CHOLESTEROL SKEPTICS AND THE BAD NEWS ABOUT STATIN DRUGS

By Maryann Napoli

The cholesterol skeptics were there. So were the physicians who challenge the safety and necessity of cholesterol-lowering drugs. And then there were the lipid researchers whose findings totally contradict the prevailing dietary advice to the public: Avoid saturated fats, limit cholesterol, and use more polyunsaturated oils. Their presentations were met with enthusiastic approval at a conference held last spring in Arlington, Virginia. But then again, the attendees were not the usual people who show up at a conference billed as "Heart Disease in the 21st Century: Beyond the Lipid Hypothesis." They were practicing physicians, biochemists, farmers, greenmarket activists, researchers, cooks, parents of young children, and people who have been told their cholesterol is too high. The general message was: Fats are extremely important to good health...the right kinds of fat, that is.
Cholesterol was the dominant topic of the two-day event, as well as the subject of the opening lecture provocatively entitled, "High Cholesterol Protects Against Disease." Uffe Ravnskov, MD, PhD, a Danish physician who has published many critical papers about the purported association between cholesterol and cardiovascular disease, led off with a slide showing the results of all the major clinical trials that attempted to prove that lowering cholesterol in healthy but high-risk people would reduce their death rate from heart disease. "The reduced rates of cardiovascular mortality were small for men and non-existent for women," said Dr. Ravnskov, who is the author of The Cholesterol Myths, a paperback that refutes the theory that cholesterol in our food and in our blood causes heart disease.
These cholesterol trials also looked at total mortality, that is, the deaths from all causes, and found little difference between the study participants who tried to lower their cholesterol and those who did not. In other words, some clinical trials showed that the heart disease death rates were, in fact, lower among men who had reduced their cholesterol levels. But this benefit was offset by a higher rate of deaths from other causes.
Given these unimpressive research results, why is high cholesterol so firmly imbedded in our consciousness as a sure-fire sign of a future heart attack? Dr. Ravnskov said that it all started with the landmark Framingham Heart Study, which began following healthy people in the early 1950s to see who had a heart attack and what distinguished them from the people who did not. High cholesterol was one risk factor--but it was only one of more than 240 others. "They [public health officials, cardiologists, etc.] have confused a statistical association with causation," he observed. "It's as if they saw a house burning and determined that the bigger the fire, the more fireman are present, and then concluded that firemen cause burning houses."
When studies failed to prove that lowering cholesterol made any lifesaving difference, researchers forged ahead with more multi-million dollar clinical trials. Not until the statin drugs (Lipitor, Mevacor, Zocor, Lescol, Crestor, Advicor) came along did cholesterol-lowering finally prove to be lifesaving to high-risk but healthy people. Whether this benefit might actually be due to the anti-inflammatory effects of statins has been the topic of controversy ever since.
As with several of the speakers who would follow him, Dr. Ravnskov is unimpressed with the reduction in heart disease mortality shown for the statin drugs "When you look at the CARE trial [Cholesterol And Recurrent Events], Pravachol did show a small benefit--after five years 5.7% had died from heart disease in the [untreated] control group, compared to only 4.6% in the treatment group, but [this benefit] was not dose related." he said, referring to the expectation that the more a person lowers his or her* cholesterol, the less likely a heart-related death. Also, the people taking Pravachol had a few more deaths from other causes. Dr. Ravnskov managed to push the envelope further by making a case for high cholesterol as a protective against cancer. He showed slides listing published studies that found higher rates of infectious disease among hospitalized people with low cholesterol levels. Also, several studies found higher cancer rates in people with low cholesterol levels.
Women told to take statin drugs should be aware of this risk found in the CARE trial: There were 12 cases of breast cancer in the women taking Pravachol, compared with only one case in the untreated (control) group. Statin drug proponents dismissed this worrisome finding as a fluke, said Dr. Ravnskov, because the control group would be expected to have had more than one case of breast cancer.
"Anyone who questions cholesterol usually finds his funding cut off," said Paul Rosch, MD, who started his talk with a reminder that half of all heart attacks occur in people with normal cholesterol levels. "Stress has more deleterious effects on the heart than cholesterol," said Dr. Rosch, who is a clinical professor of medicine and psychiatry at New York Medical College and president of the American Institute of Stress. He put a different spin on the oft-quoted studies of immigrants with low rates of heart disease that change for the worse years after they emigrated to the U.S. The shift to a Western diet is usually identified as the culprit, but Dr. Rosch suggests that the stress of adapting to a new culture is harder on the heart. For example, a study of Japanese male immigrants found a lower rate of heart attack among those who consumed a Western diet but retained a Japanese lifestyle, compared to those who continued to eat only traditional Japanese foods but lived a Western lifestyle.

Statin Drugs & Memory Loss
Duane Graveline, MD, MPH, a retired family doctor and former NASA scientist/astronaut, recounted his own hair-raising experience taking the popular statin drug Lipitor for only six weeks. Soon after he went for a walk, Dr. Graveline was found wandering, confused, and reluctant to enter his own home because he didn't recognize it or remember his wife's name. Six hours later--after being examined by a neurologist and undergoing an MRI--he came to his senses. Transient global amnesia (TGA) was diagnosed. Neither he nor his physician suspected Lipitor, so Dr. Graveline was restarted on one-half the previous dose. Again, at six weeks, the TGA returned. This time, he regressed to his teen-age years with no memory for his time in college, medical school, or the recent past. "Many decades of my life were obliterated," he said. "The diagnosis was TGA: cause unknown."
To verify his growing suspicion that Lipitor might be the cause, Dr. Graveline wrote to Joe and Teresa Graedon, the husband and wife team that writes the syndicated column called The People's Pharmacy, which specializes in warning the public about drug side effects. The Graedons asked for permission to print his letter in their column, and once it appeared, hundreds of people wrote in to say they, too, had experienced severe memory loss while on Lipitor. "Patients are reluctant to report amnesia, or they attribute the symptoms to old age or early Alzheimer's," explained Dr. Graveline. "And doctors are reluctant to see that the drug they prescribed was the cause." Still, the official word on Lipitor is that memory loss is not a statin side effect. "Thousands of cases of memory dysfunction have been reported to the FDA's Medwatch program," he said, "but after two years, the agency still hasn't acted. And most practicing physicians are unaware of the problem." Lipitor is not the only statin linked to this side effect, observed Dr. Graveline.
A reporter pointed out to that FDA-required trials do not report memory loss in people taking statins. An explanation was offered by Joel M. Kauffman, PhD, research professor of chemistry and biochemistry at the University of the Sciences in Philadelphia. "In drug trials, the pharmaceutical companies often divide similar adverse effects into six or seven different categories to keep the scarier side effects under 1%." To illustrate his point, Dr. Kauffman said that amnesia could be divided into confusion, memory loss, senility, and cognitive impairment. There is general acknowledgment, however, that muscle pain, weakness, fatigue, peripheral neuropathy, and rhabdomyolysis, a potentially fatal muscle disease, are statin side effects, though they are thought to be rare.
With a little distance from his harrowing TGA experience, Dr. Graveline said that he began to question why he took Lipitor in the first place. "I had come to think of cholesterol as my personal enemy--my cholesterol levels had climbed [over the years] despite a fat-restricted diet, but no one mentions the proper function of cholesterol in the body," he continued. "We doctors march to the low-fat, low-cholesterol band." He soon learned that cholesterol plays a critical role in the maintenance and healthy functioning of cell activity in the body.

Coenzyme Q10
Several speakers expressed the opinion that the statin drugs' ability to reduce cardiovascular mortality has nothing to do with cholesterol reduction, but instead can be attributed to their anti-inflammatory effects. (A viewpoint that has been appearing in medical journals over the last few years.) Furthermore, the physicians who addressed the conference were united in their concern that the statin drugs deplete the body of an important anti-oxidant with muscle wasting and heart failure as a result. Peter Langsjoen, MD, of Tyler, Texas, said that he left his invasive cardiology practice at the University of Texas Health Center to specialize in "congestive heart failure, primary and statin-induced diastolic dysfunction and other diseases of the heart muscle." For over 20 years, he has been using coenzyme Q10 to treat a broad range of cardiovascular diseases. Q10, as he called it, can be purchased over the counter as a dietary supplement in health food stores and pharmacies.
Dr. Langsjoen said that the research on the importance of Q10 ties in nicely with the underlying philosophy of this conference because increased levels of this "vitaminlike" substance can be found in traditional foods with high fat content like organ meats, seafood, and red meat. "I call Q10 vitaminlike because it has properties of a vitamin," explained Dr. Langsjoen, "but since we synthesize it, as well as get it in our diet, it's not truly a vitamin." All statin drugs decrease both the blood levels and cellular concentrations of Q10, observed Dr. Langsjoen, the higher the dose, the greater the decrease in Q10. "As we get older, our Q10 levels fall, but we really don't know why--could be the diet," he said. "People who make it to 90 tend to have high Q10 levels, though. Most of the Q10 research has been focused on heart failure, said Dr. Langsjoen because the heart uses a huge amount of Q10. "It has been pretty well documented from biopsies that the severity of heart failure correlates with the people who have the lowest levels of Q10."
What's more, there is a serious gap in information regarding the role of statins in treating heart failure. "All the major statin trials excluded patients with class III and IV [advanced] heart failure, so we have no safety data in these patients with heart failure, though statins are prescribed to them with reckless abandon." Dr. Langsjoen is not alone in this concern which was expressed over a year ago by Australian physicians who asked, "Statins and Chronic Heart Failure: do we need a large-scale outcome trial?" in the Journal of the American College of Cardiology.
Most medications destined to cause an adverse effect will do so early on, according to Dr. Langsjoen, who found this not to be the case with statins. "You don't realize you're in trouble until two or three years later, and it's hard to relate it to a drug you started a few years ago.

Dietary Fats and Oils
The story of how statin drugs became a multi-billion-dollar industry may have started with the identification of cholesterol as the chief culprit in heart disease, but in time the public learned that the low-fat diet would prevent heart attacks in people without symptoms of heart disease--an idea that the sponsors of this conference believe has produced numerous health problems. Mary Enig, PhD, an expert in lipid chemistry, spoke of the misinformation perpetuated upon the public by the government-sponsored "pyramid diet," which was introduced over 20 years ago and marked the beginning of the promotion of the low-fat diet. Along with the "use sparingly" advice, fats, oils, and sugar are at the very tip of the Food Guide Pyramid symbol that appears on food labels.
Dr. Enig believes that the rise of obesity is related to type of foods Americans have been encouraged to eat by the U.S. Department of Agriculture, the food industry, and consumer groups. "[People are eating] a diet high in grain and inappropriate fats, instead of the natural animal fats, such as lard, tallow, chicken fat, goose fat, and the natural vegetable fats, such as olive, palm, and coconut oils, that we used to have in our diets," and contrary to the current "propaganda," she explained that these fats and oils are essential components to a healthful diet. These so-called good fats provide the major fuel for the heart, kidneys, and skeletal muscles, said Dr. Enig, who said the inappropriate fats are the highly processed polyunsaturated fats, such as soybean, canola, and corn oils, which are promoted [ironically] as heart protective.
"Before the advent of modern vegetable oils, mankind consumed small accounts of fresh, undamaged polyunsaturated fatty acids found naturally as a component of his food," according to Dr. Enig. "Consumption of polyunsaturated fatty acids is much higher today because vegetable oils are used widely as cooking oils and in salad dressings, baked goods, and snack foods. Polyunsaturated oils should never be heated--yet during the extraction process these oils are subjected to very high temperatures that encourage rancidity and the formation of many harmful breakdown products." An example of the harmful breakdown product, she explained, is something called trans fatty acids, which are now generally recognized by mainstream medicine as harmful to the heart. Dr. Enig said that trans fatty acids do not appear on the nutrition labeling of food products, but they should. Trans fatty acids are abundant in partially hydrogenated vegetable oils, which are usually listed in the ingredients section of the food label, and are found in only small amounts in animal fats.
Dr. Enig is a leading spokesperson for the Weston A. Price Foundation, which sponsored this conference. The foundation is named for a dentist who, beginning in the 1930s, studied the dentition of healthy isolated people untouched by Western civilization. He found that they inevitably had great bone structure and beautiful straight teeth.
Primitive diets were nutrient dense, with four times the calcium and mineral and ten times the level of fat-soluble vitamins, compared to the modern American diet. Dr. Price continued to study these isolated people as Western foods were introduced. The white flour, sugar, devitalized oils, etc., gradually displaced the traditional foods, such as organ meats, fish eggs, and butter from pasture-fed cows. Changes in diet led to rampant tooth decay; narrowing of the face that brought on a susceptibility to sinus infections; narrowing of the pelvis that led to childbirth difficulties; and behavioral problems. Sally Fallon, president of the tax-exempt foundation, told the conference that its goal is to disseminate the research of this "nutrition pioneer. According to the information packet supplied to the conference attendees, the Weston A. Price Foundation takes no food industry funding.

For More Information:
-Lots of free information about the traditional foods championed by the Weston A. Price Foundation can be found on its Web site (www.westonaprice.org). Tapes of this and past conferences can be purchased via this Web site. Those without Internet access can call (202) 333-HEAL to learn the cost of receiving printed material from the Foundation.
-Visit the International Network of Cholesterol Skeptics at www.thincs.org. Most of the conference speakers belong to this Network. The 51 members are listed along with their publications.

---
*A study of elderly French women living in a nursing home showed that those with the highest cholesterol levels lived the longest (The Lancet, 4/22/89). The death rate was more than five times higher for women with very low cholesterol. Several other studies have shown similar results. Ironically, Dr. Ravnskov noted that in his practice it was usually the elderly women who were most worried about their cholesterol levels.


Maryann Napoli is the associate director of the Center for Medical Consumers in New York City. June 2003