AUTHOR=Cao Pengwei , Shui Zhihua , Zhang Xinyu , Zhou Endi , Liang Tan , Cao Feng , Yang Chuang , Zhang Daoxiang , Liu Lei , Chen Jiangming , Liu Fubao 
  
TITLE=Essential minerals and risk of pancreatic diseases: a large-scale prospective cohort study
  
JOURNAL=Frontiers in Nutrition
  
VOLUME=Volume 13 - 2026
  
YEAR=2026
  
URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2026.1773339
  
DOI=10.3389/fnut.2026.1773339
  
ISSN=2296-861X
  
ABSTRACT=ObjectivePancreatic 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.MethodsThis 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.ResultsPheWAS 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.ConclusionMineral 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.