Alpha-tocopherol

Vitamin E/Drug Interactions:

  • AbortifacientsAbortifacients: According to secondary sources, historically, vitamin E has been used to prevent abortion or miscarriage and may interact with abortifacients.
  • Alzheimer's agentsAlzheimer's agents: Vitamin E has been proposed and evaluated for the prevention or slowing of dementia (including the Alzheimer's type), based on antioxidant properties and findings of low vitamin E levels in some individuals with Alzheimer's disease (114). There is some evidence that all-rac-alpha-tocopherol (synthetic vitamin E) is similar in efficacy to selegiline (Eldepryl?) and superior to placebo for slowing cognitive function decline in patients with moderately severe Alzheimer's disease, but no additive effect was observed when used in combination with selegiline (23). Retrospective data suggest that long-term combination therapy with donepezil (Aricept?) may help slow cognitive decline in patients with Alzheimer's disease (115). Overall, the evidence remains inconclusive. In patients with Alzheimer's disease or cognitive decline, vitamin E has been associated with a statistically significant increase in falls and syncope compared to placebo (23).
  • AmprenavirAmprenavir: Vitamin E has been shown to improve the solubility and permeability of amprenavir in vitro (116). The formulation of amprenavir contains vitamin E at a dose of 109 IU per capsule and 46 IU per mL of oral solution (117). In children, tocofersolan, a vitamin E formulation that is both lipophilic and hydrophilic, has been shown to increase the bioavailability of amprenavir (86).
  • AnestheticsAnesthetics: In human research, perioperative alpha-tocopherol exhibited a protective effect against renal dysfunction in patients treated with propofol and remifentanil for hypotensive anesthesia (118).
  • AntiandrogensAntiandrogens: According to secondary sources, vitamin E may interact with antiandrogens.
  • AntiarthriticsAntiarthritics: Vitamin E has shown mixed results in reducing symptoms or preventing cartilage loss in osteoarthritis (119; 120; 121; 122; 123; 124).
  • AntiasthmaticsAntiasthmatics: In schoolchildren, lower levels of vitamin E have been associated with poorly controlled asthma (125), and maternal intake of vitamin E during pregnancy has been associated with reduced rates of asthma and wheeze in children (101). However, there is evidence that vitamin E supplementation may not provide benefits in individuals with asthma (126; 127; 128).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, reported adverse effects attributed to vitamin E included minor bleeding and epistaxis (37; 38; 39; 40) and increased risk of hemorrhagic stroke (37; 40). The amount of bleeding risk associated with vitamin E remains an area of controversy, and caution is warranted in patients with a history of bleeding disorders or those taking blood-thinning drugs such as aspirin, anticoagulants such as warfarin (Coumadin?) or heparin, antiplatelet drugs such as clopidogrel (Plavix?), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin?, Advil?) or naproxen (Naprosyn?, Aleve?) (37; 86; 38). In humans receiving warfarin, vitamin E supplementation did not result in a change in the international normalized ratio (129). A signigicant decrease in the prothrombin index was reported in rats administered delta-tocopherol in large doses (89).
  • AnticonvulsantsAnticonvulsants: In human research, anticonvulsant drugs such as phenobarbital, phenytoin, or carbamazepine have been shown to decrease blood levels of vitamin E in handicapped patients (130; 131).
  • Antidiabetic agentsAntidiabetic agents: Vitamin E has been proposed for the prevention of types 1 or 2 diabetes; for the improvement of abnormal sugar control in diabetes (20; 21; 22); and for the prevention of platelet dysfunction and atherosclerosis in diabetes (58; 132; 133; 134). However, in a systematic review and meta-analysis, vitamin E was reported to increase insulin resistance (36). In another systematic review, it was reported that two participants treated with vitamin E developed new-onset diabetes, while all participants receiving placebo or pioglitazone did not develop diabetes (76).
  • AntiestrogensAntiestrogens: According to secondary sources, vitamin E may interact with antiestrogens.
  • AntilipemicsAntilipemics: According to secondary sources, vitamin E may have additive effects with cholesterol-lowering medications. Statin treatment has been proposed as a possible confounding factor in vitamin E trials, due to enhanced antioxidant status with statin use (135). In human research, cholestyramine monotherapy has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E, as well as vitamin E levels in low-density lipoprotein (LDL) (136; 137). However, this effect was not observed in a trial of cholestyramine combined with statins (138). In human research, colestipol has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E (139; 140). According to secondary sources, vitamin E in combination with beta-carotene, vitamin C, and selenium may decrease the effects of niacin and statins. In humans, vitamin E has been reported to increase triglycerides and low-density lipoprotein cholesterol and decrease high-density lipoprotein cholesterol (35; 36).
  • AntineoplasticsAntineoplastics: Concern has been raised that antioxidants may interfere with some chemotherapy agents (such as alkylating agents, anthracyclines, or platinums), which themselves may depend on oxidative damage to tumor cells for their anticancer effects (141). Studies on the effects of antioxidants on cancer therapies have yielded mixed results, with some reporting interference, others noting benefits, and most suggesting no significant interaction. However, until additional scientific evidence is available, high-dose antioxidants should be avoided during chemotherapy administration, unless otherwise decided in discussion with the treating oncologist. In human research, a transient decrease in alpha-tocopherol in erythrocyte membranes and an increase in alpha-tocopherol in lipoprotein fractions have been associated with letrozole therapy for four months (142). In human research, a significant decrease in serum alpha-tocopherol was observed in non-small cell lung cancer patients treated with gefitinib (143). Tocofersolan, a vitamin E formulation that is both lipophilic and hydrophilic, has been shown to increase the bioavailability of amprenavir, paclitaxel, vancomycin, and cyclosporine (86).
  • Antituberculosis agentsAntituberculosis agents: Antituberculosis drugs such as isoniazid have been shown to cause liver injury (144). In theory, use of isoniazid may reduce dietary vitamin E absorption and blood levels of vitamin E due to the liver's involvement in vitamin E kinetics.
  • Aromatase inhibitorsAromatase inhibitors: In human research, a transient decrease in alpha-tocopherol in erythrocyte membranes and an increase in alpha-tocopherol in lipoprotein fractions have been associated with letrozole therapy for four months (142).
  • Cardiovascular agentsCardiovascular agents: According to review data, vitamin E may increase risk of all-cause mortality and incidence of heart failure with doses ?400 IU daily for over one year (32; 33; 34). In humans, vitamin E has been reported to increase triglycerides and low-density lipoprotein cholesterol and decrease high-density lipoprotein cholesterol (35; 36). In human research, reported adverse effects attributed to vitamin E included minor bleeding and epistaxis (37; 38; 39; 40) and increased risk of hemorrhagic stroke (37; 40).
  • CholestyramineCholestyramine: In human research, cholestyramine has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E, as well as vitamin E levels in LDL (136; 137). However, this effect was not observed in a trial of cholestyramine combined with statins (138).
  • ColestipolColestipol: In human research, colestipol has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E (139; 140).
  • CyclosporineCyclosporine: In human research, vitamin E used with cyclosporine appears to increase the area under the blood concentration-time curve of cyclosporine. A water-soluble form of vitamin E, tocopheryl succinate polyethylene glycol, may improve the absorption of cyclosporine (145; 146; 147). Tocofersolan, a vitamin E formulation that is both lipophilic and hydrophilic, has been shown to increase the bioavailability of cyclosporine (86).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: Animal and in vitro research suggest an increase in hepatic production of cytochrome P450s and multidrug resistance (MDR)-1 from vitamin E. Specifically, induction of CYP3A4 has been suggested (148).
  • GefitinibGefitinib: In human research, a significant decrease in serum alpha-tocopherol was observed in non-small cell lung cancer patients treated with gefitinib (143).
  • GemfibrozilGemfibrozil: In human research, gemfibrozil has been shown to decrease serum levels of both alpha- and gamma-tocopherol, although the clinical significance of this is not clear (149). In human research, gemfibrozil has been studied in combination with vitamin E for the prevention of cardiovascular disease (150).
  • Hormonal agentsHormonal agents: According to secondary sources, vitamin E may interact with hormonal agents or therapies, including hormone replacement therapy (HRT).
  • Hydrophilic agentsHydrophilic agents: According to secondary sources, vitamin E may interact with hydrophilic agents.
  • IronIron: According to secondary sources, vitamin E has been proposed to improve the bioavailability of iron.
  • IsoniazidIsoniazid: Antituberculosis drugs such as isoniazid have been shown to cause liver injury (144). In theory, use of isoniazid may reduce dietary vitamin E absorption and blood levels of vitamin E due to the liver's involvement in vitamin E kinetics.
  • LetrozoleLetrozole: In human research, a transient decrease in alpha-tocopherol in erythrocyte membranes and an increase in alpha-tocopherol in lipoprotein fractions have been associated with letrozole therapy for four months (142).
  • Neurologic agentsNeurologic agents: Vitamin E has been proposed and evaluated for the prevention or slowing of dementia (including the Alzheimer's type), based on antioxidant properties and findings of low vitamin E levels in some individuals with Alzheimer's disease (114). There is some evidence that all-rac-alpha-tocopherol (synthetic vitamin E) is similar in efficacy to selegiline (Eldepryl?) and superior to placebo for slowing cognitive function decline in patients with moderately severe Alzheimer's disease, but no additive effect was observed when used in combination with selegiline (23). Retrospective data suggest that long-term combination therapy with donepezil (Aricept?) may help slow cognitive decline in patients with Alzheimer's disease (115). Overall, the evidence remains inconclusive. In human research, perioperative alpha-tocopherol exhibited a protective effect against renal dysfunction in patients treated with propofol and remifentanil for hypotensive anesthesia (118). In patients with Alzheimer's disease or cognitive decline, vitamin E has been associated with a statistically significant increase in falls and syncope compared to placebo (23).
  • OrlistatOrlistat: In human research, orlistat has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E (151; 152; 153; 154).
  • PaclitaxelPaclitaxel: Tocofersolan, a vitamin E formulation that is both lipophilic and hydrophilic has been shown to increase the bioavailability of paclitaxel (86).
  • PropofolPropofol: In human research, perioperative alpha-tocopherol exhibited a protective effect against renal dysfunction in patients treated with propofol and remifentanil for hypotensive anesthesia (118).
  • RemifentanilRemifentanil: In human research, perioperative alpha-tocopherol exhibited a protective effect against renal dysfunction in patients treated with propofol and remifentanil for hypotensive anesthesia (118).
  • SucralfateSucralfate: According to secondary sources, sucralfate may reduce dietary vitamin E absorption and blood levels of vitamin E.
  • VancomycinVancomycin: Tocofersolan, a vitamin E formulation that is both lipophilic and hydrophilic, has been shown to increase the bioavailability of vancomycin (86).

    • Vitamin E/Herb/Supplement Interactions:

  • AbortifacientsAbortifacients: According to secondary sources, historically, vitamin E has been used to prevent abortion or miscarriage and may interact with abortifacients.
  • AloeAloe: Aloe is reported to enhance and slow the rate of vitamin E absorption, allowing sustained release of vitamin E into the bloodstream (155).
  • Alzheimer's agentsAlzheimer's agents: Vitamin E has been proposed and evaluated for the prevention or slowing of dementia (including the Alzheimer's type), based on antioxidant properties and findings of low vitamin E levels in some individuals with Alzheimer's disease (114). There is some evidence that all-rac-alpha-tocopherol (synthetic vitamin E) is similar in efficacy to selegiline (Eldepryl?) and superior to placebo for slowing cognitive function decline in patients with moderately severe Alzheimer's disease, but no additive effect was observed when used in combination with selegiline (23). Retrospective data suggest that long-term combination therapy with donepezil (Aricept?) may help slow cognitive decline in patients with Alzheimer's disease (115). Overall, the evidence remains inconclusive. In patients with Alzheimer's disease or cognitive decline, vitamin E has been associated with a statistically significant increase in falls and syncope compared to placebo (23).
  • AnestheticsAnesthetics: In human research, perioperative alpha-tocopherol exhibited a protective effect against renal dysfunction in patients treated with propofol and remifentanil for hypotensive anesthesia (118).
  • AntiandrogensAntiandrogens: According to secondary sources, vitamin E may interact with antiandrogens.
  • AntiarthriticsAntiarthritics: Vitamin E has shown mixed results in reducing symptoms or preventing cartilage loss in osteoarthritis (119; 120; 121; 122; 123; 124).
  • AntiasthmaticsAntiasthmatics: In schoolchildren, lower levels of vitamin E have been associated with poorly controlled asthma (125), and maternal intake of vitamin E during pregnancy has been associated with reduced rates of asthma and wheeze in children (101). However, there is evidence that vitamin E supplementation may not provide benefits in individuals with asthma (126; 127; 128).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, reported adverse effects attributed to vitamin E included minor bleeding and epistaxis (37; 38; 39; 40) and increased risk of hemorrhagic stroke (37; 40). The amount of bleeding risk associated with vitamin E remains an area of controversy, and caution is warranted in patients with a history of bleeding disorders or those taking blood-thinning drugs such as aspirin, anticoagulants such as warfarin (Coumadin?) or heparin, antiplatelet drugs such as clopidogrel (Plavix?), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin?, Advil?) or naproxen (Naprosyn?, Aleve?) (37; 86; 38). In humans receiving warfarin, vitamin E supplementation did not result in a change in the international normalized ratio (129). A signigicant decrease in the prothrombin index was reported in rats administered delta-tocopherol in large doses (89).
  • AnticonvulsantsAnticonvulsants: In human research, anticonvulsant drugs such as phenobarbital, phenytoin, or carbamazepine have been shown to decrease blood levels of vitamin E in handicapped patients (130; 131).
  • AntiestrogensAntiestrogens: According to secondary sources, vitamin E may interact with antiestrogens.
  • AntilipemicsAntilipemics: According to secondary sources, vitamin E may have additive effects with cholesterol-lowering medications. According to secondary sources, vitamin E in combination with beta-carotene, vitamin C, and selenium may decrease the effects of niacin and statins. In humans, vitamin E has been reported to increase triglycerides and low-density lipoprotein cholesterol and decrease high-density lipoprotein cholesterol (35; 36).
  • AntineoplasticsAntineoplastics: Concern has been raised that antioxidants may interfere with some chemotherapy agents (such as alkylating agents, anthracyclines, or platinums), which themselves may depend on oxidative damage to tumor cells for their anticancer effects (141). Studies on the effects of antioxidants on cancer therapies have yielded mixed results, with some reporting interference, others noting benefits, and most suggesting no significant interaction. However, until additional scientific evidence is available, high-dose antioxidants should be avoided during chemotherapy administration, unless otherwise decided in discussion with the treating oncologist.
  • AntioxidantsAntioxidants: In one trial studying vitamin E in combination with other antioxidants, five subjects dropped out due to presumed toxicity (90). In healthy men, exposure to hyperbaric oxygen after four weeks of vitamin E supplementation did not prevent oxidative stress (156). However, a nonlinear relationship has been found between supplementation of vitamin E and the accumulation of alpha-tocopherol in pork (157). This relationship is thought to be related to lipid oxidation as measured in thiobarbituric acid reacting substance (TBARS) values. Higher doses of vitamin E led to lower TBARS values, indicating a decrease in lipid oxidation.
  • Cardiovascular agentsCardiovascular agents: According to review data, vitamin E may increase risk of all-cause mortality and incidence of heart failure with doses ?400 IU daily for over one year (32; 33; 34). In humans, vitamin E has been reported to increase triglycerides and low-density lipoprotein cholesterol and decrease high-density lipoprotein cholesterol (35; 36). In human research, reported adverse effects attributed to vitamin E included minor bleeding and epistaxis (37; 38; 39; 40) and increased risk of hemorrhagic stroke (37; 40).
  • CigarettesCigarettes: In human research, cigarette smokers showed significant lowering of alpha-tocopherol levels in plasma. This lowering was also associated with lower levels of ascorbic acid in plasma (158).
  • CopperCopper: In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, vitamin E supplementation has been shown to normalize elevated copper levels and decreased zinc levels associated with the disease (159).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: Animal and in vitro research suggest an increase in hepatic production of cytochrome P450s and MDR1 from vitamin E. Specifically, induction of CYP3A4 has been suggested (148).
  • Fish oilFish oil: In human research, a fish oil-enriched parenteral nutrition regimen had a positive treatment effect on serum levels of alpha-tocopherol in patients undergoing major abdominal surgery (160).
  • Hormonal agentsHormonal agents: According to secondary sources, vitamin E may interact with hormonal agents or therapies, including hormone replacement therapy (HRT).
  • Hydrophilic agentsHydrophilic agents: According to secondary sources, vitamin E may interact with hydrophilic agents.
  • HypoglycemicsHypoglycemics: Vitamin E has been proposed for the prevention of types 1 or 2 diabetes; for the improvement of abnormal sugar control in diabetes (20; 21; 22); and for prevention of platelet dysfunction and atherosclerosis in diabetes (58; 132; 133; 134). However, in a systematic review and meta-analysis, vitamin E was reported to increase insulin resistance (36). In another systematic review, it was reported that two participants treated with vitamin E developed new-onset diabetes, while all participants receiving placebo or pioglitazone did not develop diabetes (76).
  • IronIron: According to secondary sources, vitamin E has been proposed to improve the bioavailability of iron.
  • Mineral oilMineral oil: According to secondary sources, mineral oil may reduce dietary vitamin E absorption.
  • Neurologic agentsNeurologic agents: Vitamin E has been proposed and evaluated for the prevention or slowing of dementia (including the Alzheimer's type), based on antioxidant properties and findings of low vitamin E levels in some individuals with Alzheimer's disease (114). There is some evidence that all-rac-alpha-tocopherol (synthetic vitamin E) is similar in efficacy to selegiline (Eldepryl?) and superior to placebo for slowing cognitive function decline in patients with moderately severe Alzheimer's disease, but no additive effect was observed when used in combination with selegiline (23). Retrospective data suggest that long-term combination therapy with donepezil (Aricept?) may help slow cognitive decline in patients with Alzheimer's disease (115). Overall, the evidence remains inconclusive. In human research, perioperative alpha-tocopherol exhibited a protective effect against renal dysfunction in patients treated with propofol and remifentanil for hypotensive anesthesia (118). In patients with Alzheimer's disease or cognitive decline, vitamin E has been associated with a statistically significant increase in falls and syncope compared to placebo (23).
  • Omega-6 fatty acidsOmega-6 fatty acids : According to secondary sources, increased intake of omega-6 fatty acids may increase vitamin E requirements, particularly at high doses.
  • Stanyl estersStanyl esters: Stanyl esters have been proposed by scientists to reduce the absorption of fat-soluble vitamins. In human research, stanyl esters dissolved in margarine did not significantly affect the absorption of alpha-tocopherol (161).
  • Vitamin AVitamin A: Vitamin E is involved in the absorption, storage, and utilization of vitamin A in the body and contributes to avoiding toxicity with vitamin A intake. Large doses of vitamin E may deplete vitamin A stores (86).
  • Vitamin CVitamin C: In male smokers who have high dietary intakes of vitamin C, vitamin E supplementation was linked to an increased risk of tuberculosis (30). In a randomized controlled trial, a lack of beneficial effects for several cardiovascular risk factors was observed with vitamins C and E (162).
  • Vitamin KVitamin K: In adults not taking anticoagulants, high-dose vitamin E caused an increase in PIVKA-II (protein induced by vitamin K absence), indicating poor vitamin K status (163).
  • ZincZinc: According to secondary sources, blood levels of vitamin E may be decreased with zinc deficiency. In patients with G6PD deficiency, vitamin E supplementation has been shown to normalize elevated copper levels and decreased zinc levels associated with the disease (159).

    • Vitamin E/Food Interactions:

  • High fat mealHigh fat meal: In human research, the absorption of vitamin E has been shown to be influenced by the amount of fat in a meal (164). A higher-fat meal resulted in increased concentrations of alpha-tocopherol in chylomicrons and plasma.
  • MilkMilk: In human research, milk has been shown to augment the transport of vitamin E by lipoproteins (165). The effect occurs at vitamin E doses of 100-200mg daily but not at doses of 30mg daily.
  • OlestraOlestra: Although human research is mixed, olestra may reduce dietary vitamin E absorption and blood levels of vitamin E (166; 167; 168).
  • Stanyl ester-enriched margarineStanyl ester-enriched margarine: Stanyl esters have been proposed to reduce the absorption of fat-soluble vitamins. In human research, stanyl esters dissolved in margarine did not significantly affect the absorption of alpha-tocopherol (161).

    • Vitamin E/Lab Interactions:

  • Coagulation panelCoagulation panel: In human research, reported adverse effects attributed to vitamin E included minor bleeding and epistaxis (37; 38; 39; 40) and increased risk of hemorrhagic stroke (37; 40). The amount of bleeding risk associated with vitamin E remains an area of controversy, and caution is warranted in patients with a history of bleeding disorders or those taking blood-thinning drugs such as aspirin, anticoagulants such as warfarin (Coumadin?) or heparin, antiplatelet drugs such as clopidogrel (Plavix?), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin?, Advil?) or naproxen (Naprosyn?, Aleve?) (37; 86; 38). In humans receiving warfarin, vitamin E supplementation did not result in a change in the international normalized ratio (129). A signigicant decrease in the prothrombin index was reported in rats administered delta-tocopherol in large doses (89).
  • CopperCopper: In patients with G6PD deficiency, vitamin E supplementation has been shown to normalize elevated copper levels (159).
  • Gamma-tocopherolGamma-tocopherol: According to a review, alpha-tocopherol supplements have been shown to lower levels of gamma-tocopherol in the blood (9).
  • GlucoseGlucose: Vitamin E has been proposed for the prevention of types 1 or 2 diabetes and for the improvement of abnormal sugar control in diabetes (20; 21; 22). However, in a systematic review and meta-analysis, vitamin E was reported to increase insulin resistance (36). In another systematic review, it was reported that two participants treated with vitamin E developed new-onset diabetes, while all participants receiving placebo or pioglitazone did not develop diabetes (76).
  • HemoglobinHemoglobin: In human research, vitamin E was associated with a 0.4g/dL increase in hemoglobin in preterm infants (88).
  • Lipid profileLipid profile: According to secondary sources, vitamin E may have additive effects with cholesterol-lowering medications. Statin treatment has been proposed as a possible confounding factor in vitamin E trials, due to enhanced antioxidant status with statin use (135). In human research, cholestyramine monotherapy has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E, as well as vitamin E levels in low-density lipoprotein (LDL) (136; 137). However, this effect was not observed in a trial of cholestyramine combined with statins (138). In human research, colestipol has been shown to reduce dietary vitamin E absorption and blood levels of vitamin E (139; 140). According to secondary sources, vitamin E in combination with beta-carotene, vitamin C, and selenium may decrease the effects of niacin and statins. In humans, vitamin E has been reported to increase triglycerides and low-density lipoprotein cholesterol and decrease high-density lipoprotein cholesterol (35; 36).
  • PIVKA-IIPIVKA-II: In adults not taking anticoagulants, high-dose vitamin E caused an increase in PIVKA-II (protein induced by vitamin K absence), indicating poor vitamin K status (163).
  • Soluble vascular adhesion molecule-1Soluble vascular adhesion molecule-1: In human research, supplementation of alpha-tocopherol resulted in reduced levels of soluble vascular adhesion molecule-1 in plasma (169).
  • Vitamin AVitamin A: Large doses of vitamin E may deplete vitamin A stores (86).
  • ZincZinc: In patients with G6PD deficiency, vitamin E supplementation has been shown to normalize decreased zinc levels (159).