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This feature on statins and their adverse reactions was published in Dutch on January the 10th 2004, in AD Magazine, the weekend magazine of the newspaper Algemeen Dagblad. The article led to furious attacks on the author. In a primetime television show doctors and peer journalists accused him for deliberately spreading false, biased and potentially deadly information. He finally ended up in the Dutch Press Council, accused by a pharma-sponsored patient organization. The Council concluded: ‘Although the article is coloured, the author presented enough journalistic evidence to write such a piece’. The accusation was called unfounded. Despite this judgement and although the article elicited hundreds of reactions from readers (among them doctors) who reported severe side effects, the item has never been followed up.


Statins - Miracle drug or tragedy?

 by Melchior Meijer

 Statins, drugs that lower our ’bad’ cholesterol, are being prescribed like if it were aspirin. Not only in ‘crazy’ America, also in the Netherlands. This year we swallow for about 320 million Euro and the trend points up, not in the least place thanks to our rapidly aging population. The golden milk cow of the pharmaceutical industry is saving lifes. Claims the industry. Say also most doctors. But a growing group of concerned scientists starts sending out SOS signals. “Statins prevent a few heart attacks, but they also cause chronic heart failure,” says a cardiologist. A colleague: “I think people taking those drugs should be really, really alert.”


Are you on Lipitor? Congratulations! By taking Lipitor (…) you are on the right track to healthy cholesterol levels. On Pfizers Dutch website, those who just got a prescription for the popular cholesterol drug Lipitor are welcomed like the Long Lost Son. The message is cristal clear: do exactely as Pfizer says – which usually means taking the drug for the rest of your life – and the feared black limousine will pass your front door for decades to come. On the background fit and active babyboomers ride there bicycles and have a good time. Together we will beat the bloody cholesterol. Join the club!

 Lipitor (atorvastatin) is just one of the excellent selling members of the family of HMG-CoA reductase inhibitors, most often called ‘statins’. In 1987, pharmaceutical giant Merck was first to launch this drug under the name Mevacor (lovastatine). Mevacor was nothing short of a revolution. Finally it was possible to normalize even very high levels of cholesterol. Popping just one pill a day did the trick. Gone were the days of the weird, inhumane diets, limiting the patients cuisine to cardboard bread and carrots. No more bitter powders, making you feel terribly sick. And what was even better: statines didn’t affect  the ‘good’ HDL cholesterol.

Now, seventeen years later, all the big pharmaceutical companies market their own statin. Some are a bit more potent than others, but they all basically do the same thing. Millions of people all over the world are obediantly taking their daily Zocor, Lipitor, Lescol, Crestor, Pravachol and several no name clones. ”Statins are the new aspirin,” researcher Rory Collins recently proclaimed in the medical journal The Lancet, referring to the ‘terrific’ outcome of his Heart Protection Study.

This seven-year lasting trial among 20.000 Britons, partially paid by Merck, showed that statins offer everybody a slight protection from getting a heart attack. The eldery, the young, men, women, people with very high cholesterol levels and people with normal or even low levels. Our own expert on atherogenesis Prof. Dr. Anton Stalenhoef from Nijmegen University expressed himself a little subtler, but nevertheless welcomed the results as ‘tremendously positive’. He rather calls statins ‘the new penicillin’. It must be quite nice to be employed by companies like Merck, Astra-Zeneca, Novartis and Pfizer these days. It looks like their cholesterol lowering treatments à 1000 Euro per person and year will get unmatched sales within the coming years.


There are, however, physicians and scientists who watch the crusade of this lucrative miracle pill with Argus eyes. In prominent medical journals they warn against negative side effects of long time use. Their doubts are not exactly benign. Using statins could over time promote cancer, chronic heart failure and memory problems, they say; side effects that we don’t find in the information receipt.

A heart medicine causing heart failure? Early 2002, a group of  Australian cardiologists appealed in The American Journal of Cardiology for an independent study into this supposed, paradoxical ‘side effect’. Chronic heart failure, a disabling disease in which the heart muscle slowly but steadily loses its ability to pump, is becoming more and more common in the western world. So common, that it can not be explained by the increasing age of the population and the growing number of people surviving an acute heart problem, according to the authors of the article. They add that ‘observant doctors all over the world suspect a role for the generously prescribed statins’.

 This suspicion is of course not falling out of the bright blue sky. “Statins make victims – a lot of victims – and by now it’s pretty clear how they do it,” is the bold comment of cardiologist Dr. Peter Langsjoen from Tyler, Texas, USA. Langsjoen gave up an attractive career in a university hospital to dedicate his competence to what he calls ‘statin induced congestive heart failure’. Langsjoen: “Statins block the enzyme HMG CoA-reductase.

This enzyme is responsible for the production of a substance called ‘mevalonate’. Mevalonate on its turn is the precursor of both cholesterol and co-enzyme Q10. This Q10 – also called ubiquinone because it is involved in myriads of physiological processes – is essential for the function of the mitochondria, the energy plants in our cells. Someone using statins, not only deprives the body from cholesterol, but also from a great deal of the Q10 normally being produced. The higher the statin dose, the less of both essential factors will be available to the body. The cells most depending on Q10 are those from the nerve system, the skeletal muscles, but particularly those from the heart muscle. Heart muscle cells literally stuff themselves with Q10. If they don´t get enough, they’ll say goodnight sooner or later. That’s the moment the patient presents with symptoms of heart failure. Older statin users will develop dangerously low levels within 6 to 12 months. For younger people it might take several years before problems manifest.”

What are those symptoms? Mainly extreme tiredness and muscle and joint pain, according to Langsjoen. Later on, shortness of breath may follow. “I see 2 to 3 new cases of statin induced heart failure per week in my practice. The first things I do are to measure their Q10 levels and improve them with a supplement. By the way, in Japan supplementing Q10 is a routine intervention in patients with congestive heart failure. The treatment is well documented.”

 Last year Langsjoen published own research in which he observed that two thirds of elder statin users show signs of ‘diastolic dysfunction’, one of the first signs of heart failure, after only six months of therapy. ”Physicians are prescribing these drugs with reckless abandon. We’re talking about extremely tricky stuff.”

In the summer of 2001 a striking amount of people ‘suddenly’ died of rhabdomyolysis, a ‘rare but very serious side effect of statin use’. All these people were on Baycol/Lipobay (cerivastatin), a statin that Bayer introduced three years earlier. When an aggressive strategy of denial didn’t work, the company saw no other way out than to take the pill that was meant to be their flagship from the market.

Was Baycol/Lipobay so much more dangerous than her sisters from the competitors? “It was a very potent statin,” explains Langsjoen. “But Pfizers’ Lipitor is only a little bit less potent and is thus only killing a little fewer people. A statin is a statin.” After the Baycol/Lipobay incident a group of scientists, lead by the Italian biochemist Gian Paolo Littarru, send a petition to the FDA and to the health authorities from the EU. From this petition: “It is possible that the reported statin related deaths are the top of an iceberg. (….) The extent of the observed statin induced Q10 deprivation should not be underestimated. There are indications that we doctors, with the best intentions, are creating a life-threatening situation in million of healthy patients. Conclusive research shows that supplementing this humble molecule could prevent tremendous suffering and costs.”

Would the pharmaceutical companies, with all the competence and technology they can buy, really not know what individual physicians ascertain with quite simple means? Do they possess unknown information, showing that those worried doctors got hold of the wrong end of the stick?

All too keen curiosity from outsiders is not appreciated in this business. An inquisitive person will not get real information, unless using illegal methods. But we may safely assume that the industry is aware of this hitch. Merck & Co Inc. deposited the patents US 4929437 respectively US 4933165 on the 29th of May and the 12th of June 1990, both stating: A pharmaceutical composition comprising a pharmaceutical carrier and an effective antihypercholerolemic amount of an HMG-CoA reductase inhibitor and an amount of Co-enzyme Q10 effective to couteract HMG-CoA reductase inhibitor-associated skeletal muscle myopathy. Merck claimed the exclusive rights to a combination drug of a statin and Q10. The vital combination was never realised. Apparently Merck didn’t want to make the combination drug, the competitors could not do it.

“We are at the beginning of the biggest medical tragedy that mankind ever witnessed,” cardiologist Langsjoen says. “Never before in history has the medical establishment knowingly created a life threatening nutrient deficiency in millions of otherwise healthy people, only to sit back with arrogance and horrific irresponsibility and watch to see what happens. I cannot help to view my once great profession with a mixture of sorrow and contempt.”

 Why does the pharmaceutical industry keep a simple formula that might prevent a disaster and in the worst case does no harm, off the market? Within the relatively small group of independent physicians and scientists discussing this matter openly, one explanation prevails. “A combination pill has to go through all the clinical trials again,” speculates biochemist Christian Allan, former worker on the National Institutes of Health, in the discussion forum of The International Network of Cholesterol Skeptics (THINCS). “They would have to form four groups. One group gets a placebo, one group takes the combination drug, one group gets the plain statin, and one group gets only Q10. Now, smaller studies have shown clear cardiovascular benefits of Q10-supplementation. The trial might thus find that the people in the Q10-only arm do just as fine or even better than the groups taking the combination or the statins.

This must be a nightmare for the industry. They would invest a fortune, only to prove that a ‘useless’ supplement is as effective and above all a lot safer than their multi billion dollar designer drug.” And why would the industry take such a risk? The worried scientists observe a ‘huge professional ignorance’ in the field. A majority of physicians isn’t even aware of the fact that Q10 plays a crucial role in cellular energy production. Cardiologist Langsjoen: “They think it´s some kind of snake oil, in the same category as shark cartilage and apple vinegar.” 

 To make one thing perfectly clear, statins do offer some protection against our number one cause of death, myocardial infarction. This protection is independent of cholesterol reduction. People with low levels profit just as much as people with high levels, while those whose LDL-levels remain quite high are having the best prognosis.

 Coincidentally statins possess strong anti-inflammatory properties and are able to stabilize the atherosclerotic plaques responsible for heart attacks. This does safe lives. But the drug companies really understand the business on the fair. Without lying, they paint a somewhat misleading picture; a matter of playing with numbers. A nice example is WOSCOPS, which examined the effect of pravastatin in healthy people with very high cholesterol levels. In The Netherlands, this group is almost automatically put on lifelong statin therapy. In his ads the manufacturer presents an impressive 25 percent risk reduction.

 But what does this imply? Were there 25 more heart deaths in the group not taking the drug? Not at all. After five years 98.8 percent of the patients taking Pravachol were still alive. In the placebo group ‘only’ 98,4 percent was still alive and kicking. The relative risk reduction – the difference between 1.2 and 1.6 – is indeed 25 percent, a difference just being statistically significant. This modest effect is overshadowed by several studies showing a quite sinister cancer mortality in the treated groups.

 Notorious is the so-called CARE trial. Twelve women in the statin group developed breast cancer, compared to only one in the control group. Another large study, the EXCEL project starring Merck’s lovastatine, was stopped after only eleven months, when the Mevacor group was producing 275 percent more deaths, mainly from cancer.

In animal models statin therapy almost invariably causes cancer and an untimely death, but according to the industry it is impossible to extrapolate such ‘hard endpoints’ to people. The same argument they use with regard to a Swiss study, recently published in Nature Medicine. It showed that Lipitor, Mevacor and Provachol effectively knock out the T-Helper cells, the Special Forces of the immune system. The authors find statins immunosupressive potency so impressive, that they see a role in transplantation patients. Great. For patients receiving a ‘new’ organ. But would a healthy baby boomer with a little high cholesterol happily accept a knocked down defence system? Some cancers love depressed immune systems. In 1996 scientists Newman and Hulley wrote in the Journal of the American Medical Association, regarding the cancer risk: ‘The experiments done to date suggest that statin treatment should be avoided, except in patients with a high and immediate risk of [a heart attack.]’


Dr. Jörgen Vesti-Nielsen, a physician from Karlshamn, Sweden, recently pointed out two possible mechanisms for the suggested cancer-promoting effect. In a discussion with colleagues he states: ‘In a low dose, statins stimulate angiogenesis, the formation of new blood vessels. Tumors need nutrients and thus blood for their growth. They depend on a widespread network of tiny vessels. Without the rapid formation of such a network, a tumour cannot even develop. Any substance stimulating the production of new vessels helps to start and spread cancer.

Moreover, a Finnish study suggests that statins make cells less sensitive to insulin. Who would still deny that insulin resistance is an important mechanism behind several cancer forms?’ Very high doses of statins seem to suppress angiogenesis. However, the vast majority of people with a moderate risk of cardiovascular problems are put on a lifelong low dose treatment.

To his great despair, former astronaut and retired NASA-physician Dr. Duane Graveline from Florida, lost all the memories of his adult life two times. Both times, it happened about five weeks after he was put on Lipitor. The staff in the emergency room told him he had suffered episodes of Transient Global Amnesia, a rare condition, not registered as a side effect of statin use. Graveline became extremely concerned, knowing that his problem could be a sign of a beginning dementia. Until he spoke to Dr. Beatrice A. Golomb, a neuroscientist looking for unknown side effects of statins. She made clear to him that he certainly is not the only statin user who all of a sudden fell into a ‘big black hole for a couple of hours’. Golomb, collecting data on behalf of the National Institutes of Health, will publish the results of an independent study in 2004. After a media announcement Golomb got hundreds of reactions from patients and doctors. She is convinced about a causative relation between the use of statins and TGA and other cognitive problems.

Are Graveline, Golomb and other doctors being haunted by imaginary terrors? In the data the manufacturers have to present if they want approval for a new drug, Transient Global Amnesia is not mentioned. Wouldn’t such a grave problem show up immediately? Biochemist and ‘debunker of fraud in medical science’  Joel M. Kaufmann from the University of Philadelphia (Prof. Emeritus) examined some reports and found a hardly flattering explanation. “Pharmaceutical companies sometimes split up one serious side effect into several minor side effects, in order to prevent their drug from not being approved,” he recently told the audience of a conference. “This is an established method to keep really alarming adverse effects below the 1 percent level.” Transient Global Amnesia can be split into such categories like confusion, memory weakness, senility, dementia and impaired cognitive function. One serious and rather common problem, simply falls apart in several relatively benign side effects. A smart trick that the authorities evidently not always unmask.

To swallow or not to swallow, that’s the question for almost 5 percent of our nation. Nefarma, the Organization for Dutch Pharmaceutical Companies participating in Scientific Research, asserts not to be aware of any prospective problems. When confronted with the alarming petition of biochemist Littarru and colleages, a spokesperson refers to the chief Communications and Public Relations. Why is Merck just ‘sitting’ on these patents for so long? Why doesn’t the industry inform physicians about the potentially harmful effect of blocking the Q10-synthesis? The ‘chief’ still owes an answer. During the weeks we tried to get in contact with her, she had constantly ‘just left the building’. No reaction, not even an e-mail back.

 “If your doctor prescribes it, you can be sure the advantages far outweigh the risks,” says a spokesperson for the Dutch Association for Family Physicians. It depends which way around you look at it. Dr. Marshall E. Deutsch, an expert on cholesterol who studied the effect of low fat diets in children, puts it as follows: “The total mortality in the treated groups is – despite all the fuss –  not less than in the groups not getting statins. Even in patients with very high cholesterol levels, the gains are meagre. Besides, the available data indicate that total mortality will rise disproportionally after seven years of treatment. If you absolutely don’t want to knock on Petrus’ gate with a heart attack –  if you prefer to attend the final party with cancer, chronic heart failure, a stroke, a rope around your neck or whatever ailment – you’d better take statins. If you don’t care how you die, if the quality of your remaining years means more to you, then statins might be a bad idea. To jump out of a plane without a parachute offers excellent protection against cancer. But it has such a devastating effect on total mortality, that no sane doctor will use it as an intervention. I do hope the future will tell us that this comparison was misplaced. But it might not.”  




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