DALLAS – June 30, 2025 – Researchers at UT Southwestern have uncovered a significant link between diets high in phosphate additives and increased blood pressure, revealing a new brain-mediated mechanism that could lead to novel treatment strategies for hypertension. The study, published in Circulation, highlights how these additives, prevalent in processed foods, activate the sympathetic nervous system, which regulates cardiovascular function.
The study’s first author, Dr. Han Kyul Kim, Assistant Professor of Internal Medicine, emphasized the importance of their findings:
“This research uncovers a previously unrecognized brain-mediated mechanism by which high dietary phosphate intake promotes hypertension and sympathetic overactivation, highlighting central fibroblast growth factor receptor signaling as a novel therapeutic target.”
This discovery could pave the way for new treatments targeting the fibroblast growth factor receptor (FGFR) signaling pathways.
Understanding Phosphate Additives
Inorganic phosphate is commonly used in packaged foods, processed meats, and other dietary staples as a preservative or flavor enhancer. This widespread use has led to an average phosphate consumption far exceeding the recommended daily allowance in developed countries. The study explains that excessive phosphate intake allows circulating fibroblast growth factor-23 (FGF23) to enter the brain, inducing hypertension.
Hypertension, or high blood pressure, is a condition where the force of blood against the arterial walls is too high, affecting nearly half of the U.S. population. It significantly increases the risk of heart attacks and strokes, according to the U.S. Centers for Disease Control and Prevention.
Research Findings and Implications
UT Southwestern researchers conducted experiments comparing FGF23 protein levels, mean arterial pressure, and renal sympathetic nerve activity in rats fed a high (1.2%) phosphate diet versus a normal (0.6%) phosphate diet. These tests, also performed during stress responses to exercise, showed that rats on the high phosphate diet had increased FGF23 levels in their serum, cerebrospinal fluid, and brain stem. This increase was linked to higher blood pressure both at rest and during physical stress.
Dr. Wanpen Vongpatanasin, senior corresponding author and Director of the Hypertension Section at UT Southwestern, noted:
“FGF23 can cross into the brain and influence the brain stem centers that control blood pressure.”
Further analysis revealed that inhibiting FGFR4 during simulated exercise reduced the negative effects of a high phosphate diet, suggesting a connection between FGFR4 and overactivation of the sympathetic nervous system.
Potential Treatment Strategies
The study’s findings suggest that targeting FGFR4 could be a promising strategy for managing hypertension related to high phosphate intake. The activation of FGFR4 was associated with increased levels of the protein calcineurin A and heightened brain stem activity, contributing to elevated blood pressure during stress.
Other contributors to the study include Dr. Orson Moe, Dr. Scott Smith, Dr. Beverly Rothermel, and several other esteemed researchers from UT Southwestern. Their collaborative efforts were supported by grants from the National Institutes of Health and other prestigious institutions.
Broader Implications and Future Directions
The implications of this research extend beyond individual dietary choices, highlighting the need for public health strategies to address the overconsumption of phosphate additives. As Dr. Vongpatanasin holds prominent positions in nephrolithiasis research and hypertension, her insights are pivotal in shaping future clinical practices and dietary guidelines.
Meanwhile, the National Kidney Foundation provides a list of common foods high in phosphate additives, including dark colas, processed meats, and fast foods. These findings underscore the importance of consumer awareness and potential regulatory measures to limit phosphate additives in food products.
UT Southwestern, a leading academic medical center, continues to integrate groundbreaking research with clinical care and education. With a faculty that includes Nobel laureates and members of the National Academy of Sciences, the institution remains at the forefront of medical advancements.
As research progresses, the focus will be on translating these findings into practical treatments for hypertension, potentially reducing the prevalence of this condition and its associated health risks.
