Is achlorhydria a cause of iron deficiency anemia?

Abstract

We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause of iron deficiency anemia (IDA) in humans. First, we analyzed the currently available research on the association between achlorhydria and IDA. When gastric acid secretion was measured after maximal stimulation, the frequency of achlorhydria (or severe hypochlorhydria) was 44% in patients with idiopathic IDA and 1.8% in healthy controls. In some patients with pernicious anemia, presumed achlorhydria preceded the development of IDA in time. However, we found no credible evidence that IDA caused gastritis or that IDA preceded the development of achlorhydria. Thus, correlational results favor achlorhydria as the causal factor in the association between achlorhydria and IDA. Second, we sought to determine whether gastritis and achlorhydria cause negative iron balance. When biosynthetic methods were used to isotopically label iron in food, achlorhydric patients were found to have severe malabsorption of nonheme iron, which persisted after the development of IDA. In 1 study, achlorhydria reduced the normal increase in heme-iron absorption from hemoglobin in response to iron deficiency. After an injection of isotopic iron into normal men, the physiologic loss of iron from the body was found to be 1 mg/d. Patients with chronic gastritis had excess fecal loss of isotopically tagged plasma iron. Calculations based on these results indicate that the absorption of iron from a typical Western diet by achlorhydric patients would be less than physiologic iron losses, creating a negative iron balance that could not be overcome by the adaptive increase in duodenal iron absorptive capacity that occurs in response to iron deficiency. The combination of results from these correlational and pathophysiologic studies supports the hypothesis that gastritis-induced achlorhydria can be an independent cause of IDA.

An updated systematic review and meta‐analysis on the association between Helicobacter pylori infection and iron deficiency anemia

“…9 Gastric juice ascorbic acid and low gastric pH are important factors in the absorption of dietary iron. 76,77 showed more frequent atrophic gastritis in patients with unexplained IDA than in their matched controls; the former also displayed more frequent corpus gastritis, while similar proportions of antrum gastritis were found in both groups. 79 Kaye et al 27 showed that among patients who underwent investigation for anemia, body atrophy was sevenfold more prevalent than among controls; and a positive dose-response association was found between gastric body atrophy and anemia.…”

“…The level of gastric juice ascorbic acid was found to be significantly lower in individuals infected with CagA‐positive strains than in those with CagA‐negative strains . Gastric juice ascorbic acid and low gastric pH are important factors in the absorption of dietary iron . Thus, H. pylori ‐induced alteration in gastric pH levels and/or gastric juice ascorbic acid levels may be expected to affect the homeostasis of iron biomarkers.…”

ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats

“…The stomach is an active reservoir that stores, triturates, and slowly dispenses partially digested food into the intestine for further digestion and absorption, and also controls appetite and satiety . Its main secretory function is secretion of gastric acid, which initiates peptic hydrolysis of dietary proteins, liberates vitamin B12 from dietary protein, facilitates duodenal absorption of inorganic iron and calcium, stimulates pancreatic HCO 3 − secretion via secretin release, suppresses antral gastrin release, and modulates the intestinal microbiome by killing microorganisms and preventing bacterial overgrowth . Comprehensive overviews of the regulation of gastric acid secretion (Supplement 1) and regulation of gastric mucosal barrier function (Supplement 2) are available in the Supporting Information.…”

Anemia and iron deficiency in gastrointestinal and liver conditions

“…AIG, first described by Faber in 1909 as achlorhydric gastric atrophy , is a chronic progressive inflammatory condition leading to the decrease or disappearance of parietal cells, which results in reduced or absent acid production (hypochlorhydria or achlorhydria)[ 59 ].The lack of gastric acidity has only recently been confirmed as key factor for impaired intestinal iron absorption[ 60 ]. IDA is more often associated with AIG than classical pernicious anemia and frequently precedes vitamin B 12 deficiency (at least in fertile women)[ 61 , 62 ].…”