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.


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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.

Reference

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