The results, based on a 10-week study of 72 healthy volunteers with mildly elevated cholesterol levels, are published in the March 8 issue of the American Heart Association’s journal Arteriosclerosis, Thrombosis and Vascular Biology (available online at http://www.atvbaha.org).

‘Lowering LDL cholesterol is a well-accepted means of reducing the likelihood of heart disease,’ said Sridevi Devaraj, an assistant professor of pathology and investigator in the Laboratory for Atherosclerosis and Metabolic Research at UC Davis Medical Center who led the sterol study.

‘Fortifying orange juice with plant sterols is an easy and effective way to boost a diet’s LDL-fighting power in individuals with mildly elevated cholesterol levels.

‘Fifty percent of Americans have mildly elevated cholesterol levels, defined as having a total cholesterol reading of more than 200 mg/dL. The inclusion of sterols in orange juice offers an important treatment option without increasing saturated fat and at the same time providing vitamin C, flavonoids and other essential nutrients.’

The American Heart Association and National Cholesterol Education Program recommend a diet that is low in saturated fat and cholesterol and rich in soluble fiber and plant sterols to help individuals reduce their risk of heart disease.

Sterols are present in small quantities in a variety of foods, including fruits, vegetables, nuts, seeds, cereals and legumes. Chemically similar to cholesterol, sterols are thought to lower LDL levels in the body by limiting absorption of cholesterol in the intestine.

The UC Davis study is the first to show the cholesterol-reducing effects of plant sterols in a nonfat beverage.

For the study, the UC Davis researchers enrolled healthy volunteers ages 20 to 73 with mildly elevated cholesterol levels. The volunteers were asked to eat their normal diet but to drink a cup of juice along with whatever they had for breakfast and dinner.

Half of the group had the sterol-fortified orange juice while the others drank regular orange juice by the same manufacturer. Fasting blood tests were taken before and after the study to determine total cholesterol, total triglyceride, LDL cholesterol, high-density lipoprotein cholesterol and apolipoprotein B levels.

‘Volunteers who drank the sterol-fortified orange juice had a 7.2-percent decrease in total cholesterol, 12.4-percent decrease in LDL cholesterol, and 7.8-percent decrease in non-high-density lipoprotein levels compared to baseline and to the group that received the non-sterol orange juice group,’ she said.

‘Orange juice has wide appeal since it is consumed by individuals of all ages, from early childhood to old age. And for individuals who do not want to take a drug for mildly elevated cholesterol, this may provide a healthy and attractive alternative.’

Previous studies at other institutions have evaluated plant sterols in yogurt and other low-fat and non-fat foods, with variable results. The UC Davis study may be unique in that it did not place volunteers on a special diet and only asked that they drink the juice with their normal meals.

‘The fat in the meals may have helped to emulsify the sterols, but further research will need to be done to determine the meal’s relevance,’ said Ishwarlal Jialal, professor of pathology and internal medicine and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis Medical Center.

‘We also would like to investigate whether sterols can add to the LDL-reducing effects of statin drugs in higher-risk individuals. Sterol-fortified orange juice could potentially enable more patients to meet cholesterol level goals as outlined by the National Cholesterol Education Program.’

This study was supported with grants from National Institutes of Health and Minute Maid –The Coca Cola Company.

Contact: Carole Gan
carole.gan@ucdmc.ucdavis.edu
916-734-9047
University of California, Davis – Medical Center

The study was the work of Dr Pia R Kamstrup, of Herlev Hospital, Copenhagen University Hospital in Herlev, Denmark, and colleagues, and is published in the 10 June issue of the Journal of the American Medical Association, JAMA.

Despite the fact that statins are now routinely used to lower levels of low-density lipoprotein (LDL, or “bad” cholesterol), myocardial infarction (MI or heart attack) remains a leading cause of illness and death, wrote the authors.

There is a need to identify other risk factors as targets for treatment they said. Lipoprotein (a), a cholesterol that is not included in routine cholesterol screening, has been suggested as a potential candidate, but there is not enough evidence of how closely it is linked to heart attack risk.

Lipoprotein (a) levels vary from person to person, sometimes the level in one person can be thousands of times higher or lower than the level in another person, the range is so vast. This is partly determined by genetics, and the variations in one gene in particular, known as the “Lipoprotein (a) kringle IV type 2 (LPA KIV-2) size polymorphism genotype”. The authors wrote in their background information that the number of KIV-2 repeats is already known to correlate inversely with levels of lipoprotein(a).

For the study, Kamstrup and colleagues looked at whether genetically elevated levels of lipoprotein (a) were linked to increased risk of heart attack (MI) in three studies covering about 45,000 white individuals from Copenhagen who started giving samples in 1976 until 2007.

The researchers found that risk of MI increased with increasing levels of lipoprotein (a), and with “decreasing numbers of lipoprotein(a) KIV-2 repeats associated with elevated levels of lipoprotein(a)”.

They saw a consistent increase in MI risk linked to genetically elevated levels of lipoprotein (a) in all three studies, and noted that the KIV-2 genotype explained 21 per cent and 27 per cent of the total lipoprotein (a) concentrations in two of the three studies.

Kamstrup and colleagues wrote that:

“Instrumental variable analysis (in which the increase in lipoprotein (a) levels explained by the KIV-2 genotype was related to MI) directly demonstrated that genetically elevated lipoprotein (a) is associated with increased risk of MI, like elevations in plasma lipoprotein (a).”

They suggested that while the findings appear strong enough to show that the higher levels of lipoprotein (a) probably caused the increased risk of MI, final proof should still be sought using randomized clinical trials that show MI risk going down in response to therapies that lower lipoprotein (a).

In an accompanying editorial, Drs George Thanassoulis and Christopher J. O’Donnell of the National Heart, Lung and Blood Institute’s Framingham Heart Study, commented that although Kamstrup and colleagues revealed some “interesting mechanistic insights” into the biological link between lipoprotein (a) and MI, and put forward evidence that there might be potential benefit in reducing lipoprotein (a) early in life, the “clinical implications are quite limited”.

“These results do not provide the necessary evidence that genetic testing of the LPA locus or measurements of plasma lipoprotein(a) have a role in cardiovascular risk stratification or decisions regarding lipid-lowering therapy,” they wrote, agreeing with the authors in that “ultimately, despite nature’s best efforts to provide causal evidence for lipoprotein(a), only a true randomized controlled trial demonstrating reductions in MI with targeted lipoprotein(a)-lowering therapy can provide the evidence for benefits and risks of an lipoprotein(a)-lowering strategy”.

“Genetically Elevated Lipoprotein(a) and Increased Risk of Myocardial Infarction.”
Pia R. Kamstrup; Anne Tybjaerg-Hansen; Rolf Steffensen; Borge G. Nordestgaard.
JAMA, 2009;301(22):2331-2339.
Vol. 301 No. 22, June 10, 2009

Written by: Catharine Paddock, PhD
Copyright: Medical News Today

The analysis of this large Atherosclerosis Risk in Communities (ARIC) Study, which appears in the August issue of Journal of Lipid Research, was carried out by Keri Monda and colleagues at North Carolina and Baylor. They found that over a 12 year period, all individuals who increased their exercise by about 180 metabolic units per week (equivalent to an additional hour of mild or 30 minutes of moderate activity per week) displayed decreased levels of triglycerides and increased levels of the “good” HDL cholesterol. However, statistically significant decreases in the “bad” LDL cholesterol were only observed in women, with particularly strong effects in menopausal women and African-American women. And total cholesterol levels were only significantly decreased in African-American women.

The authors speculate that these novel differences may arise from hormonal differences between the sexes, especially considering the extra effects seen post-menopause. The racial differences observed may stem from genetic variations that require further exploration.

The authors do also note that their exercise data was assessed by questionnaire and this was non-scientific, though the particular methodology used has been extremely reliable in other studies. They also note that all evaluated participants were healthy, so these results cannot be generalized to individuals with diabetes or those on cholesterol-lowering medications.

From the article: Longitudinal impact of physical activity on lipid profiles in middle-aged adults: the Atherosclerosis Risk in Communities Study, by Keri L. Monda, Christie M. Ballantyne and Kari North

Source:
Nick Zagorski
American Society for Biochemistry and Molecular Biology