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Statin Drugs: The Ultimate Manifestation of Anti-Cholesterol Stupidity?

Statin Drugs: The Ultimate Manifestation of Anti-Cholesterol Stupidity?
Source: The Omnivore
By Anthony Colpo, March 14, 2004.

The last decade has seen a rapid rise in the use of cholesterol-lowering statin drugs. Last week, media reports hailed the results of a new study as "proof" that doctors should more aggressively pursue cholesterol-lowering in CHD patients by using even higher dosages of statin drugs. While they might be hailed as "miracle drugs" by the establishment, statins have been shown to cause muscle damage, liver dysfunction, fatigue, impaired mental function, and may even contribute to heart failure and cancer. In this article we will learn why statins are anything but "miraculous". Before we do that though, let's take a quick journey back in time to learn about the plight of "Acirema"…

Once upon a time, (the late fifties, actually) there existed a prosperous kingdom known as Acirema. Although blessed in many ways, Acirema was unfortunately troubled by very high rates of coronary heart disease (CHD). In response to growing concern throughout the kingdom, the King of Acirema promised the people that he would find a cure for this terrible ailment.

The King of Acirema proceeded to establish the massive National Institutes of Health (NIH), who, along with the Acireman Heart Association (AHA), vowed to engage all their bureaucratic might in order to free the population from the dreaded scourge of CHD.

One day, the fine minds from the NIH and AHA sat down and wondered where they should start in their fight against CHD.

"What if", proffered one of them, "we convince the people of the kingdom to cut all the saturated fat from their diet, and replace it with polyunsaturated vegetable oils. That will lower their cholesterol levels, and we all know that cholesterol causes heart disease in animal studies, right?"

"What a splendid idea!", chirped his fellow bureaucrats in delighted unison.

The people of Acirema did as they were told and cut all the saturated fat from their diet, and began consuming ungodly amounts of vegetable oils. While the polyunsaturated vegetable oil manufacturers became very, very rich, the people of Acerima did not experience any respite from CHD. In fact, a steady rise in cancer became apparent after the kingdom's switch to vegetable oils.

"Oops", said the people from the NIH and AHA.

"What do we do now?" they wondered.

"What if", proffered one of them, "instead of replacing one type of fat with another, we told the villagers to simply cut out fat altogether, and eat carbohydrates instead? We all know that fat is a gooey, sticky substance that clogs up arteries, right?"

"What a splendid idea!", chirped his fellow bureaucrats in delighted unison.

So they convinced the people of Acirema to cut the fat from their diets. The Aciremans reluctantly gave up their steak and eggs, and instead began eating a bizarre array of non-fat, low-fat, and reduced-fat foods. While the manufacturers of these strange new foods became very, very rich, the people of Acirema did not experience any relief from CHD. In fact, the kingdom's switch to low-fat, high-carbohydrate foods was followed by a dramatic jump in obesity and diabetes.

"Oops", said the people from the NIH and AHA.

"What do we do now?" they wondered.

"Drugs!", shouted one of them, "Damn it, if we can't beat CHD with diet, we'll beat it with drugs!"

"What a splendid idea!", chirped his fellow bureaucrats in delighted unison.

So the bureaucrats started experimenting with all sorts of drugs. Noting that the premenopasual womenfolk of Acirema had very low rates of heart disease, they first tried giving female hormones to the menfolk. Unfortunately, the results were not quite what they expected. When the menfolk subsequently grew breasts, became impotent, and started reading Better Homes and Gardens, the bureaucrats realized they had made a big mistake.

Not to be deterred, however, the inquisitive staff from the NIH and AHA then began studying some new cholesterol-lowering drugs called fibrates. When testing the fibrates on the kingdom's guinea pigs, they found that any reduction in coronary heart disease mortality was usually countered by a corresponding increase in non-CHD mortality, usually from violent death and cancer. Mesmerized by the cholesterol-lowering capabilities of the fibrates, they nonetheless ignored the results of the guinea pig tests, and gave the people of the kingdom the drugs anyway. There was a subsequent small reduction in coronary heart disease mortality, but it was countered by a corresponding increase in non-CHD mortality, mainly from violent death and cancer.

The folks from the NIH and AHA became very disparaged. The King was angry because he had promised the kingdom a cure for CHD, and now the people of the kingdom were upset at him because, over thirty years after he had made his promise, there was still no cure for CHD. The King told the heads of the NIH and AHA that if they didn't come up with a cure for CHD soon, there would be royal hell to pay!

Things were looking very bleak indeed for the bureaucrats. They had convinced themselves, the King, and the kingdom that the key to conquering CHD was to lower cholesterol levels, but every cholesterol-lowering strategy they tried drew a blank. With the dismal results seen in their dietary fat interventions, and the poor results seen with the various drugs they had tried, some of the staff from the NIH and AHA began to realize that their cholesterol theory did not have a scientific leg to stand on. So they did what any good vested interest would do when advancing an agenda not backed by facts; they relied on propaganda. Lots of it.

For awhile, the people of the kingdom were placated by the copious daily stream of anti-cholesterol propaganda. This in turn, helped to keep the King off the bureaucrats' backs. Every now and then, though, some brave, independent-thinking practitioner would dare to ask why, if cholesterol-lowering was so beneficial, was the kingdom still experiencing such high rates of heart disease? When this happened, the bureaucrats would call the officers from the Non-Compliance Eradication Program (NCEP) who would capture the dissident, strip him of his qualifications, and banish him to an isolated section of the woods. After ridding the kingdom of the dissident, the NCEP would then institute a special Propaganda-Intensification Program (PIP) as a means of damage control. However, despite the NCEP's best efforts, and the implementation of many, many PIPs, the voices of dissent began to grow ever louder. Tension again started to mount at the NIH and AHA.

Then one day, just as things were beginning to look very shaky for the bureaucrats, along came their savior, their knight in shining armor: a miraculous new class of drugs which they promptly called the "statins"!

Unlike their earlier experiments with cholesterol-lowering pharmaceuticals, randomized trials with these new statin drugs showed decreases in total as well as CHD mortality. They did not appear to cause any increase in cancer or violent death, and they did not cause the menfolk to grow breasts. The bureaucrats were beside themselves: at last, definitive proof that cholesterol-lowering indeed saved lives, and that the massive propaganda machine they had created was good for more than just yanking people's chains! The bureaucrats excitedly reported their research findings to the King, who subsequently decreed that everyone in the Kingdom over the age of two must immediately begin taking the marvelous new statin drugs.

A huge wave of relief swept over Acirema; people were delighted that an effective treatment for CHD had finally been found. News of the magnificent statins rapidly spread to other kingdoms, and they quickly became one of the best-selling drug categories in the world. The King of Acirema was very proud and called the NIH and AHA staff to the royal palace, where they were honored in a huge celebratory feast. The drug companies of Acirema were delighted too - they had grown very, very, very rich, and showered the NIH and AHA staff with tokens of their appreciation. Some of the NIH and AHA staff were even offered prestigious, highly-paid positions within the drug companies.

All was well in the kingdom!

That is, until some of the naughty villagers began pointing out that maybe, just maybe, statin drugs were not quite as wonderful as they had been made out to be.

Uh, oh…

Waking Up From The Statin Fantasy

For those who haven't caught on yet, the above story is no fairy tale. With some name changes to protect the not-so-innocent and a few other slight twists (I made up the bit about Better Homes and Gardens), the above tale pretty well describes the course of what may well be the biggest and most successful scam of the Twentieth Century - the widely accepted theory that elevated cholesterol levels cause heart disease.

After decades of failed drug and dietary intervention trials,(1) the cholesterol hypothesis that the health orthodoxy had invested so heavily in was beginning to look like a total bust. So when the positive results from statin trials started rolling in during the mid-nineties, the powers-that-be could barely contain themselves. Finally, proof that cholesterol-lowering worked! Statins were quickly dubbed "miracle drugs", became a physician favorite, and were transformed into the second-best selling class of drugs in the world. In fact, the current number one selling pharmaceutical in the world, which amassed a staggering 6.4 billion dollars of sales in 2001, is atorvastatin, made by Pfizer and marketed under the name Lipitor.(2)

The monumental success of statin drugs is a powerful, and sad, testament to the madness inherent in the cholesterol phenomenon. While many health authorities, researchers, and physicians just about trip over themselves in their rush to praise statins, a number of safety issues raise serious concerns about their suitability for long term use. Before we address these worrying issues, let's first examine whether cholesterol reductions are in fact responsible for any reduction in CHD mortality produced by statin administration.

Just How Do Statins Work?

While heavily promoted, the claim that the CHD reductions seen in clinical trials with statins are due to their potent cholesterol-lowering action is scientifically baseless. A close look at the data from all of the major controlled, randomized clinical trials with statin drugs reveals that there was no association between the degree of total cholesterol lowering and the CHD survival rate. In other words, the risk of a fatal heart attack was similarly reduced whether cholesterol levels were lowered by a small or large amount. The same applies to LDL, which we have been brainwashed into believing is the "bad" cholesterol; death rates in those with the highest and lowest LDL levels are virtually identical.(3-9) There is one exception - the recent PROSPER trial, which recorded the highest survival rates in both the treatment and control groups among those with the highest LDL levels.(10)

If statins exert a favorable effect on coronary health, it sure as hell isn't through cholesterol reduction!

Beyond Cholesterol.

Statin drugs exert their lipid-lowering effect by blocking an enzyme in the liver that is involved in the early stages of cholesterol synthesis. Statins inhibit the synthesis of mevalonate, a precursor not only to cholesterol, but also to a substance known as geranyl-geraniol. Inhibition of geranyl-geraniol may produce beneficial effects on levels of Nitric Oxide (NO), a substance with anti-inflammatory and artery-dilating properties.(11-13) The consequences of this dual action are widespread:
- In research with mice, statins markedly reduced measures of both inflammation and atherosclerosis, even though there was little change in serum cholesterol levels.(14)

- Fluvastatin has reversed the progression of atherosclerosis in rabbits, without any accompanying change in serum cholesterol.(15)

- In an Italian study, researchers placed a collar around one of the carotid arteries in rabbits to stimulate narrowing of the arterial wall. After 14 days, the collared arteries of rabbits treated with fluvastatin, lovastatin and simvastatin narrowed significantly less than those in untreated animals. Cholesterol levels in the rabbits were unchanged.(16)

- In human volunteers with slightly elevated cholesterol, researchers found that 4 weeks of simvastatin therapy significantly enhanced forearm blood flow, a measure of arterial function. The amount of improvement was unrelated to the degree of cholesterol reduction.(17)

- In elderly diabetic patients, cerivastatin increased dilation of the brachial artery after only 3 days, before any change in cholesterol levels had occurred.(18)

- Statins have been shown to reduce blood platelet production of thromboxane, an eicosanoid that encourages blood-clotting. This effect was not seen with the older drugs that lowered total or LDL cholesterol such as cholestyramine, cholestipol, and fibrates.(19)

- Statins have also been observed to inhibit the migration of smooth muscle cells seen in atherosclerotic plaque formation.(20,21)

- In the PRISM study, the effect of statin therapy on coronary event rates was evaluated in 1616 patients with proven coronary artery disease and a history of chest pain during the 24 hours prior to hospital admission. At 30 days, statin therapy significantly reduced mortality and the incidence of nonfatal myocardial infarction compared with patients who did not receive statins. The need for revascularization, and the length of hospitalization was also decreased by statin therapy. The benefits were independent of cholesterol-reduction - total cholesterol levels were similar between treatment groups throughout the study.(22)

- Statins may prevent advanced atherosclerotic plaques, or atheromas, from rupturing. Plaque rupture is believed to be the instigating factor in a significant portion of coronary events.(23)

- Statins lower C-reactive protein, an inflammatory protein that is a far better predictor of future heart attack risk than the establishment's favorite whipping boy, cholesterol.(24,25)

- Statins have been shown to reduce the preponderance of small, dense LDL particles; individuals whose LDL profile is characterized by these oxidation-prone small LDL particles have a significantly increased risk of CHD compared to those whose LDL profiles are characterized by large LDL particles.(26, 27)

So much for the theory that statins owe their efficacy to cholesterol-lowering…now, what about their safety record?

All Is Not Well In The Kingdom

A visit to any of the numerous health-oriented forums on the internet will quickly reveal hundreds of posts from dissatisfied statin users, describing an alarming array of side-effects: the most common being extreme fatigue, nausea, gastrointestinal problems, and muscle weakness and pain. Complaints about doctors' inability to link their recent health problems with statin use are frequent. In many instances, users report that they put two-and-two together themselves, stopped taking the drugs, and experienced significant or even complete remission of their symptoms.

Frequent side effects are no doubt a major reason why up to 75% of people taking statins discontinue their use.(29-30)

Of course, defenders of statins are quick to point out the low incidence of adverse effects in controlled, randomized clinical trials as proof of their alleged safety, but as we say here in Australia, "big bloody deal!" When recruiting for statin clinical trials, researchers carefully screen for, and exclude, a wide range of individuals including women of childbearing age, those with a history of drug or alcohol abuse, poor mental function, heart failure, arrhythmia, and other cardiac conditions, liver and kidney disorders, cancer, "other serious diseases", and "hypersensitivity" to statins. Thus, the disparity between the widespread "real-world" prevalence of side effects from statin use and the low prevalence of side effects in clinical trials is hardly surprising. These trials exclude groups that comprise a significant proportion of the real world population, and can hardly be taken as a realistic barometer for the expected incidence of side effects in the general population.

And even with these strict exclusion criteria, there is evidence to show that the clinical experience with statins has been far from trouble-free. Data for the largest statin trial, the Heart Protection Study (HPS), suggest that the daily 40mg dose of simvastatin used was nowhere near as well tolerated as the authors would have us believe. A substantial number of patients did not enter the trial after a six week run-in before randomization; of the 63,603 potential trial participants who entered the original screening, only 32,145 proceeded to the run-in phase. Of these, 11,609 patients - over one third - dropped out before the official start of the trial.(31)

Regardless of what orthodoxy would have us believe, the dangers from statin use are very real, as illustrated by the tragic death of Mrs. Elnoisa Calabio. Mrs. Calabio's story was presented at an FDA public hearing in May 2000:

"On October 7, 1999, at the age of 48, registered nurse, wife and mother, Elnoisa Calabio, succumbed to the end stages of irreversible dermatomyositis and interstitial pulmonary fibrosis directly caused by her use of a prescribed cholesterol-lowering medication, simvastatin (Zocor). Mrs. Calabio had no substantial risk factors for heart disease. Her blood pressure was controlled. Her cholesterol was slightly high, but not considered dangerous. Tragically, in her last days she knew that the cholesterol lowering drug her doctor had recommended to extend her life was in fact the cause of her fatal illness."(32)

Contrary to decades of anti-cholesterol propaganda, the mere presence of elevated cholesterol does not constitute a "disease". In any sane world, prescribing potentially deadly drugs to individuals free of heart disease, simply because they failed to meet some arbitrary level of serum cholesterol, would amount to flat-out medical malpractice.

Sadly, Mrs Calabio's family is hardly alone in grieving the needless, statin-induced loss of a loved one. In August 2001, pharmaceutical giant Bayer was forced to withdraw Baycol (cerivastatin) from the market, after at least fifty-two deaths had been linked to the drug. Baycol was causing rhabdomyolysis, a condition characterized by severe muscle damage. This rare disorder occurs when a large number of skeletal muscle cells die, subsequently releasing massive amounts of muscle protein into the bloodstream. This muscle protein saturates the kidneys, effectively overwhelming their filtration capacities. Indeed, kidney failure was reportedly a major cause of death amongst the Baycol victims. Baycol is not unique in its ability to damage muscle - all the statins have been shown to produce muscle disorders in susceptible patients, and muscle pain is one of the most common reasons for patients being taken off statin drugs.(33) Researchers recently reported that some patients may suffer muscle deterioration caused by statins while still maintaining normal levels of creatine kinase, the most commonly used indicator of muscle damage.(34)

Statins have also been shown to deplete the body of Coenzyme Q10 (CoQ10). (35) CoQ10 is a crucial component of mitochondria, the intracellular "engines" responsible for producing almost all of a cell's energy requirements. In addition to this fundamental role in energy production, CoQ10 acts as a potent antioxidant. Not surprisingly, CoQ10 is extremely important for cardiovascular health, with high levels being found in healthy heart tissue.

An indication of C0Q10's vital importance for cardiovascular health can be gleaned from a recent randomized, double-blind, controlled trial, which compared the effects of oral CoQ10 (120 mg/day) with a vitamin-B placebo in 144 patients after acute myocardial infarction. Approximately half of the patients in each group were receiving lovastatin (10 mg/day). After 1 year, both fatal and non-fatal cardiac events were significantly lower in the CoQ10 group. Twenty-five percent CoQ10 patients experienced a cardiac event during the study, compared to 45% of the control subjects. When the researchers examined the incidence of adverse effects, they found that 41% of the control subjects had experienced fatigue, compared to only 7% in the CoQ10 group.(36)

Ironically, while statins reduce the risk of atherosclerotic heart disease, their CoQ10-robbing effects have been linked to an increased risk of congestive heart failure. Figures from the National Center for Health Stastistics show that since the early nineties - when statin drugs began hitting pharmacy shelves - the incidence of congestive heart failure has risen sharply.(37) CHF, in fact, is the fastest growing cardiovascular disorder in the United States. Sadly, there is no cure for CHF short of a heart transplant. Peter H. Langsjoen, MD, a foremost authority on the use of coenzyme Q10 in the treatment of heart disease, has little doubt as to the culprit behind this sharp rise in CHF:

"In my practice of 17 years in Tyler, Texas, I have seen a frightening increase in heart failure secondary to statin usage, "statin cardiomyopathy". Over the past five years, statins have become more potent, are being prescribed in higher doses, and are being used with reckless abandon in the elderly and in patients with "normal" cholesterol levels. We are in the midst of a CHF epidemic in the US with a dramatic increase over the past decade. Are we causing this epidemic through our zealous use of statins? In large part I think the answer is yes." (38)

While CoQ10 is not only critically important for healthy cardiovascular function; the brain is also highly vulnerable to CoQ10 deficiencies. When healthy young men were given either statin drugs or a placebo, those taking lovastatin displayed significant deterioration in cognitive function after only three weeks of treatment.(37) Brian Vonk, M.D., of The Optimal Wellness Center, reported recently that, in his own experience and that of his colleagues, "… statins cause depression or loss of motivation in the majority of patients, probably due to alteration of cholesterol metabolism in the brain. As a result, many of these patients are also on [antidepressant] drugs (e.g. Zoloft, Paxil, Prozac)."(40)

The deleterious effects of statins on CoQ10 levels are hardly news to drug company manufacturers. In 1989, Merck & Co., Inc. filed two patents for the use of CoQ10 with statins in order to prevent CoQ10 depletion and attendant side effects. The patent applications, which can be viewed online at the United States Patent and Trademark Office website,(41) clearly show that the statin manufacturer was aware of the link between CoQ10 depletion and heart failure. One of the Merck patent applications states that: "Since Coenzyme Q10…is of benefit in congestive heart failure patients, the combination with HMG-CoA reductase inhibitors (statin drugs) should be of value in such patients who also have the added risk of high cholesterol."

Research has shown that statin-induced CoQ10 deficiency can be prevented with supplemental CoQ10, without adverse impact on the drugs' cholesterol-lowering or anti-inflammatory properties.(42). Amazingly, even though both of the Merck patents were granted in 1990, the company has neither exercised the patents nor educated physicians or patients about the necessity of taking coenzyme Q10 along with statin drugs. The end result is that most doctors and their patients remain completely ignorant that failure to supplement statin drugs with coenzyme Q10 may have potentially life-threatening consequences.

Statins and Cancer

In 1996 the Journal of the American Medical Association published an extensive review of the research studying the link between cholesterol-lowering drugs and cancer. The authors, Dr Thomas Newman and Dr. Stephen Hulley, stated: "All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans." In light of their findings, the authors recommended that: "lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease."(43)

Newman and Hulley's recommendation has been all but ignored. Statins are being recommended and prescribed, not just to people at high short-term risk, but to perfectly healthy people who show no clinical manifestations of CHD whatsoever, except for the non-disease of hypercholesterolemia. Even children with "elevated" cholesterol levels are being urged to commence statin therapy, marking a new dismally low point in the history of cholesterol paranoia.

Drug companies and health authorities repeatedly assure us that statins are wonderful low-risk drugs that are well tolerated in most people. They claim that clinical trials have shown no increase in cancer incidence with statin use, but the longest of these studies ran for only 6 years (excepting the EXCEL trial, which showed an increase in total mortality after 1 year of lovastatin use, and for which no subsequent mortality data has ever been released(44)). Cancer is a chronic disease that may take decades to manifest itself as a life-threatening illness - can we really conclude from trials lasting five to six years that statins are safe for lifetime use? Even heavy smokers are highly unlikely to develop cancer within six years of taking their first puff; most continue for decades before they come to realize the true value of those little warnings adorning cigarette packets.

Because rodent studies routinely use far higher dosages of drugs than those prescribed to humans, some have questioned the relevance of Newman and Hulley's findings. In many studies, rodents have been shown to eliminate drugs much faster than humans, necessitating higher dosages to maintain constant blood levels of the drug. The authors noted, however, that when the drug exposure was considered in terms of blood levels, carcinogenicity occurred at levels close to those seen in humans. In the same journal in which this review appeared, a commentary critical of Hulley and Newman claimed that higher dosages used in rodents placed inordinate stress on their gastrointestinal tracts, and that most of the cancers seen in rodent studies were malignancies of the gastrointestinal tract and liver.(45) Given that gastrointestinal distress and liver toxicity are among the most frequently reported side effects in patients prescribed statins, this proffered explanation provides little reassurance.

Cancer Incidence In Human Statin Trials: A Closer Look.

The claim that statin trials have not shown any increase in cancer is disputed by the recent PROSPER trial, which found a 25% increase in newly diagnosed cancers among elderly individuals treated with pravastatin. While there were 20 less deaths from CHD and stroke in the treatment group, 24 more deaths from cancer were observed, and, in an ominous confirmation of animal findings, one of the highest increases was observed for gastrointestinal cancers.(46) The PROSPER authors dismissed these findings by referring to a pooled analysis they performed of eight statin trials that lasted three or more years, which showed no statistically significant difference in cancer incidence between the placebo and statin groups (6.9% versus 7.1%, respectively). However, most of these trials involved younger subjects. Because cancer risk increases with age, such a comparison bears little relevance to the PROSPER results. Due to their heightened risk, elderly subjects may act as a far more sensitive barometer to any cancer-promoting capacity possessed by statins.

Furthermore, as researcher Uffe Ravnskov, M.D., PhD., recently pointed out, the PROSPER researchers' analysis did not include skin cancer.(47) Considering the relatively short-term nature of statin trials, it is the incidence of such an easily detectable, superficial cancer that would provide the strongest clue as to the future cancer-causing potential of statins. Only two of the statin trials have reported skin cancer incidence; the 4S and HPS simvastatin trials. Increases in skin cancer were noted in both.(48,49)

In the CARE trial, breast cancer, another readily detectable malignancy, developed in 12 women from the treatment group but in only one of the control individuals - a highly significant difference.(50) Breast cancer was also the malignancy for which the greatest increase was noted in the PROSPER trial. The possibility that statins will lead to future increases in cancer incidence cannot be flippantly dismissed.

To maintain their lipid-lowering effects, statins must be administered on a life-long basis. The reports of carcinogenicity from rodent studies and increases in superficial cancers noted in human trials warrant extreme caution. Given the complete lack of data on the effects of decades of statin administration, users can consider themselves part of a mass experiment in progress, the outcome of which is largely unknown.

Warnings for statin use to be limited to high-risk patients - where dramatically shortened life expectancies may override any concerns about long-term side-effects -have been completely overshadowed by the relentless promotional efforts of drug companies and enthusiastic endorsements from health authorities who are besides themselves at finally having clinical data that, on the surface, appears to support the lipid hypothesis.

Are we witnessing the unfolding of another officially-endorsed health disaster? Only time will tell. For those who do not want to find out the hard way, there are numerous non-drug measures that can help alleviate the risk of CHD. Randomized trials involving increases in fish/fish oil and/or fruit and vegetable consumption have produced risk reductions in mortality similar, and in some instances superior, to those seen in statin trials;(51-57) these safe, natural food items, as well as exercise, stress reduction, sound sleep, and a low glycemic load diet (i.e.., a low-to-moderate carbohydrate diet comprised of unrefined low glycemic foods), would be a far more judicious preventive alternative for those with no clinical signs of CHD.


1. Corr LA, Oliver MF. The low fat/low cholesterol diet is ineffective. European Heart Journal, 1997; 18: 18-22.

2. Pfizer Annual Report 2001. Available online at: annual/2001/p2001ar17.html

3. Shepherd J, et al. Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia. New England Journal of Medicine, Nov 16, 1995; 333 (20): 1301-1308.

4. Sacks FM, et al. The Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholesterol Levels. New England Journal of Medicine, Oct 3, 1996; 335 (14): 1001-1009.

5. Sacks FM, et al. Relationship Between Plasma LDL Concentrations During Treatment With Pravastatin and Recurrent Coronary Events in the Cholesterol and Recurrent Events Trial. Circulation, 1998; 97: 1446-1452.

6. The Long-Term Intervention with Pravastatin In ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. New England Journal of Medicine, 1998. Vol. 339: 1349-1357.

7. Downs JR, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. Journal of the American Medical Association, 1998; 279: 1615-1622.

8. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high risk individuals: a randomised placebo-controlled trial. Lancet, 2002; 360: 7-22M.

9. Ravnskov U. Implications of 4S evidence on baseline lipid levels. Lancet, Jul 1995; 346: 181.

10. Shepherd J, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet, Nov. 23, 2002; 360 (9346): 1623-30.

11. Laufs U, et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation, 1998; 97: 1129-1135.

12. Dimmeler S, Zeiher AM. Nitric oxide-an endothelial cell survival factor. Cell Death and Differentiation, Oct, 1999; 6 (10): 964-968.

13. Laufs U, Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. Journal of Biological Chemistry, 1998; 273: 24266-24271.

14. Sparrow CP et al. Simvastatin Has Anti-Inflammatory and Antiatherosclerotic Activities Independent of Plasma Cholesterol Lowering. Arteriosclerosis, Thrombosis, and Vascular Biology, 2001; 21: 115

15. Kano H, et al. A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels: possible relevance of up-regulation of endothelial NO synthase mRNA. Biochemical and Biophysical Research Communications, 1999; 259: 414-419.

16. Soma MR, et al. HMG CoA reductase inhibitors. In vivo effects on carotid intimal thickening in normocholesterolemic rabbits. Arteriosclerosis, Thrombosis, and Vascular Biology, Apr, 1993; 13 (4): 571-578.

17. O'Driscoll G et al. Simvastatin, an HMG-Coenzyme A Reductase Inhibitor, Improves Endothelial Function Within 1 Month. Circulation, 1997; 95: 1126-1131.

18. Tsunekawa T et al. Cerivastatin, a Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor, Improves Endothelial Function in Elderly Diabetic Patients Within 3 Days. Circulation, 2001; 104: 376.

19. Schror K. Platelet reactivity and arachidonic acid metabolism in type II hyperlipoproteinaemia and its modification by cholesterol-lowering agents. Eicosanoids, 1990; 3 (2): 67-73.

20. Statins have been shown to inhibit the migration of smooth muscle cells Yasunari K, et al. HMG-CoA reductase inhibitors prevent migration of human coronary smooth muscle cells through suppression of increase in oxidative stress. Arteriosclerosis, Thrombosis, and Vascular Biology, Jun, 2001; 21 (6):937-942.

21. Hidaka Y, et al. Inhibition of cultured vascular smooth muscle cell migration by simvastatin (MK-733). Atherosclerosis, Jul, 1992; 95 (1): 87-94.

22. Heeschen C, et al, on behalf of the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Investigators. Circulation, Mar. 26, 2002; Vol. 105; No. 12: 1446-1452.

23. Brown BG, et al. Lipid-lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease. Circulation, Jun 1993; 87: 1781-1791.

24. Jialal I, et al. Effect of Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitor Therapy on High Sensitive C-Reactive Protein Levels. Circulation, Apr 2001; 103: 1933 - 1935.

25. Ridker PM, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England Journal of Medicine, March 23, 2000; 342 (12): 836-843.

26. Sone H, et al. HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes. Life Sci. 2002 Oct 4; 71 (20): 2403-2412.

27. Lariviere M, et al. Effects of atorvastatin on electrophoretic characteristics of LDL particles among subjects with heterozygous familial hypercholesterolemia. Atherosclerosis, Mar, 2003; 167 (1): 97-104.

28. Jackevicius CA, et al. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. Journal of the American Medical Association, Jul. 24-31, 2002; 288 (4): 462-467.

29. Avorn J, et al. Persistence of use of lipid-lowering medications: a cross-national study. Journal of the American Medical Association, May 13, 1998; Vol. 279, No. 18: 1458-1462.

30. Cohen JS. Over Dose: The Case Against the Drug Companies: Prescription Drugs, Side Effects, and Your Health. Penguin USA. 2001.

31. MRC/BHF Heart Protection Study Collaborative Group. Heart protection study of cholesterol lowering therapy and antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: early safety and efficacy experience. European Heart Journal, 1999; 20: 7254.

32. Barnett, BP. RE: Notice of request for participation by consumer and interested persons in public hearing June 28, June 29, 2000 [Docket No. 00N-1256]. Available online: (accessed 19th Feb. 2003)

33. Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Annals of Pharmacotherapy, Feb, 2002; 36 (2): 288-295

34. Philips, PS et al. Statin-associated myopathy with normal creatine kinase levels. Annals of Internal Medicine, Oct. 1, 2002; 137: 581-585.

35. Jula A, et al. Effects of Diet and Simvastatin on Serum Lipids, Insulin, and Antioxidants in Hypercholesterolemic Men. Journal of the American Medical Association, 2002; 287: 598-605.

36. Singh RB, et al. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Molecular and Cellular Biochemistry, Apr, 2003; 246 (1-2): 75-82.

37. See figure 1. Deaths from congestive heart failure, 1968-1993. Vital Statistics of the United States, National Center for Health Stastistics, cited in Congestive Heart Failure in the United States: A New Epidemic. Data Fact Sheet. National Heart, Lung, and Blood Institute, National Institutes of Health. Available online at: (accessed Feb 11, 2004)

38. Langsjoen PH. Statin-induced cardiomyopathy. Introduction to the citizens petition on statins. Available online: (accessed Feb 11, 2004)

39. Roth T, et al. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clinical Cardiology, 1992; 15: 426-432.

40. Vonk B. How to Determine Your Cardiovascular Health. Optimal Wellness Newsletter, Issue 391, January 4, 2003. (accessed 15 January 2003).

41. Patent applications 4,933,165 (filed January 18, 1989) and 4,929,437 (filed February 2, 1989) can be viewed by visiting and entering the patent numbers in the 'query' box, then clicking on the 'search' tab (accessed Feb 11, 2004).

42. Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors, 2003; 18 (1-4): 101-111.

43. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. Journal of the American Medical Association, Jan 3, 1996; 275: 55-60.

44. Bradford RH et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Archives of Internal Medicine, Jan, 1991; 151 (1): 43-49.

45. Dalen J, Dalton W. Does Lowering Cholesterol Cause Cancer?. Journal of the American Medical Association, Jan 3, 1996; 275: 67-69.

46. Shepherd J, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet, 2002; 360: 1623-1630.

47. Ravnskov U. Evidence that statin treatment causes cancer, and Ravnskov U, et al. Evidence from the simvastatin trials that cancer is a probable long-term side effect. Unpublished letter to the editor of Lancet, available online: (accessed March 27, 2003).

48. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet, 1994; 344:1383-1389.

49. Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet, 2002; 360: 7-22.

50. Sacks FM, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New England Journal of Medicine, 1996; 335: 1001-1009.

51. Burr ML, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet, 1989; 2: 757-761.

52. Singh RB, et al. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival-4. Cardiovascular Drugs And Therapy, 1997; 11: 485-491.

53. Marchioli R, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation, 2002; 105: 1897-1903.

54. Singh RB. Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. Magnesium and Trace Elements, 1990; 9 (3): 143-151.

55. Singh RB, et al. Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow-up. British Medical Journal, 1992; 304:1015-1019.

56. De Lorgeril M, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet, 1994; 343: 1454-1459.

57. Singh RB, et al. Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomized single-blind trial. Lancet, 2002; 360: 1455-1461.

Anthony Colpo is an independent researcher and certified fitness consultant with 20 years' experience in the physical conditioning arena. To contact:

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