Dietary Heme Iron: A Review of Efficacy, Safety and Tolerability

Abstract

Iron is a fundamental micronutrient essential for oxygen transport, enzymatic activity, and metabolic homeostasis. Yet it remains the most deficient nutrient in the world, with more than 2 billion people estimated with iron deficiency anemia. In the diet, animal foods provide iron primarily as heme iron. Dietary heme iron is absorbed through the active transport pathways catalyzed by heme oxygenase in the intestinal enterocyte. This form of heme differs in its bioavailability, absorption mechanisms, and tolerability compared to non-heme forms of iron, including iron salts and chelates. Adding more heme iron to a diet, including through iron supplements, may help to reduce the prevalence of iron deficiency. Future research should focus on research of heme iron supplementation strategies to enhance absorption efficiency, gut microbiome health, and safety, ensuring optimal iron status across diverse populations.

Keywords: ferritin; heme; hemoglobin; iron; nutrition.

Figure 1

Recommended Daily Allowance (RDA) for iron (18 mg) and the iron content of common foods. One serving of common animal proteins such as ground beef and chicken contains a fraction of the RDA, one indication that it can be challenging to meet iron intake (USDA).

Figure 2

Molecular structures of heme iron (a) and iron sulfate (b).

Figure 3

Iron absorption and transport mechanisms. Heme iron, sourced from animal foods, is actively absorbed intact into intestinal enterocytes. Heme iron bypasses dietary inhibitors to the enterocyte, where heme oxygenase re-leases ferrous iron (Fe²⁺). This is then exported into the bloodstream through ferroportin. Alternatively, non-heme iron, predominantly from synthetic or plant-based foods, often initially exists as ferric iron (Fe³⁺), requiring reduction to ferrous iron (Fe²⁺) by duodenal cytochrome B (DcytB) before approaching the competitive divalent metal-ion transporter 1 (DMT1). Absorption of non-heme iron is influenced by dietary enhancers like ascorbic acid and inhibitors such as polyphenols, phytates, and calcium, resulting in lower bioavailability compared to heme iron.

Figure 4

The complex relationship between gut microbiota and iron homeostasis, highlighting iron’s pivotal role in shaping microbial composition and activity in the gastrointestinal tract. Iron availability influences the balance between commensal and pathogenic microorganisms, with unabsorbed iron promoting the proliferation of pathogens such as Salmonella and Escherichia coli, while limiting beneficial bacteria like Lactobacillus and Bifidobacterium. Beneficial microbes contribute to intestinal health by maintaining barrier integrity and producing metabolites such as short-chain fatty acids (SCFAs), which enhance iron absorption. However, excessive free iron disrupts microbial balance, resulting in dysbiosis, oxidative stress, and inflammation in the gut. The figure emphasizes how iron supplementation strategies must carefully regulate iron availability to preserve gut microbial health and prevent adverse effects on the intestinal epithelium (adapted from [43]).