Early human intervention

NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension

Yumin Qiu, Shiyue Xu, Xi Chen, Xing Wu, Zhe Zhou, Jianning Zhang, Qiang Tu, Bing Dong, Zhefu Liu, Jiang He, Xiaoyu Zhang, Shuangshuang Liu, Chen Su, Hui Huang, Wenhao Xia, Jun Tao

Signal Transduction and Targeted Therapy · 2023 · 8:353

Original publication PubMed Full text on PMC

Study at a glance

Design: Translational study with a prospective randomized open-label 2-arm human intervention plus observational human, mouse, and cellular experiments; the publication is internally inconsistent on intervention duration (Methods: 30 days; Results: 6 weeks)
Population or model: Adults with hypertension in the clinical component
Sample size: Human intervention: 21 randomized; 19 completed (9 NMN + lifestyle, 10 lifestyle only)
Intervention: Human component: NMN 800 mg once daily plus lifestyle modification versus lifestyle modification alone; Methods specify 30 days, while the Results text describes outcomes after 6 weeks
Publication type: Translational clinical and mechanistic study
Evidence class: human-study
Research area: Hypertension and vascular mechanisms
Trial registration: NCT04903210

Study endpoints

Blood pressure
Vascular endothelial function and arterial stiffness
PBMC NAD+
CD38-related mechanistic measures
Mouse and cell mechanistic endpoints

Plain-language summary

This translational paper studied the relationship between CD38, NAD+ depletion, hypertension and vascular dysfunction using human participants, hypertensive mouse models and cellular experiments.

In the small randomized human component, NMN supplementation added to lifestyle intervention was associated with lower blood pressure and improved vascular measures compared with lifestyle intervention alone. The broader paper proposes a CD38-driven mechanism linking inflammation, NAD+ depletion and vascular dysfunction.

The human trial was small and embedded within a large mechanistic study, so its treatment findings should be considered early clinical evidence rather than a definitive hypertension result.

Key findings

Hypertensive participants had lower NAD+ measures alongside vascular dysfunction in the observational comparisons.
The human intervention component reported blood-pressure and vascular improvements with NMN plus lifestyle intervention.
Mouse and cell experiments implicated endothelial CD38 upregulation and accelerated NAD+ degradation in vascular dysfunction.
CD38 inhibition, genetic manipulation and NAD boosting improved vascular phenotypes in preclinical models.
The human intervention sample was small.

Limitations

The randomized human intervention was small, with 19 completers.
The paper combines observational, interventional and preclinical evidence, so mechanistic certainty in humans should not be overstated.
The clinical intervention was compared with lifestyle intervention rather than a large, standalone placebo-controlled efficacy trial.
Disease-treatment conclusions require larger independent trials.
Mechanistic animal and cell results cannot be assumed to translate directly to routine NMN supplementation in humans.

Funding and transparency

Funding

Supported by the National Key R&D Program of China (2020YFC2008000), Guangzhou Key-Area R&D Program (202206080004), National Natural Science Foundation of China (82270460, 92249304, 82270458, 82000461, 82270429, 82000466), and Kelin Star Talent Support Program of the First Affiliated Hospital, Sun Yat-sen University (R08019).

Competing interests

The authors declare no competing interests.

HealthspanX observation

This paper is important mechanistically, but its small human intervention should not be treated as a definitive hypertension trial.

Interpretive weight

Limited

Translational paper includes a small randomized human hypertension study plus extensive mechanistic experiments; the human efficacy component requires independent replication.

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