Scientists have recently observed that retinoids, a chemical compound found in vitamin A, can help people experiencing acute pancreatitis as an adverse drug effect of asparaginase.
A diet rich in vitamin A may be a solution to combat the life-threatening complications of acute pancreatitis from the drug asparaginase. Asparaginase is the drug of choice for treating acute lymphoblastic leukemia (ALL). ALL is the most common cancer in children and young adults. Moreover, drug-induced pancreatitis is among the leading causes of acute pancreatitis in children.
A team of scientists led by Sohail Husain, MD, chief of Pediatric Gastroenterology, Hepatology, and Nutrition at Stanford University, and Anil Goud Jegga, a computational biologist at Cincinnati Children’s Hospital Medical Center studied the effects of vitamin A, asparaginase, and pancreatitis in ALL patients.
Asparaginase-associated pancreatitis occurs in 2-10% of people with ALL treated with asparaginase, and one-third can develop acute pancreatitis. Cancer cells need asparagine but cannot make it themselves. For patients with ALL, treatment with the enzyme asparaginase helps starve cancer cells by reducing the amount of asparagine circulating in the blood. Husain and colleagues used a systems approach to evaluate the factors that affect asparaginase-associated pancreatitis.
First, gene expression experiments showed that asparaginase-induced gene expression was reversed by vitamin A and its analogs. Second, analysis of patients’ electronic health records from approved sources demonstrated a reduction in acute pancreatitis risk with concomitant exposure to vitamin A.
Furthermore, a plasma sample screening after single-dose exposure to asparaginase among patients revealed reduced circulating retinoids. Moreover, the scientists also showed that acute pancreatitis is more likely to develop with reduced dietary intake of vitamin A.
Finally, the research team also looked at data from experiments on mice. It showed that treatment with asparaginase lowers retinol levels in the blood. In human subjects, they found that only 1.4% of patients treated with asparaginase developed pancreatitis while taking vitamin A in contrast to 3.4% of patients who did not. In addition, patients’ dietary intake analysis showed that with low levels of vitamin A intake during treatment with asparaginase were more likely to develop drug-induced pancreatitis.
This study demonstrates the potential of vitamin A supplementation to protect against acute pancreatitis during ALL-associated asparaginase treatment. However, more studies are required to evaluate how much vitamin A would be needed and if dietary sources are sufficient or if supplementation is required.
- Tsai CY, Saito T, Sarangdhar M, Abu-El-Haija M, et al. A systems approach points to a therapeutic role for retinoids in asparaginase-associated pancreatitis. Sci Transl Med. 2023 Mar 15;15(687). https://doi.org/10.1126/scitranslmed.abn2110