How much NMN per day is administered to people in scientific studies? Let’s look at the overview of all clinical studies with dosages! 

Why are NMN and NR being studied in clinical trials?

In the search for substances that have anti-aging effects on humans, the molecule Nicotinamide Adenine Dinucleotide (NAD) has come into focus. NAD is a crucial molecule for storing and transferring electrons and is involved in more than 500 different metabolic reactions, including DNA repair, in the body. 

NAD levels decrease with increasing age

Many studies have shown that NAD levels naturally decrease with age, leading to the hypothesis that supplementation with NAD could help mitigate the aging process. The fact that DNA damage accumulates with age and NAD plays an important role in DNA repair supports this idea. However, since the NAD molecule is poorly absorbed through the gut, oral supplementation is impractical.

NMN and NR – NAD boosters that are well absorbed by the body

Scientists have therefore turned to biochemical precursors of NAD, Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN). Both molecules have good oral bioavailability, meaning they are well absorbed through the gut into the bloodstream. Through the blood, they are supposed to increase NAD concentration at the tissue and cellular level. Both molecules naturally occur in many plants and in all tissues of mammals and serve as direct precursors of NAD. 

Various preclinical studies4,5 have shown that NMN supplementation increases NAD concentration and may thus mitigate age-related physical changes. Some studies concluded that NMN extends lifespan in certain animal species, increases endurance in aging mice, and improves cognitive abilities in rats with Alzheimer's disease.

NMN DISCLAIMER

Disclaimer: The information provided regarding NMN dosages is derived from scientific studies and is for informational purposes only. Please note that NMN is not approved as a dietary supplement in the European Union as it is considered a novel food and is therefore not suitable for human consumption. This information should not be understood as a dosage recommendation, medical advice, or a recommendation to use NMN as a dietary supplement.

How much NMN per day has been administered to humans in clinical studies so far

Human trials have so far shown inconclusive results. While NMN intake has generally been found to be safe and well tolerated, the effects on NAD levels and age-related health conditions in humans remain uncertain. The studies vary significantly in their NMN dosages, ranging from 250 mg to 2000 mg per day. The results are also inconsistent. Some studies reported increased NAD levels, while others found no significant change or even a decrease.

Furthermore, most studies were limited in scope and often included only male or female participants or focused on subjects with specific conditions such as obesity. Therefore, further studies are needed, especially focusing on dose-dependent responses in healthy middle-aged adults of both genders, to fully understand the potential benefits of NMN supplementation.

Overview of NMN dosages in various clinical studies

How is NMN taken in studies?

In the above-mentioned human studies on NMN intake, it was administered orally with water for easy consumption. In the study by Yi et al., a significant increase in NAD concentration in the blood was measured in all three dosage variants. Similar results were seen in animal studies where NMN was also administered orally, for example dissolved in water. It therefore appears that oral intake of NMN, according to current research, leads to a significant increase in NAD concentration in the blood. There is currently no reliable data on sublingual (under the tongue) absorption of NMN.

New study (2022) shows increase in NAD levels with NMN intake

Study with high scientific standards

The study by Yi et al. was a randomized, double-blind, placebo-controlled trial designed to investigate the efficacy and safety of NMN supplementation in healthy adults aged 40 to 65 years. The study lasted a total of 60 days and included 80 healthy participants (59% female, average age 49.3 years). Participants were divided into four groups and received either a daily oral dose of NMN (300 mg, 600 mg, and 900 mg) or a placebo (n=20 per group). The subjects were randomly assigned to groups; one group received no NMN but only a placebo, and neither the supervising scientists and doctors nor the participants knew whether they were receiving placebo or NMN.

Study objectives: Does the NAD level increase and what effects can be demonstrated

The main objective was to assess the effects of NMN supplementation on NAD concentration in the blood. Secondary objectives included evaluating the safety and tolerability of NMN as well as its potential effects on physical endurance, biological age in the blood using Aging.AI 3.0, insulin resistance, and overall health. The Aging.AI 3.0 calculator is a tool that uses artificial intelligence to predict a person's biological age based on a blood sample analyzed for 19 lab test parameters, including fasting glucose and total cholesterol. The six-minute walk test describes aerobic capacity and endurance by measuring the distance one can walk in six minutes (on a treadmill in the study).

Results: NAD levels rise with NMN intake without notable side effects

The study found that NMN supplementation significantly and dose-dependently increased NAD concentration in the blood in all NMN groups compared to baseline, while values in the placebo group remained unchanged. Furthermore, it was found that NMN supplementation up to 900 mg/day over 60 days was safe and well tolerated, with no treatment-related side effects and no significant abnormal changes in laboratory parameters and physical examinations.

Increase in biological age in the placebo group and improvement in well-being in the NMN group

Biological age in the blood (Aging.AI 3.0 score) remained stable in the NMN groups, while it increased in the placebo group. The differences in biological age changes between the individual NMN groups and the placebo group all reached statistical significance (p<0.05). 

Participants receiving NMN showed significant improvements in the six-minute walk test (a test of physical fitness) and in general health status (measured by SF-36, a health questionnaire). 

The walking distance was significantly longer in all NMN groups than in the placebo group (p<0.01) and improved significantly from baseline in the 600 mg and 900 mg doses (p<0.05). 

No changes in insulin sensitivity in the NMN group and placebo group

Regarding insulin resistance, measured by HOMA-IR, it was found that NMN supplementation has no significant effects in healthy adults. When comparing the different dosage groups, the study did not find significantly better efficacy for the 900 mg/day dose compared to the 600 mg/day dose.

In summary, the study by Yi et al. shows that NMN supplementation increases NAD concentration in the blood, with the optimal effect observed at a daily dose of 600 mg.

Critique of the study

The present results confirm the hypothesis that NMN supplementation indeed leads to an increase in circulating NAD concentrations in the blood. However, it is important to note that these results do not yet prove that NMN increases intracellular NAD concentrations, which are crucial for NAD function. 

Aging.AI 3.0, a questionable tool for assessing biological age

The Aging.Ai 3.0 calculator, used to determine biological age from blood, has not yet been sufficiently validated for accuracy, validity, or reliability. Moreover, the study duration of 60 days is hardly enough time to detect significant changes in the aging process. Nevertheless, according to the Aging.Ai 3.0 calculator, the placebo group supposedly aged about 5.6 years during this period, which is not plausible with placebo administration. From our perspective, the Aging.AI 3.0 calculator therefore does not provide a reliable assessment of biological age. 

Physical fitness – spiroergometry remains the gold standard

The six-minute walk test was chosen as the measure of physical fitness in this study, which is generally used to assess exercise tolerance in older adults or patients with severe diseases such as chronic lung (e.g., COPD) and heart diseases. However, the study participants were 40 to 65 years old (mean = 49.3) and healthy. For assessing physical performance, it is unsuitable in this group because middle-aged healthy people do not reach their exercise limit and typically perform better on the second test without an actual improvement in physical fitness. A spiroergometric measurement of VO2max (maximum oxygen uptake) would have been much more appropriate for the study but also significantly more complex.

Conclusion

In summary, the study shows that oral NMN supplementation increases NAD concentration in the blood in a dose-dependent manner, with no difference whether the subjects took 600 mg or 900 mg daily. However, the results regarding clinical changes (physical performance or Aging.AI score) do not allow conclusions about the effect of NMN, as the study design was not suitable for this purpose.