Dangers of Statin Drugs: What You Haven’t Been Told About
Popular Cholesterol-Lowering Medicines
Sally Fallon and Mary G. Enig, PhD
June 14, 2004
Hypercholesterolemia is the health issue of the 21st century. It is actually an invented disease, a “problem” that emerged when health professionals learned how to measure cholesterol levels in the blood. High cholesterol exhibits no outward signs–unlike other conditions of the blood, such as diabetes or anemia, diseases that manifest telltale symptoms like thirst or weakness–hypercholesterolemia requires the services of a physician to detect its presence. Many people who feel perfectly healthy suffer from high cholesterol–in fact, feeling good is actually a symptom of high cholesterol!
How Statins Work
The diagram below illustrates the pathways involved in cholesterol production. The process begins with acetyl-CoA, a two-carbon molecule sometimes referred to as the “building block of life.” Three acetyl-CoA molecules combine to form six-carbon hydroxymethyl glutaric acid (HMG). The step from HMG to mevalonate requires an enzyme, HMG- CoA reductase. Statin drugs work by inhibiting this enzyme–hence the formal name of HMG-CoA reductase inhibitors. Herein lies one potential for numerous side effects, because statin drugs inhibit not just the production of cholesterol, but a whole family of intermediary substances, many if not all of which have important biochemical functions in their own right.
Synthesis of Cholesterol
Enter the Statins
Statin drugs entered the market with great promise. They replaced a class of pharmaceuticals that lowered cholesterol by preventing its absorption from the gut. These early drugs often had immediate and unpleasant side effects, including nausea, indigestion and constipation, and in the typical patient they lowered cholesterol levels only slightly. Patient compliance was low: the benefit did not seem worth the side effects and the potential for use was very limited. By contrast, statin drugs had no immediate side effects: they did not cause nausea or indigestion and they were consistently effective, often lowering cholesterol levels by 50 points or more.
Muscle Pain and Weakness
The most common side effect is muscle pain and weakness, a condition called rhabdomyolysis, most likely due to the depletion of Co-Q10, a nutrient that supports muscle function. Dr. Beatrice Golomb of San Diego, California is currently conducting a series of studies on statin side effects. The industry insists that only 2-3 percent of patients get muscle aches and cramps but in one study, Golomb found that 98 percent of patients taking Lipitor and one-third of the patients taking Mevachor (a lower-dose statin) suffered from muscle problems.4 A message board devoted to Lipitor a forum.ditonline.com (update 09 JUL 2007: reader alerted us the forum is now defunct) contained more than 800 posts, many detailing severe side effects. The Lipitor board at www.rxlist.com contains more than 2,600 posts (click on Message Boards at upper left and then choose Lipitor; also note that as of 09 JUL 2007 there are 3,857 messages).
Polyneuropathy, also known as peripheral neuropathy, is characterized by weakness, tingling and pain in the hands and feet, as well as difficulty walking. Researchers who studied 500,000 residents of Denmark, about 9 percent of that country’s population, found that people who took statins were more likely to develop polyneuropathy.11 Taking statins for one year raised the risk of nerve damage by about 15 percent–about one case for every 2,200 patients. For those who took statins for two or more years, the additional risk rose to 26 percent.
We are currently in the midst of a congestive heart failure epidemic in the United States–while the incidence of heart attack has declined slightly, an increase in the number heart failure cases has outpaced these gains. Deaths attributed to heart failure more than doubled from 1989 to 1997.14 (Statins were first given pre-market approval in 1987.) Interference with production of Co-Q10 by statin drugs is the most likely explanation. The heart is a muscle and it cannot work when deprived of Co-Q10.
Dizziness is commonly associated with statin use, possibly due to blood pressure-lowering effects. One woman reported dizziness one half hour after taking Pravachol.18 When she stopped taking it, the dizziness cleared up. Blood pressure lowering has been reported with several statins in published studies. According to Dr. Golumb, who notes
The November 2003 issue of Smart Money20 describes the case of Mike Hope, owner of a successful ophthalmologic supply company: “There’s an awkward silence when you ask Mike Hope his age. He doesn’t change the subject or stammer, or make a silly joke about how he stopped counting at 21. He simply doesn’t remember. Ten seconds pass. Then 20. Finally an answer comes to him. ‘I’m 56,’ he says. Close, but not quite. ‘I will be 56 this year.’ Later, if you happen to ask him about the book he’s reading, you’ll hit another roadblock. He can’t recall the title, the author or the plot.” Statin use since 1998 has caused his speech and memory to fade. He was forced to close his business and
In every study with rodents to date, statins have caused cancer.26 Why have we not seen such a dramatic correlation in human studies? Because cancer takes a long time to develop and most of the statin trials do not go on longer than two or three years. Still, in one trial, the CARE trial, breast cancer rates of those taking a statin went up 1500 percent.27 In the Heart Protection Study, non-melanoma skin cancer occurred in 243 patients treated with simvastatin (a total of 10,269) compared with 202 cases in the control group (a total of 10,267).28
The medical literature contains several reports of pancreatitis in patients taking statins. One paper describes the case of a 49-year-old woman who was admitted to the hospital with diarrhea and septic shock one month after beginning treatment with lovastatin. She died after prolonged hospitalization; the cause of death was necrotizing pancreatitis. Her doctors noted that the patient had no evidence of common risk factors for acute pancreatitis, such as biliary tract disease or alcohol use. “Prescribers of statins (particularly simvastatin and lovastatin) should take into account the possibility of acute pancreatitis in patients who develop abdominal pain within the first weeks of treatment with these drugs,” they warned. By contrast, a review of published case studies found that pancreatitis was more likely to occur after many months of statin use.30
Several studies have noted a correlation of low cholesterol with depression, suicide and violence. For example, a study of over 29,000 men in Finland found that low cholesterol levels were associated with an increased risk of hospitalization due to depression and of death from suicide.31 Another study found that women with low cholesterol are twice as likely to suffer from depression and anxiety. Researchers from Duke University Medical Center carried out personality trait measurements on 121 young women aged 18 to 27.32 They found that 39 percent of the women with low cholesterol levels scored high on personality traits that signalled proneness to depression, compared to 19
Most doctors are convinced–and seek to convince their patients–that the benefits of statin drugs far outweigh the side effects. They can cite a number of studies in which statin use has lowered the number of coronary deaths compared to controls. But as Dr. Ravnskov has pointed out in his book The Cholesterol Myths,33 the results of the major studies up to the year 2000–the 4S, WOSCOPS, CARE, AFCAPS and LIPID studies–generally showed only small differences
Honolulu Heart Program (2001)
This report, part of an ongoing study, looked at cholesterol lowering in the elderly. Researchers compared changes in cholesterol concentrations over 20 years with all-cause mortality.36 To quote: “Our data accords with previous findings of increased mortality in elderly people with low serum cholesterol, and show that long-term persistence of low cholesterol concentration actually increases risk of death. Thus, the earlier that patients start to have lower cholesterol concentrations, the greater the risk of death. . . The most striking findings were related to changes in cholesterol between examination three (1971-74) and examination four (1991-93). There are few studies that have cholesterol concentrations from the same patients at both middle age and old age. Although our results lend support to previous findings that low serum cholesterol imparts a poor outlook when compared with higher concentrations of cholesterol in elderly people, our data also suggest that those individuals with a low serum cholesterol maintained over a 20-year period will have the worst outlook for all-cause mortality [emphasis ours].”
The MIRACL study looked at the effects of a high dose of Lipitor on 3086 patients in the hospital after angina or nonfatal MI and followed them for 16 weeks.37 According to the abstract: “For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/day, reduced recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.” What the abstract did not mention was the fact that there was no change in death rate compared to controls and no significant change in re-infarction rate or need for resuscitation from cardiac arrest. The only change was a significant drop in chest pain requiring rehospitalization.
ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), the largest North American cholesterol-lowering trial ever, showed that mortality of the treatment group and controls after three or six years was identical.38 Researchers used data from more than 10,000 participants given cholesterol-lowering drugs and followed them over a period of four years, comparing the use of a statin drug to “usual care,” namely maintaining proper body
Heart Protection Study (2002)
Carried out at Oxford University,39 this study received widespread press coverage; researchers claimed “massive benefits” from cholesterol-lowering,40 leading one commentator to predict that statin drugs were “the new aspirin.” 41
PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) studied the effect of pravastatin compared to a placebo in two older populations of patients of which 56 percent were primary prevention cases (no past or symptomatic cardiovascular disease) and 44 percent were secondary prevention cases (past or symptomatic cardiovascular disease).44 Pravastatin did not reduce total myocardial infarction or total stroke in the primary prevention population but did so in the secondary. However, measures of overall health impact in the combined populations, total mortality and total serious adverse events were unchanged by pravastatin as compared to the placebo, and those in the treatment group had increased cancer. In other words: not one life saved.
The Japanese Lipid Intervention Trial was a six-year study of 47,294 patients treated with the same dose of simvastatin.45 Patients were grouped by the amount of cholesterol lowering. Some patients had no reduction in LDL levels, some had a moderate fall in LDL and some had very large LDL reductions. The results: no correlation between the amount of LDL lowering and death rate at five years. Those with LDL cholesterol lower than 80 had a death rate of just over 3.5 at five years; those whose LDL was over 200 had a death rate of just over 3.5 at five years.
In a meta-analysis of 44 trials involving almost 10,000 patients, the death rate was identical at 1 percent of patients in each of the three groups–those taking atorvastatin (Lipitor), those taking other statins and those taking nothing.46
Statins and Plaque (2003)
A study published in the American Journal of Cardiology casts serious doubts on the commonly held belief that lowering your LDL-cholesterol, the so-called bad cholesterol, is the most effective way to reduced arterial plaque.47
Statins and Women (2003)
No study has shown a significant reduction in mortality in women treated with statins. The University of British Columbia Therapeutics Initiative came to the same conclusion, with the finding that statins offer no benefit to women for prevention of heart disease.48 Yet in February of 2004, the journal Circulation published an article in which more than 20 organizations endorsed cardiovascular disease prevention guidelines for women, with several mentions of “preferably a statin.”49
ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm) was designed to assess the benefits of atorvastatin (Lipitor) versus a placebo in patients who had high blood pressure with average or lower-than-average cholesterol concentrations and at least three other cardiovascular risk factors.50 The trial was originally planned for five years but was stopped after a median follow-up of 3.3 years because of a significant reduction in cardiac events. Lipitor did reduce total myocardial infarction and total stroke; however, total mortality was not significantly reduced. In fact, women were worse off with treatment. The trial report stated that total serious adverse events “did not differ between patients assigned atorvastatin or placebo,” but did not supply the actual numbers of serious events.
Cholesterol Levels in Dialysis Patients (2004)
In a study of dialysis patients, those with higher cholesterol levels had lower mortality than those with low cholesterol.51 Yet the authors claimed that the “inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations.” Keeping an eye on further funding opportunities, the authors concluded: “These findings support treatment of hypercholesterolemia in this population.”
PROVE-IT (PRavastatin Or AtorVastatin Evaluation and Infection Study), 52 led by researchers at Harvard University Medical School, attracted immense media attention. “Study of Two Cholesterol Drugs Finds One Halts Heart Disease, was the headline in the New York Times.53 In an editorial entitled “Extra-Low Cholesterol,” the paper predicted that “The findings could certainly presage a significant change in the way heart disease patients are treated. It should also start a careful evaluation of whether normally healthy people could benefit from a sharp drug-induced reduction in
In a similar study, carried out at the Cleveland Clinic, patients were given either Lipitor or Pravachol. Those receiving Lipitor achieved much lower LDL-cholesterol levels and a reversal in “the progression of coronary plaque aggregation.”59 Those who took Lipitor had plaque reduced by 0.4 percent over 18 months, based on intravascular ultrasound (not the more accurate tool of electron beam tomography). Dr. Eric Topol of the Cleveland Clinic claimed these decidedly unspectacular results “Herald a shake-up in the field of cardiovascular prevention. . . the implications of this turning point–that is, of the new era of intensive statin therapy–are profound. Even today, only a fraction of the patients who should be treated with a statin are actually receiving such therapy. . . More than 200 million people worldwide meet the criteria for treatment, but fewer than 25 million take statins.”60 Not surprisingly, an article in the Wall Street Journal noted “Lipitor Prescriptions Surge in Wake of Big Study.” 61
With such paltry evidence of benefit, statin drugs hardly merit the hyperbole heaped upon them. Yet the industry maintains a full court press, urging their use for greater and greater numbers of people, not only for cholesterol lowering but also as treatment for other diseases–cancer, multiple sclerosis, osteoporosis, stroke, macular degeneration, arthritis and even mental disorders such as memory and learning problems, Alzheimers and dementia.63 New guidelines published by the American College of Physicians call for statin use by all people with diabetes older than 55 and for younger diabetes patients who have any other risk factor for heart disease, such as high blood pressure or a history of smoking.64 David A. Drachman, professor of neurology at the University of Massachusetts Medical School calls statins “Viagra for the brain.”65 Other medical writers have heralded the polypill, composed of a statin drug mixed with a blood pressure medication, aspirin and niacin, as a prevent-all that everyone can take. The industry is also seeking the right to sell statins over the counter.
The best advertising for statin drugs is free front-page coverage following gushy press releases. But not everyone reads the paper or goes in for regular medical exams, so statin manufacturers pay big money for creative ways to create new users. For example, a new health awareness group called the Boomer Coalition supported ABC’s Academy Awards telecast in March of 2004 with a 30-second spot flashing nostalgic images of celebrities lost to cardiovascular disease–actor James Coburn, baseball star Don Drysdale and comedian Redd Foxx. While the
Statin drugs are very expensive–a course of statins for a year costs between $900 and $1400. They constitute the mostly widely sold pharmaceutical drug, accounting for 6.5 percent of market share and 12.5 billion dollars in revenue for the industry. Your insurance company may pay most of that cost, but consumers always ultimately pay with higher insurance premiums. Payment for statin drugs poses a huge burden for Medicare, so much so that funds may not be available for truly lifesaving medical measures.
A Better Way
If statins work, they do so by reducing inflammation, not because they lower cholesterol. Statins block the production of mevalonate leading to inhibition of platelet clumping and reduction of inflammation in the artery walls. However, simple changes in the diet can achieve the same effect without also cutting off the body’s vital supply of cholesterol:
Doctors and other health professionals claim there is ample proof that animal fats cause heart disease while they confidently advise us to adopt a lowfat diet; actually the literature contains only two studies involving humans that compared the outcome (not markers like cholesterol levels) of a diet high in animal fat with a diet based on vegetable oils, and both showed that animal fats are protective.
What About Aspirin?
The other drug recommended for prevention of heart attacks and strokes is aspirin. Estimates suggest that 20 million persons are taking aspirin daily for prevention of vascular accidents. Yet at least four studies have shown no benefit. A study using Bufferin (aspirin and magnesium) showed no reduction in fatal heart attacks and no improvement in survival rate but a 40 percent decrease in the number of nonfatal heart attacks. Commentators reported these results as showing the benefit of aspirin, ignoring the fact that magnesium is of proven benefit in heart disease. Aspirin
Late-Breaking Cholesterol News
Researchers at the Tulane University School of Medicine used electron beam tomography (EBT) to measure the progression of plaque buildup in heart-attack patients taking statin drugs. EBT is a very accurate way to measure occlusion from calcium in the arteries. Contrary to expectations, the researchers discovered that the progression of coronary artery calcium (CAC) was significantly greater in patients receiving statins compared with event-free subjects despite similar levels of LDL-lowering. Said the researchers: “Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events (Arterioscler Thromb Vasc Biol, April 1, 2004).
Read the Fine Print
1. Hoffman G. N Engl J Med 1986;314:1610-24.
57. Health Sciences Institute e-alert, www.hsibaltimore.com, March 11, 2004
61. Scott Hensley. The Statin Dilemma: How Sluggish Sales Hurt Merck, Pfizer. The Wall Street Journal, July 25,