Dolichols, Personality Change and Statins

The first time I encountered the word dolichols was in 1999 when I was desperately searching the literature for help after my first encounter with statin damage in the form of a six hour episode of transient global amnesia (TGA).

My doctors at Johnson Space Center in Houston had given me Lipitor®, 10 mg daily, for moderately elevated cholesterol and six weeks later this strange defect in my ability to formulate new memory occurred.

Of course all my regular doctors and a few other specialists brought in for the occasion denied any possibility of relationship of my TGA with Lipitor, but I was suspicious.

I had been a family doctor for some 23 years and that drug was the only thing I was taking - by my standards you had to consider Lipitor. Searching the internet on statins back then did not give me much, but it did give me the fact that statins inhibited the synthesis of dolichols.

It said that dolichols were members of the isoprenoid family and were produced by the mevalonate pathway. This was all Greek to me then but it did direct my attention to the mevalonate pathway and the effect of these new reductase inhibitors on it.

Gradually in the past decade the entire story has emerged of the important role of dolichols in body function. If the importance of dolichol had ever been mentioned during my medical school training, I did not hear it and the possibility of it being inhibited by statins was of no consequence to me as a doctor.

In essence then I shrugged my shoulders and continued my research of the literature for what could be happening in my head besides a slowly growing tumor.

I had my second episode of TGA shortly after my next annual physical at Johnson Space Center. Yes, I had stopped the Lipitor on my own, the day after my first TGA. My NASA doctors were disgusted with me for stepping over the doctor/patient bounds in that manner and they requested I re-start Lipitor immediately.

Because I had no confirmation of any cognitive consequences of statin use from the 30 or so doctors and pharmacists I had interviewed during the previous year, I had no real defense and said yes to restarting Lipitor, insisting only that the dose be half the previous dose size or 5 mg daily. 

My second, much worse TGA episode, occurred 8 weeks later. Now I was absolutely convinced but remained the only one convinced for every one else thought this was just an amazing coincidence. Meanwhile dolichols were becoming more interesting to me. I had discovered their role in glycoprotein synthesis.

Hundreds of reports had come to me of aggression, hostility, sensitivity, paranoia, road rage type feelings, depression, suicidal ideation, homocidal ideation and a number of both suicides and homocide attempts all associated with statin drug use.

The glycoprotein synthesis story begins in the endoplasmic reticulum in nearly every cell in our bodies. This tiny mini-factory of tubular shape is where protein fragments are attached to certain special sugars to form our glycoproteins.

A major part of glycoproteins are those for our  emotions, our neuropeptides. These strands of chemicals, like popcorn on a string, are then transferred to the adjacent Golgi apparatus, packaged into vesicles and transferred through the axons of nerves to a storage center near the synapses where they will remain until needed for some emotional reaction, then released.

All of this glycoprotein synthesis is orchestrated by dolichols. Insufficient dolichols result in altered glycoproteins. Our hormones of emotion, commonly known as neuropeptides, are just one small part of what glycoproteins do. They also are vital for cell identification, messaging and immunodefense.

Another relevant role is the importance of a particular class of glycoproteins known as glycohydrolases.  A specific one of these is required for every mitochondrial DNA error correction required and thousands of these occur and must be corrected daily.

I hope I have convinced you of the importance of dolichols in our bodies. Most MDs would have to go back to their textbooks to refresh their minds about the many functions of dolichols yet they are liberally prescribing statins to millions of unsuspecting patients simply because their cholesterol levels exceed "desirable" levels.

In so doing they are radically altering the bioavailability of dolichols causing physiological changes in thousands of victims that we only now are beginning to define.

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

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