During my past decade of research on statins, my focus has been on the side effects of the statin class of drugs, specifically the impact of statin use on cognitive function, emotion and personality and the often permanent impact on muscles and nerves in the form of myopathy, neuropathy and ALS-like reactions.
By Dr. Duane Graveline, M.D., M.P.H.
Those unacquainted with the full range of my studies would quite naturally assume I am antagonistic to the use of statins, yet nothing could be further from the truth. In the past decade I have supported statin use for high risk people and if it were me who suddenly became high risk, I would strongly urge my doctor to put me on a low-dose statin but at a much lower dose than I was prescribed that led to my epsiodes with transient global amnesia.
Statins work to reduce cardiovascular risk but the benefit they demonstrate has no relationship to cholesterol reduction, it is apparently due to their powerful anti-inflammatory effect not even known to science until the impressive work of Ora Shovman, published in 2002.(1) Cholesterol reduction, the mantra for four decades, seemingly has nothing to do with it. During this time the scientific community has discovered the extreme importance of cholesterol to body function, not only for the brain, first reported by Frank Pfrieger in 2002(2), but also for many vital cellular processes.
Instead of being public health's greatest enemy, as we have been brainwashed to believe these past 35 years, cholesterol is probably the most important biochemical in the body. Not only is the cognitive function of our brains absolutely dependent upon ample supplies of cholesterol but cholesterol is the reservoir from which many of our most important hormones such as estrogen, testosterone and cortisone are derived.
Additionally, every cell in the body is dependent upon cholesterol for myriads of vital cellular processes such as lipid rafting, exocytosis and endocytosis, most of which have been delineated only within the past few years, long after statins were first marketed. Why then the use of heavy doses of statin drugs to reduce this vital substance?
My war is not against the statins. Rather, it is against the use of these powerful reductase inhibitors to block cholesterol synthesis when, in the opinion of myself and a rapidly growing body of others, cholesterol has nothing to do with the problem of atherosclerosis.
In the process of reducing cholesterol to lower and lower levels we have managed to create varying degrees of mevalonate pathway blockade. It is this blockade of cholesterol, dolichol, CoQ10, selenoprotein, Rho and normal phosphorylation that has caused the flood of reports of adverse effects from statins.
The blockade of cholesterol is the cause of most of the reports of cognitive dysfunction but it is the CoQ10 and dolichols inhibition that has caused most of the other adverse effects of emotional and behavioral disorders and myopathies, neuropathies and atypical ALS.
A recent study of 112 high-risk men (3) did much to reveal, at least in part, the mechanism of action of statin drugs in cardiovascular disease control. The primary mechanism appears to be that of thromboxane inhibition, although much more study remains to be done.
Thromboxane is Greek to most of us yet we all are very familiar with its effect. Anyone who has noticed a tendency for black and blue marks to appear much more easily while on aspirin knows a bit about thromboxane. So do those folks taking a small dose of aspirin for heart attack or stroke control with the understanding that it will lower the likelihood of clot formation. This is another attribute of thromboxane. Triggered by blood platelets, thromboxane contributes to platelet aggregation and clot formation.
Aspirin acts by inhibiting the ability of platelets to stimulate the formation of thromboxane from arachidonic acid, reducing the risk of clotting. Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane by platelets, producing an anti-coagulant effect making aspirin useful for reducing the incidence of heart attacks.
In a recent landmark study 112 individuals already on aspirin were given Zocor 40 mg daily with close follow-up of selected inflammatory and coagulation markers. Zocor decreased serum thromboxane by 20 percent (from 1.32 to 1.06 ng/ml). Zocor decreased hsCRP (high sensitivity C-reactive protein) very substantially from 2.06 to 1.39 inflammatory units. Zocor additionally decreased arachidonic acid levels from 9.6 to 5.4 units.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
1) Shovman.Immunol Res,25(3)2002.
2) Pfrieger. Science, 9 Nov, 2001.
3) Undas A, Int J Cardiol, Oct 28, 2010.