The most important digestive enzymes in malabsorption diseases are usually fat-digesting enzymes called lipases. Proteolytic enzymes can digest, as well as destroy, lipases. Therefore, people with enzyme deficiencies may want to avoid proteolytic enzymes in order to spare lipases.⁵⁴ If this is not possible (as most enzyme products contain both), people with malabsorption syndromes should talk with their doctor to see if their condition warrants finding products that contain the most lipase and the least protease.

In theory, too much enzyme activity could be irritating because it could start to “digest” parts of the body as the enzymes travel through the digestive system. Fortunately, that does not happen with supplemental amounts. Research has not determined the level at which such problems might arise.

A serious condition involving damage to the large intestines called fibrosing colonopathy has resulted from the use of pancreatic enzymes in children with cystic fibrosis. In some cases, the problem was linked to the use of high supplemental amounts of enzymes.^{55, 56, 57} However, the amount of enzymes used has not been linked to the problem in all reports.⁵⁸ In some cases, lower amounts of enzymes have caused fibrosing colonopathy if the enzymes are enteric-coated.⁵⁹ Some researchers now believe that some unknown interaction between the enteric coating and the enzymes themselves may cause damage to the intestines of children with cystic fibrosis.⁶⁰ Until more is known, children with cystic fibrosis needing to take pancreatic enzymes should only do so under the careful supervision of a knowledgeable healthcare professional.