Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial
Abstract
BACKGROUND: Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide. CONCLUSIONS: Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.
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In patients with diabetes or metabolic syndrome, fitness is inversely associated with inflammation, independent of fatness.
“Studies in patients with diabetes (237) or the metabolic syndrome (238,239) have consistently demonstrated inverse associations between fitness and inflammation, independently of fatness.”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [237]
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References 49 · Cited by 253
- Authors
- Engler, M. M., Engler, M. B., Malloy, M. J., Chiu, E. Y., Schloetter, M. C., Paul, S. M., Stuehlinger, M., Lin, K. Y., Cooke, J. P., Morrow, J. D., Ridker, P. M., Rifai, N., Miller, E., Witztum, J. L., & Mietus-Snyder, M.
- Affiliations
- Brigham and Women's Hospital (US)
- From the University of California at San Francisco (M.M.E., M.B.E., M.J.M., E.Y.C., M.C.S., S.M.P., M.M.-S.), San Francisco, Calif; University Clinic of Innsbruck (M.S.), Division of Cardiology, Innsbruck, Austria; Stanford University (K.Y.L., J.P.C.), Division of Cardiovascular Medicine, Stanford, Calif; Vanderbilt University Medical Center (J.D.M.), Division of Clinical Pharmacology, Nashville, Tenn; Harvard Medical School (P.M.R., N.R.), Brigham & Women’s Hospital, Boston, Mass; and the...
- ORCID
- Venue
- Circulation
- Published
- 2003-09-02
- Volume
- 108
- Issue
- 9
- Pages
- 1059-1063
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2129380027
- Cited by
- 253
- References
- 49
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 9 · 2021: 3 · 2020: 2 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 12 · 2013: 11 · 2012: 16
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Deutsches Krebsforschungszentrum
- National Institutes of Health
- U.S. Public Health Service (M01 00079)
- University of California, San Francisco
- National Institute of Nursing Research (R56NR004902, NR 04902)
- National Institute of General Medical Sciences (GM 15431)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 48831, R01DK048831)
- National Center for Research Resources (M01 RR 01271, M01RR001271)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin C, vitamin E, antioxidant therapy, endothelial function, hyperlipidemia, children, familial hypercholesterolemia, familial combined hyperlipidemia, flow-mediated dilation, oxidative stress, inflammation, atherosclerosis, oxidized LDL autoantibodies, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, C-reactive protein, asymmetric dimethylarginine
- MeSH terms
- Adolescent, Adult, Antioxidants, Ascorbic Acid, Brachial Artery, Child, Double-Blind Method, Endothelium, Vascular, Female, Humans, Hyperlipidemias, Male, Vasodilation, Vitamin E, Cross-Over Studies
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