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Nicotinamide mononucleotide: A critical player in aging and longevity

Article
June 22, 2022
By
Ehab Naim, MBA.

Nicotinamide mononucleotide (NMN) is a direct precursor to NAD+, a critical coenzyme found in every cell in your that is involved in hundreds of metabolic processes and its levels decline with age.

Nicotinamide mononucleotide (NMN) is a bioactive molecule that combines a form of vitamin B 3 (also known as nicotinamide or niacinamide) and a type of sugar known as ribose. This compound is found in the nucleus, mitochondria, cytoplasm, and bodily fluids such as blood (1). In diet, NMN can be obtained from fruits and vegetables like avocados, broccoli, cucumber, edamame, and other sources (2).

Properties

NMN is an intermediate product of nicotinamide adenine dinucleotide (NAD+) biosynthesis, which plays a critical role as a cofactor in the oxidation-reduction (redox) reactions essential for energy production (3). In addition, NAD+ is involved in a variety of biological processes related to aging, cell death, DNA repair, neuroinflammation, and other functions (1, 4-6). Research has highlighted that NAD+ levels decrease with aging due to its increased consumption by various processes and enzymes, like those related to sirtuins. The outcome of this process is downregulation in mitochondrial capacity to produce energy in various organs, like the brain, skin, liver, muscles, and others. Fortunately, as the literature mentions, NAD+ deficiency can be compensated by NMN supplementation (1, 7).

Use as a supplement

To better understand how NMN can help fight the aging process, we need to establish some of the mechanisms by which NAD+ interacts with bodily functions and enzymes. Sirtuins, a group of proteins involved in many aging- and longevity-related physiological functions, consume NAD+ to perform their roles (8). Another example is Poly (ADP-ribose) polymerase (PARP), an enzyme that utilizes NAD+ for DNA repair (9). In this context, the literature highlights that prevention of NAD+ depletion could result in beneficial outcomes in terms of aging and longevity (1). 

After establishing a proper understanding of NMN, NAD+, it is time to understand the role of NMN as an anti-aging product. Results from preclinical and clinical studies have demonstrated the value of NMN in promoting longevity and fighting age-related complications and diseases, yet it is important to understand that further research on humans is needed to draw solid conclusions on efficacy and toxicity (1). The research has highlighted the value of NMN across multiple conditions. NMN has been shown to enhance hepatic insulin sensitivity and secretion, reduce oxidative stress, normalize aortic stiffness, and activate SIRT1 (a protein highly involved in longevity). In addition, NMN has been found to be beneficial in Alzheimer’s disease (AD), where it reduces the expression of amyloid protein (a hallmark protein involved in AD pathogenesis). Other studies have highlighted its value in suppressing weight gain associated with the aging process, improving the lipid profile, enhancing physical activity, and boosting mitochondrial functionality (1). 

In our Marketplace under the vendor DoNotAge, you can find NMN in 2 dosage forms, powder (Pure NMN Powder) and capsules (Pure NMN). The literature highlights that the majority of commercially available products have an NMN concentration of 50 to 150 mg/capsule (1). In their dosage forms, DoNotAge provides 500 mg/capsule (serving is two capsules) and 500 mg/scoop (serving is two scoops), providing the necessary dose to help your body fight the aging process.

To conclude, NMN supplementation plays a significant role in restoring NAD+ levels, improving several parameters related to aging and longevity. It is essential to understand that the abovementioned information is not conclusive and requires further research. Therefore, we recommend that you discuss using the supplement with a nutritionist or a health care expert.

Side effects

It is important that NMN is not devoid of side effects as the literature mentions that it may cause nausea, stomach discomfort, headaches, and affects organs like the kidney, liver, and pancreas. High doses of nicotinamide supplementation have been associated with reduced insulin sensitivity and increased oxidative stress (1). 

References

1.            Nadeeshani H, Li J, Ying T, Zhang B, Lu J. Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns. Journal of Advanced Research. 2022;37:267-78.

2.            Shade C. The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integrative medicine (Encinitas, Calif). 2020;19(1):12-4.

3.            Sorci L, Kurnasov O, Rodionov DA, Osterman AL. 7.08 - Genomics and Enzymology of NAD Biosynthesis. In: Liu H-W, Mander L, editors. Comprehensive Natural Products II. Oxford: Elsevier; 2010. p. 213-57.

4.            Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E, et al. NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proceedings of the National Academy of Sciences. 2018;115(8):E1876-E85.

5.            Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell metabolism. 2018;27(3):529-47.

6.            Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Frontiers in Cell and Developmental Biology. 2020;8.

7.            Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. Journal of Biomedical Science. 2019;26(1):34.

8.            Hall JA, Dominy JE, Lee Y, Puigserver P. The sirtuin family’s role in aging and age-associated pathologies. The Journal of clinical investigation. 2013;123(3):973-9.

9.            Cantó C, Menzies KJ, Auwerx J. NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell metabolism. 2015;22(1):31-53.

 

Nicotinamide mononucleotide (NMN) is a bioactive molecule that combines a form of vitamin B 3 (also known as nicotinamide or niacinamide) and a type of sugar known as ribose. This compound is found in the nucleus, mitochondria, cytoplasm, and bodily fluids such as blood (1). In diet, NMN can be obtained from fruits and vegetables like avocados, broccoli, cucumber, edamame, and other sources (2).

Properties

NMN is an intermediate product of nicotinamide adenine dinucleotide (NAD+) biosynthesis, which plays a critical role as a cofactor in the oxidation-reduction (redox) reactions essential for energy production (3). In addition, NAD+ is involved in a variety of biological processes related to aging, cell death, DNA repair, neuroinflammation, and other functions (1, 4-6). Research has highlighted that NAD+ levels decrease with aging due to its increased consumption by various processes and enzymes, like those related to sirtuins. The outcome of this process is downregulation in mitochondrial capacity to produce energy in various organs, like the brain, skin, liver, muscles, and others. Fortunately, as the literature mentions, NAD+ deficiency can be compensated by NMN supplementation (1, 7).

Use as a supplement

To better understand how NMN can help fight the aging process, we need to establish some of the mechanisms by which NAD+ interacts with bodily functions and enzymes. Sirtuins, a group of proteins involved in many aging- and longevity-related physiological functions, consume NAD+ to perform their roles (8). Another example is Poly (ADP-ribose) polymerase (PARP), an enzyme that utilizes NAD+ for DNA repair (9). In this context, the literature highlights that prevention of NAD+ depletion could result in beneficial outcomes in terms of aging and longevity (1). 

After establishing a proper understanding of NMN, NAD+, it is time to understand the role of NMN as an anti-aging product. Results from preclinical and clinical studies have demonstrated the value of NMN in promoting longevity and fighting age-related complications and diseases, yet it is important to understand that further research on humans is needed to draw solid conclusions on efficacy and toxicity (1). The research has highlighted the value of NMN across multiple conditions. NMN has been shown to enhance hepatic insulin sensitivity and secretion, reduce oxidative stress, normalize aortic stiffness, and activate SIRT1 (a protein highly involved in longevity). In addition, NMN has been found to be beneficial in Alzheimer’s disease (AD), where it reduces the expression of amyloid protein (a hallmark protein involved in AD pathogenesis). Other studies have highlighted its value in suppressing weight gain associated with the aging process, improving the lipid profile, enhancing physical activity, and boosting mitochondrial functionality (1). 

In our Marketplace under the vendor DoNotAge, you can find NMN in 2 dosage forms, powder (Pure NMN Powder) and capsules (Pure NMN). The literature highlights that the majority of commercially available products have an NMN concentration of 50 to 150 mg/capsule (1). In their dosage forms, DoNotAge provides 500 mg/capsule (serving is two capsules) and 500 mg/scoop (serving is two scoops), providing the necessary dose to help your body fight the aging process.

To conclude, NMN supplementation plays a significant role in restoring NAD+ levels, improving several parameters related to aging and longevity. It is essential to understand that the abovementioned information is not conclusive and requires further research. Therefore, we recommend that you discuss using the supplement with a nutritionist or a health care expert.

Side effects

It is important that NMN is not devoid of side effects as the literature mentions that it may cause nausea, stomach discomfort, headaches, and affects organs like the kidney, liver, and pancreas. High doses of nicotinamide supplementation have been associated with reduced insulin sensitivity and increased oxidative stress (1). 

References

1.            Nadeeshani H, Li J, Ying T, Zhang B, Lu J. Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns. Journal of Advanced Research. 2022;37:267-78.

2.            Shade C. The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integrative medicine (Encinitas, Calif). 2020;19(1):12-4.

3.            Sorci L, Kurnasov O, Rodionov DA, Osterman AL. 7.08 - Genomics and Enzymology of NAD Biosynthesis. In: Liu H-W, Mander L, editors. Comprehensive Natural Products II. Oxford: Elsevier; 2010. p. 213-57.

4.            Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E, et al. NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proceedings of the National Academy of Sciences. 2018;115(8):E1876-E85.

5.            Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell metabolism. 2018;27(3):529-47.

6.            Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Frontiers in Cell and Developmental Biology. 2020;8.

7.            Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. Journal of Biomedical Science. 2019;26(1):34.

8.            Hall JA, Dominy JE, Lee Y, Puigserver P. The sirtuin family’s role in aging and age-associated pathologies. The Journal of clinical investigation. 2013;123(3):973-9.

9.            Cantó C, Menzies KJ, Auwerx J. NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell metabolism. 2015;22(1):31-53.

 

Article reviewed by
Dr. Ana Baroni MD. Ph.D.
SCIENTIFIC & MEDICAL ADVISOR
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Dr. Ana Baroni MD. Ph.D.

Scientific & Medical Advisor
Quality Garant

Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.

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