Statin Adverse Effects FAQ: STATINS & MITOCHONDRIAL CYTOPATHY,
COENZYME Q10 (UBIQUINONE) DEFICIENCY CAUSED BY STATINS,
CARNITINE DEFICIENCY CAUSED BY STATINS

(The Cholesterol-lowering 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. )

To my physician,

I believe that my symptoms may be due to the adverse effects a_ssociated
with cholesterol-lowering statin drugs.  I need your help to understand the
cause of my symptoms, treatment options, and the prognosis for my recovery.

Please review the references below, published medical studies that show
similar problems a_ssociated with statin drugs.  These are made available
via the National Institutes of Health (NIH,
http://www.ncbi.nlm.nih.gov/Entrez/) library of biomedical journal citations
and other major repositories of medical research.

Also, I am respectfully requesting that you file an adverse effects report
with the FDA (http://www.fda.gov/medwatch/how.htm), and that you please send
a copy of the report to the to the NIH-funded Statin Study, attention: Dr.
Beatrice Golomb, Principal Investigator.
Statin Study website: http://medicine.ucsd.edu/statin/
Statin Study contact info: http://medicine.ucsd.edu/statin/contactinfo.html
UCSD STATIN STUDY E-MAIL ADDRESS: statinstudy@ucsd.edu
MAILING ADDRESS: UCSD Statin Study 9500 Gilman Dr. La Jolla, CA 92093-0995
PHONE NUMBER: (858) 558-4950

Thank you

STATINS & MITOCHONDRIAL CYTOPATHY,
COENZYME Q10 (UBIQUINONE) DEFICIENCY CAUSED BY STATINS,

CARNITINE DEFICIENCY CAUSED BY STATINS

References (updated as of  January 7, 2005):

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
a_ssociated with increased oxidation injury.mild adverse effects of statins
that are difficult to a_ssess 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

Improvement of statin-a_ssociated myotoxicity by L-carnitine.Arduini A,
Peschechera A, Giannessi F, Carminati P.  J Thromb Haemost. 2004
Dec;2(12):2270-1. No abstract available. PMID: 15613049 [PubMed - in
process]

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 a_ssociated 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 a_ssociated 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 ofcoenzyme
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 riskfor 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 Itake 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 forstatin-induced
changes in diastolic LV performance: description of a
clinicalprotocol.Biofactors. 2003;18(1-4):125-7. PMID: 14695927 [PubMed -
indexed for MEDLINE] 5:  Pa_ssi S, Stancato A, Aleo E, Dmitrieva A, Littarru
GP.  Statins lower plasma and lymphocyte ubiquinol/ubiquinone without
affectingother 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 a_ssociated depletionof
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 combinedwith 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 oxidativephosphorylation.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 randomizedplacebo-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
abstractavailable. 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 abstractavailable. 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
abstractavailable. 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-a_ssociated 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

Bhuiyan J, Seccombe DW. The effects of 3-hydroxy-3-methylglutaryl-CoA
reductase inhibition on tissue levels of carnitine and carnitine
acyltransferase activity in the rabbit. Lipids. 1996;31:867-70. [PMID:
8869889]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&Dopt=r&uid=8869889

Worsening for using statin in carnitine palmityol transferase deficiency
myopathyDelgado-Lopez F, Bautista-Lorite J, Villamil-Fernandez F. Rev
Neurol. 2004 Jun 1-15;38(11):1095.  Spanish. No abstract available. PMID:
15202093 [PubMed - indexed for MEDLINE]  Statin-a_ssociated myopathy with
normal creatine kinase levels.Toma E, Loignon M. Ann Intern Med. 2003 Jun
17;138(12):1007-8; author reply 1008-9. No abstract available. PMID:
12809465 [PubMed - indexed for MEDLINE]

Metabolic intolerance to exerciseArenas J, Martin MA. Neurologia. 2003
Jul-Aug;18(6):291-302. Review.  Spanish. PMID: 12838448 [PubMed - indexed
for MEDLINE]