The Development of Acute Pancreatitis Among Individuals Who Engage in Binge Drinking May Depend on Phosphate Consumption

Researchers investigated whether low phosphate levels contribute to the development of alcohol-induced pancreatitis.

Phosphate consumption likely plays a critical role in the development of acute pancreatitis in the setting of high alcohol consumption, according to results of a study published in Gastroenterology.

To investigate this claim, mice were reared on standard or low phosphate diets. For 5 days, mice underwent orogastric gavage and received either 1.43 g/kg ethanol, 2.86 g/kg ethanol, or 2.86 g/kg ethanol with 0.3 mmol/kg Na2HPO4. Blood was collected 24 hours after final orogastric gavage. Pancreatic acini were obtained from 1 to 3 mice to assess mitochondrial activity.

The mice that were fed the low phosphate diet and exposed to high amounts of ethanol had significantly elevated pancreatic edema (P ≤.05), serum amylase (P ≤.0001), and lipase (P ≤.001). The low phosphate diet likely caused pancreatic myeloperoxidase, as indicated by neutrophil infiltration (P ≤.0001). These trends were not observed among the mice fed the standard diet.

The mice that were fed the low phosphate diet and not exposed to ethanol had slightly increased pancreatic myeloperoxidase (P ≤.05). Significant pancreatic injury was not observed among the mice that were given the low ethanol dose.

Mice that received the Na2HPO4 supplement had restored serum phosphate levels (P ≤.01), but pancreatic edema remained unchanged.

Lactate dehydrogenase (P ≤.001) and trypsin activity (P ≤.05) were significantly increased among mice fed the experimental diet and exposed to 50 mM of ethanol. Na2HPO4 exposure reduced lactate dehydrogenase (P ≤.05) and trypsin activity (P ≤.05).

Ionomycin stimulated dysregulated intracellular calcium release among all animals, but the acinar cells from mice fed the experimental diet had a more sustained dysregulation of intracellular calcium. Ethanol was not found to alter these observations.

There was evidence to suggest that depleted phosphate levels affected mitochondrial function (P ≤.01) and lowered intracellular ATP (P ≤.05). Ethanol reduced phosphate levels among the experimental diet group and caused a dose-dependent mitochondrial depolarization.

It remains unclear whether these findings could be generalizable for humans.

These data suggest that individuals who engage in binge drinking and consume a diet poor in phosphates may be at increased risk for developing acute pancreatitis.


Farooq A, Richman CM, Swain SM, et al. The role of phosphate in alcohol-induced experimental pancreatitis. Gastroenterol. Published online May 26, 2021. doi:10.1053/j.gastro.2021.05.048