Statin Associated Behavioral Change

We now have thousands of case reports of statin associated behavioral change. Road rage, extraordinary hostility, profound depression, even basic personality changes ("that is not my husband") are frequently reported.

In my book, Statin Drugs Side Effects, I have mentioned the Golgi apparatus in my discussions of neuropeptide formation and function, key to explaining behavioral side effects of the statin class of drugs. I have previously postulated a possible role of statins on this extremely complex structure.

The Golgi apparatus, along with a tubular network called the endoplasmic reticulum, is present in every cell in the body, controlling vital cell interactions. Now scientists are just beginning to reveal the actual mechanics of cholesterol's role in statin associated behavioral change - another pathway not yet dreamed of only a year ago.

Reporting in Science, Wang and Anderson have discovered a critical role for cell cholesterol in the Golgi apparatus role of cell signaling. They found that oxysterol binding protein (OSBP) is a cholesterol-binding "scaffolding" protein vital to the control of signaling pathways within the Golgi apparatus.

These researchers found this vital pathway extremely sensitive to cholesterol levels within the cells. When intracellular cholesterol was lowered by whatever means, profound degradation of this signaling pathway resulted.

Although statins were not used in this experiment, there is no doubt that the effects of statins on this pathway could be profound in susceptible individuals. This adds another mechanism, that of intracellular cholesterol lowering, to the already established mechanism of dolichol inhibition in explaining the great variety of behavioral side effects associated with statin drug use.

Both of these mechanisms come to play in the delicate process of neuropeptide formation and transport through the Golgi apparatus and endothelial reticulum. These peptides then must pass through the central canals of our axons to receptors elsewhere in the body.

Just the process of axonal delivery of biochemicals is completely alien to most physicians trained earlier than 1980. Physicians then had no information either of neuropeptides or this novel delivery system in their training, so digesting the potential effects of a statin drug on signaling systems within the Golgi apparatus and altered neuropeptide formation during transit through the endoplasmic reticulums does not come easily to their understanding.

Even younger doctors are surprised to learn that cellular inter-communication, our very thoughts, sensation and emotions, are no longer the province of our traditional hormonal and autonomic nervous system but rather this novel neuropeptide thing.

Is it any surprise that many physicians have difficulty accepting that such behavioral changes as aggressiveness, hostility, homicidal thoughts, depression and suicide may be associated with statin drug use?


"My husband was prescribed Vytorin® 3 months ago and has been experiencing severe side-effects from it. Within a month of taking this drug, his personality began changing. He has become easily agitated, and he is growing more and more hostile and aggressive when upset. Frankly, I don't like the person he has become. He is paranoid, unable to focus clearly, has no sexual interest and does not remember many things that I have told him. After reading the content on your website and several others, I am convinced that Vytorin is toxic to his system."

This is now a very common story in my repository of statin drug side effects from victims all over the world. From aggression, irritability, hostility, paranoia, homicidal ideation, road rage-like behavior, depression and suicidal ideation, all share one thread - that of neuropeptide synthesis, the magic peptide strand that makes us what we are and governs of every action. Imagine, every thought, every sensation and every emotion you have ever experienced governed by the makeup of proteins and sugars on a growing peptide strand.

Deep in the cells of all of us are tiny factories responsible for this function. Henry Ford has come to the ER (endoplasmic reticulum), for that is what this micro-assembly line resembles. Within these tubules are deposited protein after protein, the type and placement of each protein made supercritical by the insertion, here and there, of a certain kind of sugar that will tell the growing protein strand just where to fold and in what direction. The protein strand has become a glycoprotein strand with a far more complex range of possibilities as to how the final molecule looks - and structure determines function. A twist here or right angle there makes all the difference between anger and blind, berserker anger or love and passionate love.

From the ER the completed peptide strand now called a neuropeptide, passes into the so-called Golgi apparatus (named after an Italian scientist) where it is packaged into a vesicle and carried down the nerves to storage centers near the synapses until needed

Now comes the statin drug a.k.a. reductase inhibitor to do its number on the reductase step of the vital mevalonate pathway. Unfortunately, interference at this point inhibits not only cholesterol but also CoQ10, dolichols, selenoproteins and other important functions using the same pathway. It is the dolichols that are involved in the neuropeptide assembly. Imagine what would happen if we suddenly had only one-half of our normal dolichol supply?

This is almost certainly the mechanism for the behavioral side effects of statins. Our entire process of neuropeptide formation, our ER assembly line, is orchestrated by dolichols. Suddenly this entire system becomes disturbed and most doctors have not the slightest idea of this potential for statin effect, and this is not just some one in a million sensitivity reaction, this tendency is inevitable with statin use. And the severity of symptoms can vary from just barely detectable to homicides and suicides. CoQ10 deficiency associated with statin use is beginning to be understood by doctors in the U.S. but statins and personality change is a complete mystery and usually it is "off to the psychiatrist," who doesn't understand it a bit better!

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor


Books From Amazon

The Dark Side of Statins
The Statin Damage Crisis
Cholesterol is Not the Culprit
Statin Drugs Side Effects
Lipitor, Thief of Memory

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