How much NMN per day is used in science

How much NMN per day is given to people in scientific studies? Let's see 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 in the body, including DNA repair.

NAD levels decrease with age

Many studies have shown that NAD levels naturally decline with age, leading to the hypothesis that NAD supplementation may 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 intestine, 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 that they can be easily absorbed into the blood through the intestines. They are then supposed to increase the NAD concentration at the tissue and cell level via the blood. Both molecules occur naturally in many plants and in all mammalian tissues and serve as direct precursors of NAD.

Various preclinical studies4,5 have shown that NMN supplementation increases NAD concentrations and can therefore potentially attenuate age-related physical changes. Some studies have found 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 comes from scientific studies and is for informational purposes only. Please note that NMN, as a so-called novel food, is not approved as a dietary supplement in the European Union and is therefore not suitable for human consumption. This information should in no way be construed as a dosage recommendation, medical advice, or a recommendation to use NMN as a dietary supplement.

How much NMN per day has been given to people in clinical studies so far

However, human trials have so far shown ambiguous results. While NMN use has generally been shown to be safe and well tolerated, its effects on NAD levels and age-related health conditions in humans are still uncertain. Studies vary significantly in their NMN dosage, which ranges from 250 mg to 2000 mg per day. And the results are also inconsistent. Some studies reported increased NAD levels, others found no significant change or even a decrease.

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

Overview of the NMN dosages of the various clinical studies

Author	Dosage (mg)	Number of subjects (number)	Duration (days)	Gender	design	Published (year)
Irie	100, 250, 500	10	1	masculine	non-randomized intervention study	2020
Yoshino	250	25	70	female	Double-blind study, placebo-controlled	2021
Huang	150	66	60	Male Female	Double-blind study, placebo-controlled	2022
Morita	300	17	56	female	non-randomized intervention study	2022
Igarashi	250	20	84	masculine	Double-blind study, placebo-controlled	2022
Okabe	250	30	84	Male Female	Double-blind study, placebo-controlled	2022
Pencina	1000, 2000	32	14	Male Female	Double-blind study, placebo-controlled	2022
Liao	300, 600, 1200	48	42	Male Female	Double-blind study, placebo-controlled	2022
Kim	250	108	84	Male Female	Double-blind study, placebo-controlled	2022
Yi	300, 600, 900	80	60	Male Female	Double-blind study, placebo-controlled	2022

How is NMN taken in studies?

In the above studies on human ingestion of NMN, it was administered with water (orally) for easy ingestion. In the study by Yi et al. A significant increase in the NAD concentration in the blood was measured in all three dosage variants. The situation was similar in animal studies in which NMN e.g. B. was also administered orally by dissolving in water. It therefore appears that, based on current research, oral intake of NMN leads to a significant increase in blood NAD concentrations. There is currently no reliable data on the absorption of NMN under the tongue (sublingual).

New study (2022) shows an increase in NAD levels when taking NMN

Study with high scientific standards

In the study by Yi et al. was a randomized, double-blind, placebo-controlled study designed to evaluate the effectiveness and safety of NMN supplementation in healthy adults aged 40 to 65 years. In total, the study lasted 60 days and there were 80 healthy participants (59% female, mean age 49.3 years). Study participants were divided into four different 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 test subjects were therefore randomly assigned to the groups; one group did not receive NMN, but only a placebo, and neither the supervising scientists and doctors nor the test subjects knew whether they received a placebo or NMN.

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

The main objective was to evaluate the effects of NMN supplementation on blood NAD concentrations. Secondary objectives included assessing the safety and tolerability of NMN, as well as its potential effects on physical endurance, blood biological age 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 from a blood sample examined for 19 laboratory 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: The NAD level increases when taking NMN without any significant side effects

The study found that NMN supplementation significantly and dose-dependently increased blood NAD concentrations in all NMN groups compared to baseline, whereas levels remained the same in the placebo group. In addition, NMN supplementation of up to 900 mg/day for 60 days was found to be 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

Blood biological age (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 each NMN group and the placebo group all reached statistical significance (p<0.05).

Significant improvements in the six-minute walk test (a test of physical fitness) and general health status (measured by SF-36, a health questionnaire) were noted in participants who received NMN.

Walking distance was significantly longer in all NMN groups than in the placebo group (p<0.01) and improved significantly from baseline at 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, as measured by the HOMA-IR, NMN supplementation was found to have 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 dosage compared to the 600 mg/day dosage.

In conclusion, 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 .

Criticism of the study

The present results confirm the hypothesis that NMN supplementation does indeed lead to an increase in circulating NAD concentrations in the blood. Importantly, however, these results do not yet demonstrate that NMN increases intracellular NAD concentrations, which are crucial for NAD function.

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

The Aging.Ai 3.0 calculator, used to determine biological age in blood, has not yet been adequately validated for accuracy, validity or reliability. Furthermore, with a duration of 60 days, the study hardly provides enough time to detect significant changes in the aging process. Nevertheless, according to the Aging.Ai 3.0 calculator, the placebo group is said to have aged by around 5.6 years during this time, which is not understandable if a placebo was given. In our opinion, the Aging.AI 3.0 calculator 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 measure exercise tolerance in older people or in patients with serious illnesses such as chronic lung (e.g. COPD) and heart disease. However, the participants in the study were 40 to 65 years old (mean = 49.3) and healthy. It is unsuitable for assessing physical performance in this group of test subjects, as middle-aged, healthy people do not reach the stress limit and usually achieve a better result the second time the test is carried out, without any improvement in physical performance. A spiroergometric measurement of VO2max (maximum oxygen uptake) would have been much more suitable for the study, but would also have been significantly more complex.

Conclusion

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