Sunday, May 26, 2013

Bile and its role in bone health

Bile fluid is a watered-down slurry of salts, cholesterol, and bilirubin that is produced by the the liver and stored in the gallbladder. When released into the small intestine, bile fluid helps us digest fats, including improving the absorption of fat soluble vitamins such as D and K which are important to bone health. New research out of Spain shows us that there is a second mechanism whereby bile salts benefit bone...but only if the gut and its microbiota are healthy.

When fats are ingested, bile salts are released into the small intestine where they disperse fat into small digestible particles. This process is called emulsification. Without emulsification, ingested fat usually passes directly into the toilet bowl providing little or no nutrient value to the individual. Bile is therefore important for digestion but it also serves a second function. Bile acts as a medium for ridding the body of a waste product called bilirubin. Bilirubin is formed from the breakdown of old red blood cells and gives bile its yellowish color. If bile excretion is blocked, fat digestion suffers and the acid flows out into the blood stream causing the individual to turn yellow or jaundiced. This condition is called cholestasis and may be a sign of severe liver disease.

We have long known that patients with chronic cholestatic liver disease are prone to developing osteoporosis. Only recently have we understood why. We now know that the bilirubin and lithocholic acid (a secondary bile salt) in bile are toxic to osteoblastic cells and reduces their capacity to form new bone. A back-up of bilirubin and lithocholic acid laden bile in liver disease often results in the development of low-bone-turnover osteoporosis.

Dubreuil, et al. from the University of Barcelona have shown that elevated bilirubin and lithocholic acid levels can be detrimental to osteoblast cell function. In normal circumstances, when bile is secreted for fat emulsification the bilirubin within it is converted into a secondary bile acid called ursodeoxycholic acid (UDCA) by commensal (beneficial) bacteria in the gut. (The lithocholic acid is bound by fiber and excreted.*) A healthy balance of gut bacteria promotes this conversion of bilirubin to UDCA, neutralizing the bilirubin's adverse effects on osteoblasts. In other words, when the gut microbes are of the "good" kind, bilirubin is turned into UDCA which simply helps improve the digestion of fats. In dysbiosis, where there is microbial imbalance with an overgrowth of "bad" bacteria in the gut, conversion of bilirubin to UDCA does not take place, bilirubin levels increase in the blood, and osteoblastic bone formation is adversely effected.

Healthy conversion of bilirubin into secondary bile salts such as UDCA can be promoted by including pre and probiotics in the diet. Prebiotics are complex, non-digestible, but fermentable sugars such as inulin, a fructooligosaccharide that acts as a "fertilizer" for promoting "good" bacteria growth. Probiotics are the "good" bacteria themselves and can be obtained in supplement form or in cultured foods such as yogurt, kefir, kombucha, and cultured vegetables. For a great web site for learning how you can culture your own food check out Cultured Food Life. Take the time to listen to Donna Schwenk's story. If I can't convince you how important cultured foods are for maintaining health, Donna will.

I am always singing the virtues of using laboratory tests to help define and monitor treatment for patients with bone loss. The findings in this new research demonstrate why testing for bilirubin can be of help when evaluating a patient with osteoporosis. If an individual has signs and symptoms of poor digestion of fats, such as abdominal bloating, gas, steatorrhea (greasy, pale, smelly stools) or jaundice skin or sclerae of the eyes, further evaluation for gall bladder and/or liver involvement is warranted. Jaundice can be a sign of serious liver disease or even tumors. Elevated bilirubin can also indicate Gilbert's Syndrome a common hereditary condition where bilirubin levels rise due to reduced activity of an enzyme that conjugates bilirubin.

After overt liver disease and Gilbert's have been ruled out**, improving gut health with pro and prebiotics can help to lower bilirubin levels and improve osteoblastic bone formation by encouraging secondary bile salt (such as UDCA) formation.

* Lithocholic acid binds to vitamin D receptors in the gut thereby blocking its action of increasing calcium absorption. Dietary fiber binds this secondary bile acid and aids in its excretion.

** When I was first being evaluated by endocrinologists for my severe osteoporosis, my bilirubin level was elevated. I was told that I had Gilbert's Syndrome and this condition was "totally harmless and has nothing to do with your osteoporosis." (Yes...how many times have we all heard that line? "Oh don't worry about it." When someone says that to me now, especially if they are a doctor, I REALLY start worrying!) This diagnosis, turned out to be totally false AND I now know that my suspicions (that the bilirubin could somehow be connected to my bone loss) were totally founded. By changing my diet, improving my gut health, taking probiotics, drinking kefir, and taking herbs such as curcumin and milk thistle...my bilirubin level dropped to normal and it has never been elevated since. I wonder how many people being diagnosed with Gilbert's Syndrome actually have poor gut health and systemic inflammation...both which increase bilirubin levels and reduce osteoblast bone-forming activity.

Dubreuil, M., et al. 2013. Ursodeoxycholic acid increases differentiation and mineralization and neutralizes the damaging effects of bilirubin on osteoblastic cells. Liver Int March 1 [Epub ahead of print].
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