Bile Acid Replacement in Bile Acid Synthesis Defects
In my commentary, I speculated that desiccated bovine bile (or an alcoholic extract thereof) may also prove effective. The major constituents of bovine bile are the conjugates of cholic acid (1). An extract of bovine bile containing mostly conjugated bile acids is available in the United States as a dietary supplement and one such preparation has been shown to be effective in increasing intestinal absorption in 2 patients with a short bowel syndrome (2,3). Dietary supplements are not regulated by the FDA provided they appear to be safe.
Cholic acid has been marketed as a fine chemical for a century and is available in high purity and low cost from chemical supply houses. Such cholic acid comes with a label—not to be used for human studies. Nonetheless, cholic acid as a chemical has been used for numerous clinical studies without adverse events being reported. Examples can be found in references (4) and (5). The alkaline saponification and solvent extraction used in the isolation of cholic acid from bovine bile should destroy any bacteria, viruses, nucleic acids, or proteins that may be present.
The high cost of FDA- and EMA-approved cholic acid is likely to derive from the costs of preclinical and clinical studies and the administrative burden entailed in drug approval, whereas ultimately generating a profit for the sponsoring company. Indeed, Medic et al have surveyed the relationship between disease rarity and orphan drug prices in Europe. They found the greater the rarity of the disease, the higher the price of the drug (6).
In my opinion, it is highly desirable to treat the neonate with liver disease caused by either of these 2 defects in bile acid synthesis with an FDA- or EMA-approved preparation of cholic acid. But for lifelong therapy, I hope that a less expensive approach can be developed.
Finally, I must note that the opinions expressed in the above are solely my own. The great French chemist, Michel Chevreul stated “One must strive for infallibility, but never believe that one has achieved it.