Gallstones and
fatty liver are common disorders in the Western world, largely due to dietary and life style factors. Currently,
laparoscopic cholecystectomy is the main treatment option for gallbladder stones. Surgery is, however, expensive and may cause morbidity and even mortality. An effective medical treatment would be desirable, especially in patients with mild to moderate symptoms or high surgical risk. Currently, the
bile acid UDCA (
Ursodeoxycholic acid) is used for oral dissolution treatment and for the prevention of
cholelithiasis in selected cases. However, the major limitations of this treatment are its low efficacy, slow action and stone recurrence. Recently,
phospholipids rather than
bile salts were realized to be the major natural
cholesterol solubilizers in bile. They also possess anti-crystallizing activity. The sn-2
fatty acid of the
phospholipids molecule was found to be particularly important. This was the background for the development of FABACs (
Fatty Acid and
Bile Acid Conjugates), which are novel synthetic
lipid molecules. These molecules are composed of
fatty acids (with chain lengths from C-14 to C-22), that are linked to
cholic acid, by an
amide bond at position 3. In vitro and in vivo studies (in mice) have shown that FABACs can prevent the formation of
cholesterol crystals and dissolve existing ones. C20-FABAC, when given orally, is absorbed and secreted into bile. It was also found to have a series of beneficial effects on
cholesterol metabolism. The main treatment for patients with
fatty liver consists of lifestyle and
diet modifications, which are associated with low compliance. Currently there is no effective medical treatment for this disease. In the FABAC studies on the prevention and dissolution of
gallstones in laboratory animals, it was observed that this treatment also prevents the formation of diet induced
fatty liver. Further prospective studies found that FABACs indeed prevent/decrease the formation of
fatty liver induced by high fat diet. This influence was observed in all the
fatty liver parameters (histology as well as chemical analysis), and in different animal strains. Based on these findings, FABACs seem to be good candidates for the medical treatment of
hepatobiliary disorders, in particular
gallstones and
fatty liver disease.