Latest Human Trail: NMN supplement reduced BP and amelioratedvascular dysfunction in hypertensive patients
Hypertension is a major global health concern, linked to millions of deaths due to cardiovascular issues. It involves endothelial dysfunction and arterial stiffness, contributing to atherosclerotic diseases. Improving vascular function is vital for reducing complications.
Nicotinamide adenine dinucleotide (NAD+) plays a central role in cellular processes and declines with age. NAD+ supplementation is explored for age-related conditions. Studies show improvements in vascular health with NAD+ and NMN supplement on NAD level in reducing blood pressure and amelioratedvascular dysfunction in hypertensive patients.
1. NAD+ Decline Linked to Vascular Dysfunction
The study observed a substantial 44% reduction in NAD+ levels in peripheral blood mononuclear cells (PBMCs) of hypertensive patients.(as shown on Fig.1)
This decline was associated with signs of vascular dysfunction, including reduced flow-mediated dilation (FMD) and increased branchial-ankle pulse wave velocity (baPWV). Notably, a negative correlation was observed between NAD+ levels in PBMCs and blood pressure (BP).(as shown on Fig.2)
These findings highlight the association between NAD+ depletion and hypertension-related vascular damage.
2. NMN Supplementation Restores NAD+ and Improves BP and Vascular Function
In a clinical trial, NMN supplementation effectively increased NAD+ levels in PBMCs by approximately 43%.(as shown on Fig.3)
Importantly, this NAD+ boost resulted in a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and improved vascular function, as demonstrated by increased FMD and decreased baPWV.(as shown on Fig.4)
These results underscore the potential of NMN supplementation in restoring NAD+ and improving blood pressure and vascular health in hypertensive patients.
3. Role of Endothelial CD38 and Inflammation in NAD+ Regulation
The study found that CD38, an enzyme critical for NAD+ metabolism, was significantly upregulated in the aortas of hypertensive patients. (as shown on Fig.5)
In vitro experiments demonstrated that AngII stimulation increased CD38 expression in endothelial cells. (as shown on Fig.6)
Moreover, CD38 depletion led to increased NAD+ levels in endothelial cells. Figure 7 highlighted that CD38 played a role in NAD+ depletion and that NMN levels were affected by CD38.
Additionally, inflammation, specifically interleukin-1β (IL-1β), appeared to be associated with CD38 upregulation in endothelial cells through the JAK1-STAT1 signaling pathway.(as shown on Fig.8)
These findings suggest that endothelial CD38 and inflammatory pathways play a pivotal role in NAD+ regulation in the context of hypertension.
The study proposes that NAD+ depletion in endothelial cells via CD38 activation contributes to hypertension. Inflammation may impact CD38 expression. The study aims to investigate NAD+ levels in hypertensive patients, their relationship with blood pressure and vascular function, and the effects of NMN supplementation. It explores the role of macrophage-endothelium interactions in CD38 and NAD+ levels in hypertension, both in vitro and in vivo.
Qiu, Y., Xu, S., Chen, X.et al. NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension. Sig Transduct Target Ther 8, 353 (2023)