Colesterol Myth - It's official: Statins proponents have lost their minds!

The authors clarify this last qualification as such: "On the basis of the safety data pertaining to these drugs, routine monitoring of muscle enzymes and liver function tests is probably not warranted unless patients have symptoms, have baseline abnormalities of liver function tests or myopathy, or are taking other drugs that interact with statins to increase the risk for adverse events."

The medical profession, all nice'n'cosy and suckling happily away at the ever-flowing bosom of the pharmaceutical cartel, still seems to harbor this absurd illusion that statins are wonderfully safe drugs that have an extremely low incidence of side effects.

Tightly-controlled clinical trials involving statins, we are told, have shown an extremely low rate of adverse effects. So what?! Clinical trails carefully screen for and promptly exclude a wide range of folks, 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, clinical statin 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.

This sort of careful screening is par for the course with clinical trials, so it's no wonder that 51% percent of prescription drugs are subsequently found to have serious adverse effects not detected prior to regulatory approval!(1)

And even with such strict exclusion criteria, there is evidence to show that the clinical trial 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.(2)

One book I would wholeheartedly recommend to readers is Over Dose: The Case Against the Drug Companies by Jay S. Cohen, M.D. Cohen's book provides a revealing insight into the highly incestuous relationship between the medical profession, research scientists, and the drug manufacturers. One unfortunate manifestation of this overly-cosy triad is the state of denial exhibited by many doctors when it comes to pinpointing the blame for drug-induced side effects. Even when the evidence appears to be staring them in the face, many doctors appear extremely reluctant to ascribe patients' complaints to the 'wonder-drugs' they write scripts for every day.

Last night, we were visited by my wife's auntie, who recounted the recent experiences of a friend that had recently quit taking statins. This friend, aged in her sixties, had been placed on statins by her doctor. She subsequently developed severe muscle pains and weakness, a classic textbook side effect of statin drugs. She complained several times to her doctor about the muscle pains - only to be told that she was simply imagining things! Eventually, she gave up on this idiot and went and saw another doctor, who promptly told her to stop taking her statin drug.

A week or so ago I received an e-mail from a fellow Aussie, thanking me for writing my recent statin article. The reason for this lady's gratitude was that my article finally alerted her to the cause of the unexplained muscle pains she had been experiencing. Her doctor did not have the foggiest idea that her persistent muscle complaints might be due to the statin he had prescribed her.

For crying out loud! 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.

Where were all these doctors the day that Baycol got pulled - playing golf?

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.(3)

A paper that appeared in a 2002 edition of the American Journal of Cardiology claimed that statin-related liver toxicity was rare, and even discouraged routine liver testing of statin patients because it was "overly burdensome and expensive", and "may increase patient risk because of needless discontinuation of cholesterol-lowering therapy for false-positive results in patients who are benefiting from therapy."(4)

The author cited as support for his stance the low incidence of elevated liver enzyme readings in published clinical trials (see above). Seven cases of liver disease were reported in the EXCEL trial (for which one of the exclusion criteria was preexisting elevation in liver enzymes) but 'logistic regression analysis' showed that the probability of an increase in the liver enzyme alanine aminotransferase (ALT) correlated with the daily intake of alcohol, increasing weight, higher baseline ALT readings ... oh, and with increasing doses of lovastatin! As for the higher incidence of elevated liver enzyme readings in pre-marketing trials, these were dismissed by virtue of the lack of evidence for liver disease in patients with elevated liver enzyme counts who were withdrawn from statins. Gee, maybe the researchers should have let them continue, you know, just to see what would have happened.

The American Journal of Cardiology article also highlighted the low incidence of reported statin side effects on toxicology databases. Again, big bloody deal! Considering that many doctors appear to lack the ability to recognize the source of statin-induced side effects, it's no great surprise they are not frequently reported. And even if doctors did recognize the source, how many would go to the trouble of making a formal report?

Even the FDA acknowledges that adverse drug reactions are grossly underreported. In March 2000, the FDA's associate director of the Office of Postmarketing Drug Risk Asessment, Jerry Philips stated that the 250,000 adverse reports that the agency receives each year probably represent only 5% of the actual reactions that have occurred.(5)

Bottom line: if, for some strange reason, I began taking statins, I would sure-as-hell demand that my doctor kept a close eye on my liver function, and if I started feeling uncharacteristic muscle pain and weakness, I'd make some very loud noises until my doctor listened.

I would also make sure I was taking supplemental co-enzyme Q10, a crucial substrate for cellular energy production which is readily depleted by statin drugs. CoQ10 depletion may do more than just make your muscles hurt; this substance is vitally important for proper heart function, and low levels may increase the risk of heart failure. Indeed, the incidence of congestive heart failure dramatically increased soon after the first statins hit the market, and has been rising ever since.(6)

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.(7)

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,(8) 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." 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 second recent study that got yours truly riled up was a recent report in the Journal of the American Medical Association that claimed statin drugs are being 'under-utilized' in the elderly.

What a lot of rot! Only one clinical trial has examined the use of statin drugs in the elderly, and all it showed was that people in this age group should be very wary about taking statins. This was the PROSPER trial where 604 seniors aged 70-82 years with a history of, or risk factors for, cardiovascular disease were assigned to either 40 mg of pravastatin per day, or a placebo. While there were 28 fewer CHD deaths in the treatment group, there were 24 more cancer deaths. Call me a scrooge, but I wouldn't consider that a very good trade!(9)

Elderly folks should know that there is little evidence to show that cholesterol-lowering will benefit them in any way. Epidemiological research has consistently found elevated cholesterol is not a risk factor for cardiovascular disease in the elderly.(10-27) In fact, a number of studies have found that high cholesterol levels in the elderly are predictive of decreased cardiovascular mortality and increased survival!

References

1. Moore TJ, et al. Time to act on drug safety. Journal of the American Medical Association, May 20, 1998; 279 (19): 1571-1573.

2. 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.

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

4. Tolman KG. The liver and lovastatin. American Journal of Cardiology, June 15, 2002; 89: 1374-1380.

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

6. 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: http://www.nhlbi.nih.gov/health/public/heart/other/CHF.htm (accessed Feb 11, 2004)

7. 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.

8. Patent applications 4,933,165 (filed January 18, 1989) and 4,929,437 (filed February 2, 1989) can be viewed by visiting http://patft.uspto.gov/netahtml/srchnum.htm and entering the patent numbers in the 'query' box, then clicking on the 'search' tab (accessed Feb 11, 2004).

9. 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.

10. Anderson KM, et al. Cholesterol and mortality. 30 years of follow-up from the Framingham study. Journal of the American Medical Association, 1987; 257: 2176-2180.

11. Forette F, et al. The prognostic significance of isolated systolic hypertension in the elderly. Results of a ten year longitudinal survey. Clinical and Experimental Hypertension. Part A, Theory and Practice, 1982; 4: 1177-1191.

12. Siegel D, et al. Predictors of cardiovascular events and mortality in the Systolic Hypertension in the Elderly Program pilot project. American Journal of Epidemiology, 1987; 126: 385-389.

13. Nissinen A, et al. Risk factors for cardiovascular disease among 55 to 74 year-old Finnish men: a 10-year follow-up. Annals of Medicine, 1989; 21: 239-240.

14. Krumholz HM, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. Journal of the American Medical Association, 1994; 272: 1335-1340.

15. Weijenberg MP, et al. Serum total cholesterol and systolic blood pressure as risk factors for mortality from ischemic heart disease among elderly men and women. Journal of Clinical Epidemiology, 1994; 47: 197-205.

16. Simons LA, et al. Diabetes, mortality and coronary heart disease in the prospective Dubbo study of Australian elderly. Australian and New Zealand Journal of Medicine, 1996; 26:66-74.

17. Weijenberg MP, et al. Total and high density lipoprotein cholesterol as risk factors for coronary heart disease in elderly men during 5 years of follow-up. The Zutphen Elderly Study. American Journal of Epidemiology, 1996; 143: 151-158.

18. Simons LA, et al. Cholesterol and other lipids predict coronary heart disease and ischaemic stroke in the elderly, but only in those below 70 years. Atherosclerosis, 2001; 159: 201-208.

19. Abbott RD, et al. Age-related changes in risk factor effects on the incidence of coronary heart disease. Annals of Epidemiology, 2002; 12: 173-181.

20. Zimetbaum P, et al. Plasma lipids and lipoproteins and the incidence of cardiovascular disease in the very elderly. The Bronx aging study. Arteriosclerosis Thrombosis and Vascular Biology, 1992; 12: 416-423.

21. Fried LP, et al. Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. Journal of the American Medical Association, 1998; 279: 585-592.

22. Chyou PH, Eaker ED. Serum cholesterol concentrations and all-cause mortality in older people. Age and Ageing, 2000; 29: 69-74.

23. Menotti A, et al. Cardiovascular risk factors and 10-year all-cause mortality in elderly European male populations; the FINE study. European Heart Journal, 2001; 22: 573-579.

24. Räihä I, et al. Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. . Arteriosclerosis Thrombosis and Vascular Biology, 1997; 17: 1224-1232.

25. Forette B, et al. Cholesterol as risk factor for mortality in elderly women. Lancet, 1989; 1: 868-870.

26. Schatz IJ, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet, 2001; 358: 351-355.
18. Jonsson A, et al. Total cholesterol and mortality after age 80 years. Lancet, 1997; 350: 1778-1779.

27. Weverling-Rijnsburger AW, et al. Total cholesterol and risk of mortality in the oldest old. Lancet, 1997; 350: 1119-1123.

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

Disclaimer: This article is presented for information purposes only and is not intended as medical advice. Persons with medical conditions should institute dietary changes whilst being monitored by a competent medical practitioner.

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