Vitamins restore blood vessel performance in kids with high cholesterol

American Heart Association
Tuesday, 12 August 2003

Moderate doses of vitamins C and E can slow progression of atherosclerosis in children with a genetic predisposition to high cholesterol, according to research published in today's rapid access issue of Circulation: Journal of the American Heart Association.

This is the first randomized trial to show that moderate doses of the antioxidant vitamins can reverse endothelial dysfunction, which occurs when blood vessels aren't flexible enough to expand in response to increased blood flow. This is one of the earliest signs of atherosclerosis, says lead author Marguerite M. Engler, Ph.D., professor and vice chair of the department of Physiological Nursing at the University of California, San Francisco.

"There is evidence from epidemiological studies that diets rich in antioxidants can decrease the risk of coronary artery disease, which is why we decided to look specifically at these high-risk children," Engler says.

In the Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial, researchers studied 15 children and young adults (ages 9 to 20) with either familial hypercholesterolemia, a condition in which low-density lipoprotein (LDL or the "bad" cholesterol) – is elevated from childhood, or familial combined hyperlipidemia, which means that total cholesterol and/or triglycerides are elevated. Both conditions are associated with an increased risk for early heart attacks.

The study participants were put on the National Cholesterol Education Program (NCEP) Step II diet for six months. After six weeks on the diet, participants were randomized to daily vitamin therapy – 500 milligram (mg) of vitamin C and 400 international units (IU) of vitamin E – or placebo – for six weeks. Then there was a six-week "washout" period. After that, those in the placebo group switched to vitamin therapy while the vitamin group was given placebo for six weeks.

"The dose of vitamin C used in the study can be readily achieved with whole food, but only 20 percent of children consume the recommended five or more servings of fruit and vegetables a day," says Engler. "Rich sources of vitamin E and whole grains and nuts are also deficient in the typical American child's diet."

The vitamin doses are usually lower in multi-vitamins, which have about 60 mg of vitamin C and 30 IU of vitamin E, she says.

Endothelial function was measured using ultrasound to gauge the blood flow in an arm artery by calculating changes in the dilation of the artery [flow-mediated dilation (FMD)]. In healthy children, FMD ranges between 8 percent and 12 percent. On average, the FMD among study subjects was 5.7 percent at baseline. After antioxidant vitamin therapy and the NCEP diet, the FMD increased to an average of 9.5 percent.

"These findings have important implications because reduced FMD in the brachial (arm) artery is predictive of endothelial dysfunction in the coronary arteries and presents decades before the onset of symptomatic coronary heart disease," she says.

At baseline the average total cholesterol was 242 milligrams per deciliter (mg/dL) while LDL was 187 mg/dL, high density lipoprotein (HDL or "good" cholesterol) was 37 mg/dL and triglycerides 145 mg/dL.

The American Heart Association scientific position on cholesterol in children defines cholesterol of 200 mg/dL or higher and LDL of 130 or higher as high risk categories for heart disease in children and adolescents between age 2 and 19. The guidelines also state that HDL levels should be greater than or equal to 35 mg/dL and trigylerides levels should be less than or equal to 150 mg/dL.

Although the short-term NCEP Step II diet had no effect on endothelial dysfunction, Engler says the diet was associated with an 8 percent reduction in LDL cholesterol.

Co-authors are Mary B. Engler, Ph.D.; Mary J. Malloy, M.D.; Elisa Y. Chiu, RN, MS; Monique C. Schloetter, RD, MS; Steven M. Paul, Ph.D.; Markus Stuehlinger, M.D.; Ken Y. Lin; John P. Cooke, M.D., Ph.D.; Jason D. Morrow, M.D.; Paul M. Ridker, M.D.; Nader Rifai, Ph.D.; Elizabeth Miller; Joseph L. Witztum, M.D.; and Michele Mietus-Snyder, M.D.

The study was primarily funded by the National Institutes of Health.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org