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Abstract
Vitamin E in nature is comprised of a family of tocopherols and tocotrienols. The most studied of these is α-tocopherol (α-TOH), because this form is retained within the body, and vitamin E deficiency is corrected with this supplement. α-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes, and it potentially acts as a defense against oxidative stress. Many studies have investigated the metabolism, transport, and efficacy α-TOH in the prevention of sequelae associated with cardiovascular disease (CVD). Supplementation with vitamin E is considered to provide health benefits against CVD through its antioxidant activity, the prevention of lipoprotein oxidation, and the inhibition of platelet aggregation. However, the results from large prospective, randomized, placebo-controlled clinical trials with α-TOH have been largely negative. A recent meta-analysis suggests that α-TOH supplements may actually increase all-cause mortality; however, the mechanism for this increased risk is unknown. In vitro studies performed in human cell cultures and animal models suggest that vitamin E might increase the hepatic production of cytochrome P450s and MDR1. Induction of CYP3A4 or MDR1 by vitamin E could potentially lower the efficacy of any drug metabolized by CYP3A4 or MDR1. Other possibilities include an adverse effect of α-TOH on blood pressure in high-risk populations. Because of the wide popularity and use of vitamin E supplements, further research into potential adverse effects is clearly warranted.
| Abbreviations | ||
| 4-HNE | = | 4-hydroxynonenal; |
| α-CEHC | = | 2,5,7,8-tetramethyl-2 (2′-carboxyethy)-6-hydroxychroman, metabolite of α-TOH; |
| α-TOH | = | alpha tocopherol; |
| α-TQH2 | = | α-TOH hydroquinone; |
| α-TTP | = | α-TOH transfer protein; |
| γ-CEHC | = | 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (metabolite of γ-TOH); |
| γ-TOH | = | gamma tocopherol; |
| γYP | = | cylochrome P450, |
| AAPH | = | 2,2′-azobis(2)-amidinopropane (a free radical generator); |
| ABCA1 | = | ATP-binding cassette transporter A1; |
| apoE−/− mouse | = | apolipoprotein E double knock out mouse; |
| ASAP | = | Antioxidant Supplementation in Atherosclerosis Prevention; |
| ATBC, α-TOH | = | beta-Carotene Prevention Study; |
| AVED | = | ataxia with vitamin E deficiency; |
| CHAOS | = | Cambridge Heart Antioxidant Study; |
| CHD | = | coronary heart disease; |
| COX-2 | = | cyclooxygenase-2; |
| CoQ10 | = | ubiquinone-10; |
| CoQ10 H2 | = | ubiquinol-10, reduced form of coenzyme Q; |
| CVD | = | cardiovascular disease; |
| CYP3a11 | = | murine equivalent to human CYP3A4; |
| CYP3A4 | = | cytochrome P450 3A4; |
| d6 -RRR-α-TOH | = | deuterium labelled natural alpha tocopherol; |
| ECD | = | electrochemical detection; |
| FHBL | = | familial hypobetalipoproteinemia; |
| FIVE | = | familial isolated vitamin E deficiency; |
| GC/MS | = | gas chromatography mass spectrometry; |
| GISSI | = | Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico; |
| HDL | = | high-density lipoprotein; |
| HepG2 | = | human hepatoma cell line; |
| HPLC | = | high-performance liquid chromatography; |
| HOPE | = | Heart Outcomes Prevention Evaluation Study; |
| HTGL | = | hepatic triglyceride lipase; |
| LDL | = | low-density lipoprotein; |
| LOOH | = | lipid hydroperoxides; |
| LPL | = | lipoprotein lipase; |
| MDMs | = | monocyte-derived macrophages; |
| MDR1 | = | multidrug resistant protein 1; |
| MTP | = | microsomal triglyceride transfer protein; |
| NHBLI | = | National Heart, Blood and Lung Institute; |
| NO2 | = | nitrogen dioxide; |
| PGE2 | = | prostaglandin E2; |
| PXR | = | pregnane X receptor; RNOS, reactive nitrogen-oxide species; |
| RRR-α-TOH, d-α-TOH | = | natural alpha tocopherol; |
| RXR | = | retinoic acid receptor; |
| SPACE | = | Secondary Prevention with Antioxidants of Cardiovascular Disease in Endstage Renal Disease; |
| SR-BI | = | scavenger receptor class B type I; |
| SRR-∝-TOH | = | dl-α-TOH, synthetic alpha tocopherol; |
| TAP | = | tocopherol-associated protein; |
| TBP | = | tocopherol-binding protein; |
| TMP | = | tocopherol-mediated peroxidation; |
| TO· | = | tocopherol radical; |
| TOH | = | tocopherol; |
| VLDL | = | very low density lipoprotein; |
| WHHL | = | Watanabe heritable hyperlipidemic |
| Abbreviations | ||
| 4-HNE | = | 4-hydroxynonenal; |
| α-CEHC | = | 2,5,7,8-tetramethyl-2 (2′-carboxyethy)-6-hydroxychroman, metabolite of α-TOH; |
| α-TOH | = | alpha tocopherol; |
| α-TQH2 | = | α-TOH hydroquinone; |
| α-TTP | = | α-TOH transfer protein; |
| γ-CEHC | = | 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (metabolite of γ-TOH); |
| γ-TOH | = | gamma tocopherol; |
| γYP | = | cylochrome P450, |
| AAPH | = | 2,2′-azobis(2)-amidinopropane (a free radical generator); |
| ABCA1 | = | ATP-binding cassette transporter A1; |
| apoE−/− mouse | = | apolipoprotein E double knock out mouse; |
| ASAP | = | Antioxidant Supplementation in Atherosclerosis Prevention; |
| ATBC, α-TOH | = | beta-Carotene Prevention Study; |
| AVED | = | ataxia with vitamin E deficiency; |
| CHAOS | = | Cambridge Heart Antioxidant Study; |
| CHD | = | coronary heart disease; |
| COX-2 | = | cyclooxygenase-2; |
| CoQ10 | = | ubiquinone-10; |
| CoQ10 H2 | = | ubiquinol-10, reduced form of coenzyme Q; |
| CVD | = | cardiovascular disease; |
| CYP3a11 | = | murine equivalent to human CYP3A4; |
| CYP3A4 | = | cytochrome P450 3A4; |
| d6 -RRR-α-TOH | = | deuterium labelled natural alpha tocopherol; |
| ECD | = | electrochemical detection; |
| FHBL | = | familial hypobetalipoproteinemia; |
| FIVE | = | familial isolated vitamin E deficiency; |
| GC/MS | = | gas chromatography mass spectrometry; |
| GISSI | = | Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico; |
| HDL | = | high-density lipoprotein; |
| HepG2 | = | human hepatoma cell line; |
| HPLC | = | high-performance liquid chromatography; |
| HOPE | = | Heart Outcomes Prevention Evaluation Study; |
| HTGL | = | hepatic triglyceride lipase; |
| LDL | = | low-density lipoprotein; |
| LOOH | = | lipid hydroperoxides; |
| LPL | = | lipoprotein lipase; |
| MDMs | = | monocyte-derived macrophages; |
| MDR1 | = | multidrug resistant protein 1; |
| MTP | = | microsomal triglyceride transfer protein; |
| NHBLI | = | National Heart, Blood and Lung Institute; |
| NO2 | = | nitrogen dioxide; |
| PGE2 | = | prostaglandin E2; |
| PXR | = | pregnane X receptor; RNOS, reactive nitrogen-oxide species; |
| RRR-α-TOH, d-α-TOH | = | natural alpha tocopherol; |
| RXR | = | retinoic acid receptor; |
| SPACE | = | Secondary Prevention with Antioxidants of Cardiovascular Disease in Endstage Renal Disease; |
| SR-BI | = | scavenger receptor class B type I; |
| SRR-∝-TOH | = | dl-α-TOH, synthetic alpha tocopherol; |
| TAP | = | tocopherol-associated protein; |
| TBP | = | tocopherol-binding protein; |
| TMP | = | tocopherol-mediated peroxidation; |
| TO· | = | tocopherol radical; |
| TOH | = | tocopherol; |
| VLDL | = | very low density lipoprotein; |
| WHHL | = | Watanabe heritable hyperlipidemic |
Referee Dr. Jean-Marc Zingg, Vascular Biology Laboratory, JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA