What is NMN ? Nicotinamide Mononucleotide, commonly abbreviated as NMN, is a kind of vitamin B3 or, more specifically, a niacin derivative. It is a ribonucleotide at the molecular level, a basic structural unit of nucleic acid RNA. The composition of the molecule’s structure consists of a nicotinamide group, a phosphate, and a ribose group. Inside the cells, NMN is one of the main elements that increase the NAD+ levels. That’s because NMN is one of the direct precursors to the vital molecule Nicotinamide Adenine Dinucleotide (NAD+) NMN has recently become a topic of interest among some of the worlds leading scientists as it shows great potential in becoming a primary anti-aging element for drugs as a nutraceutical. By Incorporating NMN into a healthy and balanced diet, you could improve NAD+ levels within your cells, and in turn, give a boost to your body’s longevity gene, Sirtuin. How Does NMN Synthesize in Our Bodies ? As previously mentioned, NMN is a derivative of vitamin B. Nicotinamide Phosphoribosyltransferase or NAMPT is the enzyme responsible for its production in the body. NAMPT attaches the nicotinamide, a vitamin B3, to a sugar-phosphate known as PRPP (5’-phosphoribosyl-1-pyrophosphate). Another way NMN is synthesized is by joining a phosphate group to nicotinamide riboside or NR. ‘NAMPT’ is the enzyme in NAD+ production that has a rate-reducing effect. Meaning that lower levels of NAMPT will decrease NMN production, ultimately resulting in lower levels of NAD+. Although adding a precursor molecule like NMN can speed up the NAD+ production. NMN Benefits Anti-Aging Properties NAD+ supports sirtuins in its activity to maintain integrity of the genome while also repairing damaged DNA. It is essential in sirtuins’ activation. Extensive research and animal testing demonstrated that raising NAD+ levels in the body activates sirtuins, resulting in the increased lifespans of mice, worms, and yeast. Even though the research has brought forward promising anti-aging qualities, researchers are still considering how studies done on animals can be applied and made more effective in humans. Improving Heart Function Hypertension results in blocked arteries, enlarged heart, and even strokes. Hence, increasing NAD+ levels protects the heart and, in turn, improves cardiac functions. Studies on mice show that using NMN to boost the NAD+ levels in the heart prevented injuries due to low amount of blood flowing to the organ. Related studies have also demonstrated that NAD+ boosters can give protection against abnormal heart enlargement in mice. Maintaining Metabolism NAD+ plays a crucial role in sustaining mitochondrial activities and flow of energy. Fatty diets and aging tend to reduce the level of NAD+ in the body. Studies on mice show that taking NAD+ boosters such as NMN can alleviate weight gain resulting from age and diet, meanwhile improving their exercise capacity regardless of age. Another study managed to reverse the effects of diabetes in female mice. This paved the way for new ways to tackle metabolic disorders like obesity. Neurodegenerative Disorders In mice subjects with Alzheimer’s, studies suggest that increasing the NAD+ level can decrease the protein build up disrupting cell communication resulting in enhanced brain function. Increasing levels of NAD+ can also have a neuroprotectant effect that keeps brain cells from dying due to lack of blood flow. Several recent animal studies present new hope of aiding the brain staying healthy with age while improving memory and protecting from neurodegeneration. NAD+ Precursors as NMN Supplements With time, NAD+ is used up by cellular activities, resulting in a drop in the concentration of NAD+ inside the cells. Taking supplements that contain NAD+ precursors help to boost the levels back up to a healthy concentration. Especially, precursors like NMN and nicotinamide riboside have shown to work as supplements for NAD+ production. Harvard NAD+ researcher, David Sinclair, says that NAD+ can’t be used as a supplement. Taking NAD+ directly does not produce the desired effect of increasing intracellular NAD+ levels; as the molecule can’t pass through the cell membranes. So, to make up for the shortage, NAD+ precursor molecules such as NMN supplements can be administered to increase the concentration of NAD+ in the cells. These are readily absorbed by the cells. How Does the Absorption of NMN Supplements Work? The NAD+ molecule cannot enter the cell membrane due to its enormous size. The membrane doesn’t allow particles to enter inside without using transporters. However, the NMN molecule is smaller than NAD+, and it is absorbed into the cell through the transporters embedded in the surface. It was previously believed that NMN transforms its absorption. But recent studies show it uses an NMN-specific transporter to make its way into the cell. Feeding NMN supplements to mice in a study revealed an increase of NAD+ in their livers after a total of only 15 minutes. Besides using NMN supplements orally, injections also show an increase in NAD+ in various body regions, including the heart, pancreas, skeletal muscle, kidneys, fat tissues, blood vessels, etc. NMN: Precautions & Side Effects NMN molecules are generally considered safe and nontoxic, despite high concentrations. Studies showed that a one-year oral administration of the drug did not cause any toxic effects in mice. The results of these animal studies are encouraging enough that clinical trials on humans have already begun for NMN supplements. Having completed its first-ever clinical trial in humans, the results for NMN display evidence supporting the claim that its single doses are very much harmless. The only exception is a study published in Japan in 2019. Men used as subjects had increased blood levels of bilirubin following NMN administration. However, these levels did not exceed normal limits. Further studies are currently being conducted to test the effectiveness and safety of its use over the long term. As of now, NMN has no known side effects. What Dosage of NMN Is the Most Effective? To demonstrate its effectiveness against age-related ailments, NMN was given to mice at doses of up to 300 mg/kg. According to this, a man weighing 165 pounds would need to take 22,500 mg or 22.5 grams of the substance to work. At this dose, NMN would cost over $100 for each dose and more than $35,000 a year, based on its current price! Nonetheless, humans do not need to consume such high doses for it to be effective. “Volume of distribution” states that rodents like mice, as compared to human beings, require higher doses by a factor of 12.3. As a result, a 300 mg/kg dose in mice would equal 24.39 mg/kg in humans, with a 165-pound person needing only around 1.829 grams to achieve the same effect. It’s important to remember that a 300 mg/kg dose in mice is relatively large and provides more NMN than is needed for treatment. Which brings us to ask how much NMN do you need to have a noticeable effect? A study done on rodents concluded that 100 mg/kg of NMN per day resolves most physiological issues related to aging. To find out the dosage for humans, divide this amount by 12.3. Hence, calculating the optimum amount of the substance for a 137-pound adult would be 500 mg of NMN a day What Dosage of NMN Is Being Tested in Human Clinical Trials? A Japanese team of scientists conducted a study that showed 500 mg of NMN is entirely safe to ingest. With the help of human clinical trials, the team tested oral administrations of NMN supplements up to a dose of 500 mg. The results showed no changes in blood pressure or any other physiological effects. Another study performed by St. Louis’s Washington University School of Medicine noticed the effects of an oral 250 mg dose of NMN on women for 10 weeks. Findings from this study indicated that doses of 250 mg per day could safely improve insulin sensitivity in muscle, especially in women. This study by the University of Tokyo proved that men over 65 years of age could benefit from oral doses of 250 mg of NMN per day for 12 weeks. Supplementing the aged men with NMN improved their ability to have better grip, walk faster, and rise from chairs. So far, NMN has shown potential in improving cardiovascular function, glucose metabolism, and metabolic processes. In addition, testing is being carried out on middle-aged and older adults who suffer from various old age-related diseases like hypertension, obesity, diabetes, and malnutrition. Also, NMN’s safety is currently being studied in clinical trials with long-term administration of 200 to 300 mg/day for up to 24 weeks. What Amount of NMN Should I Take? David Sinclair, a professor at Harvard, has studied aging and discusses taking NMN supplements to maintain good health and reduce aging. He advises taking 1 gram of NMN every day, together with metformin, aspirin, and resveratrol. What Dose Do Scientists Recommend? Based on the studies conducted using humans and animals as subjects, it is concluded that the optimum NMN dose is about 500 milligrams per day. This is the recommended dose for both men and women from ages 30 to 60 years old. To maximize NMN’s benefits, people over 65 can be administered with 750 mg – 1000 mg of NMN supplement a day.