Nicotinamide Mononucleotide or Nicotinamide riboside chloride: Which One is Better?

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Nicotinamide Mononucleotide or Nicotinamide riboside chloride: Which One is Better?

Nicotinamide Nicotinamide, also known as niacinamide, is a form of vitamin B₃found in food and used as a dietary supplement and medication. Nicotinamide is a water-soluble form of vitamin B3 or niacin. It is made in the body by eating niacin-rich foods such as fish, poultry, nuts, legumes, eggs, and cereal grains. Studies show that nicotinamide supplements is used to prevent and treat mouth and skin conditions (pellagra), and nicotinamide may protect against some forms of skin lesions in patients with sun-damaged skin. While used for skin, nicotinamide has the benefit of not causing skin flushing. Nicotinamide was discovered between 1935 and 1937. It is on the World Health Organization's List of Essential Medicines. Nicotinamide is available as a generic medication and over the counter. Commercially, nicotinamide is made from either nicotinic acid or nicotinonitrile. In a number of countries grains have nicotinamide added to them. Nicotinamide-based substances that have been discovered are: NMN, NR, NAD+ etc. Although they all carry "Nicotinamide", the performance and efficacy of different substances are also different.

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What are Nicotinamide Mononucleotide(NMN) and Nicotinamide Riboside chloride(NRC)? (1)Nicotinamide Mononucleotide Nicotinamide Mononucleotide powder (“NMN” and “β-NMN”) is a nucleotide derived from ribose and nicotinamide. Like nicotinamide riboside, NMN is a derivative of niacin, and humans have enzymes that can use NMN to generate nicotinamide adenine dinucleotide (NADH), it is an intermediate in the biosynthesis of nicotinamide adenine dinucleotide or NAD+. NMN naturally exists in avocadoes, tomatoes, cucumber, cabbages, broccoli, and raw beef. Occurring naturally in the body, NMN (β-Nicotinamide mononucleotide) is critical for the conversion of nutrients into energy. Supplementing NMN as part of your daily regime could offer energy revitalization, protection from the aging process, and decreased risk of cardiovascular complications. NMN is a cofactor in redox reactions, a process critical to metabolic function in the formation of ATP the high-energy supplying molecule. NMN contains a Sirtuin activating compound which promotes metabolic precision and longevity. In the human body, NMN is the principal source of energy within the cells. As you age, cellular energy decreases due to the low levels of nicotinamide mononucleotide and subsequent reduction of NAD+. Administering NMN will reverse the process and compensate for the deficit. In preclinical studies, Nicotinamide Mononucleotide work on mice has proved to be handy in cellular biochemical activities, management of Alzheimer’s disease, 2

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age-related diabetes, complications that arise from obesity, and cardioprotection. New research suggests that NMN may restore cellular metabolism, and have profound anti-aging effects. (2)Nicotinamide Riboside chloride NR is a form of vitamin B3 or niacin, it is usually found in milk, fruits, vegetables and meat, and can be used as a supplement. The compound was discovered in the 1940s as a growth factor for H. influenza. At the onset of the 21st century, scores of studies would prove that NR is a precursor of NAD+. There be many NAD + precursors, but NR is considered to be more effective than other NAD + precursors. In the human body, NR lowers cholesterol levels, eases the risk of cardiovascular diseases, boosts brain functions, and alleviates arthritis, meanwhiles prevent neurodegenerative diseases and age-related physical decline. Some research shows that long-term supplementation of NR may improve the metabolism of people who eat unhealthy foods and people who suffer from metabolic diseases (such as diabetes, obesity, and metabolic syndrome). Nicotinamide riboside (NR) is a pyridine-nucleoside, serving as a precursor to NAD+ (Nicotinamide adenine dinucleotide), which means it is the raw material for your body to make NAD+ through a series of chemical transformations. NAD+ fuels most biological functions including DNA repair, generation of cellular energy, setting the body’s circadian rhythm, and more. Unfortunately, these molecules naturally decline with senescence. Nicotinamide Riboside (NR) chloride (NIAGEN) is a derivative of NR and chlorine. The 3

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compound augments the levels of NAD+ and activates SIRT1 and SIRT3. It reverses aging by enhancing oxidative metabolism and countering diet-related metabolic comorbidities. In the US, nicotinamide riboside chloride is generally recognized as safe. Therefore, it is an approved dietary ingredient for use in protein shakes, vitamin waters, gums, and related supplements.

The difference between Nicotinamide Mononucleotide and Nicotinamide Riboside Chloride Among the various types of NAD+ precursors, only NMN and NR show better pharmacokinetics and pharmacological properties. These two compounds increase NAD+ levels in the body, thereby improving cell function and slowing down aging. Similarly, these two intermediates are currently also used in clinical research. However, the question remains: which one is better? Researchers hold different opinions. (1) Bioavailability NRC is a derivative of vitamin B3, which is easier to obtain in food, and its cell permeability is very direct, because NR does not require any conversion into different intermediates. In 2018, Martens et al. also used NAD + precursors to expand NAD + bioavailability as a process to improve cardiovascular and other physiological functions in aging. They conducted a clinical trial and the results showed that long-term supplementation of NAD + precursor nicotinamide ribose (NR) can be 4

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tolerated and can fully stimulate the NAD + metabolism of middle-aged and elderly people. NMN is not in the form of vitamin B3, and the chemical does not penetrate cells until it is converted into nicotinamide ribosomes. The reason is that its molecular size is relatively larger than that of nicotinamide ribose chloride powder. Due to this characteristic, the bioavailability of NMN and the prospect of activating NAD+ levels have always been the focus of debate in the research field. (2) Benefits Nicotinamide ribose chloride and nicotinamide ribose have similar benefits because they both activate NAD and sirtuin 1 proteins. As a substitute for vitamin B3, nicotinamide ribose chloride can be directly absorbed by cells, and it will increase the NAD + level in the human body by more than 60%. It can be used to treat metabolic diseases, neuroprotection, DNA repair and anti-aging supplements. NMN has a variety of therapeutic and pharmacological effects on the human body. It can be used to protect from the aging process, extend lifespan, fight neurodegenerative diseases and reduce the risk of cardiovascular complications. Harvard University geneticist Dr. Sinclair said that the efficiency of NMN is unparalleled. He admitted to using this supplement, which made him feel young and rejuvenated. Sinclair is equivalent to the effectiveness of NMN running on a treadmill. The scientist pointed out that it can improve blood circulation, promote muscle endurance and effective metabolism. In addition, in a study evaluating the efficacy of Frederick's ataxia (FRDA), a rare type of congenital heart disease, NMN was found to 5

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be effective in the case of failure of NR treatment. (3) Security In a 12-week survey, 2000 mg of NRC was supplemented daily to assess whether the glucose metabolism and insulin sensitivity of obese subjects are sufficient. Although NRC treatment cannot improve glucose metabolism and insulin, NRC treatment is safe and sensitive. . In 2016, the FDA approved nicotinamide ribose as a recognized safe food ingredient, including energy water (a beverage with some other ingredients added to drinking water), protein shakes, nutrition bars, etc. Although NMN appears to have a beneficial effect in animal studies, these studies still require sufficient clinical and pharmacological evidence. The manufacturing cost of NMN is high, and patients must bear these costs. Although NMN has its own shortcomings, it still has potential applications because it can be used to treat Alzheimer's disease, diabetes, and heart disease. NMN has been encapsulated and is now available on the market. With a large number of clinical and preclinical studies and its potential pharmacological applications, NMN can effectively treat many diseases, especially those related to aging.

Conclusion From the discussion between NRC and NMN, we learned about the meaning, characteristics, advantages and safety of these two metabolites. Among the various types of NAD+ precursors, only NMN and NRC show better pharmacokinetics and pharmacological properties. NAD+ metabolites in the form of vitamin B3, 6

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nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can increase NAD+ levels and improve different physiological capabilities in animal studies. It has shown good effects in promoting metabolism, anti-aging and treating neurodegenerative diseases. They are different from niacinamide or niacin and have different metabolism and functions. The effect on mitochondrial metabolism suggests that it may have important applications in the treatment of age-related diseases. NMN and NRC have their own advantages. We may not be able to give a unified answer to the question of which is better. However, the product is good or bad mainly depends on the personal usage. After all, different people have different feelings about the product. In short, what suits you is the best.

Reference [1] Yoshino, Jun et al. “NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR.” Cell metabolism vol. 27,3 (2018): 513-528. doi:10.1016/j.cmet.2017.11.002 [2]Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9:1286. [3]Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948 [4]Martin AS, Abraham DM, Hershberger KA, Bhatt DP, Mao L, Cui H, et al. 7

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Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model. JCI Insight. 2017;2:93885. [5]Conze, D., Brenner, C., & Kruger, C.L. (2019). Safety and Metabolism of Long-Term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports.

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