By Duane Graveline, M.D., M.P.H.
Neuropathy is well known to be associated with statin drug use. David Gaist was one of the first physician researchers to report this to the medical community in the journal, Neurology, in the year, 2002.
(Ref: http://www.neurology.org/content/58/9/1333.abstract )
In his original paper he expressed concern for the increased susceptibility to neuropathy among diabetics placed on statin drugs. He estimated that diabetics had as much as a sixteen fold increase in risk of neuropathy when statin drugs are used but stressed that non-diabetics also are susceptible.
The symptoms of numbness, tingling, burning and pain are now known to thousands of statins users. Any peripheral nerve can be involved. We also have learned that many cases of peripheral neuropathy can be considered permanent in that they are often completely resistant to traditional medical treatments.
The mechanisms of action appear to be multiple. Some authorities feel CoQ10 (ubiquinone) deprivation secondary to statin induced mevalonate blockade leads to loss of cell wall integrity, leading to inflammatory degeneration in nerve cells as well as muscle and liver cells.
One of the important functions of ubiquinone, in the form of ubiquinol, is the maintenance of cell wall integrity. Every cell in the body depends on ubiquinol for cell wall turgidity and stability. When inadequate for whatever reason, cell wall integrity is compromised and breakdown of the cell results. Neuropathy, myopathy and even liver cell inflammation all appear to be based upon ubiquinone depletion.
Recently other researchers have pointed to dysfunction of the neuromuscular junction (NMJ) in cases of motor neuropathy. Every muscle response we make depends upon a nerve stimulus. As the stimulus arrives in the NMJ a molecule called agrin is released to react ultimately with a substance called Musk at the muscle end of the NMJ.
Only in the past few years have we learned that an LDL cholesterol type of lipoprotein called Lrp4 is required to make this connection, allowing acetylcholine finally to effect muscle response. In the presence of statins, impairment of Lrp4 synthesis can be expected, blocking the normal response. Nerve conduction up to the NMJ is normal but no muscle response occurs. This in another example of the growing research evidence of cholesterol's vital role in many aspects of our physiology.
Cholesterol is also vital to the structure of the myelin sheath surrounding every nerve, presenting another possible mechanism of action for statins. In this case the faulty reaction is due to the well-known effect of statins to reduce bioavailability of dolichols. Dolichols are absolutely essential for glycoprotein synthesis, a process taking place continuously in the endoplasmic reticulum of our cells. Myelin is composed primarily of glycoproteins. Deficiency of dolichols then leads to altered or deficient glycoproteins with resulting loss of both structural integrity and conductivity of the nerve.
The following are a just a few of the reports I have received from readers of my books on the subject of Neuropathy and Statins:
1) I have a scheduled appt. at a New England Medical Center for neuropathy. I found out my creatinine kinase was 386 on March 31, 2005 and was taken off Lipitor. I asked for my old records and found that it was at 237 in February of 2004 and had been on Lipitor 20mg for 14 months prior. With all the research I have done, I feel this was the cause, however, my doctor said he does not know what is wrong with me. MS has been ruled out and I have neuropathy from elbows to hands, loss of fine motor skills and walk unsteadily. I have weakness and loss of muscle in hands. I fell down the stairs last week. I work a physical job, need my income and I am only 55 yrs old.
2) About 2 months ago, I was prescribed Mevacor. Soon after starting the Mevacor, I developed tinnitus. This being my only new medication, I spoke with my pharmacist about side effect. He did not seem to think there was a relationship between the Mevacor and the tinnitus. Allergy season was mentioned and considered since I have allergies that have been controlled for years with the same medication. I had been taking a low dose aspirin daily. Thinking this might be causing the constant buzzing (ringing) in my ears, I discontinued the aspirin. Discontinuing the aspirin has not lessened the tinnitus. To me, the buzzing started suddenly and seems to be bilateral. Sometimes I think the right ear may be louder but I really cannot tell for sure. I have not been able to determine any other symptoms.
3) Last year a Dr prescribed Crestor, and I developed peripheral neuropathy. I went off the drug, and it went away. The Dr then prescribed Pravachol, and the neuropathy returned. I went off the drug, but this time the neuropathy stayed. I'm in pain 24/7. I went to the same Dr recently, and told him about what the drugs did and refused to go on the Zetia. He got in my face and accused me of trying to find an excuse for my chronic pain and said the drugs have no side effects like that! It was awful, and I left the office shaken. I defended myself the best I could, but he was mean and hostile. He is a cardiologist in this area and I pity all the victims that have suffered under him. He is clearly owned by the drug companies.
4) My father, in his eighties, was put on a statin for a couple of years for no particular reason, except it is apparently the new "in" drug. Despite his age, he is an unusually vital, healthy, strong individual who is usually thought to be twenty years younger than his age. His cholesterol has always been low (130 - 140) with an excellent LDL/HDL ratio. He became extremely fatigued, depressed, and developed muscle weakness while on the drug, and I finally persuaded him to stop the statin. I insisted that he take some Co-Q10, which he now takes daily.
The overwhelming fatigue and depression have gone, but he has developed increasing, and severe weakness in his legs, and is now almost unable to walk. He can hobble a block, perhaps. His doctors are mystified. Is it possible that the statin caused some sort of neuropathy, which has INCREASED, despite his stopping the statin several months ago.
He has been attempting to work out at a gym, but it hasn't helped. I had hoped all his symptoms would mitigate with stopping the statin but he now appears almost crippled. His doctors are irritated, think he should be taking the statin to prolong his life, and say there is no connection between his weakness and Statins.
5) I was happy to see that someone has put out the facts about the side effects of statin drugs. My first encounter with them was Lipitor, which I was put on about 8 years ago for high cholesterol of 299. Within 3 months, I began losing the feeling in my toes and having great pain and burning, and tingling. I reported this to the doctor who responded by saying that I must have arthritis and prescribed orthopedic inserts for my feet. He didn't listen. In Sept. 2000 my new doctor put me on Niaspan which made me deathly ill. I vomited and had diarrhea violently for 11 months, when I refused to take it any more.
In August of 2001 I had a spell where I almost passed out twice so I went to the doctor and told her I wanted to be tested for diabetes because my mother had type II. The result showed I was type II and she put me on glucophage. So now I am diabetic. I'm on 80 mg. of Lescol daily, glucophage, and accupril. I have already been diagnosed with peripheral neuropathy, and in June of 2003, my liver enzymes were elevated. The internist said it could be caused by the glucophage, which I had only been on for 7 months.
I am disgusted with all the doctors. None will listen to me about the side effects of drugs. My cholesterol is now down to 207. I just don't know what to do. Could the glucophage be causing the elevated liver enzymes? What can do? I am 55 years old and have started experiencing the short- term memory loss. I cannot concentrate like I used to be able to do, and forget whether I shut the garage door or unplugged the curling iron. I never used to have these problems. And the neuropathy in my feet and legs is worse than ever and I have aches in my back that keep me from sleeping. Thank you for listening. Keep up the good work.
6) I have been taking Lipitor for seven weeks. I have had blood work done and no signs of problems. My cholesterol is significantly lowered. I have been experiencing headaches and a "pins and needles" feeling in my extremities. My doctor does not seem to take this seriously and doesn't think they are a side effect. I do. Also, I recently could perform a mathematical function that I do on a regular basis. Now - total mind is blank.
7) This has been the most frustrating year of my life. Doctors do not want to entertain the thought that Statins could cause neuropathy. After three visits and extensive tests at our University (with no cause determined), I asked the doctor if the statin drug (Lipitor) I was taking could have caused this and the answer was, "Very unlikely" and when pressed further the response was, "You can just get neuropathy." That is taking idiopathic to a new level.
8) On January 18th I saw my doctor concerning a tingling in my head, shakiness, and an inability to think straight. He had me discontinue my 10mg of Lipitor, Prilosec, Benadryl and daily vitamins for one day. On the 19th, barely 24 hours after my last dose of Lipitor, he told me to go back on my medications since I was showing no improvement. He also added a transdermal scopolamine patch thinking I had an inner ear problem. By the afternoon of Friday, January 21st, I was barely able to function. The shakes were worse and had spread to my legs, I could not drive, and I could not concentrate on anything. I called my doctor to inform him that I was taking off the patch and discontinuing my medications.
He scheduled me for a CAT scan for Monday morning. I took the patch off immediately and then omitted the Lipitor starting Saturday morning. By Saturday night my head began to clear a bit and the shakes were diminished considerably. By Sunday I felt fine except for some minor tingling still in my head and extremities.
At this time, I started doing some of my own research online concerning Lipitor and was appalled. I had only been back on Lipitor for the last two months after considerable persuasion by my doctor and I am now sorry I conceded. I canceled the CAT scan and the appointment with my doctor this morning, Monday, January 24th as I do not want to experience more bungling diagnosis nor arguments about discontinuing the Lipitor. I have improved greatly with only the tingling, itchy feeling left. I am now concerned about permanent side effects and what to expect.
9) I have been diagnosed with peripheral neuropathy and I believe it is due to Lipitor. The physician, who prescribed the Lipitor and referred me to a neurologist when he suspected I had a problem, is now not so willing to help me in establishing the cause. He told me to stop taking Lipitor the day I met him but is now not eager to give me much help. I had planned to go to a Neuropathy Clinic nearby. I read they are doing well with peripheral neuropathy but my neurologist has been reluctant in making a referral. I am at a loss as to what to do.
10) In October of 2003 I was diagnosed as having Diffuse Peripheral Neuropathy. Since that time, I have been to three neurologists and have had numerous tests to determine the cause and find a treatment that could hopefully return me to normal. The severity of my neuropathy is due to the failure of my physician recognizing the early symptoms of neuropathy. This enabled the neuropathy to progress and as a result, I have lost the feeling in my fingers and feet and extensive damage was done to my leg muscles.
It is very difficult for me to walk due to the weakness and the loss of feeling also affects my balance. Another side of neuropathy, and probably the worse, is "fatigue." For months it was difficult to function. While the bouts of fatigue have subsided somewhat, I still have times during some days where I will be overcome and left exhausted with little or no warning. This has been going on for nineteen months!
Through a process of elimination, tests for every possible typical cause (diabetes, alcoholism, hereditary, HIV, trauma, etc.) have been conducted. The one remaining and most credible conclusion is that is that it was drug-induced as every symptom falls in place. The only drug(s) I have taken that exhibit the symptoms are the cholesterol lowering drug(s) Pravachol and/or Lipitor; both of which are members of the "statin" family of drugs.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated October 2013