Essential minerals and risk of pancreatic diseases: a large-scale prospective cohort study

Pancreatic disorders are characterised by high mortality rates and limited therapeutic options and pose a global health challenge. As a dual-function organ with endocrine and exocrine roles, the pancreas exhibits a heightened sensitivity to the disruption of mineral homeostasis. However, the pathophysiological associations between mineral imbalances and pancreatic diseases remain controversial, and large-scale population studies validating these relationships are lacking.

This prospective cohort study used data from the UK Biobank and enrolled 191,875 participants with a median follow-up of 13 years. A phenome-wide association study (PheWAS) was used to systematically evaluate the associations between mineral levels and multisystem disorders. Multivariate Cox proportional hazards regression models quantified risk associations, whereas restricted cubic spline analyses elucidated dose-response relationships.

PheWAS identified multiple significant associations within the digestive system, including cholelithiasis, gastritis/duodenitis, and pancreatic diseases. Elevated serum iodine and selenium levels demonstrated significant carcinogenic effects on pancreatic cancer. In contrast, copper, magnesium, and manganese exhibited protective effects against acute pancreatitis, with manganese displaying a U-shaped dose-response relationship. Subgroup analyses revealed increased iodine and selenium carcinogenicity in females, older individuals, and smokers, whereas metal-related protection was more pronounced in males and normal-weight individuals.

Mineral homeostasis exerts systemic effects on digestive pathophysiology. Elevated iodine and selenium levels are modifiable risk factors for pancreatic carcinogenesis, particularly in females and older populations. The inverse association of copper, magnesium, and manganese with acute pancreatitis suggests that they are potential therapeutic targets. The attenuated association in chronic pancreatitis implies an etiological predominance of non-mineral mechanisms.