In Part Two of his series seeking a better understanding of cholesterol, Dr Peter Dingle PhD urges a public debate on our nation's increasing reliance on statin drugs as the treatment of choice in lowering cholesterol ...
Millions of Australians are prescribed cholesterol-lowering drugs called statins, such as Pravachol, Zocor and Lipitor, each year at a cost of more than one billion dollars - with very little if any benefit and lots of negative side effects. Despite the media hype from poor and lazy journalism in Australia and the public relations campaigns of big drug companies, at best these drugs lower the actual risk of heart attack or stroke by less than one per cent and at the same time have serious side effects in up to 5% of the population of users.
Unfortunately, far too many people take statins and far too many prescriptions are dished out by GPs who do not read or understand the scientific literature, or are too busy and who have simply become the retail arm of the pharmaceutical industry.
The first real hint that something is wrong is that most of what we know about statins and their effects (beneficial or otherwise) actually comes directly from the scientific trials themselves, which were funded by, and even coordinated by, the drug companies1, not from long-term, independent, evidence-based observations. As a result, all the information we have received is strongly biased.
The cholesterol-lowering program used during the past 30 years has, in large part, failed to stem the epidemic of cardiovascular disease. At the same time, the focus on cholesterol reduction has deflected interest away from other therapeutic aspects of inflammation treatment that provide significantly greater benefit. It has been known now for 30 years that despite significant Low Density Lipoprotein-cholesterol (LDL-C) reduction, large numbers of subjects in the drug treatment groups continue to have heart attacks and strokes, despite achieving significant LDL-C reduction. This myopic focus on LDL alone is not surprising given the vested interests of the pharmaceutical industry, but it has distracted us from the real problem.
As highlighted in last month's article in NOVA, cholesterol is not the notorious substance that it is made out to be, it is just the messenger. Despite this, the statin drugs do have a very small benefit of reducing the risk of heart attack or stroke. One of these effects that is non-related to lipid lowering is to stimulate nitric oxide (NO) in the arteries 2 which has numerous positive effects on the arteries and blood vessels 3. A number of foods such as almonds can also achieve this outcome.
The only other scientifically proven action of statins is their capability of lowering blood levels of C-reactive protein (CRP), a marker of inflammation in the body, and a major risk factor for heart disease. Raised CRP levels and raised cholesterol levels in the blood are both the symptoms of an underlying problem, but like cholesterol, raised CRP is not the cause 4.
Therefore, the reasons that some studies have found statins to bring about a very small "real" reduction in the risk of CVD may not be attributed to the reduction in the notorious blood cholesterol level, but rather their effect on nitric oxide and its action as an anti-inflammatory agent. Unfortunately for the drug companies, there are many very cheap and natural ways to reduce inflammation and improve the nitric oxide levels, most of which involve healthy food and lifestyle changes.
Statin therapy is extremely efficient in lowering cholesterol numbers, but unfortunately not without adverse effects on the body 5. To prevent a first heart attack, for every life that is saved - 1% over 10 years of use - statins cause an equal number of adverse deaths due to accidents, infection, suicide and cancer - 1% over 10 years' use 6 and significantly greater levels of serious side effects and suffering.
Because statins interfere with major biochemical pathways they have serious side effects. Statins inhibit the production of many other vital substances, as well as cholesterol. A recent review on the adverse effects of these drugs cited more than 900 studies 7.
Statin drugs block Coenzyme Q10 which is an essential enzyme involved in energy production and also acts as an essential fat soluble antioxidant 8. Coenzyme Q10 plays a vital role in protecting the heart and cardio vascular system 9,10,11,12 and is our natural defense against atherosclerosis development, the build up of plaque in the arteries that leads to cardiovascular disease. Coenzyme Q10 inhibits the oxidation of LDL cholesterol, inappropriate clotting of the blood and ultimately lowers blood pressure 13,14.
Statin treatment may also lead to serious muscle toxicity 15. At least 5% to 7% of statin users experience significant muscle problems 16, more than 10% if higher doses are taken 17, and as many as 25% of statin users who exercise may experience muscle fatigue, weakness, aches, and cramping due to statin therapy 18. This defeats the purpose when those with elevated risk of heart attack or stroke find it hard to exercise.
Statins have also been implicated as negatively impacting brain function 19,20. Cholesterol is the most abundant organic molecule in the brain 21. The housekeeping functions in the brain, synapse function 22,23,24. and serotonin all rely on cholesterol produced in the brain because it is too large to pass through the blood-brain barrier 25. Unfortunately, the statin drugs can easily pass into the brain and directly interfere with the synthesis of cholesterol in the brain 26. No wonder a major side effect of the statin drugs is their impact on memory and thinking. Amnesia is a known adverse effect from taking Lipitor. A study by the drug company Pfizer found two per cent of people taking Lipitor have serious amnesia 27. Ironically, the amnesia was only recognised if it was remembered and observed and reported by the study participants. Many people recorded memory blanks and forgetfulness, but this was not considered as amnesia in the study 27. Even so, the two per cent is at least 385 times more likely than the general population to have amnesia.
In a study to see the effects of raising the Lipitor levels from 10 to 80 mg (more sales) on patients, those taking 80mg had increased liver problems, that is the rate of raised liver enzymes was six times higher than those given 10mg of Lipitor. Even though the total deaths due to CVD in the 80mg group was fewer (126) than in the 10mg group (155), the total deaths due to other causes was higher in the 80mg (158) than the 10mg (127) group 28. There was no difference in the overall mortality rate.
If they have so many side effects, and far too many for me to describe here, what are the benefits? While there are many wild and exaggerated claims and a lot of hype about the benefits of statins, there are almost as many studies showing no benefits at all. This is brought about by the misuse of statistics.
Various independent studies in prestigious peer reviewed scientific journals have shown that statin use in primary prevention, that is where there is no previous history of a heart attack or stroke, have minimal or no value in reducing mortality 29,30. To quote one of the papers, "primary prevention with statins provides only small and clinically hardly relevant improvement of cardiovascular morbidity/mortality." 31. Another review found "current clinical evidence does not demonstrate that titrating lipid therapy to achieve proposed low LDL cholesterol levels is beneficial or safe." 32.
So why are we using them and why are doctors so caught up in the drug scam?
In reading the scientific journals, we should not get confused between statistical significance and clinical significance. "Statistically significant" means that the outcome was likely (95% chance) a result of the treatment, whether it was 100% effective or less than 0.1% effective. That is, if you treat 1000 people to save one life (0.1%) it may be statistically significant, but it is not clinically significant. "Clinical significance" is 20 to 30% or more. The studies on statins report statistical significance, mostly 1% or less, and none at all have so far found any clinical significance. So they should not be used.
The studies on statins also report relative risk, not absolute or real risk. The relative risk reduction is highly misleading 33,34,35,36,37 , if not deceptive. An example of relative risk is where if you have four people in a study who die in the placebo group (no drug) compared to three people who die in the drug treatment group - that is four were supposed to die but only three did - then there is a 25% relative risk reduction. However, to get this effect of saving one life, you had to treat 1000 people so the real risk reduction is 0.1%.
A well known study, The JUPITER Study, found that treatment with statins went from 68 heart attacks in the placebo group to 31 heart attacks in the drug treatment group, a 58% relative risk reduction, and 64 strokes in the placebo group to 33 strokes in the treatment group, a relative risk reduction of 48% 38.
Sounds good doesn't it? However, the drug treatment group had 8901 participants in it. In real terms, the heart attack risk went from a very low 0.76% to 0.35% and the risk of stroke went from 0.72% to 0.37%. Effectively, if you treat 300 people with expensive and dangerous drugs, you might save one life. Under the best possible scenario, the real risk reduction was well under one half of one per cent. The real risk reduction of consuming a handful of raw mixed nuts is around 30% and a relative risk reduction of more than 600%. So why are we using these drugs?
Even when treating people with high cholesterol and other risk factors, the results all come in below 1% 39,40,41,42. The Heart Protection Study in the United Kingdom, with over 20,000 participants aged 40-80 years, with high risk of cardiovascular disease (CVD) produced a 25% relative risk reduction over five years 43. The real percentage improvement is actually 1.7% over five years. Over the five year study, they saved 25 people per year in a sample at high risk with previous cerebrovascular disease, peripheral artery disease, renal impairment or diabetes. These are seriously ill people and they still only get a benefit of 1.7% over five years. They also forgot to mention that around 30,000 people were dropped from the study, and not counted in the percentage of people with side affects. There were 10,269 people on statins and 10,267 people on placebo who did not get the treatment.
More recently, a meta-analysis of 10 randomised clinical trials of about 70,000 people with risk factors for cardiovascular disease, but no history of existing disease, had a relative risk reduction of 12% for total mortality, 30% for coronary event and 19% for a cerebrovascular event 44. However, the real risk reduction was 0.6%, 1.3% and 0.4% respectively. The actual number of people needed to treat to save one life was 167.
It is not just the scientists jumping up and down over the misuse of statistics and drugs, but also the health economists who are continually questioning the reason for so much statin treatment. In an economic review of statin use, the authors reported that it is not cost effective to treat low risk people 45. A recent study in the UK found statins in primary prevention cost £27, 828 per life-years gained (LYG), reaching £69, 373 per LYG in men aged 35-44 34. That is to add one year to a person's life they need to spend £69, 373 (around Aus$125,000) per year, and reported that, "amounts of NHS funding are being spent on relatively less cost-effective interventions, such as statins for primary prevention".
Perhaps you might say that every life is worth that. Unfortunately, it is a big economic price to pay and one we cannot afford. On the positive side, nutrition and lifestyle changes can bring about much greater real benefits, and at much lower costs, but not when people think drugs are the only solution.
To add another interesting dimension to this issue, the same companies who conduct the research pay the researchers and control the research including what is or is not published. Drug companies engage in censorship, bribery, corruption, fraud, suppression of negative studies and all varieties of unscrupulous tactics to sell product. At the simplest level, most medical research is financed by pharmaceutical companies who are looking for new drugs they can produce and sell. How they spin the research and what they look for is determined by the drug companies.
The pharmaceutical companies have made a complete farce of the medical system. It is completely ridiculous to think that when you publish the same information generated by a drug company enough times that it becomes fact, and despite the overwhelming scientific evidence it is impossible to convince people otherwise. Cholesterol is not the killer. It is not even a risk factor, it is a symptom.
If this does not convince you that we have a problem with these drugs, I have hundreds of other scientific studies that add weight to my argument. It is now time for a public debate on this. Please go to the NOVA website (www.novamagazine.com.au) or HYPERLINK "http://www.drdingle.com" www.drdingle.com, print a copy of this and send it to your local GP and distribute it as widely as possible.
Acknowledgment from Dr Dingle:
Thanks to Nadia Unik for doing a lot of the research that has gone into this article.
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2 Tousoulis et al. 2009
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4 Elliot et al. 2009
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6 Jackson et al. 2001
7 Golomb et al. 2009
8 Folkers et al. 1990
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10 Rosenfeldt et al. 2003
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18 Dirks and Jones 2005
19 Palomaki, 1997
20 Rise, 1997
21 Guyton, 1996
22 Mauch et al 2001
23 Koudinov and Koudinova 2001
24 Göritz et al 2002
25 Graveline, 2009
26 Takeshi et al, 2004
27 Hope, 2005
28 La Rosa. et al, 2005
29 Bartolucci et al 2009
30 Thavendiranathan et al 2006
31 Vrecer et al 2003
32 Hayward et al 2006
33 Nuovo et al.
34 Findan et al 2007
35 Franco et al 2008
36 Franco et al 2006
37 Capewell 2008
38 Ridker et al 2008
39 Medical Research Council Working Party 1985
40 Miall and Greenberg 1987
41 Shepherd 1995
42 West of Scotland Coronary Prevention Study Group
43 Heart Protection Study Collaborative Group. 2002
44 Brugts et al 2009
45 Franco et al 2005
Dr Peter Dingle PhD is an environmental and nutritional toxicologist and Associate Professor in Health and the Environment at Murdoch University.