What is NMN? Benefits, Dosage, and Risks
Introduction | What is Nicotinamide Mononucleotide (NMN)? | Overview of Potential Health Benefits and Risks | How Does NMN Work? | Potential NMN Health Benefits | Potential Risks and Side Effects | Methylation And TMG Supplementation | Lifestyle and NMN | NMN Supplements and Dosage | Conclusion: NMN, the Next Frontier in Longevity Research
If you have done any research into the latest advancements in longevity and anti-ageing technologies, you may already have heard of nicotinamide mononucleotide. Also known as NMN, nicotinamide mononucleotide is naturally produced in the human body. However, you can also take it as a supplement to address a wide range of health conditions and improve your general physical well-being.
According to Harvard University professor and longevity specialist David Sinclair, the scientific community is exploring a variety of potential health applications for NMN. It has shown initial promise in treating conditions like diabetes, liver failure and liver disease. Plus it’s helping to improve heart and brain health, enhance sleep quality, and boost physical performance.
In this guide, we’ll explore the nature of nicotinamide mononucleotide, the roles it plays in supporting human health and longevity, and the scientific data behind its benefits. Additionally, we’ll talk about safety and dosage information, provide guidance on the forms of supplements available, and discuss optimal practices to help you make the most out of NMN.
What is Nicotinamide Mononucleotide (NMN)?
Nicotinamide mononucleotide is a molecule that occurs naturally in the human body, and it is designed to assist in powering your cells. This molecule belongs to a group of molecules called nucleotides. These molecules play a variety of different roles in the body, including forming the building blocks of your DNA.
NMN is classed as a form of vitamin B3, a family of vitamins that all contain nicotinic acid as their primary constituent. This family of compounds includes niacinamide, also known as nicotinamide, nicotinamide riboside (NR), and nicotinamide mononucleotide—or NMN for short. NMN specifically is converted into nicotinamide adenine dinucleotide (NAD) in human cells and facilitates many different metabolic and energy production processes in the body.
Essentially, you can think of NMN as a raw building block and NAD as the finished product that your body can use efficiently to produce enough energy for its needs. While everyone can produce NAD, the amount you individually can produce depends on how much NMN you have in your body.
Overview of Potential Health Benefits and Risks
As with all supplements, nicotinamide mononucleotide poses benefits and potential risks for anyone who takes it.
Overview of potential NMN health benefits:
- NMN supplements may normalise blood pressure by reducing arterial stiffness, decreasing hypertension and LDL cholesterol levels, and mitigating some cardiovascular disease risk factors.
- NMN could assist in body weight management programs while addressing cardiovascular risk factors in overweight and obese patients.
- NMN may increase physical endurance levels and benefit bio-age, even in middle-aged to older individuals.
- NMN could support metabolic control by normalising blood pressure levels, basal metabolic rate, and glycation levels in the body. This helps to address conditions like insulin resistance and type II diabetes.
- NMN may increase aerobic capacity during exercise by enabling the skeletal muscles to use oxygen more efficiently.
- NMN could improve walking speeds and grip strength performance in senior patients with few side effects. In doing so, it provides an effective way to limit muscular degeneration without discomfort.
- NMN could enhance sleep quality and mitigate some mortality risk factors associated with sleep deprivation and exhaustion in older adults.
- NMN may assist in significantly lowering blood triglyceride levels without damaging healthy blood cells.
- NMN has been shown to improve longevity in mouse models and could have similar effects on human patients. However, more trials are needed to confirm these potential benefits.
Overview of potential risks and side effects:
- Current data shows few risks in taking NMN supplements, even for extended periods—however, the potential risks of taking nicotinamide mononucleotide, especially for pregnant and breastfeeding women.
- Since there are limited human studies on NMN and insufficient information regarding the optimal dosage, it cannot be easy to ascertain the correct amount to consume. Effective dosages can vary between 250mg and 1250mg per day and will depend on your health objectives.
- As with all medication, if you are taking medications or suffer from medical conditions, it is important to consult your doctor before taking any new supplements.
Most studies to date show that NMN is a safe supplement with no reports of serious side effects. Yet again, more research is needed to confirm these findings. Although side effects are rare due to the stimulant effect of NMN, some users may experience sleep disturbance, headaches or nausea. In addition, NAD boosters may also deplete methyl groups and cause fatigue. If you feel fatigued, you may wish to take a methyl donor, such as a Trimethylglycine (TMG) supplement, to replenish these groups. More on this below.
How Does NMN Work?
The purpose of NMN is to assist the body in maintaining healthy levels of NAD – a molecule that supports essential metabolic processes in the human body. One of the most efficient ways to ensure that your NAD levels are stable is to supplement with nicotinamide mononucleotide.
All the cells in the human body use NAD. Therefore, they all need their precursor NMN to function optimally. NAD is critical in facilitating energy metabolism, gene expression, DNA, and cell-level stress responses. Natural NMN levels can decrease with age, and may contribute towards some of the negative health effects that people experience as they grow older. Some research shows that people with various age-related health conditions, such as liver disease or diabetes, may have lower levels of NMN and of NAD as well. Other studies note that NMN levels may play roles in the deterioration of brain and heart health with age.
According to a study titled “Vitamins and Aging: Pathways to NAD+ Synthesis” published in the journal Cell, vitamin B3 or niacin is a building block for NAD. This compound carries two electron equivalents to oxidise carbohydrates during the synthesis of ATP. NAD is synthesized by the de novo pathway, beginning with the precursor tryptophan or via the salvage pathway using the precursor’s nicotinamide, nicotinic acid, and nicotinamide riboside (NR)—all available from dietary sources.
One leg of the aforementioned salvage pathway requires NR to be phosphorylated into nicotinamide mononucleotide by the NR kinase Nrk1. The other leg of the pathway involves the NR glycosidic bond being cleaved by Pnp1 (a phosphorylase) and Urh1 (a hydrolase) to generate free nicotinamide.
More current research suggests that the transformations between NR and NMN must occur to facilitate entry for a range of cell types. The data suggests that NMN is one of the most rapid ways to stimulate NAD production and that NMN can also be used directly by cells without first being converted to NAD. This is made possible by recently discovered transportation proteins that rise in numbers after NAD levels in the cells fall. Nicotinamide mononucleotide contributes towards cellular energy and allows each cell to grow and regenerate optimally.
Potential NMN Health Benefits
These are the potential health benefits of NMN supplementation, as outlined by the latest scientific research on the compound.
NMN may Normalise Blood Pressure
A recent 2023 review of several human trials found that NMN supplementation can decrease cardiovascular disease risk factors, including arterial stiffness, high blood pressure, and elevated LDL cholesterol levels.
The results showed that arterial stiffness was significantly decreased, specifically among test subjects with above-average blood glucose levels and body mass indexes. It also showed that blood pressure levels were greatly reduced among this subgroup as well.
NMN may Lower Cholesterol, Blood Pressure, and Body Weight
According to a recent 28-day trial, overweight or obese middle-aged men and postmenopausal women aged 45 years or older who supplemented with nicotinamide mononucleotide twice daily experienced many beneficial effects on their health statuses.
The patients displayed lowered LDL cholesterol and total cholesterol levels, lowered diastolic blood pressure, and lower body weight scores after the 28-day period had concluded. They also experienced an average 200% increase in their systemic NAD levels. The results suggest that NMN supplementation could assist with weight loss and treating cardiovascular disease markers.
NMN may Increase Endurance and Benefit Biological Age
An NMN trial conducted in 2022 looked at 80 middle-aged, healthy adults who were supplementing with nicotinamide mononucleotide in a clinical setting. When these adults were supplemented with NMN, the treatment was found to be safe and well-tolerated among the patients.
The results also showed that supplementation dramatically raised NAD blood levels while improving physical endurance and benefiting bio-age in the test group. This suggests that NMN supplementation could enhance your own endurance and physical performance, even at the middle and older ages.
NMN may Balance Hormone Levels and Reduce Glycation
In a 2022 study conducted by Yuji Morita et al, patients who took 300mg of NMN per day for eight weeks displayed no safety issues. They also displayed favourable changes in many biomarkers that link to hormone levels, basal metabolic rates, blood pressure, and glycation levels.
The researchers concluded that NMN could be a promising nutritional intervention to slow ageing and improve metabolic control in human subjects, although further research is needed. These findings could have important implications for treating and reversing insulin resistance and metabolic syndrome in the future.
NMN may Increase Aerobic Capacity
A 2021 study published in the Journal of the International Society of Sports Nutrition found that NMN supplementation effectively boosts the aerobic capacity of amateur runners.
The randomized, double-blind study found that nicotinamide mononucleotide increases human aerobic capacity during exercise, likely because it stimulates the skeletal muscles to use oxygen more efficiently.
The results suggest that supplementing with NMN could improve your athletic performance, especially during training with high aerobic requirements.
NMN may Improve Sleep Quality
A 2022 research paper published in the journal Nutrients found that NMN supplementation improved sleep quality and reduced daytime drowsiness and lethargy in adults over the age of 65.
The study’s results suggest that NMN supplementation could help to mitigate the mortality risk factors associated with poor sleep quality in older adults. Additionally, it positively impacts their quality of life and daily energy levels.
NMN may Improve Walking Speeds and Grip Strength in Elderly Patients
In a 2022 article titled “Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men”, researchers found that ongoing NMN supplementation was well tolerated among the target group. No significant adverse effects were reported, showing that the supplement is well tolerated even among individuals of advanced age.
Metabolomic analysis of blood samples found that the supplements significantly increased NAD concentrations in the blood, leading to improvements in gait speeds and left grip test performances in the subjects. The researchers suggested that ongoing oral NMN supplementation could be used as a NAD booster for preventing age-related muscle dysfunction.
NMN may Reduce Triglyceride Levels Without Harming Blood Cells
A 2022 study published in the journal Cureus found that NMN supplements dramatically reduced patients’ blood triglyceride levels by up to 75%, and increased NAD+ levels without damaging any healthy blood cells in the process.
NMN may Promote Longevity
According to a paper titled “Recent research into nicotinamide mononucleotide and aging” in Nature, stimulating NAD metabolism with NMN supplementation in mice extends their lifespans. It reduces their risk of developing premature ageing diseases.
The study noted that long-term oral supplementation of NMN suppressed age-associated weight gain, supported metabolism and insulin sensitivity, and prevented age-linked gene expression changes in rodents. Older mice displayed younger mice’s energy levels and metabolic rates within a year.
While this is an animal study, and more human trials are needed to confirm these effects in humans, it is possible that NMN could promote longevity in humans using similar mechanisms.
Potential Risks and Side Effects of NMN
Does NMN supplementation pose any significant risks, and have adverse side effects been reported? According to Healthline, nicotinamide mononucleotide is a powerful supplement for increasing cellular NAD levels. The health platform notes that the supplement is generally well tolerated in humans and animals, with studies on both observing few notable side effects.
Research in humans shows that NMN doses of up to 1,200mg per day are safe for adults. Most studies to date show that NMN is a safe supplement with no reports of serious side effects. Yet again, more research is needed to confirm these findings. Data from Health News notes that while reported side effects have been minimal, nicotinamide supplementation can still adversely affect the kidneys, pancreas, and liver. Headaches and gastrointestinal disturbances have also been reported on rare occasions and are most often caused by higher doses of NMN. Lower doses seem to exert protective effects against these side effects.
If you are pregnant or breastfeeding, taking chronic medication, or experiencing ongoing medical conditions, always approach your doctor before taking NMN. Children should not be given NMN under any condition without prior approval from a qualified medical provider.
NMN, Methylation And TMG Supplementation
David Sinclair, arguably the most well-known medical proponent for NMN supplementation, takes TMG or trimethylglycine to support his body’s methylation process. In a YouTube video on the subject, Professor Sinclair notes that when you take a NAD booster supplement, your nicotinamide levels rise rapidly before this compound is methylated and excreted via the kidneys. He believes that methyl groups are essential to support the body’s ability to complete the methylation process and eliminate any unwanted or harmful byproducts from that process.
TMG is an important cofactor in methylation and is used for synthesising neurotransmitters and melatonin, coenzyme Q10, and DNA methylation for epigenetic purposes. Methylation supports DNA repair, liver detoxification, creatine and SAMe production, and lipid metabolism. TMG is required to convert homocysteine—a potentially harmful amino acid—into inert methionine, thereby ensuring healthy homocysteine levels.
Other types of NAD boosters
While nicotinamide mononucleotide is one of the most effective supplements for boosting blood NAD levels, other supplements such as nicotinamide riboside (NR) and nicotinamide (NAM) also play a vital role in NAD synthesis.
All of these precursors are available from dietary sources. But they can also be supplemented to address deficiencies and optimize systemic levels. Many NAD+ booster supplements contain NR, NAM, NMN, and other NAD precursors in pre-adjusted dosages to improve NAD levels as much as possible.
Lifestyle and NMN
A few key factors can influence NMN levels in the body and possibly contribute to deficiencies. These lifestyle factors must be addressed before NMN blood levels can be successfully optimized.
Vitamin B3 Deficiency
If you are suffering from an active vitamin B3 deficiency, you may also have low levels of NMN and NAD in your body. All of the various B3 co-factors work together to produce NAD, so it’s important to correct your B3 deficiency before attempting to optimize your NMN levels.
Digestive Disorders
Patients suffering from conditions such as Crohn’s Disease and megaduodenum may have reduced NMN absorption in the gut, which could contribute to deficiencies. These patients may need custom-designed supplementation protocols and medical guidance to ensure that they meet their physical needs.
Physical or Mental Stress
The body’s vitamin B needs to increase during physical and mental stress periods, and over time, this could lead to low blood levels of nicotinamide mononucleotide. Supplementation during stressful periods may assist in reducing the risk of deficiency and subsequent low energy levels.
Dietary and Natural Sources
NMN is found naturally in the human body, and we obtain enough of this compound primarily through our diets. According to Healthline, some of the richest dietary sources of NMN include:
– Avocado pears – up to 1.6mg per 100g
– Cabbage – up to 0.9mg per 100g
– Broccoli – up to 1.12mg per 100g
– Raw beef – up to 0.42mg per 100g
– Tomatoes – up to 0.30mg per 100g
Smaller amounts of nicotinamide mononucleotide are also found in edamame (raw soya) beans, cucumbers, and dairy milk. Research has suggested that NMN is absorbed readily in the gut. However, further studies are needed to investigate how lifestyle factors influence systemic NMN levels and how dietary interventions may play an important role in optimizing one’s nicotinamide mononucleotide status.
Can Nicotinamide Mononucleotide Be Produced Naturally?
Yes! Nicotinamide mononucleotide is produced naturally through a reaction between a phosphate group and a nucleoside containing ribose and nicotinamide. This reaction occurs in human cells, and dietary sources supplement NMN levels.
While diet and lifestyle changes may help to provide the body with enough vitamins, minerals and nutrients to generate its own NMN, NAD, and other essential compounds, some of these compounds are challenging to consume in therapeutic quantities.
A supplement provides a standardized, consistent way to benefit from a compound’s therapeutic effects. However, more human trials are needed to explore NMN’s benefits and supplementary applications further.
NMN Supplements and Dosage
Disclaimer: Always consult your health care professional before making changes in your diet or exercise regimen, including whether to use supplements like nicotinamide mononucleotide (NMN).
In a recent study on NMN supplementation in humans in Japan, researchers found no safety issues attached to single oral doses of 100mg, 250mg, and 500mg in healthy adults. No changes in heart rates, blood pressure, blood oxygen levels, or body temperature was detected in the subjects five hours after supplementing.
Blood analysis detected minor changes in four molecules in the patients’ bodies, which rapidly returned to pre-supplementation levels. NMN also did not alter sleep duration or quality throughout the course of the study.
According to Healthline, it is difficult to determine an ideal dose for NMN. The data available on dosage is limited. But studies have found significant health benefits for doses as low as 250mg per day or as high as 1,200mg per day. A study involving amateur runners noted that NMN’s aerobic benefits were more pronounced at higher doses (1,200mg/day) than at lower doses (300mg/day)—but that doses of 600mg per day had similar effects to the 1,200mg doses.
At this time, commercially available supplements contain much lower doses. Commonly, such supplements:
- Have dosages between 250mg and 1000mg
- Are taken daily
- It can be taken with food or on an empty stomach
- Should be taken at the same time each day to maintain consistent NMN levels over time
Some of the aforementioned studies provided the full daily dose of NMN in a single dosage, while others provided two dosages per day. Speak to your healthcare provider to find the ideal dosage regime for you. If you have certain medical conditions, you may need to supplement more frequently to enjoy maximum benefit from supplementation.
The appropriate dosage of NMN may differ based on your health objectives, such as enhancing longevity, promoting skin health, or lowering your blood cholesterol levels.
Consult a trusted healthcare professional before making major changes to your diet, exercise regimen, or supplement regime.
Conclusion: NMN, the Next Frontier in Longevity Research
NMN or nicotinamide mononucleotide is a supplement with excellent safety data and very few reported side effects, even at high doses of 1,200mg per day. It poses few risks. However, it offers many potential benefits, including addressing cardiovascular disease risk factors, lowering blood pressure, cholesterol levels and body weight, and improving aerobic capacity and athletic performance. Additionally, it can reduce glycation levels in the body, thereby promoting a longer and healthier lifespan.
While these benefits are impressive, it’s important to note that more clinical trials are needed to understand the potential of NMN in human subjects fully. Consult with your healthcare provider before starting any supplement regimes or making significant changes to your diet and lifestyle to ensure that you can benefit from NMN supplements while minimising the risk of adverse effects.
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