In June of 2018, the World Health Organization (WHO) released the 11th edition of its International Classification of Diseases, and for the first time added aging.1
Nutrient sensing systems have been an intense focus of investigation, including mTOR (the mammalian target of rapamycin) for regulating protein synthesis and cell growth; AMPK (activated protein kinase) for sensing low energy states; and sirtuins, a family of seven proteins critical to DNA expression and aging, which can only function in conjunction with NAD+ (nicotinamide adenine dinucleotide), a coenzyme present in all living cells. 4
The slow process of aging has been described as a “cascade of robustness breakdown triggered by a decrease in systemic NAD+ biosynthesis and the resultant functional defects in susceptible organs and tissues.” 6 Aging is marked by epigenetic shifts, genomic instability, altered nutrient sensing ability, telomere attrition, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and dysregulated intercellular communication. 7 , 8
By middle age, our NAD+ levels have plummeted to half that of our youth. 9 Numerous studies have demonstrated that boosting NAD+ levels increases insulin sensitivity, reverses mitochondrial dysfunction, and extends lifespan. 10 , 11 NAD+ levels can be increased by activating enzymes that stimulate synthesis of NAD+, by inhibiting an enzyme (CD38) that degrades NAD+, and by supplementing with NAD precursors, including nicotinamide riboside(NR) and nicotinamide mononucleotide (NMN). 12 , 13
A conceptual framework called NAD World, formulated over the last decade by developmental biologist Shin-ichiro Imai, MD, PhD, of Washington University School of Medicine, positions NMN as a critical, systemic signaling molecule that maintains biological robustness of the communication network supporting NAD+. 6
NMN has been able to suppress age-associated weight gain, enhance energy metabolism and physical activity, improve insulin sensitivity, improve eye function, improve mitochondrial metabolism and prevent age-linked changes in gene expression.14
NMN Nicotinamide Mononucleotide is a NAD precursor and Sirtuin activator, the body’s anti-aging and longevity genes, so you may look and feel years younger. NMN also promotes new cellular growth and restores mitochondrial function to assist in fast recovery of muscle tissue and the immune system.
What is NMN or Nicotinamide Mononucleotide ?
Nicotinamide mononucleotide stands at the forefront of anti-aging research. It is a precursor to nicotinamide adenine dinucleotide (NAD+), a vital molecule found in every cell of your body.
NAD+ plays a crucial role in energy production, DNA repair, and regulating your body's internal clock. Unfortunately, as you age, NAD+ levels decline, leading to a range of age-related health issues.
NMN supplementation aims to boost these declining NAD+ levels, potentially reversing some aspects of aging.
NMN vs. NR
NMN and nicotinamide riboside (NR) are both NAD+ precursors, but they differ in their biological pathways. NMN is one step closer in the NAD+ conversion process, which could make it more efficient at increasing NAD+ levels in the body.
Potential Benefits of NAD+
Boosting NAD+ levels through NMN supplementation could have widespread benefits, including enhanced muscle function, increased energy levels, improved insulin sensitivity, and better cognitive function.
By replenishing NAD+ levels, NMN could help mitigate the cellular decline associated with aging, offering a potential pathway to healthier longevity.
Key Benefits of NMN Supplement for healthy aging
Increase NAD levels (NAD is an essential molecule in every cell, without which we cannot survive)
Mimics the effect of exercise to assist in prevention of weight gain
Improve cognitive impairment
Restored growth of new blood vessels for improved circulation and reversal of vascular atrophy
Boost Immunity & Immune System Health
Powerful Anti-Aging Support
Promotes DNA Repair Through SIRTUIN Gene Activation
Supports Cardiovascular Health
Enhance Cognitive Function
Boost Energy Levels, Metabolism & Endurance
Helps Reduce Stress & Fatigue
Effectively Increases NAD+ Levels which:
Helps Breakdown of Foods Like Sugars Into Energy
Promote Healthy Cardiovascular Function
DNA Repair - NAD+ is used to repair broken DNA strands
SIRTUIN Activator - NAD+ is required for our longevity genes to work.
Do NMN Supplements Work?
While some studies show promising results in animal models and limited human trials, more research is needed to establish conclusively the effectiveness of NMN supplements in humans. Considering the limited research on NMN, it’s too soon to verify whether the supplement alone is effective in increasing NAD+ levels. Pending human trials should help provide clarity on how well they work and in what capacity.
NMN Human Studies
Irie et al. conducted a non-blinded clinical trial using 10 healthy men to investigate the safety of oral NMN administration and the pharmacokinetics of nicotinamide metabolites at the Keio University School Medicine, Japan. They found that single oral administration of 100, 250 and 500 mg of NMN doses was well-tolerated and safe since it did not cause any observable clinical symptoms or changes in body temperature, oxygen saturation, blood pressure and heart rate. In addition, significant changes in ophthalmic, ocular fundus, and neurological system parameters were not observed after NMN administration.
There were no changes in the results of laboratory analysis of urine and blood as well as sleep quality and score before and after the NMN administration. Oral administration of NMN increased serum bilirubin contents and decreased blood glucose, chloride and serum creatine levels, but within the normal range. NMN administration did not increase nicotinamide in blood to the level which causes adverse effects associated with high dose of nicotinamide.
Since the safety of single oral administration of NMN has only been considered in this study, further clinical investigations are essential to be performed to assess the safety and efficacy of long-term administration of NMN. The organs and the tissue NMN levels have not been analysed in this study, which should be considered in future clinical studies.
As stated by Hong et al. three more human clinical studies are being carried out to evaluate the safety concerns of NMN administration. One study is a phase 2 study (UMIN000030609), which has been initiated by the Keio University School of Medicine, Japan to evaluate the safety of long-term administration of NMN, pharmacokinetics and metabolites of NMN, and its effect on glucose metabolism in healthy adults.
Another study is being performed to assess the effect of long-term intake of NMN on different hormones in healthy individuals (UMIN000025739) by the Hiroshima University, Institute of Biomedical and Health Sciences.
The third clinical study (UMIN000036321) has been designed to assess the consequences of oral administration of NMN on the body composition in elderly people at the University of Tokyo Hospital. These clinical trials are still ongoing and there is no result published yet. Yoshino et al. have also highlighted the importance of more comprehensively assessing potential adverse effects of NMN by conducting preclinical and clinical studies, considering different dietary conditions as well.
Safe NMN Dosage
A 2023 study revealed that oral dosing of 900 milligrams of NMN daily is generally safe for and well-tolerated in adults, however with that said, it’s crucial to consult with a health care provider to determine an appropriate dose based on individual factors, such as body weight, dietary intolerances, preexisting health conditions and any potential interactions with existing medications.
How to Consume More NMN Naturally
Consuming foods containing NMN could provide some benefits in increasing a person’s NAD+ levels. Such foods include edamame, cucumbers, broccoli and avocados. However, the levels of NMN obtained through diet alone may not be sufficient to create significant effects. Generally, healthy lifestyle practices, such as regular exercise and a balanced diet, can help support NAD+ production in the body.
Potential Risks and Side Effects of NMN
NMN is generally considered safe, and no major side effects have been reported in humans. However, since NMN is a relatively new supplement, long-term safety data is limited, and it’s always advisable to consult with a health care professional before starting any new supplement.
One small 2021 study in Frontiers in Nutrition observed 30 participants taking either 250 milligrams of NMN or a placebo daily for 12 weeks and concluded that NMN users may experience mild side effects including abdominal pain, diarrhea, gas and upper respiratory health issues.
FDA Issues With NMN
In 2022 the FDA ruled that NMN must be excluded from the dietary supplement category in the U.S. This decision was announced months after Inner Mongolia Kingdomway Pharmaceutical Limited (“Kingdom”) filed a new dietary ingredient (NDI) notification to the FDA for NMN, a motion that’s necessary when brands want to market dietary supplements with a “new dietary ingredient” never marketed in the U.S. prior to Oct. 15, 1994.
The FDA’s response reiterated that products classified as dietary supplements exclude ingredients “authorized for investigation as a new drug” or those in which “substantial clinical investigations have been instituted” and “made public.” Since NMN’s authorized investigation as a new drug happened before it was lawfully marketed as a dietary supplement, the FDA concluded that it should be excluded from the dietary supplement category until further notice.
Therefore, manufacturers marketing NMN products as supplements in the U.S. are doing so unlawfully, according to FDA regulations.
Green As Nature NMN formula is:
GMP (Good Manufacturing Practice) Certified
>99.5% Purity
No Added Fillers or Binders
No Artificial Ingredients
Available as NMN Powder or NMN Capsules
For more information, go to: www.greenasnature.com
Sources:
1. Zhavoronkov A, et al. Classifying aging as a disease in the context of ICD-11. Front Genet. 2015. November ( Classifying aging as a disease in the context of ICD-11 - PMC (nih.gov)
2. Blagosklonny MV. Disease or not, aging is easily treatable. Aging (Albany NY). 2018. November 17;10(11):3067-3078 ( Disease or not, aging is easily treatable | Aging (aging-us.com)
3. Editorial. Opening the door to treating ageing as a disease. Lancet Diabetes Endocrinol. 2018. August;6(8):587 ( Opening the door to treating ageing as a disease - The Lancet Diabetes & Endocrinology)
4. López-Otín C, et al. The hallmarks of aging. Cell 2013;153(6):1194-1217 [PMC free article] [PubMed] [Google Scholar] ( The Hallmarks of Aging: Cell)
5. Schultz MB, et al. Why NAD+ Declines during Aging: It’s Destroyed. Cell Metab. 2016. June 14; 23(6): 965–966 ( Why NAD+ Declines during Aging: It’s Destroyed | Request PDF (researchgate.net)
6. Imai S. The NAD World 2.0: the importance of the inter-tissue communication mediated by NAMPT/NAD+/SIRT1 in mammalian aging and longevity control. NPJ Syst Biol Appl. 2016. August 18;2:16018. The NAD World 2.0: the importance of the inter-tissue communication mediated by NAMPT/NAD+/SIRT1 in mammalian aging and longevity control | npj Systems Biology and Applications (nature.com)
7. Conboy IM, et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 2005; 433: 760–764. ( Conboy-et-al-(2005)-Nature.pdf (glennfoundation.org)
8. de Magalha~es JP, et al. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics 2009: 25: 875–881. Meta-analysis of age-related gene expression profiles identifies common signatures of aging (dntb.gov.ua)
9. Zhu XH, et al. In vivo NAD assay revels the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc. Natl. Acad. Sci. 2015; 112:2876–2881 In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences | PNAS
10. Suave AA. NAD+ and vitamin B3: from metabolism to therapies. J Pharmacol Exp Ther. 2008. March;324(3):883-93 [PDF] NAD+ and Vitamin B3: From Metabolism to Therapies | Semantic Scholar
11. Lee CF, et al. Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease. Sci Rep. 2019. February 28;9(1):3073. JCI Insight - Mitochondrial and NAD+ metabolism predict recovery from acute kidney injury in a diverse mouse population
12. Camacho-Pereira J, et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016. June 14;23(6):1127-1139 [PMC free article] [PubMed] [Google Scholar] CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism — Mayo Clinic (elsevierpure.com)
13. Longo VD, et al. Interventions to Slow Aging in Humans: Are We Ready? Aging Cell 14(4): 497-510. Interventions to slow aging in humans: Are we ready? — Research Profiles at Washington University School of Medicine (wustl.edu)
14. Mills KF, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016. December 13;24(6):795-806 Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice — Research Profiles at Washington University School of Medicine (wustl.edu)
Comentários