Provided by Sichuan International Medical Exchange and Promotion Association
Acute pancreatitis (AP), which affects people of all ages, is one of the leading causes of hospital admission due to gastrointestinal diseases. Approximately 20% of patients develop moderate or severe acute pancreatitis, which carries extremely high mortality and disability rates. Even for those who recover, lifelong complications often follow, significantly affecting their quality of life.
To date, many questions regarding the optimal treatment of acute pancreatitis remain unanswered. Most importantly, pharmacological agents that can inhibit early organ injury in the pancreas are needed.
A team led by Dr. Chuanwen Fan (Department of Gastrointestinal Surgery, West China Fourth Hospital, Sichuan University, and Department of Biomedical and Clinical Sciences, Linköping University), under the supervision of Prof. Dr. Xianming Mo (the senior author, West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Laboratory of Stem Cell Biology, State Key Laboratory, West China Hospital, Sichuan University), combined human genetic epidemiology and animal models to discover and confirm the role of vitamin B12 in the prevention and mitigation of acute pancreatitis.
Fan explained that the team first conducted meta-analyses of genome-wide association studies (GWAS) using the largest genetic datasets available for pancreatitis. They then employed a Mendelian randomization approach to investigate the relationships between various one-carbon metabolism nutrients and the risk of pancreatitis. The analysis revealed that higher serum vitamin B12 levels were strongly associated with a reduced risk of developing different types of pancreatitis.
Next, the team determined whether vitamin B12 displayed protective and potential therapeutic effects using experimental models of pancreatitis in CD320 knockout mice, which lack a key gene responsible for vitamin B12 absorption. Two distinct models of pancreatitis were used in the study: one to observe early pancreatic injury responses, and the other to track the pathological progression of acute pancreatitis.
The results revealed that VB12 directly protects acinar cells from necrosis during the early stages of acute pancreatitis and subsequently reduces T lymphocyte infiltration. Notably, artificially increasing serum B12 levels before and after the induction of pancreatitis not only reduced the severity of the condition but also promoted tissue repair after pancreatic injury.
Interestingly, despite vitamin B12's known role in the one-carbon metabolism pathway, its protective effects in pancreatitis were not mediated through the reduction of homocysteine or the glutathione (GSH) pathways, as was previously hypothesized. Instead, vitamin B12 was found to enhance ATP production in pancreatic tissue, thereby reducing acinar cell necrosis and preventing disease progression.
ATP supplementation in CD320-deficient mice also alleviated pancreatic damage, further supporting the hypothesis that vitamin B12's protective effects result from improved cellular energy supply rather than oxidative stress regulation.
"These exciting new findings add to the growing evidence that vitamin B12 can reduce the severity of acute pancreatitis by increasing ATP levels in pancreatic tissue, offering novel insights into potential therapeutic strategies for this disease. This study lays a robust foundation for future clinical applications of vitamin B12 in managing acute pancreatitis," Prof. Mo concludes.
