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August 2009 ALS AND STATINS: EPIDEMIC? I think I should apologize in advance for posting something like this, “unscrubbed” as such, but felt it worthy of posting. Very interesting read! Another case just reported to me of amyotrophic lateral sclerosis (ALS) associated with the use of statin drugs. Only a year ago the numbers of case reports of amyotrophic lateral sclerosis reported to my repository was a trickle – now it is a relative flood. There is not the slightest doubt in my mind that the numbers of reports I am seeing now are far more than usually expected in a group the size of my reporting population. One naturally wonders about this curious relationship with statin drugs and what the possible mechanism of action might be. Recently a neuroscientist, V. Meske, reported in the European Journal of Neuroscience a very relevant study about the ability of statin drugs to cause neuronal degeneration. To refresh your memory statin drugs are designed to inhibit cholesterol synthesis [in the liver] by their effect on the mevalonate pathway. It seems that a consequence of the inhibitory effect of statin drugs on the mevalonate pathway is the induction of abnormal tau protein phosphorylation. Tau protein phosphorylation goes on to form neurofibrillatory tangles, long known to be the prime suspect in causing the slowly progressive neuronal degeneration of Alzheimer’s disease. Sometimes this process is accompanied by Beta amyloid deposition but more commonly not. Research scientists are now finding that this mechanism appears to be true for ALS and many other forms of neurodegenerative diseases as well. They have even coined a new word for this, the taupathies. Statin associated taupathies or tauopathies may well be additional gross evidence of collateral damage to existing cellular chemistry that our researchers were unable to predict when they originally created the statins. All this from a class of drugs originally designed simply to inhibit the biosynthesis of cholesterol, which is a vital substance now proven to be irrelevant to the atherosclerotic process. Very few primary care physicians are familiar with the association of statin drug use with ALS and most are disinclined to use warnings from websites such as mine about statin drug side effects, saying they are anecdotal. These “anecdotes” are the patient’s histories! Doctor Ellsworth Amidon, my Vermont College of Medicine professor of medicine, used to say, “Heed well the words of your patients, my young doctors, they are telling you the diagnosis.” Most physicians feel that the pharmaceutical industry is on guard for side effects such as this and if no black box warning is out, the drug is safe. This is terribly naïve. Nor is FDA’s Medwatch an effective monitor of drug safety. My personal experience with Medwatch is that it is an adequate repository only. As an example, primary care physicians were denied the existence of statin associated amnesias until Wagstaff et al reported in Pharmacotherapy their 60 cases gleaned from a Medwatch review in 2003. I can only hope that readers of this paper, especially those having relevant symptoms, will bring this subject to the attention of their doctors. Print out this paper for them and urge them to check their own literature. My first case report will demonstrate how carefully guarded the drug industry is about this relationship. “Hundreds of folders” might be an exaggeration but, as a specialist in both family practice and preventive medicine, even [the existence of] ten folders frightens me. Duane Graveline MD MPH Author, Statin Drugs Side Effects: the misguided war on cholesterol www.spacedoc.net [log in to unmask] ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn