Because of its unique mechanism of action, NMN (β-nicotinamide mononucleotide) has become a key component in the field of anti-aging, and has attracted much attention in the scientific research community.
At present, there have been more than 100,000 academic studies on NMN, and the number of related studies has increased exponentially every year, fully reflecting its great potential as an anti-aging ingredient.
A number of clinical trial results have been published to verify the significant effect of NMN in anti-inflammatory and antioxidant aspects, and studies have also confirmed the effect of NMN in improving memory, Alzheimer’s disease prevention and treatment, and the protection of cardiovascular and cerebrovascular system, reproductive system and bone.
NMN reverses vascular dysfunction and oxidative stress
NMN supplements reverse vascular dysfunction and oxidative stress during aging in mice
Published by Aging Cell
Date: March 2016
Summary of the study: This study evaluated the effects of NMN on vascular function in mice. Although animal studies provide a basis for clinical application, the findings suggest that higher doses of NMN can significantly improve vascular function and oxidative stress.
Methods: The effects of NMN supplementation on vascular oxidative stress, NO bioavailability and collagen and elastin expression in aged mice were tested to investigate whether NMN supplementation could reverse vascular dysfunction during aging.
(1) NMN reduces vascular oxidative stress
The experimental results showed that oral NMN treatment significantly improved vascular reactivity in older people mice, and there was a significant difference between the NMN treatment group and the control group in the presence or absence of TEMPOL.
The specific performance is as follows:
Carotid endothelium-dependent dilation response (EDD) : After oral administration of NMN, EDD was significantly restored in old mice, but no significant effect was seen in young mice.
Superoxide production: NMN treatment significantly reduced superoxide production in the aorta of older mice.
Nitrotyrosine abundance: NMN treatment significantly reduced nitrotyrosine abundance in the aorta.
These results suggest that NMN therapy significantly improves vascular oxidative stress in older people mice and may an effective anti-aging strategy by reducing oxidative stress and restoring endothelial function.
(2) NMN can treat aortic stiffness
By aPWV assessment, the degree of arterial stiffness in the aged control group was significantly higher than that in the young group.
NMN treatment reversed the increase in aPWV in older mice, but had no effect on younger mice.
The elastic modulus higher in the older people group and returned to normal after NMN treatment.
The collagen type I of thoracic aorta increased significantly and the elastin decreased significantly in the aged group.
NMN treatment reduced collagen type I to a young level, and elastin returned to normal.
Chart description:
(A) Aortic pulse Wave Velocity (aPWV) (n = 5-9 per group)
(B) Elastic modulus (n = 5-6 per group)
(C) Collagen type I expression in thoracic aorta (n = 4-9 per group)
(D) Expression of elastin in thoracic aorta (n = 4-11 per group)
The data were normalized to the average value of YC group, the value was the average ± SEM, the bar = 100μm.
Compared with other groups, P < 0.05; # Compared with YC group, P < 0.05.
These results suggest that NMN reverses age-induced arteriosclerosis by restoring collagen and elastin levels.
Long-term administration of NMN alleviates age-related physiological decline in mice
Published by Cell Metabolism
Date: December 2016
The study explored the effects of long-term NMN supplementation and found that NMN supplementation significantly increased NAD+ levels, improved exercise capacity, and delayed age-related physical decline in mice. This study provides useful information for clinical dose setting.
Methods: Mice were given NMN at 300 mg/kg body weight by oral tube feeding, and plasma NMN and liver NAD + levels were measured within 30 minutes.
(1) Oral administration of NMN can increase plasma NMN and tissue NAD+ levels
Oral NMN significantly increased plasma NMN and liver NAD+ levels.
After intraperitoneal injection of 500 mg/kg of NMN, the levels of NMN and NAD+ in liver, pancreas and white adipose tissue (WAT) of mice increased significantly within 15 minutes.
To achieve long-term oral NMN, we chose a lower dose and added it to drinking water, and studies have shown that 93-99% of NMN is stable at room temperature for 7-10 days.
After oral administration of 300 mg/kg of NMN, plasma NMN rose sharply within 2.5 minutes and returned to the original level 15 minutes later, indicating rapid intestinal absorption. Liver NAD+ levels increase steadily over 15-30 minutes, suggesting rapid conversion of NMN to NAD+.
Results using the double-labeled isotope NMN (C13-D-NMN) showed that double-labeled NAD+ was detected in the liver at 10 minutes, and the level increased after 30 minutes.
The marker NAD+ was also detected in soleus muscle at 30 minutes.
Long-term oral NMN studies over 12 months showed that NMN well tolerated with a dose-dependent increase in NAD+ levels in liver and brown adipose tissue (BAT), while this trend not seen in skeletal muscle and WAT.
Long-term NMN treatment effectively prevents the decline of skeletal muscle mitochondrial respiratory capacity.
The effect of NMN on skeletal muscle mitochondrial function evaluated by comparing the control group with 300 mg/kg/ day NMN treated mice.
In the figure, red represents down-regulated genes, blue represents genes related to mitochondrial function, and significantly changed genes reflect the response to NMN treatment.
Respiratory measurements of permeated skeletal muscle showed that the maximum respiratory rate of NMN-treated skeletal muscle significantly enhanced after FCCP added.
At the same time, the oxidative metabolism of skeletal muscle mitochondria increased significantly under the stimulation of pyruvate, ADP and succinic acid, indicating that NMN promoted the oxidative metabolism of skeletal muscle.
NMN treatment also increased the ratio of MTCO1 encoded by mitochondrial DNA to ATP5A or SDHB encoded by nuclear DNA in skeletal muscle, suggesting that NMN induced mitochondrial protein imbalance and enhanced mitochondrial oxidative metabolism.
NMN plays an anti-aging role by inhibiting age-related gene expression changes, enhancing mitochondrial protein imbalance and oxidative metabolism in skeletal muscle.
A single oral dose of NMN is safely and efficiently metabolized in healthy men
Effect of oral NMN on clinical parameters and niacinamide metabolic levels in healthy Japanese men
Published by: J-STAGE
Time: 2020
Research Summary: The Clinical Trial Center of Keio University in Japan conducted a non-blind clinical trial to study the pharmacokinetics of niacinamide metabolites in 10 healthy men and to evaluate the safety of oral NMN.
Test methods: Subjects took 100, 250, or 500mg NMN capsules (96-97% NMN) orally each time, followed by a 5-hour rest with only free water, and each trial interval was greater than 1 week.
Changes of serum indexes after oral administration of NMN (A: glutamic oxalacetic transaminase; B: glutamic-pyruvic transaminase; C: Total bilirubin; D: amylase; E: Creatinine; F: Sodium and chlorine; G: Glucose; H: Insulin; I: White blood cell count)
As shown in the figure above, laboratory analysis showed no significant changes in blood and urine before and after NMN administration, except for serum bilirubin, creatinine, chloride, and glucose levels.
Serum bilirubin level significantly increased by 51.3%
Glucose, creatinine and chloride levels decreased significantly, by 11.7%, 5.1% and 2.3%, respectively, after 5 hours
A single oral dose of 500mg of NMN is safe and well tolerated in healthy men and does not cause any significant harmful effects.
Therefore, oral NMN is feasible and may be a therapeutic strategy to supplement cellular NAD+ levels to alleviate age-related dysfunction in humans.
Sum up
It can seen from NMN related scientific research and clinical trials that NMN has a lot of health benefits, and some potential mechanisms of action need to be further verified.
