I had been wondering for a long time why the symptoms associated with Gulf War Illness so closely resembled those that I knew were associated with the use of statin drugs. What was the common denominator I wondered? With entirely different biochemical pathways why were they so similar? The lack of energy, easy fatigability, muscle aches and pains, neuropathies, weakness, cognitive dysfunction, tendency for ALS and even behavioral changes seemed so unusually similar. I knew that some of these veterans must have been on statins but certainly not more than a few, what then?

          As a former flight surgeon with an Army helicopter unit I knew something of the Gulf War. As a matter of fact the only reason I was not there at the Gulf was that the war ended so soon my paper work did not have time to get through. I learned about the special chemical, biological and radiation hazards we military faced and knew the use of countermeasures. When they said during drill to “MOPP-up”, I put on my gear with everyone else. MOPP in military talk means "Mission Oriented Protective Posture", which we called MOPP-gear but it was far more than a suit. As one of the specially trained military doctors, I briefed on nerve gas and special use of acetylcholinesterase (AchE) inhibitors such as pyridostigmine bromide (PB).  When in the field they yelled “GAS” we knew what to do. I did not know then of the damage they could do. I knew only that the alternative was death.

          It is only now, 15 years later, that I learn the full story. We now know PB causes acute destructive changes at the neuromuscular junction, the site of connection between nerve cells and muscle fibers, at which nerve cells signal muscles to contract. And this is the key to the statin link. It was only a few months ago I wrote the essay,LDL Cholesterol missing link for neuromuscular communication” and published it on my website.

        In it I described this new link in explaining the effect of statin drugs on various neurodegenerative diseases. In seeking an explanation for the effect of statin drugs to trigger certain neuromuscular diseases such as myasthenia gravis and amyotrophic lateral sclerosis, scientists have identified the likely candidate in the form of a lipoprotein known as Lrp4.

          It tells of research at the NYU Langone Medical Center where they have found that this Lrp4 protein is the missing link that allows communication between two crucial molecules—one derived from the nerve and the other from muscle—that enables the formation of the synapse. Our ability to move and breathe depends upon the special connection between nerve cells and skeletal muscle fibers - the 'neuromuscular synapse,'" explains Dr. Steven J. Burden, principle investigator for this discovery.

          Previous studies demonstrated that a specific molecule on the surface of our muscle fibers, called MuSK, is critical in relaying instructions from motor neurons. Likewise, previous studies showed that a molecule called Agrin carries the instruction from our nerve cells. The missing link in the field has been how Agrin 'talks' to MuSK. It is Lrp4 that makes this communication possible. That this protein is type of cholesterol offers a likely explanation for the occurrence of certain neuromuscular diseases after statin treatment has begun. As reductase inhibitors, statin drugs were designed to block the mevalonate pathway of cholesterol synthesis. The effect of statin is to inhibit the synthesis of cholesterol, thereby possibly interfering with Lrp4 availability preventing normal communication between nerve and muscle.

          We now have an explanation for the similarities between Gulf War Syndrome and statin damage and even the surprising decision of our government to include ALS as duty related. It is at the neuromuscular synapse where both conditions come together. AChE inhibitors and statins meet at this point to prevent communication between nerve and muscle and both Gulf War veterans and statin users have elevated ALS incidence.

          I have one additional bit of information. AS a doctor I am forever focused on treatment. Recently I have deduced from my research that mitochondrial mutations are a major contributor for the chronic and permanent changes we are seeing in statin damaged people. I have proposed that treatment include those natural supplements known to be necessary for mitochondrial maintenance. I suggest the same for those afflicted with Gulf War Illness.


Duane Graveline MD MPH