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Efficacy and Safety of β-Nicotinamide Mononucleotide (NMN) Supplementation in Healthy Middle-Aged Adults: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group Clinical Trial

In animal studies, supplementation with β-nicotinamide mononucleotide (NMN) increased nicotinamide adenine dinucleotide (NAD) concentrations and improved health and lifespan with great safety. However, it is unclear whether these effects can be transferred to humans.

This randomized, multicenter, double-blind, placebo-controlled, dose-ranging clinical trial included 80 healthy middle-aged adults who were randomized to a 60-day clinical trial and received once-daily oral doses of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to determine the NAD concentration in the blood with dose-dependent administration. The secondary objectives were to assess the safety and tolerability of NMN supplementation and to assess clinical efficacy by measuring physical performance (Six-Minute Walk Test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective assessment of general health status [36-Item Short Form Survey Instrument (SF-36)].

Statistical analysis was performed using the per-protocol analysis, with the significance level set at p = 0.05. All 80 participants completed the study without violating the study protocol. Blood NAD concentrations were statistically significantly increased in all NMN-treated groups at day 30 and day 60 compared to placebo and baseline (all p ≤ 0.001).

Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues were identified during monitoring of adverse events (AEs), laboratory and clinical measurements, and NMN supplementation was well tolerated. The increase in walking distance during the Six-Minute Walk Test was significant in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both day 30 and day 60. Blood biological age increased significantly in the placebo group and remained unchanged in all NMN-treated groups at day 60, resulting in a significant difference between the treated groups and placebo (all p < 0.05).

The HOMA-IR value showed no statistically significant differences in all NMN-treated groups compared to placebo at day 60. The change in SF-36 scores at day 30 and day 60 indicated a statistically significantly better health status in all three treated groups compared to the placebo group (p < 0.05), with the exception of the change in the SF-36 score in the 300 mg group at day 30. NMN supplementation increases blood NAD concentration and is safe and well tolerated at an oral dosage of up to 900 mg NMN daily. Clinical efficacy, expressed by blood NAD concentration and physical performance, is highest at a dose of 600 mg daily oral intake.

This study was registered at ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry – India, CTRI/2021/03/032421.((https://pubmed.ncbi.nlm.nih.gov/36482258/))

From April 2023 to April 2024 alone, 169 publications were published on Pubmed.

Nicotinamide mononucleotide (NMN) is a precursor to nicotinamide adenine dinucleotide (NAD+), which is synthesized in the body through the breakdown of nucleotides. It is important to note that NMN itself is not found in significant amounts in natural foods. Instead, NAD+ and NADH (the reduced form of NAD+) are found in a variety of foods.

Foods that may contain relatively high amounts of NAD+ are generally those that are rich in niacin (vitamin B3), as niacin can be converted into NAD+ in the body. Some foods that are good sources of niacin include:

1. Meat (especially liver)
2. Fish (e.g. tuna, salmon)
3. Poultry (e.g. chicken, turkey)
4. Dairy products (especially milk and cheese)
5. Eggs
6. Whole grains (e.g. whole grain bread, whole grain pasta)
7. Legumes (e.g. beans, lentils)
8. Nuts and seeds (e.g. sunflower seeds, peanuts)

It is important to note that the intake of niacin from natural foods is usually sufficient to meet the body’s needs. Supplementation with NMN or NAD+ directly is not common and requires further research to better understand its potential effects and safety.

“Longevity” is a term that describes the longevity or lifespan of an organism. In the context of health and well-being, longevity refers to promoting a longer and healthier life. This includes strategies, interventions, and lifestyle changes that aim to delay aging, improve quality of life, and reduce the risk of age-related diseases.

Research areas that deal with longevity include, among others:

1. Healthy diet: Choosing foods that are rich in nutrients and promote a balanced diet can reduce the risk of disease and promote longevity.
2. Physical activity: Regular physical exercise and sport can improve physical fitness, reduce the risk of cardiovascular disease and other chronic diseases and promote longevity.
3. Stress management: Managing stress and promoting positive mental health are important factors for a longer and healthier life.
4. Sleep quality: Sufficient and restful sleep is important for the regeneration of the body and can reduce the risk of disease and promote longevity.
5. Preventive medicine: Early detection and prevention of diseases can help to avoid or treat health problems early and thus promote longevity.

Longevity is a multidimensional concept that encompasses many aspects of life. Scientific research and the development of new technologies play an important role in the exploration and promotion of longevity.

Epigenetics is an area of biology that deals with changes in gene activity that are not due to changes in the DNA sequence itself. These changes can be influenced by environmental factors, lifestyle, diet and other external influences. In the context of health, epigenetics plays a significant role as it can explain how environmental factors influence the risk of disease and how certain behaviors and interventions can influence genetic expression.

Some important aspects of epigenetics in relation to health are:

Development of diseases: Epigenetic changes can increase the risk of developing diseases such as cancer, cardiovascular diseases, diabetes and neurological diseases. For example, environmental toxins or an unhealthy diet can cause epigenetic changes that increase the risk of cancer.

Lifestyle and environmental factors: Lifestyle factors such as diet, exercise, stress and sleep can influence epigenetic changes. A healthy lifestyle can help to promote positive epigenetic changes and reduce the risk of disease.

Precision medicine: Epigenetics makes it possible to better understand individual differences in gene expression and to develop personalized treatment approaches for diseases. By taking into account the epigenetic profiles of an individual, doctors and researchers can make more precise diagnoses and develop tailored therapies.

Heredity and development: Epigenetic changes can be passed on from generation to generation and influence the development and health of offspring. However, these changes can also be acquired during the course of life and are often reversible, which means that lifestyle changes can have positive effects on epigenetic regulation.

Overall, epigenetics shows how environmental factors interact with genetic regulation and how these interactions can influence health and disease. A better understanding of epigenetic mechanisms can lead to the development of new approaches to the prevention, diagnosis and treatment of diseases.