ModerateTiming Sensitive
Vitamin D3
Cholestyramine can reduce absorption of fat-soluble vitamins including vitamin D.
Recommendation: Separate vitamin D from cholestyramine by at least 4 hours and monitor vitamin D status during long-term therapy.
Cholestyramine
Prescription ·Strong evidence ·Reviewed May 2026
Cholestyramine is an oral, non-absorbed anion-exchange resin used to lower elevated LDL cholesterol and to relieve pruritus associated with partial biliary obstruction. It binds bile acids in the intestine, forming an insoluble complex that is excreted in the feces, which interrupts the enterohepatic circulation of bile acids. Because it is not absorbed systemically, its effects and adverse events are largely confined to the gastrointestinal tract and to interference with the absorption of other substances.
What it's good for
The bottom line
Evidence rating strong. Most-documented uses: reduction of elevated ldl cholesterol (primary hypercholesterolemia), relief of pruritus associated with partial biliary obstruction and cholestasis, adjunct to diet in management of hyperlipidemia. 3 sources indexed (1984–2018), with 7 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Cholestyramine is a quaternary ammonium anion-exchange resin that binds negatively charged bile acids in the intestinal lumen, forming a non-absorbable complex that is eliminated in the stool. The resulting depletion of the bile acid pool removes the normal feedback inhibition of cholesterol 7-alpha-hydroxylase, increasing hepatic conversion of cholesterol into new bile acids. To replenish hepatic cholesterol, the liver upregulates LDL receptors and increases clearance of LDL particles from the circulation, lowering serum LDL cholesterol. By sequestering bile acids it also reduces the micellar solubilization needed for absorption of dietary fat and fat-soluble vitamins, and its resin can adsorb numerous co-administered drugs and luminal substances such as bile-acid-driven irritants that cause cholestatic pruritus.1,2
Class
Bile acid sequestrant
Absorption
Water-soluble; take with food
Dosing
Dosing & protocol.
Common range
Adults: typically 4 g of anhydrous resin once or twice daily initially, titrated to a usual maintenance range of 8 to 16 g per day divided into 2 doses; maximum about 24 g per day. Each dose is mixed with water or other fluid before ingestion (never taken dry).
Recommended form
Oral powder for suspension (4 g anhydrous resin per packet or scoop), available as regular and sugar-free/light formulations; also as chewable bar in some formulations.
The resin itself is not absorbed from the gastrointestinal tract. It is usually taken with meals (commonly before or with breakfast and the evening meal) because it acts in the gut on bile acids released during digestion. The powder must be mixed thoroughly with at least 60 to 180 mL of water, juice, or other fluid and allowed to hydrate; it should never be taken in dry form due to esophageal irritation and aspiration risk. Critically, cholestyramine binds and reduces absorption of fat-soluble vitamins (A, D, E, K), folic acid, and many co-administered oral drugs, so other medications should generally be taken at least 1 hour before or 4 to 6 hours after cholestyramine.3
Depletions
What it depletes.
Nutrients this medication can lower over time, and what to replace.
Vitamin D
ModerateBile acid sequestration can impair absorption of fat-soluble vitamin D.
Vitamin K
SignificantBile acid sequestration can impair vitamin K absorption and lower vitamin K dependent clotting factor activity.
Vitamin A
ModerateBile acid sequestration can impair absorption of fat-soluble vitamin A during long-term use.
Replace Vitamin A if prescribedMonitor Serum retinol if deficiency suspectedOnset Months with chronic therapy
Vitamin E
ModerateBile acid sequestration can impair absorption of fat-soluble vitamin E during long-term use.
Folate
MildCholestyramine can bind folate in the gut and lower its absorption; reduced serum and red-cell folate has been reported with prolonged therapy, with the greatest concern in children, pregnant patients, and those with marginal intake.
Replace Folic acid, taken at least 1 hour before or 4 to 6 hours after cholestyramineMonitor Serum folate and red-blood-cell folateOnset Months of continuous therapy
Safety
Full safety detail.
Side effects
- Constipation (very common, may be severe)
- Abdominal pain, bloating, and flatulence
- Nausea and dyspepsia
- Heartburn and esophageal irritation
- Steatorrhea and reduced absorption of dietary fat with high doses
- Deficiency of fat-soluble vitamins A, D, E, and K with prolonged or high-dose use
- Hypoprothrombinemia and increased bleeding tendency from vitamin K depletion
- Folic acid deficiency (relevant in children and pregnancy)
- Hyperchloremic metabolic acidosis (particularly in children and at high doses)
- Reduced absorption and efficacy of many co-administered oral drugs
Contraindications
- Complete biliary obstruction (no bile acids are secreted into the gut, so the drug is ineffective)2,3
- Known hypersensitivity to cholestyramine or any component of the formulation1,2
- Caution with phenylketonuria for formulations containing aspartame (sugar-free/light products)
- Relative caution in pre-existing constipation, hemorrhoids, or conditions worsened by constipation
- Caution in patients prone to hyperchloremic acidosis and in young children
Interactions
Interaction records.
SeriousTiming Sensitive
Vitamin K1
Cholestyramine can reduce vitamin K absorption and may increase bleeding risk or alter INR.
Recommendation: Separate vitamin K from cholestyramine and monitor INR if anticoagulated or if bleeding occurs.
ModerateTiming Sensitive
Vitamin E
Cholestyramine can reduce absorption of fat-soluble vitamin E during long-term use.
Recommendation: Separate vitamin E from cholestyramine and monitor for deficiency only when clinically indicated.
InfoTiming Sensitive
Calcium
Cholestyramine may bind or delay absorption of some supplements when taken simultaneously.
Recommendation: Separate calcium and other oral supplements from cholestyramine by at least 4 hours.
ModerateTiming Sensitive
Vitamin A
Cholestyramine impairs absorption of fat-soluble vitamin A. Long-term therapy can lower serum vitamin A and beta-carotene levels, with potential for deficiency manifestations such as impaired dark adaptation in susceptible patients.
Recommendation: Separate administration, taking vitamin A at least 1 hour before or 4 to 6 hours after cholestyramine. Monitor vitamin A status in patients on prolonged high-dose therapy or with malabsorptive conditions and supplement if needed.
ModerateTiming Sensitive
Vitamin B6
Cholestyramine can bind and reduce intestinal absorption of folate, and folate deficiency has been documented with prolonged therapy, especially in children. While this primarily affects folate, taking other supplements at the same time as the resin also risks reduced absorption.
Recommendation: Administer folate and B-vitamin supplements separately from cholestyramine, ideally at least 1 hour before or 4 to 6 hours after. Monitor folate status during long-term therapy, particularly in children and pregnant patients.
ModerateTiming Sensitive
Iron
Cholestyramine can bind oral iron in the gastrointestinal tract and reduce its absorption when taken concurrently, potentially diminishing the efficacy of iron supplementation for treating or preventing deficiency.
Recommendation: Take iron supplements at least 1 hour before or 4 to 6 hours after cholestyramine to avoid binding. Monitor hemoglobin and ferritin if iron deficiency is being treated during sequestrant therapy.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Randomized controlled trials
1- 1The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart diseaseNeeds reviewPMIDLipid Research Clinics Program · JAMA · 1984
Cholestyramine reduced total cholesterol and LDL cholesterol and was associated with a significant reduction in coronary heart disease death and nonfatal myocardial infarction compared with placebo.
Reviews & position papers
2- 2Questran (cholestyramine for oral suspension) FDA prescribing informationNeeds reviewNo linkBristol-Myers Squibb · FDA label · 2018
Label describes mechanism, indications for primary hypercholesterolemia and pruritus of partial biliary obstruction, and warnings regarding fat-soluble vitamin malabsorption and drug interactions.
- 3Bile acid sequestrants: a review of mechanism of action and clinical useNeeds reviewPMIDInsull W · Southern Medical Journal · 2006
Bile acid sequestrants reduce LDL cholesterol but interfere with absorption of fat-soluble vitamins and numerous drugs; co-administered medications should be dosed 1 hour before or 4 to 6 hours after the sequestrant.
Keep exploring
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Cholestyramine in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.