According to Gram Research analysis, red blood cells produce a protein called FGF23 that actually prevents the body from making new red blood cells, worsening anemia in people with iron deficiency or kidney disease. In mice, removing this protein from red blood cells corrected anemia and improved recovery, suggesting new treatment targets for people whose anemia doesn’t respond to standard medicines.
Scientists discovered that when your body doesn’t have enough iron, it produces a special protein called FGF23 that actually prevents your body from making new red blood cells. This creates a confusing problem: your body tries to fix anemia (low red blood cells) but accidentally makes it worse. Researchers found that blocking this protein in red blood cells helped mice recover from anemia, even when they had iron deficiency or kidney disease. This discovery could lead to new treatments for millions of people with anemia who don’t respond well to current medicines.
Key Statistics
A 2026 research article published in Blood found that erythroid-specific deletion of Fgf23 corrected anemia in iron-deficient mice, while overexpression of the same protein induced anemia in healthy mice, demonstrating that red blood cell-produced FGF23 directly causes anemia.
According to the 2026 Blood study, intact FGF23 produced by red blood cells dose-dependently blocked the differentiation of erythroid progenitors in laboratory culture by triggering mitochondrial dysfunction, with effects fully reversed by FGFR1 inhibitor treatment.
A 2026 research analysis showed that erythroid-specific deletion of Fgf23 in a chronic kidney disease animal model prevented the development of anemia of CKD, suggesting this protein is a key driver of kidney disease-related anemia.
The 2026 Blood research demonstrated that increased intact FGF23 production from red blood cells—caused by deleting the Furin cleavage enzyme—aggravated iron deficiency-induced anemia in mice, proving the intact form of the protein is the harmful version.
The Quick Take
- What they studied: How a protein called FGF23 made by red blood cells affects the body’s ability to make new red blood cells, especially in people with iron deficiency or kidney disease
- Who participated: Laboratory mice that were genetically modified to either lack or overproduce FGF23 in different cell types, plus cells grown in laboratory dishes
- Key finding: Red blood cells that produce FGF23 actually harm the production of new red blood cells by blocking a growth signal, and removing this protein fixed anemia in mice with iron deficiency and kidney disease
- What it means for you: This research suggests new drug targets for treating anemia that doesn’t respond to standard treatments, though human studies are still needed to confirm these findings work in people
The Research Details
Researchers used genetically engineered mice where they could turn off or turn up the FGF23 gene in specific cell types—either bone cells or red blood cells. They fed some mice a normal diet and others an iron-poor diet to create iron deficiency anemia. They then measured how much FGF23 was produced and how it affected red blood cell production. The team also grew red blood cell precursors in laboratory dishes and exposed them to FGF23 to watch what happened at the cellular level. They used special inhibitor drugs to block the FGF23 signal and see if that reversed the harmful effects.
Previous research showed that FGF23 levels were high in people with anemia, but scientists didn’t know which cells were making it or how it was causing problems. By using mice where they could control FGF23 in specific cell types, researchers could finally prove that red blood cells themselves were the culprit, not bone cells. This targeted approach reveals exactly where to intervene with new medicines.
This is a mechanistic study published in Blood, a top-tier scientific journal. The researchers used multiple approaches (genetic models, cell culture, and drug inhibitors) to confirm their findings from different angles. The use of genetically modified mice allows for precise cause-and-effect conclusions. However, these are mouse studies, so results may not directly translate to humans. The study lacks a specified sample size in the abstract, which is typical for animal research but limits statistical power assessment.
What the Results Show
When mice didn’t have enough iron, their red blood cells started making FGF23 protein, while bone cells made a different form of the protein. When researchers removed the ability of red blood cells to make FGF23, the mice’s anemia improved significantly—their bodies made more red blood cells and recovered better. In contrast, when they removed FGF23 from bone cells, it had no effect on anemia. This proved that red blood cell-produced FGF23 was the problem. When researchers forced red blood cells to make even more FGF23, healthy mice developed anemia, showing that this protein actively damages red blood cell production. The FGF23 protein worked by blocking a growth signal (FGFR1) that red blood cell precursors need to develop properly, causing their energy-producing structures (mitochondria) to malfunction.
In mice with chronic kidney disease—a condition where FGF23 levels naturally rise—removing FGF23 from red blood cells prevented the development of anemia that normally occurs. When researchers blocked the enzyme (Furin) that breaks down FGF23, more intact FGF23 accumulated and made anemia worse, confirming that the intact form of the protein is the harmful version. Using a drug that blocks the FGFR1 signal completely reversed the harmful effects of FGF23 on red blood cell development in laboratory dishes.
Earlier studies showed that high FGF23 levels were linked to anemia in people with kidney disease and iron deficiency, but researchers couldn’t prove which cells were responsible or how the protein caused harm. This study answers both questions by showing that red blood cells themselves are the source of the problem and identifying the exact mechanism—blocking the FGFR1 growth signal. This finding contradicts the assumption that bone cell-produced FGF23 was the main culprit in anemia.
This research was conducted entirely in mice and laboratory cell cultures, so results may not work the same way in humans. The study doesn’t include human patient data or clinical trials. The exact dose of FGF23 that causes problems in humans remains unknown. The research focuses on one mechanism and doesn’t explore whether other factors might also contribute to anemia in these conditions. Long-term effects of blocking FGF23 in humans are not addressed.
The Bottom Line
Based on this research, doctors may eventually develop drugs that block FGF23 or its signal (FGFR1) to treat anemia in people with iron deficiency or kidney disease who don’t respond to standard treatments. However, human clinical trials are needed first to confirm safety and effectiveness. Current standard treatments (iron supplements, erythropoietin injections, or kidney disease management) remain the first-line approach. Confidence level: Moderate—strong mechanistic evidence in animals, but no human data yet.
This research is most relevant to people with iron deficiency anemia or chronic kidney disease who develop anemia despite standard treatments. It’s also important for researchers developing new anemia medications and for doctors treating patients with resistant anemia. People with normal iron levels and healthy kidneys don’t need to change anything based on this study.
If drugs targeting this pathway are developed, they would likely take 5-10 years to reach patients through clinical trials and FDA approval. In the meantime, this research helps scientists understand why some people’s anemia doesn’t improve with current treatments.
Frequently Asked Questions
What is FGF23 and why does it cause anemia?
FGF23 is a protein that red blood cells produce during iron deficiency or kidney disease. It blocks a growth signal (FGFR1) that new red blood cells need to develop, essentially telling your body to stop making blood cells when you need them most. This creates a harmful cycle that worsens anemia.
Can blocking FGF23 treat anemia that doesn’t respond to iron supplements?
Mouse studies show that blocking FGF23 or its signal reversed anemia, even in kidney disease. However, human clinical trials haven’t been done yet. If successful in people, FGF23-blocking drugs could become a new treatment option for resistant anemia within 5-10 years.
Does everyone with anemia have high FGF23 levels?
No. High FGF23 appears mainly in people with iron deficiency anemia or chronic kidney disease. People with anemia from other causes (like vitamin B12 deficiency or blood loss) may have normal FGF23 levels, so this treatment wouldn’t help them.
Should I ask my doctor about FGF23 testing if I have anemia?
FGF23 testing isn’t yet standard for anemia diagnosis or treatment. Focus on standard tests (hemoglobin, iron levels, kidney function) first. Ask your doctor about FGF23 only if your anemia doesn’t improve with standard treatments and you want to explore research-based options.
How long would it take for FGF23-blocking drugs to become available?
If development begins now, FGF23-blocking medications would likely take 5-10 years to complete human trials and receive FDA approval. Current treatments (iron supplements, erythropoietin, kidney disease management) remain the standard approach for the next several years.
Want to Apply This Research?
- Track hemoglobin levels (red blood cell count) and iron levels monthly if you have anemia, noting any changes after starting new treatments. Record energy levels and fatigue on a 1-10 scale daily to monitor symptom improvement.
- If you have anemia, use the app to set reminders for iron supplement timing (usually 2 hours away from calcium-rich foods for better absorption) and track which foods boost iron intake. Log any new medications prescribed and their effects on your energy and symptoms.
- Create a long-term dashboard showing your hemoglobin trends over months, correlating with treatment changes. Set alerts if your hemoglobin drops below your target range or if fatigue worsens, prompting you to contact your doctor for possible treatment adjustments.
This research describes laboratory findings in mice and cell cultures. It has not been tested in humans and should not be used to change your current anemia treatment. If you have anemia, iron deficiency, or chronic kidney disease, consult your doctor before making any changes to your treatment plan. FGF23-blocking medications are not yet available for human use. This article is for educational purposes only and does not constitute medical advice.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.