Iron deficiency and pernicious anemia both result from destruction of parietal cells.
Gastritis destroys parietal cells
Parietal cells make two things: intrinsic factor and hydrochloric acid. Gastritis has several possible causes: autoimmune attack, H. pylori, long-term PPI use, or gastric surgery. Regardless of which one is responsible, the damage takes out acid and intrinsic factor production together.
The acid connection is specifically relevant for iron absorption. Food iron is mostly ferric (Fe3+), and stomach acid helps keep it soluble and facilitates its reduction to ferrous (Fe2+), the form DMT1 transporters in the duodenum can absorb. Achlorhydria impairs that process. So even with adequate dietary iron, absorption drops.
H. pylori overlap. Active H. pylori infection can contribute to both iron and B12 deficiency through additional mechanisms. H. pylori is also more common in younger patients with early autoimmune gastritis and becomes less detectable as gastric atrophy advances.
Sequencing. Iron deficiency can appear years before B12 deficiency becomes clinically apparent in autoimmune gastritis. The gastritis process is progressive: declining acid production impairs iron absorption early, while the body’s large B12 stores can delay B12 deficiency for years even as intrinsic factor production declines. Iron stores can deplete much sooner when absorption consistently fails to replace ongoing losses, so iron deficiency is often the first sign of the same process that eventually produces pernicious anemia. Iron deficiency surfaces years to decades earlier because it’s a symptom of earlier-stage disease.
Calcium. Low stomach acid can reduce calcium carbonate absorption, particularly when it is taken on an empty stomach. Calcium citrate is much less dependent on stomach acid.
Vitamin C. Gastric juice normally contains high concentrations of vitamin C. Atrophic gastritis and achlorhydria reduce intragastric vitamin C, which can further impair non-heme iron absorption.
PA rarely travels alone
Autoimmune atrophic gastritis frequently occurs alongside other autoimmune conditions, including autoimmune thyroid disease, type 1 diabetes, celiac disease, Addison’s disease, and vitiligo. Some of these conditions bring their own nutritional problems. Celiac disease, for example, damages the small intestine and can worsen iron deficiency while also contributing to deficiencies of folate and the fat-soluble vitamins A, D, E, and K. A broader pattern of deficiencies in someone with PA often points to overlapping autoimmune disease on top of the underlying acid and intrinsic factor loss.
Inflammation raises ferritin independently of iron stores. A normal or elevated ferritin can still mask iron deficiency. Ferritin has to be interpreted alongside transferrin saturation and the inflammatory context.
Iron deficiency in PA is likely underdiagnosed. Ferritin is unreliable in inflammatory conditions. Autoimmune disease itself is frequently misdiagnosed or dismissed. Both factors work against catching iron deficiency early. Iron deficiency shows up in roughly three-quarters of newly diagnosed PA patients, and more than a third of those cases are only caught during follow-up rather than at diagnosis.
References
Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion
Hershko et al. followed 160 patients with autoimmune gastritis and documented an age-related progression from iron deficiency to B12 depletion. The paper also explains the role of gastric acid in solubilizing and reducing food iron and documents associated autoimmune disease, making it a useful foundation for several mechanisms discussed in this article.
https://pubmed.ncbi.nlm.nih.gov/16239424/
Iron deficiency shows up before B12 deficiency
Autoimmune gastritis destroys acid production before it destroys enough parietal cell mass to also take out intrinsic factor and B12 absorption.
Autoimmune gastritis impairs both iron and vitamin B12 uptake, but iron deficiency shows up at a younger age, often many years before pernicious anemia develops.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065578/
Iron deficiency is a known complication of achlorhydria and can precede the onset of pernicious anemia.
https://link.springer.com/article/10.1007/s12026-016-8841-7
https://pubmed.ncbi.nlm.nih.gov/16239424/
Achlorhydria blocks iron absorption specifically
Reduced gastric acid impairs the conversion of dietary iron into an absorbable form, and lower ascorbic acid levels compound the problem, together driving the iron deficiency seen in autoimmune gastritis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065578/
Calcium absorption and achlorhydria
In achlorhydric patients, calcium carbonate was poorly absorbed in the fasting state compared with calcium citrate. The difference is substantially reduced when calcium carbonate is taken with food.
Recker, New England Journal of Medicine
https://pubmed.ncbi.nlm.nih.gov/4000241/
H. pylori can contribute to both iron and B12 deficiency
The nexus between Helicobacter pylori infection and anemia โ a systematic review
This systematic review examines how H. pylori may contribute to both iron and B12 deficiency. Chronic gastric inflammation can impair iron absorption, while gastric atrophy can reduce intrinsic factor production and B12 absorption.
https://www.frontiersin.org/journals/hematology/articles/10.3389/frhem.2024.1423494/full
H. pylori prevalence declines as atrophic gastritis advances
H. pylori depends on gastric epithelial cells to survive. As atrophic gastritis progresses and destroys those cells, the bacteria are eliminated on their own, without antibiotic treatment. This helps explain why H. pylori is more common in younger patients with early iron deficiency than in older patients with advanced disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794513/
https://onlinelibrary.wiley.com/doi/10.1111/hel.12669
Ferritin alone can mislead in inflammatory conditions
Ferritin rises with inflammation independent of actual iron stores, which is why transferrin saturation has to be read alongside it rather than ferritin used on its own.
Diagnosis and management of iron deficiency in chronic inflammatory conditions
Iron deficiency in pernicious anemia: prevalence and treatment response
A prospective study of newly diagnosed PA patients found iron deficiency in 75% of cases, more than a third detected only during follow-up. Iron deficiency was associated with parietal cell antibodies in the absence of intrinsic factor antibodies and with milder B12 deficiency, a profile the authors suggest may reflect earlier-stage disease.
https://www.sciencedirect.com/science/article/abs/pii/S0261561424000852
Autoimmune disease is frequently misdiagnosed
A 2025 Cambridge study of nearly 3,400 patients with systemic autoimmune rheumatic disease documented how often these conditions are misdiagnosed as psychosomatic or psychiatric.
Rheumatology, 2025
https://academic.oup.com/rheumatology/article/64/6/3842/8042899
PA rarely travels alone
Autoimmune atrophic gastritis frequently occurs alongside other autoimmune conditions, including autoimmune thyroid disease, type 1 diabetes, celiac disease, Addison’s disease, and vitiligo. Associated conditions can broaden the nutritional deficiency pattern beyond the direct effects of autoimmune gastritis. Celiac disease is particularly relevant because small-intestinal damage can contribute to iron, folate, and fat-soluble vitamin deficiencies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734642/
https://pubmed.ncbi.nlm.nih.gov/30561426/