Xanthohumol in lab tests lowers cholesterol, blood sugar and weight gain

 A recent study at Oregon State University has identified specific intake levels of xanthohumol, a natural flavonoid found in hops, that significantly improved some of the underlying markers of metabolic syndrome in laboratory animals and also reduced weight gain.

The findings were published in a special issue of Archives of Biochemistry and Biophysics that was focused on “Polyphenols and Health,” and they suggest a possible new approach to issues such as human obesity, high cholesterol and elevated glucose.

Combinations of these problems, collectively known as metabolic syndrome, are linked to some of the major health issues and causes of death in the developed world today - especially cardiovascular disease and type-2 diabetes.

In this research, laboratory mice were fed a high-fat diet, and given varying levels of xanthohumol. Compared to animals given none of this supplement, the highest dosage of xanthohumol given to laboratory rats cut their LDL, or “bad” cholesterol 80 percent; their insulin level 42 percent; and their level of IL-6, a biomarker of inflammation, 78 percent.

Because they were still growing, eating a rich diet, gaining weight and becoming obese, the weight of the lab animals increased, but by 22 percent less in those receiving xanthohumol, even though all animals ate the same amount of food. Intake of xanthohumol appears to increase their oxygen consumption and metabolic rate, with implications for weight control.

“This is the first time we’ve seen one compound with the potential to address so many health problems,” said Cristobal Miranda, a research assistant professor with OSU’s Linus Pauling Institute and lead author on this study. “These were very dramatic improvements.”

More research will be required to show safety and efficacy in humans, the researchers said.

“Work is still needed to further demonstrate the safety of high doses of xanthohumol, but dosages 15-30 times higher than we used have already been given to animals with no apparent problems,” said Fred Stevens, a professor in the OSU College of Pharmacy, principal investigator with the Linus Pauling Institute, and corresponding author on the research.

“After further study, this might provide an effective treatment for metabolic syndrome at a very low cost.”

This study for the first time also identified one of the mechanisms of action of xanthohumol – it appears to decrease plasma levels of PCSK9, a protein that plays a role in cholesterol levels. Lowering levels of PCSK9 should increase the clearance of LDL cholesterol from the blood.

Metabolic syndrome is defined by clinical diagnosis of three or more of several conditions, including abdominal obesity, elevated lipids, high blood pressure, pro-inflammatory state, a pro-thrombotic state, and insulin resistance or impaired glucose tolerance. About 25-34 percent of the adults in the United States meet these criteria, putting them at significantly increased risk for cardiovascular disease and type-2 diabetes.

Direct health care costs arising from obesity or related disorders account for up to 10 percent of U.S. health care expenditures, the researchers noted in their study.

Xanthohumol has been the subject of considerable research for its potential health benefits, as have other flavonoids such as those found in tea, garlic, chocolate, apples and blueberries.

Xanthohumol is found naturally in hops and beer, but the highest level used in this research was 60 milligrams per kilogram of body weight per day. This corresponds to a human equivalent dose of 350 milligrams per day for a 70-kilogram person, which far exceeds any amount that could be obtained by ordinary dietary intake. A level that high would equate to a beer intake of 3,500 pints per day for a human adult.

However, that amount of xanthohumol could readily be obtained in a dietary supplement that could be taken once a day.

This work was supported by the Linus Pauling Institute; OSU College of Pharmacy; Hop Steiner, Inc.; the Buhler-Wang Research Fund; and the National Institutes of Health.

How Would You Feel If You Could See the Invisible?

With over half the population of England with high cholesterol, HEART UK- The Cholesterol Charity - has partnered up with Flora ProActiv on a campaign to get cholesterol checked for National Heart Month. High cholesterol is a major risk to heart disease as it contributes to the narrowing of vital arteries which can lead to a heart attack or stroke. There are no obvious signs or symptoms with high cholesterol and HEART UK and Flora ProActiv have teamed up to prompt people to check their cholesterol levels.

For most people, there are simple and effective ways to lower cholesterol which includes changes to diet and lifestyle. Eating healthier, including super cholesterol busting food like plant sterols and getting more active helps lower cholesterol and most people will see an effect in as little as 3 weeks.

The facts you need to know about cholesterol:

•         High cholesterol is invisible, it has no symptoms but is a major risk factor for heart disease

•         One in every two people in England have elevated cholesterol – it is vital to get checked and keep your heart healthy

•         Do you know your number? Ask your GP or local pharmacist and get checked this February

What if you could see inside your arteries?

To bring the effects of cholesterol to life, HEART UK and Flora ProActiv took to the London Underground. By illustrating what is unseen in the body as cholesterol blocks the arteries, commuters had their journeys disrupted on the escalators to make them aware. 

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Menstrual Cycle Affects Cholesterol Levels

Blood cholesterol levels ebb and flow according a woman's menstrual cycle, and screening tests should be timed accordingly for the most accurate results, National Institutes of Health researchers report online in The Journal of Clinical Endocrinology and Metabolism.
In their study, total cholesterol levels varied by close to 20% over the course of women's cycles, and this was even more pronounced among obese women over 40.
"Cholesterol levels are the highest in the first half of the cycle and then after ovulation, they start to go down," says study researcher Sunni L. Mumford, PhD, of the epidemiology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Rockville, Md. "Cholesterol testing should be done at the same time of your cycle each month."

-Treatment decisions should be based on the most accurate readings.
Estrogen Affects Cholesterol Levels
The researchers measured levels of the female sex hormone estrogen, cholesterol, and other blood fats called triglycerides in 259 healthy women aged 18 and 44. They took as many as 16 measurements from the women over the course of two menstrual cycles. Study participants also charted their own ovulation using at-home fertility tests.
As the level of estrogen rises, HDL "good" cholesterol increases and peaks at ovulation. Total cholesterol, LDL "bad" cholesterol, and triglycerides dropped as estrogen levels rose. Estrogen is thought to stave off heart disease, which is why a woman's risk rises after menopause when her natural supply of the hormone diminishes.
High cholesterol levels are a known risk factor for heart disease. Total cholesterol of less than 200 milligrams per deciliter of blood (mg/dL) is considered desirable; cholesterol between 200 and 239 mg/dL is borderline high. Total cholesterol of 240 mg/dL or above is considered high, according to the National Heart, Lung, and Blood Institute.
Just 5% of women consistently had total cholesterol levels greater than 200 mg/dL at all study visits, but cholesterol levels among 19.7% of the women reached 200 mg/dL at least once.

-Cholesterol Screening for Women
"We used to give cholesterol screens in the morning when people have fasted, and now we probably need to add another layer and that is knowing where they are in their menstrual cycle," says Marc Lewis, MD, service chief of the Women's Health Services at Henry Ford Hospital in Detroit. "Not timing cholesterol screening tests with the menstrual cycle may mean that we are overtreating women and increasing their risk of drug side effects and costs for no reason."
The new study is "fascinating and important," says Marianne J. Legato, MD, a professor of clinical medicine at Columbia University College of Physicians and Surgeons in New York City and the founder and director of the Partnership for Women's Health at Columbia University.
"If it is true that cholesterol varies with a woman's menstrual cycle, then treatment decisions should be tailored accordingly," she says. "This is more evidence that we can’t use men as the norm when developing cut-off points and standards of care," she says. "We must study women directly."

**Article in WebMD

No firm conclusions about HDL cholesterol can be drawn from JUPITER sub-analysis

In the Lancet study, Paul Ridker and colleagues, from Brigham and Women’s Hospital (Boston, MA, USA), undertook a retrospective post-hoc analysis of the JUPITER trial. The results show that if a normal, healthy individual has level of low density lipoprotein (LDL), known as “bad cholesterol”, substantially lowered with a potent statin, then the level of HDL “good cholesterol” in that person no longer bears any relation to the remaining cardiovascular risk.

The original JUPITER trial was designed to answer the critical question of whether rosuvastatin prevents cardiovascular disease among healthy people with normal LDL cholesterol levels, but increased levels of high-sensitivity C-reactive protein, a marker of chronic low level inflammation, considered a new risk factor for cardiovascular events.

The current Lancet study showed that when 17,802 subjects were divided into quartiles of HDL cholesterol concentrations, HDL cholesterol concentrations were inversely related to vascular risk at the end of study for individuals randomised to placebo, with the top quartile having a 46% reduced risk compared to the bottom quartile (p=0.0039). In contrast, however, among those subjects given active treatment with rosuvastatin, vascular risk was calculated to be similar for subjects in both the top and bottom HDL quartiles (p=0.82)

“Although measurement of HDL–cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol,” the authors of the study conclude.

ESC spokesperson Professor Dan Atar, from Oslo University Hospital, Norway, believes there are dangers in interpreting the study as showing that raising HDL levels produces no beneficial cardiovascular effects. “It’s a matter of statistics. If you’re looking at populations with a very low incidence of cardiovascular events, and then with an intervention of any kind you reduce the risk of events even further, it’s logical that you’ll washout the influence of any other effect. These patients already have achieved such low levels of LDL that no other marker will prevail as a predictor of the few remaining events.”

He added that he had concerns that readers of the paper might not appreciate that more data was needed before the scientific community could make a qualified decision about whether raising HDL levels was beneficial or not. “With subgroup analyses, such as the one presented here, you just can’t make such judgements,” he said.

In fact, previous studies, such as the Helsinki Heart Study and the VA-HIT Study , have been successful in raising HDL and reducing cardiovascular events, using gemfibrozil, however this agent also concomitantly lowers LDL. Additionally, the drug nicacin has been shown to be effective at elevating HDL and reducing cardiovascular morbidity in the Coronary Drug Project Study (5), but this strategy could not easily be implemented into clinical practice due to unpleasant side effects, notably flushing. It is hoped that laropiprant, a novel flushing pathway inhibitor, will overcome this limitation.

A clearer indication of the benefit of raising HDL, Atar added, will come from the ongoing phase III Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), which has enrolled 25,000 patients to investigate whether the combination of niacin/laropiprant can further reduce the risk for myocardial infarction, stroke and the need for revascularisation in patients already treated to lower LDL.