On 5th May 2022, Frontier in Aging, an authoritative international journal on aging mechanisms, published one NMN clinical trial report with new insights and more experience being brought into the field of longevity. This human clinical trial conducted by Effepharm Ltd, was started in 2020. Previously Effepharm as one leading NMN manufacturer, finished the animal testings as well, proving that NMN has no acute toxicity.
Frontiers in Aging, one of the largest and highest-cited publishers in the world, led and peer-reviewed by editorial boards of over 100,000 top researchers, agreed to publish UTHEVER® NMN’s human clinical trials, which was reviewed by scientists, including professors at Harvard Medical School. This is the first time that Effepharm released detailed trial data to the public.
Figure 1 https://www.frontiersin.org/articles/10.3389/fragi.2022.851698/full
The main purpose of this trial is to investigate the safety of the first branded NMN ingredient– UTHEVER®. Meanwhile, this study also included some efficacy tests. Here are the conclusions of UTHEVER®NMN human trial:
The study was carried out on 66 healthy subjects between the ages of 40 and 65 years, instructed to take two capsules (each containing 150 mg. of NMN or starch powder) once a day after breakfast for 60 days.
Mild dyslipidemia occurred in two patients, one in the active UTHEVER®NMN group and another one in the placebo group. This problem can be completely solved by drug therapy, and therefore, it is not considered that 300mg/day, oral supplementation of UTHEVER®NMN60 days, subjects’ basic physiological indicators (blood routine analysis, liver and kidney function, systolic blood pressure, diastolic blood pressure, pulse pressure, etc.) did not change significantly. This fully demonstrates the safety of UTHEVER®NMN supplements under experimental conditions.
Reduction towards normalization of pulse pressure, systolic and diastolic blood pressure was considered as a parameter for evaluation of the anti-aging effect of UTHEVER® and these three indicators can verify the safety of UTHEVER® NMN as well. On day 30, mean pulse pressures showed a fall of 2.8% among the UTHEVER® group and 5.6% among the placebo group from baseline. The mean systolic blood pressure showed a fall of 0.3% among the UTHEVER® group and 1.1% among the placebo group from baseline. The mean diastolic blood pressure showed a fall of 2.2% among the Uthever group and a rise of 0.2% among the placebo group from baseline (Tables 1).
Compared with the placebo group, the blood cellular NAD+/NADH, 6 minute walking endurance test, SF-36, and HOMA IR index in UTHEVER® NMN group showed a trend of improvement and increased in the NMN group. As an endogenous compound, NMN cannot be used as a drug to rejuvenate the human body in a short time, but the experiment has fully proved the improvement trend of NMN, demonstrating the UTHEVER® NMN ‘s efficacy.
- Blood Cellular NAD+/NADH
The primary efficacy parameter, NAD+/NADH levels in the serum, had increased by 11.3% in the active group (UTHEVER® group) at day 30, whereas no change was observed in the placebo group at all. At the end of the study (day 60), the NAD+/NADH levels were increased further by 38% from baseline in the UTHEVER® group, compared to a mere 14.3% rise in the placebo group (Table 2). The increase in the placebo group may be attributed to the placebo effect in this study. The results indicate that UTHEVER® does increase the NAD+ levels in the serum after 2 months of duration as well.
- 6 Minute Walking Endurance Test
The walking endurance increased by 4.3% in the UTHEVER® group and 3.9% in the placebo group on day 30 of the treatment. So no effective difference was seen on day 30 of the treatment for walking endurance. When the same treatment was continued up to day 60, the UTHEVER® group showed a rise of 6.5% whereas, for the placebo group, it remained the same, i.e., 3.9% (Table 3). From this analysis, it was clear that the placebo effect was evident until day 30, but after that, the UTHEVER® group showed further improvement in walking endurance, whereas the placebo group remained at the same level.
The SF 36 questionnaire demonstrates the well-being of the subject. the higher the score, the better the health of the subjects. On day 30, in the UTHEVER® group, the score was raised by 4.0%,
whereas in the placebo group it was raised by 3.7%. So there is no meaningful difference in the score on day 30. On day 60, the UTHEVER® group showed a rise of 6.5%, whereas the placebo group was merely raised by 3.4%. （Table 4）The increase in scores in the UTHEVER® group was almost double the increase seen in the placebo group.
- HOMA IR
To evaluate the exploratory anti-aging effect on insulin regulation towards normalization, the HOMA IR index was assessed, along with fasting blood sugar and serum insulin (fasting). At the end of the study, the mean HOMA IR index showed a rise of 0.6% among the UTHEVER® group and a rise of 30.6% among the placebo group from baseline. Mean Glucose (Sugar) fasting showed a fall of 4.0% among the UTHEVER® group and a rise of 6.5% among the placebo group from baseline. Mean Serum Insulin fasting showed a fall of 1.9% among the UTHEVER® group whereas a rise of 26.2% among the placebo group from baseline (Tables 5).
Effepharm’s R&D Director Jianjun Yu said: “ The clinical trials of UTHEVER® NMN is to establish a more professional and scientific image, helping the downstream supplement brand side get more power to do product endorsement and give more confidence to end consumers. Up to now, more and more well-known supplement brands around the world such as Prohealth Longevity® in the USA, Do Not Age in UK, MoleQlar, Kenay® in Europe., LongLife Recipes in Russia, Vitanad+ in Japan, etc are using UTHEVER® trademark and realized the co-branding effects.”
Effepharm Ltd creatively launched a branded NMN ingredient to bring the purest and safest NMN ingredient around the world.
UTHEVER® NMN, an endogenous compound, has been clinically proven to be safe and to improve the NAD+/NADH in the human body, thus realizing the anti-aging function. Dr. Yu also advised that the first period of NMN clinical trials mainly aimed to verify the safety of UTHEVER® NMN, so we design the lower dosage to some extent. In the next few years, we will consider doing more NMN function research to explore the safety of larger doses of NMN and the effectiveness of related indications on which this trial data are based. Effepharm Ltd will apply for FDA Affirmed GRAS on NMN, which means that NMN raw material through the food regulations of various countries has taken a milestone step.