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Fluoride and Cardiovascular Diseases: Epidemiologic Investigations and Mechanistic Insights.
| Biological Trace Element Research | Yu J, Qian H, Wang M, Zhou Z, Sun S, Wan S, Sun L, Huang Y, Sun L, Huang Y, Huang Y. |
Arteriosclerosis Blood Pressure Heart Myocardial Damage Review

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s12011-025-04960-z

Fluorine is a trace element that is beneficial to human health. However, long-term and excessive fluoride exposure can damage bone and teeth, as well as the cardiovascular, nervous, and reproductive systems, etc. Since 2001, a growing body of evidences suggests that excessive fluoride exposure is associated with cardiovascular diseases. Although some original studies have focused on this topic, general and narrative reviews are rare. This article summarizes the effects of fluoride on blood pressure/hypertension, vascular sclerosis (mainly atherosclerosis), and myocardial/ cardiac damages based on epidemiologic investigations, in vivo and in vitro mechanistic studies. Most studies suggest that excessive fluoride exposure can initiate and aggravate hypertension through endothelial dysfunction (ED) manifested as abnormal endothelium metabolism, endothelium apoptosis, hyper-permeability, and impaired vasomotor function (imbalance of endothelin-1/nitric oxide), oxidative stress (over generation of ROS), and abnormal activities of the renin-angiotensin-aldosterone system covered up-regulation of AT1R, AT2R, ACE3 and down-regulation of ACE2. Besides ED, excessive fluoride exposure induced and accelerated atherosclerosis via lipid metabolism disorders (elevated plasma triglyceride, total cholesterol, and low-density lipoprotein cholesterol, etc. levels), up-regulation of adhesion molecules (P-selectin, ICAM-1 and VCAM-1), over-proliferation and phenotypic changes of vascular smooth muscle cells. Except for oxidative stress, excessive fluoride exposure caused myocardial and cardiac functional damage via myocardium injuries, inflammation (IL-6 and IL-10 increased), and mitochondrial dysfunction (ATP and ATPase decreased), then presenting electrocardiographic abnormalities. The review will help to clarify harms of fluoride on the cardiovascular system and provide basis for adjustments of drinking water standards.

Graphical Abstract

Data Availability

No datasets were generated or analysed during the current study.

Contributions

Jiale Yu: Visualization, Writing-original draft. Hongyan Qian: Data curation, Writing-original draft. Mingqi Wang: Data curation, Visualization. Zijie Zhou: Writing-original draft. Shengfeng Sun: Visualization. Siyuan Wan: Writing-review and editing. Liyan Sun: Methodology, Writing-review and editing. Yuanyuan Huang : Resources, Supervision, Writing-review and editing.

Corresponding authors

Correspondence to Liyan Sun, Yuanyuan Huang, Liyan Sun or Yuanyuan Huang.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Supplementary Information

Below is the link to the electronic supplementary material.

ESM1

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ESM2

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Funding

This work was supported by the Specialty Program for Health Professionals of Finance Department of Jilin Province, China (grant number JLSWSRCZX2023-63); the University Basic Scientific Research Operating Expenses in Heilongjiang Province of China (grant number 2020-KYYWF-0002); the Zhejiang Student’s Innovation and Entrepreneurship Training Program (grant number S202510354060).

Author information

Author notes

  1. Jiale Yu and Hongyan Qian contributed equally to this work.

Authors and Affiliations

  1. College of Medicine, Jiaxing University, 899 # Guangqiong Road, Nanhu District, Jiaxing, 314001, China

    Jiale Yu, Zijie Zhou, Liyan Sun & Liyan Sun

  2. Zhejiang Sian International Hospital, Jiaxing, 314001, China

    Hongyan Qian

  3. Department of outpatient and emergency, Children’s Medical Center, The First Hospital of Jilin University, 1 # Xinmin Stree, Chaoyang District, Changchun, 130012, China

    Mingqi Wang, Shengfeng Sun, Yuanyuan Huang, Yuanyuan Huang & Yuanyuan Huang

  4. College of Public Health, Qiqihar Medical University, Qiqihar, 161006, Heilongjiang, China

    Siyuan Wan

Cite this article

Yu, J., Qian, H., Wang, M. et al. Fluoride and Cardiovascular Diseases: Epidemiologic Investigations and Mechanistic Insights. Biol Trace Elem Res (2026). https://doi.org/10.1007/s12011-025-04960-z