Newswise — DALLAS – June 30, 2025 – Diets rich in phosphate additives, commonly found in processed foods, have been linked to increased blood pressure by triggering a brain signaling pathway and overactivating the sympathetic nervous system, according to researchers at UT Southwestern. This discovery could pave the way for new treatment strategies for hypertension caused by excessive phosphate consumption.
“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,” said Han Kyul Kim, Ph.D., Assistant Professor of Internal Medicine in the Division of Cardiology at UT Southwestern.
Understanding Phosphate’s Role in Hypertension
Inorganic phosphate, often used as a preservative or flavor enhancer, is prevalent in packaged foods, processed meats, and other dietary staples. The study reveals that the average adult in developed countries consumes phosphate well above the recommended daily allowance. When consumed in excess, circulating fibroblast growth factor-23 (FGF23) can enter the brain and contribute to hypertension, as detailed in the study published in Circulation.
Hypertension, a condition where arterial wall pressure is too high, affects 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 Methodology and Findings
UTSW researchers conducted a series of tests measuring FGF23 protein levels, mean arterial pressure, and renal sympathetic nerve activity in rats on a high (1.2%) phosphate diet compared to those on a normal (0.6%) phosphate diet. These measurements were also taken during stress responses induced by spinal cord stimulation.
The results showed that rats on the high phosphate diet had increased levels of FGF23 protein in their serum, cerebrospinal fluid, and brain stem. This protein was able to cross the blood-brain barrier, causing elevated blood pressure both at rest and during physical stress.
“FGF23 can cross into the brain and influence the brain stem centers that control blood pressure,” said senior corresponding author Wanpen Vongpatanasin, M.D., Professor of Internal Medicine at UT Southwestern.
Potential Therapeutic Targets
Further analysis revealed that inhibiting fibroblast growth factor receptor 4 (FGFR4) during simulated exercise reduced the negative effects of a high phosphate diet, suggesting a link between FGFR4 and overactivation. In contrast, inhibition of FGFR1 did not yield the same results.
Researchers discovered that FGFR4 activation, prompted by excess dietary phosphate, led to increased levels of calcineurin A and brain stem activity, potentially contributing to elevated blood pressure and sympathetic nervous system overactivation during exercise.
Contributions and Support
Other contributors to the study include Orson Moe, M.D., Scott Smith, Ph.D., Beverly Rothermel, Ph.D., and several other distinguished researchers from UT Southwestern. This research was supported by grants from the National Institutes of Health and other notable institutions.
Implications and Future Directions
The findings of this study highlight the need for public awareness regarding the consumption of phosphate-rich foods and their potential health impacts. As phosphate additives are common in many everyday foods, understanding their effects on health is crucial for developing dietary guidelines and therapeutic interventions.
UT Southwestern’s research underscores the importance of continued investigation into dietary components and their systemic effects, aiming to translate these findings into practical treatments for hypertension and related conditions.
For more information on phosphate additives and their presence in common foods, the National Kidney Foundation offers a comprehensive guide. As research progresses, it is hoped that new strategies will emerge to mitigate the health risks associated with high phosphate diets.
