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Journal of Lipid Research, Vol. 48, 935-943, April 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers

Robert J. Pawlosky^1,*, Joseph R. Hibbeln and Norman Salem, Jr.

^* Laboratory of Metabolic Control, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD
Laboratory of Membrane Biochemistry and Biophysics, National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD

Published, JLR Papers in Press, January 17, 2007.

¹ To whom correspondence should be addressed. e-mail: bpawl{at}mail.nih.gov

ABSTRACT

The effects of cigarette smoking on n-3 essential FA metabolism were studied in male and female subjects by fitting the concentration-time curves of the d₅-labeled plasma fatty acids (FAs) originating from a dose of d₅-18:3n-3 to a compartmental model of n-3 FA metabolism. For 3 weeks, female (smokers, n = 5; nonsmokers, n = 5) and male (smokers, n = 5; nonsmokers, n = 5) subjects subsisted on a beef-based diet. Beginning in the third week, subjects received a dose of d₅-18:3n-3 ethyl ester (1 g). Plasma FAs were analyzed using gas chromatography (GC) and GC-mass spectrometry, and the kinetic rate parameters were determined from the concentration-time curves for d₅-18:3n-3, d₅-20:5n-3, d₅-22:5n-3, and d₅-22:6n-3. Women smokers had a 2-fold greater percent of dose in plasma (5.8% vs. 2.9%; P < 0.01) and a higher fractional rate constant coefficient for formation of d₅-22:6n-3 from d₅-22:5n-3 (0.03 h^–1 vs. 0.01 h^–1; P < 0.01), compared with nonsmokers. Male smokers had elevated total plasma n-3 FAs, more-rapid turnover of 18:3n-3 (13.3 mg/day^–1 vs. 4.3 mg/day^–1; P < 0.001), a disappearance rate of d₅-20:5n-3 that was both delayed and slower (0.001 h^–1 vs. 0.012 h^–1; P < 0.05), and a percentage of d₅-20:5n-3 directed into formation of d₅-22:5n-3 (99% vs. 61%; P < 0.03) that was greater compared with nonsmokers. Smoking increased the bioavailability of n-3 FAs from plasma, accelerated the fractional synthetic rates, and heightened the percent formation of some long-chain n-3 PUFAs in men and women.

Supplementary key words linolenic acid • docosahexaenoic acid • isotope tracer • mass spectrometry • humans • kinetics • controlled diet

Abbreviations: ANCOVA, analysis of covariance; AUC, area under the concentration-time curve; CV, coefficient of variance; NS, nonsmoking subject; S, smoking subject

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