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(Circulation. 2001;103:2922.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Oxygenated Carotenoid Lutein and Progression of Early Atherosclerosis

The Los Angeles Atherosclerosis Study

James H. Dwyer, PhD; Mohamad Navab, PhD; Kathleen M. Dwyer, PhD; Kholood Hassan, BSc; Ping Sun, PhD; Anne Shircore, MSc; Susan Hama-Levy, BSc; Greg Hough, MSc; Xuping Wang, MD; Thomas Drake, MD; C. Noel Bairey Merz, MD; Alan M. Fogelman, MD

From the Department of Preventive Medicine (Institute for Prevention Research), Keck School of Medicine, University of Southern California (J.H.D., K.M.D., P.S., A.S.); the Departments of Medicine (M.N., K.H., S.H.-L., G.H., X.W., T.D., A.M.F.) and Laboratory and Experimental Pathology (T.D.), School of Medicine, University of California Los Angeles; and the Division of Cardiology, Department of Medicine, Cedars Sinai Medical Center (C.N.B.M.), Los Angeles, Calif.

Correspondence to Professor J. Dwyer, University of Southern California, 1000 S Fremont Ave, Unit 8, Alhambra, CA 91803. E-mail jimdwye{at}hsc.usc.edu

Background—Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease. The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis.

Methods and Results—Epidemiology: Progression of intima-media thickness (IMT) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a randomly sampled cohort of utility employees age 40 to 60 years (n=480). Coculture: The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima. Mouse models: The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein (0.2% by weight) and LDL receptor–null mice to Western diet or Western diet plus lutein. IMT progression declined with increasing quintile of plasma lutein (P for trend=0.007, age-adjusted; P=0.0007, multivariate). Covariate-adjusted IMT progression (mean±SEM) was 0.021±0.005 mm in the lowest quintile of plasma lutein, whereas progression was blocked in the highest quintile (0.004±0.005 mm; P=0.01). In the coculture, pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner (P<0.05). Finally, in the mouse models, lutein supplementation reduced lesion size 44% in apoE-null mice (P=0.009) and 43% in LDL receptor–null mice (P=0.02).

Conclusions—These epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.

Key Words: atherosclerosis • epidemiology • carotid arteries • ultrasonography • diet • lutein

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