Cholesterol-Absorption Inhibitors

Antilipemics/Nutrient Depletion:

  • Beta-caroteneBeta-carotene: According to secondary sources, cholestyramine (Questran?) and colestipol (Colestid?) may reduce absorption of fat-soluble vitamins, including beta-carotene. A clinical trial suggests that serum carotenoid concentrations were reduced in adolescents treated with colestipol (8660081). Serum levels of beta-carotene may be reduced, but this may be only in proportion to the lowering of cholesterol (on which beta-carotene is transported).
  • Beta-sitosterolBeta-sitosterol: Cholestyramine reduced beta-sitosterol concentrations in patients with sitosterolemia (1997308, 6768564, 8529322). Lifibrol, a lipid-lowering drug for the therapy of hypercholesterolemia, has been shown in clinical trials to reduce sterols including lanosterol, lathosterol, beta-sitosterol, and campesterol (7828385). According to human study, ezetimibe has been shown to decrease plasma plant sterol concentrations in individuals with sitosterolemia (14769702).
  • CalciumCalcium: According to animal study, cholestyramine (Questran?) (commonly used for high blood cholesterol) may reduce the absorption of vitamin D, which, in turn, may reduce the absorption of calcium (3987479).
  • Coenzyme Q10 (CoQ10)Coenzyme Q10 (CoQ10): Based on human study, the combination of simvastatin and ezetimibe may decrease plasma CoQ10 levels, although ezetimibe monotherapy may not (16872244). Based on human evidence, HMG-CoA reductase inhibitors (e.g. lovastatin) lead to a decreased concentration of CoQ10 (15942122, 15721028, 16003294, 16872244, 17389800). Based on human studies, CoQ10 concentrations decreased in patients treated with pravastatin and lovastatin or pravastatin and simvastatin (9266515, 8463436, 10337451).
  • FolateFolate: According to secondary sources, cholestyramine may reduce folic acid absorption by lowering serum and red blood cell folate levels in children taking large doses for several months. A clinical trial suggests that colestipol (Colestid?) may interfere with absorption of folic acid, and reduced serum folate levels may occur (8660081). The authors recommended maintenance of folate intake. Based on human evidence, cholestyramine may reduce folate concentrations within the body, resulting in a folate deficiency (1168607, 63709). This depletion was overcome by folic acid supplementation.
  • IronIron: Based on animal evidence, cholestyramine (Questran?) and colestipol (Colestid?) may bind iron in the gut, reducing its absorption (3987479). There is a current lack of literature supporting clinically significant iron deficiency induced by these drugs, and supplements are not likely to be needed. Secondary sources indicate that if taking iron supplements for other causes of deficiency, then it may be recommended that the iron and cholestyramine or colestipol doses be separated by at least four hours. Based on human study, cholestyramine may not impair iron levels (1168607). Animal study did not find a reduction of serum iron with concurrent use of cholestyramine (3186761). However, secondary studies suggest a decrease associated with cholestyramine.
  • LycopeneLycopene: Based on human evidence, bile acid sequestrants such as cholestyramine (Questran?, Prevalite?, LoCHOLEST?) and cholestipol (Cholestid?) may reduce serum levels of lycopene (7627696). In clinical study, probucol (available in Canada, not commercially available in the United States) administration was associated with a statistically significant decrease in serum carotenoid levels in hypercholesterolemic patients (7627696). Although supplementation with carotenoids such as lycopene may offset these observed reductions, the potential benefits of supplementation are not clear.
  • MagnesiumMagnesium: Preliminary evidence suggests that cholestyramine (Questran?) may slightly increase urinary magnesium excretion, possibly by binding vitamin D and leading to reduced magnesium absorption (3987479). However, evidence of clinically significant magnesium deficiency is currently lacking, and the necessity for magnesium supplementation may be unlikely.
  • PhosphorusPhosphorus: According to secondary sources, bile acid sequestrants such as cholestyramine (Questran?) and colestipol (Colestid?) may decrease oral absorption of phosphate. Therefore, oral phosphate supplements may be administered at least one hour before or four hours after these agents. Human evidence has suggested a reduction in phosphate levels associated with colestipol use (724301). Human evidence also suggests a reduction in phosphate levels with the use of cholestyramine (1168607). The clinical significance of this effect, however, may be lacking (1583392).
  • Vitamin A/retinolVitamin A/retinol: According to secondary sources, cholestyramine (Questran?) and colestipol (Colestid?) may decrease the effectiveness of vitamin A by reducing absorption of this fat-soluble vitamin (4706914, 7460169). A clinical trial, however, suggests that serum concentrations of vitamin A were not reduced in adolescents treated with colestipol (8660081). Animal studies have suggested the reduction in liver storage of dietary vitamin A due to cholestyramine (14263050).
  • Vitamin B12Vitamin B12: According to secondary sources, colestipol (Colestid?) and cholestyramine (Questran?) may decrease gastrointestinal absorption of vitamin B12. It is unlikely that this interaction may deplete body stores of vitamin B12 unless there are other factors contributing to deficiency. In a group of children treated with cholestyramine for up to 2.5 years there was no change in serum vitamin B12 levels. Based on in vitro studies, instrinic-factor mediated binding of vitamin B12 and cholestyramine may occur, resulting in decreased levels of vitamin B12 (40578,30840). Secondary studies have also suggested a decrease in serum vitamin B12 associated with cholestyramine (5023882).
  • Vitamin D/calciferolVitamin D/calciferol: Based on evidence from animal study, intestinal absorption of vitamin D may be impaired with the use of cholestyramine (Questran?) or colestipol (Colestid?) (4318526). Secondary sources indicate that individuals using cholestyramine or colestipol allow as much time as possible between the ingestion of these drugs and vitamin D. Based on human and animal evidence, conflicting data exist with regard to whether cholestyramine may reduce vitamin D levels, resulting in a possible reduction of calcium (8660081, 1583392, 2125243,3987479), 640344, 4318526). Human evidence evaluating the effect of cholestyramine on calcium levels suggests an increase in urinary excretion of calcium (5052395). Human evidence has also suggested a gradual decrease in vitamin D levels associated with colestipol use (724301). A clinical trial, however, suggests that serum vitamin D concentrations were not reduced in adolescents treated with colestipol (8660081). Secondary sources suggest that patients may be monitored if long-term therapy with bile-sequestrants is expected.
  • Vitamin EVitamin E: Based on human evidence, colestipol, cholestyramine (Questran?), and gemfibrozil (Lopid?) may reduce dietary vitamin E absorption and blood levels of vitamin E (11185669, 1089329, 3885456). Based on human evidence, conflicting results exist pertaining to whether cholestyramine may lower Vitamin E (11185669, 1168607,8660081). Based on human evidence, gemfibrozil may not affect vitamin E concentrations (9699906).
  • Vitamin KVitamin K: According to secondary sources, cholestyramine (Questran?) may decrease absorption of oral vitamin K and increase vitamin K requirements. Based on human case reports, cholestyramine may lower vitamin K (12688565). Animal studies have also suggested the reduction in vitamin K due to cholestyramine (14263050).
  • ZincZinc: Based on human study, cholestyramine may decrease zinc excretion in the urine and alkalinization of urinary zinc (3966424).