We all recall the priority for cholesterol reduction when statins first were developed. For forty years the medical community had been brainwashed with cholesterol causation of cardiovascular disease and proudly rode the anti-cholesterol bandwagon. Fresh out of internship, I lectured at service clubs, erroneously counseled thousands of patients as to the merits of the low fat / low cholesterol diet and wrote thousands of prescriptions for whatever cholesterol buster was in vogue at the time. I even raised my family on no eggs, margarine and skim milk.
For two decades medical researchers have pondered the many effects of statins drugs having no bearing on cholesterol reduction. Gradually the imprint of statin drugs on these unsuspected pathways have been elucidated and called the pleiotropic effects of statins. In my judgment no better evidence exists for my claim that statins were marketed with FDA approval long before sufficient background research had been done.
Ancel Keys was wrong in his fundamental concept and of course he was wrong to shelve 14 of his studies that failed to conform with his preconceived ideas. The point I am making here is that until the year 2000 I was just like all my peers with respect to cholesterol causation, conformity to national medical treatment guidelines and statin usage. With the exception of Uffe Ravnskov (The Cholesterol Myths) and Kilmer McCully (The Homocysteine Revolution), I was the first doctor to fall into this trap of statin pleiotropism.
My case had to do with the failure of the drug companies to anticipate glial cell inhibition of cholesterol synthesis. This is not some genetically preordained tendency on my part. This is basic neurophysiology. For a detailed presentation of my personal cognitive reaction to Lipitor please read my book, Lipitor, Thief of Memory.
Glial cell cholesterol synthesis is fundamental to the formation and function of memory synapses. We all depend upon our glial cells for this and drug company scientists had missed it. We now have 662 Medwatch reports of Lipitor associated transient global amnesia stored in FDA archives so logically might expect 2,000 total statin reports yet not one word of this has been passed on to the medical community. To me this points to a role even at the FDA level to limit medical awareness of this particular pleiotropic effect of statins.
The next event in this search for pleiotropic effects of statins has to do with reductase inhibition. The drug companies told us from the very beginning that statins were reductase inhibitors and we were happy for finally we had a cholesterol club. What they did not tell us was that to be a reductase inhibitor it is also a mevalonate blocker for the reductase step is right at the beginning of the mevalonate pathway. Had we but read our biochemistry books for a few minutes we would have known but we didn't. Actually it was Merck that first announced this.... sort of:
In 1990 Merck asked for and was granted two patents for the incorporation of CoQ10 with their lovastatin because of (their words) "inflammation to come" that they wished to avoid. Having been granted these two patents documenting the importance of supplemental CoQ10 (because of mevalonate blockade), Merck promptly shelved it without another word nor did they even caution doctors as to why they were concerned. Subsequently we have learned that this oversight of Merck's is responsible for some 60% of statin drug side effects because of CoQ10's critical role in cell wall integrity, anti-oxidation, and ATP energy production. CoQ10 levels plummet when a statin is started. Why were we not told?
The next piece of the pleiotropic puzzle was associated with the emotional and behavioral disorders of aggression, hostility, suicide, homicide ideation, depression and road rage type behavior associated with statin use. This we found was due to the inhibitory effects of all statins on dolichols and the process of neuropeptide formation. Every thought, sensation and emotion we have ever experienced is dependant upon the formation of these neuropeptides, which themselves are dependant upon dolichols. Doctors have read for a decade that dolichols are inhibited by statins as part of the mevalonate blockade but none of us really knew what dolichols did in the body. Most still do not know. Trust me, the role of dolichols is immense.
Then it was realized that the mevalonate blockade extended to selenoproteins and normal phosphorylation and Rho and thought we had covered all the pleiotropic pathways until we encountered mitochondrial mutations. Now we find these to be the truly dark side of statins. This insidious erosion of our faculties under the guise of "getting older" when what is taking place is statin associated premature aging due to a combination of CoQ10 and dolichol depletion. The CoQ10 allows runaway mutation from excess oxidation, while the dolichol lack blocks normal capacity to detect and correct these DNA errors via glycoprotein synthesis. We did not pick this up until this past year. Yes, it is important. It can't get any more important than this.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor