Findings of the study conducted by Japan’s nutraceutical firm DHC Corporation Laboratories were published in Scientific Reports.
NMN is a precursor of nicotinamide adenine dinucleotide (NAD+), which is essential in metabolic pathways.
Disorders related to metabolic health, on the other hand, are known to play a crucial role in cardiovascular diseases (CVDs), such as heart failure and atherosclerosis.
Citing past studies published in Nature Communications and Nutrition & Metabolism, the researchers from DHC highlighted that the supplementation of NAD+ precursors, including nicotinamide riboside (NR) and nicotinamide (NAM), could decrease the risk factors of CVDs, such as hypertension, arterial stiffness, and elevated level of low-density lipoprotein cholesterol.
Based on this understanding, they have therefore set out on this particular clinical trial to find out the effects of NMN supplementation on vascular function.
The 12-week randomised, double-blind, place-controlled, parallel-group clinical trial involved 36 healthy men and women aged 40 to 59.
They were randomised to take either one capsule of 125mg NMN or placebo twice per day. Both NMN and placebo capsules were provided by DHC Corporation which also funded the study.
Aside from NMN, the researchers said that the participants also took other supplements during the trial, including multivitamins, minerals, soy isoflavone, omega-3, lutein and coenzyme Q10, admitting that this could have affected the trial findings.
This is especially the case for participants taking omega-3, since it is known to improve vascular function and reduce CVD risk factors.
The percentage of people consuming other supplements in the placebo and NMN groups was 35.1 per cent and 32.4 per cent respectively.
“Eight supplements (multivitamins, multiminerals, soy isoflavone, vitamin C, vitamin B complex, omega-3 fatty acids, lutein, and coenzyme Q10) were taken by over 10 per cent of the total participants.
“Among them, the placebo group tended to consume more vitamin C, vitamin B complex, and omega-3 fatty acid supplements than the NMN group,” the researchers said.
To measure NMN’s effects on vascular health, they measured the changes in blood NAD+ metabolites level, SIRT 1 expression, ankle-brachial index and brachial-ankle pulse wave velocity – which were used to evaluate blood flow and arterial stiffness respectively.
A high brachial-ankle pulse wave velocity was shown to be associated with a higher risk of CVD based on past studies.
The serum concentrations of NMN, NAD+, and NAM were measured using isotope dilution liquid chromatography with tandem mass spectrometry analyses.
Benefits for above-average BMI, blood glucose individuals
No significant difference was observed in the average baPWV values between the intervention and placebo group.
However, when the participants were grouped and studied based on their BMI and blood glucose levels, it was found that NMN supplementation had significantly reduced the arterial stiffness of these individuals.
In participants with above-average BMI, NMN supplementation had significantly decreased their brachial-ankle pulse wave velocity (baPWV) value as compared to the placebo group, the p-value showing the differences between the two groups was lesser than 0.05 at 0.007.
Similarly, in participants with above-average blood glucose levels, NMN supplementation had reduced their baPWV as compared to the placebo, producing a p-value of 0.019.
In addition, NMN intervention had significantly decreased diastolic blood pressure in participants with higher-than-mean blood glucose levels.
In these participants, diastolic blood pressure was down 3.6 per cent to 72.6 ± 18.5 mmHg, while that of the placebo group was up 6.5 per cent to 82.1 ± 7.9 mmHg.
“As observed in the subgroup analyses limited to participants with higher-than-mean CVD risk factors, NMN’s baPWV-reducing effect was more pronounced in participants with higher BMI and blood glucose levels,” said the researchers.
Despite the improvement in baPWV, there was no change in BMI and blood glucose in these groups after the trial ended.
The researchers believe that the restoration of adiponectin production may be a reasonable mechanism by which NMN improves baPWV.
The benefit of NMN supplementation in reducing baPWV, however, was not seen in participants with other CVD risk factors, such as above-average systolic and diastolic blood pressure.
Serum NAM increased
Another finding was that NMN supplementation had significantly increased the serum level of nicotinamide (NAM) as compared to the placebo group.
In the intervention group, NAM serum level has increased from 10.4 ± 3.5 to 16.5 ± 6.3 ng/mL, up 57.6 per cent.
However, in the placebo group, NAM serum level was down 26.8 per cent from 14.9 ± 3.8 to 10.9 ± 4.8 ng/mL.
The difference between the two groups was statistically significant with a p-value of 0.037.
In contrast, NMN and NAD serum levels did not significantly differ between the two groups.
The supplementation of NMN was also not found to have significant impact on other health parameters, namely urinary 8-hydroxydeoxyguanosine (8-OHdG), SIRT1 mRNA expression in the blood, and advanced glycation end products (AGEs) in the skin.
Lastly, the researchers said that long-term NMN supplementation at 250mg per day was well tolerated and did not cause adverse events.
Source: Scientific Reports
Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial
Authors: Katayoshi, T., Uehata, S., Nakashima, N. et al.