Tocotrienols
Tocotrienols/Drug Interactions:
Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Tocotrienols are a type of vitamin E. High-dose vitamin E (greater than 400 IU daily) appeared to increase PT and INR in patients with vitamin K deficiency, and inhibit platelet aggregation (58; 59; 60; 61; 62). Antidiabetic agentsAntidiabetic agents: In human research, PalmVitee? (high in tocotrienols) reduced plasma glucose (56). Antilipemic agentsAntilipemic agents: Based on in vitro and clinical evidence, tocotrienols may lower cholesterol levels (42; 46; 48; 72; 73; 5; 74; 75; 68; 76). Antineoplastic agentsAntineoplastic agents: Based on in vitro evidence, a combination of lovastatin and d-gamma-tocotrienol has been shown to block cell growth of melanoma cells, prostate carcinoma cells, and lung carcinoma cells (77). In another study, a mixture of alpha-, gamma- and delta-tocotrienols inhibited the proliferation of estrogen receptor-negative human breast cancer cells, effects that may be synergistic with tamoxifen (78). Based on animal evidence, a combination of lovastatin and d-delta-tocotrienol resulted in lower tumor weights in mice (77). Cytochrome P450: substrates, inhibitors, inducersCytochrome P450: substrates, inhibitors, inducers: Based on secondary sources, tocopherols and tocotrienols are metabolized by side chain degradation initiated by cytochrome P450 (CYP)-catalyzed omega-hydroxylation followed by beta-oxidation (79). Examples of CYP4F2-metabolized drugs and herbs include vitamin K, warfarin, and statins. Based on gene expression analysis, delta-tocotrienol increased CYP1A1 gene, a phase I enzyme (80). Gastrointestinal agentsGastrointestinal agents: Halliwell et al. have reviewed the potential beneficial effects of tocotrienols on the gastrointestinal tract (81). Immunomodulating agentsImmunomodulating agents: The ability of tocotrienols to interfere with mast cell proliferation, survival, degranulation, and migration has been reviewed (82). Neuroprotective agentsNeuroprotective agents: Research has suggested that alpha-tocotrienol is more potent than alpha-tocopherol in vitro in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins (19). At nanomolar concentrations, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant-independent mechanism. StatinsStatins: Based on in vitro evidence, a combination of lovastatin and d-gamma-tocotrienol has been shown to block cell growth of melanoma cells, prostate carcinoma cells, and lung carcinoma cells (77). Weight loss agentsWeight loss agents: Based on secondary sources, alpha- and gamma-tocotrienol may help prevent immature fat cells from turning into mature fat cells. This would prevent the storage of more fat and may help prevent obesity.Tocotrienols/Herb/Supplement Interactions:
Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Tocotrienols are a type of vitamin E. High-dose vitamin E (greater than 400 IU daily) appeared to increase PT and INR in patients with vitamin K deficiency, and inhibit platelet aggregation (58; 59; 60; 61; 62). AntilipemicsAntilipemics: Based on in vitro and clinical evidence, tocotrienols may lower cholesterol levels (42; 46; 48; 72; 73; 5; 74; 75; 68; 76). AntineoplasticsAntineoplastics: Based on in vitro evidence, a combination of lovastatin and d-gamma-tocotrienol has been shown to block cell growth of melanoma cells, prostate carcinoma cells, and lung carcinoma cells (77). In another study, a mixture of alpha-, gamma- and delta-tocotrienols inhibited the proliferation of estrogen receptor-negative human breast cancer cells, effects that may be synergistic with tamoxifen (78). Based on animal evidence, a combination of lovastatin and d-delta-tocotrienol resulted in lower tumor weights in mice (77). AntioxidantsAntioxidants: Based on in vitro evidence, tocotrienol may exert antioxidant effects, as evidenced by inhibition of human glutathione S-transferase P1-1 (GST P1-1) (36) and reactions with peroxyl radicals in circulating human lipoproteins (37). Citrus flavonoidsCitrus flavonoids: Based on animal evidence, citrus flavonoids, when combined with tocotrienols, may inhibit proliferation of mammary tumors (83). Cytochrome P450: substrates, inhibitors, inducersCytochrome P450: substrates, inhibitors, inducers: Based on secondary sources, tocopherols and tocotrienols were metabolized by side chain degradation initiated by cytochrome P450 (CYP)-catalyzed omega-hydroxylation followed by beta-oxidation (79). Examples of CYP4F2-metabolized drugs and herbs include vitamin K, warfarin, and statins. Based on gene expression analysis, delta-tocotrienol increased CYP1A1 gene, a phase I enzyme (80). Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Halliwell et al. reviewed the potential beneficial effects of tocotrienols on the gastrointestinal tract (81). HypoglycemicsHypoglycemics: In human research, PalmVitee? (high in tocotrienols) reduced plasma glucose (56). Immunomodulating herbs and supplementsImmunomodulating herbs and supplements: The ability of tocotrienols to interfere with mast cell proliferation, survival, degranulation, and migration has been reviewed (82). Neuroprotective herbs and supplementsNeuroprotective herbs and supplements: Research has suggested that alpha-tocotrienol is more potent than alpha-tocopherol in vitro in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins (19). At nanomolar concentrations, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant-independent mechanism. Weight loss agentsWeight loss agents: Based on secondary sources, alpha- and gamma-tocotrienol may help prevent immature fat cells from turning into mature fat cells. This would prevent the storage of more fat and may help prevent obesity.Tocotrienols/Food Interactions:
CitrusCitrus: Based on animal evidence, citrus flavonoids, when combined with tocotrienols, may inhibit proliferation of mammary tumors (83). Tocotrienols/Lab Interactions:
CholesterolCholesterol: The cholesterol-lowering effects of tocotrienols have been reviewed (42; 46; 48; 72; 73; 5). Clinical support is lacking. C-reactive proteinC-reactive protein: Based on various reviews, decreases in C-reactive protein may be partially responsible for the cardioprotective effects of tocotrienols (22; 23). CytokinesCytokines: Based on various reviews, decreases in proinflammatory cytokines may be partially responsible for the cardioprotective effects of tocotrienols (22; 23). GlucoseGlucose: In human research, PalmVitee? (high in tocotrienols) reduced plasma glucose (56). IkappaB kinase-associated protein gene (IKBKAP) mRNA levelsIkappaB kinase-associated protein gene (IKBKAP) mRNA levels: IKBKAP levels were not shown to be altered in patients with familial dysautonomia who received tocotrienols (84). PT/INRPT/INR: Tocotrienols are a type of vitamin E. High-dose vitamin E (greater than 400 IU daily) appeared to increase PT and INR in patients with vitamin K deficiency, and inhibit platelet aggregation (58; 59; 60; 61; 62). Tocotrienols and tocopherolsTocotrienols and tocopherols: Based on clinical evidence, tocotrienol-rich vitamin E supplementation resulted in significantly increased alpha-, delta-, and gamma-tocotrienol concentrations (75).