If anti-cholesterol drugs are included in this rationale, then statins
should be specifically excluded.  (Statin Drug Names: Lipitor, Crestor,
Mevacor, Pravachol, Zocor, Lescol, and Baycol, aka atorvastatin,
rosuvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and
simvastatin; This class of drugs is also known as HMG-CoA Reductase
Inhibitors, short for 3-Hydroxy-3-Methyl-Glutaryl Coenzyme A Reductase. )

Statin drugs cause a coenzyme Q10 deficiency, which causes cell injury.  The
opposite effect of the stated goal.

See, among many others:

STATINS & MITOCHONDRIAL CYTOPATHY,
COENZYME Q10 (UBIQUINONE) DEFICIENCY CAUSED BY STATINS
Do statins cause a CoQ10 deficiency?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2353945&dopt=Abstract

Study report: http://www.annals.org/issues/v137n7/nts/200210010-00004.html

Dr. Phillips study mentioned in a Wall Street Journal article (This is
smooth muscle, not cardiac muscle.) Conclusion "statin therapy may be
associated with increased oxidation injury.mild adverse effects of statins
that are difficult to assess might be much more prevalent than widely
considered "

http://www.impostertrial.com Is Myopathy Part Of Statin Therapy? Dr.
Phillips study website, with info for Patient and Physician

Cohen & Gold, Mitochondrial Cytopathy in Adults: What we know so far

http://www.ccjm.org/pdffiles/COHEN701.PDF

(See "Heart" in table page 4, and section on page 7) CoQ10 If statins cause
CoQ10 deficiency, and CoQ10 deficiency causes mitochondrial disease, what
are the symptoms of mitochondrial disease? Heart pain is one of them.

Oxidation Injury in Patients Receiving HMG-CoA Reductase Inhibitors:
Occurrence in Patients without Enzyme Elevation or Myopathy.

US Patents: # 4,933,165

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/
netahtml/srchnum.htm&r=1&f=G&l=50&s1=4933165.WKU.&OS=PN/4933165&RS=PN/4933165

see also subsequent related patents: Do a search by patent number at:

http://patft.uspto.gov/netahtml/srchnum.htm

for the following:

United States Patent 5,082,650

United States Patent 5,849,777

United States Patent 6,264,960

Merck Patent application stating that statins interfere with CoQ10 and that
deficiency causes problems. They documented that they knew this about
statins in 1989, 10 years before the 100+ deaths by Rhabdomyolysis!

http://sites.huji.ac.il/malaria/maps/ubiquinonemetpath.html

Malaria Parasite Metabolic Pathways Ubiquinone Metabolism

another version:

http://www.stdgen.lanl.gov/stdgen/images/KEGG/00130.html

DEFINITION Ubiquinone biosynthesis - Reference pathway. Diagram of the
Ubiquinone (aka CoQ10) metabolic pathway, highlighting exactly where the
Statins interrupt it. All of the 17 or so steps have to happen correctly for
the body to produce CoQ10, but statins interrupt (or retard) this in step
#2.

Introduction to the Citizen's petition to the FDA:
http://www.vaccinationnews.com/DailyNews/July2002/StatinInduced8.htm by Dr.
Peter Langsjoen This is the introduction to the petition. (It is aimed at
getting attention, and the wording may be more alarming than necessary.)

To the FDA: "Citizen Petition To Change The Labeling For All Statin Drugs
(Mevacor, Lescol, Pravachol, Zocor, Lipitor, And Advicor) Recommending Use
Of 100-200mg Per Day Of Supplemental Co-Enzyme Ql0 To Reduce The Risk Of
Statin-Induced Myopathies (Including Cardiomyopathy And Congestive Heart
Failure)," by Dr. Julian Whitaker, MD:
http://www.fda.gov/ohrms/dockets/dailys/02/May02/052902/02p-0244-cp00001-01-vol1.pdf
or as html:
http://216.239.33.100/search?q=cache:4qAiX-YbZLYC:www.fda.gov/ohrms/dockets/dail
ys/02/May02/052902/02p-0244-cp00001-01-vol1.pdf+Statin-Induced+Cardiomyopathy+In
troduction+To+The+Citizen%27s+Petition+On+Statins&hl=en&ie=UTF-8

Statin Depletion of CoQ10 is linked to heart problems.

Exhibit A of FDA Petition: "The clinical use of HMG CoA-reductase inhibitors
(statins) and the associated depletion of the essential co-factor coenzyme
Ql0; a review of pertinent human and animal data." by Dr. Peter Langsjoen
MD:
http://www.fda.gov/ohrms/dockets/dailys/02/May02/052902/02p-0244-cp00001-02-Exhi
bit_A-vol1.pdf

Effect of atorvastatin on left ventricular diastolic function and ability of
coenzyme Q10 to reverse that dysfunction.

Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.

Am J Cardiol. 2004 Nov 15;94(10):1306-10.

Heart Failure Institute, Department of Medicine, Advocate Christ Medical
Center, University of Illinois/Christ Cardiovascular Disease Fellowship
Program, Oak Lawn, Illinois 60453, USA. marc.silver@advocatehealth.com
<marc.silver@advocatehealth.com>

"This study evaluated left ventricular diastolic function with Doppler
echocardiography before and after statin therapy. Statin therapy worsened
diastolic parameters in most patients; coenzyme Q(10) supplementation in
patients with worsening diastolic function with statin therapy improved
parameters of diastolic function."

Examples of the heart and other problems associated with statin depletion of
CoQ10.

1:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.

Effect of atorvastatin on left ventricular diastolic function and ability
of

coenzyme Q10 to reverse that dysfunction.

Am J Cardiol. 2004 Nov 15;94(10):1306-10.

PMID: 15541254 [PubMed - indexed for MEDLINE]

2:  Rundek T, Naini A, Sacco R, Coates K, DiMauro S.

Atorvastatin decreases the coenzyme Q10 level in the blood of patients at
risk

for cardiovascular disease and stroke.

Arch Neurol. 2004 Jun;61(6):889-92.

PMID: 15210526 [PubMed - indexed for MEDLINE]

3:  Ornato JP.

Questions & answers. I take a statin to lower my LDL (bad) cholesterol
level,

but I've heard statins inhibit the production of coenzyme Q10 (CoQ10).
Should I

take a CoQ10 supplement?

Health News. 2004 Apr;10(4):16. No abstract available.

PMID: 15088591 [PubMed - indexed for MEDLINE]

4:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.

Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy for

statin-induced changes in diastolic LV performance: description of a
clinical

protocol.

Biofactors. 2003;18(1-4):125-7.

PMID: 14695927 [PubMed - indexed for MEDLINE]

5:  Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru GP.

Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting

other antioxidants and PUFA.

Biofactors. 2003;18(1-4):113-24.

PMID: 14695926 [PubMed - indexed for MEDLINE]

6:  Langsjoen PH, Langsjoen AM.

The clinical use of HMG CoA-reductase inhibitors and the associated
depletion

of coenzyme Q10. A review of animal and human publications.

Biofactors. 2003;18(1-4):101-11. Review.

PMID: 14695925 [PubMed - indexed for MEDLINE]

7:  Pettit FH, Harper RF, Vilaythong J, Chu T, Shive W.

Reversal of statin toxicity to human lymphocytes in tissue culture.

Drug Metabol Drug Interact. 2003;19(3):151-60.

PMID: 14682607 [PubMed - indexed for MEDLINE]

8:  Wolters M, Hahn A.

Plasma ubiquinone status and response to six-month supplementation combined

with multivitamins in healthy elderly women--results of a randomized,

double-blind, placebo-controlled study.

Int J Vitam Nutr Res. 2003 May;73(3):207-14.

PMID: 12847998 [PubMed - indexed for MEDLINE]

9:  Hargreaves IP.

Ubiquinone: cholesterol's reclusive cousin.

Ann Clin Biochem. 2003 May;40(Pt 3):207-18. Review.

PMID: 12803831 [PubMed - indexed for MEDLINE]

10:  [No authors listed]

Extra co-enzyme Q10 for statin-users?

Treatmentupdate. 2001 Jun;13(2):4-7.

PMID: 11570288 [PubMed - indexed for MEDLINE]

11:  Fosslien E.

Mitochondrial medicine--molecular pathology of defective oxidative

phosphorylation.

Ann Clin Lab Sci. 2001 Jan;31(1):25-67. Review.

PMID: 11314862 [PubMed - indexed for MEDLINE]

12:  Kaikkonen J, Nyyssonen K, Tomasi A, Iannone A, Tuomainen TP,

Porkkala-Sarataho E, Salonen JT.

Antioxidative efficacy of parallel and combined supplementation with
coenzyme Q10 and d-alpha-tocopherol in mildly hypercholesterolemic subjects:
a randomized

placebo-controlled clinical study.

Free Radic Res. 2000 Sep;33(3):329-40.

PMID: 10993487 [PubMed - indexed for MEDLINE]

13:  Levin WM.

Statin drugs: a double-edged sword?

Hosp Pract (Off Ed). 1997 Aug 15;32(8):44. No abstract available.

PMID: 9275961 [PubMed - indexed for MEDLINE]

14:  De Pinieux G, Chariot P, Ammi-Said M, Louarn F, Lejonc JL, Astier A,

Jacotot B, Gherardi R.

Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA
reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio.

Br J Clin Pharmacol. 1996 Sep;42(3):333-7.

PMID: 8877024 [PubMed - indexed for MEDLINE]

15:  Fjelstrup A.

[Statin therapy and heart failure. There is a difference between statins]

Tidsskr Nor Laegeforen. 1994 May 20;114(13):1561-2.  Norwegian. No abstract

available.

PMID: 8079255 [PubMed - indexed for MEDLINE]

16:  Carlsen SM, Fougner KJ.

[Statin therapy, Q10 and heart failure. Is there any difference between
statins?]

Tidsskr Nor Laegeforen. 1994 Apr 30;114(11):1345.  Norwegian. No abstract

available.

PMID: 8079217 [PubMed - indexed for MEDLINE]

17:  Hyams DE, Roylance PJ, Kruger K, Bodd E.

[Do we kill our cardiac patients with statin therapy? Coenzyme Q10, what do
we know?]

Tidsskr Nor Laegeforen. 1994 Feb 20;114(5):590.  Norwegian. No abstract

available.

PMID: 7748252 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2
247468&dopt=Abstract

Lovastatin decreases coenzyme Q levels in humans.

Proc Natl Acad Sci U S A. 1990 Nov;87(22):8931-4.

PMID: 2247468 [PubMed - indexed for MEDLINE] A 1990 study showing depletion
of CoQ10 by Lovastatin - includes descriptions of cardiac patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
1479481&dopt=Abstract A
2001 discussion on "The effect of pravastatin and atorvastatin on coenzyme
Q10"

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellularRespiration.html
Primer on how cells breathe normally (Note the role of CoQ10, called
"Ubiquinone" in "The Respiratory Chain" section.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
1505177&dopt=Abstract
(abstract)

http://213.4.18.135/70.pdf

http://216.239.33.100/search?q=cache:IGxCBJ3vs1kC:213.4.18.135/70.pdf+gaist+stat
in+myopathy+risk+greater&hl=en&ie=UTF-8
view as html

Lipid-lowering drugs and risk of myopathy: a population-based follow-up
study. Dr. Gaist is in Denmark and studies populations of entire countries
for epidemiology information.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2011277&dopt=Abstract
Dr. Gaist's study, Statins and risk of polyneuropathy: a case-control study.
(more serious than peripheral neuropathy)

http://213.4.18.135/87.pdf Dr. Gaist's studies on Statin-induced nerve
damage (full text)

Others:

Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma
coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin.

J Clin Pathol. 1993;46:1055-7. [PMID: 8254097]

http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=PMID&colon;
8254097

Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum
coenzyme Q10 during treatment with HMG-CoA reductase inhibitors.

Mol Aspects Med. 1997;18 Suppl:S137-44. [PMID: 9266515]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=9266515

Bargossi AM, Grossi G, Fiorella PL, Gaddi A, Di Giulio R, Battino M.
Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced
by HMG-CoA reductase inhibitors. Mol Aspects Med. 1994;15 Suppl:s187-93.
[PMID: 7752830]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=7752830

Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in
familial mitochondrial encephalomyopathy. Proc Natl Acad Sci U S A.
1989;86:2379-82. [PMID: 2928337]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=2928337

Baker SK, Tarnopolsky MA. Statin myopathies: pathophysiologic and clinical
perspectives. Clin Invest Med. 2001;24:258-72. [PMID: 11603510]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=11603510

Rosenfeldt FL, Pepe S, Ou R, Mariani JA, Rowland MA, Nagley P, et al.
Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic
and ischemic stress: studies in rats and in human atrial tissue. Biofactors.
1999;9:291-9. [PMID: 10416043]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=10416043

Reust CS, Curry SC, Guidry JR. Lovastatin use and muscle damage in healthy
volunteers undergoing eccentric muscle exercise. West J Med.
1991;154:198-200. [PMID: 2006566]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=2006566

Statin-associated myopathy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2672737&dopt=Abstract

Thompson PD, Clarkson P, Karas RH.

Preventive Cardiology and Cardiovascular Research, Division of Cardiology,
Hartford Hospital, Hartford, Conn 06102, USA. pthomps@harthosp.org

"recent evidence suggests that statins reduce the production of small
regulatory proteins that are important for myocyte maintenance"

Statins and myotoxicity.

Curr Atheroscler Rep. 2003 Mar;5(2):96-100. Review.

PMID: 12573193 Farmer JA.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2573193&dopt=Abstract

Baylor College of Medicine, One Baylor Plaza, Room 525D, Houston, TX 77030,
USA. jfarmer@bcm.tmc.edu

NERVE DAMAGE & STATINS
Frequently Asked Question: What medical research studies have been done on
Statins and Nerve Damage that I can bring to my doctor's attention?

Golomb BA, Yang E, Denenberg J, Criqui M (2003),

Statin-associated adverse events. P95. Presented at the 43rd Annual
Conference on Cardiovascular Disease Epidemiology and Prevention. Miami;
March 5-8.

Chong PH, Boskovich A, Stevkovic N, Bartt RE.

Statin-associated peripheral neuropathy: review of the literature.

Pharmacotherapy. 2004 Sep;24(9):1194-203. Review.

PMID: 15460180 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15460180

"Based on epidemiologic studies as well as case reports, a risk of
peripheral neuropathy associated with statin use may exist; however, the
risk appears to be minimal. On the other hand, the benefits of statins are
firmly established. These findings should alert prescribers to a potential
risk of peripheral neuropathy in patients receiving any of the statins; that
is, statins should be considered the cause of peripheral neuropathy when
other etiologies have been excluded."

Rajabally YA, Varakantam V, Abbott RJ.

Disorder resembling Guillain-Barre syndrome on initiation of statin
therapy.

Muscle Nerve. 2004 Nov;30(5):663-6.

PMID: 15389662 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15389662

"We report a disorder resembling Guillain-Barre syndrome, occurring on
initiation of simvastatin, in a 58-year-old man, who had experienced a
similar but milder episode after starting pravastatin 6 months earlier. This
case suggests that acute polyradiculoneuropathy may represent a rare but
serious side-effect of statin treatment. It also raises the issue of the
pathophysiology of acute neuropathy on statin exposure, with a
hypersensitivity reaction resulting in an immune-mediated process being
possible instead of the hypothesized mitochondrial dysfunction in chronic
cases."

Scola RH, Trentin AP, Germiniani FM, Piovesan EJ, Werneck LC.

Simvastatin-induced mononeuropathy multiplex: case report.

Arq Neuropsiquiatr. 2004 Jun;62(2B):540-2. Epub 2004 Jul 20.

PMID: 15273860 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15273860

"The association between the use of statins and neuromuscular disease is
currently being intensely discussed. We relate a 63 years old man with
possible case of statin-induced neuropathy in a patient with dislipidemia in
use of simvastatina at high doses. The electrophysiologic studies disclosed
findings compatible with mononeuropathy multiplex, suggested by clinical
prescutation of asymmetrical numbness and weakness. More common causes of
mononeuropathy multiplex were excluded and the patient improved after the
discontinuation of the drug."

Statins and risk of polyneuropathy, A case-control study

D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. García
Rodríguez, MD, MSc;

J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD

http://213.4.18.135/87.pdf full text

From the abstract: "The authors verified a diagnosis of idiopathic
polyneuropathy in 166 cases. The cases were classified as definite (35),
probable (54), or possible (77). The odds ratio linking idiopathic
polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and
14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in
current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4)
for definite cases. For patients treated with statins for 2 or more years
the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4).
CONCLUSIONS: Long-term exposure to statins may substantially increase the
risk of polyneuropathy."

Are users of lipid-lowering drugs at increased risk of peripheral
neuropathy?

David Gaist, Luis Alberto García Rodríguez . Consuelo Huerta . Jesper
Hallas . Søren H. Sindrup

http://213.4.18.135/75.pdf full text

http://213.4.18.135/76.2.pdf full text

http://213.4.18.135/87.pdf full text text

Pharmacodynamics: Statins and peripheral neuropathy

U. Jeppesen (2), D. Gaist (1)(2), T. Smith (1), S. H. Sindrup (1)(2)

(1) Department of Neurology, Odense University Hospital, DK-5000 Odense C,
Denmark Tel.: +45-6541-2474, Fax: +45-6541-3389

(2) Department of Clinical Pharmacology Odense University, Odense, Denmark

Received: 6 July 1998 / Accepted in revised form: 1 October 1998

Abstract Volume 54 Issue 11 (1999) pp 835-838

http://link.springer-ny.com/link/service/journals/00228/bibs/9054011/90540835.htm

Association of HMG-CoA reductase inhibitors with neuropathy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2549960&dopt=Abstract

Ann Pharmacother. 2003 Feb;37(2):274-8.

Backes JM, Howard PA.

Department of Pharmacy Practice and Lipid, Atherosclerosis, Metabolic and
LDL-Apheresis Clinic, University of Kansas Medical Center, Kansas City, KS
66160-7231, USA. jbackes@kumc.edu

"Epidemiologic studies and case reports suggest an increased risk of
peripheral neuropathy with statin drugs. The majority of cases were at least
partially reversible with drug cessation." (emphasis added)

Moosmann B, Behl C.

Selenoprotein synthesis and side-effects of statins.

Lancet. 2004 Mar 13;363(9412):892-4. Review.

PMID: 15031036 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15031036

"We noted that the pattern of side-effects associated with statins resembles
the pathology of selenium deficiency, and postulated that the mechanism lay
in a well established, but often overlooked, biochemical pathway--the
isopentenylation of selenocysteine-tRNA([Ser]Sec). A negative effect of
statins on selenoprotein synthesis does seem to explain many of the
enigmatic effects and side-effects of statins, in particular, statin-induced
myopathy."

Statin therapy and small fibre neuropathy: a serial electrophysiological
study.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2639733&dopt=Abstract

Lo YL, Leoh TH, Loh LM, Tan CE.

J Neurol Sci. 2003 Apr 15;208(1-2):105-8.

Department of Neurology, Singapore General Hospital, Outram Road, Singapore.
gnrlyl@sgh.com.sg

Describes 3 patients who developed neuropathy after ONE MONTH of statin
therapy. "One patient redeveloped small and large fibre neuropathy when the
similar drug was readministered."

Peripheral Neuropathy and Lipid-Lowering Therapy

Paul E. Ziajka, MD, PhD, and Tammy Wehmeier, RN, Orlando, Fla.

Abstract: We report a case of peripheral neuropathy induced and excerbated
by several commonly used HMG-CoA reductase inhibitors including lovastatin,
simvastatin, pravastatin, and atorvastatin, and the vitamin niacin. A review
of the literature shows similar cases with individual lipid-lowering drugs,
but this case shows the cross-reactivity of the neuropathic process to
different HMG-CoA reductase inhibitors, and is the first reported case of a
peripheral neuropathy exacerbated by the use of niacin.

http://www.sma.org/smj1998/julysmj98/ziajka.pdf

Phan T, McLeod JG, Pollard JD, Peiris O, Rohan A, Halpern JP.

Peripheral neuropathy associated with simvastatin.

J Neurol Neurosurg Psychiatry. 1995 May;58(5):625-8.

PMID: 7745415 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7
745415&dopt=Abstract

Ahmad S.

Lovastatin and peripheral neuropathy.

Am Heart J. 1995 Dec;130(6):1321. No abstract available.

PMID: 7484806 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7
484806&dopt=Abstract

Jacobs MB.

HMG-CoA reductase inhibitor therapy and peripheral neuropathy.

Ann Intern Med. 1994 Jun 1;120(11):970. No abstract available.

PMID: 8172444 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8
172444&dopt=Abstract

Medication-induced peripheral neuropathy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2507417&dopt=Abstract

Curr Neurol Neurosci Rep. 2003 Jan;3(1):86-92. Review.

Weimer LH.

Neurological Institute of New York, 710 West 168th Street, Unit 55, New
York, NY 10032, USA. Lhw1@columbia.edu

PMID: 12507417 [PubMed - indexed for MEDLINE]

"Although most cases demonstrate acute or subacute onset after exposure,
recent experiences with statin drugs raise the possibility of occult toxic
causes of chronic idiopathic neuropathy."

Le Quesne PM. Neuropathy due to drugs. In: Dyck PJ, Thomas PK, Griffin JW,
et al, eds. Peripheral neuropathy. 3rd ed. Philadelphia: Saunders,
1993:1571-1581.

(Book, no link)

Of interest:

MacDonald BK, Cockerell OC, Sander WAS, Shorvon SD (2000) The incidence and
lifetime prevalence of neurological disorders in a prospective
community-based study in the UK. Brain

123:665-676

General background medical Info from

Related, but also will appear in other FAQs:

Neuromuscular Disease Center

Washington University School of Medicine, St. Louis, MO

Home: http://www.neuro.wustl.edu/neuromuscular/index.html

Under Disorders & Syndromes:

Select:

Myopathy: http://www.neuro.wustl.edu/neuromuscular/maltbrain.html

Neuropathy: http://www.neuro.wustl.edu/neuromuscular/naltbrain.html

Neuromuscular: http://www.neuro.wustl.edu/neuromuscular/syaltbrain.html

CNS (Central Nervous System):
http://www.neuro.wustl.edu/neuromuscular/syaltbrain.html#cns

Specifics,

MYOGLOBINURIA - RHABDOMYOLYSIS
http://www.neuro.wustl.edu/neuromuscular/msys/myoglob.html

Then see Lipid Lowering Agent Myopathies
http://www.neuro.wustl.edu/neuromuscular/msys/myoglob.html#lipid

Note that this connects to CARDIAC + MYOPATHY
http://www.neuro.wustl.edu/neuromuscular/msys/cardiac.html

And to TOXIC NEUROPATHIES:
http://www.neuro.wustl.edu/neuromuscular/nother/toxic.htm#statin

OR Locally supplied Search on "Statin" leads to:

TOXIC MYOPATHIES http://www.neuro.wustl.edu/neuromuscular/mother/myotox.htm

Note also tht under Mitochondrial Disorders, the list of problems associated
with Coenzyme Q10 Deficiency
http://www.neuro.wustl.edu/neuromuscular/msys/myoglob.html#coq10

MITOCHONDRIAL MYOPATHIES

Facts About Mitochondrial Myopathies from the Muscular Dystrophy Association

http://www.mdausa.org/publications/mitochondrial_myopathies.html#whatcauses

MEMORY LOSS & STATINS
Frequently Asked Question: What medical research studies have been done on
Statins and Memory Loss, or other mental problems that I can bring to my
doctor's attention?

(Statins: Lipitor, Mevacor, Pravachol, Zocor, Lescol, and Baycol, aka
atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and
simvastatin; Nerve Damage: Neuropathy, peripheral neuropathy,
polyneuropathy; See separate FAQ for memory loss, cognitive damage, amnesia
and aphasia, i.e., central nervous system (CNS) damage)

Am J Med. 2004 Dec 1;117(11):823-9.

Randomized trial of the effects of simvastatin on cognitive functioning in
hypercholesterolemic adults.

Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB.

Center for Clinical Pharmacology, University of Pittsburgh, Pennsylvania
15260, USA. mfm10@pitt.edu

"This study provides partial support for minor decrements in cognitive
functioning with statins. Whether such effects have any long-term sequelae
or occur with other cholesterol-lowering interventions is not known." This
is the second of two studies by Muldoon, both showing measurable cognitive
decline in statin groups after only 6 months, using Neuropsych testing.
Further, the cognitive deficits appear consistently in specific areas.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15589485

Golomb BA, Yang E, Denenberg J, Criqui M (2003),

Statin-associated adverse events. P95. Presented at the 43rd Annual
Conference on Cardiovascular Disease Epidemiology and Prevention. Miami;
March 5-8.

Muldoon MF, Ryan CM, Flory JD, Manuck SB (2002),

Effects of simvastatin on cognitive functioning.

Presented at the American Heart Association Scientific

Sessions. Chicago; Nov. 17-20.

Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck
SB.

Effects of lovastatin on cognitive function and psychological well-being.

After 6 months, 100% of the patients on placeboes showed a measurable
increase in cognitive function, and 100% of the statin patients showed a
measurable decrease in cognitive function.

Am J Med. 2000 May;108(7):538-46.

PMID: 10806282 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
0806282&dopt=Abstract

Cognitive impairment associated with atorvastatin and simvastatin.

King DS, Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW.

Department of Medicine, University of Mississippi Medical Center, Jackson,
Mississippi 39216, USA. dking@pharmacy.umsmed.edu

Pharmacotherapy. 2003 Dec;23(12):1663-7.

"we report two women who experienced significant cognitive impairment
temporally related to statin therapy. One woman took atorvastatin, and the
other first took atorvastatin, then was rechallenged with simvastatin.
Clinicians should be aware of cognitive impairment and dementia as potential
adverse effects associated with statin therapy."  PMID: 14695047

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=14695047

Cognitive impairment associated with atorvastatin.

King DS, Jones DW, Wofford MR et al. (2001), Presented at the American
College of Clinical Pharmacy Spring Practice and Research Forum. Salt Lake
City; April 22-25.

Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
FDA)

Volume 17, Number 3, August 1998, section 3, page 3

Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"

Recognizing the 14 reports of Amnesia under that drug, .8% of the total
adverse effects for that drug.

www.health.gov.au/tga/docs/pdf/aadrbltn/aadr9808.pdf

Statin-associated memory loss: analysis of 60 case reports and review of the
literature.

Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM.

Drug Information Service, Duke University Medical Center, Durham, North
Carolina 27710, USA.  Pharmacotherapy. 2003 Jul;23(7):871-80.

This study searched the MedWatch drug surveillance system of the Food and
Drug Administration (FDA) from November 1997-February 2002 for reports of
statin-associated memory loss. They also reviewed the published literature.
References from the study are good for follow-up research.

Abstract:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2885101&dopt=Abstract

Full Study Text free on Medscape:

http://www.medscape.com/viewarticle/458867

The Role of Lipid-Lowering Drugs in Cognitive Function: A Meta-Analysis of
Observational Studies

from Pharmacotherapy

Posted 06/30/2003

Mahyar Etminan, Pharm.D., Sudeep Gill, M.D., FRCPC, Ali Samii, M.D., FRCPC

Although this study does bring the cognitive issues to light, it is a very
poor study.  The authors left out the pivotal study by Dr. Muldoon, that
showed nearly 100% of statin users had a  measurable loss of cognitive
ability after 6 months, while 100% of the placebo group improved their
scores.

Abstract:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2820814&dopt=Abstract

Full Study Text free on Medscape:

http://www.medscape.com/viewarticle/456866

Simvastatin-Associated Memory Loss

Amanda Orsi, Pharm.D., Olga Sherman, Pharm.D., and Zegga Woldeselassie,
Pharm.D.,

Abstract: The statins are widely used to treat dyslipidemias. They are
generally associated with mild adverse effects, but rarely, more serious
reactions may occur. A 51-year-old man experienced delayed-onset,
progressive memory loss while receiving simvastatin for
hypercholesterolemia. His therapy was switched to pravastatin, and memory
loss resolved gradually over the next month, with no recurrence of the
adverse effect.

from Pharmacotherapy

Posted 06/01/2001

Page 1 of 3:
http://www.medscape.com/viewarticle/409738?WebLogicSession=PXke2H8h99pyNVSCajAh5
clptzOAHJSZuNBobSwWmi9veWjdJ2A3%7C-1468812056489609316/184161392/6/7001/7001/700
2/7002/7001/-1

full printable version: http://www.medscape.com/viewarticle/409738_print

ADR of the Month

September 2001 Vol. 6 No. 9

EDITORS

Michelle W. McCarthy, Pharm.D.

Anne E. Hendrick, Pharm.D.

University of Virginia Health System

Department of Pharmacy Services

Drug Information Center

PO Box 800674

Charlottesville, VA 22908-0674

http://hsc.virginia.edu/pharmacy-services/Newsletters/ADR%20of%20the%20Month/ADR
Month%209-01htm.html

The Tablet, a general member benefit published by the British Columbia
Pharmacy Association, September 2001, Volume 10 no 8.

Excerpt:

Do HMG-CoA reductase inhibitors impair memory? After taking simvastatin for
a year, a 51-year-old patient developed short term memory loss, to the
extent of being unable to complete his sentences because he would forget
what he was going to say. The drug was discontinued, replaced by
pravastatin, and within one month his memory returned.14 In a separate case,
a 67-year-old woman developed impaired short-term memory, altered mood,
social impairment, cognitive impairment and dementia after one year of
atorvastatin therapy. When atorvastatin was discontinued, her memory, mood
and cognition improved completely.15 Memory impairment in a patient
receiving atorvastatin has been reported to the BC Regional ADR Centre.

REFERENCES:

14. Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory loss.

15. King DS, Jones DW, Wofford MR et al. First report of cognitive
impairment in an elderly patient: case report. Pharmacotherapy 2001 Mar; 21:
371.

http://www.bcpharmacy.ca/publications/thetablet/pdf_version/BCPhA_Tablet-Sep2001.pdf

See page 11 of 16:

See also:

Statins and risk of polyneuropathy, A case-control study

D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. García
Rodríguez, MD, MSc;

J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD

http://213.4.18.135/87.pdf full text

Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase
inhibitor.

von Keutz E, Schluter G.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9
737641&dopt=Abstract

Institute of Toxicology, PH-Product Development, Bayer AG, Wuppertal,
Germany

Am J Cardiol. 1998 Aug 27;82(4B):11J-17J.

PMID: 9737641

"In dogs, the species most sensitive to statins, cerivastatin caused
erosions and hemorrhages in the gastrointestinal tract, bleeding in the
brain stem with fibroid degeneration of vessel walls in the choroid plexus,
and lens opacity."

Subchronic toxicity of atorvastatin, a hydroxymethylglutaryl-coenzyme A
reductase inhibitor, in beagle dogs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8
864188&dopt=Abstract

Walsh KM, Albassam MA, Clarke DE.

Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann
Arbor, Michigan 48105, USA.

"The toxicity of atorvastatin (AT), an inhibitor of
hydroxymethylglutaryl-coenzyme A reductase (HMG), was evaluated in beagle
dogs. hemorrhage in gallbladder and brain, demyelination of optic nerve, and
skeletal muscle necrosis"

Finally, on memory loss and statins: Sworn testimony from the Baycol trial
in Corpus Christi, Texas. From the transcript of the AM Session on 03-05-03,
in the case Hollis Haltom Vs. Bayer Corporation. Testifying under oath,., in
response to the plaintiff's attorney's question, "What is your current
position at Bayer?", LAWRENCE POSNER, M.D of BAYER stated: "I'm the --  
currently I'm the head of worldwide regulatory affairs for our prescription
drug business, which means I have responsibility in somewhere between 60 and
100 countries where we sell products for registrations, compliance, things
of that nature." Excerpts from the trial transcript follow, with the Q
indicating counsel's Question, and the A indicating Dr. Posner's Answer:

Q. So there are some concerns addressed here back in 1995 about testing up
to .8. And do you know what the nature of the concern was?

A. Yes. It was related to a side effect that occurred in the brain.

Q. Of what kind of animal?

A. It occurred in the brain of dogs.

Q. Okay. So there was a side effect that occurred in dogs, and then there
was a concern about whether you wanted to go forward and test at this higher
dose level in human beings, given what you had learned about the dogs,
right?

A. That's correct.

Q. Okay. Now, did you just say, well, let's forget about these concerns and
we'll go ahead and put .8 on the market anyway, or did you do some further
analysis that was not mentioned the other day?

A. Yes. The authors of this had -- they had two concerns. One concern was
the toxicity that they found in the brain of dogs. But the other was that
they had no way to identify this and who might be at risk before it
happened. So there was no way to detect that someone was at risk for this
side effect.

[skip some testimony on other topics]

Q. Do you remember in one kind of animal there had been some studies done
that there could be a particular kind of problem with one kind of animal?

A. Oh, yeah. Yes, from the -- that's correct, from the toxicology studies.

Q. Okay. And were you able to demonstrate to your own satisfaction, to
SmithKline's satisfaction, to the FDA's satisfaction, that that particular
problem that showed up with that kind of animal is not something that
happens in human beings?

A. Yes. We did it -- we did it by explaining the toxicology data. We also
explained it on the basis of kinetic data. That actually at the higher
levels of drug, what happens is a certain amount of drug is bound to
proteins in the body that circulate; and therefore, is not -- cannot cause
side effects. And actually, a much smaller proportion of the drug is free.
And that what you corrected for that, you actually found out that the
margins of safety were in fact greater than you would predict just from the
animal data.

Q. And as you move forward then and got approval and sold Baycol from 1997
through 2001, did that problem that had shown up with that one kind of
animal ever become a problem with human beings?

A. It was actually shown with other statins as well. It wasn't unique to
cerivastatin. It was a problem -- it was identified early on with lovastatin
and some of the others. In fact, for none of the statins did it ever predict
for any clinical problem or toxicity.

Q. So these animals would have that same problem regardless of which
statin -- or at least with other statins?

A. Certainly with lovastatin it was true.

Q. But when it came time to human beings, that just wasn't something that
happened to human beings?

A. And I think today no one pays much attention to it.

AMNESIA & STATINS
Frequently Asked Question: Amnesia is one of the Lipitor side effects
reported by Pfizer on the Physician's Information, where can I find out more
about people who have had amnesia episodes while taking the drug?

Lipitor, Thief of Memory, by Duane Graveline M.D.
Dr. Graveline, retired family MD, USAF Flight Surgeon, researcher in space
medicine and US Astronaut, who suffered adverse effects from Lipitor,
maintains several websites and is working on a second book about statin
adverse effects, including statin-related memory loss and amnesia at:

www.spacedoc.net (you can start here and read about his life and his books)

http://www.spacedoc.net/lipitor_thief_of_memory.html

http://www.spacedoc.net/lipitor.htm

http://www.spacedoc.net/statin_dialogues.htm

Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
FDA)

Volume 17, Number 3, August 1998, section 3, page 3

Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"

Recognizing the 14 reports of Amnesia under that drug, .8% of the total
adverse effects for that drug.

www.health.gov.au/tga/docs/pdf/aadrbltn/aadr9808.pdf

CHEST PAIN & STATINS
Frequently Asked Question: Chest pain, that my cardiologist cannot explain
via angiogram, stress test, EEG or EKG, is one of the side-effects I see is
reported by many people. Is there any information on chest pain associated
with statins?

Naturally, chest pain should be first evaluated by a cardiologist. If the
usual explanations for chest pain do not apply to you, and you believe that
statin adverse-effect may be the cause, here are some articles that may give
you some background, or may be useful to give to your doctor. Some are
specific to statins and cardiomyopathy, some are background on how statins
affect CoQ10 production and how a CoQ10 deficiency affects the cells.

Most of these research articles have been found via a search of the National
Institutes of Health website
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=&DB=PubMed , a repository
for hundreds of medical journals. In most cases, only the abstract is
available and the full article must be purchased. Many of the others can be
found via a Google or other net search, or were discovered via posts on the
Lipitor message boards.

See:

http://www.lipitor.com/pi/default.asp Pfizer's Physician's Info for
prescribing Lipitor, includes documented known adverse effects. Note "Body
as a Whole: Chest pain," the italics indicate that the incidence was > 2% in
original trials.

Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK, Haas RH.

Statin myotoxicity is associated with changes in the cardiopulmonary
function.

Atherosclerosis. 2004 Nov;177(1):183-8.

PMID: 15488882 [PubMed - in process]

Scripps Mercy Clinical Research Center, Scripps Mercy Hospital, Cardiology
(Mer 74), Catheterization Laboratories, Scripps Mercy Hospital, 4077 Fifth
Avenue, San Diego, CA 92103, USA. phillips.paul@scrippshealth.org

"The mechanism of the muscle toxicity associated with lipid-lowering therapy
remains obscure. Pathological and biochemical findings in patients with
statin myotoxicity suggest impaired fatty acid oxidation. Exhaled gas
analysis can be used to assess substrate utilization including fatty acid
oxidation. In order to determine if muscle toxicity due to lipid-lowering
therapy might be related to abnormalities in lipid oxidation, exhaled gas
analysis was performed in the fasted state on 11 patients subsequent to
statin-associated myositis reactions. Results were compared to those of 16
normal controls who were measured both on and off statin therapy.
Post-myositis patients showed a depressed anaerobic threshold (AT) (P=0.009)
compared to controls while age-adjusted maximal oxygen consumption (VO2max)
and ventilatory efficiency (VE/VCO2) were not significantly different. The
fasting respiratory exchange ratio (RER) of post-myositis patients off
statins was abnormally increased (P=0.00001) as was their S1-slope
(P=0.023). Controls demonstrated a significant increase in their RER while
taking statins consistent with decreased lipid oxidation (P <0.00001). These
findings suggest that abnormal lipid oxidation in certain patients may
predispose them to the myotoxicity caused by lipid-lowering therapies."

1:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.

Effect of atorvastatin on left ventricular diastolic function and ability
of coenzyme Q10 to reverse that dysfunction.

Am J Cardiol. 2004 Nov 15;94(10):1306-10.

PMID: 15541254 [PubMed - indexed for MEDLINE]

"This study evaluated left ventricular diastolic function with Doppler
echocardiography before and after statin therapy. Statin therapy worsened
diastolic parameters in most patients; coenzyme Q(10) supplementation in
patients with worsening diastolic function with statin therapy improved
parameters of diastolic function."

2:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.

Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy for

statin-induced changes in diastolic LV performance: description of a
clinical protocol.

Biofactors. 2003;18(1-4):125-7.

PMID: 14695927 [PubMed - indexed for MEDLINE]

"Lipid-lowering statins are thought to have a favorable safety profile.
Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase,
the rate-limiting step of mevalonate synthesis. Mevalonate is the substrate
for further synthesis of cholesterol and Co Enzyme Q10 (CoQ10). CoQ10 plays
an important role during oxidative phosphorylation in the myocardial cell.
Since myocardial diastolic function is a highly ATP dependent, we reasoned
that early changes of diastolic function may be an early marker of
ventricular dysfunction. METHODS: Patients who are to commence on statin
therapy will be enrolled in the trial. Baseline measurements of plasma
CoQ10, total cholesterol, LDL, HDL, CoQ10/LDL ratio, peak E, peak A
velocities, E/A ratio, deceleration time, isovolumetric relaxation time,
color M-mode propagation velocity will be performed and patients will then
begin to take Oral atorvastatin (Lipitor, Parke-Davis) 20 mg daily for three
to six months. All baseline measurement will be repeated after 3 to 6 months
of statin therapy. Those patients demonstrating > 1 measurement of diastolic
LV function that worsened during the 3 to 6 months of statin therapy will be
supplemented with CoQ10 300 mg. daily for 3 months. A followup
echocardiogram and blood CoQ10 level will be measured in patients who
received CoQ10 supplementation. RESULTS: Statistical analysis will be
performed using the paired t test to compare coenzyme levels and
echocardiographic indices at baseline and after treatment and after
supplementation."

3:  Langsjoen PH, Langsjoen AM.

The clinical use of HMG CoA-reductase inhibitors and the associated
depletion of coenzyme Q10. A review of animal and human publications.

Biofactors. 2003;18(1-4):101-11. Review.

PMID: 14695925 [PubMed - indexed for MEDLINE]

"The depletion of the essential nutrient CoQ10 by the increasingly popular
cholesterol lowering drugs, HMG CoA reductase inhibitors (statins), has
grown from a level of concern to one of alarm. With ever higher statin
potencies and dosages, and with a steadily shrinking target LDL cholesterol,
the prevalence and severity of CoQ10 deficiency is increasing noticeably. An
estimated 36 million Americans are now candidates for statin drug therapy.
Statin-induced CoQ10 depletion is well documented in animal and human
studies with detrimental cardiac consequences in both animal models and
human trials. This drug-induced nutrient deficiency is dose related and more
notable in settings of pre-existing CoQ10 deficiency such as in the elderly
and in heart failure. Statin-induced CoQ10 deficiency is completely
preventable with supplemental CoQ10 with no adverse impact on the
cholesterol lowering or anti-inflammatory properties of the statin drugs. We
are currently in the midst of a congestive heart failure epidemic in the
United States, the cause or causes of which are unclear. As physicians, it
is our duty to be absolutely certain that we are not inadvertently doing
harm to our patients by creating a wide-spread deficiency of a nutrient
critically important for normal heart function."