The People's Perspective on Medicine

What Is the Link between Statins and ALS?

Amyotrophic Lateral Sclerosis or ALS is a devastating neurological disease that is ultimately fatal. Also know as Lou Gehrig’s disease, it leads to loss of muscle control. People eventually lose the ability to speak, swallow or even breath. A new study from the University of California at San Diego describes an ALS-like condition linked to the use of statin-type cholesterol-lowering drugs. The investigators studied 10 patients who reported developing ALS-like symptoms while taking statins. Some patients noted an improvement in symptoms when their cholesterol drug was discontinued and deterioration if the drug was restarted.

This supports other research demonstrating that people with ALS get worse more rapidly if they are taking statin-type medications. Although some patients reported temporary improvement when statins were discontinued, the disease eventually returned and progressed. The authors conclude that statin-type medications may affect a susceptible subgroup of people and either trigger or worsen neuromuscular degeneration.

[Drug Safety, Aug 8, 2009]
http://tinyurl.com/mlomrl

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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My husband who been on statins for last 10 years recently got diagnose with als, when he went on Lipitor about five years ago he started feeling serious changes in his muscles aches, pains and weakness. He told his doctors that he started to feel these thing since he went on these meds but they said most likely not there is no proven link between als and statins

I also stumbled on this website by chance. I’m doing a lot of research on vitamin D3, which lead me via cholesterol to statins.
There are, I believe, a few things I’ve learned that might be relevant to this debate. I haven’t read the entire correspondence, so please forgive me if somebody else has already mentioned this.
It is suspected that statins not only lower blood cholesterol, but might also lower cholesterol in the brain and as well as other parts of the body. This might be the cause of cognitive impairment reported by individuals on statins.
Considerable doubt now exists re low cholesterol equals lower risk of cardio-vascular disease. It has also been established that statins reduce or ameliorate inflammatory processes in the arteries, but nobody knew why.
Until quite recently – there is mounting evidence that statins are vitamin D3 analogue, i.e. activate vitamin D receptors in the body – i.e. all the beneficial functions statins have could be solely due to their mimicking vitamin D.
It is well established that individuals with sufficient vitamin D blood levels have lower incidents of heart disease, diabetes, depression, certain cancers, and high blood pressure.
Inversely vitamin D deficiency has now been associated with auto-immune diseases such as rheumatoid arthritis, type1 diabetes and multiple sclerosis.
I would like to see trials where one third of participants is given statins, one third placebo, and one third high dose vitamin D3. Does anybody believe there’s a drug company that manufactures statin medication willing to finance this? I don’t think so…..

Thank you, Gail for bringing reason to the discussion.

After nearly 20 years on Lipitor and 5 years of muscle/neurologic problems, I was diagnosed with ALS. Not one of the 10 doctors I saw for my problems was aware of any possible connection to statins even though they all knew I was on Lipitor. So much for hysteria!

My pharmacist said problems with Lipitor occurs in only about 1/1000 people. While we are all busy quoting statistics – remember the incidence of ALS in the general population is approximately 5/100,000. How many of us do you REALLY think made it into clinical trials??

I accidentally stumbled on this thread. When I brought this to the attention of my Neurologist, he said that considering the diagnosis and outcome of ALS, he didn’t think I need worry about heart disease. My regular doctor agreed.

I am very grateful that my physician is both open-minded and practical.

I just read over the discussion about ALS and statin drugs. I have a sneaking suspicion that the connection is there and we need to continue that discussion.
Please post if you were on a statin drug before your diagnosis/symptom onset!
My story…
I was diagnosed with an aortic aneurysm about 4 years ago. While my cholesterol was not high my cardiologist put me on Pravastatin “just in case”. “The lower your cholesterol the better” he insisted. I took it for about 6 months and just didn’t like it, (muscle aches soreness etc.) so stopped taking it. About 4 months later I started tripping over my toes and we were off to the races! I was diagnosed with ALS about a year later.
I asked my cardiologist about a connection and he sloughed it off. “Oh, no, there’s no connection”. How does he KNOW? They dismiss our questions and hand out the drug companies money makers like candy.
Everyone I know is being given statins! I advise people now of my suspicions and beg them not to go on any drug unless absolutely necessary. These “just in case” prescriptions are going to come back to haunt us.
(I just had a Hickman placed so I can begin the Ceftriaxone trial and the doctor doing the procedure commented that so many discoveries are made by accident. Weird connections turn out to be the answer sometimes. He said “hey viagra started out as a headache drug but when *other* results happened a new treatment was discovered!” You just never know.
The more we share the more we will someday know.
I’ve asked the National ALS registry to develop a “survey” about prescriptions taken by patients prior to diagnosis and hope they will. We all know that often, where there’s smoke there’s fire and it is just not fair to dismiss our concerns outright. Gather the anecdotal, patient information and we may make the connection that could save me…and many others.
Julie
PEOPLE’S PHARMACY RESPONSE: WE DO NOT YET KNOW WHETHER THE LINK BETWEEN STATINS AND ALS IS “REAL,” BUT IT IS CERTAINLY WORTH SOME ATTENTION.
THE DOCTOR WHO TOLD YOU ABOUT VIAGRA GOT THE STORY ALMOST RIGHT. IT WAS SUPPOSED TO HAVE BEEN A HEART DRUG.

Hi: I haven’t read all the info on this site r/t statins and ALS, however, I must say it was with some consternation that I found that the 2011 Mosby’s Drug Reference book has a Black Box Warning which correlates the risk of taking Crestor to ALS!
Yikes. I’ve been on statins for about 12 years plus Ezetrol for the last 3. The Ezetrol is what really worked – it was amazing! Prior to the Ezetrol ordered by an Internist, the effect of the statins on my LDL, Triglycerides and HDL, was minimal, but, anything was better than what it had been.
The aches and pains that many have referred to can truly reduce one’s quality of life and I agree that when mentioned to the physician there seems to be little recognition that the side effects of these statins can be quite debilitating.
I have to really think long and hard about continuing taking the statins. I might stroke, but at least with a stroke I have a chance of surviving with some deficits maybe, but, hopefully not too severe. With ALS… well we know the prognosis.
I will await hearing back from my family Doc., and decide which route to take after our discussion.

I have come to this debate late but I’m hoping that some of you are still following.
I am a statin victim and was ultimately disabled by the adverse effects of this horrible drug after 5 years on 20mg zocor.
After months of providing info to my doctor he finally admitted that the statins were the cause! He went on to say unequivocally that he would admit that to no one else and refused to report my case to Medwatch! Underreporting of statin damage is extremely high. I offer the following to MDA in the hopes that he will temper his BLIND FAITH in studies that have been repeatedly questioned. Understand also that I am not questioning the value of statins used in middle aged men with known CAD but the use of statins for primary prevention,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079612/
Next an excellent dissertation on “the academical philosophy of mitigated skepticism” written hundreds of years ago but very relevant to this whole discussion…and just an awesome read:
from public domain:
“THERE is, indeed, a more mitigated scepticism or academical philosophy, which may be both durable and useful, and which may, in part, be the result of this Pyrrhonism, or excessive scepticism, when its undistinguished doubts are, in some measure, corrected by common sense and reflection.
The greater part of mankind are naturally apt to be affirmative and dogmatical in their opinions; and while they see objects only on one side, and have no idea of any counter-poising argument, they throw themselves precipitately into the principles, to which they are inclined; nor have they any indulgence for those who entertain opposite sentiments. To hesitate or balance perplexes their understanding, checks their passion, and suspends their action. They are, therefore, impatient till they escape from a state, which to them is so uneasy: and they think, that they could never remove themselves far enough from it, by the violence of their affirmations and obstinacy of their belief. But could such dogmatical reasoners become sensible of the strange infirmities of human understanding, even in its most perfect state, and when most accurate and cautious in its determinations; such a reflection would naturally inspire them with more modesty and reserve, and diminish their fond opinion of themselves, and their prejudice against antagonists. The illiterate may reflect on the disposition of the learned, who, amidst all the advantages of study and reflection, are commonly still diffident in their determinations: and if any of the learned be inclined, from their natural temper, to haughtiness and obstinacy, a small tincture of Pyrrhonism might abate their pride, by showing them, that the few advantages, which they have attained over their fellows, are but inconsiderable, if compared with the universal perplexity and confusion, which is inherent in human nature. In general, there is a degree of doubt, and caution, and modesty, which, in all kinds of scrutiny and decision, ought for ever to accompany a just reasoner. David Hume”
now an explanation of how this “bad science” can come about, again from hundreds of years ago during the beginning of the enlightenment.
excerpt from the preface to “Elements of Chemistry” by A. Lavoisier again from the public domain:
“When we begin the study of any science, we are in a situation, respecting that science, similar to that of children; and the course by which we have to advance is precisely the same which Nature follows in the formation of their ideas. In a child, the idea is merely an effect produced by a sensation; and, in the same manner, in commencing the study of a physical science, we ought to form no idea but what is a necessary consequence, and immediate effect, of an experiment or observation.[4] Besides, he that enters upon the career of science, is in a less advantageous situation than a child who is acquiring his first ideas. To the child, Nature gives various means of rectifying any mistakes he may commit respecting the salutary or hurtful qualities of the objects which surround him. On every occasion his judgments are corrected by experience; want and pain are the necessary consequences arising from false judgment; gratification and pleasure are produced by judging aright. Under such masters, we cannot fail to become well informed; and we soon learn to reason justly, when want and pain are the necessary consequences of a contrary conduct.[5]
In the study and practice of the sciences it is quite different; the false judgments we form neither affect our existence nor our welfare; and we are not forced by any physical necessity to correct them. Imagination, on the contrary, which is ever wandering beyond the bounds of truth, joined to self-love and that self-confidence we are so apt to indulge, prompt us to draw conclusions which are not immediately derived from facts; so that we become in some measure interested in deceiving ourselves. Hence it is by no means to be wondered, that, in the science of physics in general, men have often made suppositions, instead of forming conclusions. These suppositions, handed down from one age to another, acquire additional weight from the authorities by which they are supported, till at last they are received, even by men of genius, as fundamental truths.
The only method of preventing such errors from taking place, and of correcting them when formed, is to restrain and simplify our reasoning as much as possible. This depends entirely upon ourselves, and the neglect of it is the only source of our mistakes. We must trust to nothing but facts: These are presented to us by Nature, and cannot deceive. We ought, in every instance, to submit our reasoning to the test of experiment, and never to search for truth but by the natural road of experiment and observation. Thus mathematicians obtain the solution of a problem by the mere arrangement of data, and by reducing their reasoning to such simple steps, to conclusions so very obvious, as never to lose sight of the evidence which guides them.”
PEOPLE’S PHARMACY RESPONSE: WE DELETED A URL DAVID SUPPLIED RELATED TO ALL-CAUSE MORTALITY BECAUSE IT REQUIRES JAPANESE FONTS. BUT TWO RECENT PUBLICATIONS IN THE ARCHIVES OF INTERNAL MEDICINE SUPPORT HIS ARGUMENT THAT STATINS SHOULD NOT BE USED INDISCRIMINATELY FOR PRIMARY PREVENTION:
http://archinte.ama-assn.org/cgi/content/short/170/12/1024
and
http://archinte.ama-assn.org/cgi/content/short/170/12/1032

I’m not sure about the argument between the usage of statins and muscle degeneration, but what I do know is that my husband has been taking statins for a couple of years and has recently discovered muscle atrophy in his right calf. He has undergone multiple test by the practicing neurological surgeon for nerve damage due to a back surgery for a ruptured disk 9 years ago. He has also been tested by a neurologist for evidence of nerve damage to explain muscle degeneration with no obvious result.
Tests have shown that the calf muscle is not receiving nourishment as it should, but neither specialist knows why. Now they are sending my husband to Emory for further testing and telling him they don’t see any reason why this should be happening. The idea of some kind of nerve disease has been suggested and the term Lou Gehrigs disease has been mentioned without any real explanation. So, why would this correlation be made by these specialist if there were not some question as to whether or not the idea of using a statin for cholesterol were not of concern.
The specialists do not make a direct link, but they both have his medical history and know he has been taking this medication for several years, so why does this disease come to mind if there is no real proof or, is it that we just don’t really know if there is a connection or not? I really do not know what to think at this point. It is what the doctors don’t say that really has me worried.
I just want to know why my husband’s muscle is slowly getting smaller and weaker. And, if the degeneration proves to be a side effect from taking a medication for cholesterol that has been deemed safe, well that’s just very sad. And the mere fact that medications are being given to patients before the long term effects have been determined is just inhumane. Studies should be done before giving so many people this medication, especially if the side effects/results are a disease that can kill you within a few years. How do you test for ALS anyway?

MDA:
I fully sympathize with physicians whose patients read the drug info on side effects and then decide the drugs are the cause of their problems (and not the condition itself or something wholly unrelated).
As I have posted before, I also think it’s true that the full impact of drugs on a population is not known at the time they are approved and released “into the wild” after clinical trials (in which populations are controlled). Therefore it’s not surprising that new and real symptoms and side effects pop up as more people are taking a drug.
One of the problems of course is who would fund studies to determine that–pharma doesn’t have much to gain by proving their drug has some untoward effects.
ALS aside, I would like to see some studies that focus on side effx from statins. It’s clear that some people have none whatsoever, and some DO have some that they consider serious.
In the meantime, I would take seriously any patient’s complaint of muscle weakness and cognitive changes. This is where clinical judgment would come in, and perhaps the physician might make different decisions for patients –one with many risk factors and cholesterol of 400, a different one for a patient with few risk factors and cholesterol only somewhat elevated above the magic 200 mark. Today, they’d both likely be advised to stay on the statin.
Unfortunately, I think physicians are more hampered nowadays from using that kind of judgment. The more guideline (derived from population stats) and litigation driven our system becomes, the less the physician’s judgment counts for individual care.

SH and JH: No, I am not saying that statistics can ever be used to discount the possibility that an individual is having a particular side effect from a particular drug. What I am saying is that just because an individual who develops ALS is a statin user does not prove that that person’s ALS is due to the statin. That’s where statistics need to be considered, such as the 2008 FDA analysis (referenced above) of data from over 40 clinical trials that did not show a link between statins and a higher risk of ALS. Is it possible that there is a link despite that negative analysis? Of course! It’s just a whole lot less likely.
I’m all in favor of more research.
SH: Your point about identifying factors that increase individual susceptibility to a particular side effect as a way of identifying people who perhaps should not be exposed to a particular drug is excellent. But the premise (i.e. that a particular condition is indeed a side effect of the drug; typically defined as occurring more commonly in those on the drug than in the general population) needs to be established first in order to make that endeavor worthwhile.

MDA MD:
You seem intent on offering statistics as proof that people are not having these side effects, and seem to want to be strictly scientific about it. Surely you then know that statistics are meaningful for populations, but not necessarily for individuals (otherwise there would be 100%’s, and there rarely are).
Seems to me the scientific mind would be asking: what is the difference between people who experience side effects and those who don’t, and if we find that out, we could predict who would benefit and who would be at greater risk and should NOT take these drugs.
There are plenty of models for this in medicine.

MDA,
Despite your statistics, “anecdotal” reports should not be considered “not useful.” These are real people, experiencing real life health disasters. Every effort should be made to do more indepth research and studies on this subject. Your statistics do not eliminate the possibility of statins being a factor in some persons developing ALS, or an ALS-like condition.
Statins have been shown to cause muscle and nerve damage, so a possible relationship to ALS in perhaps certain people, should not be discounted. The fact is that in the “anecdotal” reports, the indication is strong that the initial nerve problems were statin related in some way. Then things progressed from there.
With such a serious condition, every effort should be made to do the much needed real and complete studies. (not funded by the drug companies) Continuing to play down and ignore the overwhelming reports coming in does no service to people’s real health concerns.

Leigh, according to The ALS Association: “Based on U.S. population studies, a little over 5,600 people in the U.S. are diagnosed with ALS each year. (That’s 15 new cases a day.) It is estimated that as many as 30,000 Americans have the disease at any given time.” (http://www.alsa.org/als/who.cfm).
About 10% of the adult U.S. population takes statins.
10% of 5,600 is 560. 10% of 30,000 is 3,000. So one would expect (assuming – for the sake of argument – a neutral effect on statins on ALS risk) that there would be about 560 new cases of ALS per year among statin users in the U.S., and at least 3,000 Americans with ALS at any given time who are (or were) statin users. So anecdotal reports are not useful. All that matters is whether statin users have a higher incidence of ALS than nonusers.
A 2008 analysis by the FDA of data from over 40 clinical trials did not show a link between statins and higher risk of ALS. Reference: http://www.medicalnewstoday.com/articles/123519.php
Article Date: 30 Sep 2008

Now there are at least 11 people who are experiencing ALS-like symptoms and had been taking a statin: my father. And he has personally has come into contact with eight people who are having the same problems from taking statin.
I believe this has been previously under reported for various reasons. I am going to learn more about this study and offer another example to add to it. Second neurological opinion at Washington U in St. Louis SOM is tomorrow – taking the pdf with us. The is what is called emerging science.
As an aside, we are professionals with high IQs, and we’re not imagining this. This really is happening.

On the subject of research and one’s genetic make-up, I have a theory that being a HLAB27 gene carrier may have in some way predisposed me to the symptoms I have experienced – particularly those which have affected my joints/muscles.
There is a school of thought which suggests statin side-effects may be afflicting anywhere between 10-20% of those taking them, and co-incidentally roughly 14% of the population carry the HLAB27 gene which is notorious for erroneously tricking the body’s autoimmune system into attacking itself.

I have followed this thread with interest (and also commented previously).
Here’s something that has occurred to me:
In cancer research, a growing trend is to identify molecular and genetic differences in tumors, and for many kinds of cancers it is now known that there are subsets of what we used to consider the same tumor types, and these subsets behave differently in terms of the chemotherapy agents they respond to.
Now my point is this: as we progress in medicine, I think we will find that there are differences (perhaps genetic) between people that determine how they will respond to a given drug.
So, Dr. A’s large studies, while valid for whole populations, do not negate the experience of people who experience different effects.
Outcomes/Evidence-based medicine is generally a good thing, but we must remember that individuals vary. A risk of 1% might seem very low to a doctor, but if you’re that patient in that category–well, not so trivial to you.

I’m convinced I was only a few weeks away from rhabdomyolisis induced kidney failure and possible death if I had stayed on the statin any longer. I felt like death was approaching rapidly, and I was suffering from muscle destruction, and cognitive deterioration. What would the doctors have said? “Oops, but it’s rare.” One severely damaged life is too many. Let’s stop the madness. Now I feel better each day since I stopped the statin and researched alternative approaches to heart health. Go with what your body is telling you and do your own research, and make informed medical choices.

Another interesting story showed that patients taking statins were almost 50 percent less likely to die from flu. It was reported by Reuters on Oct 29, 2009, citing research by Meredith Vandermeer of the Oregon Public Health Division.

Mike, sorry, but many years of multicenter, randomized, prospective, double-blind placebo-controlled statin studies involving many tens of thousands of study participants simply do not support the contention that “multitudes of people” experience the side effects you report. They typically show little (1-2%) to no difference from placebo in regard to muscle symptoms, and no difference from placebo in regard to cognitive issues. That is not to say that no one experiences side effects or that we should not remain alert to the possibility. But it is important for people to understand that the true incidence is very small, so that people are not frightened away from these life-saving drugs. Again, the benefit to risk ratio of statins has been estimated at 400:1 (reference above).
By the way, have you seen this yet: (Internal Medicine News Volume 42, Issue 18, Page 5, October 15 2009)
Use of Statins May Halve The Risk of Dementia BY Michele G. Sullivan
“Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has shown.” Dr. Alina Solomon of the University of Kuopio, Finland, wrote a poster presented at the International Conference on Alzheimer’s Disease.
PEOPLE’S PHARMACY RESPONSE: WE’LL BE WATCHING THE MEDICAL LITERATURE FOR DR. SOLOMON’S PAPER TO BE PUBLISHED. THIS IS A SUMMARY OF A PRESENTATION AT A CONFERENCE. SOMETIMES SUCH PRESENTATIONS DON’T PAN OUT LATER, THOUGH IT CERTAINLY IS INTERESTING.

Firstly, I must say what a fascinating debate this has been to follow.
My reason for finding this website is because I too am suffering from many of the side-effects listed above, not least those of a cognitive nature which are by far the most worrying. Everyone close to me has noticed my mental decline, and yet on reporting this to my GP (MD) I was simply told to expect this as part of ‘getting older’. I received short shrift when I asked my GP how it could be so noticeable to people around me, and yet of so little concern to her personally.
The bottom line is that I know my body better than anyone else – I must do, because I physically feel the aches/pains and suffer the embarrassment caused by my constant absent-mindedness. However, it is nothing short of patronizing when members of the medical profession suggest that I should simply accept that the numerous health issues I have experienced in the last 20 months are ‘to be expected as part of getting older’ or worse still, imaginary because all the basic tests (bloods, x-rays etc.) show nothing untoward.
My GP also likes to suggest my anxiety is a reason for all these diverse symptoms, but wouldn’t she be anxious too if all these things happened to her in such a short space of time after enjoying more than 50 years of distinct good health?
Since discovering that my problems are statin-related, I have raised the issue with a number of friends who I know to be on statins too. WITHOUT EXCEPTION, they confirmed similar problems (eg. muscle problems) which they never attributed to their statins, and had never been advised by their GPs could be the root of the problem.
I have a feeling that this issue will not go away, and Dr A might just have to revise his views once the multitudes of people who don’t like consulting their GPs for fear of being told they are ‘getting old’ finally decide to stand up and fight their corner.

So, that brings us to the stroke data, without which no discussion of the cognitive effects of statins would be complete. Each year in the U.S. about 795,000 people experience a new or recurrent stroke and about 610,000 of these are first attacks. Strokes of course are devastating brain injuries which can cause severe and often permanent cognitive and other functional deficits.
On Feb. 19, 2009 an analysis from the JUPITER study was presented at the International Stroke Conference (ISC) in San Diego, describing details of the stroke data according to gender, ethnicity and baseline risk factors. This data added to the primary analysis of the JUPITER study which showed that Crestor 20mg significantly reduced the risk of stroke by nearly half (48%; p=0.002) compared to placebo among men and women with elevated high-sensitivity C-reactive protein (hsCRP) but low to normal cholesterol levels.
This analysis of the JUPITER data evaluated Crestor 20 mg across a number of subgroups with notable benefits in higher risk patients, including those older than 70 years, cigarette smokers, hypertensives, those with an elevated Framingham risk score, and those with a high-sensitivity C-reactive protein level at or above 5 mg/L at baseline.

Yes, out of an abundance of caution the FDA did not approve the 80 mg dose of Crestor. But the significance of the mild transient urinary protein seen in some patients on statins is unclear. It does not appear to be associated with kidney damage. (Lot’s of things – even exercise – commonly cause mild transient appearance of protein in the urine of no apparent significance in normal people. Diabetes and high blood pressure – common comorbidities in people on statins – commonly cause protein in urine).

From FDA Public Health Advisory for Crestor (rosuvastatin) 5/13/09:
“Mild, transient proteinuria (or protein in the urine, usually from the tubules), with and without microscopic hematuria (minute amounts of blood in the urine), occurred with Crestor, as it has with other statins, in Crestor’s pre-approval trials. The frequency of occurrence of proteinuria appeared dose-related. In clinical trials with doses from 5 to 40 mg daily, this effect was not associated with renal impairment or renal failure (i.e., damage to the kidneys). It is recommended, nevertheless, that a dose reduction and an investigation into other potential causes be considered if a patient on Crestor develops unexplained, persistent proteinuria.”

correction on earlier comment, I meant Henry Lorin’s father in-law, not brother in-law.

MDA, I don’t know, but this JUPITER trial involving Crestor seems a bit fishy in regard to frequency of myopathy symptoms. It is true various statin drugs are formulated a bit differently, but the way they work is basically the same. I would be interested to know how they determined the frequency of the reporting of myopathy symptoms. Also, if the drug industry in some way manipulated/influenced the study and these results.
You ask “why is that?” as far as these low amounts of reported myopathy symptoms in the JUPITER trial. “Why IS that?” indeed. I have a “why is that?” for you. Crestor (rosuvastatin) and muscle breakdown: Crestor is on the USA market despite being the only statin that caused life-threatening rhabdomyolysis in pre-approval clinical trials, along with elevations of protein in urine. So much so that the proposed 80mg dose was abandoned, and the 40mg dose was to be sold with special restrictions. Public Citizen made a presentation to the FDA on 7/3/03 opposing the approval of the drug in any dose.
Life-threatening muscle breakdown with Crestor in pre-approval trials, yet low or no myopathy symptoms reported in this study. “Why is that?”
Also, in my own informal survey of friends and relatives prescribed statins, (about 80% of the people I know who are middle age and up have at one time or another been prescribed statins) Virtually 100% of them had muscle, tendon and joint issues clearly related to their statins. Most of them had to stop their statins to get relief. Others would get relief, but pain/weakness would return upon restarting the statin. Their symptoms were all to a degree unusual for people in their 50’s. “WHY IS THAT?”
Likely none of these cases got past the wall of doctor statin effects denial to get reported to the FDA. Probably not even a note in their medical records that incriminated the statin in any way… The denial continues, but many know from personal experience the truth of statins and their serious effects.

MDA, In reply to your reference on high and borderline cholesterol levels in midlife being associated with later Alzheimer’s. The book I have been getting my low cholesterol/Alzheimer’s information is a book by Henry Lorin called “Alzeimer’s Solved”.
He addresses the information you mention, but makes the point that it is the semi-starvation/low cholesterol of LATER life that triggers the Alzheimer’s. So this midlife high or borderline cholesterol is not involved. The development of Alzheimer’s in Henry Lorin’s brother in-law began his research into Alzheimer’s. His brother in-law was overweight and had high cholesterol at midlife. He worked hard to reduce his weight and cholesterol and took statin medication. In his later life, and in the semi-starved and low cholesterol condition, was when he developed Alzheimer’s.
Myself, I don’t know. But nevertheless, I find Lorin’s exhaustive research, and his theory compelling.
Also, I wonder at what point these high and borderline cholesterol at midlife person’s, might have been put on a statin; and what effects long term statin use might have had on their cognitive function. While on the statin I found my memory and concentration getting weaker and weaker. I had difficulty following the plot in simple TV shows. I had a feeling of cobwebs closing in on my brain. It felt easier not to put forth the effort to fight it. The fog built and got harder to resist. When I came off the statin, the first week I remember sitting and feeling a clarity I hadn’t felt in quite some time, returning. The fog began to lift, and has been improving ever since! I wonder, how many elderly patients are drifting into a statin induced cognitive fog, and it is put off to aging and cognitive problems “common” to aging. How do we know?

This is a repeat entry, as I am still awaiting a reply to my “Why is that???” question:
Joe, in the JUPITER trial (published in NEJM 2008), in which 17,802 men and women were randomized to Crestor vs. placebo, myopathy did not occur more frequently with Crestor than with placebo. Specifically, a total of 19 myopathic events were reported: 10 in subjects receiving rosuvastatin and 9 in subject receiving placebo (p=0.82). The median follow-up of subjects was 1.9 years, and no increased myopathy was detected in an analysis of participants who continued to receive Crestor for 4 or more years.
According to your claim of a 10-15% incidence of myopathy symptoms, of the 8901 patients randomized in that study to Crestor, one would expect 890 (10%) or 1335 (15%) patients to have reported myopathy symptoms. Yet there were only 9 (nine). Why is that???
Ridker PM, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM. 2008:359:2195-2207

Joe, as you know, there are methodologic reasons that may well explain why certain recent studies did not demonstrate that tight control of blood sugar will produce desirable outcomes. So those study findings of course do not mean that tight control of blood sugars does not produce desirable outcomes in the real world.

Dear Dr. A.
Well, I am glad you have moved from the position that statins lower the risk of developing Alzheimer’s disease [AD] to “it’s just too early to know what the overall long-term impact of statins is on cognitive functioning…”
Just because there has been a study linking high cholesterol to the development of AD does not mean that taking statins will reduce the risk of developing this dreadful disease. Please remember the data on tight control of blood glucose and long-term outcomes. As an endocrinologist we know you are fully aware of the most recent data. Sometimes what we believe intuitively is not demonstrated by high-quality research, ie that tight control of blood sugar will produce desirable outcomes.
The Cochrane Collaboration examined ALL the data available, focusing on high quality randomized, double-blind, placebo-controlled trials. The conclusion as described above found no evidence that statins reduce the risk of developing AD.
Joe

Joe, sure, I would be glad to quote the most recent data (August 2009 being more recent than your April 2009 data). A study published August 2009 online in the journal Dementia & Geriatric Cognitive Disorders (2009;28:75–80; available online at http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=231980&Ausgabe=250346&ProduktNr=224226&filename=231980.pdf) showed that those with cholesterol over 240 were 57 percent more likely to have developed Alzheimer’s disease than those with optimal levels.
Perhaps the key is “statins given in late life” in the Cochrane database. By that point maybe the horse is already out of the barn. In contrast, the Dementia & Geriatric Cognitive Disorders journal article I referenced “points out the importance of addressing risk factors as early as midlife, before the underlying disease(s) or the symptoms appear.”
From what I’ve read, it’s just too early to know what the overall long-term impact of statins is on cognitive functioning, particularly since Alzheimer’s disease, vascular (multi-infarct) dementia, transient global amnesia, etc. are very different disorders, with very different mechanisms.

JM, your statement about high cholesterol being associated with a reduced risk of Alzheimer’s disease is not consistent with the data. For example, The New York Times (August 6, 2009) had the following article, about a study published online in the journal Dementia & Geriatric Cognitive Disorders, showing those with cholesterol over 240 were 57 percent more likely to have developed Alzheimer’s disease than those with optimal levels:
Mildly High Cholesterol at Midlife Linked to Alzheimer’s
“Adults who had just slightly elevated blood cholesterol when they were in their early 40s were at greater risk of developing dementia decades later, compared with those whose cholesterol was at optimal levels, a new study has found.
The findings, which analyzed data from almost 10,000 health care plan members followed for four decades, surprised the investigators.
While earlier studies have shown an association between high cholesterol in midlife and an elevated risk of Alzheimer’s disease, “we were surprised to see the association with borderline levels,” said Rachel A. Whitmer, an epidemiologist with the Kaiser Permanente Division of Research and the paper’s senior author.
The study followed 9,844 members of the Kaiser Permanente Northern California Medical Group who had blood work done between 1964 and 1973, when they were 40 to 45 years old. All had remained members of the plan until at least 1994, when computerized outpatient diagnoses of dementia were made available.
Some 598 of the original participants were diagnosed with Alzheimer’s disease or vascular dementia, a less common form of dementia, between 1994 and 2007, when they were between 61 and 88 years old.
Those whose total blood cholesterol had been high — over 240 milligrams per deciliter — were 57 percent more likely to have developed Alzheimer’s disease than those with optimal levels. Those who had borderline cholesterol values — between 200 and 239 milligrams per deciliter — were at 50 percent greater risk of developing vascular dementia.
“What’s good for the heart is good for the brain,” Dr. Whitmer said, adding, “Midlife is not too soon to be thinking about risk factors for dementia. This is a modifiable risk factor. This is something you can change.”

PEOPLE’S PHARMACY RESPONSE:
Dear Dr. A.
I have resisted responding to your repeated assertions that statins reduce the risk for Alzheimer’s disease…but I can remain silent no longer.
You are, no doubt, familiar with the Cochrane Library and systematic review of the scientific literature. The Cochrane Collaboration is dedicated to determining the value of clinical research and its publications are valued throughout the world. This is the evidence-based medicine that you cherish.
On April 15th, 2009 the Cochrane Database Systematic Review concluded that: There is good evidence from RCTs [randomized controlled trials] that statins given in late life to individuals at risk of vascular disease have no effect in preventing AD [Alzheimer’s Disease] or dementia. Biologically it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. Indication bias may have been a factor in these studies however and the evidence from subsequent RCTs has been negative.”
I would hope that you would allow the most recent and objective data to take precedence over some of the earlier studies you cite above.
Joe

MDA, Here are a few points on the statin/Alzheimer’s subject. They show how the results of studies can so easily be misinterpreted.
(Keeping in mind the theory that long term semi-starvation with long term low cholesterol levels, are a key cause of Alzheimer’s.)
1)Who do doctor’s usually place on statins? Those with consistently HIGH cholesterol levels. These are the ones LEAST likely to develope Alzheimer’s! (It would likely take quite some time for the recently lowered by the statin cholesterol levels , to begin the Alzheimer’s process.)
2)People with LOW cholesterol levels are not likely to be placed on a statin, and these are the people MOST likely to develope Alzheimer’s! So now you have this group of people developing Alzheimer’s, who are not placed on statins.
So, you see how easily it could be misinterpreted from statistics, that statins might protect against Alzheimer’s. I wouldn’t run so quickly with that 47% reduction of Alzeimer’s risk figure. Statins can absolutely destroy the quality of life for an elderly person during their last years. I’ve personally experienced what a statin can do to an active and healthy 50 year old. I shudder to think what these same effects would do to an elderly person. Just read some of the accounts right here on the People’s Pharmacy site. There are accounts from loved ones who saw the health of their formerly very active elderly loved ones, go right off a cliff after being put on a statin. These accounts are so tragic they bring tears to your eyes. Of course the prescribing physician puts it all off to normal aging. They close their eyes and will never see or admit the truth. They don’t listen to the relatives of the elderly one who are much closer to the situation, being with the older one every day. The doctor only sees them from time to time among many patients. Doctor MDA, I say it again, the statins you give your elderly patients are doing much more damage than you realize. The risks are off the charts, and check your much cited major statin studies, the benefits for the elderly simply don’t show in the studies. ELDERLY PATIENTS SHOULD NOT BE PRESCRIBED STATINS! “Do no harm.”

Dr Graveline,
Two questions for you:
What is the annual incidence of transient global amnesia in the general population?
How do you balance your concerns with the evolving body of evidence showing reduction in Alzheimer’s Disease (AD) risk for people taking statins:
47% reduction in AD(J Neurol NeuroSurg Psychiatry Oct. 17, 2008), discussed above;
67% reduction in the risk of AD (Current Alzheimer Research 2008; 5: 416-421);
48% reduction in risk of dementia or cognitive impairment for statin users (Neurology 2008; 71; 344-350);
74% unadjusted lower risk of AD for statin users (Arch Neurol 2002; 59: 223-227);
69.6% lower prevalence of AD for statin users (Arch Neurol 2000; 57: 1439-1443);
71% lower relative risk of AD for statin users (Lancet 2000; 356:1627-1631).
Thanks,
MDA, MD
PEOPLE’S PHARMACY RESPONSE:
Dear Dr. A.
I have resisted responding to your repeated assertions that statins reduce the risk for Alzheimer’s disease…but I can remain silent no longer. You are, no doubt, familiar with the Cochrane Library and systematic review of the scientific literature. The Cochrane Collaboration is dedicated to determining the value of clinical research and its publications are valued throughout the world. This is the evidence-based medicine that you cherish.
On April 15th, 2009 the Cochrane Database Systematic Review concluded that: There is good evidence from RCTs [randomized controlled trials] that statins given in late life to individuals at risk of vascular disease have no effect in preventing AD [Alzheimer’s Disease] or dementia. Biologically it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. Indication bias may have been a factor in these studies however and the evidence from subsequent RCTs has been negative.”
I would hope that you would allow the most recent and objective data to take precedence over some of the earlier studies you cite above.
Joe

My first book, Lipitor, Thief of Memory, was written after my two bouts of transient global amnesia associated with the use of Lipitor in the year 2000. Predictably at that time, I was focused on cognitive dysfunction and Lipitor.
The work of Frank Pfrieger on the importance of cholesterol to brain function was published in 2001. Then for the first time the medical and scientific community learned of glial cell synthesis of cholesterol and its necessity for both the formation and function of memory synapses. Abruptly I had my answer as to to my amnesia episodes. Until that time no one in our medical community seemed to understand how a statin drug could adversely affect cognitive function.
I had been left knowing that my MRI was normal and now even though several other statin users had shared my TGA experience by reporting to the statin study I was still concerned about the possibility of underlying organic disease because we, as yet, had no mechanism. The work of Pfrieger was of immense importance to me for it described an unequivocal reason for my amnesia.
Cholesterol in our blood must be carried about attached to lipoprotein so that the resulting molecule is much too large to pass our so-called blood brain barrier so is therefore unavailable to our brain. Our brain cholesterol comes from specialized housekeeper cells in our brain known as gial cells, whose task it is, among many others, to produce cholesterol upon demand. Only in the presence of this cholesterol can memory function take place. We humans had evolved with this mechanism of brain function and cholesterol was absolutely vital. One can easily imagine the sensitivity of these glial cells to the reductase inhibition effect of statins – inhibition of cholesterol synthesis. No further questions necessary.
I finally had my mechanism for memory impairment and by now hundreds of emails were coming in to my website from those now aware that statin drugs had the ability to seriously impair cognitive function. In just a few months we had 30 cases of transient global amnesias reported to me and Dr. Beatrice Golomb, director of the new, NIH funded, statin study at UCSD college of medicine invited me to co-author a paper for submission to The Archives of Internal Medicine to pass this information on to the medical community.
As a former USAF and civilian flight surgeon, I was particularly concerned that pilots and others on flying status were being permitted use of these statin drugs. What if I had been flying my plane when one of these amnesia episodes hit? In my first episode of TGA I retrograded 10 years. In my second, 56 years. I was 13 years old for an amazing 12 hours. Obviously in my second experience, my flying training, like my marriage with children and my training as a doctor, had not yet taken place. To abruptly “awaken” in the cockpit of a strange, never before entered, flying machine would have been an incredible experience and almost certainly deadly. Our medical community needed to have this information.
You can imagine my reaction to learn that the Archives rejected it. Two months later we submitted this paper to the Annals of Internal Medicine and they rejected it! Both Golomb and I had abundant experience with submitting papers for publication. It was a very well written paper disclosing a new reality, one that the “powers that be” controlling our peer review process simply were not ready to accept. Statins were too good. If anything they should be put in the drinking water. That was the prevailing climate at that time. MDs did not want to hear of annoying side effects of their promising statins and the last thing the drug companies wanted to see on their golden goose was tarnish.
Finally, in August of 2003 a team of researchers lead by Wagstaff at Duke Universaity managed to publish their paper on titled, “Sixty cases of transient global amnesia reported to FDA’s Medwatch (ref). Medwatch is the formal electronic reporting system for post-marketing surveillance of new drugs. Wagstaff and his team had gotten permission from FDA to review the raw data from Medwatch for amnesia and serious memory impairment reports, finding 60 on which their report was based. Pharmacotherapy journal was sufficiently liberal to publish what should have been a headline-grabbing article. However the readership of this journal is such that there was not the slightest impact on the MD prescribing habits or evidence of awareness of cognitive side effects. There was simply no discernable reaction from the community of clinicians who write the prescriptions for statins.
In 2007, I managed to acquire a CD of Medwatch raw data for Lipitor from the period 1998 through 2006, and using the same criteria as used in the Wagstaff paper, found 662 reports of TGA or comparable memory dysfunction (ref). On the basis of reported rates of TGA seen throughout 2005-2006 I could project with reasonably validity that the total number of such reports received at the time of this writing would exceed 1,000.
Far more important than the numbers, knowing that five more commonly used statins also have contributed their share of cognitive dysfunction during this same time period, not one word of this observation has been officially reported to the medical and scientific communities. The average MD is still completely unaware of the cognitive impact of statins.
And we must remember that TGA is only the tip of the iceberg in that for every case of TGA reported, hundreds of cases of statin associated confusion, disorientation and increased forgetfulness have occurred and many cases are misdiagnosed as Alzheimers. Additionally, hundreds of short term TGA’s measured in minutes rather than hours almost undoubtedly have occurred during this time period only to be completely missed unless an attentive observer was present to document it. The victim would be completely amnestic for this experience.
The classic definition for transient global amnesia is abrupt inability to formulate new memory for a time period ranging from 2 to 24 hours. Any thing longer than 24 hours is increasingly likely to have an organic basis. No mention is generally made of the fact that there is no neurophysiologic reason why TGAs measured in minutes can not occur. A TGA lasting for minutes would be impossible to detect by the victim and quite difficult even for a perceptive observer. When a TGa victim is unobserved, only the passage of time as evident by the position of the sun in the sky or time passage as recorded by a time-piece (if one is available) might provoke a TGA victim to consider that a serious time loss had occurred.
I soon became aware that much more was happening to statin users than cognitive dysfunction. Statin drugs are reductase inhibitors and what does this really mean? From the very beginning Merck proudly announced the fact that their statins worked by a mysterious process known as reductase inhibition. We physicians perhaps should have been more perceptive and might even have consulted our biochemistry books, for only a glance would have told us something very worrisome was possible but we trusted our drug companies. We were all on the same team, weren’t we? We were so pleased with this new statin, Lovastatin, with its capacity to drastically lower cholesterol that we simply forget to ask picky questions of the drug companies. After 40 years of anti-cholesterol brainwashing we all agreed that cholesterol was our enemy and none of the many drugs we had used during that time really had much effect on cholesterol. Any drug that could almost guarantee to lower this biochemical by 40-50 points in a few weeks simply had to be good. Statins were our friend, no questions asked.
It was in this climate that I wrote my second book, Statin Drugs Side Effects (ref), for our problems were far more than cognitive and all statins were contributing to our rising tide of side effects, not just Lipitor. This is when I learned what reductase inhibition really meant. The reductase step that all biochemists know as very susceptible to blockade was at the very beginning of the mevalonate pathway. Yes, this pathway to cholesterol synthesis is also shared by many extremely important biochemical substances, including Coenzyme Q10, dolichols, selenoproteins, normal phosphorylation, Rho (vital for cognition) and nuclear factor kappa B.
Trust me –these all are extraordinarily vital to human function and to block this pathway (with statins) sufficiently to reduce cholesterol synthesis must also inhibit synthesis of these other biochemicals. It is not just possible, it is virtually guaranteed. One cannot reduce cholesterol by the use of statins without simultaneously blocking these other mevalonate pathway users. This is much like the girding of a tree trunk – all the branches are inhibited, not just the cholesterol branch.
This is the cause of most of our side effects. Our neuropathies, myopathies, rhabdomyolysis, emotional and behavioral disorders and even certain neuro-degenerative conditions such as ALS are side effects based on mevalonate pathway inhibition. Even the one solid good that statins appear to do, the reduction of atherosclerosis in middle aged men, is actually a previously unsuspected side effect from the inhibition of nuclear factor-kappa B, a powerful anti-inflammatory substance felt by most biochemists to be dependent upon the mevalonate pathway for synthesis. Cholesterol lowering has nothing to do with it.
The results of our longitudinal studies had strongly suggested the presence of non-cholesterol factors from observations of a positive cardiovascular protective effect to be evident in many studies even when cholesterol failed to respond to statins and, of course, our new myocardial infarction cases consistently showed that 50% had normal to low cholesterol values. These observations have made most objective researchers (like Kilmer McCully) to seek other, non-cholesterol factors such as inflammation due to homocysteine elevation as a major cause of atherosclerosis. Transfats, oxycholesterol, cigarette smoking and hidden chronic infections are other well-known triggers to inflammation. This is further supported by the more recent demonstration of a solid relationship between CRP (C- reactive protein) elevation (measure of inflammation) and underlying cardiovascular risk.
My second book, Statin Drugs Side Effects, continues to be relevant and mevalonate blockade remains a major cause of side effects but something new has been added. Recently I began to ask the question, “Why do the neuropathies, myopathies and other neurodegenerative conditions such as ALS become permanent? If CoQ10 deficiency played such a major role in the etiology of these conditions, why is it that these conditions persisted despite vigorous attempts at restoration of CoQ10? What was causing this failure of response in so many cases? This is a fair question and a reasonable answer was long in coming but finally it came, and the answer was mitochondrial mutations.
This is when I discovered that although mevalonate inhibition of CoQ10 made have played a major role in causing the initial problem, the mitochondrial change it triggered had made the condition permanent. Now, even an over-abundance of CoQ10 could not reverse the course. This made sense to me and I soon found plenty of support from the research community.
I knew I was on the right tract with my third book, Statin Damage Crisis. This is now a crisis, for to give statins without also giving CoQ10 is to invite disaster. Other countries such as Canada had specifically warned of this and strongly advised CoQ10 supplementation from the very beginning. The United States did not. Could this be because of our powerful statin lobby? This has been the cause of our thousands of cases of permanent damage and disability from statin use.
Few of us knew of Merck’s request to the U.S. Patent Office back in 1990 (ref) to permit them the addition of CoQ10 to their new (then) statin, lovastatin, commonly known as Mevacor. If our vigilant media took special interest in this unusual request on the part of a drug company, I must have missed it. Merck lawyers cited “for the reduction of the anticipated inflammation to come” in their justification for change and when their patents were granted, promptly, shelved them and went on about its business of selling plain Mevacor, inflammation be damned! No more was ever said about CoQ10 until Julian Whittaker MD first raised the issue (ref) and I have since been his strong ally with my website papers (www.spacedoc.net).
Obviously we doctors are no longer on the same side as the drug companies. Merck is beholden to its stockholders first. The health and well being of the public is much further down on the list, barely evident at times and the other statin makers have just played follow the leader.
Then in the era 2005-2007 came news about cholesterol’s possible irrelevance. (You mean I can eat eggs and butter again?) Statins worked, we were gradually discovering, not by cholesterol reduction but by their powerful anti-inflammatory action. Atherosclerosis was basically an inflammatory process starting first in the subendothelial region of our arteries and demonstrating the four major elements of inflammation: platelet activation, monocyte adhesion, macrophage attraction and smooth muscle migration, all inhibited by statin’s novel anti-inflammatory action.. Now the proper treatment began to involve the use of anti-inflammatory agents. Study after study proved this effect of statins. Yes, aspirin has a very similar effect, justifying the use of the term, super-aspirin, in vogue for a while to describe statin action. However, the drug companies were quick to inform us that statins worked better than anything else we had for vascular inflammation and could be used successfully for almost anything having an inflammatory component such as auto-immune diseases and organ transplant rejection. But they made certain to keep the waters muddy with respect to cholesterol. After four decades of brainwashing and almost two decades of use what doctor seriously wanted to accept a new inflammatory hypothesis. How do you tell your patients you have been wrong all this time. What doctor can do this gracefully?
Our new cholesterol disease was rapidly disappearing. In its place was rising a new edifice to the role of inflammation. How best to handle this confusing fact from the viewpoint of the drug industry – pretend it isn’t happening! Keep the doctors focused on cholesterol as long we can, for billions of dollars are at stake and if we play our cards right we might slide cholesterol out and inflammation in and never miss a statin sale. As to the side effects of statins, we will pretend we do not hear them. After all we do control the communication channels.

MDA
Thanks for the references. And for the interesting discussion.
I will say that your patients are fortunate indeed to have a physician who is dedicated and invested in doing right by them. I totally understand your frustration with patients who don’t want to try a drug that may benefit them, and also with their tendency to ascribe symptoms to medication side effects before considering other causes. I might add that many of them are happy to take “natural” supplements, seemingly unaware that if those agents have any effect, they are also capable of side effects.
I also fully understand people’s reluctance, and I know that in many cases, they are dead right about side effects. IN many cases, their docs do not take the time (or have the skills) to explain why that may or may not be so, or whether in their case it is to their benefit to put up with said ill effects (which in some cases is true–chemotherapy, for example).
I’ll add this other thing to the mix, and that is about what I would call a “culture” change. We have morphed from a society that generally blindly trusted their physician’s recommendations to an information age wherein people have access to unlimited information (some of it bad) and are also more skeptical and less trusting. In some ways, we are in the worst part of that morph, because many folks are unable to correctly interpret what they read, particularly where risk statistics are involved. In essence, many now know enough to be dangerous (to themselves). It poses a challenge to healthcare professionals to say the least.

To add another fair-balance dimension to this dialogue, several studies have provided evidence that statins substantially reduce the risk of Alzheimer’s Disease, the leading cause of dementia in the elderly, afflicting an estimated 4.5 million people in the U.S.
For example, a major long-term study (J Neurol NeuroSurg Psychiatry Oct. 17, 2008) showed older men and women who took statins during the multi-year study had a 43% lower risk of Alzheimer’s Disease. No such reduction in Alzheimer’s Disease risk was found for non-statin cholesterol lowering medication.
The study was part of the Rotterdam Study, a highly respected long term prospective study of factors that determine the occurrence of common diseases of the elderly, such as heart disease and Alzheimer’s disease. Researchers followed 6,992 men and women recruited at age 55 years or older from baseline (1990-1993) until January 2005 for incident Alzheimer’s Disease. During this period, participants were screened periodically for signs of dementia and those with suspected cognitive decline were referred for exhaustive in-depth evaluation for dementia and Alzheimer’s Disease diagnosis. They were also continuously monitored for incident dementia through access to medical records databases. The researchers had complete access to the participants’ prescription medication records, including statins, thus eliminating a potential source of error compared to earlier studies that relied on self-reported drug use.
The 47% reduction in Alzheimer’s Disease (AD) risk for people taking statins was similar in size to the positive effect for statins found in some earlier large scale observational or prospective studies: 67% reduction in the risk of AD (Current Alzheimer Research 2008; 5: 416-421); 48% reduction in risk of dementia or cognitive impairment for statin users (Neurology 2008; 71; 344-350); 74% unadjusted lower risk of AD for statin users (Arch Neurol 2002; 59: 223-227); 69.6% lower prevalence of AD for statin users (Arch Neurol 2000; 57: 1439-1443); 71% lower relative risk of AD for statin users (Lancet 2000; 356:1627-1631).
Given a choice between the above-claimed 0.5% risk of transient global amnesia (which, incidentally, I have never seen despite 24 years of experience prescribing statins, to thousands of patients, mostly high risk/elderly/diabetic; and for which the incidence in non-statin patients has not yet been stated in this discussion) and the potential to reduce my risk of Alzheimer’s Disease by 47%, I will accept the purported TGA risk in a heartbeat. Again, it’s not about denying that there are risks. There are risks, with every drug. It’s about balancing benefits and risks.

Dr. Graveline, I want to take this opportunity to thank you for your post, and express my deep heartfelt appreciation for all the work you have done over the last decade or so, in increasing people’s awareness of the statin crisis.
Your books have been of just tremendous benefit to me.
Your information in the above post, about the frequency of TGA and memory problems with statins is important. Interestingly, I have a friend who is a cab driver. (they know their way around) He came off his statin because of extreme leg pain. But, I found out, that while still on the statin, he had a likely statin related memory episode. He had picked up his wife from a meeting, and within a mile from home he could not find the way home. His wife asked him where he was going. I’m not talking about a wrong turn. He literally could not find the way home! This scared them so badly that they went to the hospital. He was admitted, but 2 days of tests revealed no cause. Sounds familiar, doesn’t it? Yet the perceptions persist that “statins don’t do that.”
Thank you again, my friend.

The reference for the 400:1 statement is is Am J Cardiol 2006; 97(suppl):95C.
PEOPLE’S PHARMACY RESPONSE: THANK YOU.

Dr Graveline,
What is the annual incidence of transient global amnesia in the general population?
Also, is there a reference for “FDA now has well over 1,000 reports of TGA in their Medwatch files just for Lipitor alone”? Is that available on their website?
Thanks,
MDA, MD

SH, Interesting point on the 200 total cholesterol level, although I have not come across that specific point yet in my ongoing research on statins and cholesterol.
I have read repeatedly that cholesterol is vital to your body and brain function and that low levels are repeatedly found in studies to have higher overall mortality. Especially in the elderly does cholesterol seem to have a protective mechanism. I am currently reading a very well researched book that makes the case for low cholesterol levels due to semi-starvation in the elderly, being the main trigger for most cases of Alzeimers.
Higher total cholesterol levels above say 300, seem to not be the actual cause of problems, but the body’s attempt to cope with other underlying issues.
There is actually an international organization of cholesterol skeptics who have various ideas on health issues, but hold in common that high levels of cholesterol are not the underlying cause of heart disease. Many members have high credentials.
The human bodies functions are very complex, and people should be more open to various theories rather than accepting without question the theories of those who benefit most financially from the currently popular ideas.

I am the author of Lipitor, Thief of Memory, Statin Drugs Side Effect and Statin Damage Crisis and after 23 years of family practice, my personal experience with the statin, Lipitor, in the form of harrowing transient global amnesia following both my initial trial with this drug during my astronaut physical at NASA’s Johnson Space Center and my rechallenge at half dose the following year, eight years of research on these little publicized side effects of the statin drugs and with over 8,000 email reports of damage from statin users worldwide now in my repository, I feel well qualified to talk on this subject.
Now, eight years later, to find so many MDs completely unaware of the cognitive side effects of statins is extremely discouraging, especially since FDA now has well over 1,000 reports of TGA in their Medwatch files just for Lipitor alone, yet not one word of this truth has been passed on to the medical community. Our doctors are not to blame, they are simply not aware for neither FDA nor the drug companies have been completely honest with them. And they both knew this was coming for during the clinical evaluation phase of Lipitor, the first time it has been used on humans, some 2500 volunteers were given Lipitor with the result that during the trial year, 11 had TGA or its equivalent in serious memory disruption (not including confusion, forgetfulness or disorientation).
You check my math on this but 11 out of 2500 come close to 0.5%, which is likely why they neglected to mention this to the medical community. But this just happens to be the best evidence we have for true incidence of cognitive disturbance associated with the taking of a statin drug, any statin, for they all do it. Our 0.5% means one case for every 200 people taking the drug – right? This means 5 cases of serious cognitive impairment in every 1,000 people, or 50 for every 10,000 people, or 500 for every 100,000 people or 5,000 for every million!
With close to 30 million Lipitor users we can expect close to 150,000 TGA episodes or its equivalent in memory impairment from this one statin alone. Were we warned of this? You know the truth – not one word and what about the pilots and school bus drivers (did I mention that TGA occurs instantaneously without the slightest warning, suddenly incapacitating you)! And this does NOT include the simple confusion, disorientation and forgetfulness cases. And this FDA failure to pass on vital information to the medical community is not true only for cognition, it is true for emotional and behavioral side effects, permanent myopathy, permanent neuropathy, our hundreds of ALS-like cases of weakness, atrophy and increasing disability.
I should mention here that Ralph Edwards of WHO warned us over two years ago of excess ALS-like cases associated with statin use world-wide but our FDA failed to see it in their clinical studies. The point here is that our MDs are the last to know in our country so when someone tells me that a Chief of Endocrinology somewhere gave him a figure of 400:1 benefit to cost ratio for statin use I felt sorry for him. This 400:1 figure has warped his mind and it was nothing more than a “guesstimate” from someone who should have known but did not have the slightest basis for a estimate for he had never been told the truth.
Do you know that our figure for myopathy incidence is much closer to 20% than to 2% usually given? And did you know that of this number 68% will be permanent. Two of my astronaut friends are in this boat. And did you know that 100% of our peripheral neuropathy cases associated with statin use are permanent and resistant to all forms of traditional treatment? And do you know that now both Dr. Golomb of the NIH funded statin study and I agree that the basis of statin damage is mitochondrial mutation?
That is what make so many of our cases of muscle and nerve damage permanent. Can you think of anything more serious that a drug that affects your mitochondria? I cannot. Everything I say here is fully documented on my website at (www.spacedoc.net).
Duane Graveline MD MPH

MDA, My statement about there “being no scientific basis for the incredibly widespread use of statins” was in reference to the fact that despite the studies you site, I feel statins are being overprescribed to groups of people falling outside virtually all of the major studies. For example, as I mentioned in other comments, the studies do not support use of statins in women, and especially the elderly. There are elderly people being prescribed statins whose health goes off a cliff, and they deteriorate rapidly.
So, I say again, there is no scientific basis for such routine prescribing of statins to the elderly. It’s a crime and a shame. Statins have serious damaging effects on the entire human organism. Doctors who choose to stick their head in the sand because of pride and/or a feeling they will be losing one of their major treatment tools, and thus feel they don’t know what else to do, are doing their patients a great harm.
This notion that statins are so great that just about everybody will benefit from them is simply nonsense. It is irresponsible in the extreme, for statins to be promoted and overprescribed to the extent they are. Statins affect the body in deep and serious ways. They should be prescribed very narrowly, and only to those most likely to benefit. The so called “side effects” seen in people, are really symptoms of statin poisoning. These symptoms are like the canary in the coal mine.
When doctors like you are skeptical of patients complaints, feeling strongly they are not likely due to statins, serious and likely permanent changes to the organism will continue to progress until it is too late. It is often not a matter of just stopping the statin and everything wiii return to normal. I deal with this every day, all day. It could have been prevented with more honest statin information being more widely available. I should have been more skeptical and did my own research. But I misplaced my trust in persons like you.
Wake up Doc. You’re like some religious leader stubbornly clinging to your dogma, fighting off the heretics, mind tightly shut to the growing evidence of statin damage all around you. You try and attribute this huge wave of statin damage to ignorance and “noise”, increasing “hysteria”. The unwashed commoners spreading statin gossip among themselves, feeding the “hysteria”. You insult all those many thousands of people who will never be the same due to statin damage.
LONG LIVE “STATIN PHOBIA” !!!

Very interesting discussion continues.
I think another aspect of this is the circumstance in which statins are prescribed. Every medication has a risk vs benefit ratio. Currently, these drugs are prescribed to pretty much anyone whose total cholesterol is 201 or more.
How was that magic 200 number arrived at? I have read that it was chosen in the first place in order to be able to conveniently randomize a study population–which had nothing to do with whether a total cholesterol count at that level had any clinical significance (and not to say those researchers ever intended that). But thereafter, the number 200 just fell into being the parameter used. I could be wrong, but don’t believe there was every anything magic about the 200 number.

JM, regarding your various assertion that “there is no scientific basis for the incredibly widespread use of statins” every lipid expert in the country (referring to physician/scientific lipid researchers at academic centers) would disagree with you.
In addition to numerous studies showing reductions in cardiovascular events, there clearly is strong evidence of a survival benefit. For example, a meta-analysis by Wilt and colleagues of 17 placebo-controlled, secondary prevention (i.e. patients with prior cardiovascular events) statin trials yielded an absolute reduction of all-cause mortality of 1.8% over an average trial duration of approximately 5 years.
This is a rate of 360 per 100,000 person-years, due entirely to reduction of cardiovascular mortality. Results from the Heart Protection Study suggest that statin treatment would be effective in the vast majority of the 13 million people with known coronary artery disease (CAD) in the United States. In this group alone, widespread statin treatment could save 40,000 lives each year. The actual potential for mortality reduction is much greater taking into account high-risk primary prevention, including widespread statin treatment in patients with type 2 diabetes.
In the JUPITER randomized trial of 17,802 apparently healthy men and women healthy men and women with elevated levels of high-sensitivity C-reactive protein, Crestor significantly reduced the incidence of major cardiovascular events, despite the fact that nearly all study participants had lipid levels at baseline that were well below the threshold for treatment according to current prevention guidelines. Crestor also significantly reduced the incidence of death from any cause. (By the way, in this trial with median follow-up of subjects of 1.9 years, myopathy, did not occur more frequently with Crestor than with placebo, despite the fact that LDL cholesterol levels below 55 were achieved in half the participants receiving Crestor)
REFERENCES:
Wilt TJ, Bloomfield HE, MacDonald R, Nelson D, Rutks I, Ho M,Larsen G, McCall A, Pineros S, Sales A. Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med 2004;164:1427–1436.
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:23–33.
American Heart Association. Heart and Stroke Facts 2005 Statistical
Update. [American Heart Association Web site.] Available at: http://
heart.org/presenter.jhtml?identifier3000090. Accessed August 29,
2005.
Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis [review]. BMJ 2003;326:1423.
Ridker PM, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM. 2008:359:2195-2207

Joe, in the JUPITER trial (published in NEJM 2008), in which 17,802 men and women were randomized to Crestor vs. placebo, myopathy did not occur more frequently with Crestor than with placebo. Specifically, a total of 19 myopathic events were reported: 10 in subjects receiving rosuvastatin and 9 in subject receiving placebo (p=0.82). The median follow-up of subjects was 1.9 years, and no increased myopathy was detected in an analysis of participants who continued to receive Crestor for 4 or more years.
According to your claim of a 10-15% incidence of myopathy symptoms, of the 8901 patients randomized in that study to Crestor, one would expect 890 (10%) or 1335 (15%) patients to have reported myopathy symptoms. Yet there were only 9 (nine). Why is that???
Ridker PM, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM. 2008:359:2195-2207

JM, regarding your assertion that “there is no scientific basis for the incredibly widespread use of statins” every lipid expert in the country (referring to physician/scientific researchers at academic centers) would disagree with you. In addition to numerous studies showing reductions in cardiovascular events, there clearly is survival benefit.
For example, a meta-analysis by Wilt and colleagues of 17 placebo-controlled, secondary prevention (i.e. patients with prior cardiovascular events) statin trials yielded an absolute reduction of all-cause mortality of 1.8% over an average trial duration of approximately 5 years. This is a rate of 360 per 100,000 person-years, due entirely to reduction of cardiovascular mortality.
Results from the Heart Protection Study suggest that statin treatment would be effective in the vast majority of the 13 million people with known coronary artery disease (CAD) in the United States. In this group alone, widespread statin treatment could save 40,000 lives each year. The actual potential for mortality reduction is much greater taking into account high-risk primary prevention, including widespread statin treatment in patients with type 2 diabetes.
In the JUPITER randomized trial of 17,802 apparently healthy men and women with elevated levels of high-sensitivity C-reactive protein, Crestor significantly reduced the incidence of major cardiovascular events, despite the fact that nearly all study participants had lipid levels at baseline that were well below the threshold for treatment according to current prevention guidelines.
Crestor also significantly reduced the incidence of death from any cause. (By the way, in this trial with median follow-up of subjects of 1.9 years, myopathy, did not occur more frequently with Crestor than with placebo, despite the fact that LDL cholesterol levels below 55 were achieved in half the participants receiving Crestor)
REFERENCES:
Wilt TJ, Bloomfield HE, MacDonald R, Nelson D, Rutks I, Ho M,
Larsen G, McCall A, Pineros S, Sales A. Effectiveness of statin
therapy in adults with coronary heart disease. Arch Intern Med 2004;
164:1427–1436.
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection
Study of antioxidant vitamin supplementation in 20,536 high-risk
individuals: a randomised placebo-controlled trial. Lancet 2002;360:
23–33.
American Heart Association. Heart and Stroke Facts 2005 Statistical
Update. [American Heart Association Web site.] Available at: http://
heart.org/presenter.jhtml?identifier3000090. Accessed August 29,
2005.
Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low
density lipoprotein cholesterol, ischaemic heart disease, and stroke:
systematic review and meta-analysis [review]. BMJ 2003;326:1423.
Ridker PM, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM. 2008:359:2195-2207

MDA, Thank you for your reply/comments on determining when to stop statins, and the possible dangers of stopping suddenly. This is well taken. I am a 50 year old heart patient for the last 2 1/2 years. When I stopped my statin I first reduced the dosage for a little while. Your point on the rapid on/off anti-inflammatory effects is an important one. (In fact I believe that the anti-inflammatory effects of statins are what account for most of any statistical evidenced heart help of statins. I don’t believe the trials/studies show correlation between cholesterol and heart disease. But that’s another controversial subject.)
I believe stress is an important factor in heart disease. Interestingly, as my statin damage progressed, I became very passive and calm. I simply had no vigor or energy to be anxious or stressed. All my strength was needed just to get through each day. I didn’t even get nervous before public speaking. The strength just wasn’t there. Immediately upon stopping the statin I felt vigor and energy returning. Along with it I felt a return of enough energy to again become stressed or anxious about things again! It made me laugh on reflection. Imagine, anecdotal, but a possible stress reducing effect from statins that could take stress off the heart? Who knows.
But Doctor MDA, my original objection to the tone of your posts remains. I feel you underestimate the effects of statins and are unduly dismissive of patient concerns. For example “knee pain” was one of the first symptoms I had noticed from statins. I had some knee strain that simply would not heal, so I could no longer ride my bike the 1 mile to work. I had tennis elbow that simply would not heal. I had to discontinue my kettle bell routine. Heart patients need some activity! You dismiss these “minor” symptoms in your patients, yet when I stopped my statin, immediately I felt the healing process begin in my knees and elbows! I believe that one of the effects of statins is the aggravation of minor injuries, also making you more open to injury, and slowing or stopping the healing process of joints, ligaments and muscles. Your patients may be sensing the connection to statins, even after 10 years of relatively symptom free treatment.
Listen to them, they feel their body every day, you don’t. Just because some may exaggerate, most don’t. In fact, many like myself hesitate to bring up with their doctors what may appear to be minor aches and pains.
Statins are a serious drug. Statins act early in the acetyl and mevalonate pathway affecting CoQ10 and dolichols as well as other vital things. If you liken cholesterol to a single branch in a tree that you want to trim and make smaller, statins would be acting at the BASE of the tree trunk, restricting vital biological activity of the whole tree! Over time the WHOLE TREE DETERIORATES in the attempt to reduce the one branch! Often when statins are stopped there is immediate improvement in muscle related problems, but for some, the deterioration resumes and is permanent. Muscle and nerve damage can be permanent and even progressive. There is evidence that the effect of statins on CoQ10 and dolichols leads to damage to the DNA of the mitochondrial life-force within the cells. This can be seen as premature old age. This can also be an ALS like deterioration. It is dangerous to be dismissive of patient complaints and concerns. You treat the whole person, not just heart concerns. “Do no harm.”

Joe, I agree. Our difference lies in the frequency, the “noise vs. signal” of the issue. The likely reason is that the people you hear from are disproportionately those who have had true myopathy, while those of us on the front lines see many, many people with clearly unrelated musculoskeletal symptoms for every one with statin-induced myopathy. That is true even if one takes the broadest possible approach to erring on the side of diagnosing improbable presentations as probable statin myopathy.
By the way, do you remember people complaining of statin side effects during the first decade they were on the market?
Dr. A.
People did not complain about heart attacks and strokes caused by Vioxx until headlines brought this to public awareness. Even the FDA’s MedWatch system did not discover this problem because heart attacks (like muscle pain) are common.
Most physicians did not realize that sexual side effects (impotence, reduced libido and delayed orgasm) could be caused by SSRI-type antidepressants in the first decade of use. That is because the clinical trials did not report problems in more than about 5 percent of patients. We now know the true incidence of sexual dysfunction brought on by SSRIs is closer to 60 percent. By the way Dr. A., we received reports of sexual side effects from readers way before the research demonstrated this was a common complaint.
How long did it take for the FDA to issue a black box warning about tendonitis and tendon rupture linked to quinolone antibiotics? How long did it take the FDA to issue a black box warning about tardive dyskinesia linked to Reglan (metoclopramide)? If you check, you will see that Reglan was approved in 1980. It was taken by countless numbers of patients for heartburn and most physicians thought of Reglan as a benign medication. It was only this year that the black box warning about tardive dyskinesia was issued by the FDA (that’s 29 years!).
Bottom line, it can take a very long time to recognize the severity (or the commonality) of a drug-induced side effect. How many people experienced a heart attack because of a COX-2 inhibitor like Vioxx? We’ll probably never know.
How many people are experiencing muscle or joint pain because of a statin? Even if it is “only” 5 percent (as you suggested) instead of 10 or 15 percent, that would still represent a huge number of people. If there are 15 million Americans taking statins, that would suggest that 750,000 are experiencing muscle problems (at the low end) and as many as 2.25 million at the high end. We would not consider that “noise.”
Joe

Joe, regarding “your assertion the most of the muscle aches and pains and weakness that people are complaining about are figments of their imagination” I never said that! What I have said repeatedly in this discussion is that most (90 plus percent) of the musculoskeletal symptoms that people on statins present to their physicians about (and stop statins because of) are due to musculoskeletal maladies clearly unrelated to their statins. Examples: localized overuse muscle strains, tendonitis, plantar fasciitis, repetitive motion injuries, etc. The types of common maladies that caused human beings to have aches and pains for thousands of years before statins were developed. I’ve had patients take a statin for 10-15 years with absolutely no difficulty, strain their back, stop their statin, heal their back over 2-3 weeks, conclude that since the back pain got better off the statin it must have been due to the statin, and refuse to ever take a statin again. That’s what I’m talking about here.
PEOPLE’S PHARMACY RESPONSE:
Dear Dr. A.
No doubt some patients do attribute their aches and pains to statins when they may well be “normal aging” or a response to straining or some other physical activity. But we have received thousands of reports of severe myopathy associated with statin use that have sometimes led to restriction of physical activity. When the drug is discontinued, many patients recover, though for some it takes months or longer to overcome the disability.
We trust that you would agree that physical activity is one of the most important things people can do for their general health as well as for heart health. When a statin limits a person’s ability to exercise, it is time to reevaluate the drug regimen.
Now that we know there is actual structural damage to muscle that can be seen on biopsy without any abnormal blood tests (CK elevation), physicians must take muscle pain into consideration when patients complain of symptoms while taking drugs like Crestor, Lipitor or Zocor. There is no simple way (short of sophisticated biopsy analysis) to tell whether someone’s muscle pain is “normal aging” or induced by statins.
Joe

JM, regarding your suggestion “Perhaps some of the patients you have who have reported possible statin effects should try lower dosage or temporary stoppage to check correlation” please be assured that I routinely do exactly that. When I stop the statin it is usually for 6-12 weeks. That’s how I can say that over 90% of the musculoskeletal complaints that patients attribute to their statin are not as best we can tell correlated to the statin. That is the point I have been trying to make. Not that there is no such thing as statin myopathy. We all know there is. The conundrum is what to do about the other 90 plus percent – those who decline the opportunity to resume the medication in spite of a lack of correlation with their own symptoms, plus the occasional patient who declines the opportunity to even start statin treatment because of what they have read or heard.
Regarding “they won’t keel over and die if you try this method of verifying their complaints” that is, fortunately, almost always true. On the other hand, statins have anti-inflammatory effects that are rapid on/rapid off with starting/stopping therapy. It is theoretically possible that withdrawal of a statin could lead within a matter of days to weeks to an abrupt rise in inflammation in the lining of arteries, leading in turn to rupture of a vulnerable arterial plaque and sudden death. So yes, one must always weigh the risks.
The easiest thing for me to do as a physician when a patient expresses reluctance to take a statin is to say “that’s fine.” It’s much more labor-intensive to have a meaningful evidence-based discussion of the issues. In doing so, I have nothing to gain except knowing I have done the right thing.

MDA, The long term compliance with statins has always been poor. This is definitely not a recent development due to the “hysteria” you talk about. Even in the early studies done by the statin sellers there was a high drop out rate due to statin induced symptoms. This, in fact, hid some of the frequency of side effects, because those who drop out of the study by discontinuing the statin, are not counted in the study results.
You have the whole thing dramatically backwards. People have NEVER complied well with long term statin use, because it is much more often the case that the gradual onset of symptoms only becomes obvious over time. Then they stop, often after the severity of their statin-induced symptoms has been downplayed or ignored by their doctors. Statins cause a wide range of symptoms as the body deteriorates with statin use. In fact, the term side effects is a poor one for statin problems, because really these “side effects” are in reality the symptoms of much more serious damage progressing in the body.
Statins interfere with cholesterol production very early in the biological process, dramatically affecting very important processes vital to cell function, throughout the body, including the brain. Statins eventually manifested their effects throughout my body. I’m 50 years old, and felt like I aged to the point I felt I was almost done with life. In fact the younger and more active a person is, the earlier it may become clear statins are affecting you.
Athletes notice quickly because they are in tune with their bodies performance. In sedentary and older people, it can be more easily missed. Especially since many symptoms of statin damage are common to aging, but the aging just happens very suddenly where it doesn’t make sense. Many elderly patients, when put on statins (no studies support prescribing statins for the elderly) go from being very active, into RAPID DETERIORATION!
Of course the doctors would never suspect the statin. The destruction unknowingly being foisted upon the organism of older people is especially tragic. THE FREQUENT PRESCRIBING OF STATINS TO ELDERLY PATIENTS FINDS ABSOLUTELY NO BASIS IN THE STUDIES. Also, the lower the cholesterol levels in elderly people, the higher the mortality! The persons who should be prescribed statins are in reality a much smaller group.
There is no scientific basis for the incredibly widespread use of statins. Your fears that people are being unduly influenced against statins is laughable. More people than ever are being put on statins every day. You must have an unusually informed group of patients, for you to be running into all this anti-statin “hysteria”. Perhaps you are one of those doctors who resents any perceived threat to your unquestioned position? Patients are perhaps in your view, the ignorant, easily manipulated masses. Of course, some are, as they give in to the commercial’s encouragement to “ask your doctor about”…any number of overprescribed drugs
It works both ways. Open your eyes.

MDA
I do fully appreciate your (well articulated) position. I do concede to you that many people attribute all their symptoms to their medication when that may or may not be the cause. And your observation about the baby and the bathwater is apt in many cases.
I am dealing right now with an elderly parent who is convinced that all his problems are due to medication side effects (and not to the conditions he has, which are all chronic and one is quite serious, requiring serious medication).
It is a huge challenge for physicians. There is also the phenomenon of people abruptly discontinuing their medications (sometimes bringing on rebound effects or other problems), doubling up on them, taking their own remedies that interact with prescribed meds, or otherwise not using as directed. That’s part of “the wild”, to be sure.
Then as the Graedon’s reply to you points out, there is the issue of numerical illiteracy when it comes to statistics. People do not fully appreciate risks, and the media publications of studies do nothing to help people interpret results, in fact often make it worse.
As for statins, one needn’t have full blown rhabdo to feel debilitated by significant muscle weakness, particularly in someone strong and healthy. In my own case, that’s the situation. Fortunately for me, my cholesterol is not very high. I have a friend on Crestor who has no such side effects, and her cholesterol is in the 400’s, so I would say that in her case, she would derive benefit from the stain even if she did have side effx.

Joe,
I have reviewed the articles. The issue is not whether some patients have statin-induced myopathy. Clearly they do. They issue I’m raising is that – in my clinical judgment dealing with this every day – for every patient who has true or likely statin-induced myopathy (probably in the range of 2-5%) there are many other patients who attribute a wide range of musculoskeletal and other nonspecific symptoms (many of which are very clearly not statin-induced myopathy) to their statins. There are also some patients who refuse to even start statins because of “all the horror stories” they have heard.
I believe that there is a mass public hysteria, largely fed by word of mouth and fueled by the media, regarding the magnitude (frequency) of statin side effects. There is an overwhelming background of exaggerated preconceived perceptions about the side effects of statins that is interfering with cardiovascular disease prevention to a much greater degree than is warranted by the actual magnitude of risk. When one looks at long-term compliance with prescribed statins it is clear that the baby has, to a significant degree, been thrown out with the bathwater.
It is John Guyton, MD in the endocrinology department at Duke who quotes (confirmed by him today via email) that the statin class has an approximate 400 to 1 benefit to risk ratio. The reference is Am J Cardiol 2006; 97(suppl):95C.
By the way, do you remember people complaining of statin side effects during the first decade they were on the market?
Thanks for continuing this dialogue, which incidentally just to clarify for your readers is now rather off of the original blog topic of “What Is the Link between Statins and ALS?”
MDA

This is in further reply to MDA. I’m sorry, but this really gets me going. As a sufferer EVERY DAY due to entirely preventable statin damage, likely permanent, I am angered. When the drug industry, and sometimes the medical community hides, ignores, or ridicules reported statin damage, it keeps people like me who TRUSTED doctors and reported drug company research, in the dark as symptoms advance to permanent damage.
I just did not know what was happening to me; because the statin would be the last thing I suspected, due to the “statins are safe” publicity. Only the mention of the “rare” side effects mentioned in the commercials for statins lead me to even bring up that possibility with my doctor. Meanwhile, every night I faithfully took my 80mg and continued the assault on my body until perhaps too late to avoid permanent damage.
Rosuvastatin (Crestor) was launched, in it’s first year, with $1 BILLIOIN spent on sales and advertising! This is only the amount spent on one of about six widely promoted statins. That buys a lot of publicity. Yet you attack the relatively unknown and helpful to patient information posted on The Peoples Pharmacy!
Here are three facts from the major statin studies. 1) Statins do not reduce overall mortality in women. 2) Statins do not reduce overall mortality in men without heart disease. 3) Therefore statins do not reduce overall mortality in >95% of the adult population. If statins reduce death from cardiovascular diseases, yet there is no impact on overall mortality, people taking statins must die at a higher rate from other causes.
Dr. Graham Jackson, in the UK, looked at all of the statin studies up to the year 2000. His conclusion, published in the British Journal of Clinical Pharmacology said: “Long term use of statins for primary prevention of heart disease produced 1% greater risk of death over ten years vs. placebo when the result of all the big controlled trials reported before 2000 were combined.”
So while there is some evidence of secondary prevention of heart disease in men, statins are promoted aggressively as a universal cure and prevention of heart disease. This is simply not proven by the trials. Ever lower levels of cholesterol are being pushed in doctors guidelines. The perception being promoted is that statins have no real side effects worth mentioning. To me this is criminal. We are witnessing just the tip of the iceberg when it comes to statin damage.
PEOPLE’S PHARMACY RESPONSE: WE WERE UNABLE TO FIND THE QUOTE FROM GRAHAM JACKSON. THE EPIDEMIOLOGICAL FACTS IN JM’S PREVIOUS PARAGRAPH CAN BE FOUND IN NUMEROUS SOURCES.

This is in further reply to MDA’s original strong objection to the People’s Pharmacy posting the information on the new statin/ALS study.
The FDA study of over 40 previous studies you mentioned is really not as strong as you imply. It is a “data mining” study of studies that had a different purpose than that of looking for a potential ALS like link. The studies were also relatively short term. What is needed is deeper more specific long term research. Even the FDA acknowledged that in the light of the seriousness of ALS and the widespread use of statins, further research is warranted.
The study mentioned by the Graedon’s had subjects who improved with statin withdrawal, and deteriorated when the statin was restarted. This is strong correlation and needs to be investigated further. I personally, and many other statin sufferers report dramatic non placebo like improvement in symptoms when the statin is stopped, and renewal of deterioration upon restarting.
Perhaps some of the patients you have who have reported possible statin effects should try lower dosage or temporary stoppage to check correlation. They won’t keel over and die if you try this method of verifying their complaints. It has been wisely said: “LISTEN to the patient, he’s telling you the diagnosis.”

sh, your point about patients being carefully selected for clinical trials may well have some validity. I have practiced clinical endocrinology since the early 1980’s, which is when statins first came on the market (“into the wild” as you aptly put it). But it was a good 10 years later before statin users started complaining about statins causing aches and pains and weakness. Did people have those side effects during that decade and just not connect it with their statin use? Perhaps.
By the mid 1990’s muscle complaints went from rare to common very soon after the statin companies started direct to consumer advertising, which included FDA-mandated warnings about muscle symptoms (warnings which were due to the very rare cases of rhabdomyolysis). Now I deal every day with patients blaming every ache and pain (left knee pain, right shoulder pain, left thumb pain, woke up this morning with neck pain, you name it) on their statins, often with no logical temporal connection.
And they are telling all their family, friends and neighbors about it. I believe that some people do have muscle symptoms from statins. I also believe that the vast majority of aches and pains that are blamed on statins are not due to statins, but rather to this mass public hysteria, fed by word of mouth and fueled by the media.
Those of us trying to do the best we can for our patients are overwhelmed by the background noise of a multitude of complaints making it very hard to find the occasional (rare) patient with actual muscle side effects. The baby (a class of drugs with a 400 to 1 benefit to risk ratio) has largely been thrown out with the bathwater.
PEOPLE’S PHARMACY RESPONSE:
Dear Dr. MDA,
We know that you believe the ratio is 400 to 1 in favor of statins, but we would love to see evidence behind this assertion. It is important to distinguish between relative risk and absolute risk reduction:
For example, in the Lipitor ads you will see the following:
“In patients with multiple risk factors for heart disease, LIPITOR REDUCES RISK OF HEART ATTACK BY 36%*…”
On the surface, this seemed fabulous. Reducing the risk of a heart attack by a third is something a lot of people would like to do. They might interpret this to mean that out of 100 people, Lipitor would protect 36 from having a heart attack. Those would indeed be impressive odds.
But the asterisk tells a different story. In fine print the ad explains: “That means in a large clinical study, 3 percent of patients taking a sugar pill or placebo had a heart attack compared to 2 percent of patients taking Lipitor.”
What this means is that if 100 people took the drug and 100 people took the placebo, there would be 2 heart attacks among Lipitor users and 3 among placebo takers—1 fewer heart attack over the course of the study (which actually had many more people and ran longer than a single year). In other words, 99 people out of 100 who took the drug did not get any obvious heart attack protection. All of a sudden the odds don’t seem as appealing as a 36 percent relative reduction in risk.
Finally, regarding your assertion the most of the muscle aches and pains and weakness that people are complaining about are figments of their imagination, driven by the media. we would ask you to read two recent articles. Both point out that observational studies report an incidence of myopathy (muscle pain) that is 10 to 15 percent. These articles present a very different perspective and possible mechanisms for the myopathy. As a physician, we would hope you would take time to review these articles carefully:
Mohaupt, M.G., et al. “Association Between Statin-Associated Myopathy and Skeletal Muscle Damage.” Canadian Medical Association Journal, July 7, 2009.
and
Joy, T.R. and Hegele, R.A. “Narrative Review: Statin-Related Myopathy.” Annals of Internal Medicine 2009;150:858-868. [This is the June 16th issue]
You may also find the book by Nortin Hadler, MD “Worried Sick” of some interest in this discussion.
Once you have reviewed these articles, we would be delighted to continue the discussion.

To attack the Graedon’s for reporting on this new study seems unbalanced to me. Coming from the other room I just heard another Lipitor commercial on the radio. To imply that the valuable reporting on potential drug side effects done by the Graedon’s is somehow causing your heart patients to avoid ever starting on a statin against your recommendations, strikes me as absurd. The overwhelming BILLIONS of dollars spent on promoting statin drugs is going to be swamped by this information? Come on!
Also, you seem to give patients little credit for making an informed decision. The ignorant masses are being swayed by anti-statin propaganda? This is ridiculous in the extreme. I believe when drug companies and doctors make big money on a particular treatment, it can sway their judgment. An MD after a person’s name doesn’t mean they can’t be biased.

One of the problems with studies is that in clinical trials the populations are carefully chosen. Once the trials are over and drugs are released into the wild, so to speak, things show up that didn’t appear in the trials.
It is therefore somewhat ostrich-like to simply cite clinical trials and deny what happens in the real world.

You’re missing my point. Patients who have had side effects from statins are not statin-phobic. Patients who have refused to even try a statin, because of what they have read or heard in the media, are statin-phobic. When the benefit to risk ratio for a class of drugs is 400 to 1, and those (such as the Graedons), who are in a position to determine which articles the public hears about, choose to publicize the one negative study that contradicts the 40 other positive studies (see FDA link above), something is wrong, and people suffer needless cardiovascular morbidity and mortality.
Your newspaper columns repeatedly emphasize the negative perceptions of statins, rather than putting the known risks in proper balance with the benefits. Those of us why try to do the best we can for our patients are thwarted, every day, by that imbalanced reporting.
PEOPLE’S PHARMACY RESPONSE: DEAR DR. A,
WE THINK AND HAVE SAID THAT STATINS ARE A USEFUL THERAPEUTIC TOOL WHEN USED APPROPRIATELY, BUT WE OFTEN SEE THEM BEING PRESCRIBED INDISCRIMINATELY.
WE ARE VERY INTERESTED IN THE SOURCE OF YOUR 400:1 BENEFIT:RISK RATIO.

People’s Pharmacy: I appreciate your articles.
Skepticism about statins is warranted. Some people apparently can take them without side effx, and that’s great. For those who do experience side effects, I hardly think it’s useful for physicians to label them derogatorily. Lipitor gave me side effects I am not willing to live with. Call me “statin phobic”.
No matter who you are, or what the drug, it’s a matter of weighing the potential benefits against the risks and the side effects.

Messengers in your position have certain responsibilities. I am not suggesting that “research be ignored or squelched.” I also don’t want my patients stopping their statins because of the scare tactics in your column. I am asking that individual studies be put in their proper context. When one study is inconsistent with the other 40 clinical trials, it is irresponsible to present only the one study without mentioning the broader context of studies reaching the opposite conclusion.

There are “far more ‘statin-phobic’ patients suffering and dying needlessly from preventable cardiovascular disease than are harmed by statins” ?! Are you kidding me?!!! In my opinion statins are the most over prescribed drug in human history. (and the most profitable in history) If statins are so effective in “preventing” heart disease, where is the drop in overall mortality in the statin studies? Where is the drop in heart disease in the general population that should be the result of all these statins being prescribed?
Statins have been so effectively promoted by the big drug companies as being a ‘safe, low side effect’ drug, that the reality is that even when people are experiencing serious and long term damage due to statins, both the patient and the doctor very frequently don’t suspect the statin as the cause.
People who dropped out of statin studies due to side effects aren’t included in the drug companies studies. The serious side effects of statins are under reported by doctors. When my doctor stopped my statin due to the damage it was causing my body, I doubt he reported this. But he did acknowledge that “maybe this drug is not as great as we hoped it would be.” (That is, the medical community.)
The so called “statin bashing” is the result of real people suffering real and serious permanent damage to their bodies, and sometimes even death from kidney failure due to the muscle damage. People like myself are upset because we never suspected the things happening to our bodies were due to the statins. WE WERE NOT ALERT TO THE SIDE EFFECTS, AS A DIRECT RESULT OF DRUG COMPANIES OVERPLAYING THE STATINS ARE SAFE PROPAGANDA; FOR PROFITS AT THE EXPENSE OF PEOPLES LIVES.
Yes I am bitter, because if the drug companies were more honest in presenting the true side effects to the patients and doctors, the drug could be stopped perhaps before permanent damage was done. When early on I experienced joint and ligament pain and muscle weakness and fatigue, this was discounted, and my dosage was even increased to 80mg.
If I had known then what I know now, I could have stopped the drug perhaps before permanent damage. I personally know many people who had to stop their statin due to side effects. I doubt any of these reached the FDA or anywhere else.
“Statin-phobic” patients dying all over the place from heart disease is quite a stretch!

“A new analysis by the US Food and Drug Administration (FDA) of data from over 40 clinical trials did not show a link between statins, drugs used to lower cholesterol, and higher risk of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease often referred to as “Lou Gehrig’s Disease”. The FDA said there is no need to change prescribing practice.”
Reference: http://www.medicalnewstoday.com/articles/123519.php
Article Date: 30 Sep 2008
Is there some reason to believe that the one study from the University of California at San Diego referenced by the Graedons trumps the analysis of over 40 other clinical trials?
The benefit to risk ratio of statins has been estimated at 400:1. As an endocrinologist with a focus on preventive cardiology I can assure your readers that far more “statin-phobic” patients are suffering and dying needlessly from preventable cardiovascular disease than are harmed by statins. Yet, the wildly-exaggerated and irresponsible statin-bashing continues.
PEOPLE’S PHARMACY RESPONSE:
Please do not shoot the messenger. We are merely summarizing the results of a new study in the journal Drug Safety. This article was published in our health news section. As a physician, you surely do not wish for research to be ignored or squelched.

I am 50, and I too had the same symptoms and more from statins. My doctor blood tested for CK as an indicator of muscle damage, which I did have. I came off the statin a month ago and am feeling MUCH better! My research of the past month revealed to me how statins work and how serious and PERMANENT the damage can be. I also came across many books that do a good job calling into question the whole cholesterol/heart disease hypothesis. I have become a bit of a cholesterol skeptic. I am looking into alternatives to fight my heart issues. There is a lot of good information out there.

I have been on Lipitor for several years now. I’m 60 years old and at times feel 80 when I first stand up or get out of bed. Every major joint aches and needs to be loosened up before I can function.
If the Lipitor, which by the way has done it’s job with my cholestoral, is the blame for these aches and joint movement pain, what is the alternative?
Obviously diet and exercise did not work prior to taking this drug, so the alternative treatment has to be other than that. My Doctor, when told of these aches, chalked them off to old age or possibly arthritis, but has not tested for such. He assumes because I have arthritis in my fingers (only) that it has spread to other parts of my body.

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