Statins' anti-inflammatory action is the most effective treatment we have for treatment of atherosclerosis and lowering of cardiovascular risk. However, I am a proponent of low, anti-inflammatory dosing of statins not the current cholesterol lowering dosing when cholesterol is not even the problem.
My concern is solely with the effect of statins on the mevalonate pathway. If you have not recently reviewed the relevant biochemistry, you should.
Twenty years ago the drug companies discovered the reductase inhibition step of this pathway and gave us truly effective inhibition of cholesterol synthesis but at the cost of inhibiting all the other vital components of the mevalonate pathway, namely CoQ10, dolichols, tau protein phosphorylation and selenoprotein metabolism. No one ever told us that blocking the mevalonate pathway at the reductase step to inhibit cholesterol synthesis would also just as effectively inhibit all these other components as well. We had to find this out for ourselves. We had become a nation of guinea pigs to the experimental whims of the drug companies.
This is not conjecture - this is real. Merck took out a patent on a statin/CoQ10 pill testifying to their awareness of this but they never marketed it. Dolichols and all the rest were simply ignored. The absolute necessity of cholesterol for proper brain function was first recognized by Pfrieger only a few years ago! You can imagine what Statins do to glial cells, our sole source of brain cholesterol. When he announced this to the world in 2003, you might have thought the drug industry would have reacted, at least a little. What did we get from them at the announcement of this incredible role for cholesterol? Dead silence.
It had just been announced that the biggest money-making class of drugs of all time had the unfortunate side effect of inhibiting cholesterol synthesis in the glial cells of our brain. Pfrieger had just proved these same glial cells were our sole source of cholesterol for synaptic formation and function.
Without sufficient cholesterol our memory was blocked. Our brains could not use blood cholesterol for this purpose because when combined with our lipoprotein carrier the resulting molecule is much too large to pass our blood brain barrier. We had evolved this glial cell pathway for brain cholesterol. This was all we had.
Is there now any doubt as to why cognitive problems are the most frequent problems cited by statin victims? Did we get a black box warning for physicians about the likelihood of cognitive side effects? No black box and not a word. Management had decided to simply ignore this message of warning from the research community. In their colossal cynicism they knew most physicians don't read the journals and believe only what their PDR and drug reps tell them.
Am I being too harsh? No, especially when hardly a day goes by without my getting a report that a primary care physician "had no idea statins could do that." I have been hearing that since the year 2000, when I experienced my own two cases of Lipitor associated TGAs and tried to report it to the medical community.
As to dolichols, most of us had not even heard the word in our medical training but now we know it is imperative for such vital functions as neuropeptide formation and glycolysis, the basis of much of our cell messaging, cell identification and immunodefence. The side effects from this combination could be anything.
The side effects of this collateral damage to the mevalonate pathway are not only wide-ranging they are predictable and dose dependent. We need a statin that is not firmly based in mevalonate pathway origin. We need a pure, non-mevalonate corrupting statin. Until then physicians should use caution, especially with high dose use. Only by prompt recognition of the full range of side effects can they be minimized.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor