Beta-sitosterol

Beta-sitosterol/Drug Interactions:

  • AcarboseAcarbose: A controlled clinical trial investigated the impact of starch malabsorption on colon carcinogenesis and found that the alpha-glucosidase inhibitor acarbose decreases fecal concentration of beta-sitosterol by approximately 40%, indicating that absorption may be increased (21).
  • Activated charcoalActivated charcoal: In human research, activated charcoal (8g given three times a day) slightly decreased serum levels of beta-sitosterol (180).
  • Alpha1-blockersAlpha1-blockers: In human clinical studies, beta-sitosterol relieves symptoms of benign prostatic hyperplasia, possibly mediated through mechanisms similar to those of finasteride and alpha-blockers (81; 82; 181).
  • Antiarthritic agentsAntiarthritic agents: In human research, anti-arthritic effects appear to be related to the inhibition of IL-6 and TNF-alpha-activated monocyte activation (179).
  • AntibioticsAntibiotics: Beta-sitosterol may protect and improve the oral absorption of acid-labile antibiotics, particularly, the potassium salts of penicillin G and penicillin V and erythromycin lactobionate (62).
  • Antidiabetic agentsAntidiabetic agents: In animal research, beta-sitosterol had hypoglycemic effects (71). Two human clinical trials have shown either a lowering of HbA1C or a lack of effect of plant sterols in diabetic subjects (94; 95). Also, in an animal study, fractions obtained from the leaves of Morus insignis, a source of beta-sitosterol, demonstrated hypoglycemic effects (71).
  • AntihistaminesAntihistamines: In human research, improvement in allergic symptoms, including a decrease in rhinorrhea and post-nasal drip, appears to be achieved through a decrease in the synthesis of IL-4 (182).
  • AntilipemicsAntilipemics: Plant sterols, including beta-sitosterol, have been shown to lower TC as well as LDL-C in randomized controlled trials (RCTs) (43; 183; 44; 45; 46; 47; 184; 177; 129; 185; 186; 32; 158; 49; 18; 89; 187; 54; 90; 188; 132; 189). HDL-C has been shown in clinical trials to be increased by about 5% with supplementation of plant sterols, including beta-sitosterol, in the diet (45; 189). Data from other clinical trials contradict this and suggest that a lack of effect of beta-sitosterol on HDL-C (46; 47; 185; 190; 18; 191; 178; 192; 54; 89). In children with familial hypercholesterolemia, there was a 15% reduction in HDL-C with treatment with beta-sitosterol (90).
  • Antineoplastic agentsAntineoplastic agents: Epidemiological, in vitro, and animal studies suggest that dietary phytosterols, including beta-sitosterol, have anti-cancer effects against several types of cancer, including breast, colon, esophageal, rectal, stomach and prostate (14; 2; 3; 4; 20; 193; 194; 17; 195; 196; 197; 16; 198; 26; 31; 149; 32; 33; 35; 199; 36; 200; 201; 23; 202; 38; 3; 156; 66; 203).
  • AntiplateletsAntiplatelets: Certain plant species, which contain beta-sitosterol, exhibit anti-platelet aggregation activities in vitro (66). The contribution of the beta-sitosterol constituent to this activity is unknown.
  • Antituberculosis agentsAntituberculosis agents: Beta-sitosterol and beta-sitosterol glucoside have been shown in randomized controlled trials to improve weight gain, and increase lymphocyte and eosinophil counts from baseline when used in combination with various antituberculosis agents (179).
  • Beta-lactoglobulin tryptic hydrolysate (LTH)Beta-lactoglobulin tryptic hydrolysate (LTH): Beta-lactoglobulin tryptic hydrolysate (LTH) reduced serum cholesterol (204).
  • Cardiovascular agentsCardiovascular agents: In vitro, beta-sitosterol inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), the concentrations of monocyte chemoattractive protein-1 (MCP-1) as well as the migration and adhesion of THP-1 cells to the human umbilical venous endothelial cells (HUVEC) in the presence of oxidized LDL-C (205).
  • CholestyramineCholestyramine: Cholestyramine doses of up to 32g daily reduced beta-sitosterol concentrations in patients with sitosterolemia (162; 168; 154).
  • Cyclooxygenase inhibitorsCyclooxygenase inhibitors: In vitro analysis of some plant species containing beta-sitosterol suggests that components of the plants exhibit anti-cyclooxygenase effects (64).
  • DalcetrapibDalcetrapib: Dalcetrapib doses of 900mg daily for seven days resulted in increased beta-sitosterol by 32% in healthy subjects (206).
  • DiosgeninDiosgenin: Data from animal studies suggest that the co-administration of beta-sitosterol and diosgenin affects the uptake of diosgenin by the liver (207).
  • EzetimibeEzetimibe: Ezetimibe has been shown in reviews, randomized controlled trials, and observational clinical trials to decrease sitosterol concentrations in children and adults with sitosterolemia, hyperlipidemic individuals, and individuals with and without type 2 diabetes (208; 209; 210; 211; 212; 213; 214; 215; 216). Doses of 40mg daily of ezetimibe have been shown to have greater effects on reducing plasma plant sterol concentrations in individuals with sitosterolemia compared to doses of 10mg daily (217). The effects of ezetimibe on sitosterol levels are significantly more potent in individuals with the CC genotype of the sterol regulatory binding protein-1c (SREBP-1c) polymorphism than the G allele-carriers (218). The effects of ezetimibe on sitosterol levels are increased with co-administration of rifampin (219).
  • High-lipase pancreatinHigh-lipase pancreatin: High-lipase pancreatin may alter fecal excretion of beta-sitosterol (220).
  • Hormone replacement therapyHormone replacement therapy: Beta-sitosterol has demonstrated estrogenic/antiestrogenic activity in vitro and in animal studies (76; 108).
  • ImmunomodulatorsImmunomodulators: Beta-sitosterol and beta-sitosterol glucoside have been used to decrease immunosuppressive responses as a result of strenuous exercise; effects have also been shown in vitro (26; 15; 26; 109; 110).
  • LifibrolLifibrol: 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 (221).
  • NMDA receptor antagonistsNMDA receptor antagonists: NMDA receptor antagonists block the neurotoxic actions of sterol glucosides according to in vitro bioassays, although they do not compete for binding at the NMDA receptor (103).
  • RifampinRifampin: The effects of ezetimibe on sitosterol levels are increased with co-administration of rifampin (219).
  • StatinsStatins: Simvastatin has been shown in a randomized controlled trial to elevate the ratio of plant sterol to cholesterol in patients with the highest baseline campestanol levels (107). Simvastatin and niacin in combination have been shown in a randomized controlled trial to elevate beta-sitosterol levels in patients with low high density cholesterol (HDL-C) (174). Atorvastatin and simvastatin have been shown to independently elevate the ratio of plant sterol to cholesterol in patients with and without coronary heart disease (222; 223; 224) and atorvastatin has been suggested to increase levels of plasma plant sterols in diabetics (225). Co-administration of ezetimibe with statins has significantly decreased plasma sitosterol (226). A clinical trial has shown pravastatin treatment increases sitosterol levels in children with heterozygous familial hypercholesterolemia (227). Pravastatin, an HMG-CoA reductase inhibitor, significantly reduced sitosterol in clinical trials of hypercholesterolemic subjects; however, it lacked effect in an individual with sitosterolemia (105). In human research, atorvastatin dosed at 40mg daily for 12 weeks has been reported to significantly increase sitosterol (228). In vitro studies report that beta-sitosterol decreased the activities of HMG-CoA reductase (229).

    • Beta-sitosterol/Herb/Supplement Interactions:

  • Alpha-tocopherol (vitamin E)Alpha-tocopherol (vitamin E): In clinical trials bioavailability of alpha-tocopherol decreased with concurrent administration of plant sterols (230).
  • Antiarthritic agentsAntiarthritic agents: In human research, anti-arthritic effects appear to be related to the inhibition of IL-6 and TNF-alpha-activated monocyte activation (179).
  • AntibacterialsAntibacterials: Beta-sitosterol may protect and improve the oral absorption of acid-labile antibiotics, particularly, the potassium salts of penicillin G and penicillin V and erythromycin lactobionate (62).
  • AntihistaminesAntihistamines: In human research, improvement in allergic symptoms, including a decrease in rhinorrhea and post-nasal drip, appears to be achieved through a decrease in the synthesis of IL-4 (182).
  • AntilipemicsAntilipemics: Plant sterols, including beta-sitosterol, have been shown to lower TC as well as LDL-C in randomized controlled trials (RCTs) (43; 183; 44; 45; 46; 47; 184; 177; 129; 185; 186; 32; 158; 49; 18; 89; 187; 54; 90; 188; 132; 189). Plant sterols, including beta-sitosterol, have been shown to lower TC as well as LDL-C in randomized controlled trials (RCTs) (43; 183; 44; 45; 46; 47; 184; 177; 129; 185; 186; 32; 158; 49; 18; 89; 187; 54; 90; 188; 132; 189). HDL-C has been shown in clinical trials to be increased by about 5% with supplementation of plant sterols, including beta-sitosterol, in the diet (45; 189). Data from other clinical trials contradict this and suggest that a lack of effect of beta-sitosterol on HDL-C (46; 47; 185; 190; 18; 191; 178; 192; 54; 89). In children with familial hypercholesterolemia, there was a 15% reduction in HDL-C with treatment with beta-sitosterol (90).
  • Antineoplastic agentsAntineoplastic agents: Epidemiological, in vitro and animal studies suggest that dietary phytosterols, including beta-sitosterol, have anti-cancer effects against several types of cancer, including breast, colon, esophageal, rectal, stomach and prostate (14; 2; 3; 4; 20; 193; 194; 17; 195; 196; 197; 16; 198; 26; 31; 149; 32; 33; 35; 199; 36; 200; 201; 23; 202; 38; 3; 156; 66; 203).
  • AntioxidantsAntioxidants: In vitro, replacement of cholesterol with sitosterol in the cell membrane resulted in a significant decrease of thiobarbituric reactive substances (TBARS) (231).
  • AntiplateletsAntiplatelets: Certain plant species, which contain beta-sitosterol, exhibit anti-platelet aggregation activities in vitro (66). The contribution of the beta-sitosterol constituent to this activity is unknown.
  • Antituberculosis agentsAntituberculosis agents: Beta-sitosterol and beta-sitosterol glucoside have been shown in randomized controlled trials to improve weight gain, and increase lymphocyte and eosinophil counts from baseline when used in combination with various antituberculosis agents (179).
  • Beta-caroteneBeta-carotene: In human clinical trials, plant sterols, including beta-sitosterol, given in doses of up to 9g daily reduced beta-carotene blood levels (131; 232; 44; 45; 48; 190; 191; 178; 54). This is thought to be a result of reductions in LDL-C, which carries beta-carotene, by beta-sitosterol (23). Randomized controlled trials indicate that the lowering of beta-carotene is counterbalanced by consuming an additional daily serving of a high-carotenoid vegetable or fruit when consuming spreads containing sterol or stanol esters (50).
  • Beta-lactoglobulin tryptic hydrolysate (LTH)Beta-lactoglobulin tryptic hydrolysate (LTH): Beta-lactoglobulin tryptic hydrolysate (LTH) reduced serum cholesterol (204).
  • Cardiovascular agentsCardiovascular agents: In vitro, beta-sitosterol inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), the concentrations of monocyte chemoattractive protein-1 (MCP-1) as well as the migration and adhesion of THP-1 cells to the human umbilical venous endothelial cells (HUVEC) in the presence of oxidized LDL-C (205).
  • Cyclooxygenase inhibitorsCyclooxygenase inhibitors: In vitro analysis of some plant species containing beta-sitosterol suggests that components of the plants exhibit anti-cyclooxygenase effects (64).
  • Hormonal agentsHormonal agents: Beta-sitosterol has demonstrated estrogenic/antiestrogenic activity in vitro and in animal studies (76; 108).
  • HypoglycemicsHypoglycemics: In animal research, beta-sitosterol had hypoglycemic effects (71). Two human clinical trials have shown either a lowering of HbA1C or a lack of effect of plant sterols in diabetic subjects (94; 95). Also, in an animal study, fractions obtained from the leaves of Morus insignis, a source of beta-sitosterol, demonstrated hypoglycemic effects (71).
  • ImmunomodulatorsImmunomodulators: Beta-sitosterol and beta-sitosterol glucoside have been used to decrease immunosuppressive responses as a result of strenuous exercise; effects have also been shown in vitro (26; 15; 26; 109; 110).
  • LuteinLutein: Clinical trials demonstrated that beta-sitosterol in doses of up to 1.5g daily reduced blood levels of lutein and lycopene (131).
  • LycopeneLycopene: Clinical trials demonstrated that beta-sitosterol in doses of up to 1.5g daily reduced blood levels of lutein and lycopene (131).
  • OlestraOlestra: Olestra, a nonabsorbable fat substitute comprising of long-chain fatty acid esters of sucrose, has been shown in clinical trials to decrease the amount of beta-sitosterol in stools (233).
  • Plant stanols and sterolsPlant stanols and sterols: Numerous studies investigating the consumption of plant sterols and stanols have measured serum sitosterol and increases were noted in the majority of studies (113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127; 128; 129; 130; 131; 132; 133; 134; 135; 91; 136). A case study of patient with short bowel syndrome supplementing with commercially available plant sterol products revealed a decrease in sitosterol when switching to a lower sterol containing product (122).
  • Vitamin AVitamin A: Clinical trials demonstrate a lack of effect of plant sterols, including beta-sitosterol, in doses of up to 9g daily on blood levels of fat-soluble vitamins (Vitamins D and A [retinol]) (44; 45; 32; 51).
  • Vitamin DVitamin D: Clinical trials demonstrate a lack of effect of plant sterols, including beta-sitosterol, in doses of up to 9g daily on blood levels of fat-soluble vitamins (Vitamins D and A [retinol]) (44; 45; 32; 51).

    • Beta-sitosterol/Food Interactions:

  • CarbohydratesCarbohydrates: A 12 week randomized controlled trial revealed that diets with oat, wheat bread, and potato as the main carbohydrate source compared to rye bread and pasta increased sitosterol in subjects with the metabolic syndrome (234).
  • Fruit drinkFruit drink: Consumption of beta-glucan within a fruit drink increased plasma sitosterol (235).
  • Dietary carotenoidsDietary carotenoids: Consumption of equal to or greater than five servings of fruits or vegetables per day (with at least one serving of beta-carotene rich food) was effective in maintaining plasma carotenoid concentrations during consumption of plant sterols (50).
  • NutsNuts: Increasing phytosterol ingestion from natural foods such as nuts increased serum sitosterol compared to a low-fat diet with less phytosterol intake (236).
  • Plant stanols and sterolsPlant stanols and sterols: Numerous studies investigating the consumption of plant sterols and stanols have measured serum sitosterol and increases were noted in the majority of studies (113; 114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126; 127; 128; 129; 130; 131; 132; 133; 134; 135; 91; 136; 125). A case study of patient with short bowel syndrome supplementing with commercially available plant sterol products revealed a decrease in sitosterol when switching to a lower sterol containing product (122).
  • Soluble fiberSoluble fiber: In a randomized clinical trial, 25g daily of soluble fiber intake in individuals on lipid-lowering therapy reduced phytosterolemia as measured by beta-sitosterol (237).
  • Trans fatty acidsTrans fatty acids: In randomized controlled trials, diets high in trans fatty acids have significantly decreased beta-sitosterol in healthy young men (106).

    • Beta-sitosterol/Lab Interactions:

  • ApolipoproteinsApolipoproteins: Combination studies of beta-sitosterol, campesterol, and b-sitostanol in phytosterol enriched low-fat milk have demonstrated improvements in Apo B-100 levels and Apo B-100/ApoA-I ratio (132).
  • Beta-acetyldigoxinBeta-acetyldigoxin: Administration of beta-sitosterol may change resorption of beta acetyldigoxin (238).
  • Beta-caroteneBeta-carotene: In human research, plant sterols, including beta-sitosterol, given in doses of up to 9g daily reduced beta-carotene blood levels (131; 232; 44; 45; 48; 190; 191; 178; 54). This is thought to be a result of reductions in LDL-C, which carries beta-carotene, by beta-sitosterol. (23). Randomized controlled trials indicate that the lowering of beta-carotene is counterbalanced by consuming an additional daily serving of a high-carotenoid vegetable or fruit when consuming spreads containing sterol or stanol esters (50).
  • Beta-sitosterolBeta-sitosterol: Increased intake of dietary beta-sitosterol from plant sterols has resulted in higher serum, red blood cell, and skin concentrations of beta-sitosterol (131; 4; 239; 240; 48; 32; 241; 35; 242; 243; 54; 132).
  • Biliary cholesterolBiliary cholesterol: Biliary cholesterol saturation may decrease with increased consumption of beta-sitosterol (77; 244).
  • Blood sugarBlood sugar: In animal research, beta-sitosterol had hypoglycemic effects (71). Two human clinical trials have shown either a lowering of HbA1C or a lack of effect of plant sterols in diabetic subjects (94; 95). Also, in an animal study, fractions obtained from the leaves of Morus insignis, a source of beta-sitosterol, demonstrated hypoglycemic effects (71).
  • CD3 and CD4 cellsCD3 and CD4 cells: In human research, beta-sitosterol and beta-sitosterol glucoside increased CD3 and CD4 cells (179).
  • Cholesterol acyltransferase (LCAT)Cholesterol acyltransferase (LCAT): In vivo data suggest that cholesterol acyltransferase (LCAT) activity increases with supplementation of beta-sitosterol (192).
  • Classical (CP) and alternative (AP) complement pathwaysClassical (CP) and alternative (AP) complement pathways: In vitro, beta-sitosterol inhibited the classical (CP) and alternative (AP) activation pathways of the human complement system resulting in altered blood levels of certain complement system compounds (245).
  • CortisolCortisol: In human research, beta-sitosterol and beta-sitosterol glucoside decreased levels of cortisol (179).
  • Cortisol/DHEA-s ratioCortisol/DHEA-s ratio: In human research, beta-sitosterol and beta-sitosterol glucoside caused a slight decrease in cortisol/DHEA-s ratio (179).
  • HbA1CHbA1C: Two human clinical trials have shown either a lowering of HbA1C or a lack of effect of plant sterols in diabetic subjects (94; 95).
  • HDL cholesterolHDL cholesterol: HDL-C has been shown in clinical trials to be increased by about 5% with supplementation of plant sterols, including beta-sitosterol, in the diet (45; 189). Data from other clinical trials contradict this and suggest that a lack of effect of beta-sitosterol on HDL-C (46; 47; 185; 190; 18; 191; 178; 192; 54; 89). In children with familial hypercholesterolemia, there was a 15% reduction in HDL-C with treatment with beta-sitosterol (90).
  • IgE plasma levelsIgE plasma levels: In vivo studies show that beta-sitosterol and beta-sitosterol glucoside decrease IgE plasma levels.
  • InterleukinsInterleukins: In human research, beta-sitosterol and beta-sitosterol glucoside decreased levels of pro-inflammatory monokines IL-2 and IL-6 in the blood (15; 179).
  • Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH): In vitro bioassays demonstrate that sterol beta-d-glucosides activate the release of LDH (103).
  • LathosterolLathosterol: Very high intake of plant stanols at 8.8g daily increased lathosterol by 30% (246).
  • LDL cholesterolLDL cholesterol: Serum LDL-C may be reduced by as much as 23% with administration of plant sterols, including beta-sitosterol (43; 183; 44; 45; 46; 47; 184; 48; 177; 129; 185; 186; 32; 158; 49; 190; 18; 50; 89; 191; 52; 90; 178; 54; 247; 188; 246). Combination products of sitosterol with sitostanol, camposterol, campostenol, and avenasterol have been shown to decrease LDL-C cholesterol (132; 189). Similarly, combination products of cholestyramine plus sitosterol have been show to lower LDL-C (248).
  • Lutein/zeaxanthineLutein/zeaxanthine: In human trials, plant sterol functional foods altered lutein and zeaxanthine concentrations (249).
  • ProgesteroneProgesterone: Data from some human trials suggest that plant sterols, including beta-sitosterol, reduce progesterone levels in healthy males and females, though the extent and significance of the reduction is unclear (43; 250).
  • Total cholesterolTotal cholesterol: Studies in both humans and animals suggest that increased amounts of dietary plant sterols, including beta-sitosterol, decrease TC in serum by as much as 10-18% (43; 77; 44; 45; 46; 47; 184; 177; 129; 185; 186; 158; 49; 10; 92; 18; 89; 52; 90; 187; 178; 192; 54; 251; 247; 252). Membrane cholesterol in cells may decrease by as much as 26% with beta-sitosterol supplementation (2). Combination products of sitosterol with sitostanol, camposterol, campostenol, and avenasterol have been shown to decrease TC (132; 189). Similarly, combination products of cholestyramine plus sitosterol have been show to lower TC(248).
  • Ubiquinol-10Ubiquinol-10: Randomized controlled trials demonstrate that absolute plasma ubiquinol-10 concentrations can be lowered by up to 15.4% vs. control with plant sterol, including beta-sitosterol, supplementation between 2.6-3.7g daily (23).
  • WBCs and neutrophilsWBCs and neutrophils: In human research, beta-sitosterol and beta-sitosterol glucoside increased WBC and neutrophil levels (179).