Hey there!
Welcome to my roundup of the best NMN supplements on the market in March 2024.
lll assume you landed here on a search for NMN, one of the most potent anti-aging supplements available today.
I too was curious to learn more about NMN after reading David Sinclair’s book, “Lifespan” and listening to many podcasts with him and other longevity experts.
In turn, I spent over 20 hours researching and personally testing NMN to find the 5 best NMN supplements available today.
Each of these supplements are high-quality, lab-tested products from reputable vendors who specialize in longevity and human optimization.
It’s also important to know that as of March 2023, NMN supplements are no longer sold on Amazon. In my opinion the following vendors are selling superior NMN supplements to anything you could find on Amazon.
So if you’re ready for an NMN masterclass and discover the best NMN supplement, let’s jump into the review!
Biohack Your Brainpower
Best NMN Supplement – Quick Answers
NMN Supplement FAQs
Best NMN Supplement Full Reviews
Lipo NMN by Renue by Science
Special formulation is easily absorbed and utilized by the body
Increases energy levels, cognitive function, and overall health in people with low NAD+ levels.
Can help improve mitochondrial function and energy levels
Improves skin health and appearance
Affiliate Disclosure: Holistic Nootropics is an affiliate for Renue By Science and will earn commissions if you purchase through these links.
Renue By Science Lipo NMN is my #1 choice for NMN supplements.
Not only do their products provide you with a potent dose of NMN, which is known to help improve cellular function and protect your DNA, but they have the biggest selection of NMN to choose from.
They offer pure NMN powder and tablets, liposomal NMN, NMN sublingual delivery, NMN nasal spray, and NMN blended with other anti-aging nutrients.
Each of these products are guaranteed to give you the NAD+ boost you need to feel more energetic and youthful.
Be sure to check out Renue By Science NMN customer reviews below!
“I’ve been using the sublingual NMN for the past year and wouldn’t do without it! From the first time I used it, to each time I use it, I can feel an uptick in energy and notice that my immune system seems to function better overall. I haven’t been sick since we started using it! I originally tried NMN supplements because I had come down with a really bad flu last February (not Covid) and was having a hard time recovering. While I was sick I read Dr. David Sinclair’s book, Lifespan, and decided to try using NMN. Wow, what a difference it made in my recovery! I got better so quickly after I started taking the supplements.
During my recovery, I took four of the sublingual tablets/day to boost my DNA repair mechanisms, and now for maintenance, I take the recommended 2/day. I’ve also tried both the LSG NMN and the SLC NMN and have found both to be equally as effective. I like switching the delivery mechanism for the NMN periodically to get the best response from my body. ”
– Jesse K.
“The darkening of my hair has been noticeable over the last 3 months or so. I take RBS Liposomal NMN and Fisetin amongst a range of other supplements.
The improvement to my facial skin & back of my hands is absolutely associated with the Renue applications. I had noticed it but when other people started commenting I felt that I had something more concrete to contribute. So in summary this is a remarkable result by any standards.”
– Lloyd D.
“I have spent most of my life struggling with chronic pain and disease. I was pleased to not have any stimulating effects, but rather subtle yet very powerful changes after using nmn for only a couple of weeks. I notice deeper sleep, better recovery, and more strength during heavy lifts. I also noticed subtle mood changes, like not having that sort of blah feeling when it’s dark, gray, and raining outside.
I have since tried more products by Renue by Science and have noticed benefits with each and every one. Their formulations are excellent and the quality of their products is Dependable through and through.”
– Rebekah F.
Comparison Of The Different Renue By Science NMN Products
Youngr NMN+ by Wonderfeel
900mg Lab-tested, and cGMP-certified patented NMN formula
Other ingredients include Ergothioneine 4 mg (from mushrooms), Resveratrol 100 mg, Hydroxytyrosol 20 mg (from olive fruit), Vitamin D3 20 mcg
Engineered by Andrew Salzman, a prominent Harvard MD, professor, and scientist with over 50 patents and nearly 30 years of expertise in NAD and cellular health
Subscribe and save $15 and get free shipping for orders over $60 in the US.
Customers report benefits such as enhanced mood and better sleep in as soon as a few weeks after continuous use
Pros
- 900mg NMN, a high dose supported by the latest and most comprehensive human clinical study.
- Emergent antioxidants and sirtuin activation, a multi-targeted approach to defend and slow down biological aging.
- Developed by Andrew Salzman, a Harvard MD and leading scientist.
- Available with great subscription discounts
Cons
- Offers only one SKU
- Doesn’t offer a money-back guarantee
Hello 100 NMN
Hello 100 is a high-quality NMN Supplement encapsulated in a liposome for maximum absorbability
Produced in GMP and HACCP-compliant facilities
Each ingredient is 3rd party, independantly lab tested w. certificate of analysis
Formula includes: 200mg NMN, Betaine, Resveretrol, Methylated B12/Folate for best methylation and longevity benefits
Lipo NAD⁺ Complete – NAD⁺, NMN, & NR
Includes NAD+, NMN & NR via nanoscale liposomes to increase your body’s NAD+ levels.
Each ingredient supports optimal cellular health and anti-aging benefits.
Formulation features proprietary powder-based liposomes that protect NAD,⁺ NMN & NR from digestive enzymes and carry them into the bloodstream for targeted systemic delivery.
Renue By Science offers fast shipping (domestic/int’l) and competitive prices
Do Not Age NMN
Do Not Age NMN contains the highest NMN Content per serving
Industry standard NMN
3rd Party Lab tested and produced according to GMP and ISO9001 standards. Stored in cool, dark and dry environments prior to delivery
What Is NMN (Nicotinamide mononucleotide)
NMN is a NAD+ precursor and one of the products of nicotinamide adenine dinucleotide (NAD+) synthesis.
Chemically, it is a product of the reaction of a phosphate group and a nucleoside that contains ribose and nicotinamide in the form of nicotinamide adenine mononucleotide or NAM. 1Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
NAM is then converted to nicotinamide mononucleotide NMN through the action of nicotinamide phosphoribosyltransferase or NAMPT.2Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 20183Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021
This enzyme essentially takes away the adenine from NAM, forming NMN.
A number of recent studies show that NMN can increase NAD+ levels to address NAD+ deficiency, translating to more cellular energy and overall longevity.4Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
How Do NMN Supplements Raise NAD+?
NMN increases NAD+ levels by acting as a precursor or a starting material to produce NAD+. 5Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 2018 6Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
NMN supplements are made to address NAD+ deficiency.
The conception and creation of NMN supplements is based on the premise that NMN is converted to NAD+ through the salvage pathway.
This is advantageous for us since in the salvage pathway, NMN is readily converted to NAD+, meaning there are no additional steps in the formation of NAD+ unlike that in de novo synthesis. 7Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 20208Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 2018
It is safe to say that the use of an NMN supplement is the fastest way compared to other essential compounds such as tryptophan, nicotinamide, and nicotinic acid. 9Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 201810Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
In addition, NMN is soluble and is orally bioavailable, meaning the NMN supplement is readily available in the bloodstream once taken orally.
In a study, it was found that NMN is absorbed from the gut and is absorbed into the bloodstream within 2-3 minutes and is completely absorbed into the body tissues and cells within 15 minutes.
NMN is then immediately converted to NAD+ and stored in tissues such as the liver, skeletal muscle, and brain. 11Saikat Kumar Poddar et al, Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential MoleculeBiomolecules. 2019
This is another advantage of an NMN supplement being that it is a sound delivery system as it is not invasive like injectable medications.
It can just be taken by mouth and even as a sublingual powder. 12Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
What is NAD+?
Nicotinamide adenine dinucleotide or NAD+ is a compound that is essential in cellular function. 13Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020 14Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021
Without NAD+, all cells in the body will cease to function since many reactions will rely on NAD+ as a coenzyme. 15Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020 16Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
It serves as a coenzyme in many enzymatic reactions in the cell, ultimately leading to increased cellular energy levels.
It is involved in processes such as glycolysis, beta-oxidation of fatty acids, and the Krebs cycle. 17Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 2018 18Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
NAD+ acts in the different biochemical pathways mainly as a redox agent by easily changing from NAD+ to NADH and vice versa in many key reactions.
How is NAD+ made?
NAD+ is made by using five compounds: tryptophan, nicotinamide, nicotinic acid, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). 19Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 2018 20Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
De novo synthesis of NAD+
NAD+ can be made from scratch or de novo by converting the amino acid tryptophan to nicotinic acid mononucleotide (NaMN), which is then converted to nicotinic acid dinucleotide (NaAD+) through the enzyme NMN/NaMN adenylyltransferase (NMNAT). 21Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
Finally, it is then amidated to form nicotinamide adenine dinucleotide (NAD+) by NAD+ synthetase.22Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 2018 23Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021 24Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
Preiss-handler pathway of nad+
In this pathway, nicotinic acid is converted to nicotinic acid mononucleotide (NAMN) by nicotinic acid phosphoribosyltransferase (NAPRT).
Then, NAMN serves as a precursor to the production of nicotinic acid adenine dinucleotide (NAAD+) by NMNAT.
Finally, NAAD+ is then converted to NAD+ through the enzyme NAD+ synthetase using ammonia and adenosine triphosphate (ATP) as additional ingredients for the reaction. 25Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
Salvage Pathway Of NAD+
NAD+ biosynthesis in mammals is done through the salvage pathway, a major biosynthetic pathway.
In this pathway, nicotinamide is converted by nicotinamide phosphoribosyltransferase (NAMPT) to form nicotinamide mononucleotide (NMN) a key intermediate of NAD+.
Then, the enzyme NMN/NaMN adenylyltransferase (NMNAT) converts NMN to NAD+. 26Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
From this pathway, it can be inferred that to produce NAD+, NMN has to be converted by NMNAT, making the enzyme a key player in the biosynthesis of NAD+. 27Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 201828Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021 29Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
This is also the reason that raising NAD+ levels is possible through the use of NMN supplements.
NMN Supplement Benefits
Cellular Health Benefits
Because NMN is a precursor to NAD+ and NAD+ is an essential coenzyme contributing to cell function
NAD+ Cellular Function
NAD+ acts as a contributor of an electron to the different biochemical pathways such as glycolysis, resulting in the production of pyruvate and the subsequent conversion to acetyl coenzyme A.30Laura D. Osellame, B.Sc et al, Cellular and molecular mechanisms of mitochondrial functionBest Pract Res Clin Endocrinol Metab. 2012
In the next pathway, the central biochemical pathway Krebs cycle, NAD+ is again used as a redox agent in converting the many interchangeable products of the pathway to be used in other biochemical pathways. 31Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 201832Laura D. Osellame, B.Sc et al, Cellular and molecular mechanisms of mitochondrial functionBest Pract Res Clin Endocrinol Metab. 2012
This can range from the storage of excess energy to fatty acids in adipose cells and to glycogen in the liver to the production and conversion of amino acids that are found essential in the building of collagen and maintaining muscle health.
In the ultimate production of ATP, NAD+ acts again as a contributor and as a receiver of an electron in the electron transport chain and finally oxidative phosphorylation. 33Laura D. Osellame, B.Sc et al, Cellular and molecular mechanisms of mitochondrial functionBest Pract Res Clin Endocrinol Metab. 2012
All of these reactions are found mainly in the mitochondria and the cytoplasm.
From the endless list of reactions that NAD+ is a part of, we can say that NAD+ and in conjunction, NMN, play a role in maintaining cellular health through the optimal functioning of these different biochemical reactions that are necessary for maintaining life.
NMN and Cellular Health
NMN supplements give the cells another chance at life by providing more NMN to produce NAD+.
NMN acts as a precursor in the cells to produce NAD+ once it is absorbed from the gut to the bloodstream and is immediately stored.34Saikat Kumar Poddar et al, Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential MoleculeBiomolecules. 2019
As a result, the increase in NAD+ levels will cause the cell’s many organelles, such as the mitochondria and the cytoplasm, and their enzymes within, to function optimally.
This causes an increase in the production of ATP as NAD+ is required in many of the cell’s processes, from the metabolism of sugars down to fatty acids.
How does NMN supplementation affect cellular function?
NMN supplements affect cellular function by improving cellular respiration.
Cellular respiration is the process wherein from the processing of the macronutrients such as carbohydrates, protein, and fat, the building blocks of those compounds are converted to pyruvate and acetyl coenzyme A (acetyl CoA). 35Kathryn F. Mills et al, Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in miceCell Metab. 2017
These compounds are then transported into the tricarboxylic acid cycle or the Krebs cycle.
Further, into the process, the product of the tricarboxylic cycle is a constant turn which allows for the use of the byproducts of the biochemical process in other ATP-producing means. 36Kathryn F. Mills et al, Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in miceCell Metab. 2017
The next stop is the process called the electron transport chain or ETC wherein an electron is passed along a series of proteins and enzymes and is ultimately passed into the ATP synthase to produce ATP from adenosine diphosphate or ADP. 37Laura D. Osellame, B.Sc et al, Cellular and molecular mechanisms of mitochondrial functionBest Pract Res Clin Endocrinol Metab. 2012
One particular study on the use of NMN supplements’ effects on respiration in athletes showed that NMN supplementation increased the aerobic capacity of humans during exercise which is especially evident in the skeletal muscle, the organ tested, and the one essential in maintaining muscle health.38Bagen Liao et al, Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind studyJ Int Soc Sports Nutr. 2021
NMN, NAD+, & Longevity
The aging process is an inevitable effect of life.
It results from wear and tear in cells and is a cause of the decline in the body’s physiology.
Effects of aging
A lot of anti-aging research was done to find that fountain of youth, to stave off the dreaded aging symptoms of wrinkling, cognitive decline, poor memory, worsening of the body physiology, and loss of mobility.
It was found that processes such as DNA methylation and shortening of the telomeres in chromosomes are correlated with the deterioration of cells as a result of the aging process. 39Yasmeen Salameh et al, DNA Methylation Biomarkers in Aging and Age-Related DiseasesFront Genet. 202040Adiv A. Johnson et al, The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related DiseaseRejuvenation Res. 2012
In addition, DNA damage may also be a result of depleting NAD+ levels.
During the aging process, there is a proportional decrease in NAD+ levels, which causes problems in the many biochemical processes that require NAD+. 41Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021
Extensive research was done to delve deeper into the understanding of how aging affects NAD+ levels.
It was found that the decline in NAD+ levels due to the aging process is coincidentally linked to the development and progression of diseases associated with aging.42Mounica Soma et al, The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditionsMol Biol Rep. 202243Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 201844Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021
These include atherosclerosis, arthritis, hypertension, cognitive decline, and neurological disorders, diabetes, and cancer.
These diseases cause an imbalance in the body that requires more NAD+ to maintain healthy levels of NAD+ but with the already-depleted NAD+ from aging alone, it can lead to a downward spiral. 45Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021
How NMN Supplements Affect Aging
NMN supplements, still with the premise that they are readily absorbed and converted into NAD+ through the salvage pathway, can have anti-aging benefits.
In addition, it was found in studies that NMN supplements restored gene expression that is linked to many bodily functions that are affected by aging such as the circadian rhythm, inflammatory response, oxidative stress, and insulin sensitivity. 46Harshani Nadeeshani et al, Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concernsJ Adv Res. 2022
47Kathryn F. Mills et al, Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in miceCell Metab. 2017As a result, NMN supplements can be used to treat and prevent the age-related disorders of atherosclerosis, arthritis, hypertension, cognitive decline and neurological disorders, diabetes, and cancer. 48Mounica Soma et al, The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditionsMol Biol Rep. 2022
There are studies that suggest that NMN supplements can even reverse some of these conditions. 49Mounica Soma et al, The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditionsMol Biol Rep. 2022
With the increase in NAD+ levels, other studies also revealed that there is reduced DNA damage from the compromised DNA repair brought about by aging. 50Harshani Nadeeshani et al, Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concernsJ Adv Res. 2022
This is due to the effects of NMN increasing NAD+ levels as a co-factor and as a redox agent.
Lastly in further research, NMN supplements have been shown to reverse age-associated gene expression and can even improve mitochondrial function in tissues. 51Kathryn F. Mills et al, Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in miceCell Metab. 2017
NMN supplements and Telomeres
The anti-aging benefit was also demonstrated in human trials by measuring telomere length, a good indicator of longevity and lifespan determination.
It was revealed that giving an NMN dose resulted in an increase in the length of the telomere after 30 days of giving the NMN dose.52Kai-Min Niu et al, The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging PhaseFront Nutr. 2021
These anti-aging benefits result from NMN products protecting the body from further harm by providing the much-needed NAD+ to maintain the biochemical processes in the body, prolonging life. 53Mounica Soma et al, The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditionsMol Biol Rep. 2022 54Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 201855Anthony J. Covarrubias et al, NAD+ metabolism and its roles in cellular processes during ageingNat Rev Mol Cell Biol. 2021
This makes NMN a good anti-aging supplement that promotes healthy aging.
NMN, Sirtuins, and Cerebral Blood Flow
The mechanism of cerebral blood flow heavily relies on the action of nitric oxide.
Nitric oxide is an important vascular health component and a major vasodilator, especially in small arteries and vessels.
The brain comprises many small arteries that arise from the centrally located Circle of Willis, a continuous network of interconnecting cerebral arteries that arise in the brain.
The precursor NMN acts to increase NAD+, which in turn increases the levels of sirtuins.
Sirtuins are enzymes that are vital in the pro-survival biochemical pathways and mitochondrial function in endothelial cells, the cells that make up the walls of the blood vessels.
Sirtuins then decrease the number of reactive oxygen species in the mitochondria or mtROS to prevent or mitigate cellular damage from oxidation.
The decrease in mtROS leads to the production of nitric oxide which promotes vasodilation.
Improved vasodilation in the cerebral blood vessel results in the upregulation of neurovascular coupling.
Neurovascular coupling occurs when the brain cells attempt to promote cerebral blood flow in response to vasodilation.
This then allows for increased blood flow to the brain tissue, promoting cognitive function.56Stefano Tarantini et al, Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged miceRedox Biol. 2019
NMN Supplementation and Cognition
The cognitive benefits of NMN supplements lie in the premise of increasing amounts of NAD+ in the system mentioned.
An increase in NAD+ levels demonstrates a decrease in cognitive decline.
In animal studies, the NMN supplement works specifically to increase NAD+, which effect improvement in cerebral blood flow in the brain, improving neurovascular coupling, which finally translates to improved neuronal activity. 57Stefano Tarantini et al, Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged miceRedox Biol. 2019
It was found in the study’s results that NMN supplementation significantly improved spatial working memory and gait coordination. 58Stefano Tarantini et al, Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged miceRedox Biol. 201959Sean Johnson et al, NAD + biosynthesis, aging, and diseaseVersion 1. F1000Res. 2018
This is helpful when it comes to the vascular health of the brain as it improves blood flow and at the same time, improves brain function both as an effect of improved blood flow and the innate maintenance of cellular homeostasis in neurons.
NMN and Cardiovascular Health
Heart health is an essential component of maintaining life.
Heart failure is the result of prolonged heart injury from a variety of cardiovascular diseases and has a direct link to mitochondrial respiratory dysfunction stemming from impaired balance of the NADH/NAD+ ratio, leading to decreased NAD+ in the cells. 60Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
The decrease in NAD+ leads to the lack of the redox capability of the system, leading to premature cell death, which leads to the development of heart failure.
How do NMN supplements affect cardiovascular health?
The premise of maintaining proper cardiovascular function is by reversing or inverting the NADH/NAD+ ratio.
Reversal of this ratio favors NAD+, which promotes oxidation or the contribution of an electron in the vital biochemical pathways.
This is possible due to the provision of nicotinamide mononucleotide which leads to its conversion to NAD+, increasing the amount of NAD+ present. 61Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020 62Luis Rajman et al Therapeutic potential of NAD-boosting molecules: the in vivo evidenceCell Metab. 2019
Another application of NMN supplementation is the maintenance of pro-survival capabilities of cardiac cells by maintaining optimum levels or sirtulins which protect cardiac cells from oxidative damage from ROS. 63Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
Studies on NMN and cardiac function
It was reported in a study that giving NMN improves cardiac energy utilization and decrease energy wastage in a heart failure model.
NMN in this case, normalizes ventriculoarterial coupling or how the ventricular contraction affects arterial dilation.
Another study reports that there was improved energy for cardiac activity by giving NMN.
It was shown that the NMN prolongs ejection time in the heart.
This means that prolongation of ejection time allows for more blood to flow to the peripheral vessels which then in turn supply blood to the farthest tissues, maintaining cellular homeostasis. 64Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
Lastly, cardiac aging was averted by NMN supplements.
Increasing NAD+ by NMN allows to counteract the effects of aging which is the decreasing levels of NAD+.65Zisong Wei et al, Nicotinamide mononucleotide: An emerging nutraceutical against cardiac aging?Curr Opin Pharmacol. 2021
Neurological Disorders
Aside form cognitive decline, mitochondrial dysfunction from altered levels of NAD+ can also lead to developments of neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. 66Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
In these neurological disorders, mitochondrial dysfunction is a feature.
Problems in mitochondrial function are caused and effected by defects in the electron transport chain and the production of ATP by oxidative phosphorylation.
Another contributing factor is the decrease in NAD+ found in mitochondrial dysfunction.
This can be due to aging and also can be due to the dysmorphic mitochondria and the altered positioning of the enzymes that are vital in ATP production. 67Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 202068Sofie Lautrup et al, NAD+ in Brain Aging and Neurodegenerative DisordersCell Metab. 2020
According to science, NMN causes an increase in NAD+ which is a premise for its use on neurological disorders.
In studies, giving an NMN supplement causes improvement in the shape of the mitochondria as well as the positioning and dynamics between energy-producing enzymes.69Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
In another similar study, there was a relationship between the shape of the mitochondria as well as the levels of oxidative damage and the abnormal protein folds found in neurodegenerative disorders such as Alzheimer’s disease.
In this study, NMN was given and showed improvement in the mitochondrial shape, and reducing the levels of reactive oxygen species by increasing the activity of sirtulins which protect the neurons. 70Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020
The decrease in ROS resulted in reduced instances of abnormal protein folding and thus reducing the formation of amyloids. 71Weiqi Hong et al Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ MetabolismFront Cell Dev Biol. 2020 (22)
NR vs NMN supplements
What is NR?
Nicotinamide riboside or NR is one of the most studied compounds that is a precursor of NAD+ through the salvage pathway.
In the salvage pathway, nicotinamide riboside is converted into nicotinamide mononucleotide or nicotinamide adenine mononucleotide (NAM), which ultimately leads to the production of NAD+.72Mario Mehmel et al, Nicotinamide Riboside The Current State of Research and Therapeutic UsesNutrients. 2020
From this pathway, the increased levels of NAD+ directly influence the NADH/NAD+ ratio and NADPH, reduced forms of NAD+, which have vital functions.
NADH/NAD+ ratio is important in inhibiting protein hyperacetylation especially in mitochondria to maintain function, whereas NADPH is important in inhibiting oxidative stress as it functions as an electron donor in the Glutathione system.
The Glutathione synthesis pathway is the most important pathway in eliminating oxidative stress through the action of glutathione, the strongest antioxidant produced in the body.73Mario Mehmel et al, Nicotinamide Riboside The Current State of Research and Therapeutic UsesNutrients. 2020
How does it differ from NMN?
Nicotinamide riboside differs from nicotinamide mononucleotide NMN mainly in the part of the salvage pathway in which it is located in.
Nicotinamide riboside is present as the main starting material for the ultimate production of NAD+, which may involve more steps to produce NAD+.
In studies, NR supplementation increased levels of NAD+ in the body at a great level of significance.74Mario Mehmel et al, Nicotinamide Riboside The Current State of Research and Therapeutic UsesNutrients. 2020
Nicotinamide mononucleotide, on the other hand, is just one step away from being converted into NAD+, which is one advantage of taking NMN supplements. 75Raymond D. Palmer et al, Precursor comparisons for the upregulation of nicotinamide adenine dinucleotide. Novel approaches for better agingAging Med (Milton). 2021
An NMN supplement delivers NMN readily into the cells for conversion to NAD+. 76Mario Mehmel et al, Nicotinamide Riboside The Current State of Research and Therapeutic UsesNutrients. 2020
Which is better, NR or NMN?
Now for this question, both are similar in terms of bioavailability but NMN clearly has the advantage of being more readily converted to NAD+ than NR. 77Raymond D. Palmer et al, Precursor comparisons for the upregulation of nicotinamide adenine dinucleotide. Novel approaches for better agingAging Med (Milton). 2021 78Mario Mehmel et al, Nicotinamide Riboside The Current State of Research and Therapeutic UsesNutrients. 2020
It should be noted that enzymes are saturable and that no larger amount of the precursor needed can be converted at an increased rate.
This means that no matter how much of NR you put into the body, the rate at which it is converted into NAD+ will depend on the number of enzymes present.
The same goes for NMN but the added benefit of it being readily converted into NAD+ will only require it to pass through one enzyme whereas NR requires to first be converted into NMN which, in the salvage pathway, can go one of two ways, with both paths in the pathway requiring the action of at least 2 enzymes. 79Raymond D. Palmer et al, Precursor comparisons for the upregulation of nicotinamide adenine dinucleotide. Novel approaches for better agingAging Med (Milton). 2021
NMN Supplements Safety
Much has been said on the NMN supplements, the benefits of NMN, and identifying the best NMN supplements in the market in terms of value and price.
Now, one question remains: are NMN supplements safe?
The answer is a very resounding yes!
Animal studies and clinical trials were done to test for the safety of NMN in mice and humans, respectively.
It is important to note that animal studies and especially clinical trials are done to not only determine the efficacy of a given medication or supplement but also the safety of these.
Animal Studies on Safety of NMN
In animal studies, each set amount of NMN dose was given for 91 days in Sprague-Dawley rats in oral doses of 500 mg/kg/day, 1,000 mg/kg/day, and 2,000 mg/kg/day.
It was revealed in the study that no adverse effects were noted when giving the low NMN dose of 500 mg/kg/day and the 1,000 mg/kg/day, and some adverse effects were noted with doses of 2,000 mg/kg/day, which comprised of reduced body weight, reductions in body weight gains, and diminished food consumption.80John Turner et al, Safety Evaluation for Restorin® NMN, a NAD+ PrecursorFront Pharmacol. 2021
Human Studies on Safety of NMN
In clinical trials, 30 healthy volunteers were given NMN for 12 weeks, with an NMN dose of 250 mg/day compared a placebo.
In addition to the assessment of safety, NAD+ was also measured in the blood.
In the trials, administration of NMN caused a significant increase in NAD+ in the blood.
The increase in NAD+ was then correlated with the vital signs comprising the body weight, the body mass index (BMI), the blood pressure, and the pulse rate.
Despite the increase in NAD+ in the blood, there was no significant difference in the vital signs between NMN and the placebo.
The concluded that NMN supplementation resulted in sustained increase of NAD+ levels with the absence of adverse effects.81Keisuke Okabe et al, Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy SubjectsFront Nutr. 2022
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