By Duane Graveline MD, MPH
Statins and Mitochondrial Damage Part 2 of 11
My first book, LipitorTM, Thief of Memory (1), was written after my two bouts of transient global amnesia associated with the use of LipitorTM in the years 1999 - 2000. Predictably at that time, I was focused on cognitive dysfunction and LipitorTM.
The work of Frank Pfrieger (2) 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 to my amnesia episodes. Until that time no one in the 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. 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 the blood must be carried about attached to lipoprotein. The resulting molecule is much too large to pass the so-called blood-brain barrier, and is therefore unavailable to the brain.
Brain cholesterol comes from specialized housekeeper cells in the brain known as glial 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. Humans have evolved with this mechanism of brain function, and cholesterol is 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 me from those now aware that statin drugs had the ability to seriously impair cognitive function. In just a few months I had 30 cases of transient global amnesias reported to me.
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?
They give no warning. In my first episode of TGA I retrograded 10 years. In my second TGA, I lost 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. The 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 the 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 egg was tarnish.
Finally, in August of 2003 a team of researchers lead by Wagstaff at Duke University managed to publish their paper titled, "Sixty cases of transient global amnesia reported to FDA's Medwatch." (3) Medwatch is the formal electronic reporting system for post-marketing surveillance of new drugs in the U.S. Wagstaff and his team gained entry to 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. The readership of this journal, however, is such that there was not the slightest impact on the MD prescribing habits, or evidence of MD awareness of cognitive side effects. There was simply no discernible reaction from the community of clinicians who write the prescriptions for statins.
1. Graveline D. Lipitor, Thief of Memory. 2002
2. Pfrieger F. Science. 9 November 2001
3. Wagstaff L and others. Pharmacotherapy 23(7):871-880, 2003
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor