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Daily Mail -
By Daily Mail Reporter Broccoli may combat prostate cancer by altering the genes involved in tumour growth, a study has shown. Scientists made the discovery after adding either peas or broccoli to the diets of two groups of men for a year.
//////////////////////////The Statin Showdown
Matthew Herper 06.30.08, 3:56 PM ET
When the blockbuster cholesterol pill Vytorin failed to best the less potent generic in a clinical trial earlier this year, many cardiologists were shocked. Prescriptions for Vytorin sunk by a third, and the stock prices of makers Merck and Schering-Plough plummeted.
But James K. Liao, the head of vascular medicine at the Harvard-affiliated Brigham & Women’s Hospital in Boston, wasn’t surprised. He says he never thought it made sense that Vytorin would do better than the generic, Zocor, at the main measure used in the study: preventing the artery thickening that can lead to heart attacks.
That's because Liao believes drugs like Zocor, Lipitor and Crestor, known collectively as statins, work not just by cutting levels of cholesterol in the blood but by reducing levels of inflammation in the arteries, another cause of heart attacks and strokes. Vytorin gets extra cholesterol-lowering oomph by combining Zocor with a newer drug, Zetia. But Liao argues that Zetia might actually make this inflammation worse and therefore may have less benefit at preventing heart attacks or even, theoretically, cause some harm.
"The burden of proof is on the company," says Liao. "Drugs are expensive, and drugs can have side effects. They have to show us that what they have is better than what we have. We never know for sure what the mechanism for some of these drugs are. What we know for sure is if people with heart disease take a statin, they do better."
Vytorin’s bad result added new urgency to a highly technical debate about how, exactly, statins save lives. With no hard data about whether adding Zetia to Zocor prevents heart attacks or strokes, doctors and patients are left balancing two scientific arguments: the mainstream idea that cholesterol drugs work just by lowering cholesterol; and the case made by a handful of rebels who say that their benefit is more complex. Muddying matters further, scientists have battling theories of how Zetia works, and a few critics argue that it might have its own unexpected effects--and that these may in fact increase cardiovascular risk, diluting or overriding Zetia’s benefits.
The stakes are huge. Zetia and Vytorin brought in $5.2 billion in sales last year. If Liao and his comrades are right, Zetia doesn’t prevent heart attacks and Vytorin adds nothing to Zocor. Millions of patients have swallowed $3-a-day pills only to be shortchanged. If they are wrong, the scare over Vytorin caused patients and doctors to flee a potentially lifesaving drug. Heart attacks and strokes kill 900,000 Americans a year. Merck (nyse: MRK - news - people ) and Schering have stood resolutely behind the safety and effectiveness of Zetia and Vytorin.
Just the fact that researchers are arguing over how and whether one of the drug industry's top-sellers works is evidence of how difficult the drug business is getting. Only giant clinical trials measuring hard outcomes like heart attacks, strokes and deaths can tell doctors whether a heart drug's benefits outweigh its risks. "Until you put a drug in 10,000 people, you don't know what result you're going to get," says Robert Vogel, a cardiologist at the University of Maryland.
Cholesterol's importance emerged from a government study of 5,000 people from Framingham, Mass., who agreed to be followed for their entire lives to figure out what causes heart attacks. In 1961, the Framingham study pointed to blood levels of cholesterol, a fat molecule used for making hormones and cell membranes, as an important risk factor for heart disease.
Plaques of cholesterol build up inside the walls of arteries, where they become inflamed and can rupture, creating clots that block blood flow and cause heart attacks. But how does cholesterol get into the arteries? Cholesterol, an oily fat, doesn't dissolve in blood, which is mostly water. A spherical protein called low-density lipoprotein (LDL), which can carry more than 1,000 cholesterol molecules within it but also dissolves in water, ferries cholesterol throughout the body. In 1977, Framingham had proved LDL as a risk factor.
Early studies of LDL-lowering drugs were promising, but not definitive. In a 1984 study, lowering LDL 12% with the Bristol-Myers Squibb (nyse: BMY - news - people ) drug Questran showed a benefit only after seven years. Through the early nineties, cardiology journals were filled with debates about how useful lowering cholesterol was and whether lowering it too much might even be dangerous.
Those debates were blown away when a 1994 study showed Merck's Zocor substantially lowered the death rate of heart patients in Scandinavia. A study of Bristol's Pravachol in Scotland followed. With drug after drug, in population after population, statins reduced the rates of heart attacks and strokes. U.S. treatment guidelines now advocate getting LDL levels down to 100 milligrams per deciliter, 20% below levels that would be considered normal. For heart patients, there's an optional target of 70 mg/dL.
But when he saw that Scandanavian study, James Liao wasn't immediately convinced about the benefits of LDL. He was surprised, because Zocor not only prevented heart attacks but also strokes. The Framingham study hadn't uncovered a link between strokes and cholesterol levels. Might Zocor be doing more than just cutting cholesterol levels?
In 1997, Liao published one of the first papers showing that statins like Zocor might have extra, unknown benefits, which he called "plieotropic effects." The idea was so novel Harvard patented it.
Statins work to stop the production of cholesterol in the liver by blocking an enzyme called HMG-CoA reductase. This enzyme helps break down chemicals already present in the liver into which in a whole class of molecules called isoprenoids. Since cholesterol is made from these molecules, blood levels of LDL plummet 30% or more when a patient takes a statin.
But Liao showed first in cell cultures and then in animal models that this isn't all the isoprenoids do. He found they also activate an enzyme called Rho kinase, which negatively affects the way that arteries expand and contract and increasing the inflammation within cholesterol plaques in the artery wall. Blocking HMG CoA reductase not only prevents the formation of cholesterol, but also the creation of Rho kinase.
Zetia lowers LDL 15% by preventing cholesterol from being absorbed from food in the intestine. But Liao says the body ups production of cholesterol to compensate, turning on the HMG CoA pathway. That could mean more inflammation in the artery wall. "I don't think it's ethical to give [Zetia] by itself," Liao says. He would make an exception for patients who can't take other drugs because of side effects.
When combined with Zocor in Vytorin, Zetia does lower C-reactive protein (CRP), which doctors use to try and measure artery inflammation. But Liao says that he worries this change is only "cosmetic." Without more data, it's difficult to say for sure, he says. "You may shortchange your patients," Liao says.
Complicating matters further: nobody knows exactly how Zetia works at the cellular level. In 2004, two years after it was approved, Schering-Plough (nyse: SGP - news - people ) scientists published a paper in Science arguing that the drug blocks a newly discovered protein that seemed to be involved mostly in absorbing cholesterol out of the intestines. But more recently outside researchers have argued that it may block a second protein that is pivotal to the way cholesterol is moved in and out of cells. "That could offset any benefit of LDL lowering," argues Allen Taylor of Walter Reed Army Medical Center, one of Zetia's most outspoken critics.
Zetia and Vytorin remain big sellers, and they also have their defenders. Roger Blumenthal, director of the Johns Hopkins Ciccarone Preventative Cardiology Center, says that statins should always be used before turning to Zetia, but that everyone can't tolerate high doses and Zetia is still one of the best options for these patients.
Daniel Rader of the University of Pennsylvania, one of the world's top experts on the science of cholesterol, says a laser-like focus on LDL-lowering has been one reason deaths from cardiovascular disease are dropping. "I'm firmly in the camp that says lowering LDL more is better," says Rader. "We cannot afford to backtrack from our focus on aggressive LDL lowering. There's no way ENHANCE should cause us to reconsider that position."
Merck and Schering-Plough are funding an 18,000 patient study comparing Vytorin and Zocor that could settle all the debate for good. But results are not expected until 2012.
/////////////////////////Ooguay: “One often meets his destiny on the road he takes to avoid it.”
//////////////////Ooguay: “There are no accidents.”=all ATO-BY PHYSICALISM
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////////////////////Rising gas & food prices have nearly everyone looking for clever ways to save money. Check out some easy suggestions from the EP community:
- When shopping, make a shopping list and STICK to it - otherwise you may end up buying things you don't really need
- Round "up" all purchases when balancing your checkbook & by the end of the year you might have saved over $1000
- Leave lights off & turn down the thermostat while you're out for the day
- Try doing social things that don't require money - go to the park, attend a free art exhibit, or just have coffee at a friend's house.
- Direct deposit a portion of your paycheck straight into a savings account - if you never see it, you don't miss it.
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NATRS WAY TO UPDATE MODEL VERSIONS
/////////////MATING IS AN EVOLUTIONARY DANCE OF SHUFFLING GENES
//////////////BIG BRAINS AND BIPEDALISM CAUSES HUMAN CHILDBIRTH RISKIER
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