Ursodeoxycholic acid (UDCA) is a chemical called a bile acid. It occurs naturally in bile and can be used to dissolve gallstones. The liver produces bile that is stored in the gall bladder. Bile is released by the gall bladder to aid the digestion of fats. It consists of cholesterol dissolved within bile salts. Gallstones occur in the gall bladder as a result of too much cholesterol, or too few bile salts within the bile. The imbalance causes excess cholesterol to separate out of the bile and form stones. Ursodeoxycholic acid causes gallstones to dissolve by a mechanism that is not fully understood. It is known to reduce the production of cholesterol by the liver and also to reduce the absorption of cholesterol from the gut. Both of these actions decrease the amount of cholesterol that passes into the bile. Also, since ursodeoxycholic acid is a bile acid itself, it increases the level of bile acids within the bile. The combination of these two factors reverses the imbalance and stops the cholesterol separating out of the bile. The gallstones then begin to dissolve.
Besides existing in its natural form, UDCA has been synthesized, and all pharmaceutical formulations are synthetic. Besides dissolving gallstones, UDCA exerts other actions of more interest to AAS using bodybuilders. Oral 17 alpha alkylated steroids often cause a condition called cholestasis. Cholestasis is any condition in which bile excretion from the liver is blocked, which can occur either in the liver where bile is formed, or in the bile ducts.
Extrahepatic cholestasis -- which occurs outside the liver -- can be caused by bile duct tumors, strictures, cysts, diverticula, and other damage. Other potential causes for this type include stones in the common bile duct, pancreatitis, pancreatic tumor or pseudocyst, primary sclerosing cholangitis, and compression due to a mass or tumor on a nearby organ.
Intrahepatic cholestasis -- which occurs inside the liver -- can be caused by sepsis (generalized infection), bacterial abscess, drugs, total parenteral nutrition (being fed intravenously), lymphoma, tuberculosis, sarcoidosis and amyloidosis. Other causes of this form of the disorder include primary biliary cirrhosis, primary sclerosing cholangitis, viral hepatitis (A,B,C, etc.), alcoholic liver disease, pregnancy, Sjogren's syndrome and others.
-Symptoms include the following: -Itching -Jaundiced (yellow) skin or eyes -Inability to digest certain foods -Nausea, vomiting -Right upper quadrant abdominal pain -Organ failure in cases of sepsis (but not from cholestasis itself) -Rash or fever in some cases of drug-induced cholestasis -Clay-colored or white stools -Dark urine
Often times a panel of standard liver function tests will show cholestasis before the symptoms even manifest themselves, but in general laboratory tests have limited diagnostic value. Transaminase (ALT, AST), alkaline phosphate, and bilirubin levels are typically elevated in proportion to the severity of the disease. AST and ALT can be elevated by exercise, so those are not particularly helpful in diagnosing cholestasis (1).
It is intrahepatic cholestasis caused by drugs (i.e.oral 17 alpha alkylated anabolic steroids) that is of greatest concern to bodybuilders. It has been proposed that oral steroids interfere with the pump that exports bile out of liver cells.
UDCA exerts a number of therapeutic effects which prevent and treat cholestasis. For instance, we mentioned the bile transport pump. UDCA has been shown to stimulate enzymes that increase the density of these bile transporters, allowing bile to exit the liver more readily (2,3). UDCA also protects hepatocytes (liver cells) against bile induced apoptosis (programmed cell death) (2).
Whatever the primary mechanism is for AAS induced cholestasis, UDCA has proven effective in treating the condition. Quoting from one study,
"A 28-year-old body builder was admitted because of jaundice. For 80 days, until 3 weeks before hospitalization, he had been taking moderately high doses of anabolic steroids: metandienone (methandienone), 10-50 mg daily by mouth, and stanozolol, 50 mg intramuscularly every other day. Physical examination was unremarkable except for yellow discoloration of the skin and sclerae...Liver biopsy was compatible with cholestasis induced by anabolic steroids...The patient's state improved simultaneously with the administration of ursodeoxycholic acid and the biochemical values gradually reached normal levels after several weeks. CONCLUSION: Anabolic steroids can cause severe cholestasis and acute renal failure. In this case there was a notable temporal coincidence between the administration of ursodeoxycholic acid and the marked clinical improvement. (4).
Interestingly, there seems to be a genetic disposition to the development of drug induced cholestasis (5). This may explain why only some oral AAS users develop the disease and others can endure heavy cycles of 17-alpha alkylated orals. Cholestasis as well as hepatitis caused by non 17-alpha alkylated injectable steroids has been reported, but is rare.
Cholestasis can be caused by estrogen as well, both synthetic and endogenous. It is not uncommon for cholestasis to develop during pregnancy, when estrogen levels are high. It’s possible the rare reported cases of testosterone induced cholestasis might be due to elevated estrogen levels in susceptible individuals.
It should be stressed that if one develops the symptoms of drug induced cholestasis, the first line of treatment is to immediately discontinue the drug, and begin treatment with UDCA. Although there are no studies showing UDCA exerts any prophylactic effects against AAS induced cholestasis, the proposed mechanism whereby it upregulates hepatic bile transporters suggests it may very well help prevent the disease by increasing bile flow out of the liver. Once the offending drug is withdrawn, and UDCA therapy begun, the disease typically resolves.
UDCA has also been shown to lower both total cholesterol and LDL (bad) cholesterol via at least two different mechanisms. In one study (6) researchers observed that UDCA lowered the hepatic (liver) production of cholesterol by interfering with a key enzyme in cholesterol synthesis.
In another study, UDCA was administered to animals with moderately elevated cholesterol, somewhat typical of what is seen in many people subsisting on high fat western diets (and typical of what is seen in oral AAS users). Here UDCA lowered plasma LDL by increasing the number of LDL binding sites on the liver, allowing for greater LDL uptake by the liver (7).
So we see an added health benefit to UDCA use, even in those AAS users who do not experience cholestasis. Most bodybuilders watch their fat intake, but on a high protein diet that includes red meat, UDCA might be a worthwhile supplement to consider if one is concerned about cholesterol (and who isn’t these days).
When bile enters the digestive tract, a certain portion is reabsorbed, leading to cholesterol reuptake. UDCA seems to block a portion of this cholesterol reuptake, providing for yet another mechanism whereby UDCA lowers cholesterol (8).
Dosages of commercial brands of UDCA vary depending on the type and severity of liver disease. For preventative purposes 500 mg per day might be sufficient. Once liver disease has developed, one ought to see their doctor, but a typical recommended dose is 13 to 15 mg/kg/day which may be given in 2 divided doses, i.e. in the morning and at bedtime, with food. But again, if any of the symptoms listed above develop, or liver tests come out showing cholestasis or some other liver disorder, don’t self medicate; see your doctor, and lay off the orals.
Not sure if anyone else uses this, please post any other information known.