nicotinamide mononucleotide, is a naturally occurring biologically active nucleotide, NMN exists in 2 irregular forms, α and β; the β isomer is the active form of NMN with a molecular weight of 334.221 g/mol.

Figure 1 - Chemical structural formula of NMN

NMN belongs to the category of vitamin B derivatives, which are widely involved in many biochemical reactions in the human body and are closely related to immunity and metabolism.

 

 

2. What are the sources of NMN?

 

NMN is widely distributed in daily food, vegetables such as cauliflower and cabbage, fruits such as avocados and tomatoes, and meat such as raw beef are rich in NMN [1].

NMN can also be synthesised endogenously as shown below:

Figure 2 - Synthesis and conversion of NMN [2].   PNP: purine nucleoside phosphorylase; NRK: nicotinamide riboside kinase;   QPRT: quinolinic acid phosphoribosyltransferase;  NAPRT: nicotinic acid phosphoribosyltransferase; NAMPT: nicotinamide phosphoribosyltransferase;   NMNAT: nicotinamide mononucleotide adenylyltransferase

 

 

3. What are the roles of NMN?

 

NMN is an intermediate of the coenzyme NAD+ and its function is also manifested primarily through NAD+.Increased levels of NAD+ have the following benefits:

 

Activation of DNA repair pathways PARPs

PARPs, whose full name is poly ADP-ribose polymerase, are a class of proteins involved in cellular DNA repair, genome stability and programmed cell death.

PARPs consume a small portion of NAD+ in the normal state of the cell and become the major NAD+ "consumers" in the cell when acute DNA damage occurs. In experimental models, if PARPs are over-activated, they may lead to cellular NAD+ depletion, triggering progressive ATP depletion and eventual cell death.

Other studies have found that high activity of PARPs appears to be associated with long lifespan. Lymphoblastoid cell lines from centenarians have more active PARPs than average, younger individuals (20-70 years old). These phenomena are reminiscent of the damage accumulation doctrine of aging theory, which suggests that the accumulation of DNA damage in the nucleus with age is the main cause of cellular and even organismal aging, and that whoever has a greater capacity for DNA repair is likely to have a longer lifespan.

 

Synthesis of NADP+ against oxidative damage

Normally, about one-tenth of NAD+ is catalytically converted to NADP+ and NADPH by NAD kinase and NADP+-dependent dehydrogenase, and the ratio of these two is important for maintaining the intracellular reducing environment.

The higher NADPH/NADP+ ratio in the cytoplasm and mitochondria of our cells helps to provide reducing equivalents for biosynthetic reactions, as well as maintain the level of glutathione (reduced form), which helps the cells to resist oxidative damage.

In addition, NADPH/NADP+ is involved in lipid synthesis, such as fatty acid chain elongation and cholesterol production. During the immune response, in order to kill pathogens, NADPH can be transformed into a substrate for NADPH oxidase, which is prompted to induce large amounts of ROS to attack the pathogen and fight infection.

Interconversion of NADH/NAD+ and NADPH/NADP+

 

Activation of histone deacetylases sirtuins

One of the most important health effects of increased NAD+ is its involvement in the activation of histone deacetylases sirtuins.

Sirtuins, also known as silencing regulator proteins, have the function of deacetylating chromatin histones and thus silencing genes. In addition to epitope modification of histones, more enzymatic activities of sirtuins have been discovered, and NAD+ is required as a substrate for all enzymatic catalytic effects exerted by sirtuins, so we often regard sirtuins as NAD+-dependent enzymes.

Sirtuins can respond to intracellular NAD+ levels, and thus convert the signal of "NAD+ increase" into several biological activities involving cell damage repair and metabolism regulation, which gives NAD+ enhancers great healthcare and therapeutic potential, including biological clock regulation, neuroprotection, skeletal muscle protection, anti-aging, cardiovascular protection, and anti-aging. Anti-aging, cardiovascular protection, metabolic disorder improvement, liver and kidney function protection, etc.

 

Reversal of vascular aging

Increasing NAD+ levels in the endothelium of aging blood vessels will be a potential therapy that holds promise for the treatment of diseases that develop as a result of reduced blood flow, such as ischaemia-reperfusion injury, slow wound healing, and liver dysfunction.

Because of the relationship between SIRTs and vascular aging, NMN has already demonstrated effects in several studies:

(i) NMN treatment of aged mice (300 mg/kg administered daily for 8 weeks) restored endothelium-dependent dilation of carotid arteries (a measure of endothelial function), increased arterial elasticity, and reduced the level of oxidative stress in aging vessels.

(ii) NMN (500 mg/kg/day in water for 28 days) achieved significant efficacy in mice: it improved blood flow and endurance in aged mice by promoting sirt1-dependent increases in capillary density.

(iii) NMN significantly improved cognition in aged mice by ameliorating age-induced vascular endothelial dysfunction as well as neurovascular coupling (NVC) responses, and NMN reduced mitochondrial ROS and restored NAD+, mitochondrial energy in cerebral microvascular endothelial cells of aged mice.

 

Hepatorenal protective effect

Fatty liver often occurs in middle-aged or elderly people or those with excess visceral fat, and as mentioned earlier, these individuals often have inadequate NAD+ levels.

NAD+ precursors not only improve liver health, but also enhance its regenerative capacity and protect the liver from hepatotoxic damage. Compared to untreated controls, mice that had been treated with NAD+ precursors had increased and more homogeneous liver regeneration, shorter duration of steatosis, increased DNA synthesis, and significantly improved lipid metabolism after partial hepatectomy.

There is also evidence from several studies arguing for the importance of NAD+ for renal function from different perspectives: in rodents, activation of SIRT1 and SIRT3 by NAD+ supplementation protects against high glucose-induced hypertrophy of renal mesangial cells; and treatment of mice with NMN protects against cisplatin-induced acute kidney injury (AKI) via SIRT1.

 

Skeletal muscle anti-aging

Muscle aging is one of the main reasons for the decline of mobility and labor force in the elderly, and muscle aging is also the most easily "perceived" aging.

Compared with young mice, aged mice have atrophied muscles, retarded insulin signaling and reduced glucose uptake by skeletal muscle cells. It was found that treatment of aged mice with NAD+ precursors (e.g., NR and NMN) significantly improved muscle function in aging mice. Treatment of aged mice with NMN for 7 consecutive days resulted in enhanced mitochondrial function, increased ATP production, reduced levels of inflammation, and a gradual conversion of metabolically preferred glycolysis to aerobic oxidation in skeletal muscle, with many unfavorable physiological processes associated with increasing age being reversed.

Muscle stem cells are the tissue cellular reserve of muscle and play a key role when muscle needs to be regenerated. Tissue stem cell senescence is one of the major causes of tissue and even organismal cellular senescence, and NAD+ precursors can significantly delay muscle stem cell aging and maintain their quantity and quality by improving mitochondrial function.

In addition to older individuals, those who are "fat and weak" may also benefit from NAD+ precursors. Studies have shown that mice fed a high-fat diet improved skeletal muscle oxidative metabolism, energy production, muscular endurance, and athletic ability after taking NAD+ precursors.

 

Protecting the damaged heart

Maintaining NAD+ levels to ensure SIRT3 activity is critical for the maintenance of cardiac function, as well as for recovery after cardiac injury, as has been corroborated by numerous rodent studies:

(i) SIRT3-deficient rats develop cardiac fibrosis and cardiac hypertrophy at 13 months of age, which is further exacerbated with age, and the use of NMN reverses this change.

(ii) When NAMPT was overexpressed, or treatment with NMN was, it was able to significantly prevent the area of myocardial infarction caused by cardiac ischemia-reperfusion (about 44% reduction).

(iii) NAD+ precursor treatment improved heart failure and optimized mitochondrial function in mice caused by iron deficiency.

(iv) NAD+ precursor protects and even restores cardiac function to essentially normal levels in a mouse model of Friedreich's ataxia (FRDA) cardiomyopathy through SIRT3 activation.

The evidence suggests that NAD+ precursors might serve as potential agents to ameliorate the adverse outcomes of cardiovascular events.

 

 

4. Health benefits of NAD+ precursors

 

As the body's NAD+ levels tend to decline with age, the demand for the major pathways that deplete NAD+, sirtuins, PARPs, etc., may be stronger in the elderly.

In addition, metabolic syndrome, represented by obesity, and acute neurological, vascular, hepatic, and renal injuries caused by modern people's poor lifestyle habits may also result in NAD+ deficiency and insufficient sirtuins activity.

Therefore, supplementing NAD+ levels in the body through various precursors can prevent and alleviate many aging-related or acute pathophysiological processes.

Negative correlation between age and NAD+ levels in males(first) and females(second)

 

Regulates the biological clock and slows down biological aging

NAMPT, the key enzyme for NAD+ synthesis, is regulated by BMAL1:CLOCK, the core component of the biological clock, and sirtuins, which use NAD+ as a substrate, have a regulatory and modifying effect on BMAL1:CLOCK.

As a result, "NAD+ concentration → sirtuins → biological clock → NAD+ synthesis" forms a feedback loop, in which the concentration of NAD+ and the activity of sirtuins oscillate diurnally along with the biological clock; in turn, interfering with the concentration of these two substances will have an effect on the core component of the biological clock, BMAL1:CLOCK.

NAD+, SIRT1, NAMPT and the biological clock regulate each other

 

A 2014 study found that SIRT1 of the sirtuins protein family is a major player in central biological clock aging (i.e. master clock aging). Insufficient NAD+ levels in the SCN of aged mice, and consequently decreased SIRT1 activity, predispose them to metabolic syndrome, and sleep, exercise, and eating behaviors become disrupted.

By supplementing NAD+ precursors and increasing SIRT1 activity, it can theoretically enhance the circadian rhythm of the body, improve sleep and boost energy.

 

Protecting the central nervous system

SIRT1 has an important regulatory role in normal neuronal development and formation. It promotes neurite growth through inhibition of mTOR, neural axon growth via the Akt-GSK3 pathway, and dendrite shaping through inhibition of ROCK kinase.

The concentration of NAD+, a common substrate of the SIRTs family SIRT1~SIRT7, decreases significantly with age, and the addition of NAD+ precursors to the diet may be beneficial in the prevention and treatment of neurodegenerative disorders, and there are countless animal and cellular experiments of this kind, a few of which are briefly listed below:

-Cognitive performance and synaptic plasticity in a mouse model of Alzheimer's disease can be improved by the NAD+ precursors NMN, NR.

-The NAD+ precursor nicotinamide improves somatic cell survival in a Drosophila model of Parkinson's disease (PD).

-Several human studies have shown that a dietary regimen rich in the NAD+ synthetic raw material niacin reduces the risk of Parkinson's disease in the elderly or improves physical functioning in Parkinson's patients.

of PD, ALS.

-NAD+ precursor is able to prevent or even reverse neuronal damage, degeneration associated with hearing loss, retinal injury, traumatic brain injury (TBI) and peripheral neuropathy under certain experimental conditions, reflecting a powerful and broad neuronal protective function.

 

Improvement of metabolic syndrome

In 2016, Front Pharmacol's article confirmed through animal models that NMN significantly improved glucose tolerance, hepatic lipid metabolism, and mitochondrial function in female obese mice, and in some indexes was even better than the effect of long-term exercise (6 weeks):

(i) The muscle NAD+ level of female obese mice rebounded after exercise, and the NADH level fell back, indicating that exercise improved the cellular oxidative respiratory capacity to a certain extent.

(ii) Obese mice without exercise but supplemented with NMN also showed a significant increase in muscle NAD+ levels, but at the same time NADH was maintained at a high level, suggesting that NMN supplementation not only improves oxidative respiration, but also promotes rapid interconversion between NAD+ and NADH.

(iii) Exercise did not significantly improve the liver NAD+ and NADH content in obese female mice.

(iv) No exercise but NMN supplementation had a significant effect on hepatic energy metabolism in obese mice, with a substantial increase in NAD+ and NADH levels; and mice liver weight and hepatic triglycerides also decreased significantly.

 

Reversal of vascular aging

Increasing NAD+ levels in the endothelium of aging blood vessels would be a potential therapy that holds promise for treating diseases that develop as a result of reduced blood flow such as ischemia-reperfusion injury, slow wound healing, and liver dysfunction.

Because of the relationship between SIRTs and vascular aging, NMN has already demonstrated effects in several studies:

(1)NMN treatment of aged mice (300 mg/kg administered daily for 8 weeks) restored endothelium-dependent dilation of carotid arteries (a measure of endothelial function), increased arterial elasticity, and reduced the level of oxidative stress in aging vessels.

(ii) NMN (500 mg/kg/day in water for 28 days) achieved significant efficacy in mice: it improved blood flow and endurance in aged mice by promoting sirt1-dependent increases in capillary density.

(iii) NMN significantly improved cognition in aged mice by ameliorating age-induced vascular endothelial dysfunction as well as neurovascular coupling (NVC) responses, and NMN reduced mitochondrial ROS and restored NAD+, mitochondrial energy in cerebral microvascular endothelial cells of aged mice.

 

Hepatorenal protective effect

Fatty liver often occurs in middle-aged or elderly individuals or those with excess visceral fat, who, as mentioned earlier, often have insufficient levels of NAD+. Studies in rodents have shown that obesity, alcoholic steatohepatitis, and nonalcoholic steatohepatitis due to metabolic disorders or aging can be prevented and obesity, alcoholic steatohepatitis and nonalcoholic steatohepatitis due to metabolic disorders or aging can be prevented, and glucose homeostasis and mitochondrial dysfunction can be improved, either through the inhibition of PARPs, CD38 (a NAD+ depleting enzyme), and nicotinamide N-methyltransferase (NNMT), or by supplementing NAD+ precursors.

NAD+ precursors not only improve liver health, but also enhance its regenerative capacity and protect the liver from hepatotoxic damage. Compared to untreated controls, mice that had been treated with NAD+ precursors had increased and more homogeneous liver regeneration, shorter duration of steatosis, increased DNA synthesis, and significantly improved lipid metabolism after partial hepatectomy.

There is also evidence from several studies arguing for the importance of NAD+ for renal function from different perspectives: in rodents, activation of SIRT1 and SIRT3 by NAD+ supplementation protects against high glucose-induced hypertrophy of renal mesangial cells; and treatment of mice with NMN protects against cisplatin-induced acute kidney injury (AKI) via SIRT1.

 

Skeletal muscle anti-aging

Muscle aging is one of the main reasons for the decline of mobility and labor force in the elderly, and muscle aging is also the most easily "perceived" aging.

Compared with young mice, aged mice have atrophied muscles, retarded insulin signaling, and reduced glucose uptake by skeletal muscle cells. It was found that treatment of aged mice with NAD+ precursors (e.g., NR and NMN) significantly improved muscle function in aging mice. Treatment of aged mice with NMN for 7 consecutive days resulted in enhanced mitochondrial function, increased ATP production, reduced levels of inflammation, and a gradual conversion of metabolically preferred glycolysis to aerobic oxidation in skeletal muscle, with many unfavorable physiological processes associated with increasing age being reversed.

Muscle stem cells are the tissue cell reserve of muscle and play a critical role when muscle needs to be regenerated. Tissue stem cell senescence is considered to be one of the major causes of tissue and even body cellular senescence, and NAD+ precursors can significantly delay muscle stem cell aging and maintain their quantity and quality by improving mitochondrial function.

In addition to older individuals, those who are "fat and weak" may also benefit from NAD+ precursors. Studies have shown that mice fed a high-fat diet improved skeletal muscle oxidative metabolism, energy production, muscular endurance, and athletic ability after taking NAD+ precursors.

 

Protecting the damaged heart

Maintaining NAD+ levels to ensure SIRT3 activity is critical for the maintenance of cardiac function, as well as recovery from cardiac injury, as has been corroborated by numerous rodent studies:

(i)SIRT3-deficient rats develop cardiac fibrosis and cardiac hypertrophy at 13 months of age, which is further exacerbated with age, and the use of NMN reverses this change.

(ii) When NAMPT was overexpressed, or treatment with NMN was, it was able to significantly prevent the area of myocardial infarction caused by cardiac ischemia-reperfusion (about 44% reduction).

(iii) NAD+ precursor treatment improved heart failure and optimized mitochondrial function in mice caused by iron deficiency.

(iv) NAD+ precursor protects and even restores cardiac function to essentially normal levels in a mouse model of Friedreich's ataxia (FRDA) cardiomyopathy through SIRT3 activation.

These evidences suggest that NAD+ precursors might serve as potential agents to ameliorate the adverse outcomes of cardiovascular events.

 

 

5. BalanceGenics PURE NMN

 

Balancegenics' Pure NMN is a supplement that utilizes golden standard high-purity (>99.5%) NMN (nicotinamide mononucleotide), a powerful longevity ingredient that can boosts NAD, reduces physical and neurological decline.

 

Key Features:

• Made in USA.

• This Uthever® NMN from BalanceGenics is the gold standard for purity.

• Tested independently by third-party laboratories to confirm high purity and low heavy metal content.

• Next-generation stabilization technology for the NMN, with the crystal arrangement optimized to ensure long-term stability.

• The ultimate longevity elixir crafted with the most potent, pharmaceutical-grade NMN available.

• Recommended to take Balancegenics' Pure NMN in combination with Balancegenics’ 12 Rev-Time product for best results

• 120 CAPSULES

• 250mg/Capsule

• 30,000mg Per Bottle

 

For more information, please see our Product page：

The PURE NMN from BalanceGenics is the Gold Standard for Purity.

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