Longevity Briefs: NMN Supplements Reduce Blood Pressure In Hypertensives

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Blood pressure inevitably increases with increasing age, which in turn increases the risk of cardiovascular diseases, dementia and more. One of the factors that contributes to hypertension is the decline in levels of a molecule called NAD+ during ageing. NAD+ (nicotinamide adenine dinucleotide) is essential for the production of ATP, the cell’s universal fuel source, and also many other processes such as the repair of damaged DNA. NAD+ protects the lining of blood vessels from inflammation and is involved in the production of nitric oxide (which dilates blood vessels), thereby protecting against high blood pressure. 

NAD+ levels can be increased by taking supplements such as NMN (nicotinamide mononucleotide), a precursor molecule that cells can use to synthesise NAD+. NMN is marketed as an anti-ageing supplement, though many are sceptical of this claim due to the sparsity of human clinical trial data. Mouse experiments have shown that boosting NAD+ levels with NMN can improve vascular health and protect against hypertension. They’ve also shown that CD38, an enzyme produced by immune cells that breaks down NAD+, plays an important role in cardiovascular health. When this CD38 enzyme is inhibited in mice, NAD+ levels are restored and the cardiovascular system is protected from damage. However, it’s not clear whether this relationship between CD38 and NAD+ exists in humans with hypertension.

What did the researchers do: In this study, researchers recruited 102 people, about half of whom had been recently diagnosed with hypertension. They began by measuring NAD+ levels and CD38 expression in the blood vessels of participants and looked at whether these measurements were correlated with blood pressure. They also cultured cells from human aortas and either boosted or blocked their production of CD38 to see what effect this would have.

They then conducted a clinical trial in which 19 participants with hypertension were treated with lifestyle modifications, and 10 of those participants were randomly selected to receive NMN. This trial lasted 6 weeks, with the goal being to see whether taking NMN could boost NAD+ levels and thereby reduce blood pressure relative to those who only received lifestyle modifications.

Key takeaway(s) from this research: In the initial measurements, researchers found that hypertensive patients had far lower NAD+ levels in their blood vessels than the non-hypertensive participants on average, while the opposite was true of CD38. The cell culture experiments provided evidence that NAD+ and CD38 levels were linked: inhibiting CD38 production in human aorta cells resulted in an increase in NAD+ levels and vice-versa. Inhibiting CD38 also improved the ability of the aortic cells to repair themselves.

But what about the most important part: the human trial? Systolic blood pressure in the group receiving NMN was reduced by 7 mm Hg, compared to a 2.5 mm Hg reduction in the group who only received lifestyle interventions. This was a statistically significant difference, but there was no significant difference when it came to diastolic blood pressure.

So, while this study is quite small, it suggests that supplements that can increase NAD+ levels, such as NMN and NR (nicotinamide riboside), may be effective in lowering blood pressure in hypertensive people. Both of these supplements are safe with few side effects. It also suggests that CD38 plays an important role in lowering NAD+ levels in the blood vessels of hypertensives, providing another potential therapeutic target. Unfortunately, there’s currently no drug to safely lower CD38 levels in humans, so it will be some time before we know whether this strategy can be effective.