July 2009

Cholesterol drugs and peripheral neuropathy in your practice

by Joe Di Duro, DC

Using data from the 1999-2004 National Health and Nutrition Examination Survey, researchers found that 33.5 million older Americans (men age 50 years and older and women age 60 years and older) are currently taking a statin drugs (24.4%). That's a lot of people taking drugs!

While the FDA has deemed statins to be safe to use for their intended purpose -- lowering cholesterol -- no drug is totally without side effects in susceptible individuals. As the use of statin drugs continues to increase, and people have been taking statins for a prolonged period that is significantly longer than the time period required for testing drugs, the side effects of statins affect more people than ever before.

Since the drug companies that manufacture statins have become aware of the incidence of serious side effects, they've added a warning to statin advertising that was not present early on. This warning states, "Unexplained muscle pain and weakness could be a sign of a rare but serious side effect and should be reported to your doctor right away." People who take statin drugs need to heed this warning immediately because in extreme cases the side effects of statins can be fatal.

The major side effects of statin drugs

Neuropathy, muscle pain, and muscle weakness are three of the main side effects of statin drugs. Chiropractors are directly in line to visit patients with these side effects. Chronic pain and pain not relieved by medical means drives millions of people to the chiropractic office. Unknowingly, these chiropractors may face clinical failure in cases that are caused not predominately from spinal malfunction, but by toxic neuropathy.

Other symptoms of neuropathy include: pain, numbness, tingling, and pricking sensations; burning pain (especially at night); and/or sensitivity to touch. If left undiagnosed, neuropathy can lead to deterioration of the muscles and paralysis. Remember that we all need throat muscles to swallow, chest muscles to breathe, and that the heart is a muscle. In the extreme, severe neuropathy as a side effect to statin use can lead to death.

Some researchers estimate the 1 in 10 people who take statin drugs will experience a mild form of neuropathy where the symptoms may be pain or even a feeling of tiredness, difficulty in arising from a low chair or getting out of bed, shortness of breath or difficulty walking. Isolated cases of statin-associated neuropathy have been reported since 1994 [1].

Statin drugs and neuropathy

Statin-induced neuropathy is increasingly described in the scientific literature. Proposed mechanisms include an alteration in cholesterol synthesis, producing a disturbance in the cholesterol-rich neuronal membrane, or in the activity of ubiquinone (coenzyme Q10), a mitochondrial respiratory chain enzyme inhibited by statins leading to neuronal damage. [1] Statins are hydroxymethyl glutaryl coenzyme A reductase (HMGCoA reductase) inhibitors, this action is responsible for the lipid-lowering effect but can also explain the nervous toxicity. Statins interfere with cholesterol synthesis that may alter myelin and nerve membrane function and they prevent mitochondrial respiratory chain enzyme synthesis which may disturb neuron energy use. [2] The entire class is implicated, and both polyneuropathy and mononeuropathy have been described. [3]

Epidemiological and case-control studies from the U.K. suggest elevated odds ratios (ORs) of 2.5 times (95% CI 0.3--14.2) the risk of developing neuropathy while on statin drug therapy. [4]

Small countries like Demark or Iceland are great for studying medical conditions. Because the population is genetically similar as opposed to the vast melting pot of the United States, it is easier to conduct a controlled study. A famous Danish study of neuropathy [5] as a side effect to statin drug use concluded that individuals who were current statin users were four times more likely to have developed peripheral neuropathy than nonusers. Among patients diagnosed with "definite" peripheral neuropathy, current statin users had 16 times the risk of nonusers. In addition, more years of statin use was associated with higher risk of developing peripheral neuropathy. Typically, long-term use of statins is defined as two years or more but neuropathy can occur even after just a few days of use in a susceptible individual.

Drugs in a chiropractic office?

In our practice in southern Arizona, we specifically marketed to this patient group. In the first three months of starting my new practice, we saw 267 new patients. There were 246 patients (female 59.2%) over the age of 50 who we screened for peripheral neuropathy: 30.9% were age 50-63; 46.2% were 64-74 years of age; and 22.9% were 75+ years old. In this group as a whole, 48.4% tested positive for peripheral neuropathy.

Within the age breakdown testing positive: 37.7% (n=23) were age 50-63; 60.2% (n=62) were 64-74 years of age; and 72.9% (n=35) were 75+ years old, respectively. Relevant risk factors for neuropathy were noted with just 19% of this group being diabetic while 38.6% were taking statin drugs.

Basically, our marketing worked in getting neuropathy people into our office with almost 40% taking statin drugs. Both young and old patients came in with neuropathy, and not all from statins.

Doctor awareness is low

More surprisingly, in a study by Dr. Beatrice Golomb [6] at UCSD, patients reportedly spoke to their physician about the possible connection between statin use and their symptom. Patients reported that they and not their doctor most commonly initiated the discussion regarding the possible connection of the statin drug to their symptoms -- 98% v 2% cognition survey, 96% v 4% neuropathy survey, 86% v 14% muscle survey; p < 10(-8) for each. Physicians were reportedly more likely to deny than affirm the possibility of a connection between statin drug therapies and patient symptoms. Doctors even rejected a possible connection for symptoms with strong literature support for a drug connection, and even in patients for whom the symptom met presumptive literature-based criteria for probable or definite drug-adverse effect causality.

Chiropractors should become aware of the damaging effects of statin drugs on their patients' health and their own clinical outcomes. With the high percentage of people taking statin drugs in the general public and in those entering the chiropractic clinics, proper diagnosis and treatment of drug-induced neuropathies is essential.

The topic of neuropathy as it relates to diabetes or cholesterol drugs is far more extensive than can be covered in this short article. To learn more, call 520-876-0308 or visit www.concentrolabs.com.

References

1. Jacobs MB: "HMG-CoA reductase inhibitor therapy and peripheral neuropathy." Ann Intern Med. 1994 Jun 1;120(11):970.

2. Formaglio M, Vial C: "Statin induced neuropathy: myth or reality?" Rev Neurol (Paris). 2006 Dec;162(12):1286-9.

3. de Langen JJ, van Puijenbroek EP: "HMG-CoA-reductase inhibitors and neuropathy: reports to the Netherlands Pharmacovigilance Centre." Neth J Med. 2006 Oct;64(9):334-8.

4. Law M, Rudnicka AR: "Statin safety: a systematic review." Am J Cardiol. 2006 Apr 17;97(8A):52C-60C.

5. Gaist D, Jeppesen U, et al: "Statins and risk of polyneuropathy: a case-control study." Neurology. 2002 May 14;58(9):1333-7.

6. Golomb BA, McGraw JJ, Evans MA, Dimsdale JE: "Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance." Drug Saf. 2007;30(8):669-75.

(A 1986 Palmer College graduate, Dr. Joe Di Duro is president of Concentro Laboratories LLC, a learning center that aids doctors in the diagnosis and treatment of patients with peripheral neuropathy pain. He is a Chiropractic Neurologist who completed a Masters of Science Degree in Clinical Research from Palmer Center for Chiropractic Research at Palmer College in 2006. Dr. Di Duro is currently in practice in Arizona and is the founder of Neuropathy Treatment Centers of America.)