How Does Iron Deficiency Cause Changes to Epithelial Cells?

November 17, 2025 •

4 min read

Iron deficiency is the most common nutritional disorder in the world, affecting 29.9% of the global population, and its impact extends far beyond blood health. This critical mineral is a vital component of essential enzymes, and its deficiency profoundly impacts epithelial cells throughout the body, leading to structural and functional changes.

Quick Summary

Iron deficiency disrupts fundamental metabolic processes within epithelial cells, impairing cellular division, maturation, and energy production. This leads to visible tissue atrophy and compromised function in various systems, including the oral and gastrointestinal mucosa, demonstrating the systemic consequences of low iron status.

Key Points

Impaired DNA Synthesis: Low iron levels reduce the activity of ribonucleotide reductase, directly inhibiting DNA synthesis and slowing the proliferation of rapidly dividing epithelial cells.
Reduced Cellular Energy: Iron is a key component of enzymes in the electron transport chain, and its deficiency impairs mitochondrial function and ATP production, compromising cellular energy.
Tissue Atrophy: The decreased cell production and functional capacity lead to thinning and atrophy of epithelial tissues, commonly seen in the oral mucosa (atrophic glossitis) and the lining of the stomach and esophagus.
Compromised Wound Healing: In the gastrointestinal tract, iron deficiency can impair the repair mechanisms of the epithelial barrier, particularly after injury, by reducing cell proliferation.
Increased Oxidative Stress: An imbalance in iron-dependent enzymes and reactive oxygen species can lead to increased oxidative stress and cell damage in iron-deficient states.
Enhanced Vulnerability to Infections: The combination of epithelial atrophy and compromised immune function increases susceptibility to infections, such as oral candidiasis.

The Fundamental Role of Iron in Cellular Health

Iron is more than just a component of hemoglobin; it is a vital cofactor for many enzymes involved in critical cellular processes. These include DNA synthesis, which is necessary for cell proliferation, and the electron transport chain, which generates cellular energy (ATP). Epithelial cells, characterized by their high turnover rate and rapid division, are particularly sensitive to fluctuations in iron supply. Without adequate iron, these essential metabolic pathways become compromised, directly impacting the epithelial cells' ability to grow, repair, and mature properly.

Disruption of Cellular Proliferation and Energy

One of the most significant effects of iron deficiency on epithelial cells stems from its impact on the enzyme ribonucleotide reductase (RNR). RNR is an iron-dependent enzyme essential for converting ribonucleotides into deoxyribonucleotides, the building blocks of DNA. Without sufficient iron, RNR activity is reduced, halting DNA synthesis and impairing cell division. Epithelial tissues, which require constant renewal, suffer from this slowed proliferation, leading to atrophy. Additionally, iron-containing proteins such as cytochromes are central to mitochondrial respiration and ATP production. Reduced function of these proteins starves the cells of energy, further contributing to cellular dysfunction and tissue fragility.

Manifestations of Epithelial Cell Changes

Iron deficiency manifests in various epithelial tissues, leading to a range of noticeable clinical signs and symptoms. These effects can often appear even before overt anemia develops.

Oral Epithelial Abnormalities

Atrophic Glossitis: The tongue's surface can become smooth, red, and sore due to the atrophy of the filiform papillae. Studies show a reduction in overall epithelial thickness, especially in the maturing cell layers.
Angular Cheilitis: Painful fissures or cracks can form at the corners of the mouth.
Mucosal Atrophy: The general oral mucosa thins, potentially causing a burning sensation.
Increased Susceptibility to Infection: Atrophic mucosal changes, combined with altered immune responses due to iron deficiency, increase the risk of oral fungal infections like candidiasis.

Gastrointestinal Tract Abnormalities

Gastric Atrophy: The lining of the stomach can become thin and inflamed.
Duodenal Mucosal Hyperplasia: The mucosal lining of the duodenum, the primary site for iron absorption, can thicken and expand in a compensatory effort to increase iron uptake. However, this adaptive response is often insufficient.
Compromised Repair: Low dietary iron can impair the regenerative capacity of intestinal epithelial cells following injury, delaying wound healing in the gut.

Esophageal Changes

Plummer-Vinson Syndrome: In rare, severe, and prolonged cases of iron deficiency, this syndrome can develop, characterized by post-cricoid dysphagia (difficulty swallowing), iron-deficiency anemia, and upper esophageal webs. The atrophy of the pharyngeal and esophageal mucosa is believed to contribute to web formation.

Comparison of Normal vs. Iron-Deficient Epithelial Cells


Characteristic	Normal Epithelial Cells	Iron-Deficient Epithelial Cells
Cell Proliferation	Rapid, well-regulated division.	Reduced due to impaired DNA synthesis.
Maturation	Proceeds through distinct layers, culminating in mature cells.	Delayed or incomplete, leading to reduced maturation compartment thickness.
Cell Size	Consistent, normal cell dimensions.	Smaller cell size and reduced cytoplasmic diameter.
Energy (ATP) Production	Efficient due to iron-dependent mitochondrial enzymes.	Impaired due to reduced enzyme function in the electron transport chain.
Tissue Integrity	Robust mucosal barrier and tissue thickness.	Atrophic, thinner, and fragile mucosa, increasing vulnerability to damage.
Inflammatory Response	Balanced and appropriate.	Oxidative stress and chronic inflammation can be induced, potentially leading to increased damage.

The Mechanism of Epithelial Atrophy

The atrophy observed in epithelial tissues in cases of iron deficiency is not simply a passive process but a direct consequence of the disruption of core cellular functions. This includes the reduced DNA synthesis and the metabolic compromise, which collectively slow the production of new, fully functional cells. The existing cell population may also shrink in size, contributing to the overall thinning of the tissue. In the context of the GI tract, this can compromise the delicate intestinal barrier, potentially contributing to further health issues.

The altered cell kinetics, such as a shortened DNA synthesis (S) phase observed in some studies, suggests the body is trying to compensate by speeding up cell production, but this is met with smaller, less mature cells that fail to properly replace the shedding ones. This leads to a vicious cycle of insufficient repair and regeneration, leaving the mucosa susceptible to persistent injury and inflammation.

Conclusion

Iron deficiency imposes a significant burden on epithelial cells by disrupting key metabolic processes, including DNA synthesis and energy production. This systemic impact leads to observable atrophy and functional impairment in various tissues, such as the oral mucosa, gastrointestinal tract, and esophagus. The resulting changes, including atrophic glossitis and compromised tissue repair, highlight the widespread consequences of iron deprivation beyond simple anemia. Recognizing these early epithelial changes can be crucial for diagnosing iron deficiency, as they often precede severe hematological symptoms. Therefore, addressing iron deficiency is not only vital for blood health but also for maintaining the integrity and function of the body's epithelial barriers. For further details on specific epithelial syndromes related to iron deficiency, refer to the National Institutes of Health on Plummer-Vinson Syndrome.

Frequently Asked Questions

The primary reason is the disruption of key cellular metabolic processes that depend on iron, particularly DNA synthesis and energy production. Iron is required for the enzyme ribonucleotide reductase (RNR), which is critical for cell division, and for components of the mitochondrial electron transport chain, which provides energy.

Iron deficiency can cause the oral mucosa to become atrophic and thin. This leads to conditions like atrophic glossitis (a smooth, sore tongue), angular cheilitis (fissures at the mouth corners), and a general burning sensation in the mouth.

Low iron impairs the regenerative capacity of intestinal epithelial cells. After an injury, the cells' ability to proliferate and migrate to repair the damage is compromised, leading to delayed wound healing.

Plummer-Vinson Syndrome is a rare condition specifically associated with severe, prolonged iron deficiency, but not all iron deficiency leads to it. Its characteristic esophageal webs are thought to be caused by iron deficiency-induced mucosal atrophy.

Yes, epithelial abnormalities can occur in earlier stages of iron deficiency, sometimes before overt iron-deficiency anemia is fully developed. For instance, oral mucosal changes can be early indicators.

The atrophic changes in the oral mucosa make it more susceptible to infection. The compromised mucosal barrier, combined with potential immune system impairments related to iron deficiency, creates a more favorable environment for fungal overgrowth.

While iron is a double-edged sword, causing oxidative stress in excess, iron deficiency can also induce oxidative stress through impaired enzymatic function and disrupt the balance of pro-oxidant and antioxidant systems. This can lead to cellular damage and contribute to the observed epithelial changes.