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The International Network of Cholesterol Skeptics

There is an organization that calls itself The International Network of Cholesterol Skeptics (THINCS). Its members “thinc” they are smarter than the average doctor. They “thinc” that cholesterol has nothing to do with cardiovascular disease and that we have been deluded into waging a “cholesterol campaign” for which the scientific evidence is non-existent. They say, “What we all oppose is that animal fat and high cholesterol play a role.” I find even the wording of this statement problematical: one does not usually hear scientists “opposing” matters of fact or non-fact. They go on to say, “The aim with this website is to inform our colleagues and the public that this idea is not supported by scientific evidence; in fact, for many years a huge number of scientific studies have directly contradicted it.”

They tell us about those contradicting studies; but they don’t tell us about the flaws in those studies, they misrepresent some of the results, and they don’t tell us about the many good studies that support the cholesterol/heart link. The issue is a complex one, and it is easy to find studies to support any claim. Good science is about weighing all the evidence pro and con before reaching a conclusion. As far as I can see, these folks have cherry-picked the literature to support an agenda. They seem to have a vendetta against statin drugs in particular.

The website solicits complaints of adverse effects from statin drugs. It features a petition to the WHO that you can sign requesting an investigation of statin side effects. It alleges that lowering cholesterol endangers the elderly. It provides “what the medical journals and newspapers won’t let you hear” – letters and papers that have been rejected for publication. It lists books, published papers and talks by its members. It solicits financial contributions to the cause.

This movement seems to have started with Uffe Ravnskov’s book The Cholesterol Myths, published in Swedish in 1991 and in English in 2000. That book has been severely criticized, for instance in The Skeptic’s Dictionary , where Bob Carroll points out some of the distortions and deceptive techniques found in the cholesterol skeptics’ arguments. A typical claim: “Cholesterol is highly protective against cancer, infection and atherosclerosis” and “high TC [total cholesterol] and LDL levels are beneficial at all ages.” These statements are not only false, they are potentially dangerous to the health of those who believe them.

I’ll admit there is a grain of truth in what they say. The public may falsely perceive cholesterol as some kind of “Great Satan” of heart disease, and diet has been overemphasized, and some doctors may be over-prescribing statins. But there is plenty of evidence from multiple avenues of research to show that high cholesterol is a risk factor for heart disease and that lowering it reduces risk. A Lancet article from December 2007 reviewed trials involving nearly a million people and found that “Total cholesterol was positively associated with IHD [ischemic heart disease] mortality in both middle and old age and at all blood pressure levels.”

Another Lancet meta-analysis of over 90.000 patients concluded “Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual’s absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.”

Most doctors follow guidelines like those in a recent issue of American Family Physician. The article reviews the evidence, makes evidence-based practice recommendations for treating cholesterol abnormalities, and grades the quality of the evidence for each recommendation. It gives most of the recommendations the highest “A” rating.

Prevention is much more complex than just throwing statins at patients with high cholesterol. There are other ways to lower cholesterol, including weight loss. It makes a difference whether you are aiming for primary prevention (preventing disease in the first place) or secondary prevention (preventing further harm to someone who already has cardiovascular disease). A high LDL may not be as significant in a patient whose HDL (“good” cholesterol) is also high. Before prescribing, a good doctor looks at the whole patient: all the other risk factors, such as age, sex, weight, diet, exercise, family history, smoking, blood pressure, and past history. He looks at the risk/benefit ratio of statins in the patient’s particular situation. He considers the NNT (number needed to treat) to prevent one death or heart attack (which may vary from 5 to 333 depending on the situation). He looks at what other medications the patient is on, at the cost and convenience, at the patient’s personal philosophy and preferences. Ideally, the decision to use statins should be a joint decision of the patient and the doctor based on all the information available.

The cholesterol skeptics doubt that all-cause mortality can be reduced by statins. It clearly can for secondary prevention. In primary prevention, it at least reduces the rate of cardiovascular events. It’s not entirely clear whether the risk reduction with statins is due solely to the lowered cholesterol; statins may have other beneficial effects. But at least it appears that the degree of risk reduction can be measured by the degree of cholesterol lowering.

If you have the right genes, a high cholesterol level may not hurt you. And if you are at low risk, you can’t eat yourself into a heart attack just by overindulging in dietary fats and cholesterol. Some of the cholesterol skeptics’ objections are based on a misunderstanding of the relationship between dietary cholesterol and blood cholesterol levels. We used to recommend a low cholesterol diet, then a low fat diet, then a low saturated fat diet, and now we are concerned about trans-fats. We are refining our knowledge, and recommendations are changing accordingly. A reduced fat diet is still recommended for those with elevated blood cholesterol levels, but it may only lower the cholesterol level by 3 – 6%.

When I first went to the THINCS website, the first thing that popped up was a letter warning that statins caused cancer. When I checked the recent articles on “cancer” and “statins” in PubMed, most of the studies showed either no correlation with cancer or an apparent protective effect, especially for colorectal cancer and skin cancer. The NIH is studying statins for cancer prevention, and there is a plausible biologic rationale to support that concept (statins work against cellular functions that may help control tumor initiation, tumor growth and metastasis).

There are even suggestions that statins might benefit other diseases like Parkinson’s disease and Alzheimer’s.

The skeptics cite studies where elderly people with low cholesterol had worse outcomes, but the elderly often have confounding factors: in that age group low cholesterol can be a marker for inadequate diet and chronic disease. A 2008 study shows that “Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated.”

My impression is that the general trend of recent statin studies in the better journals has been to show even more efficacy and fewer side effects than previously thought. For instance, the 2007 West of Scotland Coronary Prevention Study, reported in the New England Journal of Medicine was very encouraging.

The cholesterol skeptics’ website rejects the consensus of medical science, saying that consensus is politics, not science. I beg to differ. Consensus based on opinion is politics. Consensus based on the evidence is an integral part of the scientific enterprise: when the evidence is convincing, the majority will be convinced.

Dissent, debate, and questioning the status quo are important in keeping science honest, but science doesn’t advance through activist groups like this. We didn’t need an “X-Ray Skeptics” group to realize that routine annual chest x-rays were a bad idea; we saw the evidence and stopped x-raying everybody.

We are still struggling to understand all the ins and outs of preventing cardiovascular disease. Current guidelines have been criticized because they are often based on extrapolations and on insufficient data about actual outcome. A letter to the editor of the American Family Physician compared guidelines in six different countries, and found that the American guidelines would save a few more lives but only at much greater expense: 198 patients treated at an expense of over $198,000 to prevent one death. I’m sure we’ve gotten some things wrong, and our present approach will surely be revised as we continue to learn. But to reject the cholesterol connection and statins entirely is to throw the baby out with the bathwater. In my opinion, THINCS is spreading misinformation that could lead patients to refuse treatment that might prolong their life or at least prevent heart attacks and strokes.

Posted in: Pharmaceuticals, Science and Medicine

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364 thoughts on “The International Network of Cholesterol Skeptics

  1. Michelle B says:

    This site has excellent writers. However, Harriet is my favorite; I always look forward to reading her pithy but easy-to-understand writings. Thank You.

  2. Darkwinter says:

    While this is far from being an area I have any knowledge in, one thing did strike me about this organisation, THINCS – the fact that they call themselves skeptics. I do wish people who are determined to ignore compelling evidence would not describe themselves thus – it gives the rest of us a bad name. Just wrote a post on the subject, so thanks for the inspiration!

  3. Wicked Lad says:

    Thank you, Dr. Hall. I’ve never had heart disease, and I take a statin for mildly high LDL. I’m grateful for your summary of the research and for the links you provide.

    Although I hadn’t heard of THINCS, I did read last week in the New York Times that there are doubts about the health effects of serum cholesterol and what benefits statins do or do not offer. The net lesson I take away is that although statins may not increase my life span, they may well improve my quality of life.

    One quality-of-life issue I worry about is statins’ effect on muscle strength. I don’t have muscle pain, but as a weightlifter, I’ve seen a significant drop-off in my strength in the year or so I’ve been taking a statin. I wonder if there’s any evidence statins have that effect, short of the serious muscle disorder a few statin-takers suffer from.

  4. jayemcee says:

    There appears to be a strong reluctance among practitioners of medicine to overturn, or even to examine, the meme that lowering cholesterol by means of HMG-CoA inhibition is a desirable objective.

    This notion refuses to die despite the shoddy science of Ancel Keys or the inability of the first 22 years of Framingham to find any relationship between dietary intake of cholesterol and in vivo cholesterol levels. That is also to say nothing about the collected works of Professor Bruce Ames, Drs Peter and Ali Langsjoen, Duane Graveline, Uffe Ravnskov, Malcolm Kendrick and many others.

    It is never profitable to attempt to educate the unwilling so I will leave you with a patent application from Merck from 1990. You may read the application for yourselves but the synopsis is that the Merck were applying for a patent to combine CoQ10 with a statin for the purpose of “counteracting HMG-CoA reductase inhibitor-associated myopathy” (later referred to as skeletal muscle myopathy)

    The case for iatrogenic harm is flimsy at best (if ever justifiable) and thoroughly incompetent medicine at worst. The evidence is provided that Merck knew with certainty that statins were harmful. Q.E.D

    United States Patent 4,933,165
    Brown June 12, 1990
    Coenzyme Q.sub.10 with HMG-CoA reductase inhibitor

    Abstract

    A pharmaceutical composition and method of counteracting HMG-CoA reductase inhibitor-associated myopathy is disclosed. The method comprises the adjunct administration of an effective amount of a HMG-CoA reductase inhibitor and an effective amount of Coenzyme Q.sub.10.
    Inventors: Brown; Michael S. (Dallas, TX)
    Assignee: Merck & Co., Inc. (Rahway, NJ)
    Appl. No.: 07/298,535
    Filed: January 18, 1989

    Current U.S. Class: 424/94.1 ; 514/415; 514/460; 514/510; 514/689; 514/922
    Current International Class: A61K 31/20 (20060101); A61K 31/185 (20060101); A61K 31/35 (20060101); A61K 31/403 (20060101); A61K 31/405 (20060101); A61K 031/405 (); A61K 031/35 (); A61K 031/21 (); A61K 031/12 ()
    Field of Search: 424/10,510 514/415,690,460,922,689

    Other References

    The New England Journal of Medicine, Scott M. Grundy 319 No. 1, pp. 24-33 Jul. 7, 1988. .
    Folkers et al, Proc. Natl. Acad. Sci., 82, 901(1985). .
    Folkers et al, Proc. Natl. Acad. Sci., 82, 4513(1985). .
    M. S. Brown & J. Goldstein, J. Lipid Res., 21, 505 (1980). .
    H. Mabuchi et al, N.E.J. Med., 478 (1981)..

    Primary Examiner: Robinson; Douglas W.
    Assistant Examiner: Henley, III; Raymond J.
    Attorney, Agent or Firm: Winokur; Melvin DiPrima; Joseph F.
    Claims

    What is claimed is:

    1. A pharmaceutical composition comprising a pharmaceutical carrier and an effective antihypercholesterolemic amount of an HMG-CoA reductase inhibitor and an amount of Coenzyme Q.sub.10 effective to counteract HMG-CoA reductase inhibitor-associated skeletal muscle myopathy.

    2. A composition of claim 1 in which the HMG-CoA reductase inhibitor is selected from: lovastatin, simvastatin, pravastatin and sodium-3,5-dihydroxy-7-[3-(4-fluorophenyl)-1-(methylethyl)-1H-Indole-2yl]- hept-6-enoate.

    3. A method of counteracting HMG-CoA reductase inhibitor-associated skeletal muscle myopathy in a subject in need of such treatment which comprises the adjunct administration of a therapeutically effective amount of an HMG-CoA reductase inhibitor and an effective amount of Coenzyme Q.sub.10 to counteract said myopathy.

    4. A method of claim 3 in which the HMG-CoA reductase inhibitor is selected from the group consisting of: lovastatin, simvastatin, pravastatin and sodium-3,5-dihydroxy-7-[3-(4-fluorophenyl)-1-(methylethyl)-1H-Indole-2yl]- hept-6-enoate.
    Description

    BACKGROUND OF THE INVENTION

    Coenzyme Q.sub.10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone) is a redox component in the respiratory chain and is found in all cells having mitochondria. It is thus an essential co-factor in the generation of metabolic energy and is particularly important in muscle function. For example, Folkers et al., Proc. Natl. Acad. Sci., 82: 901 (1985) have measured the levels of Coenzyme Q.sub.10 (CoQ.sub.10) in endomyocardial biopsy samples taken from patients with varying stages of cardiomyopathy. Folkers et al. states that these data show decreasing tissue levels of CoQ.sub.10 with increasing severity of the symptoms of cardiac disease. Folkers et al., Proc. Natl. Acad. Sci., 82: 4513 (1985) in a double-blind study have reported improved cardiac output for some patients upon receiving an oral administration of CoQ.sub.10.

    HMG-CoA reductase inhibitors represent a new class of cholesterol-lowering drugs. Relatively low doses of these drugs effectively reduce plasma cholesterol levels. These drugs are believed to function by inhibiting the chemical transformation HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol. A branch of the mevalonate cholesterol biosynthetic pathway in mammalian cells leads to the formation of CoQ.sub.10. [reviewed by Brown and Goldstein J. Lipid Res., 21, 505 (1980)]. Furthermore high levels of lovastatin can reduce CoQ.sub.10 in the liver (MK-803 NDA report) and compactin reduces LDL-bound CoQ.sub.10 at doses employed in humans [H. Mabuchi et al, N. E. J. Med., 478 (August 1981].

    The Physician’s Desk Reference, 42d Ed., 1366 (1988) states that myalgia has been associated with lovastatin therapy. Tobert, N. E. J. Med., 48 (Jan. 7, 1988) states that in a very small number of patients (0.5 percent) myopathy appeared to be associated with lovastatin therapy. Concomitant therapy with immunosuppressant drugs, including cyclosporine, with gemfibrozil or niacin or a combination, appears to increase the risk of myopathy. (J. A. Tobert, Am. J. Cardiol. 1988, 62: 28J-34J). The myopathy is reversible upon discontinuance of lovastatin therapy.

    Although cholesterol-lowering therapy through the use of HMG-CoA reductase inhibitors is generally free of side reactions, it would be of considerable benefit to counteract the myopathy observed in a small percent of patients. Since CoQ.sub.10 is of benefit in congestive heart failure patients the combination with HMG-CoA reductase inhibitors should be of value in such patients who also have the added risk of high cholesterol levels.

    DETAILED DESCRIPTION OF THE INVENTION

    The present invention relates to a method of counteracting HMG-CoA reductase inhibitor-associated myopathy in a patient receiving HMG-CoA reductase therapy which comprises the adjunct administration of an effective amount of an HMG-CoA reductase inhibitor and an effective amount of Coenzyme Q.sub.10. Included within the scope of the present invention is the treatment of those patients receiving HMG-CoA reductase therapy and who are also taking immunosuppressant drugs, gemfibrozil or niacin.

    The HMG-CoA reductase inhibitor employed may be lovastatin, simvastatin, pravastatin, XU-62-320 (Sodium-3,5-dihydroxy-7-[3-(4-fluorophenyl)-1(methylethyl)-1H-Indole-2yl]- hept-6-enoate) or any other member of the class of compounds that inhibit HMG-CoA reductase. The preparation of lovastatin (U.S. Pat. No. 4,231,938), simvastatin (U.S. Pat. No. 4,444,784) and pravastatin (U.S. Pat. No. 4,346,227) have been described in the patent literature. The preparation of XU-62-320 is described in WIPO Pat. No. WO84/02131, published June 7, 1984. These methods of preparation are hereby incorporated by reference.

    Coenzyme Q.sub.10 is manufactured by the Kanegafuchi Chemical Industry Co., Ltd. and is widely available.

    In its application to the counteraction of myopathy the present invention is accordingly to be understood as providing for the avoidance of myopathy where this may otherwise occur as well as the amelioration of myopathy. The term counteracting is accordingly to be understood as connecting both a precautionary or prophylactic as well as curvative or treatmental function.

    In accordance with the method of the present invention, an HMG-CoA reductase inhibitor and CoQ.sub.10 can be administered separately at different times during the course of therapy or concomitantly in divided or single combination forms. Thus treatment with CoQ.sub.10 can commence prior to, subsequent to or concurrent with the commencement of HMG-CoA reductase treatment. The present invention is to be understood as embracing all such regimes of treatment and the term “adjunct administration” is to be interpreted accordingly.

    The compounds of the instant invention may be administered orally or parenterally in the form of a capsule, a tablet, an injectable preparation or the like. The general amounts of HMG-CoA reductase inhibitor will be of the same or similar order to that employed in HMG-CoA reductase therapy. In general, satisfactory results are obtained by administration of 0.10 to 80 mg/day of the HMG-CoA reductase inhibitor in a single or divided dose. Doses of CoQ.sub.10 may vary from 25 mg to 1 g day in a single or divided dose. Tablets or capsules may also be administered which contain both compounds in the dosage ranges indicated.

    EXAMPLE 1

    As a specific embodiment of a composition of this invention, 20 mg of lovastatin and 35 mg of Coenzyme Q.sub.10 are formulated with sufficient finely-divided lactose to provide a total amount of 580 to 590 mg to fill a size 0 hard-gelatin capsule. Optionally added are a excipient such as finely divided cellulose, a disintegrant such as Explotat and a lubricant such as magnesium stearate.

  5. fls says:

    Jayemcee,

    Why are you under the impression that medical professionals are unwilling to examine the idea that statins are effective/useful in the treatment of high cholesterol?

    I don’t understand your point about the Merck application. Is it not useful to try to make effective drugs safer?

    Linda

  6. Harriet Hall says:

    Wicked Lad,

    This recent large study found no decrease in muscle strength with statins. http://www.medscape.com/viewarticle/555363_print

    This doesn’t rule out the possibility of an effect in subgroups of the population. Further research is needed to really answer the question.

  7. Harriet Hall says:

    Jayemcee,

    I thought what I had just done WAS to re-examine the meme that lowering cholesterol with statins was beneficial and I found clear evidence that it was, at least when statins are prescribed according to evidence-based guidelines.

    You mention one individual who you say has done shoddy science. Whether or not that is true, there is a wealth of other good science done by large numbers of other researchers. And most importantly, there is coherence between different avenues of investigation.

    I can’t understand why you mention the Framingham study’s failure to find an association between dietary cholesterol and cholesterol levels. You’re beating a dead horse. We now recognize that eliminating cholesterol from the diet has little effect. However, we know that blood cholesterol is a risk factor for cardiovascular disease and that lowering blood cholesterol reduces risk. A low fat (not just low cholesterol) diet, exercise, weight reduction and statins can all contribute to that goal.

    Statins may lower CoQ10 levels, but it is not clear that this has clinical significance for the average patient, and it is not clear that supplementing with CoQ10 has clinical benefits. Research is in progress. We need not just lab studies, but POEMS – patient-oriented evidence that matters.

    Merck knew that statins had side effects. Instead of trying to cover up the side effects, they were trying to be proactive about one side effect. Was the patent application approved? It was dated 1990. I don’t see any such product listed on Merck’s website today.

    It is silly to say that Merck knew that statins were harmful. They knew that statins were beneficial but had side effects, like any other effective drug.

  8. There’s a great 5-part history of the “cholesterol controversy,” written by Dan Steinberg, one of the major players, in J Lipid Research. All five parts are available for free online:

    http://www.jlr.org/cgi/content/full/47/7/1339

    (That’s the link to the 5th part, which cites the other 4 at the beginning of its references)

  9. qetzal says:

    Darkwinter wrote:

    While this is far from being an area I have any knowledge in, one thing did strike me about this organisation, THINCS – the fact that they call themselves skeptics. I do wish people who are determined to ignore compelling evidence would not describe themselves thus – it gives the rest of us a bad name.

    I agree. Such people are not skeptics. They are denialists.

  10. There is some preliminary evidence that taking CoQ10 may reduce the risk of muscle side effects from taking a statin. This notion has high plausibility, is relatively benign, and so far the evidence is pointing in that direction. But, we still need more definitive trials.

  11. PalMD says:

    A number of cardiologists have starting using the CoQ despite current lack of evidence because of, as you said, the plausibility and lack of harm.

    The evidence that statins lower risk of stroke and heart attack in many groups of patients, and that LDL-C and CRP serve as markers for this risk reduction is really unassailable at this point.

    It is essentially malpractice not to give a statin to a patient with CAD (which costs maybe 4.00/mo at target). Studies have found the earlier the statin is started, the better.

    Denialists can schrie about it all they want, but facts is facts.

    Side-effects are much less prevalent than at first believed. Mild, subclinical elevations of liver enzymes happen, and very few people develop actual myopathy. Everyone will feel bad at some point with or without a statin…unfortunately, if they just started a statin, they may blame it.

  12. daedalus2u says:

    I don’t know enough about cholesterol metabolism to understand how elevated cholesterol is causal in these problems, or what is causing the elevated cholesterol.

    Statins do have other effects on physiology. They do raise NO levels, and I do know about NO physiology. Raising NO levels all by itself would be protective for all of the bad things associated with elevated cholesterol, and the NO level is elevated before cholesterol is lowered.

    http://circres.ahajournals.org/cgi/content/full/97/12/1232

    What bothers me about the TINCS site is that they don’t offer an alternative explanation for the data, all of the data. All they do is throw stones at cholesterol. That does make them denialists, not collaborative scientists.

    NO is what regulates cytochrome P450 enzymes by inhibiting them. Inhibition of nitric oxide synthase increases blood cholesterol in rats.

    http://www.ncbi.nlm.nih.gov/pubmed/8857518?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    My suspicion would be via disinhibiting the cytochrome P450 enzymes that make cholesterol downstream of HMG-CoA reductase. If inhibiting nitric oxide synthase increases cholesterol, then HMG-CoA reductase is likely not the “rate limiting enzyme” in cholesterol synthesis.

    Without looking up the details of cholesterol synthesis, cholesterol would seem to be far too important for the “rate limiting step” to be 5 steps before the final synthesis without multiple control points in between. Cholesterol is far too important as a substrate for steroid synthesis. I suspect that HMG-CoA reductase is called the “rate limiting step” because HMG-CoA reductase inhibitors (the statins) reduce cholesterol synthesis. But they might do so via NO physiology (which is why increased NO precedes cholesterol reductions).

  13. jayemcee says:

    @ fls:
    Cholesterol is essential to all cellular life that respires and to the production of myelin. It has not been shown to be the cause of heart disease. The need for its reduction is unproven. One director of the Framingham study, Dr William B Kannel, gave an interview to the newspaper “The News, Framingham & Natick” and these statements appear on page 36 of the issue dated Friday-October 30th 1970.

    Although there is no discernible relationship between reported diet intake and serum cholesterol levels in the Framingham Diet study group, “it is incorrect to interpret this finding to mean that diet has no connection with blood cholesterol” Dr William B Kannel, director of the Framingham heart study has stated.

    “It has been repeatedly demonstrated that blood cholesterol levels can be altered by changes in diet; and dietary alteration is still the most acceptable form of medical management for persons with elevated blood lipids” Dr. Kannel said.

    Which studies support the change of in vivo cholesterol levels that are attributed to diet? Dr Kannel stated “no discernable relationship” and the study commenced with the original cohort in 1948.

    Dr Kannel was being interviewed in 1970, twenty two years after the study was started. His statement about it being incorrect to interpret the finding of no discernable relationship between dietary intake of cholesterol and serum cholesterol levels appears to be based on what he would rather have found rather than what he did find.

    You may say (with the kindest possible interpretation) that Dr Kannel was being very cautious about the finding. I would say that after 22 years of intense expert study and analysis, that not believing the finding was a foolhardy act. I belabour this point because it is clear to me… following extensive dialogue with the department of health, that the UK system of cardiovascular healthcare (with regard to statins, heart disease and the cholesterol hypothesis) is still largely based upon Framingham.

    It is settled ground that statin producers and prescribers are ‘certain of the rightness of reducing ‘bad cholesterol’ and thus the usefulness of statins. One lunatic has even gone as far as to suggest that statins ought to be put into our drinking water. (reminiscent of the proponents of the polypill for all)

    The medical profession have been singularly blind to a raft of debilitating adverse reactions to statins and I personally know of many people who have and are still suffering. Many clinicians appear to think that statinisation has benefits that outweigh risks and medicating people for life is the chosen method to secure the supposed benefits of statin therapy.

    Turning the populace into statin junkies, with the corollary of requiring medical attention for life, is a medical strategy for good health that is bereft of merit. The quality of life gained in exchange for a decade and a half of statinisation is vanishingly small. The disruption of vital processes (that have their genesis in the MMP) is far more serious than the relative risk of dying from a cardiac event that is supposedly caused by a surfeit of LDL cholesterol.

    The so-called ‘opinion forming clinicians’ who apparently speak for the medical profession, despite there having been no election or such a position, are open about the myriad consultancies and research grants which tie them to pharmaceutical manufacturers. The clinical trials that are funded by pharmaceutical companies where the research workers are pressured to find desirable results.

    The adverse reactions that always fall below the clinically significant level. The underreporting of adverse reactions. It was a recent NEJM study that indicated that a large proportion of their respondents were connected to pharmaceutical companies. In the UK the average GP earns an extra £121k on top of the normal salary. The payment is a bonus for meeting targets set by the government. The cardiac domain accounts for around £62k of the additional payments… all of this is stated in the government’s own figures.

    The national policy on prescribing statins is decided by several bodies, among which there are drug company funded charities and the ludicrous position they find themselves in… of deciding the national policy for statinisation, when they are funded by statin producers to promulgate the viewpoint that statins are the saviour of everyone and the cholesterol/heart disease hypothesis is a real danger that will kill us all.

    It has not escaped my notice that the use of statins appears to be ineffective in reducing cardiac events. How does one explain the statinised post CABG patients who go on to require several more CABG surgical episodes, for example?

    The point of my inclusion of the Merck patent application… the drugs were marketed without the addition of CoQ10. Merck believed its addition would have counteracted the propensity of statins (if the patent application was an honest appraisal of the harm that could be caused by statins) to cause skeletal muscle myopathy.

    What possible reason could there be for Merck not to have added any substance that would have lessened the impact of a very serious adverse reaction such as skeletal muscle myopathy? At the very least there would appear to have been some element of duplicity in marketing a drug that they knew was going to hurt people.

  14. cjbrooksjc says:

    It only seems prudent, as a Statin side effect sufferer, for me to add a brief but undeniable counterpoint to the proposition that Statins are primarily beneficial, cancer preventing, minimally health threatening medications. At 60 I was healthy, robust and my appearance belied my age. After a small increase in my cholesterol levels (with favorable “good” cholesterol readings) I was placed on a Statin drug which was, in time, increased in dosage to 40 Mg. I won’t belabor my current, statin-related symptoms, but suffice to say I am a shell of my former self. With the aid of a host of OTC supplements I am trying to recover some semblance of my former health AND during my time on Statins I DEVELOPED heart muscle irregularities. One day the truth will out, and Statins will be labeled for what they truly are: an effective anti-inflammatory but otherwise, a HEME, Dolichol, and CoQ10 reducing poison to human physiology.

  15. pec says:

    There is research showing associations between elevated cholesterol and heart disease.

    There is research showing that statins lower cholesterol.

    There is research showing that statins decrease the risk of heart disease.

    So you might conclude that elevated cholesterol causes heart disease and that statins prevent heart disease by lowering cholesterol.

    Or you might not.

    Statins have an anti-inflammatory effect which might decrease the risk of heart disease.

    The fact that statins lower cholesterol might be incidental.

    The fact that elevated cholesterol and heart disease are associated says nothing about causation. Elevated cholesterol might be an effect, rather than cause, or it might be an irrelevant third variable.

    Where is the research showing elevated cholesterol as a cause of heart disease?

    Heart disease, and artery disease in general, might be an inflammatory process. The plaques that lead to clogged arteries might be the body’s attempt to patch up damaged blood vessels. If that is true — at least in some cases — then you would not prevent artery disease by keeping cholesterol levels down.

    The idea that lowering cholesterol prevents heart disease might be a mistake arising from the fact that statins lower cholesterol AND ALSO decrease inflammation.

    An additional source of confusion is the fact that some individuals may have a genetic defect resulting in extremely high cholesterol levels and early death from artery disease. In those individuals — a small percentage of all adults — cholesterol-lowering makes sense.

    The cholesterol story might not be altogether true. And therefore, the effort to keep cholesterol levels very low might be ineffective and harmful.

  16. Harriet Hall says:

    Jayemcee,

    I don’t think anyone is saying cholesterol causes heart disease. Cholesterol is one risk factor among many in a disease with multifactorial causes.

    I don’t understand why you are quoting a 1970 statement about diet that is not pertinent to this discussion. I don’t think anything is “largely based on Framingham.” Scientific consensus is based on the totality of the evidence, never on one study. There are plenty of other good studies.

    You give us no data to support your claims that statins cause poorer quality of life or disrupt vital processes. The evidence shows otherwise.

    You mention debilitating reactions to statins but recent well-designed studies have found reactions to be few and mild. Are you citing testimonials, or do you have data from double-blind studies?

    You persist in saying, “the use of statins appears to be ineffective in reducing cardiac events.” even after you have been shown incontrovertible evidence that they are effective.

    You ask, “How does one explain the statinised post CABG patients who go on to require several more CABG surgical episodes, for example?” The same way one explains the patients who die from pneumonia despite antibiotics. The evidence shows that treatment reduces the rate of cardiovascular events, repeat surgeries, and death. It doesn’t guarantee a perfect outcome for every patient.

    Your comments about financial influences fall under the “cui bono” fallacy unless you can support them with convincing evidence. In the US, there is no national policy on statins, just clinical guidelines developed by concerned independent physicians who have carefully reviewed the evidence.

    As to why Merck didn’t add CoQ10, I can think of 3 probable reasons right off the bat: not every patient needed it, it was expensive, and until there was better research they couldn’t know that adding it would do more good than harm.

    I’ll point out for a second time that it is disingenuous to say that Merck was marketing a drug that it knew was going to hurt people; it was marketing a drug that it knew was going to help a great many people but had side effects like any other effective drug. The benefits far outweigh the harms.

    Your bias is showing. You are giving us unsupported opinions and innuendo. This is a science-based medicine blog: show us the scientific evidence.

  17. wertys says:

    Well put Dr Hall, and might I add that you have showed commendable restraint. I think that the controversy about statins is an excellent example of the difficulty in doing very large-scale population-based studies, and the need to be cautious about interpreting any individual study in isolation.

    Jayemcee has made a number of gross misrepresentations and assertions without adducing any evidence to support them, and in particular I fail to see how paying UK doctors to reach their prevention targets (which are set by the Department of Health presumably in accord with Government policy) is evidence of anything apart from conscientious doctoring..

  18. Actually, there is quite solid evidence that cholesterol (really LDL cholesterol) is involved in—not merely associated with, in the epidemiological sense—the formation of atherosclerotic plaques. “Cause and effect” evidence did not exist, however, prior to the publication of the NIH Coronary Primary Prevention Trial in 1984, in which the intervention was cholestyramine. Thus any statements about cholesterol and heart disease made in 1970 were not so unreasonable for their time, although the circumstantial evidence was building.

    It was the advent of statins that clinched it, as described by Steinberg in the history that I previously cited:

    because the statins decreased blood cholesterol so much more than any of the existing diet or drug treatments, it suddenly became much easier to demonstrate the decrease in coronary heart disease events and to do so in a statistically significant, unarguable way. For example, in the groundbreaking 1984 NIH Coronary Primary Prevention Trial, using the drug cholestyramine (39, 40), total blood cholesterol in the treated group decreased by only 10% and LDL cholesterol by 20%. This was enough to reduce the heart attack rate, but only by 20%. The result barely reached statistical significance. By contrast, in one of the first large-scale statin trials, total cholesterol was reduced by 25%, LDL cholesterol by 35%, and coronary heart disease deaths by 42%. This reduction was highly significant (P < 0.00001). This trial, the so-called 4S study (for Scandinavian Simvastatin Survival Study) in Scandinavia (41), was done using simvastatin, the second Merck statin, which was discovered while the company was assessing the safety of lovastatin. The 4S study showed, for the first time in any cholesterol-lowering trial, a significant decrease in all-cause mortality. A new era in the treatment of hypercholesterolemia and coronary heart disease had arrived.

    A recent meta-analysis of 14 statin trials with an astonishing total of 90,056 individuals randomized (using lovastatin, simvastatin, pravastatin, fluvastatin, or atorvastatin) showed that the decrease in coronary events was best predicted by the absolute decrease in LDL levels. The incidence of major vascular events was reduced by 20% for each 1 mm/l (40 mg/dl) decrease in LDL cholesterol (42). Thus, an individual starting with an LDL of 280 mg/dl whose level decreased to 200 mg/dl on therapy (a 29% decrease) would be predicted to have a 40% decrease in risk over a 5 year period.

  19. jayemcee says:

    Dr Hall, I’ll start with your opening post. Your own words will appear between square brackets, thus: [quote] [unquote]

    The tenor of your writing is needlessly and gratuitously offensive, in my considered opinion, especially when you deign to mock clinicians and scientists, from your own lofty vantage point, despite them being honourable clinicians and scientists who have taken great pains to make clear their position vis a vis the cholesterol/heart disease hypothesis.

    [quote]There is an organization that calls itself The International Network of Cholesterol Skeptics (THINCS). Its members “thinc” they are smarter than the average doctor. They “thinc” that cholesterol has nothing to do with cardiovascular disease and that we have been deluded into waging a “cholesterol campaign” for which the scientific evidence is non-existent.[unquote]

    I would doubt that any of the THINCS membership believe that they are smarter than the average doctor. You seem to “thinc” that they do believe that. Well, as this is supposed to be an evidence-based scientific website, please produce the evidence for this ersatz ‘fact’, that you have used to dress-up your unseemly diatribe. I would guess by your comment under the general head “cholesterol campaign” that you have avoided apprising yourself of anything that would impinge on your own worldview. more of this anon…

    You appear, Dr Hall, to be in thrall to your own press. Nevertheless, you are one and the same Dr Hall that writes for eSkeptic and you appear not to want other people to exhibit any skepticism. Perhaps you will be good enough to provide the evidence for viewpoint that only you can be right in demanding proof of cause and effect and all other clinicians, whom you happen to disagree with, have no business telling you that they disagree with your well-researched viewpoint. It appears that you believe that everyone you feel is actually wrong (or leastways ought to be wrong according to your own dim lights) is in some way holding an inferior viewpoint to your finely honed mind.

    I nearly forgot the evidence for my own assertion… try reading any of your own numerous diatribes (which I have recently had the misfortune to read) that pollute large amounts of the internet. You are a prolific writer and I see little evidence of any willingness, on your part, to see a point of view that you happen to disagree with. Your articles for eSkeptic and Quackwatch adequately demonstrate your hectoring tone, your belligerence and your intransigent stance, as you declaim to all and sundry from your pulpit. Albeit unintentionally, your writing reveals much about you, Dr Hall.

    [quote]I find even the wording of this statement problematical: one does not usually hear scientists “opposing” matters of fact or non-fact. They go on to say, “The aim with this website is to inform our colleagues and the public that this idea is not supported by scientific evidence; in fact, for many years a huge number of scientific studies have directly contradicted it.”[unquote]

    A matter of opinion, even your own opinion, Dr Hall, does not become a fact by dint of your wishes; no matter how many times you choose to repeat it.

    [quote]They tell us about those contradicting studies; but they don’t tell us about the flaws in those studies, they misrepresent some of the results, and they don’t tell us about the many good studies that support the cholesterol/heart link.[unquote]

    The studies used to support the notion that statins are good have always told the truth, have they? They have never mis-respresented the facts? They have never deliberately obfuscated the truth? They have never consigned viatl adverse reaction data to the realm of the clinically insignificacant? Atorvastatin/Torcetrapib cancelled study? Vytorin and the withholding ofinformation? I suppose that you wont be able to recall either of those studies. Given the relationship between the pharmaceutical industry and clinicians in the USA, as was recently revealed by the New England Journal of Medicine, I presume that there can be no possibility that any pro-statin clinical trials are using false information to promulgate a viewpoint that supports the meme?

    [quote]As far as I can see, these folks have cherry-picked the literature to support an agenda. They seem to have a vendetta against statin drugs in particular.[unquote]

    Clearly, you cannot see very far. Once again it is necessary to point out to you, Dr Hall, that the gratuitous addition of the emotionally loaded term, “vendetta” is evidence for your closed mind and your unwillingness to brook any opinion that is not your own. When I want you tell me what my opinion ought to be, you can be certain that you will be the first to know.

    [quote]The website solicits complaints of adverse effects from statin drugs.[quote]

    It is a great sadness that you appear unable to pass on information without putting your own little spin on it. (there is no case for allowing you one iota of journalistic licence, on a website that purports to promulgate facts) It is true that the THINCS website does ask people if they have complaints about statin side effects. Naturally enough, if one is concerned about the possibility of iatrogenic harm, one needs to assess the extent of it and the possibility of further harm. I would have expected that as the minimum response from any clinician worth the epithet.

    Why did you hide the fact that the request was made on behalf of another agency that is interested in the side effects of statins?

    from the THINCS website… [quote] Have you had side effects from cholesterol lowering (statin) treatment, in particular from the nervous system? Researchers from University of California, San Diego are studying side effects from statin treatment and are also interested in hearing from you [unquote]

    I would have thought that an eminent clinician, such as yourself, who was keen to see the promotion of evidence-based medicine, would have known of the work being carried out by Dr Beatrice Golomb. She is a very well-published and prolific research scientist with a formidable CV. Indeed, she published her findings at an interim point in her study and I would find it hard to believe that you are unaware of the publication, given your expertise with, and your interest in, the promotion of statins.

    You then move on to trashing the work of Dr Ravnskov. You referred to his book, entitled ‘The Cholesterol Myths’ in the same sentence as you mentioned that the book had been “That book has been severely criticized, for instance in The Skeptic’s Dictionary , where Bob Carroll points out some of the distortions and deceptive techniques found in the cholesterol skeptics’ arguments.”

    I attempted to find the accreditation for the Skeptic’s Dictionary, from among the various medical databases. I was surprised to learn that the Skeptic’s Dictionary has no locus as a repository for medical knowledge. I had found the Bob Carroll to whom youy had referred. It appears that he is not a medical doctor and has no medical training of any description. As far as I can see he was not even a member of the domestic staff in a hospital. His credentials are that he was a teacher of philosophy and he has written a textbook entitled ‘Becoming a Critical Thinker’. He states that he has taught classes in Logic & Critical Reasoning, Law, Justice, & Punishment, Critical Thinking About the Paranormal, Introduction to Philosophy, History of Modern Philosophy, and World Religions.

    Help me out here, Dr Hall. You claim to stand for science and evidence, and yet you refer to the criticism of a book (written by an eminent clinician) by a person bereft of medical training, who runs a sensationalist website that is redolent of the nonsense to be found in the National Enquirer. You are not seriously suggesting that the criticism of Dr Ravnskov’s book, by a person who could hardly have managed to be less qualified to analyse the content of that book, even if he arranged it personally, is evidence for the rejection of Dr Ravnskov’s work?

    You stated…
    [quote]But there is plenty of evidence from multiple avenues of research to show that high cholesterol is a risk factor for heart disease and that lowering it reduces risk. A Lancet article from December 2007 reviewed trials involving nearly a million people and found that “Total cholesterol was positively associated with IHD [ischemic heart disease] mortality in both middle and old age and at all blood pressure levels.”

    Another Lancet meta-analysis of over 90.000 patients concluded “Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual’s absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.[unquote]

    I will refer you to issue 48 of Therapeutics Initiative, which was published for April to June 2003 (a Canadian Publication from the University of British Columbia) and it is a publication that is devoted to evidence-based drug therapy.

    The question that was asked was ‘Do Statins Have A Role In Primary prevention.’ The meta-analysis encompassed PROSPER, ALLHAT-LLT, ASCOT-LLA, AFCAPS & WOSCOP. The conclusions were…

    “If cardiovascular serious adverse events are viewed in isolation, 71 primary prevention patients with cardiovascular risk factors have to be treated with a statin for 3 to 5 years to prevent one myocardial infarction or stroke”.

    “This cardiovascular benefit is not reflected in 2 measures of overall health impact, total mortality and total serious adverse events. Therefore, statins have not been shown to provide an overall health benefit in primary prevention trials”.

    The URL follows… http://www.ti.ubc.ca/en/node/52

    Of course, you may say that this was only one study and I will say that there are many studies that support the proposition that statins are only vaguely useful.

    The explanation you give about NNT and the weighing of risk versus benefit are the supposed ideal. Once again the NEJM would suggest that in the USA, the truth may be somewhat removed from your rose-coloured view.

    [quote]The cholesterol skeptics doubt that all-cause mortality can be reduced by statins. It clearly can for secondary prevention. In primary prevention, it at least reduces the rate of cardiovascular events. It’s not entirely clear whether the risk reduction with statins is due solely to the lowered cholesterol; statins may have other beneficial effects. But at least it appears that the degree of risk reduction can be measured by the degree of cholesterol lowering.[unquote]

    It does not reduce the rate of cardiovascular events in primary prevention, according to the study to which I have referred you… immediately preceding this section. Having witnessed your predilection for managing the truth, within your writing, I would much rather accept the work of the University of British Columbia, in preference to your own viewpoint. unless you are prepared to be brutally honest about the current situation apropos statinisation and cholesterol and heart disease, then we cannot proceed any further with this conversation. I find it unacceptable to be lied to to for any reason. That any clinician would do so in order to further their own personal agenda, is truly shocking to me.

    [quote]My impression is that the general trend of recent statin studies in the better journals has been to show even more efficacy and fewer side effects than previously thought[unquote]

    Thus spake the avowed devotee of science and evidence-based medicine. ??? Science is not about your impressions and current trends and fashions and it is thoroughly dishonest of you to include a reference to your impressions in a supposedly scientific treatise (it was not) in an effort to give the impression that you have thoroughly researched your viewpoint. Our discussion ends here…

    Harriet, you are a charlatan and your ‘science’ is nothing but a worthless simulacrum of scientific endeavour!

  20. Harriet Hall says:

    I’m flattered that my critic has run out of good arguments and has had to resort to ad hominem attacks and name-calling. To my mind, that is a sign that I have won the debate. :-)

    Just for the record, I have no personal agenda. I don’t take or prescribe statins, I don’t have any ties to Big Pharma, and if the evidence showed statins did more harm than good, caused cancer, or failed to improve cardiovascular risk, I would gladly follow the evidence.

  21. teeps29 says:

    It must be the TV writers’ strike: jayemcee is making a bid to replace a comedy writer. I laughed out loud at numerous places in his diatribe. Funny guy.

  22. Frankie says:

    All the citations below exhibit:
    * Statins decrease CoQ10 levels in humans
    * Decreased levels of CoQ10 cause various side effects
    * Statins can cause additional ADR’s not previously disclosed

    The FDA does not acknowledge that statins deplete CoQ10 (Ubiquinone), but Canada and the UK do. They’ve undated their statins to reflect this documented fact.

    Why are we in the USA kept in the dark? Why don’t our statins contain this warning?

    My husband experienced all of the following from statins and even after stopping statins over 3 years ago, these symptoms persist: sleep disturbances, memory loss, sexual dysfunction, depression.

    Our doctors completely denied any connection while the data has been there all along. At least give us the facts so we can make an informed decisions.

    FDA’s MedWatch is a joke. Are our doctors reporting adverse effects to MedWatch each time they switch their patient from one statin to another? Or are they too busy writing a prescription for another statin? That’s the typical scenario… try all the statins, then the non-statins and last resort try the good old fibrates.

    The main problem right now other than statins are over-prescribed is that doctors do not have a clue once things go terribly wrong. They want to try Aricept or Prednisone or anything else they can think of… stopping statins does not always resolve side effects and I’m living through that scenario right now. One day my husband is going to wake up and say, “Who the hell are you?” And that, my friends, was caused by Lipitor.

    Frankie
    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
    “Statins sold in Canada are required to carry on their labels a precautionary warning expressly stating that such CoQ10 depletion can lead to impaired cardiac functioning in patients with congestive heart failure. The US government requires no such warning, despite an emerging generation of “super-statins” (rosuvastatin, pitavastatin) that may further increase the risk and rate of CoQ10 depletion in patients taking the drugs.”

    http://lefcms.lef.org/magazine/mag2004/aug2004_report_coq10_02.htm
    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
    MHRA – Drug Safety Update from the UK – February 2008
    Statins: class effects identified

    Keywords: atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, statins, sleep disturbance, insomnia, nightmares, memory loss, sexual dysfunction, depression, interstitial lung disease, class effects

    “Several additional side-effects—sleep disturbances, memory loss, sexual dysfunction, depression, and interstitial lung disease—have been recognised with statins. The product information for the class as a whole is being updated.”

    New advice for healthcare professionals
    • Patients should be made aware that treatment with any statin may sometimes be associated with depression, sleep disturbances, memory loss, and sexual dysfunction
    • Statins may very rarely be associated with interstitial lung disease. Patients should seek help from their doctor if they develop presenting features of interstitial lung disease such as dyspnoea, non-productive cough, and deterioration in general health (eg, fatigue, weight loss, and fever)

    Reporting of adverse events
    Healthcare professionals and patients are encouraged to report any suspected adverse drug reactions with statin treatment to us via the Yellow Card scheme.

    See http://www.mhra.gov.uk/mhra/drugsafetyupdate
    See http://www.yellowcard.gov.uk/
    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
    “Cognitive impairment associated with atorvastatin and simvastatin.”
    PMID: 14695047
    http://www.ncbi.nlm.nih.gov/pubmed/14695047
    “Clinicians should be aware of cognitive impairment and dementia as potential adverse effects associated with statin therapy.”

    “Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study.”
    PMID: 8463436
    http://www.ncbi.nlm.nih.gov/pubmed/8463436
    “CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.”

    “Lovastatin decreases coenzyme Q levels in humans.”
    PMID: 2247468
    http://www.ncbi.nlm.nih.gov/pubmed/2247468
    “Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.”

    “Metabolism and function of coenzyme Q.”
    PMID: 14757233
    http://www.ncbi.nlm.nih.gov/pubmed/14757233
    “Coenzyme Q (CoQ) is present in all cells and membranes and in addition to be a member of the mitochondrial respiratory chain it has also several other functions of great importance for the cellular metabolism.”

    “Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke.”
    PMID: 15210526
    http://www.ncbi.nlm.nih.gov/pubmed/15210526
    “CONCLUSIONS: Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.”

    “Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio.”
    PMID: 8877024
    http://www.ncbi.nlm.nih.gov/pubmed/8877024
    “Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction.”
    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

  23. jayemcee says:

    Dear precious Harriet,

    You’ve won absolutely nothing and yet still you preen and flatter yourself. What colossal arrogance!

    All you have managed to do is to underscore the maxim that there is no profit in trying to educate the wilfully ignorant.

    Res ipsa loquitur

    bye

  24. David Gorski says:

    I love it when people like jayemcee declare victory and then exit with a flourish of ad hominems. It amuses me to no end.

    Of course, he’ll be back. They always come back.

  25. I want to correct a glaring factual error in jayemecee’s email (he did squeeze in a couple factual claims amid the personal attacks).

    He wrote: “It does not reduce the rate of cardiovascular events in primary prevention,”

    This is clearly wrong, even from reading his own quoted articles. In the meta-analysis it did reduce cardiovascular events, just not total major adverse events (which includes things other than cardiovascular).

    I also disagree with the articles conclusions from their own data. Treating 71 people for 3-5 years to prevent one MI or stroke sounds good to me. It’s probably even cost effective if you consider the total health care cost of a stroke or heart attack. These numbers are much better than the use of ASA or Plavix for stroke prevention – which is not controversial at all.

    Regarding Frankie’s comments:
    You should be wary of subjective assessments about what is “typical” for doctors to do. Unless you can reference data measuring practices.

    I and other neurologists in the US already prescribe CoQ10 for neurological side effects of statins. Taking patients off statins is not a last resort – I often see it as a first resort when symptoms appear. Also I doubt that it is common practice to use dietary methods of cholesterol management only as a last resort, that is certainly NOT the standard of care.

  26. farmgal says:

    I hope all the scientific experts here will tolerate a comment by an ordinary person.

    First for Wicked Lad: You best educate yourself on statin adverse effects. Losing muscle strength is a big red flag.

    To Harriet: The most telling comment in all your arguments is that you “don’t take statins.” Perhaps, in the name of science, you should give them a go.

    Unfortunately, I DID take a statin. To make a very long story short, I will never have a life again. I have been told that damage to my muscles and nerves (yes statins can cause nerve damage) is permanent. I can only walk a few feet with the help of a cane, any farther I must use a wheelchair. I was in my early 40′s when my life was destroyed by statin therapy for a slightly elevated cholesterol level.

    Lest you think I am one of the very “rare” examples of those that experience serious life changing problems after taking statins, I can assure you I have lots of unfortunate company. I have encountered perfect strangers, using canes and wheelchairs, that had no problems what so ever, prior to taking statins.

    My own husband had major trouble with Lipitor, his personality changed drastically, he lost muscle mass, his memory was awful, and he could barely pick up a sack of groceries. Before starting Lipitor, he was a strong, athletic, healthy man in his 40′s. He has been extremely lucky to recover most of his abilities, although he will never be quite the same.

    I have talked to many, many folks (in person) that have had statin problems. At least 80% of them have had problems severe enough to throw their statin in the garbage.

    While I have done plenty of research, trying to find a way to get my life back, I’m not going to belabor repetitive scientific pro/con arguments.

    I have a perfectly clear view from my wheelchair, every day of what statins can do. That’s all I need.

  27. Wicked Lad says:

    Interesting article, interesting debate in the comments. Thank you, Dr. Hall and Dr. Novella for the information you’ve provided in the comments regarding statins’ effects on muscles.

    What a great blog you people have put together. It’s an instant success in my estimation.

  28. apteryx says:

    Steven Novella writes:

    “I also disagree with the articles conclusions from their own data. Treating 71 people for 3-5 years to prevent one MI or stroke sounds good to me. It’s probably even cost effective if you consider the total health care cost of a stroke or heart attack. These numbers are much better than the use of ASA or Plavix for stroke prevention – which is not controversial at all. ”

    I understand there is some controversy about Plavix now. Anyway, whether it is good to treat 71 people for 5 years to prevent one nonfatal cardiac event depends less upon the financial cost than upon what the number needed to harm is. If you give 71 people statins for 5 years, will there be at least one extra case of clinically significant liver, muscle, or kidney damage, brain dysfunction, or cancer? (Yes, statin promoters would like us to believe statins prevent cancer, based on the same sort of evidence that said HRT prevented cancer. However, since statins cause cancer in animal studies, the elevated cancer rates in some of the RCTs are cause for concern.) It appears that the answer is yes, meaning that people given statins as primary prevention will experience just as many illnesses, but be poorer.

    My father’s MD socked him on not only statins but one or two of the in-patent blood pressure drugs a few years ago (and talked about putting him on even more toxic drugs) as primary prevention, even though his cholesterol levels were already unusually low and his BP normal. He’s an obedient sort of patient who will not seek a second opinion, and suffered some months of muscle pain in silence before being diagnosed with rhabdomyolysis, whereupon he was graciously allowed to quit the statin. It seems like some of these promoters of “aggressive treatment” think an iatrogenic illness is more acceptable than a natural one, because they’ll do anything to prevent the latter, while refraining from doing something to prevent the former is not in their repertoire. “Primum non nocere” doesn’t seem to fit into American medicine anymore.

    Of course the vast majority of patients are neither visibly harmed nor helped by the statin, but all of them can be persuaded that the MD may be “saving their lives” with every prescription written — and the MD can persuade himself of the same thing, which makes him feel good in a way that extends far beyond his bank account. If the MD does nothing, he cannot give himself credit for his patients’ health. There is therefore a psychological motive to overestimate the value of prophylactic treatment of the healthy.

  29. farmgal says:

    Wicked Lad:

    Regarding muscle issues with statins, this study should be of interest to you.

    http://www.jci.org/117/12/3940?content_type=abstract

  30. farmgal says:

    apteryx:

    All I can say to your above post is: AMEN!

    Not only did my insurance company pay for the initial statin costs, they also ended up with major bills to treat the side effects and all the tests I had to have done. I don’t have an exact total but I can say without hesitation it is in the tens of thousands of dollars.

    Not to mention 2 medications I will need to be on for the long term, perhaps for life, for permanent side effects.

    How cost effective is that?

  31. mgl says:

    To the poster who mentioned meta analysis of statin use, Please remember the meta analysis of HRT use in women and positive correlation to breast cancer and coronary heart disease reduction. Once a prospective study was completed, those meta analyses were proven to be completely incorrect. Meta analyses require further study….
    Prior to lowering LDL to such levels, a few things to consider: Barres and Smith’s in vitro findings of importance of brain cholesterol (recalling that fat soluble statins cross the BBB) synopsis: http://www.sciencemag.org
    Neurons need cholesterol secreted by glial cells to form and maintain functional synapses. In addition to synaptogenesis, cholesterol is probably responsible for production and transport of vesicles necessary for neurotransmission. If one accepts the concept of neuronal plasticity in the adult brain, then deliberately
    suppressing cholesterol metabolism in the brain seems more than questionable.
    Also consider Dr. Xuemei Huang’s findings of positive correlation btn low LDL and Parkinson’s (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1906875), and her study proposal to determine if statins are linked to Parkinson’s.
    and Ralph Edwards’ reporting excessive # of cases of ALS like syndrome reported by pts on statins from WHO drug safety data:
    http://www.ncbi.nlm.nih.gov
    “…The aim of this paper is to present the upper motor neurone lesion cases, with other evidence, as a signal of a relationship between statins and an amyotrophic lateral sclerosis (ALS)-like syndrome. The paper also presents some arguments for considering that a spectrum of severe neuromuscular damage may be associated with statin use, albeit rarely. ”
    and.
    In addition, report by Meske, etal.
    tinyurl.com
    ” Experimental data suggest that manipulation of cholesterol levels may lead to changes in tau phosphorylation. These changes vary depending on how cholesterol metabolism is manipulated. ”
    Increases in tau phosphorylation via statins is not considered an especially favorable response….granted, study involved rat neuronal cultures….
    V. Meske, F. Albert, D. Richter, J. Schwarze, T. G. Ohm (2003)

    Blockade of HMG-CoA reductase activity causes changes in microtubule-stabilizing protein tau via suppression of geranylgeranylpyrophosphate formation: implications for Alzheimer’s disease

    Histopathologically, Alzheimer’s disease is characterized by plaques and tangles that develop progressively over time. Experimental data described a statin-induced decrease in β-amyloid production, a major constituent of the plaques. Others reported data on statin-mediated changes in neuronal survival and cytoskeleton, including the microtubule-associated protein tau, a major constituent of the tangles. However, these latter reports remain contradictory. To clarify and extend our knowledge on the effect of statin on the cytoskeleton, we challenged rat primary neuron cultures by lovastatin and determined the metabolite that is critical for structural integrity and survival of neurons. During the blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the neuritic network was affected and eventually was completely destroyed. This process was not part of the execution phase of apoptosis and was marked by alterations in the microfilament and microtubule system. The distribution and phosphorylation of protein tau changed. Immunoblot analysis and indirect immunofluorescence revealed a transient increase in tau phosphorylation, which ceased during the execution of apoptosis. All of these effects could be linked to the lack of the geranylgeranylpyrophosphate intermediate. Inhibition of the geranylgeranylation of Rho family GTPases (geranylgeranyl-transferase I) evoked similar changes in neurons. These data and our findings that statin treatment reduced the membrane-bound fraction of RhoA-GTPase in neurons suggest that reduced levels of functional small G proteins are responsible for the observed effects. Our data demonstrate that lovastatin concentrations able to suppress not only cholesterol but also geranylgeranylpyrophosphate formation may evoke phosphorylation of tau reminiscent of preclinical early stages of Alzheimer’s disease and, when prolonged, apoptosis.
    Data suggest statins are protective for middle aged men who have suffered a cardiac event; beyond that, there are no good data for use in other populations –ie men who have not suffered a cardiac event, women, men >age 65. Statins are powerful anti-inflammatory agents and increase perfusion everywhere initially. Over time, all the “pleiotropic effects” are of major concern–aptly summarized in the following:
    Drugs Today 2005, 41(4): 267

    Statin-associated neuromyotoxicity
    Baker, S.K., Tarnopolsky, M.A.

    The sequelae of cardiovascular disease contribute significantly to morbidity and mortality in developed nations. As a class, the statins have been shown to measurably reduce the burden of atherosclerotic illness. However, muscle- and, more recently, nerve-related toxicity have emerged as potential complications leading to treatment withdrawal. Generally, the myopathic signs and symptoms of tenderness, myalgias, cramping and elevated serum creatine kinase (CK) activity are fully reversible after drug discontinuation. Growing evidence suggests that latent or previously minimal symptomatic muscle disease may predispose to the development of myopathy. Less information is available regarding the natural history of the sensorimotor neuropathy, but it appears to be less reversible if large fiber function is clinically manifest. Pathophysiologic clues regarding the potential causes of statin myopathy with or without neuropathy are discussed with particular attention paid to the implications of disrupted mevalonate metabolism. For example, secondary defects in isoprenoid biosynthesis are expected to impair the production of a variety of intermediaries such as dolichols, which are crucial for N-linked glycosylation; geranylgeranyl pyrophosphate, which is necessary for coenzyme Q10 and G-protein synthesis; farnesyl-pyrophosphate, which facilitates the endoproteolytic cleavage and maturation of prelamin A and modifies B-type lamins and G-proteins; and isopentenylpyrophosphate, which is involved in a nucleoside modification of selenocysteinyl-tRNA and thus indirectly related to the synthesis of all selenoproteins (estimated at 35). The nature of statin neuromyotoxicity remains unresolved; however, investigating the cellular corollaries of deranged isoprenoid metabolism may uncover clues that lead to a more complete understanding of the elusive pathophysiology.

    Just a review of selenoproteins function should give one pause…..not to mention review of N-linked glycosylation and isoprenoid metabolism……..and coenzyme Q10 function.

  32. pec says:

    I have never taken statins or any cholesterol or blood pressure drugs (I try to avoid MDs as much as possible) but I have close relatives who have been on them for decades. As skeptical as I am, I trusted their MD’s decisions on this.

    NOT ANY MORE. Since reading this blog my skepticism has increased, from moderately high to very high! I am going to warn my trusting relatives about statins and cholesterol-lowering drugs in general.

    Oh by the way, these poor trusting patients have psychiatric problems, including depression and memory loss. No problem — their MDs just prescribed more drugs!

  33. Apteryx wrote: “My father’s MD socked him on not only statins but one or two of the in-patent blood pressure drugs a few years ago (and talked about putting him on even more toxic drugs) as primary prevention, even though his cholesterol levels were already unusually low and his BP normal.”

    This story is so unusual that either this is an anomalous incompetent doctor or the story is inaccurate. Either way it is irrelevant because is has nothing to do with the evidence -based standard of care or with common practice. It is an absurd straw man.

    The discussion of all the benefits, risks, and statistics involving statin use is very constructive. It seems most commenters agree with the actual evidence that statins work as they are claimed to, but the real question is what are the benefit compared to the risks and in which populations? Can we maximize the benefit to risk ratio by optimizing the target population – primary vs secondary prevention, by cholesterol profile, by other vascular risk factors, by response to prior treatment with diet and exercise, etc. ?

    I think the primary point of Harriet’s article is that these are all good questions and, guess what, doctors and medical scientists are actively and sincerely asking these questions. It is childishly naive to assume that they are not, that the medical profession is just simplistically and stupidly prescribing drugs when any lay person with a modicum of common sense can discuss the pros and cons at length. It’s just anti-establishment conspiracy mongering, and it’s insulting to one’s intelligence. It also bears no resemblance to medicine as it is actually practiced – its a paranoid straw man version of medicine.

    Regarding cost effectiveness, the average cost of the first 90 of stroke management is $15,000 (http://www.theuniversityhospital.com/stroke/stats.htm) this does not include long term treatment and lost productivity. But the total cost of treatment vs non treatment is complex and more complete data is necessary to make any final conclusions, that’s why I said “may” be cost effective.

  34. raygee says:

    I am an 86 year old, badly damaged by statin use. 4 years of simvastatin left me very weak and with considerable muscle loss. My doctor, while sympathetic, put it all down to age and previous polio, and really had no alternative but to leave me to deteriorate. I scoured the internet to no avail, but eventually found clues to the causes of my problems from a small polio network which had done much research of the literature.
    As previous contributors have mentioned, Merck knew very well that the reduction of coenzyme Q10 was the cause of statin side effects, but kept this knowledge away from general knowledge, so I was given a drug, without any warning that it could deplete of one of the most necessary factors in life, without which the Krebs cycle cannot be completed, and the production of Adenosine triphosphate (ATP), the whole body’s power supply, is damaged in the mitochondria of whatever part of the anatomy happens to fall foul of this shortfall. But Coenzyme Q10 appears to be a dirty word in medical circles, a leading medical journal’s web page once carried a remark from a doctor ” What does it matter if Q10 is reduced?” A Biology A-level biology student is expected to know the answer, and those whose heart has been adversely affected, as was mine, know only too well that heart failure symptoms arise, as insufficient energy is available for its needs. The use of Q10 to treat heart failure is well known in Japan, where it has 75% success rate, but the medical research bodies will not investigate that “dirty word” The answer probably lies in the fact that Merck knew all about the benefits of Q10 in 1990, but sold the rights off to Japan, sending them well away from the lucrative statin marketplace, and there are several reports of research folk being forbidden to research Q10.

    As for THINCS, it was in place long before Uffe Ravenskov wrote his book, and for good reason, he is not the only one to write on this matter, there at least two other similar studies, very well researched.
    I have read some of the so-called scientific evidence based trials on which cholesterol lowering is founded, I am extremely sceptical of the veracity of the final results published. In the first place, in UK, 70% of drug research funding comes from industry, so the research bodies, who have to get individual project funding. are virtually employees of Big Pharma, and must produce something of financial benefit to their employer.
    The HPS trial, a very large one, and “gold standard RCT” may have theoretical correctness, but the depth of treatment, for such large expenditure, is little advanced from the old monk with his physic garden produce, trying it out on the locals. No attempt was made to look into the biology of possible side effects, and the level of CPK thought significant for mention was much too high. Then here was that “Run in” period, when drugs were taken, but any who dropped out in the first 3 months were not interrogated, the participants falling from 30.000 to 20.000 in this period. It is no wonder that the recorded side effects were so few, in my experience, many have problems very early in statin use, although, conversely, they can surface after many years.
    Within the trial outcomes, events were observed with little variation in those with low, medium, or high cholesterol levels, and the improvement in the treatment was similarly distributed. By hopeful expectation rather than logic, the thought was that greater lowering would give greater benefit, but what is obvious to an unbiassed observer, is that it is the use of the statin, and not the cholesterol level reached, that give the only benefit from its use, and that this is by preventing inflammation in the endothelium. Dr McMully found that homocysteine was one of the major causes of inflammation, but his work went against the great cholesterol theory golden egg, and he was relieved of his post. It is now well recognised that homocysteine level is a much better predictor than cholesterol of heart problems, but trials such at the NORVIT had so many confounders that one could be forgiven for believing that it was designed to fail.
    I know 3 patients who were given statins after heart attacks, with disastrous results and having given them up, have not had further heart problems, but have been left to rot in pain and many other problems because medicine has no answers, but the “dirty word Q10″ and carnitine yield great benefits for them.
    These substances are named alternative medicine, they certainly are not drugs which interfere with vital functions, it seems to be a badge of honour for a drug that it must have side effects. How can the supplementation of a necessary body product be other than true science based medicine, is blood transfusion, insulin, iron sodium, potassium or calcium supply alternative medicine, Only in that it does not involve the use of expensive patented medications.
    I know many of the contributors and some THINCS members, they are genuinely interested in truthful science based medicine, and I am grateful to some of them for giving the last 5 years of my life, snatched from the jaws of a very misguided and only supeficially researched mass medication regime, which will ruin many more lives before the real truth of its damaging potential is realised.

  35. pec says:

    “what is obvious to an unbiassed observer, is that it is the use of the statin, and not the cholesterol level reached, that give the only benefit from its use, and that this is by preventing inflammation in the endothelium.”

    That’s what I keep trying to tell them here, but they can’t hear it. I knew this decades ago from the Dr. Atkins radio show. He based his opinions on logic, rather than peer pressure, and was extremely informative.
    Of course, Atkins is not my only source of CAM knowledge. But he was so logical and knowledgeable, a genuine skeptic — he understood the dangers of “syndrome X” and insulin resistance, and he understood that refined carbohydrates, not fat or cholesterol, is the major cause of heart disease in America.

    The low fat diet craze has caused tremendous damage, and may have actually caused the current obesity epidemic.

    Everyone is suffering except the medical industry and Big Drug.

  36. apteryx says:

    Steven,

    Looking back at this thread, I observe that there are statin-promoters and statin-skeptics who argue politely from logic, and statin-skeptics and statin-promoters who argue rudely using emotive language. The same is more generally true on other threads. My rationale for trying to stay in the former category is that I feel more likely to convince an open-minded reader by appealing to his intellect than by demeaning his intellectual ability if he initially does not embrace my views.

    You could note that my story about my father is merely a single anecdote, but your insinuation that it maybe didn’t happen will not win you converts, since many readers of this thread seem to have seen or experienced side effects of statins given to healthy people. One thing I did not mention is that about 15 years previously, my father had experienced what might or might not have been a TIA (a brief period of hand numbness, not treated at the time), which his new doctor considered to place him in the high-risk category. However, he had had no similar problems in the intervening years, his heart was fine, and his cholesterol level was well below average. Statinization of people with already-good cholesterol levels may not be standard practice, but I doubt that it is so vanishingly rare as to make mere mention of the practice “irrelevant” or “absurd,” given that many doctors are trained to read “aggressive” as a complimentary term; my father’s doctor is no more an extremist than those folks who have publicly suggested putting statins in the water supply. I will certainly inform my father that someone online who considers himself to be a medical expert thinks that his care has been inappropriate, and once again urge him to get a second opinion.

  37. Harriet Hall says:

    At the risk of invoking more invective, I’d just like to say that testimonials and personal horror stories generate more heat than light. Statins may get the blame for things they didn’t do as well as things they did do. For instance, 3.5% of patients on Zocor reported headaches – but so did 5.1% of patients on placebo. The actual rate of severe reactions is very low. From the Merck website:

    The incidence of
    myopathy/rhabdomyolysis was <0.1% in patients treated with ZOCOR.All patients starting therapy with simvastatin or whose dose of simvastatin is being increased,
    should be advised of the risk of myopathy and told to report promptly any unexplained muscle
    pain, tenderness or weakness. Simvastatin therapy should be discontinued immediately if
    myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved
    when treatment was promptly discontinued. Periodic CK determinations may be considered in patients
    starting therapy with simvastatin or whose dose is being increased, but there is no assurance that such
    monitoring will prevent myopathy.
    Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had
    complicated medical histories, including renal insufficiency usually as a consequence of long-standing
    diabetes mellitus. Such patients merit closer monitoring.

  38. Beauzeaux says:

    Thanks, Dr Hall. My husband takes a statin and I’m happy to know it’s doing what it’s supposed to.

    I prefer scientific evidence to anecdotes. Silly me.

    And I love the idea that lowfat diets are contributing to the obesity epidemic. Those cheeseburgers and fries, chips and ice cream, are totally irrelevant.

  39. apteryx says:

    pec writes:

    “[Atkins] understood that refined carbohydrates, not fat or cholesterol, is the major cause of heart disease in America.”

    I am not a big fan of the Giant Slabs o’Meat diet (if you will forgive a little snarkiness) but the evidence that refined carbohydrates are a major contributer to the harm done by the Western diet seems to be building. A new study (Katcher et al. 2008, Am. J. Clin. Nutr. 87:79-90) gave a group of fat people dietary advice and told half to eat only refined grain, half to eat only whole grains. Over 12 weeks the two groups lost identical amounts of weight, but CRP in the whole-grain group decreased 38% in the whole-grain group, not at all in the refined-grain group. In other words, they may believe that weight loss is reducing their risk for heart disease, but biochemical markers of risk suggest that as long as they keep scarfing that Wonder bread, it won’t do any good.

  40. cjbrooksjc says:

    What a great relief to read so many responses by statin-injured individuals. I suppose the proponents here of statin use still deny, even in the face of so many injured patients’ narratives, that any serious problem exists. Dr. Hall, They call it Ubiquinone because it’s need in human physiology is ubiquitous. I refer to a quote from one of your earlier posts:
    “As to why Merck didn’t add CoQ10, I can think of 3 probable reasons right off the bat: not every patient needed it, it was expensive, and until there was better research they couldn’t know that adding it would do more good than harm.”
    ‘Not every patient needed it’?… I’m sure ubiquitous means the same in the King’s English as it does here in the US… please! It might do more harm than good’?… again… please! ‘It was expensive.?… ah, now there dr., I think you are in the proper arena; the money game. This manufacturer’s motives are and were entirely motivated by net profits, and we are left to pay price for their gluttony. Shame on you!

  41. regarding statin anecdotes – don’t fault me for laying out all logical possibilities. In my experience whenever (almost 100% of the time) I hear a story about what some other doctor did, then I have an opportunity to compare the story to documentation, the story is inaccurate. This is true of positive and negative stories – human beings are notoriously bad historians, we alter the details to fit the theme and emotion of the story. This is one reason that anecdotes are so misleading.

    As far as I can tell there are no statin promoters in these comments. The authors promote scientifically rational evidence-based standards of care. We can reasonably argue and disagree about what the evidence says those standards should be regarding statins. What I reject are the ad hominem logical fallacies against doctors, the medical profession, scientific researchers, etc. and the promotion of lone dissenters as if they were the second coming, just because they take a contrarion view. This is not a constructive approach.

    It is also not constructive to present anecdotal accounts of aberrant clinical decision making as if it represents anything. That is the very definition of a straw man argument.

  42. pec says:

    MDs who encouraged their patients to follow a low-fat diet did not always warn them about the dangers of a high-carbohydrate diet. Carbohydrates, especially if they are processed, can lead to elevated insulin levels. This is turn can cause hypoglycemia, which can lead to increased desire for carbohydrates. Some call this carbohydrate addiction, and it can lead to something called syndrome x, which in turn can lead to type 2 diabetes.

    As we know diabetes 2 is now becoming an epidemic, even in young adults. Aside from cigarette smoking, it is the leading cause of heart disease and stroke.

    If you want to lower your risk of artery disease, do not worry about cholesterol or natural fat (trans-fat is another story). Instead, worry about carbohydrate addiction and lack of physical exercise. And of course, do not smoke.

    The extreme Atkins diet was for extreme cases of carbohydrate addiction, and its purpose was to break the addiction. Most people do not need to follow an extremely low-carb diet. Just be reasonable and avoid processed flour and sugar.

    If you suspect you have hypoglycemia DO NOT eat frequent high-carb snacks. That leads to insulin spikes and carbohydrate addiction, and can result in obesity and diabetes 2, and then heart disease or stroke.

    Unfortunately, MDs have NOT been warning their patients about any of this.

    The food industry is still caught up in the low fat, high carb craze. I cannot find plain natural yogurt in the grocery store. It’s all low-fat and no-fat, and it’s all full of refined sugar.

  43. “Unfortunately, MDs have NOT been warning their patients about any of this.”

    Any evidence for this, or is this just blind prejudice?

    Your claims are overstated. This should be a separate thread – and plan on a future article about this. But, our knowledge of fats and sugars have been increasing over the last few decades and our recommendations along with them. For heart health the evidence suggests that type of fat is more important than total fat – vegetable and legume based fats are good, animals fats are bad, and trans fats are very bad (but don’t tell this to the cholesterol “skeptics”). Likewise, total carbohydrates does not appear to be a problem for most people, but high glycemic index foods (simple sugars and refined starches) may be a problem, and are definitely a problem with those who are overweight or predisposed to problems with glucose metabolism.

    None of this appears to matter significantly for weight control – total caloric intake and exercise are what appear to matter.

    The problem with Atkins is that he didn’t ever do the research to support his claims – he just made his millions. Meanwhile nutrition research just moved past him.

    But this topic really needs an article length discussion with references.

  44. Synaptix says:

    Sob stories are nice but none of them are convincing in the least.

  45. apteryx says:

    One wonders why the Maasai and Inuit don’t all have heart attacks by the time they’re 30. I’m not suggesting that it’s ideal to live on cow blood or fish, but the relative health of some people following animal-heavy traditional diets shows that it is too simplistic to label all animal fats “bad.” Likewise, there is evidence that omega-6-laden plant oils are not something the Western diet needs more of. The tragic flaw of the reductionist approach to nutrition has always been to label certain molecules “good” and others “bad” (much like “good cholesterol” vs. “bad cholesterol,” itself necessary for brain function), which inspires gorging on the one hand and paranoid avoidance on the other. I really like Michael Pollan’s latest book, “In Defense of Food,” which cites historical flip-flopping and modern studies contradicting the fat-phobic paradigm to explain why the “nutritionist” emperor has no clothes.

  46. Wicked Lad says:

    Wow! I haven’t plowed through all the comments here, but farmgal, thank you for the link to that study:

    http://www.jci.org/117/12/3940?content_type=abstract

    It’s always useful to have good sources like that. I haven’t gotten through the whole thing yet, and I’m not sure how much I’ll understand, but the abstract and intro seem consistent with what Dr. Hall and Dr. Novella have been writing here.

  47. raygee says:

    Dr Hall

    Anyone who believes the unbelievably low figure quoted by Merck for muscle problems is very naive, to say the least, and a very large pinch of salt is needed to swallow it. Studies elsewhere, not Pharma sponsored, put the figure near 20%, and although you would speak of personal horror stories, a website for statin damaged people in April 2006 had a forum enquiry asking for help for unbearable leg muscle pain. A reply was made to him, suggesting the beneficial effects of carnitine supplementation to alleviate his problem, which worked. In the ensuing 22 months, nearly 23,000 visits have been made to that individual thread, so not just a personal story, but one affecting a great many people who were frightened by an allegedly dangerous cholesterol figure into a statin regime because their life was said to be in danger. How many now curse their doctors for setting them on this so-called safe medication. I recently heard a radio doctor compare statin muscle pain to the odd ache he felt when getting up in the morning!!! If only it was so mild!! I know 2 men who had to give up work because of the severity of the problem. I read many cursing their doctors for setting them on this path, and telling them that “Statins don’t do that”

    The UK Yellow card scheme for doctors to report events believed to be caused by drugs has 80 deaths total against the two most recommended statins in the current guidelines, atorvastatin and simvastatin, but the authorities either haven’t noticed or don’t care, so much for regulatory authorities.

    Periphal neuropathy is now quite often seen, and is not relieved by Q10 or carnitine, often persisting for a very long time, possibly permanently, as are the deficiencies of Q10 and carnitine production, not measured in trials, but at least one THINCS member, and also the Mayo clinic are able to demonstrate the numerical value of Q10 level. Again, so much for the assumed superiority of “science based medicine”, which does not even acknowledge the existence of such vital substances, let alone quantify them. A large dose of humility is needed in high places in medicine, and a lot less of what one author recently named as “Eminence based medicine”

    The many unbelievable uses to which statins have been thought to be useful prompted me to remark that they would be advising them for ingrowing toenails next, until I heard of a statin victim whose nails and hair stopped growing when taking them. The loss of Q10 was the probable cause of this cessation of a normal body function. There is virtually no body function which is exempt from damage due to statin depletion of Q10, but no pharmaco will fund research into this important area, which has little large profit prospect, and probable damage to the sales of the most profitable, but certainly not the safest, drug on earth.

    I have no longer any trust in the pronouncements of much medical research, and believe that many of those who set Government guidelines are not serving the public, but their commercial paymasters.

  48. David Gorski says:

    I have no longer any trust in the pronouncements of much medical research, and believe that many of those who set Government guidelines are not serving the public, but their commercial paymasters.

    And there you have it, from the proverbial horse’s mouth, the reason why no amount of evidence, logic, or reason will ever persuade raygee. His prejudice against “conventional” medicine and “big pharma” is such that he is clearly not persuadable.

  49. pec says:

    “high glycemic index foods (simple sugars and refined starches) may be a problem”

    MAY be a problem!!! I guess you have to wait for the formal research before you acknowledge the obvious.

    Atkins was right — the current heart disease epidemic results from high insulin levels, caused by carbohydrates, not cholesterol or fat, but you refuse to admit it. He didn’t care what mainstream medicine said, he cared about what made sense.

    I am not saying Atkins was god and knew everything. But I was impressed by his skeptical and scientific attitude. Most MDs are more interested in belonging and acceptance (peer pressure) than in science, but he didn’t care about that.

    You very grudgingly admit there might be a problem with carbohydrates. You brush it aside because you don’t want to admit that the MOST IMPORTANT FACTOR, probably the biggest influence on health in America today, has been practically ignored by the medical industry.

    I can’t help wondering why. Is it because you would rather sell statins?

  50. jayemcee says:

    Dr Novella said…
    [quote]I also disagree with the articles conclusions from their own data. Treating 71 people for 3-5 years to prevent one MI or stroke sounds good to me. It’s probably even cost effective if you consider the total health care cost of a stroke or heart attack.[unquote]

    Permit me to disagree with your support for the practice of initiating treatment in 70 people for a period of between 3 ~ 5 years, when it is known that the treatment will not have prevented a stroke or an heart attack, which is touted as the raison d’être for prescribing the medication in the first instance.

    Furthermore there is evidence that links the administration of statins to adverse reactions that run a rather full gamut from mild to fatal. My question is to do with the risk/benefit equation… What possible justification can there be to needlessly expose 70 people to the risk of statin-mediated adverse reactions, when none of them will benefit from taking the statin?

    Additionally, how many years must patients be dependent on both statins and their attending clinician, before they derive any of the benefits that statins allegedly bestow upon them?

    [quote]These numbers are much better than the use of ASA or Plavix for stroke prevention – which is not controversial at all.[unquote]

    Clopidogrel is most definitely not a statin. Is comparing one type of pharmaceutical with another type of medication, a valid method of determining the safety of a medication that is used differently and which belongs to another pharmaceutical group with different bio-availability characteristics, therapeutic range and a different mode of action?

    While it may well be the case that the use of clopidogrel (as an agent to prevent strokes) may be uncontroversial among the neurology community, it cannot be right to extend that specific uncontroversial approval from the nuerologists to include the use of statins and then go on to assume that they are just as effective or as clopidogrel in stroke prevention, with the obvious corollary that statins are uncontroversial too.

    As to the concept of stroke prevention… how can one know that the drug prescribed was the agent that prevented the stroke? When is the conclusion of ‘effective prevention’ made? Does the patient (for example) have to survive for ten years since treatment was first commenced, for a positive finding to be made; that effective stroke prevention was achieved?

    What would the situation be if the patient were to suffer a stroke one day after the ten years were up? Would that happenstance presage a change in the finding of ‘effective prevention of stroke’ to a finding of ‘unable to prevent stroke’? Attributing the lack of a stroke to the initiation of a drug regime, sounds more than a little like superstition rather than the practice of clinical medicine, to me.

  51. raygee says:

    David
    I no longer have faith in so much medical so-called research because it is so unbelievably unbalanced, negligible amounts of money are spent on what one might call Devil’s advocate views to counteract the might of the drug industry, which is often comparable with that of government.
    I have been in a scientific career all my life, and some of the logic which I read in trials and studies, is not logic at all.

    Having found the real reason for statin damage 5 years ago I have written to authorities from Prime Minister, to professors, consultants and anyone I could think of who might listen and take note, but I find that most do not even know the vital need for substances such as Q10, and I believe their personal status might be compromised if they even admitted to the existence of and need for such a substance, their financial backers might prejudice that position.
    A very sorry state of affairs, I am not prejudiced, I have convinced my local medical personnel of the facts of statin damage, and only keep alive by taking quite large doses of the two substances depleted permanebntly by statins, Q10 and carnitine, any shortfall of the first, my heart complains and my blood pressure rises, of the second, my muscle wastage CK figure rises. All very scientific, but there is little doubt that money and not truthful science is at the heart of much of medicine today.
    Particular specialties take possession of some problems and muddy the scene, eg post polio is in the territory of Neurology, whereas it is a metabolic problem, and ME/CFS belongs to Psychiatry, but a Pathologist has had success with prolonged anti biotic treatment. In the statin case, cardiology appears to reign supreme, leaving no room for the experts in bio energetics and those conversant with the real functions of the mevalonate pathway.

    Perhaps one day truth will prevail and conventional medicine will catch up with the whole range of beneficial body necessities, and stop labelling them alternative medicine because they are not in the fortune makers for Big Pharma. in the meantime be aware that the once well respected name of medicine is not as unblemished as it was in days before business interests took over control of the finances. I have no time for complementary medicine, real scientific knowledge must always reign supreme.

  52. jayemcee wrote: “Permit me to disagree with your support for the practice of initiating treatment in 70 people for a period of between 3 ~ 5 years, when it is known that the treatment will not have prevented a stroke or an heart attack, which is touted as the raison d’être for prescribing the medication in the first instance.”

    This is a gross misunderstanding of the application of statistics in medicine. The “number needed to treat” is just a way to express risk vs benefit and cost effectiveness. You can’t know ahead of time who is going to benefit or not. It’s statistical. All preventive medicine is statistical.

    Also – as I wrote previously, we need to identify those groups for whom the net benefit outweighs the net risk. Stop pretending like we are saying something else.

    Jayemcee wrote: “Clopidogrel is most definitely not a statin. Is comparing one type of pharmaceutical with another type of medication, a valid method of determining the safety of a medication that is used differently and which belongs to another pharmaceutical group with different bio-availability characteristics, therapeutic range and a different mode of action?”

    Complete non-sequitur. I made a very specific comparison – the number needed to treat over how long compared to the number of adverse events prevented. For clopidogrel estimates range from 50-125 people for 1 year (for secondary prevention) to prevent one vascular event (which can be a TIA or stroke). The number is higher for strokes alone. It’s lower if you include heart attacks as well.

    Of course for any drug the NNTT has to be compared to adverse events. Most preventive treatments will be studied to look at all outcomes to measure a net risk/benefit.

    I was not trying to extend any other analogy to statins. They have to stand on their own evidence.

    Jayemcee wrote: “As to the concept of stroke prevention… how can one know that the drug prescribed was the agent that prevented the stroke? When is the conclusion of ‘effective prevention’ made? Does the patient (for example) have to survive for ten years since treatment was first commenced, for a positive finding to be made; that effective stroke prevention was achieved?”

    These are good basic (first year medical student) questions, but I get the sense that Jayemcee is implying the medical community doesn’t ask such questions.

    As I stated, preventive measures are always statistical. You never know in an individual patient what would have happened to them if they had not been given a specific preventive treatment. So what? Or are you arguing against all preventive medicine, or the application of all statistics in medicine? If not, then what (if anything) is your point?

    Jayemcee wrote: “Attributing the lack of a stroke to the initiation of a drug regime, sounds more than a little like superstition rather than the practice of clinical medicine, to me.”

    Then you should read a basic book on medical statistics.

  53. pec wrote: “MAY be a problem!!! I guess you have to wait for the formal research before you acknowledge the obvious.”

    Yes. The obvious is often wrong, formal research will tell.

    pec wrote: “Atkins was right — the current heart disease epidemic results from high insulin levels, caused by carbohydrates, not cholesterol or fat, but you refuse to admit it. He didn’t care what mainstream medicine said, he cared about what made sense.”

    What Atkins cared about was making millions. How can you say he cared about science when he never did any. If he cared about patients then why not conduction the research necessary to convince the scientific community he was right?

    pec wrote: “I am not saying Atkins was god and knew everything. But I was impressed by his skeptical and scientific attitude. Most MDs are more interested in belonging and acceptance (peer pressure) than in science, but he didn’t care about that.”

    You are easily impressed. What science did he do?

    pec wrote: “You very grudgingly admit there might be a problem with carbohydrates. You brush it aside because you don’t want to admit that the MOST IMPORTANT FACTOR, probably the biggest influence on health in America today, has been practically ignored by the medical industry.

    I can’t help wondering why. Is it because you would rather sell statins?”

    You have an active imagination. How do you imagine I “grudgingly” admitted the problem or that I “brushed it aside?” Carbohydrates and insulin are part of the problem – but this varies in different people. It is also not the only problem, animal fat plays a role too.

    What is your evidence (apart from your paranoid imagination) that any of this had been ignored by the medical profession?

    Also – I don’t sell statins or any drugs. I am a salaried academic. I have no financial ties to any of this. But I guess it is beyond your narrow view of reality to consider that perhaps I have looked at the evidence and honestly came to a different conclusion than you.

  54. mgl says:

    Noticed the incidence of rhabdomyolysis was taken from Merck’s web site. Would be useful information if adverse events were reported in all the statins studies. Many of these studies do not include the actual #’s of serious adverse events. In fact, Two of the very large statin studies did not publish the total # of SAEs. ALLHAT-LLT did not publish the total serious adverse events, nor did the ASCOT-LLA study. It is difficult to determine one’s risk/benefit ratio when the true risk #’s are not published.
    Concerning the individual with post polio syndrome, there has been published 4 case reports of individuals whose neuromuscular diseases were “unmasked” by statin use:

    Jul 25 Lomasin.com
    Statins May Unmask Underlying Neuromuscular Disease
    NEW YORK (Reuters Health) Jul 26 – Patients with asymptomatic neuromuscular disorders may have their condition precipitated by statin use, according to investigators from the University of Athens Medical School…
    Dr. Panagiota Manta and colleagues describe four such cases in the July 24th issue of the Archives of Internal Medicine…
    … Statin-induced neuropathy is well recognized and reported more and more often, Dr. Manta’s group notes. These four cases show that statins can also trigger underlying neuromuscular conditions.
    The investigators suggest that if neuromuscular symptoms persist after discontinuation of statin therapy, clinicians should “pursue further diagnostic evaluations for the detection of underlying neuromuscular disease.”
    Arch Intern Med 2006;166:1519-1524.
    Copyright © 2007 lomasin.com. All rights reserved.

    A more recent report of atrogin-1 gene being turned on by statin use–
    Discovery of gene responsible for statin-induced muscle pain.
    Wed, 28 Nov, 2007
    Statins, the popular class of drugs used to lower cholesterol, are among the most commonly prescribed medications in developed countries. But for some patients, accompanying side effects of muscle weakness and pain become chronic problems and, in rare cases, can escalate to debilitating and even life-threatening damage.
    Now a study led by investigators at Beth Israel Deaconess Medical Center (BIDMC), helps explain the source of these problems. Published in the December 2007 issue of The Journal of Clinical Investigation, the findings offer the first evidence that a gene known as atrogin-1 plays a key role in statin-related muscle toxicity.
    “Although it is not known exactly how many of the 500 million individuals who take statins experience muscle pain and weakness, muscle symptoms are generally considered the most common side effects of these medications,” explains co-senior author Vikas P. Sukhatme, MD, PhD, Vice Chair of Medicine for Interdepartmental and Translational Programs, Chief of the Division of Nephrology, and Chief of the Division of Interdisciplinary Medicine and Biotechnology at BIDMC.
    “Statin users describe a wide spectrum of symptoms – at the most extreme end is a severe breakdown of skeletal muscle known as rhabdomyolysis,” says Sukhatme, who is also the Victor J. Aresty Professor of Medicine at Harvard Medical School (HMS). “At the other end is ‘grumbling muscles,’ milder, more diffuse muscle soreness and cramps. This kind of symptomatic muscle weakness and pain is quite frequent, but often difficult to quantitate.”
    Known by such trade names as Lipitor, Zocor, Pavacol and Mevacor, statins lower cholesterol by inhibiting HMG-CoA reductase, a key enzyme in cholesterol synthesis.
    Approximately five years ago, the study’s co-senior author Stewart Lecker, MD, PhD, and colleagues in the HMS laboratory of Alfred Goldberg, MD, first discovered the atrogin-1 gene, so named for its role in muscle atrophy.
    “We learned that atrogin-1 is rapidly turned on in wasting muscle,” explains Lecker, who is an investigator in the Division of Nephrology at BIDMC and Assistant Professor of Medicine at HMS. Muscle wasting occurs in a large number of disease states, including cancer, AIDS, and kidney disease and can also occur when muscles are underused due to injury or lack of exercise. “In the absence of atrogin-1 activation,” he adds, “muscle atrophy is diminished.”
    Since this initial discovery, atrogin-1 has been found in every existing model of muscle wasting, prompting Lecker and Sukhatme to investigate whether cholesterol-lowering statins might also be “turning on” this gene.
    “We reasoned that since atrogin-1 plays a key role in the development of wasting in skeletal muscle, it might also mediate part of [patients'] sensitivity to statins,” the authors write.
    They proceeded to conduct three separate experiments to test this hypothesis. They first examined the expression of the atrogin-1 gene in biopsies of 19 human quadricep muscles from five control patients, six patients with muscle pain who were not being treated with statins and eight patients with muscle pain/damage who were using statins. Their results showed that atrogin-1 expression was significantly higher among the statin users.
    Next, the scientists studied statins’ effects on cultured muscle cells treated with various concentrations of lovastatin. Compared with control samples, the lovastatin-treated cells became progressively thinner and more damaged. But remarkably, say the authors, the cells lacking the atrogin-1 gene were resistant to statins’ deleterious effects.
    Finally, the authors tested the drug in zebrafish. And, they showed that just as in mammalian muscle cell culture, lovastatin led to muscle damage, even at low concentrations; as the concentration was increased, so too was the damage. And, once again, they observed that fish lacking the atrogin-1 gene were resistant to statin-induced damage.
    “These three complementary experiments demonstrate that atrogin-1 has a fundamental role in statin-induced toxicity,” notes Lecker. “Future experiments will be aimed at understanding how statins turn on the atrogin-1 response in muscle, and in ascertaining what transpires in muscle following atrogin-1 activation that leads to muscle damage and atrophy. The hope is that eventually patients will be able to glean statins’ positive benefits to cholesterol metabolism and reduction of cardiovascular events while being spared accompanying muscle toxicities.”
    http://www.bidmc.harvard.edu/

  55. Harriet Hall says:

    I don’t think the Merck website data on myopathy/rhabdomyolysis is significantly different from the data from the many, many statin trials and meta-analyses in the published literature. The risk was greater with the now-withdrawn cerivastatin than with the currently used drugs, it is greater with larger statin doses and with pre-existing conditions, it is greater with combined therapy than with monotherapy, and prompt recognition and discontinuance of the drug usually solves the problem.

    This article estimates a NNH of 22,727 for rhabdomyolysis.
    http://www.jr2.ox.ac.uk/bandolier/band131/b131-2.html

  56. pec says:

    “Carbohydrates and insulin are part of the problem – but this varies in different people. It is also not the only problem, animal fat plays a role too.”

    The syndrome that leads to diabetes 2 can also cause high blood pressure and high cholesterol.

    Therefore your belief that high cholesterol, caused by dietary fat, is not carefully considered.

    Conventional medicine is notorious for being reductionist and for failing to consider complex relationships between variables.

    And how in the world can you claim to know what Atkins cared about? You probably don’t even know what he said, let alone his private thoughts. He was a famous CAM physician and you don’t like CAM, so you have no curiosity about his ideas.

    Atkins’ ideas made more sense than the conventional approach to heart disease because he considered the whole system. Mainstream medicine frequently mistakes correlations for causative relationships, partly because of your habit of looking at variables in isolation.

  57. N.B. says:

    Man, this blog makes me glad I don’t get many comments on my own. I don’t know how in the world I’d keep up with the trolls without making it a full-time job.

  58. farmgal says:

    Just a couple of studies that are self explanatory. In short, the studies need to be reliable, and doctors need to pay better attention to complaints:

    “Drug Safety. 30(8):669-675, 2007.
    Golomb, Beatrice A 1 2; McGraw, John J 1 3; Evans, Marcella A 1; Dimsdale, Joel E 4

    Abstract:
    Objective: Using a patient targeted survey, we sought to assess patient representations of how physicians responded when patients presented with possible adverse drug reactions (ADRs). As a demonstration case, we took one widely prescribed drug class, the HMG-CoA reductase inhibitors (‘statins’). This information was used to assess whether a patient-targeted ADR surveillance approach may complement provider reporting, potentially fostering identification of additional patients with possible or probable ADRs.

    Methods: A total of 650 adult patients taking statins with self-reported ADRs completed a survey. Depending on the problems reported, some patients completed additional surveys specific to the most commonly cited statin ADRs: muscle, cognitive or neuropathy related. Patients were asked to report drug, dose, ADR character, time course of onset with drug, recovery with discontinuation, recurrence with rechallenge, quality-of-life impact, and interactions with their physician in relation to the perceived ADR. This paper focuses on patients’ representation of the doctor-patient interaction and physicians’ attribution, when patients report perceived ADRs.

    Results: Eighty-seven percent of patients reportedly spoke to their physician about the possible connection between statin use and their symptom. Patients reported that they and not the doctor most commonly initiated the discussion regarding the possible connection of drug to symptom (98% vs 2% cognition survey, 96% vs 4% neuropathy survey, 86% vs 14% muscle survey; p < 10-8 for each). Physicians were reportedly more likely to deny than affirm the possibility of a connection. Rejection of a possible connection was reported to occur even for symptoms with strong literature support for a drug connection, and even in patients for whom the symptom met presumptive literature-based criteria for probable or definite drug-adverse effect causality. Assuming that physicians would not likely report ADRs in these instances, these patient-submitted ADR reports suggest that targeting patients may boost the yield of ADR reporting systems.

    Conclusions: Since low reporting rates are considered to contribute to delays in identification of ADRs, findings from this study suggest that additional putative cases may be identified by targeting patients as reporters, potentially speeding recognition of ADRs.”

    AND THE OTHER STUDY:

    Drug company funding of drug trials greatly influences outcome

    In head-to-head trials of two drugs, the one deemed better appears to depend largely on who is funding the study, according to an analysis of nearly 200 statin-drug comparisons carried out between 1999 and 2005.

    UCSF researchers examined 192 published results of trials comparing one cholesterol-lowering statin drug to another, or to a non-statin drug.

    Their findings found that two links stood out. If the reported results favored the test drug, the trial was about 20 times more likely to be funded by the maker of the statin rather than the comparison drug company. Even more striking, they say, if the conclusions or interpretation of the drug trial – which reflect the impressions of the trial investigators — favored the test drug, the trial was about 35 times more likely to be funded by the maker of that drug rather than the comparison drug.

    The results of the new analysis are reported in the June 7 online edition of the journal “PLoS Medicine.”

    “Many people are concerned about the growing proportion of drug trials funded by the drug’s manufacturers,” says Lisa Bero, PhD, UCSF professor of clinical pharmacy and health policy studies. “Results of drug trials affect what drugs are covered by medical plans, and so what drugs physicians will prescribe. If drug trial outcomes are largely determined by who pays for the trial, we don’t really know what the best drug is.” Bero is senior author on the PLoS paper.

    The UCSF study examined the links between reported outcomes of the statin trials and many factors, including study design, sample size, thoroughness and type of analysis, as well as funding source. They examined only published randomized controlled trials. The trials involved seven different statins overall, all studied in head-to-head drug comparisons.

    The analysis found that about half of the trials were funded by industry, and about a third did not disclose any funding source. Among those declaring industry funding, about one fifth explained the role of the sponsor, such as data analysis, or writing and preparing the manuscript. Trials with no disclosed funding sources were less likely to have conclusions favoring the test drug, compared to trials with industry funding, the researchers report.

    The researchers note that a number of factors can result in the drug trial results favoring the trial drug’s sponsor. Drug companies could selectively fund trials on drugs that are likely to produce a statistically significant result, the researchers explain. This can be accomplished, they say, by selecting non-equivalent doses of drugs for testing. Also, sponsors may choose not to report results that don’t favor the drugs they sell. Or, they may report positive results in more than one journal, skewing the number of positive articles about their drug.

    In addition, almost half of the trials lacked adequate blinding – assuring that study scientists don’t know which drug the patients were taking until the end of the trial. Blinding is considered of paramount importance in clinical trials. The researchers found that those studies with adequate blinding were less likely to report results favoring the test drug. This finding was independent of who funded the study – in other words, funding source was a stronger predictor of outcome than blinding, but both had independent effects on outcome.

    The most important weakness found in most of the trials was a lack of clinical measures of outcome, such as heart attacks or mortality — considered better indicators in trial design than less direct measures such as lipid levels.

    “The lack of true clinical outcome measures in these direct head-to-head comparisons of drugs is disappointing because the studies don’t give us the best information we need to choose one statin over another,” Bero says.

    The analysis is one of the first large studies examining the influence of funding source on the outcomes of head-to-head drug comparisons, rather than comparing the effectiveness of one statin with no drug at all. The market for statins is competitive, so it is important to have valid information to choose one statin versus another, Bero explained. For policy makers, the relevant choice is not to select a statin versus a placebo, but to select one statin compared to another.

    The study also differed from most other assessments of influences on drug trials by examining 11 different factors, and how they may interact to affect trial results. Most previous studies examined the link of results to one factor alone, such as funding source. But this analysis adjusted for “confounders” – study aspects that can influence the results, such as study design, including randomization, blinding, sample size, even choice of comparison drug in the study.

    Inclusion of the confounders still pointed to industry sponsorship as the most influential factor related to positive results and conclusions.

    The study examined trials by all funding sources, as well as a subset of studies that were only industry funded. Favorable results and conclusions were associated not so much with industry sponsorship, but with the specific company that funded the study, Bero points out.

    “The data available on choosing between statins based on head-to-head drug comparisons appears to be influenced by financial conflicts of interest,” Bero concludes. “So decision makers — those choosing drugs for a formulary or insurance plan — should be skeptical about these kinds of trials. We need to know if a newer, more expensive drug is really better compared to older, less expensive drugs.”

    Co-authors of the study are Peter Bacchetti, PhD, professor of epidemiology, and Kirby Lee, PharmD, assistant professor of clinical pharmacy, both of UCSF; and Fieke Oostvogel, University of Leiden, Netherlands.

    The research was funded by a California Tobacco Related Disease Research Program grant.

    UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

  59. PalMD says:

    Your point is?

  60. marblue says:

    This is one reason why I’m jaded:

    http://www.nytimes.com/2008/02/07/business/media/07jarvik.html?_r=1&hp&oref=slogin

    Plus, exercise should be the primary prescription and doctors who ask their patients to come in to get their cholesterol checked yearly or blood pressure routinely, should require patients to bring in their exercise diaries. Shame on docs who prescribe statins without doing what’s outlined below.

    Studies show patients are far more likely to give up smoking if their doctor tells them to. They will more likely exercise if told by their doc.

    Aspirin (25% reduction), exercise (42% reduction), 8 serving of fruits and veggies (30% reduction), beta blockers if necessary(33%) : ALL far less expensive and more beneficial in reducing risk.

  61. Frankie says:

    Re: my (Frankie’s) post… “The main problem right now other than statins are over-prescribed is that doctors do not have a clue once things go terribly wrong. They want to try Aricept or Prednisone or anything else they can think of… stopping statins does not always resolve side effects…”

    # Steven Novellaon 06 Feb 2008 at 8:21 am, stated…
    Regarding Frankie’s comments: “You should be wary of subjective assessments about what is “typical” for doctors to do. Unless you can reference data measuring practices.
    I and other neurologists in the US already prescribe CoQ10 for neurological side effects of statins. Taking patients off statins is not a last resort – I often see it as a first resort when symptoms appear.”

    Hello Dr Novella,

    From the over 800 correspondences with statin users experiencing side effects (not just my own experiences over the past 11 years with my husband’s Doctors) Physicians are not listening to their patients when they complain of the ‘known’ statin ADR’s much less the ‘rare’ side effects. Our Neurologist, when told I suspected my husband’s cognitive issues (TGA and short term memory loss) were from Lipitor, his only recommendation was to start Aricept and to RESUME Lipitor. Believe me, hubby’s cholesterol levels were the least of our worries, as he was experiencing numerous other side effects from Lipitor. When I asked our PCP, Cardiologist & Neurologist if it was possible to test to make sure he was getting enough CoQ10, I was told there was no such test. None of them suggested a CK/CPK (numerous muscle/joint pain complaints over the years) or to supplement with CoQ10. So if you and other Neurologists are prescribing CoQ10, I applaud you. My experience and that of others wish we had walked into your offices.

    Yes, my over 800 correspondences are anecdotal, but they are what’s going on in the real world. And these are just the people that are looking for answers… most still have complete faith in their physicians and are also clueless that their sleep disturbances (one of the 1st signs of adverse effects), memory loss (which is usually observed by others long before the patient knows) and the more common side effects… they are just chalking them up to ‘something else’. I did too much yard work or exercised too hard at the gym.

    My husband’s doctors told him he was trying to do too much ‘for his age’… good grief… he was in his 50′s… could hardly walk and finally forced to give up golf… initially due to the pain, then because he couldn’t keep track of his score. His buddies were no help, they insisted he was fudging his score.

    Fact: albeit anecdotal ~ Statin side effects can be and for some are permanent. And some are maimed so much that their quality of life now ‘sucks’ to put it bluntly.

    We are real people, not clinical trial, hand picked data producers. And there are many, not just the 1 or 2% quoted in clinical trials.

    I’m glad some of them are starting to speak out. Why is no one listening…

    Frankie

  62. farmgal says:

    Dr. Novella,

    I add my applause to Frankie. I too wish I had you for my doctor when the statin was attacking my body.

    Please understand the anger many of us have toward the many doctors we saw looking for help, and got brushed off.

    Just to see a neurologist “use” the phrase Co Q10 is refreshing.

    The fact that you recognize statin damage is also wonderful.

    I envy your future patients, how I wish you had been on my team when I needed you.

    The first neurologist I saw confirmed muscle weakness, gave me a permanent handicapped permit for parking, and referred me to another neurologist.

    At any rate, thanks for listening.

  63. raygee says:

    Dear mgl
    Statins do not unmask an underlying neuromuscular disease in post polios, but create a greater deficiency of carnitine, already in short supply because of metabolic changes in muscle energy source needs, and cause muscle loss through simulated starvation conditions. I have written a (lay) paper on this and associated matters, it is available via Dr Graveline’s website http://www.spacedoc.net, medical journals said it was of too little general interest to publish, but there is far more interest now and need for more understanding of the factors involved.

    Dr Hall
    I see you are still hung up on trial outcome reports of problems from statins, as I explained earlier, at least 3 of the major trials had the notorious run-in period at the start, when those leaving trial medication were not included in reported results. From the experiences of those whom I know personally, side effects can occur after taking only 2 small dose statin tablets, and are often quickly apparent. Conversely, others find the sudden onset of problems years later.

    The conditions of trial reporting rule out the inclusion of many people in these categories, and the reported results reflect little of life in the real world. Why are these problems written off as anecdotal, as if that meant they are only hearsay, is my near visit to nemesis to be thought of as irrevelant? I took the writer of a statin-praising article in the Lancet to task for having her head firmly in the statistical sand beneath Oxford’s gleaming spires, and being totally unaware of the scale of suffering outside affecting real living people. But then, epidemiologists only deal with statistical people, and have little direct knowledge of what each unit in their statistics represents in terms of human suffering.

  64. Harriet Hall says:

    The comments so far are divided between those who accept the scientific consensus and those who don’t. Those who dispute the scientific consensus have presented two kinds of evidence:
    (1) studies that the scientific community is already aware of and that were not considered sufficient to change the consensus
    (2) emotional testimonials and estimates based on personal experience.

    This discussion has generated a great deal of heat, but also considerable light. I hope readers will not lose sight of my original point – that scientific consensus does not change through activism, but through convincing scientific evidence. The evidence is clear that statins can save lives and prevent cardiovascular events WHEN USED APPROPRIATELY. We recognize that not all providers are prescribing them appropriately, and the emphasis should be on getting those providers to follow evidence-based guidelines and to accumulate more long-term data about effectiveness and safety, especially in subgroups.

    No one is disputing that statins, like any effective pharmaceutical, can produce side effects, and that sometimes those effects can be devastating. The dispute is only about how often that occurs. I suspect it happens more often than Merck would like us to believe but less often than some of the commenters would like us to believe. Even where we have reliable NNT and NNH numbers, individuals will make different decisions based on factors like their personal willingness to accept risks. Science should not presume to tell patients they “should” take statins – that is a value judgment. Science can only present the best available evidence so patients can make an informed decision for themselves.

  65. jayemcee says:

    Dr Novella stated:
    [quote] This is a gross misunderstanding of the application of statistics in medicine. The “number needed to treat” is just a way to express risk vs benefit and cost effectiveness. You can’t know ahead of time who is going to benefit or not. It’s statistical. All preventive medicine is statistical. [unquote]

    I agree that it is unknowable as to whom will be a beneficiary of any particular treatment. What concerns me about the statistician’s approach to prophylaxis is that the numbers can only reveal the cases which fall within closely proscribed limits.

    In the case of the patient who has taken statins for 5 years and does not go on to suffer with a stroke or any other sort of cardiovascular system related malady, we can conclude that our preventative measure was successful, if it meets with our target time that the patient must be free from cardiovascular system related incidents.

    Where the patient has developed Amyotrophic Lateral Sclerosis, and it was attributable to statinisation, the incident does not get recorded as a caution against statins, for the patient did not even suffer with a non-fatal stroke or heart attack. If you gave me the choice between having a non-fatal cardiovascular event and ALS or ALS-like condition that was apparently induced or mediated by statins, then I would rather suffer with the cardiovascular incident.

    The joining of the relevant dots is apparently taking a very long time for the medical profession, en masse, to get to grips with. Meanwhile rather a lot of recipients of statin therapy have developed conditions that would appear to have been caused by statin toxicity. The toxicity of statins appears to be unrelated to either the duration or the dose of statin therapy and I can produce many accounts of people who have suffered within a short time of commencing taking statins.

    Having any neurologist consider the possibility of profound statin-mediated damage to the neurological system is a new and an exciting step forward in the campaign to remove statins from the armamentarium of clinicians. ALS and ALS-like symptoms, peripheral neuropathy, CIDP, dysarthria, tinnitus, neuromata, parasthesia, neuralgia and neural damage have all been mentioned in association with statin use.

    Neurology has, strictly speaking, little interest in the cardiovascular system other than on a gross level. I would hope that there would be less investment in expending huge amounts of energy in defending the preservation of the cholesterol heart disease hypothesis (by the neurology community) and far more professional interest (of neurologists) in discovering the aetiology of the multitude of neurological phenomena that have developed in the statinised patient.

    [quote] Also – as I wrote previously, we need to identify those groups for whom the net benefit outweighs the net risk. Stop pretending like we are saying something else. [unquote]

    No reasonable person would disagree with that which you have outlined above. I am not pretending anything and your imputation may have come about because you have misunderstood my position. My initial response on this forum was to Dr Hall. It was not the way I would have wished to open a discussion with anyone but her judgement on the position of Dr Ravnskov was both flawed and deeply offensive to me.

    I have corresponded with Dr Ravnskov less than 10 times in my life and I am certain that I do not have to defend him. He happens to be an internationally known clinician and he is a research worker of high reknown. It was not appropriate to dismiss his work through the device of quoting the opinions of a non-medically qualified individual and his misguided opinions about the work of Dr Ravnskov.

    I am belabouring this point with you because I want you to know that without that egregious inclusion in Dr Hall’s posting, I would have been considerably less combative. I would not want you to think that I don’t genuinely want answers here. I am committed to doing what I can to prevent any more patients from suffering needless harm from taking statins and that harm is ultimately iatrogenic harm so it is obviously the medical profession which needs to be addressed. this forum represents one means of doing this.

    In return, I would prefer it if you could refrain from loading your words so that don’t I gather the notion that your interest in having a reasonable conversation with me is precisely none at all. Even if that was your intention, you should just say that was the case rather than comparing me with a first year medical student, which I most-assuredly am not. Trading insults is not the way forward. I hope that I have now made my position clear enough for there to be some forward motion in this debate.

    [quote] Complete non-sequitur. I made a very specific comparison – the number needed to treat over how long compared to the number of adverse events prevented. For clopidogrel estimates range from 50-125 people for 1 year (for secondary prevention) to prevent one vascular event (which can be a TIA or stroke). The number is higher for strokes alone. It’s lower if you include heart attacks as well. [unquote]

    This is a completely pointless game that I can play just as well as you can… I was not interested in making a point to be dissected to the nth degree for the purpose of dismissing the point. The idea was to demonstrate the general point inherent in the difficulty there was with discussing prevention. specifically, you had raised clopidogrel as a stroke prevention strategy and then followed it by stating that the treatment was uncontroversial.

    I was attempting to clarify that statins in general (and as a treatment for stroke) are not uncontroversial and I was unwilling to let the reference pass, lest observers would believe that you were stating, by implication, that the use of statins for stroke prevention was also uncontroversial.

    [quote] Of course for any drug the NNTT has to be compared to adverse events. Most preventive treatments will be studied to look at all outcomes to measure a net risk/benefit. I was not trying to extend any other analogy to statins. They have to stand on their own evidence. [unquote]

    I accept what you say. The probability for statin mediated adverse reactions is that there appears to have been some general failure of the medical profession to log many adverse reactions as devolving from statin use.

    General twinges and muscle aches with associated non-specific pains that would otherwise be unremarkable in any general practice, when a 60 year old person complains, take on an altogether different aspect when the patient is taking statins.

    Many initial warnings of adverse reaction are likely to dismissed and may be accounted for simply because the patient is already aged to the degree where such complaints are common. CPK has been shown (in the literature) to be an unreliable indicator of early statin damage.

    [quote] These are good basic (first year medical student) questions, but I get the sense that Jayemcee is implying the medical community doesn’t ask such questions. [unquote]

    You have misunderstood my reason for asking such basic questions. Had the medical community asked (and answered) these questions it is probable that we would not need to have this discussion. Something has prevented the help, which is needed by statin-damaged patients, from being given. The rush to statinate large swathes of the populace (with the corollary that they will stay medicated and thus treated for life) appears to me to be the antithesis to good health.

    We have all watched the acceptable level for total cholesterol levels fall and it continues to fall. The notion that cholesterol levels must fall is predicated on the cholesterol/heart disease hypothesis. The damage being done to the body at cellular level is profound. It is not a case of if the statinised patient will suffer statin-related damage, but when and how much damage will the patient sustain. To state anything else is to misinform the patient.

    The mevalonate metabolic pathway is responsible for processes other than the biosynthesis of cholesterol. Statins inhibit cholesterol early on in the pathway without any regard for the fate of ubiquinone, prenylated proteins, dolichols and heme a.

    The initiation of apoptosis may be linked to a reduction in heme a. Cell wall integrity may be harmed by the reduction in cholesterol. Myelin sheath may be affected by the reduction in cholesterol. On its face, one could possibly make out a case that statins are inimical to life itself.

    [quote] As I stated, preventive measures are always statistical. You never know in an individual patient what would have happened to them if they had not been given a specific preventive treatment. So what? [unquote]

    So perhaps the practice of the statistical measurement of the effectiveness of any specific preventative action ought to be deprecated. Statistical manipulation can be used to prove or disprove anything. It is not unknown for statistics to be used to obfuscate reality and prevent knowledge of poor performance from becoming widely known.

    [quote] Or are you arguing against all preventive medicine, or the application of all statistics in medicine? If not, then what (if anything) is your point? [unquote]

    Many statin studies have regarded the statin-damaged as clinically insignificant. It is possibly a dishonesty that is inherent in the tool of clinical study. More telling is that product maker involvement usually presages favourable findings for the product maker. The clever academic game of removing unpleasant findings from the final paper is a common and widely understood gambit, that is frequently used to curry favour with the sponsors.

    I would want to see all clinical studies conducted because of a clear clinical need rather than having projects suggested by sponsors with goods to peddle in related clinical areas. I would remove the possibility of product suppliers having any input into which clinical studies are carried out. If they wished to sponsor genuine clinical advances, then the money should all go into a central pot.

    Senior clinicians should be responsible for devising clinical research projects and they should be permitted to fund them from the central pot. They should be protected from interference from outside agencies and they should be encouraged to publish actual results. A requirement of all clinical research should be that a log of all outcomes is kept, even if they are not clinically significant.

    All clinical research that is published, should be freely available from a central repository, so that members of the public could make truly informed choices about treatment options before being coerced, either by national policy or unscrupulous clinicians, into following any treatment regime. Such a step would require each publication to be summarised in lay language so that clarity of purpose would be assured.

    [quote] Jayemcee wrote: “Attributing the lack of a stroke to the initiation of a drug regime, sounds more than a little like superstition rather than the practice of clinical medicine, to me.”
    Then you should read a basic book on medical statistics. [unquote]

    Done

  66. Frankie, et al

    I understand your frustration. No one is saying that the practice of medicine is perfect. But I find that frequently those criticizing the practice of medicine in extreme terms are describing something that I do not recognize from my daily practice and interaction with other physicians.

    I admit my own experience is biased, but I am a neuromuscular specialist. This means I get patients referred to me every week with muscle symptoms. In almost every case, if they were on statins when their symptoms occurred the FIRST thing their doctor did was take them off the statins. (In addition to other routine stuff.) If their symptoms persisted, then they referred them to me.

    Doctors are generally aware of the side effects of statins, and will stop them when appropriate. Of course, there are many doctors and many patients out there. The internet can now act as a filter to collect all the negative outcomes and frustrated patients. This creates a very distorted view of what is happening “in the real world”.

    Hopefully we can use this blog to bridge the gap of communication. The situation is not as bad as it may seem – the best academic researchers and physicians are actually quite on top of things, asking the right questions, etc. They are not all blithering idiots or corrupt fiends, and some would have you believe.

  67. Synaptix says:

    jayemcee is halarious

    “Where the patient has developed Amyotrophic Lateral Sclerosis, and it was attributable to statinisation, the incident does not get recorded as a caution against statins, for the patient did not even suffer with a non-fatal stroke or heart attack. If you gave me the choice between having a non-fatal cardiovascular event and ALS or ALS-like condition that was apparently induced or mediated by statins, then I would rather suffer with the cardiovascular incident.”

    If you think that researchers haven’t looked at things like this you are seriously naieve. Give me a break man, you waste so many words with crap like this.

    “The joining of the relevant dots is apparently taking a very long time for the medical profession, en masse, to get to grips with.”

    Oh but you have the inside line on this! Connecting those relevant dots is but a cakewalk for one man – but the whole medical profession, en masse, just cant get it. Sure buddy. You are over reaching.

    “I can produce many accounts of people who have suffered within a short time of commencing taking statins.”

    Ahh so all you really have is stories. Nice way to eliminate bias there.

    “Neurology has, strictly speaking, little interest in the cardiovascular system other than on a gross level. I would hope that there would be less investment in expending huge amounts of energy in defending the preservation of the cholesterol heart disease hypothesis (by the neurology community) and far more professional interest (of neurologists) in discovering the aetiology of the multitude of neurological phenomena that have developed in the statinised patient. ”

    Not only an authority on Statins but on Neurology as well. Impressive.

    “I was not interested in making a point to be dissected to the nth degree for the purpose of dismissing the point.”

    If your point is a non-sequiter it’s invalid. Think of a better one. One that isn’t a logical fallacy.

    “The probability for statin mediated adverse reactions is that there appears to have been some general failure of the medical profession to log many adverse reactions as devolving from statin use.”

    Sounds like the words of a man talking out his ass! There “appears” to be some kind of “general failure” for you to “log many” facts that stand up to scrutiny. Evidence for your assertions should be forthcoming when making blanket statements conjured from the depth of limited reasoning.

    “General twinges and muscle aches with associated non-specific pains that would otherwise be unremarkable in any general practice, when a 60 year old person complains, take on an altogether different aspect when the patient is taking statins.”

    Did you get this from the stories you’ve been told as well?

    The rest is just more of the same – anyone with a baloney detection kit can discover the cheap meat in your posts. I’m no professional but I think Steve adressed every point of all your posts, you just ignore and repeat the same ish over and over.

  68. PalMD says:

    Just to echo Novella, I prescribe statins every day, and very rarely, but occasionally see myopathic side effects. I certainly monitor for them.

    As you said, most doctors aren’t idiots (most). We actually did a bit of training to do this stuff. It wasn’t a day or two a “google university”.

  69. Harriet Hall says:

    Jayemcee mentions “a new and an exciting step forward in the campaign to remove statins from the armamentarium of clinicians.” A scientific mind doesn’t embark on “campaigns” to impose his own version of the truth but tries to keep an open mind and hone in on where the truth lies – which is usually somewhere between the extremes of opinion.

    I was particularly amused by his comments on the Skeptic’s Dictionary critique of Ravnskov’s book. He protests that Bob Carroll is not a scientist, but a professor of logic and critical thinking. Yes, that is precisely the point: a non-scientist was able to point out serious logical flaws in Ravnskov’s arguments. Even if the evidence those arguments are based on is good science, his interpretation of that evidence is faulty. Carroll did not offer “opinions” but analyses of logical errors.

    I have had a several-year ongoing e-mail discussion with another cholesterol skeptic that has remained polite and courteous on both sides. Neither of us felt any need to offer ad hominems or insults. Jayemcee’s personal attack on me was entirely unwarranted, inappropriate, and offensive. The language he used has no place in a respectlful scientific discussion. Fortunately, I was more amused than offended. When someone “loses his cool” that way, he has already lost the argument.

    I have only seen such behavior in people who have been unable to defend their position with logical arguments and good data, and who have felt the need to strike out to defend themselves the only way they can. The last time it happened to me was on a chiropractic forum where I was “flamed” as an IGNORANT HO. That time, 3 forum members wrote me offlist to apologize for the behavior of their colleague and to tell me they couldn’t object to anything I had said.

    Personally, I couldn’t care less, but I think perhaps Jayemcee owes an apology to the rest of you for violating the conventions of polite discourse.

  70. pec says:

    We still have not heard an explanation here for the possible confound relating to the cholesterol hypothesis. Statins lower cholesterol and also have an anti-inflammatory effect. We know that artery disease is related to inflammation. Therefore, we don’t know if the effectiveness of statins results from their cholesterol-lowering effect or their anti-inflammatory effect, or both.

    It’s possible that cholesterol-lowering is incidental to the effectiveness of statins. And in that case the cholesterol hypothesis might be wrong. And that would mean prescribing statins to people with high cholesterol but no health complaints would be a mistake.

    I know people who have been on statins for many years. I would like to find out if cholesterol level is relevant or not. I suspect it is not, or that it is much less important than has been assumed.

    I believe, and I think this is well accepted, that the major cause of heart disease, aside from cigarette smoke, is hyper-insulinism. High insulin may cause high cholesterol, and this is another possible confound in the hypothesis.

    To summarize: high cholesterol may be an effect of cardiovascular disease, rather than a cause. The general metabolic imbalance sometimes known as syndrome x (which is caused by the American lifestyle) involves many complicated variables. This syndrome is known to be a major cause of heart disease. Therefore it is a mistake to focus on one variable, cholesterol levels, in isolation. It is a mistake to treat a complex syndrome by attacking one symptom, rather than searching for and treating the cause or causes.

    No one at this blog has addressed this question, which I have brought up several times. Is there any research which tries to separate out various factors and determine directions of causality?

    If high cholesterol predicts heart disease, we should not jump to the conclusion that high cholesterol is the cause. Something else might cause both the high cholesterol and the heart disease.

    If lowering cholesterol with statins prevents heart disease, we should not jump to the conclusion that the effectiveness of statins depends on their ability to lower cholesterol. It might be the anti-inflammatory property of statins. And in that case, lowering cholesterol might be irrelevant to preventing heart disease.

    How can we find out? Has anyone tried? Or are medical researchers entirely satisfied with their assumption that cholesterol is the culprit?

  71. farmgal says:

    Dr. Novella,

    I appreciate your reply to Frankie. Just to make my position clear, the folks I referenced as having statin problems are not anyone I encountered online.

    They are people I know in real life, some family, some friends, and some strangers. The subject only comes up because of my cane, or wheelchair.

    Over and over again, if they ask, “My goodness, what happened to you?” I tell them. Just a simple statement, “I took a statin drug for cholesterol, and it messed me up.” THAT is when I get feedback.

    I originally assumed that I was just a very unlucky individual.

    Then more and more, over the last 4 years, SO many folks have told me they too had problems, and chucked the statin in the garbage. Some had recovered, some have partially recovered, and some ended up like me. These are just chance encounters.

    And yes, many of these folks are angry for ever being put on these drugs. VERY angry.

    Two people I know have major heart disease problems and EVERY reason to take a statin. They ditched the stuff several years ago, and are still with us to tell about it. They haven’t dropped dead for lack of statins, and they are quite elderly.

    I do think that doctors are more on the ball now, than back when I first started having problems in 2001. I am glad you are one of them.

    According to a recent study date of 2007 (that I posted above), it appears that in not always the case:

    “Results: Eighty-seven percent of patients reportedly spoke to their physician about the possible connection between statin use and their symptom. Patients reported that they and not the doctor most commonly initiated the discussion regarding the possible connection of drug to symptom (98% vs 2% cognition survey, 96% vs 4% neuropathy survey, 86% vs 14% muscle survey; p < 10-8 for each). Physicians were reportedly more likely to deny than affirm the possibility of a connection. Rejection of a possible connection was reported to occur even for symptoms with strong literature support for a drug connection, and even in patients for whom the symptom met presumptive literature-based criteria for probable or definite drug-adverse effect causality. Assuming that physicians would not likely report ADRs in these instances, these patient-submitted ADR reports suggest that targeting patients may boost the yield of ADR reporting systems.

    Conclusions: Since low reporting rates are considered to contribute to delays in identification of ADRs, findings from this study suggest that additional putative cases may be identified by targeting patients as reporters, potentially speeding recognition of ADRs.”

    That study, in addition to my own real life encounters of folks that have had a bad statin experience has formed my opinion regarding that class of drugs.

    I accompanied a cardio patient to an appointment. The cardiologist told me he has seen “hardly any” adverse statin events. My answer to him, “Then you are not looking very hard, or something is obscuring your vision. Have you considered seeing a Proctologist?”

    In defense of cardiologists, it was one that told me to ditch the statin. I wasn’t there because of actual heart problems, I was referred because my health had declined while on the statin to the point my primary said I had developed complete heart failure, and didn’t have long to live. My heart checked out amazingly fine, to the total surprise of the cardio clinic.

    My primary has since told me he has seen “more and more” cases of statin problems, but most are recovering as he takes them off the drug immediately”….guess I was the canary in the mine.

    I do realize what you are saying about bias of like minded folks that gather online with similar experiences.

    But I’m here because of what I have observed in the real world.

    You said you do advise Co Q10 for statin problems. Is there is anything else you recommend, for nerve and muscle damage? I hope it’s not inappropriate to ask, but the neurologists around here haven’t been much help.

  72. Harriet Hall says:

    pec,

    You’re not paying attention. These issues have been fully addressed. Please go back and read more carefully. This is not the first time you have misunderstood or missed what was really said.

    To quote from my article above, “It’s not entirely clear whether the risk reduction with statins is due solely to the lowered cholesterol; statins may have other beneficial effects. But at least it appears that the degree of risk reduction can be measured by the degree of cholesterol lowering.”

    Of course medical researchers are not “entirely satisfied with their assumption that cholesterol is the culprit.” No one assumes that cholesterol is ‘the’ culprit, but it is definitely involved and it is perverse to deny that it has anything to do with heart disease as the cholesterol skeptics do. Research is ongoing. We know inflammation is involved. We are rapidly refining our knowledge.

    Hyperinsulinism is not “the major cause of heart disease” – wherever did you get that idea? Have you been reading the pseudoscientific nonsense on Mercola’s website?

  73. mgl says:

    great to see a neurologist on this blog—am acquainted with 8 individuals diagnosed with Parkinson’s disease who all attribute their disease to lipophilic statin therapy. given the Phase IV studies of megadose coenzyme Q10 for early PD, would one not suspect lowering coq10 via statins is not a good idea?????

  74. PalMD says:

    Admittedly I have not read every article in every journal (but i’ll go to medline in a minute), but I’ve never heard of Parkinson’s or Parkinsonism being caused by statin therapy. Ever. There’s not even a way to try to explain that.
    Do you have any data to go with that, because it would be pretty earth-shattering.

  75. jayemcee says:

    PMID: 17177184 [PubMed - indexed for MEDLINE]

    PMID: 15734664 [PubMed - indexed for MEDLINE]

    http://www.bmj.com/cgi/eletters/325/7369/851

  76. raygee says:

    I would like to bring the discussion back to the original article, in which Harriet Hall gratuitously rubbishes THINCS as folk who set themselves up as being more smart than doctors. There are some members who have personally contributed greatly to the knowledge of what statins really do. Is disagreement with less than perfect research to become a subject for ridicule? Free speech is a vital ingredient of any walk of life.
    Dr Langsjoen’s “Introduction to Coenzyme Q10″ is one of the few sources of information on this subject, his father was associated with Dr Karl Folkers, who when at Merck, first synthesised Q10 and discovered that statins reduced Q10 levels. The mainstream medical journals would not publish the papers, the dead hand of drug financial power lurks in the background, and Folkers spent the rest of his life touring Europe to get the message across unaided.
    Dr Langsjoen is a cardiologist, specialising in non-invasive techniques, and has stated that he sees 2 or 3 new cases of statin induced cardiomyopathy each week. With others, he has done trials where the levels of Q10, heart ejection fraction, flow velocity and other important factors in affected patients before and after using Q10 have been carefully recorded. The benefits are indisputable. However, these are dismissed by his critics as having insufficient power compared with the expensive major statin trials. In my book, a handful of carefully made measurements is of far greater value as evidence than thousands of trial reports solely looking for symptoms, where no measurements had been made of Q10 or carnitine levels, which are the major factor in statin side effects. Even the CPK limit suggested in some trials (10x normal) is too high to show up incipient muscle wastage, mine was serious at twice normal, and far too low to denote rhabdomyolysis. I have been in contact with people with figures in the thousands.
    I thank God for Dr Langsjoen, my life would have ended 5 years ago without his knowledge so published.

    Then there is the remark which you made about Uffe Ravnskov mixing up dietary and serum cholesterol. In his book, he tells how he ate eggs each day, increasing the daily total until he got up to 8 eggs per day, meanwhile measuring his own cholesterol, which was actually lower on the highest egg consumption. He did this just to show the LACK of connection between dietary and serum cholesterol. I wonder how many professional researchers would undertake such a personal approach to their work.
    I think you owe the THINCS members an apology for your offensive remarks about them, such treatment of a group of people who are doing their best to counter the excesses of medicine which HAS to be believed because of the intensity and so often repeated message “Statinate or die”
    The failed ENHANCE trial, where cholesterol level lowering had some negative effects, should also give food for thought and encourage a wider vision of cardiovascular problems.

  77. pec says:

    [Hyperinsulinism is not “the major cause of heart disease”]

    Of course it is Harriet. Where have you been? Insulin resistance, in type 2 diabetes, results in high insulin levels. Type 2 diabetes is known to be the leading cause of cardiovascular disease, and it is not at all ridiculous to think that high levels of insulin in the bloodstream contribute.

    And by the way, you call the cholesterol skeptics pseudoscientists and then admit they do have a point — the assumption that cholesterol causes heart disease is not supported by scientific evidence. So maybe they aren’t complete fools?

  78. PalMD says:

    @ jaymcee

    one reference is a letter, and not a great one.
    One is a preliminary study with conflicting conclusions (“Thus, our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation”)
    The other was a negative study (“Statins although they may affect Co-enzyme Q10 levels in the body and the brain, do not worsen PD at least as assessed by stage, and prevalence of wearing-off, dyskinesia, and dementia.”)

  79. raygee says:

    @PalMD

    Just a little to add to the point of PD

    I have a friend who has Parkinsons, and has been taking Q10 in an attempt to stave off deterioration.

    I take a lot of Q10 myself, but only the best Kaneka manufactured type in the capsules gives me certainty of satisfactory dosage, I have tried many different brands, with less success. I had bought 2 packs of 300 mg Q10, but found it was not working well. I did not wish to waste it, so I gave it to my friend to add to his dose, as the higher dose the better in his circumstances, according to trials which have been made.

    He did this, and in just a week, his wife told me he went up the stairs without using the stairlift, and he has been able to swallow his food much better. I realise that this may only be a transient or “placebo” like effect, but if Q10 makes such a difference, is it not a corollary that reduction of Q10 through statin use could worsen the condition.

    (As far as I am aware, he has not taken statins.)

  80. jayemcee says:

    @ PaIMD

    [quote] but I’ve never heard of Parkinson’s or Parkinsonism being caused by statin therapy. Ever. There’s not even a way to try to explain that. [unquote]

    [quote] one reference is a letter, and not a great one.
    One is a preliminary study with conflicting conclusions (”Thus, our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation”)
    The other was a negative study (”Statins although they may affect Co-enzyme Q10 levels in the body and the brain, do not worsen PD at least as assessed by stage, and prevalence of wearing-off, dyskinesia, and dementia.”) [unquote]

    I had provided a few links to articles that addressed the possibility of the association between statins and Parkinsonism. Now you have heard of it and you can choose to ignore it or to do your own research. Your complaints about the quality of the links provided, are irrelevant within the context I had provided them to you.

  81. pec says:

    Harriet thinks the cholesterol skeptics should be ignored. She insists that cholesterol is involved in heart disease, but can’t tell us if it has an important role. She can’t admit that the cholesterol skeptics are doing everyone a great service by pointing out that the connection between heart disease and cholesterol is far from clear.

    Harriet would like us to be trusting sheep and follow the medical industry’s recommendations. Since we do not have medical degrees, she thinks, we are incapable of thinking for ourselves. Trust the experts is her message.

    I have a Ph.D. and, although it is not in medical research, I am capable of noticing confounds in medical research. Sometimes I can see it better than MDs, since most MDs are not Ph.D.s and have no direct experience with statistics and methodolgy.

    But even if I had no direct research experience or advanced education, I would still be capable of reading and thinking. Sometimes non-MDs have more common sense than MDs because they have not gone through the subliminal brain-washing of medical school.

  82. pec says:

    http://money.cnn.com/2008/02/04/technology/simons_cholesterol.fortune/index.htm

    “Anti-cholesterol drugs are a $36 billion segment of the world’s second-most profitable legal industry behind Big Oil. Roughly, 19 million American adults take a cholesterol-lowering medicine of some kind. And according the most recent National Cholesterol Education guidelines – the suggestions most doctors adhere to – about 36 million Americans should be on some form of statin therapy.”

    “The national guidelines state that use of a statin to reduce LDL cholesterol is recommended for people at high or moderately-high risk of heart disease. People in the high-risk group should aim for a LDL cholesterol count of less than 70 mg/dL, and those in the moderately high-risk group should have a count between 129 and 100 mg/dL.
    The guidelines were published by the National Cholesterol Education Program (NCEP), a branch of NIH’s National Heart, Lung, and Blood Institute. Critics of the drug industry claim that the guidelines themselves are biased toward drug therapy because a majority of the medical experts who drew up those suggestions have financial relationships with drug companies.”

    “As with so much health science, it may be years before doctors and patients receive more data on just how useful it is to reduce cholesterol – and even then it may not be definitive.”

    BE SKEPTICAL NOW.

  83. PalMD says:

    “I had provided a few links to articles that addressed the possibility of the association between statins and Parkinsonism. Now you have heard of it and you can choose to ignore it or to do your own research. Your complaints about the quality of the links provided, are irrelevant within the context I had provided them to you.”

    Sorry. I was simply pointing out that the references cited, while containing the words “Parkinsons” and “statins” did not provide any evidence of a connection.

    They did however provide me with a context to understand the earlier comments, which I appreciate.

  84. pec says:

    “the statin trials of people without existing heart disease showed no reduction in deaths or serious health events, despite the small drop in heart attacks. “We should tell patients that the reduced cardiovascular risk will be replaced by other serious illnesses,” says Dr. John Abramson, clinical instructor at Harvard Medical School and author of Overdosed America.”

  85. pec says:

    http://www.businessweek.com/magazine/content/08_04/b4068052092994_page_6.htm

    Oh look Harriet — I’m not the only one saying that statins prevent heart attacks by decreasing inflammation, and cholesterol is irrelevant.

    “current evidence supports ignoring LDL cholesterol altogether,”

  86. PalMD says:

    I wish my med school profs had told me that business week was such a good source for all my medical information.

    Ill make a note..

  87. Joe says:

    “I wish my med school profs had told me that business week was such a good source for all my medical information.

    I’ll make a note..” PalMD

    If you didn’t know about that, you shouldn’t be so flip. And don’t overlook People Magazine and the National Inquirer.

    Can somebody tell us how to do the distinctive quotation here (the big, blue mark?

  88. pec says:

    Sometimes it’s easier for outsiders to see that the emperor has not clothes. Besides, the article has plenty of expert testimony. You might try reading it.

  89. jayemcee says:

    Science… for anyone who may be interested

    Statin-Associated Myopathy with Normal Creatine Kinase Levels
    http://www.annals.org/cgi/content/abstract/137/7/581

    Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient
    http://www.fda.gov/bbs/topics/NEWS/2006/NEW01514.html

    Cardiovascular risk estimation: important but may be inaccurate
    http://www.bmj.com/cgi/content/full/332/7555/1422

    Statins and risk of polyneuropathy: a case-control study.
    http://www.ncbi.nlm.nih.gov/pubmed/12011277

    Serious Adverse Event Analysis: Lipid-Lowering Therapy Revisited
    http://www.ti.ubc.ca/node/58

    Carcinogenicity of lipid lowering drugs
    file:///Volumes/Cyclops%20II/files%20from%20Cyclops%20II/THINCS/Statins/Entrez%20PubMed4.webarchive

    Heme deficiency selectively interrupts assembly of mitochondrial complex IV in human fibroblasts: Relevance to aging
    http://www.jbc.org/cgi/content/abstract/M108362200v1

    The Role of Heme and Iron-Sulfur Clusters in Mitochondrial Biogenesis, Maintenance, and Decay with Age
    http://www.ncbi.nlm.nih.gov/pubmed/11795893?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging
    http://www.pnas.org/cgi/content/abstract/99/23/14807?etoc

    Heme, iron, and the mitochondrial decay of ageing
    http://cat.inist.fr/?aModele=afficheN&cpsidt=15943712

  90. Harriet Hall says:

    I’ll try once more to make my point, although I fear that the emotions and biases of my critics will make it impossible for them to understand.

    I have no agenda. I have no bias for or against cholesterol or statins. I have done my best to look at the evidence objectively, and I have found no support for the claims of THINCS that cholesterol has nothing to do with heart disease, that low cholesterol is harmful and high cholesterol desirable, or that statins cause cancer. It seems clear to me that THINCS is not considering the evidence objectively, and that there are logical flaws in their arguments. There is some truth in some of their arguments, and I have said that.

    There are many unanswered questions about the heart disease/cholesterol/statin connection. The medical scientific establishment is doing a pretty good job of asking questions on its own, without any need for prompting from activist groups. I will continue to follow the evidence wherever it leads. I will try not be swayed by horror stories and testimonials or by opinions.

  91. pec says:

    “I have found no support for the claims of THINCS that cholesterol has nothing to do with heart disease”

    Right Harriet, you are absolutely correct, on the most literal of levels. If THINCS says that cholesterol has NOTHING TO DO WITH HEART DISEASE, they are wrong. It has something to do with heart disease. But it doesn’t cause it. And lowering cholesterol in many or most cases does not to prevent it.

    You found something THINC is wrong about. Great for you! But you steadfastly ignore everything they are RIGHT about, and everything we have been deceived about.

    You should be a public relations spokesperson. Have you considered working for the tobacco industry?

  92. PalMD says:

    Hmm…someone clearly isn’t a fan of Haldol.

  93. jayemcee says:

    @ PaIMD
    [quote] Hmm…someone clearly isn’t a fan of Haldol. [unquote]

    An in joke if you are a medic (albeit rather tasteless) and an insult if you are not.

    Was that really necessary?

    “The growth of knowledge depends entirely on disagreement”
    (Karl R. Popper, 1902-1994)

    Despite a shaky start, I had thought it possible to make further progress. One could perhaps be forgiven for assuming that medics were; individuals who were worthy of the esteem that society holds them in and by and large that they are intelligent, compassionate beings.

    You have already seen that I am rather swift to anger. I have been around the block more than once and have a very accurate BS meter. I have no problem with using the same literary coin as an adversary, especially when it emanates from ignorance.

    In this case I will make an exception and refrain from replying in kind to your unkind comment to pec because there will be never be progress if you cannot keep this type of juvenile comment out of the discourse. In another life, I too could make smart-arsed remarks and think them funny… this is neither the time nor the place.

    I would sincerely hope that is an end to it for further progress depends on consensus to abide by rules and a combative stance is the end of civil discussion. If you wish to withdraw from the debate then say it aloud so that we all can understand it. Don’t dress up your unwillingness to face the issues (that the opening post has raised) as puerile humour.

  94. PalMD says:

    Excuse the ad hom, but there is no discourse when one of the parties has fixed, false beliefs.

  95. Harriet Hall says:

    Jayemcee says, ” there will be never be progress if you cannot keep this type of juvenile comment out of the discourse…
    I would sincerely hope that is an end to it for further progress depends on consensus to abide by rules and a combative stance is the end of civil discussion.”

    After the ad hominem insults he spouted at me (above) this is really rich! Talk about the pot calling the kettle black!

    He has missed his calling as a comedian.

  96. jayemcee says:

    [quote] I’ll try once more to make my point, although I fear that the emotions and biases of my critics will make it impossible for them to understand. I have no agenda. I have no bias for or against cholesterol or statins. [unquote]

    Your summary dismissal of Dr Ravnskov’s work would suggest that you do have an agenda and a bias, especially when combined with some of the content from some of your numerous blog entries.

    [quote]I have done my best to look at the evidence objectively, and I have found no support for the claims of THINCS that cholesterol has nothing to do with heart disease, that low cholesterol is harmful and high cholesterol desirable, or that statins cause cancer.
    [unquote]

    The small list of scientific references which I have provided may point you towards some areas of special interest that you have not yet considered. The last 4 references are highly detailed technical papers, from the widely regarded Professor Bruce Ames and co-workers, about the impact on cellular life when there is disruption in the cycle of processes involving heme a.

    The mevalonate metabolic pathway is where heme a is synthesised. This is the exact same pathway where cholesterol is inhibited by statins. Heme a is only found in the mitochondria and when it is depleted, apoptosis (programmed cell death) and premature aging appear to be the logical outcome.

    Pfizer’s had stopped their phase 3 clinical trial of the compound atorvastatin/torcetrapib. Not because they had especially wanted to do so but because the independent monitor (DSMB) had noticed the number of deaths associated with the compound on trial and had informed Pfizer.

    Luckily, the link to the FDA notice of the closure of the trial on December 3rd 2006 has never been removed, in contradistinction to the notice of cessation on Pfizer’s website, where a copy of the document (with similar wording to the FDA document) announcing the cessation of the trial had stayed visible for around 24 hours. One could say that Pfizer were burying bad news… literally as well as figuratively in this case.

    [quote] It seems clear to me that THINCS is not considering the evidence objectively, and that there are logical flaws in their arguments. [unquote]

    Here we will have to disagree. I have been in contact with many of the members of the THINCS group. I find them to be a caring group of people who have the best interests of patient at heart. I see that they want to halt the sheer madness that shouts ‘statins for life for everyone’, so as to prevent yet more terrifying cases of iatrogenic damage that is so ably demonstrated by the statinated populace.

    [quote] There are many unanswered questions about the heart disease/cholesterol/statin connection. The medical scientific establishment is doing a pretty good job of asking questions on its own, without any need for prompting from activist groups. [unquote]

    It don’t understand why a well paid group of clinicians would jeopardise their careers, face the misplaced opprobrium of the profession and lose their clinical friends through isolating themselves by taken a controversial stance on statins. The activist group would suggest that they are fringe clinicians with nothing to offer other than snake oil. why would they inhabit that uncomfortable space?

    The answer may lie in the viewpoint that they are ashamed of the way the profession has been subsumed into the maw of the pharmaceutical manufacturers. Furthermore, that for a fat consultancy fee or the promise of a research grant, be willing to prostitute the profession and say what the drug company bosses want to hear.

    When I was younger, systolic hypertension was calculated by the following formula… your age plus 100. Today anyone with a systolic reading of 130 is almost abnormal. Total cholesterol reading guidelines have also fallen… soon it is likely to be 4.0… more statins and lets have then put in our drinking water, courtesy of the the unfortunately named Dr John Reckless.

    Is it any wonder that concerned clinicians should want to be anti-statin activists?

    [quote]I will continue to follow the evidence wherever it leads. I will try not be swayed by horror stories and testimonials or by opinions. [unquote]

    I guess that on its face you have espoused a truly laudable aim and it is certain that scientists will agree with you and applaud your position. The horror stories ought to sway you for they are the stories of the mounting pile of corpses and permanently statin-damaged people, who trusted their medical practitioner to care for their health and who will never be able to get your attention any other way. Ignore them at your peril.

  97. apteryx says:

    Holding stubbornly to a suspicious view of statins (based on their proven side effects, high NNT, carcinogenicity in animal studies, and near-total lack of evidence of efficacy in women and the elderly) is not the same as holding, say, to a positive view of homeopathy (based on no facts at all). It’s more comparable to holding stubbornly to a rosy view of statins despite the abovementioned facts. Of course, I see in reading the homeopathy threads that believers in that practice are being called not just deranged and incapable of discourse but “psychopaths” and “bloodsuckers,” so perhaps jayemcee can console himself here with the thought that the attacks on his character have been pretty mild by quackbuster standards.

    OTOH, jayemcee, if you don’t mind my pointing it out, you addressed Harriet Hall in similar tones above and called her belligerent (which she may be) and a charlatan, which reduces your ability to grouse about ad hominem attacks. I too have a good BS detector and a short temper, but let’s both try to maintain a higher rhetorical standard than is resorted to by some of the anti-CAM writers on this site. When you let them get your goat, it only makes them happy.

  98. Harriet Hall says:

    pec,

    I wrote: “There is some truth in some of their arguments, and I have said that.”

    You answered: “you steadfastly ignore everything they are RIGHT about”

    Can you see any discrepancy there? I’m sure everyone else can.

  99. marblue says:

    Raygee:

    “In his book, he tells how he ate eggs each day, increasing the daily total until he got up to 8 eggs per day, meanwhile measuring his own cholesterol, which was actually lower on the highest egg consumption. He did this just to show the LACK of connection between dietary and serum cholesterol. I wonder how many professional researchers would undertake such a personal approach to their work.”

    Dietary cholesterol has little if any effect on blood cholesterol. Eggs are very low in saturated fat. Eggs are high in lecithin. Lecithin binds sterols in the gut, blocking absorption.

    This is why the advice to cut down on egg consumption is wrong. The average Japanese eats 6 eggs per week and they avg. a total cholesterol of 135.

    If I may, I suggest uncaged hens and eggs fed omega 3s.

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