Given that statins lower cholesterol, perhaps this is why those that follow a low fat diet see benefits in relation to MS!
Cholestrol drug may be a lot more 25 December 2005
Cancer. Alzheimer's. Diabetes. Osteoporosis. These are just some of the diseases that researchers hope can be treated or prevented with statins.
By Ronald Kotulak
Not since aspirin has a class of drugs come along that does so much more than originally intended that it could end up being used as a preventive against many major diseases.
Statins, which lower cholesterol, have been proved in clinical trials to reduce heart attacks and strokes by 30 to 50 percent. They are the most widely prescribed drugs in the U.S.; 1 in 10 adults take them.
But their full value in improving the nation's health rests with research attempting to establish the ability of statins to prevent cancer, Alzheimer's disease, diabetes, osteoporosis, high blood pressure, multiple sclerosis and macular degeneration.
Already, observational studies suggest that people who take statins are at lower risk of developing those illnesses. Researchers are exploring why the drugs might have such a broad protective effect and are finding the drugs may affect critical systems of the body in ways that head off disease.
"Statins are one of the real miracle drugs from the last generation of research," said Dr. Thomas H. Lee, a cardiologist at Harvard Medical School and Brigham and Women's Hospital. "No one realized when they came out just how broad their impact would be. There are reasonable people who believe that if statins were completely free, everyone should take them."
Lee and others caution, however, that the drugs still must undergo rigorous clinical trials to prove that they can safely and effectively do all the things they have been billed to do.
"If we determine down the road that statins help reduce things like Alzheimer's disease, osteoporosis and cancer, they still should be given to people who are at higher risk of developing those things, [rather] than just to everybody across the board," said Dr. Mathew Sorrentino, director of preventive cardiology at the University of Chicago.
Statins are taken to lower levels of cholesterol, especially low-density lipoprotein or LDL, the so-called "bad cholesterol" linked to heart disease. They do that work very well.
"The average cholesterol level in the country has been going down and the number of heart attacks and strokes have clearly been reduced," Sorrentino said. "Statins are changing the health of the whole United States. It's pretty remarkable to have an agent that's doing that."
Cholesterol, which is made naturally in the liver, is a vital component used to build all cells in the body and to maintain their function. It becomes dangerous when blood levels are too high--usually due to diet--and excess cholesterol builds up in artery walls, causing heart disease.
Statins work against cholesterol in two ways: They reduce the liver's ability to manufacture it, and they speed the elimination of LDL from the body.
But researchers are discovering that statins have other surprising effects. In the process of reducing cholesterol, the drugs set in motion a chain of events that appears to improve many functions in the body, from blood pressure to inflammation.
In the body, a long series of chemical steps leads up to the manufacture of cholesterol, and each of those steps plays a role in cellular function. Trouble appears to occur when cholesterol levels get too high and the chemical steps begin to behave abnormally, helping to set the stage, scientists believe, for such disorders as cancer, heart disease and Alzheimer's.
By slowing the first step of the chemical pathway to cholesterol production, statins help prevent that from happening.
Evidence suggests that statins thereby help the body in many ways, such as getting rid of cancer cells, improving the flow of blood through arteries, eliminating brain plaques in Alzheimer's disease, beefing up immunity, reducing inflammation, thwarting blood clots, reducing fractures, preventing arterial blockages from breaking off and causing heart attacks or strokes, and snuffing out free-radical damage.
"Three of every 100 proteins need something from this cholesterol pathway to function," said Jim Dimitroulakos of the Ottawa Regional Cancer Center, who is trying to determine how statins may block cancer. "There could be thousands of proteins affected by these drugs, and they seem to be beneficial for disease prevention. I don't think there's been another drug that affects so many different things."
Dr. Gregory R. Mundy of the University of Texas Health Science Center, San Antonio, found, for instance, that one product of the cholesterol pathway stimulates bone growth, a finding that suggests why statins may be useful against osteoporosis.
This broad range of metabolic activity even surpasses that of aspirin. Initially marketed in 1899 as a pain reliever, aspirin over time was found to have a role in reducing the risk of heart attacks, strokes, arthritis, inflammation and colon cancer.
The first statin, Mevacor, was marketed in 1987, but doctors were nervous about prescribing it, fearing side effects. Those fears evaporated by the mid-'90s after several studies showed statins effectively reduced the risk of heart attacks and were relatively safe. The floodgates opened, and physicians now write about 150 million statin prescriptions annually.
Studies indicate statins pose no cancer risk and side effects are minimal. Doctors check patients for elevated liver enzymes, but so far not one case of liver damage has been tied to statins. Serious side effects causing muscle damage and kidney failure occur in about one in a million users. Muscle aches are the most common complaint, affecting about 1 in 100 people. Liver and muscle side effects are reversible when the drugs are discontinued or the dose lowered.
"The most serious side effect from statins is on par or even less than a serious bleeding side effect of aspirin," Sorrentino said.
The United Kingdom recently approved over-the-counter sales of a low dose of one statin, Zocor, to reduce the risk of heart attacks, and experts believe that the U.S. Food and Drug Administration also may eventually allow the purchase of statins without prescriptions. The American College of Physicians last year recommended that everyone with adult onset or type 2 diabetes should be on statins.
"At this point the evidence is pretty overwhelming that statins reduce everyone's risk of heart attack by about a third," Lee said. "It doesn't matter whether your risk is elevated because of high cholesterol, or whether your risk is elevated because of diabetes, high blood pressure or cigarette smoking."
Although a number of population studies suggest statins may protect against a large number of diseases, these studies cannot prove a cause-and-effect relationship. For that, researchers must turn to controlled clinical trials where the medication is compared to an inactive placebo. Such trials are under way for cancer, Alzheimer's disease and multiple sclerosis.
The most impressive population research involves a series of retrospective studies on half a million veterans conducted by Dr. Vikas Khurana of the Overton Brooks VA Medical Center in Shreveport, La. Men who took statins for up to four years had about 50 percent fewer cancers of the lung, prostate, pancreas and esophagus. For those taking statins longer, the reduction was much greater, he said.
Looking at nearly 40,000 female veterans, Khurana found that those taking statins had approximately 50 percent fewer breast cancers. The studies attempted to rule out other factors such as cigarette smoking, alcohol consumption, diet, income and physical activity.
Statins may have at least two mechanisms for destroying cancer cells. Dimitroulakos' research suggests that when statins reduce the body's production of cholesterol they also reduce some chemicals that cancer cells need to grow, causing them to self-destruct.
Biochemist Khandan Keyomarasi of the University of Texas M.D. Anderson Cancer Center found preliminary evidence that statins can also act directly on cancer cells in laboratory tests to shut down their division, also leading to cell death.
"Statins are very promising but they are still not ready for prime time. We need randomized clinical studies and more convincing results," said Khurana, also an assistant professor of medicine at Louisiana State University. "Before people with low or normal cholesterol start using these drugs in the hope of preventing cancer, we need to make sure that the side effects are going to be minimal as compared to the potential cancer benefits they're going to get."
Depending on the outcome of clinical trials, Alzheimer's disease may become the latest disorder that statins are used both to treat and to prevent.
Cholesterol's link to Alzheimer's disease became the primary focus of Dr. Larry Sparks of the Sun Health Research Institute in Sun City, Ariz., when he discovered from autopsy studies in 1986 that people with heart disease and high cholesterol levels had plaques in their brains. The plaques were exactly like those of Alzheimer's patients, though they had not been diagnosed with the disease. Subsequent studies of rabbits fed high-cholesterol diets showed they too developed the brain-clogging hallmarks of Alzheimer's.
As a result of population studies suggesting that people taking statins seemed to have a lower risk of Alzheimer's, Sparks undertook a small phase one clinical trial of Alzheimer's patients in which 32 people took Lipitor and 31 a placebo.
After three months both groups continued to deteriorate at the same rate, Sparks reported recently. After six months, however, placebo patients continued their steady decline, but the memory of those taking Lipitor began to improve until it was superior to when the study started. After that, the memory enhancement began to wane.
"Lipitor gave them a boost," Sparks said. "It slowed things down. We were able to demonstrate that the progression of the disease had probably been slowed. At the end of a year of treatment the Lipitor population were almost exactly the same as they were when they started the trial."
Based on Sparks' findings Pfizer Inc., maker of Lipitor, launched a large clinical trial of 600 patients to determine if the drug can effectively treat Alzheimer's disease. The National Institutes of Health started another study with 450 patients to determine if Zocor slows the disease's progression.
The mechanism by which cholesterol influences Alzheimer's disease is not known. Studies indicate that cholesterol may trigger a malfunction in the brain's garbage-removal detail, allowing a buildup of neuron-killing debris.
What's needed next, Sparks said, are clinical trials to determine if statins can prevent the disease in healthy people. "The predominant weight of the data is that there is an influence of prior statin use on your later risk of Alzheimer's disease," Sparks said.
As research into statins continues, many physicians are excited about the drugs' potential for healing--but also taking a wait-and-see approach.
"Are they a wonder drug? That's hard to say," said Dr. Gerald McGwin Jr. of the University of Alabama, Birmingham, who is studying statins and macular degeneration. "They've been associated with a lot of things, but we haven't translated that research into clinical trials. Once we've done that and they are shown to be as good as we think, then maybe I'd call them a wonder drug."
Source: Chicago Tribune Copyright © 2005
It seems from recent research that statins are also antibacterial--Here are two links to abstracts pertaining to yet another possible mode of action in MS treatment with statins
http://ttp.northwestern.edu/abstracts/v ... 42&cat=103
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