Bile. Also known as gall. Memorialised as “that green monster” in Shakespeare. Bile is a bitter-tasting, dark green to yellowish brown liquid produced by our liver, stored in the gallbladder, and known to aid in the digestion of lipids and fats in the small intestine. Bile acids are actually steroids derived from cholesterol.
But bile acids, it turns out, are enormously beneficial, in ways we had never expected—and expanding far beyond the process of digestion. First, the vaunted “green monster” is intimately linked to what is known as metabolic syndrome—the modern day epidemic of high cholesterol, Type 2 diabetes, glucose intolerance, obesity, insulin resistance, hypercoagulability and high blood pressure. It turns out that a major receptor, called the farnesoid X receptor (FXR) is activated by bile acids. The FXR and glucose signal each other, and in diabetic mice, activation of this receptor improves high blood sugar and excess lipids.1
Inflammatory bowel disease may be regulated in part by bile acids. This painful condition is in part driven by the master regulator of inflammation in our body, NF-kappa B. Higher than usual amounts of NF-kappa B have been shown to inhibit FXR activity.2
It is fascinating that bile is not limited to the digestive system, as we long thought. There are bile acids in the blood and in the cerebrospinal fluid, and one of them has a potential role in protecting neurons in Huntington’s Disease and Alzheimer’s disease.3 The FXR is also found in the endothelial (blood vessel) lining, suggesting a role for bile acids in vascular tone and the health of blood vessels. And FXR may actually help increase blood vessel dilation, lower blood cell adhesion and clumping, and be anti-inflammatory. In other words, bile may be protective of the vascular system.1
In fact, a 2010 review from the Netherlands concludes that bile salts and bile salt receptors have a potent impact on the progression or regression of atherosclerosis. “Bile salts have emerged as important modifiers of lipid and energy metabolism,” the authors write. “At the molecular level, bile salts regulate lipid and energy homeostasis mainly via the bile salt receptors FXR and TGR5. Activation of FXR has been shown to improve plasma lipid profiles.” They also note that there is increasing evidence for a role of FXR in ‘nonclassical’ bile salt target tissues such as the vasculature and even our immune system cells known as macrophages. “In these tissues, FXR has been shown to influence vascular tension and regulate the unloading of cholesterol … Bile salt metabolism and bile salt signaling pathways represent attractive therapeutic targets for the treatment of atherosclerosis.”4
Bile acids may even help us avoid toxic or septic shock from bacterial infection. The bile acts like a detoxifying detergent, splitting the bacterial endotoxin into fragments. Researchers at the National Center for Public Health and the National Research Institute for Radiobiology and Radiohygiene in Budapest, Hungary, suggest that “bile acids may be useful for the prevention and therapy of sepsis, parvovirus infection, herpes” and other conditions.5
Hungarian research suggests that bile acids might help in the treatment of psoriasis—theoretically through its detoxifying detergent action. 800 patients were studied; 551 were treated with oral bile acid (dehydrocholic acid) supplementation for 1-8 weeks, and 249 were treated with conventional drugs. Patients were evaluated clinically and with a Psoriasis Area Severity Index (PASI score). 434 of the 551 bile acid patients (78.8%) became asymptomatic, while only 62 of the 249 (24.9%) conventional patients recovered. The researchers found that acute psoriasis responded best, but that even so, at follow-up two years later 319 of the bile acid psoriasis patients remained asymptomatic (57.9%). The researchers conclude, “The results suggest that psoriasis can be treated with success by oral bile acid supplementation presumably affecting the microflora and endotoxins released and their uptake in the gut.”6
Interestingly, bile salts may actually be antimicrobial as well. A 1987 study found that bile salts were fungistatic.7 A 1986 study found the salts antimicrobial; bile salts were added to a special broth to simulate the milieu in the gastrointestinal tract of humans. Antimicrobial activity increased and microbial growth decreased in the presence of high concentrations of bile salts.(8) It makes sense that bile salts are antimicrobial, since when healthy the biliary tract is completely microbe-free. A 2009 study speculates that bile salts stimulate a potent antimicrobial peptide: “We hypothesise that bile salts may stimulate the expression of a major antimicrobial peptide, cathelicidin, through nuclear receptors in the biliary epithelium.”(9) Perhaps it is not surprising that acids from an organ as essential to our health as the liver, an organ that detoxifies so many substances, has such wide-ranging benefit across so many body systems. Nature is both simple and profound, and the body tends to conserve and utilise its most precious substances in many target organs and receptors.
For a further review on bile acids and their role in antiaging therapies read: Bile Acids Make You Live Longer
- Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev. 2009 Jan;89(1):147-91. PMID: 19126757
- Gadaleta RM, Oldenburg B, Willemsen EC, Spit M, Murzilli S, Salvatore L, Klomp LW, Siersema PD, van Erpecum KJ, van Mil SW. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Biochim Biophys Acta. 2011 Aug;1812(8):851-8. PMID: 21540105
- Sharma R, Long A, Gilmer JF. Advances in Bile Acid Medicinal Chemistry. Curr Med Chem. 2011 Aug 9. PMID: 21824088
- Hageman J, Herrema H, Groen AK, Kuipers F. A role of the bile salt receptor FXR in atherosclerosis. Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1519-28. PMID: 20631352
- Bertók L. Bile acids in physico-chemical host defence. Pathophysiology. 2004 Dec;11(3):139-145. PMID: 15561510
- Bertók L. Bile acids and endotoxins: physico-chemical defense of the body. Orv Hetil. 1999 Jan 3;140(1):3-8. Review. Hungarian. PMID: 9989105
- Marshall SE, Marples BA, Salt WG, Stretton RJ. Aspects of the effect of bile salts on Candida albicans. J Med Vet Mycol.1987 Oct;25(5):307-18. PMID: 3323449
- Fernandesa CF, Shahani KM, Amer MA. Effect of Nutrient Media and Bile Salts on Growth and Antimicrobial Activity of Lactobacillus acidophilus. Journal of Dairy Science Volume 71, Issue 12, December 1988, Pages 3222-32299.
- D’Aldebert E, Biyeyeme Bi Mve MJ, Mergey M, Wendum D, Firrincieli D, Coilly A, Fouassier L, Corpechot C, Poupon R, Housset C, Chignard N. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology. 2009 Apr;136(4):1435-43. PMID:19245866