Cholelithiasis or gallstones are hardened deposits of digestive fluid that can form in your gallbladder. The gallbladder is a small organ located just beneath the liver. The gallbladder holds a digestive fluid known as bile that is released into your small intestine. In the United States, 6% of men and 9% of women have gallstones, most of which are asymptomatic. In patients with asymptomatic gallstones discovered incidentally, the likelihood of developing symptoms or complications is 1% to 2% per year. Asymptomatic gallbladder stones found in a normal gallbladder and normal biliary tree do not need treatment unless they develop symptoms.

Cholelithiasis means you have stones inside the gallbladder. The gallbladder is a small pouch under your liver that stores bile (a fluid that helps digest fat). Gallstones form when the normal mix of bile becomes unbalanced—most often when there is too much cholesterol for bile to keep dissolved, or when bile doesn’t empty well. Many people have no symptoms (“silent” stones). When a stone blocks the cystic duct or common bile duct, you can get biliary colic (sudden right-upper-belly pain), acute cholecystitis (gallbladder inflammation), cholangitis (bile-duct infection), or pancreatitis (inflamed pancreas). Ultrasound is usually the first test, and laparoscopic cholecystectomy (keyhole removal of the gallbladder) is the standard cure for repeated pain or complications. NCBINICEPubMed

Types of Cholelithiasis

Depending on the etiology, gallstones have different compositions. The three most common types are

• Cholesterol gallstones
• Black pigment gallstones
• Brown pigment gallstones – Ninety percent of gallstones are cholesterol gallstones.
• Mixed stones –  Mixed (brown pigment stones) typically contain 20–80% cholesterol (or 30–70%, according to the Japanese- classification system). Other common constituents are calcium carbonate, palmitate phosphate, bilirubin, and other bile pigments (calcium bilirubin, calcium palmitate and calcium stearate). Because of their calcium content, they are often radiographically visible.

The two main kinds of gallstones are

• Cholesterol stones – These are usually yellow-green. They’re the most common, making up 80% of gallstones.
• Pigment stones – These are smaller and darker. They’re made of bilirubin.

Causes of Cholelithiasis

There are three main pathways in the formation of gallstones

• Cholesterol supersaturation – Normally, bile can dissolve the amount of cholesterol excreted by the liver. But if the liver produces more cholesterol than bile can dissolve, the excess cholesterol may precipitate as crystals. Crystals are trapped in gallbladder mucus, producing gallbladder sludge. With time, the crystals may grow to form stones and occlude the ducts which ultimately produce the gallstone disease.
• Excess bilirubin – Bilirubin, a yellow pigment derived from the breakdown of red blood cells, is secreted into bile by liver cells. Certain hematologic conditions cause the liver to make too much bilirubin through the processing of breakdown of hemoglobin. This excess bilirubin may also cause gallstone formation.
• Gallbladder hypomotility or impaired contractility – If the gallbladder does not empty effectively, bile may become concentrated and form gallstones.
• There’s too much bilirubin in your bile – Conditions like cirrhosis, infections, and blood disorders can cause your liver to make too much bilirubin.
• Your gallbladder doesn’t empty all the way – This can make your bile very concentrated.
• There’s too much cholesterol in your bile – Your body needs bile for digestion. It usually dissolves cholesterol. But when it can’t do that, the extra cholesterol might form stones.
• Your gallbladder doesn’t empty correctly – If your gallbladder doesn’t empty completely or often enough, bile may become very concentrated, contributing to the formation of gallstones.

The following factors are known to increase the risk of gallstones

• Age – The risk of developing gallstones increases with age, especially after you reach the age of 40.
• Genes – If someone in your family has had gallstones.
• Sex – Women are more likely to get gallstones than men. The female sex hormone estrogen is believed to increase the risk of gallstones.
• Cirrhosis – A severe liver disease caused by metabolic disorders or excessive consumption of alcohol.
• Being very overweight.
• Losing a lot of weight in a short time – This happens a lot in very obese people who have surgery to make their stomach smaller.
• Functional problems of the gallbladder – The organ cannot contract (squeeze bile out) properly.
• Short bowel syndrome – A disorder that can develop after surgical removal of a large segment of the small bowel.
• Special high – calorie liquid food.
• Hemolysis – A disease that causes an increased breakdown of red blood cells.
• Pregnancy.
• Using the contraceptive pill or estrogen tablets during menopause (hormone therapy).
• Diabetes.

Symptoms of Cholelithiasis

• Sudden and rapidly intensifying pain in the upper right portion of your abdomen
• Sudden and rapidly intensifying pain in the center of your abdomen, just below your breastbone
• Back pain between your shoulder blades
• Pain in your right shoulder
• Nausea or vomiting
• Pain in your upper belly, often on the right, just under your ribs
• Pain in your right shoulder or back
• An upset stomach
• Other digestive problems, including indigestion, heartburn, and gas

See your doctor or go to the hospital if you have signs of a serious infection or inflammation

• Belly pain that lasts several hours
• Fever and chills
• Yellow skin or eyes
• Dark urine and light-colored poop

Diagnosis of Cholelithiasis

Your doctor will do a physical exam and might order tests including

• Blood tests – These check for signs of infection or blockage and rule out other conditions.
• Ultrasound – This makes images of the inside of your body.
• Abdominal ultrasound – This test is the one most commonly used to look for signs of gallstones. Abdominal ultrasound involves moving a device (transducer) back and forth across your stomach area. The transducer sends signals to a computer, which creates images that show the structures in your abdomen.
• CT scan – Specialized X-rays let your doctor see inside your body, including your gallbladder.
• Magnetic resonance cholangiopancreatography (MRCP) – This test uses a magnetic field and pulses of radio wave energy to take pictures of the inside of your body, including your liver and gallbladder.
• Cholescintigraphy (HIDA scan) – This test can check whether your gallbladder squeezes correctly. Your doctor injects a harmless radioactive material that makes its way to the organ. A technician can then watch its movement.
• Endoscopic retrograde cholangiopancreatography (ERCP) – Your doctor runs a tube called an endoscope through your mouth down to your small intestine. They inject a dye so they can see your bile ducts on a camera in the endoscope. They can often take out any gallstones that have moved into the ducts.
• Endoscopic ultrasound (EUS) – This procedure can help identify smaller stones that may be missed on an abdominal ultrasound. During EUS your doctor passes a thin, flexible tube (endoscope) through your mouth and through your digestive tract. A small ultrasound device (transducer) in the tube produces sound waves that create a precise image of surrounding tissue.

Treatment of Cholelithiasis 

Non-Pharmacological

1. Supportive therapy and dietary modifications –  elective cholecystectomy only for symptomatic patients who are surgical candidates or asymptomatic patients at risk of gallbladder cancer
2. Supportive therapy – Fasting or dietary modification (decreased fat intake)
3. Cholesterol gallstones – can sometimes be dissolved with ursodeoxycholic acid taken by mouth, but it may be necessary for the person to take this medication for years.^[rx]
4. Gallstones may recur, however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP).^[rx]
5. Regular, balanced meals — Purpose: prevent gallbladder over-concentrating bile. Mechanism: consistent eating triggers gallbladder emptying so cholesterol is less likely to crystallize. Frontiers

6. Gradual weight loss (not crash diets) — Purpose: cut risk of attacks during dieting. Mechanism: rapid weight loss makes bile cholesterol-rich; slow loss keeps bile composition steadier. Nature

7. Mediterranean-style pattern — Purpose: fewer symptoms/attacks long term. Mechanism: more fruits/vegetables/whole grains/olive oil improves lipid profile and bile composition. Frontiers

8. Physical activity (150–300 min/week) — Purpose: weight and insulin control. Mechanism: better insulin sensitivity reduces biliary cholesterol saturation. (Dietary-pattern evidence supports combined lifestyle.) Frontiers

9. Healthy fats, not trans fats — Purpose: reduce risk over time. Mechanism: mono-/poly-unsaturated fats help bile flow; trans/saturated fats worsen cholesterol balance. Frontiers

10. High-fiber intake — Purpose: smoother digestion, better cholesterol handling. Mechanism: soluble fiber increases bile acid use/excretion and may reduce bile cholesterol saturation. PubMed

11. Adequate hydration — Purpose: prevent overly concentrated bile. Mechanism: keeps bile less viscous (supportive principle; clinical endpoints depend on broader diet).

12. Coffee (moderate) — Purpose: lower risk of symptomatic gallstones in some cohorts. Mechanism: caffeine may stimulate gallbladder contraction and affect bile composition. (Not for everyone; avoid if sensitive.) JAMA NetworkGastro Journal

13. Nuts (handful a few times/week) — Purpose: potentially lower risk. Mechanism: unsaturated fats and phytosterols improve lipid handling. PubMed

14. Manage diabetes / insulin resistance — Purpose: reduce gallstone risk and complications. Mechanism: improved lipid/bile metabolism via glycemic control. (Lifestyle and medical care combined.) Frontiers

15. Avoid prolonged fasting — Purpose: prevent stasis. Mechanism: long fasting reduces gallbladder emptying, promoting sludge. (General pathophysiology principle.)

16. Post-bariatric counseling — Purpose: lower new-stone risk after major weight loss. Mechanism: structured diet and (often) UDCA prophylaxis during rapid loss. PMC

17. Limit refined sugars — Purpose: reduce lithogenic bile. Mechanism: spikes in insulin/lipids worsen cholesterol saturation. Frontiers

18. Stop smoking — Purpose: better overall GI and vascular health; mixed direct evidence but beneficial globally.

19. Treat hemolytic conditions (clinical care) — Purpose: reduce pigment stone formation. Mechanism: less bilirubin load to bile. NCBI

20. Pregnancy/estrogen counseling — Purpose: plan management if symptomatic. Mechanism: estrogen slows gallbladder emptying and increases cholesterol in bile. (Surgical and OB guidance available.) PMC

21. Pain self-care during mild colic — Purpose: comfort while awaiting care. Mechanism: rest, warm compress, low-fat intake for 24–48 h may reduce gallbladder stimulation (if no red flags).

22. Dietary pattern coaching after cholecystectomy — Purpose: reduce post-op bloating/diarrhea. Mechanism: gradual fat reintroduction; fiber helps stool consistency. (Patient-education consensus.)

23. Medication review — Purpose: identify drugs that worsen bile stasis (e.g., high-dose estrogen). Mechanism: adjust therapy with your clinician. PMC

24. Education on warning signs — Purpose: act early for complications. Mechanism: faster treatment prevents sepsis/pancreatitis (see “When to see a doctor”). BioMed Central

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Drug treatments

Always individualize with your clinician, especially for kidney/liver disease, pregnancy, older age, drug interactions.

1. NSAIDs (e.g., diclofenac IM 75 mg once; or ketorolac 15–30 mg IV q6h PRN short course)
   Class: anti-inflammatory analgesic. When: acute biliary colic. Purpose: pain relief; may reduce progression to complications. Mechanism: inhibits prostaglandins → less cystic duct edema/inflammation. Side effects: GI upset/ulcer, renal effects, bleeding risk. Strong evidence that NSAIDs relieve biliary pain and reduce complications vs placebo/spasmolytics. PubMedCochrane

2. Opioid rescue (e.g., morphine or hydromorphone short course if NSAIDs contraindicated)
   Class: opioid analgesic. When: severe pain not controlled with NSAID. Purpose: short-term rescue. Mechanism: central pain relief. Side effects: nausea, constipation, sedation; careful use (short courses). Trials show similar analgesia to ketorolac in ED settings. PubMedScienceDirect

3. Antiemetic (ondansetron 4–8 mg IV/PO PRN)
   Class: 5-HT3 antagonist. When: nausea/vomiting with biliary colic. Purpose: symptom control. Mechanism: blocks serotonin receptors in GI/CNS. Side effects: headache, constipation, rare QT prolongation. (Supportive therapy per general acute care.)

4. Antispasmodic (hyoscine butylbromide/scopolamine-butylbromide 20 mg IM/IV)
   Class: anticholinergic. When: colicky spasm. Purpose: smooth-muscle relaxation. Mechanism: blocks muscarinic receptors. Side effects: dry mouth, blurry vision, urinary retention. Diclofenac outperforms hyoscine for biliary colic relief in trials. PubMed

5. Ursodeoxycholic acid (UDCA/ursodiol 8–10 mg/kg/day in 2–3 doses; up to 6–12 months)
   Class: bile acid. When: selected patients with radiolucent cholesterol stones, functioning gallbladder, small/floatable stones, poor surgical candidates or refusing surgery. Purpose: stone dissolution and symptom reduction in some cases. Mechanism: reduces bile cholesterol saturation; improves bile flow. Side effects: mild GI upset. Notes: works slowly; recurrence can happen after stopping; not for calcified/pigment stones. DailyMedAAFP

6. Chenodeoxycholic acid (chenodiol 13–16 mg/kg/day in 2 doses; limited use)
   Class: bile acid. Purpose: alternative dissolution agent with more side effects (diarrhea, liver enzyme rise); far less used today. Mechanism: similar to UDCA. When: very selected cases; monitor LFTs. NCBIRxList

7. Antibiotics for acute cholecystitis or cholangitis (only if infection)
   Class: e.g., ceftriaxone + metronidazole, piperacillin-tazobactam, ertapenem depending on severity and local resistance. When: fever, leukocytosis, positive imaging/labs suggesting infection. Purpose: treat infection plus source control (surgery/ERCP). Mechanism: targets Gram-negatives/anaerobes typical of biliary infection. Duration: often ≤4 days after successful source control; avoid prolonged courses in mild/moderate cases. Side effects: drug-specific. PMCPubMed

8. UDCA + omega-3 (EPA/DHA) — emerging
   Class: bile acid + PUFA. When: investigational adjunct for cholesterol stones. Purpose: may improve dissolution vs UDCA alone in small studies. Mechanism: further lowers cholesterol saturation. Side effects: fishy taste, GI upset. Note: promising but not yet standard of care. PMC

9. Bile-acid sequestrant for cholestatic itch (cholestyramine 4 g 1–4×/day)
   Class: resin. When: pruritus from cholestasis (e.g., stone-related obstruction, while awaiting ERCP). Purpose: symptom relief. Mechanism: binds bile acids in gut. Side effects: bloating, constipation, drug binding. (Adjunct; not for stone removal.)

10. Prophylactic UDCA after bariatric surgery (e.g., 300 mg BID for ~6 months) where used
    Class: bile acid. Purpose: lowers new gallstone formation during rapid weight loss, though results vary across trials; consider in high-risk patients per bariatric team. Mechanism: keeps bile less lithogenic during catabolic state. Side effects: mild GI. PMC+1

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Dietary “molecular” supplements

Plain English, typical consumer doses, function, mechanism, evidence level.
Important: No supplement can break established gallstones reliably. Use as supportive care only and discuss with your clinician—especially if you may need surgery or have liver disease.

1. Psyllium husk (7–10 g/day): helps bowel rhythm and cholesterol handling; may increase bile acid turnover → less cholesterol saturation of bile (evidence for cholesterol effects; gallstone endpoints limited). PubMed

2. Vitamin C (500–1000 mg/day): cofactor for bile-acid synthesis enzyme (CYP7A1); some human data link higher vitamin C status with lower gallstone prevalence, especially in women (observational). JAMA Network

3. Fish oil (EPA/DHA) (1–2 g/day): may favorably alter bile lipids; early data plus combination trials with UDCA suggest potential benefit (not definitive). PMC

4. Phosphatidylcholine (lecithin) (1–3 g/day): key bile phospholipid; conceptually stabilizes micelles; human prevention data are limited/indirect. JLR

5. Magnesium (200–400 mg/day): general metabolic benefits; direct gallstone evidence is weak; consider only if deficient.

6. Taurine (500–1000 mg/day): aids bile-acid conjugation in theory; clinical evidence in humans for gallstones is limited.

7. Curcumin (500–1000 mg/day with pepper/ginger): choleretic effects in models; human gallstone data lacking; watch for drug interactions.

8. Artichoke leaf extract (approx. 600–1000 mg/day): may stimulate bile flow; evidence for symptom help is modest and not gallstone-dissolving.

9. Probiotics (labeled dose): may indirectly help lipid and bile acid metabolism; human gallstone endpoints lacking.

10. Vitamin E or mixed antioxidants: no reliable evidence for stone prevention; avoid high-dose self-supplementation without medical advice.

(For supplements above, the best evidence supports diet pattern change rather than any single pill.) Frontiers

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Regenerative / stem cell drugs

For cholelithiasis, there are no evidence-based “immunity booster,” regenerative, or stem-cell drugs that treat or prevent gallstones. Major guidelines (NICE, WSES, ASGE, SAGES) do not recommend any such agents—management is lifestyle, evidence-based medications (e.g., UDCA in selected cases), and procedures (ERCP/cholecystectomy) when indicated. Using unproven “stem cell” or “regenerative” products for gallstones is not recommended. Safer alternatives are listed in the drug/surgery sections above. NICEBioMed CentralPubMedSAGES

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Surgeries / procedures

1. Cholecystectomy (gall stones removal) has a 99% chance of eliminating the recurrence of cholelithiasis. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population—between 10 and 15%—who develop a condition called postcholecystectomy syndrome^[rx] which may cause nausea, indigestion, diarrhea, and episodes of abdominal pain.^[rx]

2. Laparoscopic cholecystectomy (standard of care) — Keyhole removal of the gallbladder through small incisions. Why: best long-term cure for recurrent biliary colic and for complications (cholecystitis), with faster recovery than open surgery. Early cholecystectomy (during the same admission) for acute cholecystitis shortens length of stay and doesn’t raise major complication rates when expertise is available. Cochrane LibraryJAMA Network

3. Open cholecystectomy — Larger incision; used if anatomy is unsafe for laparoscopy or severe inflammation/scar tissue exists. Why: safety in complex cases. SAGES

4. ERCP with sphincterotomy and stone extraction — Endoscopic removal of common bile duct stones; can place stents if needed. Why: treats jaundice/cholangitis/pancreatitis from duct stones; therapeutic first-line for choledocholithiasis. PubMed

5. Laparoscopic common bile duct exploration (LCBDE) — Surgeon clears duct stones during the same operation as gallbladder removal. Why: single-stage solution in experienced hands. SAGES

6. Percutaneous cholecystostomy (drain) — Needle catheter placed into gallbladder by interventional radiology. Why: temporary source control in very high-risk or critically ill patients who cannot undergo immediate surgery. BioMed Central

There are two surgical options for cholecystectomy

• Open cholecystectomy is performed via an abdominal incision (laparotomy) below the lower right ribs. Recovery typically requires 3–5 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release.^[rx]
• Laparoscopic cholecystectomy, introduced in the 1980s, is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one-night hospital stay, followed by a few days of home rest and pain medication.^[rx]
• Laparoscopic cholecystectomy (removal of the gallbladder through multiple small incisions; this is less invasive and a more commonly used technique)
• Lithotripsy (the technique that uses electric shock waves to dissolve gallstones; it is not commonly used today)
• Open cholecystectomy (removal of the gallbladder through a single, large incision; this is a more invasive and less commonly used technique)

(Extracorporeal shock-wave lithotripsy and EUS-guided gallbladder drainage exist for select scenarios but are not routine for uncomplicated stones.) BioMed Central

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Preventions

1. Maintain healthy weight; avoid rapid weight loss. Nature

2. Follow a Mediterranean-like pattern long term. Frontiers

3. Exercise most days of the week. Frontiers

4. Eat more fiber (whole grains, legumes, fruits, vegetables). PubMed

5. Choose unsaturated fats (olive oil, nuts, fish) over saturated/trans fats. Frontiers

6. Consider UDCA prophylaxis after bariatric surgery if your bariatric team recommends it. PMC

7. Keep diabetes and triglycerides under control. Frontiers

8. Do not skip meals for long periods; avoid very-low-calorie crash diets. Nature

9. Discuss estrogen therapies and pregnancy-related biliary symptoms early with your clinician. PMC

10. Learn warning signs and seek care early (see below). BioMed Central

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When to see a doctor (red flags)

• Severe right-upper-abdominal pain (often after a fatty meal) lasting > 6 hours.

• Fever or chills (possible infection).

• Jaundice (yellow eyes/skin), dark urine, pale stools (possible duct blockage).

• Nausea/vomiting, inability to keep fluids down.

• Severe belly pain with back pain or chest symptoms (rule out pancreatitis or heart disease).

• After bariatric surgery if you develop new RUQ pain.
  These need urgent assessment because complications like acute cholecystitis, cholangitis, or gallstone pancreatitis can be dangerous without rapid treatment and source control (ERCP or surgery). BioMed Central

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What to eat” and “what to avoid

Eat more of:

1. Fruits (esp. citrus, berries)

2. Vegetables (leafy greens, crucifers)

3. Whole grains (oats, brown rice)

4. Legumes (lentils, beans)

5. Fish (omega-3 sources)

6. Nuts and seeds (almonds, walnuts)

7. Olive oil (replace butter/ghee where possible)

8. Low-fat dairy or fortified alternatives

9. Plenty of water

10. Moderate coffee (if tolerated; avoid if it worsens symptoms) FrontiersPubMedJAMA Network

Limit/avoid:

1. Trans fats (fried/packaged foods)

2. Very high-saturated-fat meals (deep-fried, fatty cuts)

3. Large, heavy, late-night meals

4. Rapid-weight-loss diets/long fasting

5. Sugary drinks and refined carbs

6. Excess alcohol (also harms the pancreas/liver)

7. Ultra-processed snacks

8. High-fat desserts

9. Oversized portions (opt for smaller, regular meals)

10. Any food you notice triggers your pain personally Frontiers

Complications

Complications of gallstones may include:

• Inflammation of the gallbladder – A gallstone that becomes lodged in the neck of the gallbladder can cause inflammation of the gallbladder (cholecystitis). Cholecystitis can cause severe pain and fever.
• Blockage of the common bile duct – Gallstones can block the tubes (ducts) through which bile flows from your gallbladder or liver to your small intestine. Severe pain, jaundice, and bile duct infection can result.
• Blockage of the pancreatic duct – The pancreatic duct is a tube that runs from the pancreas and connects to the common bile duct just before entering the duodenum. Pancreatic juices, which aid in digestion, flow through the pancreatic duct. A gallstone can cause a blockage in the pancreatic duct, which can lead to inflammation of the pancreas (pancreatitis). Pancreatitis causes intense, constant abdominal pain and usually requires hospitalization.
• Gallbladder cancer – People with a history of gallstones have an increased risk of gallbladder cancer. But gallbladder cancer is very rare, so even though the risk of cancer is elevated, the likelihood of gallbladder cancer is still very small.

References

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