Long-term statin treatment may be associated with chronic peripheral neuropathy

This paper was published in the European Journal of Clinical Pharmacology 1999 Jan;54(11):835-8

 

Study title and authors:

Statins and peripheral neuropathy.

Jeppesen U, Gaist D, Smith T, Sindrup SH.

Department of Neurology, Odense University Hospital, Denmark.

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10027656

This paper reports of seven cases of peripheral neuropathy associated with long-term statin therapy.

(i) Diagnosis of neuropathy by statin therapy was confirmed after all other causes of neuropathy were thoroughly excluded.
(ii) Neuropathy symptoms manifested up to seven years after initiation of statin therapy.
(iii) In all seven cases the neuropathy affected the nerve fibres and with affection of both thick and thin nerve fibers.
(iv) The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to one year in four cases after statin treatment had been withdrawn.

Jeppesen concluded: "Long-term statin treatment may be associated with chronic peripheral neuropathy".

Doctor says that simvastatin should be considered among the causes of peripheral neuropathy

This study was published in the Journal of Neurology, Neurosurgery and Psychiatry 1995 May;58(5):625-8

Study title and authors:
Peripheral neuropathy associated with simvastatin.

Phan T, McLeod JG, Pollard JD, Peiris O, Rohan A, Halpern JP.
Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Australia.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/7745415

This paper describes four patients who developed sensorimotor neuropathy (sensorimotor neuropathy is a type of peripheral neuropathy that damages the motor nerves and the sensory nerves) while being treated with simvastatin and had complete or partial recovery after the withdrawal of statin treatment.

Case 1
A man aged 52 started treatment with simvastatin (10 mg/day).

Soon after he noticed generalised muscle weakness and fatigue. The weakness became progressively worse and he had difficulty in ascending stairs and running. After six months his right foot and subsequently his left foot became numb.

Treatment with simvastatin was withdrawn and on review six weeks later muscle cramps and weakness had improved although he still had the symptoms and signs of peripheral neuropathy.

On his last review, 18 months after the withdrawal of simvastatin, there had been furter clinical improvement.

Case 2
A women of 66 had started two years previously with simvastatin (10 mg/daily) which was subsequently gradually increased to 40 mg/daily after one year.

After the two years of statins the woman had weakness of the lower limbs and difficulty in rising from a chair. After three more months she was severely incapacitated and confined to a wheelchair. By four months she was unable to feed herself or to comb her hair and was admitted to a nursing home. She had pain in the fingers, the front of her legs, lower chest and abdominal wall.

Simvastatin was stopped and improvement followed. Nine months later she could feed herself, comb her hair and walk with the aid of a stick. Power in all muscle groups in the lower limbs also increased greatly.

Case 3
A women of 65 had started two years previously with simvastatin (10 mg/daily) which was subsequently increased to 20 mg/daily after one year.

After two years of statins the woman developed upper and lower limb weakness. Initially she had difficulty in rising out of chairs and climbing stairs and weakness progressed over a period of six weeks untill she was unable to lift her arms above her head, rise from a chair unaided, or walk without support. She complained of a burning sensation in her left foot.

Simvastatin treatment was withdrawn and four months later she had completely recovered clinically.

Case 4
A women ages 39 was given a daily dose of 10 mg of simvastatin.

Within 24 hours of starting the drug she developed pain in her right calf, and later pain in her right groin and pains down both arms. These symptoms were followed by the development of a sensation of pins and needles in her fingertips and later the toes.

Simvastatin was discontinued after a total dose of 180 mg. On review three months later she reported almost complete recovery from her symptoms except for a few patches of tenderness over her body.

Conclusion

The researchers suggest that statins may damage the peripheral nerves because they block the production of ubiquinone (Coenzyme Q10). Without the presence of ubiquinone within the body’s cells, cellular energy cannot be generated or sustained.

The head of the study, Dr Tai Phan, concluded that: "Simvastatin should be considered among the causes of peripheral neuropathy".

Statins increase the risk of peripheral neuropathy by 30%

This study was published in the Journal of Diabetes 2012 Nov 1

Study title and authors:
The association of statin use with peripheral neuropathy in the US population 40 years of age or older.

Tierney EF, Thurman DJ, Beckles GL, Cadwell BL.
Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/23121724

Peripheral nerves carry information to and from the brain. They also carry signals to and from the spinal cord to the rest of the body. Peripheral neuropathy means these nerves don't work properly. Peripheral neuropathy may be damage to a single nerve. It may be damage to a nerve group. It may also affect nerves in the whole body.

This study assessed the association between statin use and peripheral neuropathy. The study was based on data collected in the 1999-2004 National Health and Nutrition Examination Survey (NHANES) on people aged 40 or over.

The study found that those on statins had a 30% increased risk of peripheral neuropathy.

Statins cause definite damage to the peripheral nerves

This study was published in Neuro Endocrinology Letters 2011;32(5):688-90

Study title and authors:
Treatment with statins and peripheral neuropathy: results of 36-months a prospective clinical and neurophysiological follow-up.

Otruba P, Kanovsky P, Hlustik P.
Department of Neurology, Palacky University Medical School, University Hospital, Olomouc, Czech Republic. pavel.otruba@fnol.cz

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22167150

 

This study investigated the effects of statin treatment on lower-limb peripheral nerves. The study included 42 patients on statin therapy who were followed for three years.

The study found that long-term treatment with statins caused definite damage to peripheral nerves when the treatment lasts longer than two years.

Statins and fibrates are associated with an increased risk of peripheral neuropathy

This study was published at the Journal of Epidemiology and Community Health 2004 Dec;58(12):1047-51

Study title and authors:
Lipid lowering drugs prescription and the risk of peripheral neuropathy: an exploratory case-control study using automated databases.

Corrao G, Zambon A, Bertù L, Botteri E, Leoni O, Contiero P.
Dipartimento di Statistica, Università degli Studi di Milano-Bicocca, Via Bicocca degli Arcimboldi 8, Edificio U7, 20126 Milan, Italy. giovanni.corrao@unimib.it

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15547071

Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body.

Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years. Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails. These more general degenerative changes also can result from sensory or autonomic nerve fiber loss.

This study explored the association between prescription of cholesterol lowering drugs and the risk of peripheral neuropathy. 2,040 patients with peripheral neuropathy and 36,041 controls were included in the study.

The study found:
(a) Those that took statins had a 19% increased risk of peripheral neuropathy.
(b) Those that took fibrates had a 49% increased risk of peripheral neuropathy.
(c) Those that had higher doses of statins and fibrates had a higher risk of peripheral neuropathy.

This study shows that both statins and fibrates are associated with an increased risk of peripheral neuropathy.

Adverse Effects of Statins

This post features a summary of a study published in the International Journal of Pharmacology 1 (3): 210-225, 2005

Study title and authors:
Adverse Effects of Statins
Anna Jamroz-Wisniewska and Jerzy Bettowski
This study can be accessed at: http://198.170.104.138/3/detail.php?id=1&jid=ijp&theme=3&issueno=157&articleno=55015

Dr Anna Jamroz-Wisniewska reviewed the evidence concerning the adverse effects of statins.

The review found:
(i) Statins inhibit the production of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, an enzyme in cholesterol biosynthesis pathway, which initially converts HMG-CoA to mevalonate. Mevalonate is the precursor to cholesterol.
(ii) Apart from cholesterol, mevalonate is also a precursor for nonsteroid isoprenoids including farnesylpyrophosphate, geranylgeranylpyrophosphate, coenzyme Q, dolichol and isopentenylpyrophosphate which play an essential role in cellular physiology. 
(iii) The authors report that myopathy (muscle disease) is the most frequent side effect of statins. Other's include peripheral neuropathy (damage to nerves of the peripheral nervous system), hepatotoxicity (liver damage), increased risk of cataract and, according to some studies, increased risk of breast cancer.
(iv) Some studies suggest that statins may sometimes even be the cause of clogged arteries and heart failure.

Statins And Cancer: Cause For Concern

This post featues a paper published in the British Medical Journal 17 November 2001;323:1145

Study title and authors:
Statins And Cancer: Cause For Concern
Uffe Ravnskov, Paul J. Rosch, Peter H.Langsjoen, Joel M. Kauffman, and Kilmer S. McCully
Magle Stora Kyrkogata 9, S-22350 Lund, Sweden.
This paper can be accessed at: http://www.bmj.com/cgi/eletters/323/7322/1145#26439
 
Dr Uffe Ravnskov has published over 80 scientific papers regarding the cholesterol, saturated fat, heart disease hypothesis. Here he questions the wisdom of recommending statin treatment for a large segment of the world’s population simply because they have elevated cholesterol levels or are assumed to be at increased risk for coronary events because of the presence of other risk markers.

He finds:
(i) It is already known that statins may induce fatal rhabdomyolysis, cardiac insufficiency, peripheral polyneuropathy, hepatic toxicity, and mental disturbances.
(ii) A much more momentous issue is that all statins have proven carcinogenic.
(iii) In the Heart Protection Study non-melanoma skin cancer was seen in 243 patients treated with simvastatin compared with 202 cases in the control group. 
(iv) In the Scandinavian Simvastatin Survival Study non-melanoma skin cancer was seen in 13 patients treated with simvastatin compared with six in the control group.
(v) Also disquieting was the significant increase in breast cancer rates in patients treated with pravastatin in the Cholesterol and Recurrent Events trial.

Statin side effects

This post includes a summary of a study published in Biofactors 2005;25(1-4):147-52

Study title and authors:
Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation.

Books:

Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA.

East Texas Medical Center and Trinity Mother Francis Hospital, Tyler, 75701, USA. langsjoen@compuserve.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16873939

This study investigated the effects of discontinuing statin drugs and beginning Coenzyme Q10 supplementation in cardiology (heart disorder) clinic patients. The study included  The study included fifty new cardiology clinic patients who were on statin drug therapy (for an average of 28 months), who on their initial visit were evaluated for possible adverse statin effects (muscle pain, fatigue, shortness of breath, memory loss, and peripheral neuropathy). All patients discontinued statin therapy due to side effects and began supplemental Coenzyme Q10. The patients were followed for an average of 22 months.

The study found that after stopping statins and starting Coenzyme Q10:
(a) Fatigue decreased from 84% to 16%.
(b) Muscle pain decreased from 64% to 6%.
(c) Shortness of breath decreased 58% to 12%.
(d) Memory loss decreased from 8% to 4%.
(e) Peripheral neuropathy decreased from 10% to 2%.
(f) Measurements of heart function either improved or remained stable in the majority of patients.
(g) There was no adverse consequences from statin discontinuation.

The researchers conclude that: "Statin-related side effects, including statin cardiomyopathy, are far more common than previously published and are reversible with the combination of statin discontinuation and supplemental Coenzyme Q10".

*Dietary sources of Coenzyme Q10 include all animal products, particularly heart meat.

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