Highlights

  • Supplementing hypertension patients with 800 mg of oral NMN per day for six weeks significantly lowers their blood pressure.
  • Hypertension patients display significantly lower blood cell NAD+ levels, and taking NMN increases their blood cell NAD+ levels by ~43%..
  • Adults with hypertension have cells lining blood vessels — endothelial cells — with elevated concentrations of the NAD+ consuming enzyme CD38, which partially explains their lower NAD+ levels.

Elevated blood pressure associated with hypertension drives an estimated 8.5 million deaths globally per year due to stroke, heart disease, and kidney failure. Falling NAD+ levels with age have been linked to age-related cardiovascular decline, but whether NAD+ levels fall in hypertension patients hadn’t been examined until a recent publication based on a human study. Moreover, the study examined the effects of NMN on blood pressure in these patients.

Published in Signal Transduction and Target Therapy, Tao and colleagues from the First Affiliated Hospital of Sun Yat-sen University in China show that NMN significantly lowers blood pressure in hypertension patients between ages 18 and 80 years of age. The researchers showed that hypertension patients exhibit lower NAD+ levels but that NMN increases their NAD+ by ~43%. Furthermore, hypertension patients display endothelial cells lining their blood vessels with higher NAD+ consuming enzyme CD38 levels, which helps explain their lower NAD+ levels. These findings show that supplementing with NMN helps to counteract high blood pressure in hypertension patients.

“Hypertension is acknowledged as a kind of aging-related disease and NAD+ supplement may be a promising clinical strategy as an aging-targeted intervention for hypertension,” said Tao and colleagues.

NMN Increases NAD+ Levels and Lowers Blood Pressure in Hypertension Patients

To find whether NMN has any effect on blood pressure in hypertension patients, Tao and colleagues examined 19 adults between ages 18 and 80 with mild hypertension. All 19 hypertensive adults underwent lifestyle modifications that included a low-salt and high-fiber diet along with aerobic activity four days per week. A group of nine of these adults took 800 mg of NMN per day for six weeks in addition to lifestyle modifications while the other group of 10 only underwent lifestyle modification. Interestingly, the group that took NMN displayed markedly reduced systolic blood pressure — a blood pressure reading from when the heart pumps blood — showing that NMN reduces this key reading of hypertensive blood pressure.

(Qiu et al., 2023 | Signal Transduction and Target Therapy) NMN lowers systolic blood pressure in hypertension patients. Adults with hypertension display lower systolic blood pressure (SBP) after six weeks of NMN supplementation (NMN; red line) compared to hypertension patients who only undergo lifestyle modifications (LM; blue line).

Since NAD+ levels fall in a number of age-related diseases, Tao and colleagues sought to find whether NAD+ levels fall in hypertensive patients and, furthermore, whether NMN restores it. Compared to healthy adults, hypertension patients displayed significantly lower blood cell NAD+ levels. Supplementing with NMN in addition to lifestyle modifications significantly increased NAD+ levels in hypertensive patients compared to lifestyle modifications without NMN. These findings show that NMN restores blood cell NAD+ levels in hypertension patients.

(Qiu et al., 2023 | Signal Transduction and Target Therapy) Hypertension patients have lower NAD+ levels, and NMN restores NAD+ levels in hypertension patients. Left) Compared to healthy individuals (CTL), hypertension patients (HTN) have significantly lower NAD+ blood cell concentrations (pmol/mg protein). Right) After six weeks of NMN supplementation (NMN; red line), hypertensive patients have higher NAD+ levels than hypertensive adults who only undergo lifestyle modifications (LM; blue line).

For a better idea of how NAD+ levels decline in hypertension, Tao and colleagues measured levels of the NAD+ consuming enzyme CD38 in endothelial cells from the body’s largest artery emanating from the heart, the aorta. Intriguingly, the China-based researchers found that CD38 levels were more than twice as high in hypertension patients compared to healthy adults without hypertension. These results suggest that elevated CD38 levels in endothelial cells of hypertension patients contributes to their lower NAD+ levels. Thus, inhibiting CD38 could be another way to increase NAD+ levels and alleviate high blood pressure from hypertension.

(Qiu et al., 2023 | Signal Transduction and Target Therapy) Hypertensive patients have about twice the aorta endothelial cell CD38 levels of healthy individuals. Compared to healthy individuals (CTL), patients with hypertension (HTN) have about twice the CD38 enzyme levels as measured by fluorescent staining intensity in endothelial cells of the aorta.

“The present study demonstrates that NAD+ augmentation lowered [blood pressure] and improved vascular dysfunction in the context of hypertension, and provides robust evidence to support vascular aging-targeted intervention as an alternative and novel means to control [blood pressure] and improve vascular function in hypertension,” said Tao and colleagues. “Overall, the present study may shed new light on novel strategies in which NAD+ boosting therapy, including NMN supplement and CD38 inhibition, may turn out to be a promising therapeutic measure to treat patients with hypertension.”

Increasing NAD+ with Precursors and CD38 Inhibitors

The study provides the first human trial evidence that NMN lowers blood pressure in patients with hypertension. Moreover, no other study had yet correlated falling blood NAD+ levels with hypertension. By showing elevated NAD+ consuming enzyme CD38 levels, Tao and colleagues also provide support that using CD38 inhibitors like the pharmaceutical agent 78c may reduce blood pressure to alleviate hypertension. 78c is only available for laboratory use at this time, but future research and updated regulations may propel this potent CD38 inhibitor for use against age-related diseases like hypertension.

NMN is generally regarded as safe. Moreover, this study adds to the accumulating human trials showing that NMN increases blood NAD+. The new findings from the study showing that NMN reduces blood pressure in hypertension patients provides hope that NMN alleviates age-related conditions in humans, similar to its benefits against aging-associated conditions in rodents.