The gallbladder and the importance of bile

Bile acids are diverse molecules that act as physiological detergents to assist bile flow. They are primarily synthesized in the liver from cholesterol and play a major role in the intestinal absorption and transport of lipids, vitamins and minerals.^{1, 2} Bile acids further act as signalling molecules that activate nuclear and cell signalling pathways that play a role in regulating lipid, glucose and energy metabolism. As well as, cholesterol homeostasis, calcium mobilisation, cyclic AMP synthesis, protein kinase C activation and systemic endocrine functions.^{1, 2}

The liver produces between 0.2–0.6g of bile acids on a daily basis. Once conjugated they are secreted and stored in the gallbladder ready for food to be consumed.^{1, 2} After a meal the gallbladder contracts and pushes bile acids into the duodenum and intestinal tract. During this process approximately 95% of the bile acids secreted are actively re-absorbed through passive diffusion and transport within the terminal ileum, to the portal vein to return to the liver. Bile acids will complete this cycle anywhere between 4-12 times daily with the remaining 5% being eliminated via faeces.^{1, 2}

What is sludge and why is it relevant

Gallbladder sludge is a result of particulate solids that have precipitated from bile. Sludge generally consists of cholesterol monohydrate crystals, calcium bilirubinate pigment and/or granules, calcium carbonate salts or small gallstones <2mm mixed with mucin, proteins and generally consist of an elevated level of unconjugated bilirubin.^3-5

One aspect that can play a role in the development of gallbladder sludge is the elevated presence of mucus concentrated from mucins.⁴ The elevated mucus within the gallbladder can cause stasis, this results in pooling of bile which then binds to biliary lipids such as bilirubin. This process of stagnation does not interfere with gallbladder contractions, it is however one causative factor in the future development of gallstones.⁴   

Within common allopathic diagnostic criteria, controversy surrounds pathophysiology for the formation of gallbladder sludge and how to diagnose the condition.² If gallbladder sludge is detected and the patient is asymptomatic or their symptoms are not considered severe it is left untreated. However if sludge is accompanied with severe symptoms the treatment is the same as for gallstones – a cholecystectomy.^{3, 6}

Predisposing risk factors, signs and symptoms

Biliary sludge formation is associated with³:

• Hormonal changes during pregnancy
• Rapid weight loss, particularly in the obese
• Critical illness involving low or absent oral intake of food and the use of total parenteral nutrition
• Gastric surgery
• Medications such as ceftriaxone and octreotide
• Bone marrow or organ transplant
• Imbalanced amounts of cholesterol, phospholipids and bile salts in bile concentrations
• Biliary tract infection
• Obesity
• Excessive consumption of dietary fats
• Being female
• Age – over 50 years increases risk
• Food allergy and/or intolerance may be involved in delayed gallbladder emptying which may play a role in gallstone formation.⁷

Whilst not all gallbladder sludge produces clinically detectable symptoms⁶, sludge can be associated with: biliary pain, pancreatitis, acalculous cholecystitis⁸, biliary colic, acute cholangitis³ and can lead to the progression of gallstones.⁸ Common symptoms of sludge may include: restlessness, vomiting, nausea, fat intolerance, epigastric tenderness, fever, colicky pain in the right upper quadrant that may radiate to the back or right shoulder.⁹ Highlighting the clinical significance of treating sludge before it progresses into gallstones.

Image 1. Gallstones10 

Did you know:

Gallstones vary in size and can be either singular or present in multiples

• Microlithiasis = stones equal to or less than 3mm
• Stones less than 5mm
• Stones 5-19mm
• Stones 20-29mm
• Stones > 30mm

The average diameter of the bile duct is between 2.0 mm to 7.9 mm, with most being less than 6mm.¹¹ This highlights the significance of knowing the size of the gallstones and understanding limitations when stimulating gallbladder.  

The gallbladder flush – what are you flushing

The gallbladder or liver flush – a potentially outdated naturopathic treatment to promote the elimination of gallbladder stones. While there are varied protocols for the gallbladder flush the core treatment involves fasting for 12 hours, during which time the patient consumes only apple juice throughout the day and at 5-6pm commences consuming 18mL of good quality olive oil followed by 9mL of fresh squeezed lemon juice every 15 minutes until approximately 500mL of olive oil in total has been consumed.⁷

This treatment is believed to help soften the stones and aid the effective passage to excretion, often passing of multiple soft green and brown spheroids or gallstones is expected and can be accompanied with nausea and diarrhea. However, several analyses of the passed stones have been evaluated and found that they consisted predominantly of fatty acids and contained no cholesterol, bilirubin, or calcium⁷, suggesting that gallstones were not effectively passed it is mainly emulsified fat.

Herbal considerations for sludge  

Turmeric

Turmeric has cholagogue activity, it works through promoting the stimulation and production of bile within the liver and excretion of bile from the gallbladder, as well as aiding the digestion of fats. Traditionally, utilised to strengthen liver and gallbladder and as a digestive bitter and carminative.¹²

Globe artichoke

One main role of globe artichoke is through the stimulation of bile via the liver and gallbladder. Both the dried and fresh leaves have traditionally been used to promote bile production.¹³ In a hamster study, they utilised a fortified controlled diet containing artichoke leaf extract and a control diet for 6 weeks. After 42 days the study revealed that there was a significantly lower result in total cholesterol (15%), non-HDL cholesterol (29%) and triglycerides (22%) compared with controls and bile acids concentrations significantly increased by up to 53% in male hamsters and 25% in female hamsters when compared with the control group.¹⁴

A further study investigated bile flow and the formation of bile compounds after oral consumption of an artichoke leaf extract over 7 days in rats. They authors concluded that a statistically significant increase of bile flow was observed after an acute dosage, the highest being 400mg/kg and after repeated ingestion twice daily for 7 days, results were similar to dehydrocholic acid a  common synthetic bile acid.¹⁵

Bupleurum

Bupleurum has long been utilised to soothe and/or adjust liver Qi.^{16, 17} Its cold and bitter in nature and works via the liver, gallbladder, pericardium, to release and clear heat, release depression, and settle and relieve pain.¹⁶

In a study utilising Bupleurum on rats with induced hepatic cholestasis the results highlighted that treatment with bupleurum resulted in promoting bile secretion and flow, reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL) levels.¹⁷ Highlighting the hepatoprotective and bile stimulating activity bupleurum produces.¹⁷

Dandelion

Dandelion root has traditionally been used to aid with eliminating toxins from the liver and kidneys, stimulate bile and assist with dissolving gallstones.¹⁸ Dandelion root contains bitter compounds to help aid digestion, increase bile production from the liver and stimulate bile flow from the gallbladder.¹⁹ Oral administration of dandelion root extracts have been shown to increase bile flow in multiple preliminary studies acting as a cholagogue.^{19, 20}

What can we do clinically?

As our lifestyles and diets are changing, in particular the development of the modern Western style diet and increased rates of obesity, the incidence of gallstones is on the rise.²¹ As natural healthcare practitioners we can provide preventative support through diet, lifestyle and both herbal and nutritional interventions for these individuals when they present with signs of gallbladder sludge. Early interventions may help prevent sludge from forming into stones which could potentially result in a cholecystectomy, which can go on to impact quality of life. 

References

1. Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. The EMBO journal. 2006;25(7):1419-25.
2. Ko CW, Schulte SJ, Lee SP. Biliary sludge is formed by modification of hepatic bile by the gallbladder mucosa. Clinical Gastroenterology and Hepatology. 2005;3(7):672-8.
3. Shaffer EA. Gallbladder sludge: what is its clinical significance? Current gastroenterology reports. 2001;3(2):166-73.
4. Lee S, Nicholls J. Nature and composition of biliary sludge. Gastroenterology. 1986;90(3):677-86.
5. Venneman NG, van Brummelen SE, van Berge-Henegouwen GP, van Erpecum KJ. Microlithiasis: an important cause of ‘idiopathic’acute pancreatitis? Annals of hepatology. 2003;2(1):30-5.
6. Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acute pancreatitis. New England Journal of Medicine. 1992;326(9):589-93.
7. Gaby AR. Nutritional approaches to prevention and treatment of gallstones. Alternative medicine review. 2009;14(3):258.
8. Janowitz P, Kratzer W, Zemmler T, Tudyka J, Wechsler JG. Gallbladder sludge: spontaneous course and incidence of complications in patients without stones. Hepatology. 1994;20(2):291-4.
9. Wesdorp I, Bosman D, de Graaff A, Aronson D, van der Blij F, Taminiau J. Clinical presentations and predisposing factors of cholelithiasis and sludge in children. Journal of pediatric gastroenterology and nutrition. 2000;31(4):411-7.
10. Sanders G, Kingsnorth AN. Gallstones. Bmj. 2007;335(7614):295-9.
11. Lal N, Mehra S, Lal V. Ultrasonographic measurement of normal common bile duct diameter and its correlation with age, sex and anthropometry. Journal of clinical and diagnostic research: JCDR. 2014;8(12):AC01.
12. Debjit Bhowmik C, Kumar KS, Chandira M, Jayakar B. Turmeric: A herbal and traditional medicine. Archives of applied science research. 2009;1(2):86-108.
13. Bekheet S. In vitro biomass production of liver-protective compounds from Globe artichoke (Cynara scolymus L.) and Milk thistle (Silybum marianum) plants. Emirates Journal of Food and Agriculture. 2011;23(5):473.
14. Qiang Z, Lee SO, Ye Z, Wu X, Hendrich S. Artichoke extract lowered plasma cholesterol and increased fecal bile acids in Golden Syrian hamsters. Phytotherapy Research. 2012;26(7):1048-52.
15. Rodriguez TS, Giménez DG, De la Puerta Vázquez R. Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine. 2002;9(8):687-93.
16. Lee H-J, Lee C, Yim Y-K. Effects of Intravenous Pharmacopuncture with Harmonizing and Releasing Formulas on Hepatic Recovery after Partial Hepatectomy in Rats. Journal of acupuncture and meridian studies. 2017;10(1):39-44.
17. Sun P, Li Y, Wei S, Zhao T, Wang Y, Song C, et al. Pharmacological Effects and Chemical Constituents of Bupleurum. Mini reviews in medicinal chemistry. 2019;19(1):34-55.
18. Mahboubi M, Mahboubi M. Hepatoprotection by dandelion (Taraxacum officinale) and mechanisms. Asian Pacific Journal of Tropical Biomedicine. 2020;10(1):1.
19. Singh A, Malhotra S, Subban R. Dandelion (Taraxacum officinale)-hepatoprotective herb with therapeutic potential. Pharmacognosy Reviews. 2008;2(3):163.
20. Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine. Expanded Commission E monographs: Integrative Medicine Communications; 2000.
21. Kaechele V, Wabitsch M, Thiere D, Kessler AL, Haenle MM, Mayer H, et al. Prevalence of gallbladder stone disease in obese children and adolescents: influence of the degree of obesity, sex, and pubertal development. Journal of pediatric gastroenterology and nutrition. 2006;42(1):66-70.