Vitamins C and E Improve Cardiovascular Health in Children With High Cholesterol

August 11, 2003
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An estimated 50 million children have high levels of the "bad" cholesterol -- known as LDL -- that puts them at high risk for suffering heart attacks as adults. Most of these children have inherited disorders causing these abnormal cholesterol levels. Because prescription drugs that successfully lower cholesterol levels in adults are not usually recommended for use in children, scientists have begun to look at possible dietary interventions for children with these disorders.

In a study appearing in the August 11 online edition of Circulation, a UCSF-led team of researchers reports that adding antioxidant vitamin supplements to the diets of children with inherited lipid disorders increased their cardiovascular health. "When we gave these children moderate doses of vitamins C and E for six weeks, we saw a significant improvement in blood-vessel function, which is an important indicator of cardiovascular health" said lead author, Marguerite M. Engler, Ph.D., R.N., UCSF professor and vice chair of physiological nursing.

The findings, to published in the September 2 print issue of the journal, are the first to be reported from the EARLY (Endothelial Assessment of Risk from Lipids in Youth) trial, a five-year study sponsored by the National Institute of Nursing Research (NINR). The goal of the study is to determine whether or not dietary interventions can improve cardiovascular health in children with inherited hyperlipidemias, the genetic disorders that cause abnormally high cholesterol levels.

"The findings of this study suggest hope for children with abnormally high cholesterol levels that their condition can be improved through vitamin supplements," said NINR'S director, Patricia Grady, Ph.D., R.N., F.A.A.N. "We look forward to additional research from the EARLY project, which is designed to uncover and verify ways to promote lipid control in this difficult to treat population," Grady said.

Over the years, large population studies have revealed that diets rich in fresh fruits and vegetables lower the risks of heart attack and strokes in adults. Engler and her colleagues predicted that, when given as vitamin supplements, the antioxidants normally found in fruits and vegetables might benefit children with high cholesterol. "We wanted to see if vitamin supplements could improve cardiovascular health in children at high risk of heart disease," said Engler, who serves as principal investigator for the EARLY study.

Engler and her colleagues looked at cardiovascular health by measuring the function of the endothelium, or inner lining of the blood vessels. Normally, this lining releases nitric oxide which allows the blood vessels to open, or dilate. When the lining releases too little nitric oxide, blood vessels are more constricted and blood flow is reduced. Endothelial dysfunction is a precursor to atherosclerosis, or the plaque build-up characteristic of cardiovascular disease. Endothelial function can be easily measured using ultrasound of a major artery in the arm, called the brachial artery. "These measurements are good indicators of blood vessel function in the heart," Engler said.

For the current study, researchers measured endothelial function in 15 subjects with inherited lipid disorders: seven females and eight males between the ages of 9 and 20. All received nutritional counseling and were put on the National Cholesterol Education Program Step II diet, a diet low in saturated fats and cholesterol, for the duration of the six-month study.

After the first six-week period, the children were randomly given either 500 mg of vitamin C and 400 IU of vitamin E per day or placebos for six weeks. They then went through a six-week washout period in which they got neither vitamin nor placebo supplements. In the final six weeks, the participants received whichever treatment they had not received during the randomized portion of the study. A single investigator who was blinded to each participant's assigned group measured endothelial function in the brachial artery of the arm using ultrasound every six weeks.

Researchers found that the NCEP Step II diet had no effect on endothelial dysfunction, but it was associated with an 8 percent reduction in LDL cholesterol. The addition of vitamin supplements, however, did improve endothelial function, on average, to normal levels found in healthy children. "The impact was quite significant," Engler said.

"These results are encouraging and, if confirmed in further studies, we may be able to improve the cardiovascular health of children with inherited lipid disorders using vitamin supplements," she added.

Additional authors included Mary B. Engler, Ph.D., R.N., UCSF professor of physiological nursing; Dr. Mary Malloy, UCSF clinical professor of medicine and pediatrics; Elisa Y. Chiu, R.N., M.S., UCSF clinical nurse coordinator; Monique C. Schloetter, R.D., M.S., UCSF research dietitian; Steven M. Paul, Ph.D., UCSF senior statistician; and Dr. Michele Mietus-Snyder, UCSF project director and adjunct associate professor of physiological nursing; Dr. Markus Stuehlinger, University Clinic of Innsbruck, Austria; Ken Y. Lin and Dr. John P. Cooke, Ph.D., of Stanford University; Dr. Jason D. Morrow of Vanderbilt University Medical Center; Dr. Paul M. Ridker and Nader Rifai, Ph.D., of Harvard University; Elizabeth Miller and Dr. Joseph L. Witztum of the University of California, San Diego.

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