The liver makes bile acid from cholesterol through a complex process which involves about 17 enzymes and multiple steps. Interruptions in the process can lead to bile acid deficiencies and more. Research published in Gastroenterology in May 2013 pointed to genetics as a potential cause of these interruptions and alterations.
Understanding Bile Acid Deficiency
Bile acid deficiency can result from the body being genetically predisposed to produce faulty or impaired bile acid. Genetic researchers have found that there are moments along the pathway of creating and releasing bile acid when the body’s genetic coding is disrupted, altering the process and resulting in deficiency and possibly, harmful chemical byproducts that damage the liver. “We’ve defined at least three bile acid defects that clearly have fat-soluble vitamin deficiency, and all are autosomal recessive genes,” noted James E. Heubi, MD, co-director of the Cincinnati Center for Clinical and Translational Research and Training at the University of Cincinnati College of Medicine. These genetic diseases are rare, affecting between one in 60,000 and one in 200,000 people. Dr. Heubi is among the researchers interested in exploring the genetic risk for bile acid deficiency and the potential for treatment with the right bile acid replacement therapy.
Warning Signs of Bile Acid Deficiency
People with a bile acid deficiency may exhibit various signs or symptoms, including:
Vitamin deficiencies, specifically of fat-soluble vitamins such as A, D, E, and KJaundice, the classic yellowing of the skin and whites of the eyesStunted or abnormal growthDiarrheaLoss of liver functionLiver failure
Bile acid deficiency with a genetic cause can lead to a wide range of effects, from relatively mild to those requiring early medical intervention. “Patients who would likely be deficient because of bile acid defect would be ones that have identifiable liver disease and also some have a history of chronic diarrhea," Heubi said. “They may or may not have much liver disease, but they don’t complete the cycle for making complete bile acids.” In severe cases, he said, children may die before age 5 if the condition is not identified and treated in time. Others can face liver failure or need a liver transplant.
Vitamin D and Bile Acids
Of the fat-soluble vitamins that can be affected by bile acid, vitamin D seems to have attracted the most attention. Vitamin D plays a leading role in helping the body use calcium to build bones, which is why children with bile acid deficiency may have stunted growth. And, new research suggests that women with osteoporosis and vitamin D deficiency might have some degree of bile acid impairment, according to a study published in Nuclear Medicine Communications in June 2013. Whether the study participants’ bile acid deficiencies had genetic roots, though, was not part of the study. If you’re concerned that your vitamin D deficiency could be due to a lack of bile acid, stay calm. “It really only accounts for a small fraction of vitamin D deficiency,” Heubi said. Close to 60 percent of the general population is vitamin D deficient, he explained, but that’s most often related to a lack of sun exposure or a lack of vitamin D in the diet. Also, he added, anyone with a bile acid deficiency would probably be low in all fat-soluble vitamins, not just D.
Treating a Bile Acid Deficiency
Bile acid deficiencies are sometimes referred to as “orphan diseases” — conditions that occur so rarely that major research groups and pharmaceutical companies have yet to adopt them for study — so few treatments have been developed. Nonetheless, two investigational treatments exist, said Heubi, who’s part of a national network hoping to create research centers that will focus on orphan diseases, including bile acid deficiency diseases. “We are in the process of getting a bile acid, called cholic acid, approved by the European Medicines Agency (EMA) and ultimately the FDA (U.S. Food and Drug Administration) so people could get this by prescription," he said. The other potential treatment is glycocholic acid, another bile acid replacement therapy that Heubi and his colleagues are testing in eligible patients. That treatment is complicated, he explained, because taking action at the wrong point in the body’s bile acid-making process could actually be harmful, not helpful. A third bile acid, ursodeoxycholic acid, can be prescribed for people with primary biliary cirrhosis and also to treat gallstones, but it’s not appropriate for other bile deficiency diseases, Heubi said. About the only option remaining is to take vitamin supplements to address a vitamin deficiency, he said, but that’s generally not as effective as addressing the bile acid impairment directly. However, as researchers continue to explore the genetic risks for bile acid deficiency, what they learn could point the way toward more effective treatments.
