Iron2026-08

Heme Iron Polypeptide Resolves Iron-deficiency Anemia in Rats and Mice.

He Yue, Shine Jacob S, Sriram Sitara, Fraga Melissa et al. — Biological trace element research

Summary

This animal study explored how effectively a specific type of iron, called heme iron polypeptide (HIP), can treat iron deficiency. Researchers found that HIP successfully corrected iron-deficiency anemia in rats and mice, performing similarly to other common iron sources. This suggests HIP is an effective iron source and validates these animal models for studying how the body absorbs heme iron.

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Key points

Heme iron polypeptide (HIP) is a form of iron derived from animal blood products.
This study found that HIP effectively treated iron-deficiency anemia in rats and mice.
HIP's effectiveness was comparable to other common iron sources tested in the animals.
The research confirms that rats and mice are useful models for studying how the body absorbs heme iron.

What the study looked at

This study aimed to answer two main questions: first, how effective is heme iron polypeptide (HIP) in treating iron deficiency compared to other iron sources, and second, whether animal models like rats and mice are suitable for studying how the body absorbs heme iron. To investigate this, researchers used rats and mice that were made iron-deficient. They then divided the animals into groups and fed them different diets for several weeks. One group received a diet with HIP, another received a common non-heme iron source (iron sulfate), and a third received heme iron from red blood cells. The researchers monitored the animals' iron levels and anemia status. What they found was that all three experimental diets, including the one containing HIP, successfully corrected the iron-deficiency anemia in both rats and mice. The animals' iron-related blood markers returned to normal levels. This indicates that HIP is an effective source of iron for improving iron status, and it also confirms that these animal models are valuable tools for understanding the complex process of heme iron absorption and utilization in the body.

Dietary takeaway

This animal study suggests that heme iron polypeptide, a form of iron found in animal products, can be an effective way to improve iron levels. While this research was conducted in rats and mice, it supports the idea that diverse sources of iron, including those from animal-derived supplements or foods, can help address iron deficiency. It's important to remember that findings from animal studies don't always directly apply to humans, and more research is needed to confirm these effects in people.

Abstract

Dietary iron exists mainly as non-heme iron (NHI) and heme iron (HI). Mechanisms of NHI absorption have been recently revealed, but details of HI absorption remain uncertain. Heme is likely absorbed by receptor-mediated endocytosis, but to date, no receptor (or transporter) has been identified. Within enterocytes, heme may be catabolized by heme oxygenase in the ER, thus liberating ionic iron that then joins the labile cytosolic iron pool. One limiting factor in HI absorption research has been the lack of tractable experimental models. We addressed this shortcoming by establishing a nutritional paradigm that enables investigation of this process using pre-clinical rat and mouse models (. 2025;10(11):e184742). The approach utilized specially formulated diets containing lyophilized porcine RBCs that contained ~ 85% HI and 15% NHI. We have expanded upon these studies here to include heme iron polypeptide (HIP) as an iron source (Proferrin; Colorado Biolabs). HIP, a partially proteolyzed form of hemoglobin, is highly enriched for HI (~ 93% HI, 7% NHI). We again utilized a classic depletion/repletion experimental design in SD rats and C57BL/6 mice to compare outcomes when using three AIN-93-based test diets with ~ 50 ppm total iron: a HIP diet, a NHI diet containing FeSO and a HI-enriched diet formulated with porcine RBCs. Outcomes notably showed that all three experimental diets similarly corrected the anemia and normalized erythropoietic biomarkers in iron-depleted rats and mice within the 24-28-day test periods. These results solidify the concept that laboratory rodents are useful in vivo models to study intestinal HI absorption and utilization.

View on PubMed →DOI: 10.1007/s12011-026-05094-6