What are the effects of protease inhibitors?

 In experimental animals, they have been found to be associated with growth inhibition and pancreatic hypertrophy. A negative feedback mechanism in the small intestines has been postulated for these effects. In the presence of trypsin inhibitors, iqactivation and loss of intestinal trypsin can take place. These can trigger the release of cholecystokinin (CCK) from the intestinal mucosa. CCK then can induce the pancreas to produce more trypsin. However, excess of hypsin inhibitors can reduce the protein available thus explaining the growth inhibition seen in animals, as well as, the pancreatic hypertrophy.

Moreover, trypsin is rich in sulphur-containing amino acids; hence increased synthesis of trypsin (the more the inhibitor, the more trypsin that is made) increases the requirements for these amino acids, ultimately leading to weight loss. Also, the stress of the pancreas results in pancreatic hypertrophy and hyperplasia of the acinar (exocrine) cells. Feeding purified trypsin inhibitor or raw soy flour containing protease inhibitors potentiated the effects of pancreatic carcinogens. It must be noted that most of the effects have been observed in some species of animals only, whose pancreas constitute a fairly higher percentage of body weight (0.29-0.8%) e.g. in rats, mice, chickens, hamsters and guinea pigs but not in large animals with a small pancreas (0.06-0.24% of body weight) e.g. dogs, calves, monkeys. In human subjects, provision of raw soy flour or purified trypsin inhibitor directly to the duodenum, increased secretion of pancreatic enzymes and serum level of CCK. This suggests that a negative feedback mechanism also exist in humans. However, it is interesting that among populations with fairly high intake of soybeans or other foods rich in protease inhibitors, e.g. in Japanese and Seventh Day Adventists, the incidence of pancreatic cancer is lower.