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Vitamin E kinetics in smokers

Institution: University of California, Davis
Investigator(s): Maret Traber, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0160 Award: $332,110
Subject Area: General Biomedical Science
Award Type: Research Project Awards

Initial Award Abstract
The purpose of this study is to measure how much vitamin E humans utilize daily and whether people who smoke cigarettes use more vitamin E.

Why should cigarette smoking use up vitamin E? Both smokers and non-smokers have similar vitamin E concentrations in their blood (plasma). So it would seem that smoking has no effect on plasma vitamin E levels. However, if plasma is directly exposed to smoke in a test tube, the vitamin E is used up. This seems contradictory - how can cigarette smoke destroy the vitamin E in test tubes, but not in people? This study focuses on this paradox. Thc answer may be that cigarette smoking actually uses up the vitamin E in the body, but the body replaces it from its stores.

The specific questions to be addressed in this project are as follows: does cigarette smoking increase the use of plasma vitamin E in vivo? Are there regulatory mechanisms that increase plasma vitamin E in response to oxidative stress? Do different forms of vitamin E have different susceptibilities to cigarette smoke in vivo?

The rate of vitamin E use will be measured in smokers and non-smokers in two different trials. In the first trial, non-smokers and smokers will be given vitamin E labeled with deuterium, a stable (non-radioactive) isotope of hydrogen. This will allow us to track how much vitamin E comes in and goes out of the circulation. Thc labeled vitamin E will be taken daily for 1 week; and blood samples will be taken daily during vitamin E administration and for the subsequent week, then biweekly for 30 days. In the second trial, non-smokers and smokers will be given three different forms of vitamin E with differing amounts of deuterium, administered with breakfast in a single gelatin capsule: a natural form of -tocopherol, a synthetic form of -tocopherol; and a natural form of -tocopherol. This second trial will investigate in detail the ability of the liver to maintain plasma vitamin E levels. In addition, we will test whether smoking specifically destroys -tocopherol. Urine samples will be collected in both trials to measure vitamin E metabolites. The appearance and disappearance of the deuterated tocopherols from plasma will be calculated using computer-assisted models. Statistical comparisons will be made between smokers and non-smokers for each of the forms of Vitamin E.

We expect that if there is increased "oxidative stress" in smokers, then vitamin E use should be higher in smokers than in non-smokers. This will be tested in trial 1. In trial 2, different forms of vitamin E will be used to measure the release of vitamin E (stored in the liver) into the circulation. In addition, this second trial will measure how much -tocopherol the body uses. This is important because -tocopherol is a major dietary form of vitamin E and -tocopherol has been shown to be a precursor of a kidney hormone.

The information obtained from this study will indicate the daily requirements for vitamin E in normal subjects and will demonstrate if cigarette smoking increases the daily requirement for vitamin E. The data will also indicate if dietary supplementation is warranted for smokers.

Micronutrient antioxidants and smoking
Periodical: British Medical Bulletin Index Medicus:
Authors: Cross CE, Traber MG, Eiserich J, van der Vliet A ART
Yr: 1999 Vol: 55 Nbr: Abs: Pg: 691-704

Tobacco-related diseases. Is there a role for antioxidant micronutrient supplementation?
Periodical: Clinics in Chest Medicine Index Medicus:
Authors: Traber MG, van der Vliet A, Reznick AZ, Cross CE ART
Yr: 2000 Vol: 21 Nbr: Abs: Pg: 173-187

Quantitative analysis by lquid chromatography-tandem mass spectrometry of deuterium-labeled and unlabeled vitamin E biological samples
Periodical: Analytical Biochemistry Index Medicus:
Authors: Lauridsen C, Leonard SW, Griffin DA, McLure T, Liebler D, Traber MG ART
Yr: 2001 Vol: 289 Nbr: Abs: Pg: 89-95

Apha- and y-Tocotrienols are metabolized to carboxyethyl-hydroxychroman (CEHC) derivatives and excreted in human urine
Periodical: Lipids Index Medicus:
Authors: Lodge JK, Riddlington J, Vaule H, Leonard SW, Traber MG ART
Yr: 2001 Vol: 36 Nbr: Abs: Pg: 43-48

A rapid method for the extraction and determination of vitamin E metabolites in human urine.
Periodical: Journal of Lipid Research Index Medicus:
Authors: Lodge JK, Traber MG, Elsner A, and Brigelius-Flohe R ART
Yr: 2000 Vol: 41 Nbr: Abs: Pg: 148 - 154

Antioxidant supplementation decreases lipid peroxidation biomarker F2-Isoprostane in plasma of smokers.
Periodical: Cancer Epidemiology Biomarkers and Prevention Index Medicus:
Authors: Dietrich M, Block G, Hudes M, Morrow J, Norkus e, Traber MG, et al. ART
Yr: 2002 Vol: 11 Nbr: Abs: Pg: 7 - 13

Vitamin E Kinetics in smokers and non-smokers.
Periodical: Free Radical Biology and Medicine Index Medicus:
Authors: Traber MG, Winklhofer-Roob BM, Roob JM, Khoschsorur G, Aigner R, Cross C, et al. ART
Yr: 2001 Vol: 31 Nbr: Abs: Pg: 1368 - 1374

Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid.
Periodical: Toxicology Index Medicus:
Authors: Nardini M, Finkelstein EI, Reddy S, Valacchi G. Traber M, Cross CE, et al. ART
Yr: 2002 Vol: 170 Nbr: 3 Abs: Pg: 173 - 185

iNOS-inductin by LPS or 03-exposure is attenuated in TTP knockout mice.
Periodical: Free Radical Biology and Medicine Index Medicus:
Authors: Schock BC, Corbacho AM, Leonard S, Obermueller-Jevic UC, Yalacchi G, et al. ART
Yr: 2001 Vol: 31 Nbr: 10 Abs: Pg: S37