Unveiling the clinical connections between vitamin B12 deficiency anemia, Hashimoto thyroiditis, and hypothyroidism:...

Clinical evidence indicates a strong association between nutritional anemia and hypothyroidism. However, whether nutritional factors contribute directly to the onset of hypothyroidism remains unclear. In this study, we aimed to address this knowledge gap by examining the causal relationship between nutritional anemia and hypothyroidism. We conducted rigorous univariate and multivariate Mendelian randomization (MVMR) analyses using data from the Integrative Epidemiology Unit Open Genome-wide Association Studies database. We found that both vitamin B12 deficiency anemia (B12DA) and iron deficiency anemia (IDA) have a positive influence on hypothyroidism. However, whereas MVMR analysis revealed that the causal relationship between B12DA and hypothyroidism persisted after adjusting for IDA, no significant causal associations were observed between IDA (adjusted for B12DA) and hypothyroidism. In addition, we detected a causal relationship between Hashimoto thyroiditis and hypothyroidism, and that B12DA had a significant causal effect on Hashimoto thyroiditis. MVMR analysis further revealed that after adjusting for each other, the causal relationships among B12DA, Hashimoto thyroiditis, and hypothyroidism persisted. Finally, although B12DA and Hashimoto thyroiditis are both risk factors for thyrotoxicosis, the relationship between B12DA and thyrotoxicosis disappeared after adjusting for Hashimoto thyroiditis in MVMR analysis. Our findings indicate the role of B12DA in hypothyroidism development and that Hashimoto thyroiditis mediates the causal pathway between B12DA and hypothyroidism. These findings emphasize the importance of considering nutritional status, particularly B12 deficiency, in the context of hypothyroidism and anemia, and potentially provide new insights for their management.