Vitamin B12 may play a protective role in acute pancreatitis by preventing pancreatic cell death and supporting energy production, according to a new study.
Researchers analyzed genetic data from thousands of individuals and conducted laboratory experiments using mouse models to assess the effects of vitamin B12 on pancreatitis.
Acute pancreatitis is a condition characterized by inflammation of the pancreas, often triggered by gallstones, alcohol use, or infections. It can lead to abdominal pain, digestive issues, and, in severe cases, organ failure. The condition’s early phase involves damage to acinar cells, which are responsible for producing digestive enzymes.
To examine vitamin B12’s potential impact, the researchers first used Mendelian randomization to analyze over 6,000 pancreatitis cases and over 700,000 controls from two large European genetic databases. Higher genetically predicted levels of vitamin B12 were associated with a lower risk of developing acute pancreatitis. No protective association was found for folate or homocysteine, other metabolites involved in one-carbon metabolism.
In mouse models, the protective role of vitamin B12 was further explored. Mice lacking CD320—a receptor necessary for vitamin B12 uptake—developed more severe pancreatitis, exhibiting greater acinar cell necrosis, increased inflammatory markers, and lower ATP levels.
Conversely, mice treated with vitamin B12 either prior to or following pancreatitis induction showed reduced pancreatic damage and higher ATP levels. These mice also had lower serum levels of amylase and lipase, enzymes typically elevated in pancreatitis. Vitamin B12 treatment reduced signs of ductal metaplasia and T-cell infiltration, particularly in the L-arginine-induced model.
The researchers ruled out folate- and homocysteine-mediated effects. They also tested whether glutathione, a key antioxidant, contributed to vitamin B12’s benefit. However, glutathione alone didn't protect pancreatic tissue in CD320-deficient mice. As a result, the researchers focused on vitamin B12’s role in cellular energy metabolism, particularly its function in the succinyl-CoA pathway to boost ATP production.
To confirm the mechanism, ATP was administered directly to mice with impaired vitamin B12 uptake. This reduced acinar-cell necrosis similarly to B12 treatment, reinforcing the idea that vitamin B12’s protective effect stems from restored energy metabolism.
The researchers concluded that vitamin B12 protects against pancreatic damage in acute pancreatitis by enhancing mitochondrial ATP production during the early disease phase. They noted that further clinical trials are necessary to determine whether early administration of vitamin B12 in patients can reduce disease severity.
“V[itamin] B12 treatments can directly prevent the necrosis of acinar cells, subsequently reduce the inflammatory response, especially the inflammatory response of T lymphocytes in the pancreas during the occurrence of acute pancreatitis, and displays therapeutic effects on acute pancreatitis in mouse models,” concluded lead study author Yulin Chen, of Sichuan University, and colleagues.
The authors declared no conflicts of interest.
Source: MedComm
