Exploratory Study on the Efficacy of Betaine Hydrochloride in Treating Autoimmune Gastritis

Autoimmune gastritis (AIG) is a chronic progressive autoimmune disorder characterized by the destruction of gastric parietal cells, leading to atrophy of the acid-secreting gastric mucosa. The loss of parietal cells results in gastric acid deficiency and intrinsic factor deficiency, which in turn impairs the absorption of iron and vitamin B12, leading to clinical manifestations such as iron deficiency anemia, pernicious anemia, and neuropsychiatric symptoms. Studies indicate that 4-12% of AIG patients develop type 1 gastric neuroendocrine tumors (NETs), and these patients also face a 3-7 times higher risk of gastric adenocarcinoma, with an incidence rate ranging from 0.9% to 9%.

Currently, there are no anti-inflammatory, immunosuppressive, or biologic therapies available for AIG. Standard treatment involves iron and vitamin B12 supplementation. Due to progressive parietal cell destruction, AIG patients exhibit a hypochlorhydric state, which reduces pepsin activity, impairs gastric motility, and may lead to small intestinal bacterial overgrowth (SIBO), often causing symptoms such as dyspepsia. Additionally, low gastric acid levels can interfere with the absorption of trace elements like iron and calcium. Insufficient gastric acid also promotes bacterial overgrowth in the stomach and increases N-nitroso compounds, elevating the risk of gastric cancer. Furthermore, gastric hypochlorhydria triggers a feedback mechanism that stimulates gastrin secretion from antral G cells, resulting in hypergastrinemia, which increases the risk of neuroendocrine tumors. Supplementation with betaine hydrochloride (with pepsin) can lower gastric pH in AIG patients, restore gastric acidity, improve protein digestion, alleviate dyspeptic symptoms, enhance the absorption of vitamins and minerals, correct gastric dysbiosis and SIBO, and reduce the risk of gastric cancer and neuroendocrine tumors.

This study aims to evaluate the effects of betaine hydrochloride (with pepsin) on gastrin levels, gastrointestinal symptoms, exhaled gas markers (NO, H2S, H2, and CH4), iron deficiency anemia parameters, AIG atrophy scores, and the incidence of gastric complications (hyperplastic polyps, neuroendocrine tumors, and gastric cancer). The study is divided into two groups: Group A (follow-up only, serving as the control group) and Group B (oral betaine hydrochloride). The study adopts a non-randomized, open-label, parallel-controlled design, where participants choose either the experimental group (oral betaine) or the control group (follow-up only) based on their preference. Both groups will be followed in parallel, and outcome differences will be compared, supplemented by within-group pre- and post-intervention analyses.

The study population consists of AIG patients diagnosed at the Second Affiliated Hospital of Zhejiang University School of Medicine. The diagnostic criteria for AIG are based on our team's published article in Clinics and Research in Hepatology and Gastroenterology: "A real-world study on the characteristics of autoimmune gastritis: A single-center retrospective cohort in China." Inclusion criteria include: serum gastrin levels >300 pmol/L or a history of type 1 gastric NETs or early gastric cancer treated with endoscopic submucosal dissection (ESD), age between 18 and 80 years, and signed informed consent. Exclusion criteria include: allergy to betaine hydrochloride, presence of peptic ulcers, other conditions causing elevated gastrin levels, and refusal to sign informed consent.

Group A (control group) will undergo follow-up only without intervention, while Group B will receive oral betaine hydrochloride (2 capsules three times daily with meals). The primary outcomes include changes in serum gastrin levels and improvements in the Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcomes include changes in iron deficiency anemia markers (serum iron, ferritin, hemoglobin), exhaled gas markers (NO, H2S, H2, CH4), AIG atrophy scores, and the incidence of gastric complications (hyperplastic polyps, NETs, and gastric cancer).