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van Kempen TATG, Benítez Puñal S, Huijser J, De Smet S. Tocopherol more bioavailable than tocopheryl-acetate as a source of vitamin E for broilers. PLoS One 2022; 17:e0268894. [PMID: 35613141 PMCID: PMC9132266 DOI: 10.1371/journal.pone.0268894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/10/2022] [Indexed: 01/10/2023] Open
Abstract
Vitamin E is typically supplied in the form of tocopheryl-acetate (T-Ac) since tocopherol (T) has stability issues. Tocopheryl-acetate, however, must be hydrolyzed in the intestines before it can be absorbed, a step that is purportedly rate-limiting for its bioavailability. The objective of this study was to compare the efficiency of absorption of T-Ac and T in broilers. In addition, two test procedures were evaluated in which animals received the test substances for either 2 or 4 days only. Animals were adapted to diets without supplemental vitamin E (feedstuffs contributed 14±1 ppm natural vitamin E (RRR-tocopherol)) till the age of 25 d (individual housing) or 28 d (group housing). Subsequently, they were fed T-Ac at 80, 53, 36, 24, or 16 ppm or T at 80, 40, 20, 10, or 5 ppm for a period of 4 d (4-di) or 2 d (2-dg), after which serum and liver were collected for analysis of vitamin E. Measured feed vitamin E levels were used for the data analysis; the recovery of T-Ac was 85%, and that of T was 39%. Both test procedures (2 or 4 days) yielded good quality data. Based on linear regression analysis, the relative efficiency with which T-Ac raised tissue levels as compared to T was 0.24 (2-dg) to 0.37 (4-di), with liver and serum yielding similar results. Analysis using more complex dose response models imply that the hydrolysis of T-Ac was strongly dose-dependent and that it could be saturated at doses above approximately 50 ppm in animals only briefly fed T-Ac; for T there was no evidence of saturation. These data imply that T, provided that stable forms can be developed, has the potential to be much more efficient at providing vitamin E to the animal, and on top, can yield much higher tissue levels, than T-Ac.
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Affiliation(s)
- Theo A. T. G. van Kempen
- Trouw Nutrition, Boxmeer, Netherlands
- Department of Animal Science, North Carolina State University, Raleigh, NC, United States of America
- * E-mail:
| | - Samuel Benítez Puñal
- Department of Animal Science, North Carolina State University, Raleigh, NC, United States of America
| | - Jet Huijser
- Department of Animal Science, North Carolina State University, Raleigh, NC, United States of America
| | - Stefaan De Smet
- Laboratory of Animal Nutrition and Animal Product Quality, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
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Lashkari S, Jensen S, Vestergaard M. Response to different sources of vitamin E orally injected and to various doses of vitamin E in calf starter on the plasma vitamin E level in calves around weaning. Animal 2022; 16:100492. [DOI: 10.1016/j.animal.2022.100492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 02/14/2022] [Accepted: 02/21/2022] [Indexed: 10/18/2022] Open
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Absorption of α-tocopheryl acetate is limited in mink kits (Mustela vison) during weaning. Sci Rep 2021; 11:2686. [PMID: 33514760 PMCID: PMC7846754 DOI: 10.1038/s41598-020-80902-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 12/30/2020] [Indexed: 11/10/2022] Open
Abstract
Bioavailability of α-tocopherol varies with source, dose and duration of supplementation. The effect of source and dose of α-tocopherol on response of α-tocopherol stereoisomers in plasma and tissues of mink kits during the weaning period was studied. Twelve mink kits were euthanised in CO2 at the beginning of the experiment, and 156 mink kits (12 replicates per treatment group) were randomly assigned to thirteen treatment groups: no added α-tocopherol in the feed (0 dose) or four different doses (50, 75, 100 and 150 mg/kg of diet) of RRR-α-tocopherol (ALC), RRR-α-tocopheryl acetate (ACT) or all-rac-α-tocopheryl acetate (SYN). Six mink kits per treatment group were euthanised 3 weeks after initiation of the experiment, and the remaining six were euthanised 6 weeks after initiation of the experiment. The RRR-α-tocopherol content in plasma, liver, heart and lungs was affected by interaction between source and dose (P < 0.01 for all). The highest RRR-α-tocopherol content in plasma (13.6 µg/ml; LS-means for source across dose and week), liver (13.6 µg/mg), heart (7.6 µg/mg) and lungs (9.8 µg/mg) was observed in mink kits fed ALC. The RRR-α-tocopherol content in plasma and tissues depended on source and dose interaction and increased linearly with supplementation. In conclusion, the interaction between source and dose reveals a limitation in hydrolysis of ester bond in α-tocopheryl acetate in mink kits around weaning as the likely causative explanation for the higher response of ALC at the highest doses. Thus, considerable attention has to be paid to the source of α-tocopherol during weaning of mink kits fed a high dose of α-tocopherol.
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Cuerq C, Bordat C, Halimi C, Blond E, Nowicki M, Peretti N, Reboul E. Comparison of α-Tocopherol, α-Tocopherol Acetate, and α-Tocopheryl Polyethylene Glycol Succinate 1000 Absorption by Caco-2 TC7 Intestinal Cells. Nutrients 2020; 13:nu13010129. [PMID: 33396478 PMCID: PMC7823802 DOI: 10.3390/nu13010129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/21/2020] [Accepted: 12/24/2020] [Indexed: 12/12/2022] Open
Abstract
(1) Background: vitamin E is often supplemented in the form of tocopherol acetate, but it has poor bioavailability and can fail to correct blood tocopherol concentrations in some patients with severe cholestasis. In this context, α-tocopheryl polyethylene glycol succinate 1000 (TPGS) has been of value, but very little is known about the mechanisms of its absorption. The aim of our work was to evaluate the mechanisms of absorption/secretion of TPGS compared to tocopherol acetate (TAC) and α-tocopherol by human enterocyte-like Caco-2 TC7 cells. (2) Methods: two weeks post-confluence Caco-2 cells were incubated with tocopherol- or TAC- or TPGS-rich mixed micelles up to 24 h and, following lipid extraction, TAC and tocopherol amounts were measured by high performance liquid chromatography (HPLC) in apical, cellular, and basolateral compartments. (3) Results: at equivalent concentrations of tocopherol in the apical side, the amounts of tocopherol secreted at the basolateral pole of Caco-2 cells are (i) significantly greater when the tocopherol is in the free form in the micelles; (ii) intermediate when it is in the TAC form in the micelles (p < 0.001); and (iii) significantly lower with the TPGS form (p < 0.0001). Interestingly, our results show, for the first time, that Caco-2 cells secrete one or more esterified forms of the vitamin contained in TPGS at the basolateral side.
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Affiliation(s)
- Charlotte Cuerq
- Biochemistry Department, Hospices Civils de Lyon, 69495 Pierre-Benite , France; (C.C.); (E.B.)
- CarMeN Laboratory, INSERM U1060, INRA UMR 1397, INSA-Lyon, Université Lyon 1, 60310 Pierre-Benite, France;
| | - Claire Bordat
- CarMeN Laboratory, INSERM U1060, INRA UMR 1397, INSA-Lyon, Université Lyon 1, 60310 Pierre-Benite, France;
- AMU, INRAE, INSERM, C2VN, 13005 Marseille, France; (C.H.); (M.N.)
| | - Charlotte Halimi
- AMU, INRAE, INSERM, C2VN, 13005 Marseille, France; (C.H.); (M.N.)
| | - Emilie Blond
- Biochemistry Department, Hospices Civils de Lyon, 69495 Pierre-Benite , France; (C.C.); (E.B.)
- CarMeN Laboratory, INSERM U1060, INRA UMR 1397, INSA-Lyon, Université Lyon 1, 60310 Pierre-Benite, France;
| | - Marion Nowicki
- AMU, INRAE, INSERM, C2VN, 13005 Marseille, France; (C.H.); (M.N.)
| | - Noël Peretti
- CarMeN Laboratory, INSERM U1060, INRA UMR 1397, INSA-Lyon, Université Lyon 1, 60310 Pierre-Benite, France;
- Pediatric Hepato-Gastroenterology and Nutrition Unit, Hôpital Femme Mère Enfant de Lyon, Hospices Civils de Lyon, 69677 Bron, France
- Correspondence: (N.P.); (E.R.)
| | - Emmanuelle Reboul
- AMU, INRAE, INSERM, C2VN, 13005 Marseille, France; (C.H.); (M.N.)
- Correspondence: (N.P.); (E.R.)
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Schubert M, Kluge S, Schmölz L, Wallert M, Galli F, Birringer M, Lorkowski S. Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins? Antioxidants (Basel) 2018; 7:antiox7010010. [PMID: 29329238 PMCID: PMC5789320 DOI: 10.3390/antiox7010010] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 01/05/2018] [Accepted: 01/11/2018] [Indexed: 02/06/2023] Open
Abstract
Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins A and D, a metabolic conversion of precursors to active metabolites has already been described. During the metabolism of vitamin E, the long-chain metabolites (LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are formed by oxidative modification of the side-chain. The occurrence of these metabolites in human serum indicates a physiological relevance. Indeed, effects of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory actions as well as tocopherol and xenobiotic metabolism have been shown. Interestingly, there are several parallels between the actions of the LCMs of vitamin E and the active metabolites of vitamin A and D. The recent findings that the LCMs exert effects different from that of their precursors support their putative role as regulatory metabolites. Hence, it could be proposed that the mode of action of the LCMs might be mediated by a mechanism similar to vitamin A and D metabolites. If the physiological relevance and this concept of action of the LCMs can be confirmed, a general concept of activation of lipid-soluble vitamins via their metabolites might be deduced.
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Affiliation(s)
- Martin Schubert
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
| | - Stefan Kluge
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
| | - Lisa Schmölz
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
| | - Maria Wallert
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Baker IDI Heart and Diabetes Institute, Melbourne VIC 3004, Australia.
| | - Francesco Galli
- Department of Pharmaceutical Sciences, Laboratory of Nutrition and Clinical Biochemistry, University of Perugia, 06123 Perugia, Italy.
| | - Marc Birringer
- Department of Nutrition, Food and Consumer Sciences, University of Applied Sciences Fulda, 36037 Fulda, Germany.
| | - Stefan Lorkowski
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
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Schmölz L, Birringer M, Lorkowski S, Wallert M. Complexity of vitamin E metabolism. World J Biol Chem 2016; 7:14-43. [PMID: 26981194 PMCID: PMC4768118 DOI: 10.4331/wjbc.v7.i1.14] [Citation(s) in RCA: 135] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/25/2015] [Accepted: 01/19/2016] [Indexed: 02/05/2023] Open
Abstract
Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their side-chain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for detecting and quantifying vitamin E and its metabolites are crucial. The latest methods in analytics are presented.
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Traber MG, Leonard SW, Bobe G, Fu X, Saltzman E, Grusak MA, Booth SL. α-Tocopherol disappearance rates from plasma depend on lipid concentrations: studies using deuterium-labeled collard greens in younger and older adults. Am J Clin Nutr 2015; 101:752-9. [PMID: 25739929 PMCID: PMC4381779 DOI: 10.3945/ajcn.114.100966] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Accepted: 01/23/2015] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Little is known about α-tocopherol's bioavailability as a constituent of food or its dependence on a subject's age. OBJECTIVE To evaluate the α-tocopherol bioavailability from food, we used collard greens grown in deuterated water ((2)H collard greens) as a source of deuterium-labeled ((2)H) α-tocopherol consumed by younger and older adults in a post hoc analysis of a vitamin K study. DESIGN Younger (mean ± SD age: 32 ± 7 y; n = 12 women and 9 men) and older (aged 67 ± 8 y; n = 8 women and 12 men) adults consumed a test breakfast that included 120 g (2)H collard greens (1.2 ± 0.1 mg (2)H-α-tocopherol). Plasma unlabeled α-tocopherol and (2)H-α-tocopherol were measured by using liquid chromatography-mass spectrometry from fasting (>12 h) blood samples drawn before breakfast (0 h) and at 24, 48, and 72 h and from postprandial samples collected at 4, 5, 6, 7, 9, 12, and 16 h. RESULTS Times (12.6 ± 2.5 h) of maximum plasma (2)H-α-tocopherol concentrations (0.82% ± 0.59% total α-tocopherol), fractional disappearance rates (0.63 ± 0.26 pools/d), half-lives (30 ± 11 h), and the minimum estimated (2)H-α-tocopherol absorbed (24% ± 16%) did not vary between age groups or sexes (n = 41). Unlabeled α-tocopherol concentrations were higher in older adults (26.4 ± 8.6 μmol/L) than in younger adults (19.3 ± 4.2 μmol/L; P = 0.0019) and correlated with serum lipids (r = 0.4938, P = 0.0012). In addition, (2)H-α-tocopherol half-lives were correlated with lipids (r = 0.4361, P = 0.0044). CONCLUSIONS Paradoxically, α-tocopherol remained in circulation longer in participants with higher serum lipids, but the (2)H-α-tocopherol absorbed was not dependent on the plasma lipid status. Neither variable was dependent on age. These data suggest that plasma α-tocopherol concentrations are more dependent on mechanisms that control circulating lipids rather than those related to its absorption and initial incorporation into plasma. This trial was registered at clinicaltrials.gov as NCT0036232.
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Affiliation(s)
- Maret G Traber
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
| | - Scott W Leonard
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
| | - Gerd Bobe
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
| | - Xueyan Fu
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
| | - Edward Saltzman
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
| | - Michael A Grusak
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
| | - Sarah L Booth
- From the Linus Pauling Institute, Oregon State University, Corvallis, OR (MGT, SWL, and GB); the USDA Human Nutrition Center on Aging, Tufts University, Boston, MA (XF, ES, and SLB); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (MAG)
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Borel P, Preveraud D, Desmarchelier C. Bioavailability of vitamin E in humans: an update. Nutr Rev 2013; 71:319-31. [PMID: 23731443 DOI: 10.1111/nure.12026] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Vitamin E is essential for human health and may play a role in the prevention of some degenerative diseases. Its bioavailability, however, is wide ranging and is affected by numerous factors. Recent findings showing that the intestinal absorption of vitamin E involves proteins have raised new relevant questions about factors that can affect bioavailability. It is, therefore, opportune to present a current overview of this topic. This review begins by exploring what is known, as well as what is unknown, about the metabolization of vitamin E in the human upper gastrointestinal tract and then presents a methodical evaluation of factors assumed to affect vitamin E bioavailability. Three main conclusions can be drawn. First, the proteins ABCA1, NPC1L1, and SR-BI are implicated in the absorption of vitamin E. Second, the efficiency of vitamin E absorption is widely variable, though not accurately known (i.e., between 10% and 79%), and is affected by several dietary factors (e.g., food matrix, fat, and fat-soluble micronutrients). Finally, numerous unanswered questions remain about the metabolization of vitamin E in the intestinal lumen and about the factors affecting the efficiency of vitamin E absorption.
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Affiliation(s)
- Patrick Borel
- Institut National de la Santé et de la Recherche Médicale INSERM, Unité Mixte de Recherche UMR 1062, Nutrition, Obesity and Risk of Thrombosis, Marseilles, France.
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Finno C, Valberg S. A Comparative Review of Vitamin E and Associated Equine Disorders. J Vet Intern Med 2012; 26:1251-66. [DOI: 10.1111/j.1939-1676.2012.00994.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Revised: 05/29/2012] [Accepted: 07/18/2012] [Indexed: 12/12/2022] Open
Affiliation(s)
- C.J. Finno
- Department of Veterinary Population Medicine; College of Veterinary Medicine; University of Minnesota; St. Paul; MN
| | - S.J. Valberg
- Department of Veterinary Population Medicine; College of Veterinary Medicine; University of Minnesota; St. Paul; MN
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Gee PT. Unleashing the untold and misunderstood observations on vitamin E. GENES & NUTRITION 2011; 6:5-16. [PMID: 21437026 PMCID: PMC3040795 DOI: 10.1007/s12263-010-0180-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2010] [Accepted: 07/07/2010] [Indexed: 02/07/2023]
Abstract
Paradoxically, meta-analysis of human randomized controlled trials revealed that natural but not synthetic α-tocopherol supplementation significantly increases all-cause mortality at 95% confidence interval. The root cause was that natural α-tocopherol supplementation significantly depressed bioavailability of other forms of vitamin E that have better chemo-prevention capability. Meta-analysis outcome demonstrated flaws in the understanding of vitamin E. Reinterpretation of reported data provides plausible explanations to several important observations. While α-tocopherol is almost exclusively secreted in chylomicrons, enterocytes secrete tocotrienols in both chylomicrons and small high-density lipoproteins. Vitamin E secreted in chylomicrons is discriminately repacked by α-tocopherol transfer protein into nascent very low-density lipoproteins in the liver. Circulating very low-density lipoproteins undergo delipidation to form intermediate-density lipoproteins and low-density lipoproteins. Uptake of vitamin E in intermediate-density lipoproteins and low-density lipoproteins takes place at various tissues via low-density lipoproteins receptor-mediated endocytosis. Small high-density lipoproteins can deliver tocotrienols upon maturation to peripheral tissues independent of α-tocopherol transfer protein action, and uptake of vitamin E takes place at selective tissues by scavenger receptor-mediated direct vitamin E uptake. Dual absorption pathways for tocotrienols are consistent with human and animal studies. α-Tocopherol depresses the bioavailability of α-tocotrienol and has antagonistic effect on tocotrienols in chemo-prevention against degenerative diseases. Therefore, it is an undesirable component for chemo-prevention. Future research directions should be focused on tocotrienols, preferably free from α-tocopherol, for optimum chemo-prevention and benefits to mankind.
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Affiliation(s)
- Ping Tou Gee
- Palm Nutraceuticals Sdn. Bhd., Batu 7, Jalan Mawai, 81900 Kota Tinggi, Johor Malaysia
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Bostanci MO, Bas O, Bagirici F. Alpha-tocopherol decreases iron-induced hippocampal and nigral neuron loss. Cell Mol Neurobiol 2010; 30:389-94. [PMID: 19798567 PMCID: PMC11498760 DOI: 10.1007/s10571-009-9461-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2008] [Accepted: 09/16/2009] [Indexed: 01/25/2023]
Abstract
There are many studies about iron-induced neuronal hyperactivity and oxidative stress. Some reports also showed that iron levels rise in the brain in some neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's disease (AD). It has been suggested that excessive iron level increases oxidative stress and causes neuronal death. Tocopherols act as a free radical scavenger when phenoxylic head group encounters a free radical. We have aimed to identify the effect of alpha-tocopherol (Vitamin E) on iron-induced neurotoxicity. For this reason, rats were divided into three groups as control, iron, and iron + alpha-tocopherol groups. Iron chloride (200 mM in 2.5 microl volume) was injected into brain ventricle of iron and iron + alpha-tocopherol group rats. Same volume of saline (2.5 microl) was given to the rats belonging to control group. Rats of iron + alpha-tocopherol group received intraperitoneally (i.p.) alpha-tocopherol (100 mg/kg/day) for 10 days. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using standard histological techniques. The numbers of neurons in hippocampus and substantia nigra of all rats were estimated by stereological techniques. Results of present study show that alpha-tocopherol decreased hippocampal and nigral neuron loss from 51.7 to 12.1% and 41.6 to 17.8%, respectively. Findings of the present study suggest that alpha-tocopherol may have neuroprotective effects against iron-induced hippocampal and nigral neurotoxicity and it may have a therapeutic significance for neurodegenerative diseases involved iron.
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Affiliation(s)
- C J Bates
- MRC Dunn Nutrition Unit, Milton Road, Cambridge CB4 1XJ, UK
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Brisson L, Castan S, Fontbonne H, Nicoletti C, Puigserver A, Ajandouz EH. Alpha-tocopheryl acetate is absorbed and hydrolyzed by Caco-2 cells. Chem Phys Lipids 2008; 154:33-7. [DOI: 10.1016/j.chemphyslip.2008.04.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2007] [Revised: 03/28/2008] [Accepted: 04/08/2008] [Indexed: 10/22/2022]
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Clifford AJ, de Moura FF, Ho CC, Chuang JC, Follett J, Fadel JG, Novotny JA. A feasibility study quantifying in vivo human alpha-tocopherol metabolism. Am J Clin Nutr 2006; 84:1430-41. [PMID: 17158427 DOI: 10.1093/ajcn/84.6.1430] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Quantitation of human vitamin E metabolism is incomplete, so we quantified RRR- and all-rac-alpha-tocopherol metabolism in an adult. OBJECTIVE The objective of the study was to quantify and interpret in vivo human vitamin E metabolism. DESIGN A man was given an oral dose of 0.001821 micromol [5-14CH3]RRR-alpha-tocopheryl acetate (with 101.5 nCi 14C), and its fate in plasma, plasma lipoproteins, urine, and feces was measured over time. Data were analyzed and interpreted by using kinetic modeling. The protocol was repeated later with 0.001667 micromol [5-14CH3]all-rac-alpha-tocopheryl acetate (with 99.98 nCi 14C). RESULTS RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate were absorbed equally well (fractional absorption: approximately 0.775). The main route of elimination was urine, and approximately 90% of the absorbed dose was alpha-2(2'-carboxyethyl)-6-hydroxychroman. Whereas 93.8% of RRR-alpha-tocopherol flow to liver kinetic pool B from plasma was returned to plasma, only 80% of the flow of all-rac-alpha-tocopherol returned to plasma; the difference (14%) was degraded and eliminated. Thus, for newly digested alpha-tocopherol, the all-rac form is preferentially degraded and eliminated over the RRR form. Respective residence times in liver kinetic pool A and plasma for RRR-alpha-tocopherol were 1.16 and 2.19 times as long as those for all-rac-alpha-tocopherol. Model-estimated distributions of plasma alpha-tocopherol, extrahepatic tissue alpha-tocopherol, and liver kinetic pool B for RRR-alpha-tocopherol were, respectively, 6.77, 2.71, and 3.91 times as great as those for all-rac-alpha-tocopherol. Of the lipoproteins, HDL had the lowest 14C enrichment. Liver had 2 kinetically distinct alpha-tocopherol pools. CONCLUSIONS Both isomers were well absorbed; all-rac-alpha-tocopherol was preferentially degraded and eliminated in urine, the major route. RRR-alpha-tocopherol had a longer residence time and larger distribution than did all-rac-alpha-tocopherol. Liver had 2 distinct alpha-tocopherol pools. The model is a hypothesis, its estimates are model-dependent, and it encourages further testing.
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Affiliation(s)
- Andrew J Clifford
- Department of Nutrition, University of California, Davis, Davis, CA 5616-8669, USA.
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Hughes L, Slaby M, Burton GW, Ingold KU. Synthesis of α- and γ-tocopherols selectively labelled with deuterium. J Labelled Comp Radiopharm 2006. [DOI: 10.1002/jlcr.2580280909] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Park MJ, Lee SK, Lim MA, Chung HS, Cho SI, Jang CG, Lee SM. Effect of alpha-tocopherol and deferoxamine on methamphetamine-induced neurotoxicity. Brain Res 2006; 1109:176-82. [PMID: 16844102 DOI: 10.1016/j.brainres.2006.06.030] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2006] [Revised: 06/12/2006] [Accepted: 06/13/2006] [Indexed: 11/29/2022]
Abstract
Methamphetamine (MA)-induced dopaminergic neurotoxicity is believed to be associated with the increased formation of free radicals. This study examined the effect of alpha-tocopherol (alpha-TC), a scavenger of reactive oxygen species, and deferoxamine (DFO), an iron chelator, on the MA-induced neurotoxicity. Male rats were treated with MA (10 mg/kg, every 2 h for four injections). The rat received either alpha-TC (20 mg/kg) intraperitoneally for 3 days and 30 min prior to MA administration or DFO (50 mg/kg) subcutaneously 30 min before MA administration. The concentrations of dopamine (DA), serotonin and their metabolites decreased significantly after MA administration, which was inhibited by the alpha-TC and DFO pretreatment. alpha-TC and DFO attenuated the MA-induced hyperthermia as well as the alterations in the locomotor activity. The level of lipid peroxidation was higher and the reduced glutathione concentration was lower in the MA-treated rats. These changes were significantly attenuated by alpha-TC and DFO. This suggests that alpha-TC and DFO ameliorate the MA-induced neuronal damage by decreasing the level of oxidative stress.
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Affiliation(s)
- Mee-Jung Park
- Dept. of Forensic science, National Institute of Scientific Investigation, Yangchon-ku, Seoul, 158-707, Korea
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19
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Kim JY, Lee SM. Vitamins C and E protect hepatic cytochrome P450 dysfunction induced by polymicrobial sepsis. Eur J Pharmacol 2006; 534:202-9. [PMID: 16483564 DOI: 10.1016/j.ejphar.2006.01.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2005] [Revised: 01/10/2006] [Accepted: 01/11/2006] [Indexed: 01/30/2023]
Abstract
The effect of vitamins C and E on the activity and gene expression of hepatic microsomal cytochrome P450 (CYP) during polymicrobial sepsis was studied. The serum aminotransferase and lipid peroxidation levels increased 24 h after the cecal ligation and puncture, and this increase was attenuated by vitamins C and E. The hepatic concentrations of the reduced glutathione decreased in the septic animals, which was inhibited by vitamin C. Both the activities and mRNA expression of CYP1A1 and CYP2E1 decreased after cecal ligation and puncture, which was prevented by vitamins C and E. The decrease in CYP1A2 activity in the liver from cecal ligation and puncture was prevented by vitamins C and E. Our findings suggest that vitamins C and E improve hepatic drug metabolizing dysfunction as indicated by abnormalities in CYP isoforms during sepsis, and this protection is, in major part, caused by decreased oxidant stress and lipid peroxidation.
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Affiliation(s)
- Joo-Young Kim
- College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, South Korea
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20
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Gu F, Netscher T, Atkinson J. 5-Trideuteromethyl-α-tocotrienol and 5-14CH3-α-tocotrienol as biological tracers of tocotrienols. J Labelled Comp Radiopharm 2006. [DOI: 10.1002/jlcr.1090] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Kim JY, Lee SM. Effect of alpha-tocopherol on the expression of hepatic vascular stress genes in response to sepsis. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2005; 68:2051-62. [PMID: 16326423 DOI: 10.1080/15287390491009327] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Sepsis is the leading cause of death in critically ill surgical patients. Septic hepatic dysfunction, an important determinant of outcome, although poorly understood, includes inappropriate expression of vasoregulatory genes. In this study the effect of alpha-tocopherol was determined on the expression of hepatic vascular stress genes in response to sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). Rats received either vehicle or alpha-tocopherol (AT, 15 mg/kg), intraperitoneally injected for 3 d prior to CLP procedure. Serum aminotransferase activities and hepatic lipid peroxides levels markedly increased 24 h after CLP, and this rise was attenuated by AT treatment. The hepatic concentrations of reduced glutathione decreased in CLP animals, which was inhibited by AT. CLP significantly increased mRNA levels of endothelin (ET)-1 and ET(B) receptor in livers, which was not prevented by AT treatment. There were no significant changes in ET(A) mRNA expression among any of the experimental groups. There were significant increases in the mRNA expression of inducible nitric oxide synthase and heme oxygenase-1 in livers of CLP animals, and this was prevented by AT treatment. The expression of tumor necrosis factor-alpha and cyclooxygenase-2 mRNA increased 4.9-fold and 4.4-fold, respectively, in livers of CLP animals. This increase was attenuated by AT treatment. Our data suggest that sepsis induces an imbalance in hepatic vasoregulatory gene expression and that AT ameliorates altered expression of vasodilators through its free radical scavenging activity.
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Affiliation(s)
- Joo-Young Kim
- College of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon-si, Gyeonggi-do, South Korea
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22
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Lee WY, Lee SM. Protective effects of α-tocopherol and ischemic preconditioning on hepatic reperfusion injury. Arch Pharm Res 2005; 28:1392-9. [PMID: 16392674 DOI: 10.1007/bf02977907] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This study evaluated the effect of alpha-tocopherol (alpha-TC), ischemic preconditioning (IPC) or a combination on the extent of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Rats were pretreated with alpha-TC (20 mg/kg per day, i.p.) for 3 days before sustained ischemia. A rat liver was preconditioned with 10 min of ischemia and 10 min of reperfusion, and was then subjected to 90 min of ischemia followed by 5 h or 24 h of reperfusion. I/R increased the aminotransferase activity and mitochondrial lipid peroxidation, whereas it decreased the mitochondrial glutamate dehydrogenase activity. alpha-TC and IPC individually attenuated these changes. alpha-TC combined with IPC (alpha-TC+IPC) did not further attenuate the changes. The mitochondrial glutathione content decreased after 5 h reperfusion. This decrease was attenuated by alpha-TC, IPC, and alpha-TC+IPC. The significant production of peroxides observed after 10 min reperfusion subsequent to sustained ischemia was attenuated by alpha-TC, IPC, and alpha-TC+IPC. The mitochondria isolated after I/R were rapidly swollen. However, this swelling rate was reduced by alpha-TC, IPC, and alpha-TC+IPC. These results suggest that either alpha-TC or IPC reduces the level of mitochondrial damage associated with oxidative stress caused by hepatic I/R, but alpha-TC combined with IPC offers no significant additional protection.
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Affiliation(s)
- Woo-Yong Lee
- College of Pharmacy, Sungkyunkwan University, Suwon, Korea
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23
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Abstract
O termo biodisponibilidade representa a parte do nutriente ingerido que tem o potencial de suprir as demandas fisiológicas em tecidos alvos; por definição, não corresponde, na maioria das vezes, à quantidade ingerida. Apesar da concordância entre alguns pesquisadores no que se refere ao conceito de biodisponibilidade, vários termos são comumente utilizados em trabalhos científicos como sinônimos desse, em função das peculiaridades dos métodos empregados na sua determinação. Estudos de balanço, relação dose-efeito e uso de isótopos são alguns dos métodos mais comumente utilizados para determinar a biodisponibilidade de vitaminas. Tais metodologias, além de avaliar a biodisponibilidade do nutriente, devem tanto quanto possível procurar elucidar ou levar em consideração os fatores que interferem na sua absorção e utilização. Dentre esses fatores, estão a interação com outros nutrientes ou componentes da dieta e as condições fisiológicas dos organismos submetidos ao estudo. As vitaminas lipossolúveis, devido ao seu metabolismo complexo, diversidade funcional e mecanismo de absorção relacionado a lipoproteínas, apresentam alguns problemas específicos no que se refere à avaliação de sua biodisponibilidade em alimentos ou dietas, necessitando, por ocasião dos ensaios, de um criterioso planejamento e análise de resultados. Dessa forma, ressaltaram-se, nesta revisão, alguns aspectos importantes com relação à biodisponibilidade das vitaminas lipossolúveis, como: diversidade de termos usados, metodologia para avaliação, fatores que interferem na absorção e utilização, entre outros, visto que a avaliação da biodisponibilidade de algumas vitaminas lipossolúveis ainda não possui métodos validados, gerando uma grande variação nos resultados obtidos nas pesquisas realizadas nesta área.
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Abstract
The alpha-tocopherol transfer protein (alpha-TTP) is required to prevent vitamin E deficiency in humans and in alpha-TTP null mice. Whereas alpha-TTP is not required to facilitate intestinal absorption of vitamin E, it is required to maintain normal alpha-tocopherol concentrations in plasma and extrahepatic tissues. alpha-Tocopherol secretion from the liver in very low density lipoproteins (VLDLs) is impaired in humans with a defect in the alpha-TTP gene. In perfusions of isolated cynomolgus monkey livers, VLDLs were preferentially enriched in RRR-alpha-tocopherol. The mechanism by which alpha-TTP incorporates alpha-tocopherol into nascent VLDLs is the topic of this report. VLDL assembly is a multistep secretory process that occurs within the membrane compartments of the endoplasmic reticulum and Golgi apparatus. Thus, we postulated that alpha-TTP might transfer alpha-tocopherol onto nascent VLDLs either in the endoplasmic reticulum or in the Golgi apparatus. To test these possibilities, we isolated nascent VLDLs from highly purified RER and Golgi apparatus membrane fractions from livers of rats fed equimolar ratios of RRR- and SRR-alpha-tocopherols labeled with different amounts of deuterium. Although the plasma was enriched in RRR-alpha-tocopherol 14 hours after the dose, no enrichment of nascent VLDL precursors from either of the secretory compartments was detected, indicating that VLDL enrichment with alpha-tocopherol may occur as a post-VLDL secretory process. Therefore, we hypothesize that alpha-TTP may facilitate movement of alpha-tocopherol to the hepatocyte plasma membrane (by unknown mechanisms) where newly secreted, nascent VLDLs could acquire both alpha-tocopherol and unesterified cholesterol while within the space of Disse. Clearly, critical information is lacking in our understanding of the mechanism by which alpha-TTP facilitates the preferential enrichment of VLDLs with alpha-tocopherol.
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Affiliation(s)
- Maret G Traber
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.
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25
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Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2004; 1660:171-99. [PMID: 14757233 DOI: 10.1016/j.bbamem.2003.11.012] [Citation(s) in RCA: 730] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Coenzyme Q (CoQ) is present in all cells and membranes and in addition to be a member of the mitochondrial respiratory chain it has also several other functions of great importance for the cellular metabolism. This review summarizes the findings available to day concerning CoQ distribution, biosynthesis, regulatory modifications and its participation in cellular metabolism. There are a number of indications that this lipid is not always functioning by its direct presence at the site of action but also using e.g. receptor expression modifications, signal transduction mechanisms and action through its metabolites. The biosynthesis of CoQ is studied in great detail in bacteria and yeast but only to a limited extent in animal tissues and therefore the informations available is restricted. However, it is known that the CoQ is compartmentalized in the cell with multiple sites of biosynthesis, breakdown and regulation which is the basis of functional specialization. Some regulatory mechanisms concerning amount and biosynthesis are established and nuclear transcription factors are partly identified in this process. Using appropriate ligands of nuclear receptors the biosynthetic rate can be increased in experimental system which raises the possibility of drug-induced upregulation of the lipid in deficiency. During aging and pathophysiological conditions the tissue concentration of CoQ is modified which influences cellular functions. In this case the extent of disturbances is dependent on the localization and the modified distribution of the lipid at cellular and membrane levels.
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Affiliation(s)
- Mikael Turunen
- Department of Biochemistry and Biophysics, Stockholm University, Arrhenius Laboratories for Natural Sciences, SE-106 91 Stockholm, Sweden.
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26
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Schwedhelm E, Maas R, Troost R, Böger RH. Clinical pharmacokinetics of antioxidants and their impact on systemic oxidative stress. Clin Pharmacokinet 2003; 42:437-59. [PMID: 12739983 DOI: 10.2165/00003088-200342050-00003] [Citation(s) in RCA: 115] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Dietary antioxidants play a major role in maintaining the homeostasis of the oxidative balance. They are believed to protect humans from disease and aging. Vitamin C (ascorbic acid), vitamin E (tocopherol), beta-carotene and other micronutrients such as carotenoids, polyphenols and selenium have been evaluated as antioxidant constituents in the human diet. This article addresses data provided from clinical trials, highlighting the clinical pharmacokinetics of vitamin C, vitamin E, beta-carotene, lycopene, lutein, quercetin, rutin, catechins and selenium. The bioavailability of vitamin C is dose-dependent. Saturation of transport occurs with dosages of 200-400 mg/day. Vitamin C is not protein-bound and is eliminated with an elimination half-life (t((1/2))) of 10 hours. In Western populations plasma vitamin C concentrations range from 54-91 micro mol/L. Serum alpha- and gamma-tocopherol range from 21 micro mol/L (North America) to 27 micro mol/L (Europe) and from 3.1 micro mol/L to 1.5 micro mol/L, respectively. alpha-Tocopherol is the most abundant tocopherol in human tissue. The bioavailability of all-rac-alpha-tocopherol is estimated to be 50% of R,R,R-alpha-tocopherol. The hepatic alpha-tocopherol transfer protein (alpha-TTP) together with the tocopherol-associated proteins (TAP) are responsbile for the endogenous accumulation of natural alpha-tocopherol. Elimination of alpha-tocopherol takes several days with a t((1/2)) of 81 and 73 hours for R,R,R-alpha-tocopherol and all-rac-alpha-tocopherol, respectively. The t((1/2)) of tocotrienols is short, ranging from 3.8-4.4 hours for gamma- and alpha-tocotrienol, respectively. gamma-Tocopherol is degraded to 2, 7, 8-trimethyl-2-(beta-carboxyl)-6-hyrdoxychroman by the liver prior to renal elimination. Blood serum carotenoids in Western populations range from 0.28-0.52 micro mol/L for beta-carotene, from 0.2-0.28 for lutein, and from 0.29-0.60 for lycopene. All-trans-carotenoids have a better bioavailability than the 9-cis-forms. Elimination of carotenoids takes several days with a t((1/2)) of 5-7 and 2-3 days for beta-carotene and lycopene, respectively. The bioconversion of beta-carotene to retinal is dose-dependent, and ranges between 27% and 2% for a 6 and 126mg dose, respectively. Several oxidised metabolites of carotenoids are known. Flavonols such as quercetin glycosides and rutin are predominantly absorbed as aglycones, bound to plasma proteins and subsequently conjugated to glucuronide, sulfate, and methyl moieties. The t((1/2)) ranges from 12-19 hours. The bioavailabillity of catechins is low and they are eliminated with a t((1/2)) of 2-4 hours. Catechins are degraded to several gamma-valerolactone derivatives and phase II conjugates have also been identified. Only limited clinical pharmacokinetic data for other polyphenols such as resveratrol have been reported to date.
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Affiliation(s)
- Edzard Schwedhelm
- Institute of Experimental and Clinical Pharmacology, Clinical Pharmacology Unit, University Hospital of Hamburg-Eppendorf, Hamburg, Germany.
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27
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Borel P. Factors affecting intestinal absorption of highly lipophilic food microconstituents (fat-soluble vitamins, carotenoids and phytosterols). Clin Chem Lab Med 2003; 41:979-94. [PMID: 12964802 DOI: 10.1515/cclm.2003.151] [Citation(s) in RCA: 141] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Highly lipophilic food microconstituents (HLFMs) with octanol-water partition coefficients log10 P(c) > 8 include the fat-soluble vitamins (A, E, D and K) and phytochemicals with potential health benefits, the carotenoids and phytosterols. It has been assumed that these compounds have the same metabolism in the human upper gastrointestinal tract and that they follow the same fate as lipids. However, a literature review shows that the metabolism of HLFMs in the upper gastrointestinal tract depends on each HLFM species. For example, some HLFM esters are hydrolyzed mainly by pancreatic lipase, others by bile salt-stimulated lipase; some HLFMs are apparently absorbed by passive diffusion, others by a transporter. Also, although some factors (HLFM molecular species, fat, food matrix) affect absorption efficiency of most HLFMs, other factors (fibers, microconstituents) apparently affect absorption only of some HLFMs. The mnemonic acronym SLAMENGHI, previously proposed to list the factors affecting the bioavailability of carotenoids, was used here to review current knowledge of the factors suspected to affect the intestinal absorption of HLFMs. The available data reveal numerous gaps in the knowledge of the metabolism of HLFMs and the factors that affect their absorption. These gaps need to be filled to be able to formulate HLFMs so as to promote greater absorption efficiency.
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Affiliation(s)
- Patrick Borel
- Unité 476 INSERM, Faculté de Médecine, Nutrition Humaine et Lipides, Marseille, France.
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28
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Lei H, Atkinson J. Hydrogen-deuterium exchange during the reductive deuteration of ?- and ?-tocopherol chromenes. J Labelled Comp Radiopharm 2001. [DOI: 10.1002/jlcr.449] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Roxborough HE, Burton GW, Kelly FJ. Inter- and intra-individual variation in plasma and red blood cell vitamin E after supplementation. Free Radic Res 2000; 33:437-45. [PMID: 11022852 DOI: 10.1080/10715760000300971] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
To establish the range of individual blood responses to supplemental vitamin E, 30 healthy subjects ingested 75 mg of deuterium-labelled alpha-tocopherol with a standard breakfast. Blood was collected at 6, 9, 12, 27 and 51 h post ingestion and deuterated (d6) and non-deuterated (do) alpha-tocopherol concentrations were determined in plasma and red blood cells (RBC) by GC-MS. To examine intra-individual responses, 6 of these subjects were re-examined at 6-month intervals over a 30-month period. Post ingestion, the amount of d6-alpha-tocopherol in blood increased rapidly with time with maximal concentrations seen at 12 h (plasma) and 27 h (RBC) in most subjects. At these times, d6-alpha-tocopherol concentration ranged from 0.3-12.4 micromol/l in plasma and 0.6-4.09 micromol/l packed cell in RBC. Area under the curve calculations indicated inter-individual differences of alpha-tocopherol uptake to be 40-fold for plasma (12.9-493.3 micromol h/l) and 6-fold for RBC (24.4-146.1 micromol h/l packed RBC). Intra-individual variation in alpha-tocopherol uptake was small in comparison and remained relatively constant over the 30-month period. We conclude that vitamin E uptake varies widely in the normal population, although it is comparatively stable for an individual over time. These differences likely arise from variations in the regulation of vitamin E uptake and metabolism between subjects. Factors regulating this process must be better understood before the optimal intake of vitamin E can be ascertained.
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Affiliation(s)
- H E Roxborough
- The Rayne Institute, St. Thomas' Hospital, King's College London, UK
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30
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Ametaj BN, Nonnecke BJ, Franklin ST, Horst RL, Bidlack WR, Stuart RL, Beitz DC. Dietary vitamin A modulates the concentrations of RRR-alpha-tocopherol in plasma lipoproteins from calves fed milk replacer. J Nutr 2000; 130:629-36. [PMID: 10702596 DOI: 10.1093/jn/130.3.629] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The practice of supplementing milk replacers fed to neonatal calves with high concentrations of vitamin A has raised concerns regarding the effect of excess vitamin A on the bioavailability of vitamin E. A 4 x 2 factorial experiment evaluated the effects of four dietary amounts of vitamin A [0, 1.78 [National Research Council (NRC)(6) requirement, control], 35.6 and 71.2 micromol daily as retinyl acetate] and two forms of vitamin E (RRR-alpha-tocopherol and RRR-alpha-tocopheryl acetate, 155 micromol daily) on plasma RRR-alpha-tocopherol and RRR-gamma-tocopherol and RRR-alpha-tocopherol associated with plasma lipoproteins (Lp) from milk replacer-fed Holstein calves from birth to 28 d of age. The VLDL, LDL, HDL and very high-density lipoprotein (VHDL) fractions were separated by ultracentrifugal flotation, and the amount of vitamin E associated with each fraction was determined by normal-phase HPLC. The amount and distribution of RRR-alpha-tocopherol in Lp fractions were unaffected by the form of dietary vitamin E. Plasma and Lp RRR-alpha-tocopherol concentrations increased with age (P < 0.0001) and were maximal at 28 d of age. Concentrations of RRR-alpha-tocopherol associated with Lp were 25% (P < 0.01) to 39% (P < 0.0001) lower in calves fed 35.6 and 71.2 micromol of vitamin A daily than in control calves at 28 d of age. The RRR-gamma-tocopherol concentrations were unaffected by dietary vitamin A (P >/= 0.05). In conclusion, dietary vitamin A modulated the amount and distribution of RRR-alpha-tocopherol in the circulation of milk replacer-fed neonatal calves. Because of the essential antioxidant role of vitamin E, the health-related consequences associated with the depression of the LP RRR-alpha-tocopherol concentrations in calves fed vitamin A at 35.6 and 71.2 micromol need to be investigated.
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Affiliation(s)
- B N Ametaj
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
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31
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Reduced fat diets influence α-tocopherol concentrations in plasma lipoproteins and tissues of male and female rats. Nutr Res 2000. [DOI: 10.1016/s0271-5317(99)00139-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Affiliation(s)
| | - Maret G. Traber
- Department of Nutrition and Food ManagementLinus Pauling InstituteOregon State University Corvallis Oregon 97330 USA
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Kramer-Stickland K, Liebler DC. Effect of UVB on hydrolysis of alpha-tocopherol acetate to alpha-tocopherol in mouse skin. J Invest Dermatol 1998; 111:302-7. [PMID: 9699734 DOI: 10.1046/j.1523-1747.1998.00273.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
We have assessed the hydrolysis of alpha-tocopherol acetate (alpha-TAc) to the active antioxidant alpha-tocopherol (alpha-TH) in mouse epidermis and in supernatant from epidermal homogenates. Topically administered alpha-TH prevents UVB photocarcinogenesis in C3H mice, whereas alpha-TAc does not. Hydrolysis in skin was monitored in mice treated topically with deuterium labeled alpha-TAc (d3-alpha-TAc). Epidermal samples were isolated from mice and analyzed for endogenous (d0-alpha-TAc) and d3-alpha-TH by gas chromatography-mass spectrometry. Within 24 h, the levels of d3-alpha-TH increased up to 10-fold over endogenous d0-alpha-TH levels; however, in mice irradiated with UVB prior to the application of d3-alpha-TAc, levels of d3-alpha-TH increased up to 30-40-fold over endogenous d0-alpha-TH. This enhancement of alpha-TAc hydrolysis increased with increasing UVB dose. Prior UVB exposure may increase hydrolysis of alpha-TAc by increasing epidermal esterase activity. Nonspecific esterase activity was measured in the 2000 x g supernatant from epidermis of unirradiated and irradiated mice. Alpha-napthyl acetate, a nonspecific esterase substrate, was converted to alpha-napthol in supernatants from unirradiated mice. Hydrolysis to alpha-napthol increased approximately 3-fold in supernatants from irradiated mice. Hydrolysis of alpha-TAc to alpha-TH also occurred in supernatant from unirradiated mice, and this hydrolysis increased approximately 3-fold in supernatant from irradiated animals. These data indicate that nonspecific esterase activity was increased by UVB in the skin, that alpha-TAc is converted to alpha-TH in the homogenate fraction containing nonspecific esterase, and that UVB exposure modulates the metabolism of alpha-TAc to alpha-TH in vivo.
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Affiliation(s)
- K Kramer-Stickland
- Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson 85721, USA
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McGuire SO, Alexander DW, Fritsche KL. Fish oil source differentially affects rat immune cell alpha-tocopherol concentration. J Nutr 1997; 127:1388-94. [PMID: 9202096 DOI: 10.1093/jn/127.7.1388] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
We have previously reported that both the source of dietary fish oil and the chemical form of vitamin E supplied in the diet affect the vitamin E status of immune cells in rats. The purpose of this study was to investigate further the effect of fish oil source on immune cell vitamin E status using free alpha-tocopherol (alpha-T) at the AIN recommended level as the sole source of vitamin E. Sixty weanling female rats were fed semipurified, high fat (20 g/100 g) diets containing either tocopherol-stripped lard (LRD), menhaden fish oil (MFO), sardine fish oil (SRD) or cod liver oil (CLO) as the primary lipid source. Endogenous alpha-T concentration was measured and equalized to 150 mg/kg oil by addition of free RRR-alpha-T to each lipid source, allowing for a final concentration of alpha-T in the mixed diet of 30 mg/kg. An additional group of rats was fed LRD without supplemental vitamin E (LRD-) as a negative control. After feeding experimental diets for 5 or 10 wk, tissues were collected for alpha-T analysis by HPLC. After 5 wk, plasma and liver alpha-T (micromol alpha-T/g lipid) were significantly lower in SRD- and CLO-fed rats compared with LRD-fed rats. At 10 wk, only plasma alpha-T in CLO-fed rats remained significantly depressed. Plasma and liver alpha-T concentrations (micromol alpha-T/g lipid) were not significantly lower in MFO-fed rats than LRD-fed rats at either time point. Compared with LRD, feeding MFO to rats for 5 or 10 wk resulted in significantly greater alpha-T content of immune cells. In similar fashion, SRD-fed rats, compared with LRD-fed rats, also had significantly greater alpha-T content in splenocytes at both time points and greater thymocyte alpha-T at 10 wk. In all instances, the alpha-T status of rats fed CLO was indistinguishable from that of rats fed the vitamin E-free diet (LRD-). These data further demonstrate the complexity of the relationship between vitamin E status and dietary (n-3) polyunsaturated fatty acids (PUFA).
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Affiliation(s)
- S O McGuire
- Graduate Nutritional Sciences Program and Department of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
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35
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Abstract
The conversion of alpha-tocopheryl quinone into alpha-tocopherol in humans has been demonstrated. A male subject was given an oral dose of 400 mg of alpha-3,5-[(C2H3)2]-tocopheryl quinone with an evening meal. Analysis of plasma 15 h later by lipid extraction and subsequent GC-MS single ion monitoring revealed the presence of alpha-[5,7-(C2H3)2]-tocopherol at a concentration of 0.4 microM, representing 0.8% of the total tocopherol in the plasma sample. This experiment clearly demonstrates that orally administered alpha-tocopheryl quinone is converted in a low overall yield to alpha-tocopherol in humans. The conversion to alpha-tocopherol of that portion of the quinone dose which was actually absorbed into the blood stream may, however, have been fairly efficient.
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Affiliation(s)
- A N Moore
- Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Ontario, Canada
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36
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MITCHELL GERALDINEV, GRUNDEL ERICH, JENKINS MAMIEY. Bioavailability for Rats of Vitamin E from Fortified Breakfast Cereals. J Food Sci 1996. [DOI: 10.1111/j.1365-2621.1996.tb10974.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Brink EJ, Haddeman E, Tijburg LB. Vitamin E incorporated into a very-low-fat meal is absorbed from the intestine of young rats. Br J Nutr 1996; 75:939-48. [PMID: 8774238 DOI: 10.1079/bjn19960199] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Vegetable fats and oils are major sources of dietary vitamin E. Consequently the current trend to reduce fat consumption is accompanied by a reduction of the intake of vitamin E. In addition, the absorption of vitamin E is thought to be dependent on the hydrolysis of dietary lipids in the small intestine. It is therefore conceivable that a lower dietary fat intake also diminishes the intestinal absorption of vitamin E. The present 3-week feeding study in young male rats was designed to investigate whether different concentrations of vitamin E added to a very-low-fat product (0, 330 or 1350 mg DL-alpha-tocopheryl acetate/kg product) were absorbed. We therefore incorporated these products into a very-low-fat meal (final fat concentration: 7 g/kg) or a low-fat meal containing 52 g fat/kg. The magnitude of vitamin E absorption from these meals was compared with that from meals containing similar amounts of vitamin E, but a high fat concentration of 190 g/kg. Apparent vitamin E absorption was defined as intake of alpha-tocopherol equivalents (alpha TE) minus faecal alpha TE excretion over 4 d during week 3 of the experimental period. The results of this study showed that apparent absorption of vitamin E from a very-low-fat meal varied, depending on the vitamin E concentration, from 73 to 83%. The magnitude of this vitamin E absorption was not significantly different from that from meals containing a high amount of fat. Liver vitamin E status was equal in rats fed on the very-low-fat meals compared with those fed on the high-fat meals. We conclude that, when very-low-fat or low-fat products are used as a replacement for full-fat products, addition of vitamin E to these products, as DL-alpha-tocopheryl acetate, might be useful in meeting the vitamin E requirements.
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Affiliation(s)
- E J Brink
- Unilever Research Laboratory, Vlaardingen, The Netherlands
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38
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Affiliation(s)
- M G Traber
- Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA
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Cheeseman KH, Holley AE, Kelly FJ, Wasil M, Hughes L, Burton G. Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E. Free Radic Biol Med 1995; 19:591-8. [PMID: 8529918 DOI: 10.1016/0891-5849(95)00083-a] [Citation(s) in RCA: 92] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The bioavailability of RRR-alpha-tocopherol from the oral administration of RRR-alpha-tocopherol itself and its acetate and succinate esters was determined in healthy human subjects. Venous blood samples were withdrawn periodically over a 51-h period following oral administration of a gelatin capsule containing an equimolar mixture of RRR-alpha-tocopherol and RRR-alpha-tocopheryl acetate. In a second study, subjects received a capsule containing an equimolar mixture of RRR-alpha-tocopheryl acetate and RRR-alpha-tocopheryl succinate. In Study 1, RRR-alpha-tocopherol was absorbed at similar rates from both the free phenol, and the acetate ester and maximum plasma levels occurred at 12 h in most subjects. The extent of absorption of RRR-alpha-tocopherol varied considerably between subjects in absolute terms, but the relative absorption from the two forms was remarkably consistent, and a ratio of 1.0 was found for parameters of relative bioavailability in plasma. The concentration of RRR-alpha-tocopherol from each form was maximal at approximately 27 h in red blood cells and, as seen with the plasma data, there was a large interindividual variability. In Study 2, there was no significant difference in the extent of absorption of RRR-alpha-tocopherol from the acetate ester and the succinate ester, although there was an apparently higher initial rate of absorption from the acetate ester.
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Affiliation(s)
- K H Cheeseman
- Department of Biology & Biochemistry, Brunel University, Uxbridge, UK
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40
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Traber MG, Diamond SR, Lane JC, Brody RI, Kayden HJ. beta-Carotene transport in human lipoproteins. Comparisons with a-tocopherol. Lipids 1994; 29:665-9. [PMID: 7861932 DOI: 10.1007/bf02538909] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The purpose of this study was to investigate the temporal relationships of the transport of beta-carotene in human lipoproteins. We administered 60 mg beta-carotene with breakfast to nine fasting subjects, then blood samples were collected at intervals of up to 75 h, lipoproteins were isolated, and beta-carotene was quantitated. beta-Carotene concentrations in chylomicrons and very low density lipoproteins (VLDL) peaked at 6 and 9 h, respectively. Nonetheless, at all time points the majority of plasma beta-carotene was contained in low density lipoproteins (LDL), while high density lipoproteins (HDL) carried a smaller portion (at 24 h, 73 +/- 8% in LDL as compared with 23 +/- 5% in HDL). In three subjects, transport of beta-carotene was compared with the results of earlier studies on the transport of stereoisomers of alpha-tocopherol. Unlike plasma RRR-alpha-tocopherol concentrations, which are maintained by the preferential incorporation of RRR-alpha-tocopherol into VLDL by the liver, beta-carotene increased and decreased in VLDL similarly to SRR-alpha-tocopherol, a stereoisomer whose concentrations are not maintained in plasma. In conclusion, beta-carotene is primarily transported in the plasma in LDL, but its incorporation by the liver into lipoproteins does not appear to be enhanced.
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Affiliation(s)
- M G Traber
- Department of Medicine, New York University School of Medicine, New York 10016
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Traber MG, Rader D, Acuff RV, Brewer HB, Kayden HJ. Discrimination between RRR- and all-racemic-alpha-tocopherols labeled with deuterium by patients with abetalipoproteinemia. Atherosclerosis 1994; 108:27-37. [PMID: 7980705 DOI: 10.1016/0021-9150(94)90035-3] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The ability to discriminate between stereoisomers of alpha-tocopherol was studied in five patients with abetalipoproteinemia (ABL) because an impairment in secretion of apolipoprotein B-containing lipoproteins might impede the normally enhanced plasma transport of RRR-alpha-tocopherol. An oral dose containing 3.7 g of each 2R, 4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate) and 2RS,4'RS,8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6 all rac-alpha-tocopheryl acetate) was administered, then the labeled and unlabeled alpha-tocopherol contents of plasma and red blood cells from multiple blood samples obtained at selected times up to 72 h following the dose were quantitated. ABL plasma contained about 1%-10% of the d3-RRR-alpha-tocopherol concentrations of normal subjects given only 150 mg of each isotope. Three of the patients discriminated between forms of alpha-tocopherol with ratios of RRR-/allrac-alpha-tocopherol > or = 1.8, similar to normals. These data suggest that the hepatic tocopherol binding protein is present and functional in ABL patients. Although two of the patients did not discriminate between stereoisomers of alpha-tocopherol, it is likely that this resulted from nearly a complete block in very low density lipoprotein (VLDL) secretion. Thus, the ability of ABL patients to absorb and transport orally administered vitamin E is markedly impaired and variable among patients.
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Affiliation(s)
- M G Traber
- Department of Medicine, New York University School of Medicine, NY 10016
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Traber MG, Pillai SR, Kayden HJ, Steiss JE. Vitamin E deficiency in dogs does not alter preferential incorporation of RRR-alpha-tocopherol compared with all rac-alpha-tocopherol into plasma. Lipids 1993; 28:1107-12. [PMID: 8121253 DOI: 10.1007/bf02537078] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The plasma and lipoprotein transport of RRR and all rac-alpha-tocopherols, labeled with different amounts of deuterium [2R,4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate] and 2RS, 4'RS, 8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6all rac-alpha-tocopheryl acetate), was studied in adult beagle dogs that had been fed a vitamin E-deficient (-E; two dogs) or supplemented (+E; two dogs) diet for two years. We set out to test the hypothesis that the activity of the hepatic tocopherol binding protein (which is thought to preferentially incorporate RRR-alpha-tocopherol into the plasma) is up-regulated by vitamin E deficiency. Labeled alpha-tocopherols increased and decreased similarly in plasma of both -E and +E dogs. Irrespective of diet, d3RRR-alpha-tocopherol was preferentially secreted in plasma. Thus, vitamin E deficiency in dogs does not markedly increase the apparent function of the hepatic tocopherol binding protein. We also studied vitamin E transport in a German Shepherd dog with degenerative myelopathy (DM). Based on the coincident appearance of d3RRR-alpha-tocopherol in plasma and chylomicrons, we suggest that the abnormality in DM may be associated with abnormal vitamin E transport resulting from an impaired function of the hepatic tocopherol binding protein.
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Affiliation(s)
- M G Traber
- Department of Medicine, New York University School of Medicine, New York 10016
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Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res 1993. [DOI: 10.1016/s0022-2275(20)40727-8] [Citation(s) in RCA: 422] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Traber MG, Sokol RJ, Kohlschütter A, Yokota T, Muller DP, Dufour R, Kayden HJ. Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency. J Lipid Res 1993. [DOI: 10.1016/s0022-2275(20)40747-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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Abstract
Vitamin E (alpha-tocopherol), the principal chain-breaking antioxidant in biological membranes, prevents toxicant- and carcinogen-induced oxidative damage by trapping reactive oxyradicals. Although alpha-tocopherol antioxidant reactions appear to be not under direct metabolic control, alpha-tocopherol may function through redox cycles, which deliver reducing equivalents for antioxidant reactions and link antioxidant function to cellular metabolism. This review describes the antioxidant chemistry of alpha-tocopherol and evaluates the experimental evidence for the linkage of alpha-tocopherol turnover to cellular metabolism through redox cycles. Numerous in vitro experiments demonstrate antioxidant synergism between alpha-tocopherol and ascorbate, reduced glutathione, NADPH, and cellular electron transport proteins. Nevertheless, evidence that a one-electron redox cycle regenerates alpha-tocopherol from the tocopheroxyl radical is inconclusive. The difficulty of separating tocopheroxyl recycling from direct antioxidant actions of other antioxidants has complicated interpretation of the available data. A two-electron redox cycle involving alpha-tocopherol oxidation to 8a-substituted tocopherones followed by tocopherone reduction to alpha-tocopherol may occur, but would require enzymatic catalysis in vivo. Metabolism of antioxidant-inactive alpha-tocopheryl esters releases alpha-tocopherol, whereas reductive metabolism of alpha-tocopherylquinone, an alpha-tocopherol oxidation product, yields alpha-tocopherylhydroquinone, which also may provide antioxidant protection.
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Affiliation(s)
- D C Liebler
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721
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Traber MG, Lane JC, Lagmay NR, Kayden HJ. Studies on the transfer of tocopherol between lipoproteins. Lipids 1992; 27:657-63. [PMID: 1487963 DOI: 10.1007/bf02536020] [Citation(s) in RCA: 71] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The net transfer of labeled alpha-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) following in vitro addition of [3,4-3H] all rac-alpha-tocopherol to plasma, or ii) from plasma obtained 12-16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4'R,8'R-alpha-[5,7-(C2H3)2]tocopheryl acetate and 2S,4'R,'R-alpha-[5-C2H3]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37 degrees C. No discrimination between stereoisomers of alpha-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (> 60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observed in vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the % HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r2 = 0.37, P < 0.05).
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Affiliation(s)
- M G Traber
- Department of Medicine, New York University School of Medicine, New York 10016
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Traber MG, Burton GW, Hughes L, Ingold KU, Hidaka H, Malloy M, Kane J, Hyams J, Kayden HJ. Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism. J Lipid Res 1992. [DOI: 10.1016/s0022-2275(20)40769-2] [Citation(s) in RCA: 64] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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Drevon CA. Absorption, transport and metabolism of vitamin E. FREE RADICAL RESEARCH COMMUNICATIONS 1991; 14:229-46. [PMID: 1874454 DOI: 10.3109/10715769109088952] [Citation(s) in RCA: 119] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Vitamin E includes eight naturally occurring fat-soluble nutrients called tocopherols and dietary intake of vitamin E activity is essential in many species. alpha-Tocopherol has the highest biological activity and the highest molar concentration of lipid soluble antioxidant in man. Deficiency of vitamin E may cause neurological dysfunction, myopathies and diminished erythrocyte life span. alpha-Tocopherol is absorbed via the lymphatic pathway and transported in association with chylomicrons. In plasma alpha-tocopherol is found in all lipoprotein fractions, but mostly associated with apo B-containing lipoproteins in man. In rats approximately 50% of alpha-tocopherol is bound to high density lipoproteins (HDL). After intestinal absorption and transport with chylomicrons alpha-tocopherol is mostly transferred to parenchymal cells of the liver were most of the fat-soluble vitamin is stored. Little vitamin E is stored in the non-parenchymal cells (endothelial, stellate and Kupffer cells). alpha-Tocopherol is secreted in association with very low density lipoprotein (VLDL) from the liver. In the rat about 90% of total body mass of alpha-tocopherol is recovered in the liver, skeletal muscle and adipose tissue. Most alpha-tocopherol is located in the mitochondrial fractions and in the endoplasmic reticulum, whereas little is found in cytosol and peroxisomes. Clinical evidence from heavy drinkers and from experimental work in rats suggests that alcohol may increase oxidation of alpha-tocopherol, causing reduced tissue concentrations of alpha-tocopherol. Increased demand for vitamin E has also been observed in premature babies and patients with malabsorption, but there is little evidence that the well balanced diet of the healthy population would be improved by supplementation with vitamin E.
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Affiliation(s)
- C A Drevon
- Institute for Nutrition Research, University of Oslo, Norway
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Traber MG, Rudel LL, Burton GW, Hughes L, Ingold KU, Kayden HJ. Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-alpha-tocopherol: studies using deuterated tocopherols. J Lipid Res 1990. [DOI: 10.1016/s0022-2275(20)42837-8] [Citation(s) in RCA: 79] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. J Lipid Res 1990. [DOI: 10.1016/s0022-2275(20)42836-6] [Citation(s) in RCA: 163] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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