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

Pomegranate juice is thought to have a number of health benefits, from lowering cholesterol and blood pressure to protecting against some cancers, but until now there has been no evidence to demonstrate its effects on the uterus. Researchers investigated pomegranate seed extract – more highly concentrated than pomegranate juice – and its effect on uterine smooth muscle samples.

Professor Sue Wray, from the University’s Department of Physiology, said: “Previous study has suggested that the pomegranate’s antioxidant and anti-inflammatory properties have a positive impact on health. We wanted to understand its effect on uterine contractions to help us explore new ways of treating women who may experience difficult labours. Currently the only available drug to treat women with a poorly contracting uterus is oxytocin, a hormone which only works approximately 50% of the time.

“It is important for us to investigate how the uterus works and what happens when it does not contract normally so that women experiencing problems during labour do not have to undergo major surgery to deliver a healthy baby.”

Dr Sajeera Kupittayanant, from Suranaree’s Institute of Science, explains: “We found that beta-sitosterol was the main constituent of pomegranate extract, a steroid present in many plant species, but particularly rich in pomegranate seed. We added the extract to uterus tissue samples from animals and found that the muscle cells increased their activity. Our work suggests that the increase is due to a rise in calcium, which is necessary in order for any muscle to contract, but is usually affected by hormones, nerve impulses and some drug treatments.

“The next step is to investigate how beta-sitosterol in pomegranate extract could increase calcium, but it could prove to be a significant step forward in identifying new ways of treating dysfunctional labour.”

The research, published in Reproductive Sciences, will support work being conducted at a new centre dedicated to improving experiences in pregnancy and childbirth for women across the world. The Centre for Better Births will bring together researchers and clinicians to improve understanding in areas such as premature labour, recurrent miscarriage and prolonged labour.

Advice to patients: Researchers used pomegranate seed extract, which is more highly concentrated than pomegranate juice. More research is needed to understand if eating the fruit or drinking its juice has any impact on uterine contractions.

Source: Samantha Martin
University of Liverpool

The main explanation for the relatively low increase of blood fat levels with butter is that about 20 percent of the fat in butter consists of short and medium-length fatty acids. These are used directly as energy and therefore never affect the blood fat level to any great extent. Health care uses these fatty acids with patients who have difficulty taking up nutrition in other words, they are good fatty acids.

“A further explanation, which we are speculating about, is that intestinal cells prefer to store butter fat rather than long-chain fatty acids from vegetable oils. However, butter leads to a slightly higher content of free fatty acids in the blood, which is a burden on the body,” explains Julia Svensson, a doctoral candidate in Biotechnology and Nutrition at Lund University.

The greater difference in men is due to, among other things, hormones, the size of fat stores, and fundamental differences in metabolism between men and women, which was previously known. This situation complicates the testing of women, since they need to be tested during the same period in the menstruation cycle each time in order to yield reliable results.

“The findings provide a more nuanced picture of various dietary fats. Olive oil has been studied very thoroughly, and its benefits are often extolled. The fact that butter raises blood cholesterol in the long term is well known, whereas its short-term effects are not as well investigated. Olive oil is good, to be sure, but our findings indicate that different food fats can have different advantages,” emphasizes Julia Svensson.

“Finally, all fats have high energy content, and if you don’t burn what you ingest, your weight will go up, as will your risk of developing diseases in the long run,” she reminds us.

Here’s how the test was done: 19 women and 28 men participated in the study. Each individual ate three test meals containing canola-flaxseed oil, butter, or olive oil. The day before the test they had to fast after 9 p.m. The following morning a fasting blood sample was drawn to check their health status and all blood fats. The test meal consisted of the test fat mixed into hot cream of wheat, 1.5-% milk, blackberry jam, and a slice of bread with ham. The meal contained 35 g of test fat and about 810 Kcal. Blood samples were then drawn 1, 3, 5, and 7 h after the meal, and all blood fats were analyzed. The participants fasted during the day.

Julia Svensson is on parental leave until April. When she returns she will primarily finish studying how women react to various fats.

She and her colleagues will also be studying whether fats lead to varying degrees of satiety. What’s more, they will be evaluating parameters such as hormone status, exercise, waist measurement, and how the daily diet otherwise affects how the body takes up fat after a meal.

Source: Expertanswer

More importantly, according to two new studies led by a University of Utah human geneticist, fruit flies use the same molecular mechanisms as humans to help maintain proper balances of cholesterol and a key form of stored fat that contributes to obesity. The findings mean that as researchers try to learn more about the genetic and biological processes through which people regulate cholesterol and fat metabolism, the humble fruit fly, also called Drosophila, can teach humans much about themselves.

“Not a lot is known about these regulatory mechanisms in people,” says Carl S. Thummel, Ph.D., professor of human genetics at the U of U School of Medicine and senior author on the two studies. “But we can learn a lot by studying metabolic control in fruit flies and apply what we learn to humans.”

High cholesterol and obesity, which affects an estimated 25 percent to 30 percent of the U.S. population, are linked to heart disease, diabetes, and other diseases that take huge tolls on health and add billions of dollars to the nation’s medical bills. Understanding the processes that regulate cholesterol and fat in humans could be critical for addressing those health risks in people, Thummel believes.

The two studies identify a nuclear receptor, DHR96, which plays a critical role in regulating the balance or homeostasis of cholesterol and another fat molecule called triacylglycerol (TAG). Nuclear receptors are proteins that sense the presence of chemical compounds within cells. DHR96 corresponds closely to a nuclear receptor in humans, called LXR, that is known to regulate cholesterol levels.

In a study published Dec. 2 in Genes & Development, Thummel and colleagues at the U of U and two Canadian universities show that DHR96 helps regulate cholesterol in fruit flies by binding with this compound. When this binding occurs, it allows DNA to be read, which switches genes on and off that help maintain proper levels of cholesterol, according to Thummel, who also holds an H.A. and Edna Benning Presidential Endowed Chair in Human Genetics.

The researchers used a technique developed by University of Utah biologist Kent Golic, Ph.D., in which they silenced or disabled the DHR96 protein so it couldn’t function in fruit flies. They then grew flies in which DHR96 was silenced. Depending on what the fruit flies were fed, lean or fat diets, they had either too little or too much cholesterol. Flies fed too little cholesterol died, while those with too much developed hypercholesterolemia or chronically excessive cholesterol levels. At the same time, flies in which DHR96 functioned normally maintained a proper level of cholesterol.

“When they lacked the DHR96 receptor, the flies were unable to maintain cholesterol homeostasis,” Thummel says. “This is similar to what happens in humans who have high cholesterol levels.”

Fruit flies are good for such research insights in large part because of the insects’ short life span – about 30 days – meaning their development and biological processes are more easily observed than in other, longer-lived models, such as mice. Fruit flies also are easy to manipulate genetically and are less expensive to study compared to mice or other models, according to Thummel. In addition, the mechanisms by which metabolism is controlled in fruit flies are very similar to those in mice or humans.

“We can do a lot more mechanistic studies in a fly than are possible in a mouse,” he says. “We can study metabolic pathways faster and more in-depth.”

Along with its important role in helping to maintain proper levels of cholesterol, DHR96 also plays an integral part in regulating dietary fat metabolism, Thummel and another U of U researcher report in a Dec. 2 study in Cell Metabolism.

In flies in which DHR96 was silenced, TAG levels were markedly reduced in the intestine, making the insects resistant to diet-induced obesity. But when DHR96 was overexpressed, meaning there were higher levels of the protein, it led to increased TAG levels and made the flies more prone to being overweight. These findings show that DHR96 is required for breaking down dietary fat in the intestine of fruit flies and provide insight into how dietary fat metabolism is regulated in Drosophila.

“This nuclear receptor plays a major role in sensing and regulating cholesterol and TAG uptake in the intestine in fruit flies,” Thummel says. “It functions similarly to the way LXR functions in humans, although we have a relatively poor understanding about how LXR controls these pathways.”

In his future studies, Thummel intends to learn more about how DHR96 regulates metabolism by studying the functions of the genes that it controls.

Source: Phil Sahm
University of Utah Health Sciences

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

Selenium is a trace essential mineral with anti-oxidant properties. The body naturally absorbs selenium from foods such as vegetables, meat and seafood. However, when the balance is altered and the body absorbs too much selenium, such as through taking selenium supplements, it can have adverse affects.

A team led by Dr Saverio Stranges at the University’s Warwick Medical School has found high levels of selenium are associated with increased cholesterol, which can cause heart disease.

In a paper recently published in the Journal of Nutrition, the research team examined the association of plasma selenium concentrations (levels of selenium in the blood) with blood lipids (fats in the blood).

The researchers found in those participants with higher plasma selenium (more than 1.20 µmol/L) there was an average total cholesterol level increase of 8% (0.39 mmol/L (i.e. 15.1 mg/dL). Researchers also noted a 10% increase in non-HDL cholesterol levels (lipoproteins within your total cholesterol that can help predict the risk of someone suffering a heart attack or chest pain). Also, of the participants with the highest selenium levels, 48.2% admitted they regularly took dietary supplements.

The study was conducted among 1042 participants aged 19-64 in the 2000-2001 UK National Diet and Nutrition Survey. All participants were interviewed face-to-face to assess lifestyle factors such as diet and drinking habits. Blood samples were then taken for analysis.

Dr Saverio Stranges said although high selenium levels were not exclusively caused by people taking dietary supplements, the results of the study were concerning because the use of selenium dietary supplements had risen considerably in the UK in recent years. He said this was largely due to the perception that selenium can reduce the risk of cancer and other diseases.

He said: “This use has spread despite a lack of definitive evidence on selenium supplements efficacy for cancer and other chronic disease prevention. The cholesterol increases we have identified may have important implications for public health. In fact, such a difference could translate into a large number of premature deaths from coronary heart disease.

“We believe that the widespread use of selenium supplements, or of any other strategy that artificially increases selenium status above the level required is unwarranted at the present time. Further research is needed to examine the full range of health effects of increased selenium, whether beneficial or detrimental.”

Source: Kelly Parkes-Harrison
University of Warwick