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 | | From: | Sharon Hope | | Subject: | FAQ: Statin adverse effects | | Date: | Thu, 30 Dec 2004 22:09:41 GMT |
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 | Updated 30 December 2004:
Frequently Asked Questions about Statin Adverse Effects
What are the names of the Statin drugs?
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.
http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%0A%09%09%09%09%20%20%20from%20TB_PRODUCT_PPI%20%0A%09%09%09%09%20%20%20where%20PPI_SEQ%20=%2056&key=PPI
http://www.ca.pharma.novartis.com/downloads/e/lescol_scrip_e.pdf
http://www.merck.com/product/usa/pi_circulars/m/mevacor/mevacor_pi.pdf
http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf
What is the "Statin Study"?
Dr. Beatrice Golomb is doing research for the National Institutes of Health
(NIH) into "non-cardiac endpoints" of the statin drugs. In other words,
what do statins do besides reducing serum cholesterol? The UCSD Statin
Study is conducted at the University of California, San Diego, and it
accepts NO INDUSTRY FUNDING. You can, and should, contact the Statin Study
with information on any adverse effects. It is to everyone's benefit that
the UCSD Statin Study has the most complete set of information on statin
adverse effects in the world. You can email, write, or call:
statinstudy@ucsd.edu
UCSD Statin Study
9500 Gilman Dr.
La Jolla, CA 92093-0995
(858) 558-4950
More information at the website: http://medicine.ucsd.edu/statin/index.htm
Where can I look to find information on research studies of statin drugs?
The National Institutes of Health has a website,
http://www.ncbi.nlm.nih.gov/Entrez/ that offers a search engine that is
useful in finding the latest studies that have been published in medical
journals (over 11,000,000 biomedical journal citations) and other major
repositories of medical research. Each study usually comes with an Abstract,
or summary of the findings. In most cases, should you want to see the full
text of the study, the full article can be purchased online for
approximately $25 to $40, depending on the journal, which is much cheaper
than a subscription.
Note that journals publish new studies every month, so revisit the site
often. Also, if you find a study that is pertinent to what you are looking
for, check the links to the right that will take you to similar studies on
the same topic. Finally, if you don't get a 'hit' on what you are looking
for, try medical terminology synonyms. Search results are different when
using different search terms. So, for example: "statin" or "atorvastatin" or
"lipitor" or "reductase inhibitor" or "HMG-CoA". Similarly, "cholesterol"
will return different results from "Dyslipidemia."
Why does my physician have such a difficult time believing that my physical
problems might be an adverse effect of Lipitor or one of the other statins?
Statins are now the most widely prescribed of all prescription drugs, making
them very big business. The Wall Street Journal Online, in a June 13, 2003
article, "As Drug Sales Teams Multiply, Doctors Start to Tune them Out;
'Arms Race' by Pfizer and Rivals Boosts Pill Prices, Ire, but No One Dares
Retreat", reported that Pfizer's sales of Lipitor alone were $8 BILLION for
the year 2002. That is just for Lipitor alone, one of FIVE statins on the
market today. The article states that in 2002 the drug companies spent over
$12 Billion on their sales forces. According to the article, "Last year, a
few Pfizer reps brought along a guest speaker who was both a doctor and
lawyer to a lunch meeting with doctors at Clinical Associates, a group
practice in suburban Baltimore. He said they risked being sued if their
patients didn't reach their cholesterol goals". Doctors are the ones who are
primarily targeted by the advertising blitz to make the expectations of
increased sales come true. In addition, consumers are marketed with slick
commercials and ads. Doctors are very busy, and they are inundated with
positive statin spin. They may think that, since everyone is taking it, if
there were problems they would have heard about it. They may not take the
time to dig out negative information, and there are no major sponsors to
fund equal time for negative reports.
Only last year, in 2002, did the Journal of the American Medical Association
begin annotating publications with the author's ties to the company studied,
citing potential conflict of interest.
The British Journal of Medicine in their May 31, 2003 issue on the theme
"Time to untangle doctors from drug companies", ran no less than 6 articles
saying that too many of the published drug studies are no more than
industry-sponsored infomercials, and cited the selective reporting bias
whereby only pro-industry studies are published. These articles were
entitled: "Research sponsored by drug companies is biased"; " Drug
representatives may increase unnecessary GP prescribing"; "Reporting of
clinical trials of drugs shows bias"; "Characteristics of General
Practicioners who Frequently see Drug Industry Representatives: National
Cross-Sectional Study "; "No more free lunches; Patients will benefit from
doctors and drug companies disentangling"; "Information from drug companies
and opinion leaders; Double standards in information for medical journals
and practitioners should go" http://bmj.com/content/vol326/issue7400/
The Canadian CBC News ran a series of consumer articles on March 25, 2003,
on the prevalent problem of medical ghostwriting. In this scheme, drug
companies write a study favorable to their product and then "reward" a
doctor who prescribes the drug by listing his name as the "author" in the
publication.
http://www.cbc.ca/consumers/market/files/health/ghostwriting/links.html
Your physician should look into your physical adverse effects, regardless of
suspected cause. Do not permit your physician to put you off when you
express a concern. Too many people are reporting long-term, perhaps
permanent, damage when statin therapy is continued despite the appearance of
adverse effects. With rhabdomyolysis, death can result. With other side
effects, disability can result.
Oddly, people consistently report doctors who are dubious of reported
problems being due to statins, even when the problem is listed by the
manufacturer on the Physicians' Information page for the drug. It may help,
if you identify your problems with the findings of a published study, to
print out a copy and bring it with you to the doctor's appointment. In some
cases, the doctor may simply be terrified of a malpractice charge.
That is one of the purposes for this FAQ - to give people an additional tool
to help them to communicate with their doctors.
Note: These articles documenting or speculating on adverse effects of
statins are in the vast minority. Hundreds, even thousands, of articles and
research have praised statins. Certainly the people with side effects are in
the minority, and the benefits are fantastic. Still, the doctors who do
attempt to publish about problems associated with statins are often very
bitter: they feel they are up against a tremendous political bias and going
against an incredibly powerful industry. Med Journal editors tend to insist
that all negative findings be couched in terms of how, overall, the statins
are doing tremendous good, and the major studies finding problems with
statins have been the subject of a pro-statin editorial in the same journal.
Further, the popular press is extremely reluctant to cover negative research
findings for the companies who are among their heaviest advertisers.
OK, I understand the doctor's need to read clinical study results, but where
can I find out what other people are experiencing in plain language, and
maybe share my experiences?
The Dispace statin boards are an excellent source:
Lipitor: http://forum.ditonline.com/viewboard.php?BoardID=38
Zocor: http://forum.ditonline.com/viewboard.php?BoardID=41
Lescol: http://forum.ditonline.com/viewboard.php?BoardID=37
Pravachol: http://forum.ditonline.com/viewboard.php?BoardID=40
Mevacor: http://forum.ditonline.com/viewboard.php?BoardID=39
AARP ran an article on statin drugs and asked for responses, these posts
start at:
http://community.aarp.org/n/mb/message.asp?webtag=rp-health&msg=743.1
(at the bottom of the page, you can click to the next post)
Another board:
http://www.rxlist.com/rxboard/lipitor.pl
http://www.rxlist.com/rxboard/lescol.pl
http://www.rxlist.com/rxboard/mevacor.pl
http://www.rxlist.com/rxboard/pravachol.pl
http://www.rxlist.com/rxboard/zocor.pl
WebMD has a roundtable on Cholesterol:
http://boards.webmd.com/roundtable_topic/1121
Also, there is a newsgroup (access via your email program):
sci.med.cardiology
Are there any books on the topic?
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 has written an excellent book about
statin-related memory loss and amnesia, "Lipitor, Thief of Memory",
available through Amazon.com and elsewhere, with more info available 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
As of mid-January, 2005, you can buy Dr. Graveline's second statin book,
"Statin Drugs - Side Effects and the Misguided War on Cholesterol."
See:
http://www.spacedoc.net/statin_side_effects.html
What are the Liptior warnings and side-effects listed by the manufacturer on
the physicians' information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp . Summary of some of the items on the
website includes Warnings of liver dysfunction, and skeletal muscle
rhabdomyolysis for the physicians information updated as of July 2004.
What are the Lipitor Adverse Events in Placebo-Controlled Studies listed by
Pfizer in the Physician's information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp, the information below is from the
version updated as of April 2002:
Body as a whole: Infection, Headache, Accidental Injury, Flu Syndrome,
Abdominal Pain, Back Pain, Allergic Reaction, Asthenia;
Digestive system: Constipation, Diarrhea, Dyspepsia, Flatulence;
Respiratory system: Sinusitis, Pharyngitis;
Skin and Appendages: Rash;
Musculoskeletal system: Arthralgia, Myalgia.
What are the Lipitor Averse Events reported in patients treated with Lipitor
in clinical trials listed by Pfizer in the Physician's information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp, the information below is from the
version updated as of April 2002:
Body as a Whole: Chest pain, face edema, fever, neck rigidity, malaise,
photosensitivity reaction, generalized edema.
Digestive System: Nausea, gastroenteritis, liver function tests abnormal,
colitis, vomiting, gastritis, dry mouth, rectal hemorrhage, esophagitis,
eructation, glossitis, mouth ulceration, anorexia, increased appetite,
stomatitis, biliary pain, cheilitis, duodenal ulcer, dysphagia, enteritis,
melena, gum hemorrhage, stomach ulcer, tenesmus, ulcerative stomatitis,
hepatitis, pancreatitis, cholestatic jaundice.
Respiratory System: Bronchitis, rhinitis, pneumonia, dyspnea, asthma,
epistaxis.
Nervous System: Insomnia, dizziness, paresthesia, somnolence, amnesia,
abnormal dreams, libido decreased, emotional lability, incoordination,
peripheral neuropathy, torticollis, facial paralysis, hyperkinesia,
depression, hypesthesia, hypertonia.
Musculoskeletal System: Arthritis, leg cramps, bursitis, tenosynovitis,
myasthenia, tendinous contracture, myositis.
Skin and Appendages: Pruritus, contact dermatitis, alopecia, dry skin,
sweating, acne, urticaria, eczema, seborrhea, skin ulcer.
Urogenital System: Urinary tract infection, urinary frequency, cystitis,
hematuria, impotence, dysuria, kidney calculus, nocturia, epididymitis,
fibrocystic breast, vaginal hemorrhage, albuminuria, breast enlargement,
metrorrhagia, nephritis, urinary incontinence, urinary retention, urinary
urgency, abnormal ejaculation, uterine hemorrhage.
Special Senses: Amblyopia, tinnitus, dry eyes, refraction disorder, eye
hemorrhage, deafness, glaucoma, parosmia, taste loss, taste perversion.
Cardiovascular System: Palpitation, vasodilatation, syncope, migraine,
postural hypotension, phlebitis, arrhythmia, angina pectoris, hypertension.
Metabolic and Nutritional Disorders: Peripheral edema, hyperglycemia,
creatine phosphokinase increased, gout, weight gain, hypoglycemia.
Hemic and Lymphatic System: Ecchymosis, anemia, lymphadenopathy,
thrombocytopenia, petechia.
What are the Lipitor Adverse events associated with Lipitor therapy reported
since market introduction, that are not listed above, listed by Pfizer in
the Physician's information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp It includes the following:
anaphylaxis, angioneurotic edema, bullous rashes (including erythema
multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), and
rhabdomyolysis.
REPORTING ADVERSE EFFECTS FROM STATINS
Where should I report adverse effects from statins?
Report to the FDA, http://www.fda.gov/medwatch/how.htm
Also, it is important to report side-effects to the Statin Study, funded by
the National Institutes of Health and conducted at the University of
California, San Diego.
Statin Study website: http://medicine.ucsd.edu/statin/
with contact info at:
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
Dr. Golomb, the principal investigator of the Statin Study, is an incredibly
intelligent and active woman. Take a look at her Curriculum Vitae at:
http://www.medicine.ucsd.edu/faculty/golomb/
OK, what should I take to my doctor?
The citations below are grouped by different categories of damage. You can
take the entire list, but it may be better to select those areas that
describe the adverse effects you are concerned with. You would do well,
however, to look at all of them, as people frequently have other concerns
they thought were unrelated until viewing the list of adverse effects.
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?
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=Abstract&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=Abstract&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=Abstract&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=12549960&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=Abstract&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=12639733&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=7745415&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=7484806&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=8172444&dopt=Abstract
Medication-induced peripheral neuropathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12507417&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)
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
Studies & Links in chronological order, with the latest on top:
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=12885101&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 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=12820814&dopt=Abstract
Full Study Text free on Medscape:
http://www.medscape.com/viewarticle/456866
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=10806282&dopt=Abstract
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=PXke2H8h99pyNVSCajAh5clptzOAHJSZuNBobSwWmi9veWjdJ2A3%7C-1468812056489609316/184161392/6/7001/7001/7002/7002/7001/-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/ADRMonth%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=9737641&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=8864188&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?
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 book about 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
forstatin-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."
COENZYME Q10 (UBIQUINONE) DEFICIENCY CAUSED BY STATINS
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12353945&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/dailys/02/May02/052902/02p-0244-cp00001-01-vol1.pdf+Statin-Induced+Cardiomyopathy+Introduction+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-Exhibit_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
"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 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: Passi 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 associated 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=2247468&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=11479481&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=11505177&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+statin+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=12011277&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:
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=12672737&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=12573193&dopt=Abstract
Baylor College of Medicine, One Baylor Plaza, Room 525D, Houston, TX 77030,
USA. jfarmer@bcm.tmc.edu
CARNITINE DEFICIENCY CAUSED BY STATINS
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
JOINT PAIN AND STATINS
Frequently Asked Question: Can statins have something to do with my joint
pain?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11707010&dopt=Abstract
Four cases of tendinopathy in patients on statin therapy.
Joint Bone Spine. 2001 Oct;68(5):430-3. PMID: 11707010 [PubMed - indexed for
MEDLINE]
Abstract on a report of 4 cases of people with painful tendons & statins.
Included to show that the pain and damage shows up in a variety of areas.
QUITTING STATINS
Frequently Asked Question: Can it be dangerous to just stop taking statins?
One study indicates that there are more coronary events when people stop
taking statins (Definitely talk with your doctor on this):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11914253&dopt=Abstract
Withdrawal of statins increases event rates in patients with acute coronary
syndromes. The dangers of getting off statins. See also:
http://www.lipidsonline.org/commentaries/al_abstract.cfm?abs_id=Abs030
STATIN BIRTH DEFECTS
Frequently Asked Question: Is statin intake during pregnancy dangerous for
unborn children?
Edison RJ, Muenke M.
Central nervous system and limb anomalies in case reports of
first-trimester statin exposure.
N Engl J Med. 2004 Apr 8;350(15):1579-82. No abstract available.
PMID: 15071140 [PubMed - indexed for MEDLINE]
VIOLENCE AND LOW CHOLESTEROL
Frequently Asked Questions: Can it be the statins making me so irritable and
prone to angry outbursts?
It may be that the angry outbursts are caused by the Low Cholesterol, the
result of taking Lipitor or other statins.
Dr. Beatrice Golomb, who is now conducting the NIH funded Statin Study,
published 2 articles/studies on the connection between violence and low
cholesterol levels.
See:
Low cholesterol and violent crime. Golomb BA, Stattin H, Mednick S.
Department of Medicine, University of California, Los Angeles, CA
92093-0995, USA. J Psychiatr Res 2000 Jul-Oct;34(4-5):301-9
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11104842&dopt=Abstract
and
Cholesterol and violence: is there a connection? Golomb BA. Ann Intern Med
1998 Mar 15;128(6):478-87
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9499332&dopt=Abstract
IMMUNE SYSTEM AND STATINS
Frequently Asked Question: Can statins depress my immune system?
It is a tribute to the imaginations of the drug marketers to see how
successfully they have put positive "spin" on a very alarming proposition,
that statins depress the immune system (or is it just arrogance?). If the
known side effect of statins is to depress your immune system, and it is so
beneficial to transplant recipients and others with autoimmune disease, what
about people with pre-statin 'normal' immune systems?
I'm not the only one astonished and disgusted with this, check out Dr.
Mercola's comment (scroll down for his response to the article) on
http://www.mercola.com/2000/dec/24/statins.htm
Excerpts: "This is an amazing example of positive "spin" put on a very
negative result. People with high cholesterol certainly don't need their
immune systems suppressed...If suppressing the helper T cells is considered
such great benefit then there is a disease going around that does this quite
well - AIDS...if the mechanism of action of the drug is not understood, how
can the manufacturer or the FDA claim that it is safe"
It sounds like he is talking about this article
http://pub.ucsf.edu/today/print.php?news_id=200211062 , but actually he is
describing the last time the drug companies tried to feed us a myth about
how great it is that statins depress immune systems: (available for online
purchase from Nature Medicine:
http://www.nature.com/dynasearch/app/dynasearch.taf?sp-w=Exact&_action=search&search_fulltext=&sp-p=All&search_volume=&search_startpage=&search_title=&search_author=&search_abstract=statins+as+immunosuppressors&issue_start_month=12&issue_start_year=2000&issue_end_month=01&issue_end_year=2001&pickerCount=You+have+selected+1+journal+to+search.&rolloverMessage=&sp_k=NM
Atorvastatin suppresses interferon-gamma -induced neopterin formation and
tryptophan degradation in human peripheral blood mononuclear cells and in
monocytic cell lines.
Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D.
Summary: Recent findings indicate that statins also have anti-inflammatory
properties and can modulate the immune response.statins inhibit T cell
activation within the cellular immune response.atorvastatin directly
inhibits IFN-gamma-mediated pathways in monocytic cells, suggesting that
both immunoreactivity of T cells and of monocyte-derived macrophages are
down-regulated by this statin.
Clin Exp Immunol 2003 Feb;131(2):264-7
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12562386&dopt=Abstract
A novel anti-inflammatory role for simvastatin in inflammatory arthritis.
Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R,
Campbell C, Gracie JA, Liew FY, McInnes IB.
J Immunol. 2003 Feb 1;170(3):1524-30.
PMID: 12538717 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12538717&dopt=Abstract
Immunomodulation: a new role for statins?
Wulf Palinski
SUMMARY: Statins reduce the expression of the class II major
histocompatibility complex (MHCII) by arterial cells, leading to a decreased
T-cell response. This indicates that statins...
Nature Medicine6, 1311 - 1312 (01 Dec 2000) News and Views
HMG-CoA reductase inhibitors as immunomodulators: potential use in
transplant rejection.
Raggatt LJ, Partridge NC.
These findings suggest that statins have the potential to regulate an immune
response in vivo and that more investigation is essential in order to
explain the opposing clinical data.
Drugs. 2002;62(15):2185-91.
PMID: 12381218 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12381218&dopt=Abstract
Statins as a newly recognized type of immunomodulator
Brenda Kwak, Flore Mulhaupt, Samir Myit, François Mach
SUMMARY: Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase, or statins, are effective lipid-lowering agents, extensively used
in medical practice. Statins have never been shown to...
Nature Medicine 6, 1399 - 1402 (01 Dec 2000) Article
and could a depressed immune system lead to infection? See:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11936540&dopt=Abstract
Statin-induced fibrotic nonspecific interstitial pneumonia.
Eur Respir J. 2002 Mar;19(3):577-80.
PMID: 11936540 [PubMed - indexed for MEDLINE]
STATINS AND CANCER
Frequently Asked Question: What are the cancer rates for people on statins?
Despite the infomercial-type hype in recent press releases under titles
like, "Does Lipitor prevent cancer?" (note it is a question, not an
assertion), the numbers from recent studies tell the opposite story:
Statin use and the risk of breast cancer.
Beck P, Wysowski DK, Downey W, Butler-Jones D.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12725884&dopt=Abstract
J Clin Epidemiol. 2003 Mar;56(3):280-5.
PMID: 12725884 [PubMed - in process]
"Stratified analyses revealed increases in risk in short-term statin users
and statin users with long-term hormone replacement therapy (HRT) exposure."
The PROSPER Study (PROspective study of pravastatin in the elderly at risk)
[Article in French]
Kulbertus H, Scheen AJ.
Service de Diabetologie, Nutrition et Maladies metaboliques et deMedecine
Interne Generale, CHU Liege.
Rev Med Liege. 2002 Dec;57(12):809-13.
"New cancers were more frequent amongst pravastatin-treated individuals
(+25%; p = 0.020)."
Major Outcomes in Moderately Hypercholesterolemic, Hypertensive Patients
Randomized to Pravastatin vs Usual Care
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT-LLT)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12479764&dopt=Abstract
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research
Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial.
Deaths by cancer during the ALLHAT study: Pravastatin= 163; Usual Care= 148
6-year rate per 100 Participants: Pravastatin= 4.1; Usual Care= 3.7
ERECTILE DYSFUNCTION (ED) AND STATINS
Frequently Asked Question: Can statins interfere with my life?
Do lipid-lowering drugs cause erectile dysfunction? A systematic review.
Rizvi K, Hampson JP, Harvey JN.
University of Wales College of Medicine, Wrexham Academic Unit, Wrexham, UK.
Fam Pract. 2002 Feb;19(1):95-8. PMID: 11818357
BACKGROUND: Erectile dysfunction (ED) is common although under-reported by
patients. Along with the better known causes of ED, drug-induced impotence
needs to be considered as a cause of this symptom. Lipid-lowering drugs have
been prescribed increasingly. Their relationship to ED is controversial.
OBJECTIVES: Our aim was to clarify the relationship between lipid-lowering
therapy and ED. A secondary aim was to assess the value of the systematic
review procedure in the area of adverse drug reactions. METHODS: A
systematic review was carried out using computerized biomedical databases
and Internet sources. Terms denoting ED were linked with terms referring to
lipid-lowering drugs. Information was also sought from regulatory agencies.
RESULTS: A significant literature was identified, much from obscure sources,
which included case reports, review articles, and information from clinical
trials and from regulatory agencies. Information from all of these sources
identified fibrates as a source of ED. A substantial number of cases of ED
associated with statin usage have been reported to regulatory agencies. Case
reports and clinical trial evidence supported the suggestion that statins
can also cause ED. Some information on possible mechanisms was obtained, but
the mechanism remains uncertain. CONCLUSIONS: The systematic review
procedure was applied successfully to collect evidence suggesting that both
statins and fibrates may cause ED. More numerous reports to regulatory
agencies complemented more detailed information from case reports to provide
a new perspective on a common area of prescribing.
lementRay MoynihanBMJ 2003; 326: 1189-1192.http://bmj.com/cgi/content/full/326/7400/1189 full texthttp://bmj.com/cgi/reprint/326/7400/1189 pdfWho pays for the pizza? Redefining the relationships between doctors anddrug companies. 2: DisentanglementRay MoynihanBMJ 2003; 326: 1193-1196.http://bmj.com/cgi/content/full/326/7400/1193 full texthttp://bmj.com/cgi/reprint/326/7400/1193 pdfHow to dance with porcupines: rules and guidelines on doctors' relationswith drug companiesElizabeth WagerBMJ 2003; 326: 1196-1198.http://bmj.com/cgi/content/full/326/7400/1196 full texthttp://bmj.com/cgi/reprint/326/7400/1196 pdfHow can research ethics committees protect patients better?Silvio Garattini, Vittorio Bertele, and Luca Li BassiBMJ 2003; 326: 1199-1201.http://bmj.com/cgi/content/full/326/7400/1199 full texthttp://bmj.com/cgi/reprint/326/7400/1199 pdfMedical journals and pharmaceutical companies: uneasy bedfellowsRichard SmithBMJ 2003; 326: 1202-1205.http://bmj.com/cgi/content/full/326/7400/1202 texthttp://bmj.com/cgi/reprint/326/7400/1202 pdfUnhealthy spinBob Burton and Andy RowellBMJ 2003; 326: 1205-1207.http://bmj.com/cgi/content/full/326/7400/1205 texthttp://bmj.com/cgi/reprint/326/7400/1205 pdfRelationships between the pharmaceutical industry and patients'organisationsAndrew HerxheimerBMJ 2003; 326: 1208-1210.http://bmj.com/cgi/content/full/326/7400/1208 texthttp://bmj.com/cgi/reprint/326/7400/1208 pdfJournals should select drug advertisements more carefullyJames J Oliver and Simon R MaxwellBMJ 2003; 326: 1211. http://bmj.com/cgi/content/full/326/7400/1211Charities and patient groups should declare interestsJenny HirstBMJ 2003; 326: 1211.http://bmj.com/cgi/content/full/326/7400/1211-aBioethics are difficult to balanceAsad J RajaBMJ 2003; 326: 1215.http://bmj.com/cgi/content/full/326/7400/1215-cThen check out the astonishing articles on medical ghostwriting, starting athttp://www.cbc.ca/consumers/market/files/health/ghostwriting/index.htmlIt may inspire you to earn extra income, because it points out that aMedical Ghostwriter can make $100,000 per year writing favorable drugreports! YMMVDifficult to question if there is bias in drug-industry studies afterreading the above.Two recent examples of bias in the presentation of pivotal findings are:1) Dr. Gaist's study that proves statins cause polyneuropathyhttp://213.4.18.135/87.pdf. If you read the entire research article, youwill note the vast difference between his findings and the tone of thedescriptive abstract, which tends to water down the findings. Further, thejournal ran an editorial that provided further pro-statin spin as damagecontrol.2) The ALLHAT study, published in JAMA, was the largest to date. It ran foryears and encompassed 10,000 people. Their study websitehttp://allhat.sph.uth.tmc.edu/default.htm These folks were funded by NIH,and they have published what the drug companies do not want to hear: thatstatins do not prevent deaths. Again, there was a pro-statin damage controleditorial in the same issue, and the news carriers did not highlight thefindings. In fact, CNN buried it inside an article on the other finding:that diuretics worked better than other blood-pressure medications, where noreader looking for cholesterol drug results would find it.======Glossary of some search terms & equivalents:Lipitor = atorvastatinCoenzyme Q10 = CoQ10 = Ubiquinone = UbidecarenoneStatins = hydroxymethylglutaryl coenzyme A reductase inhibitors = HMG-CoAReductase InhibitorsLipitor, Mevacor, Pravachol, Zocor, Lescol, and Baycol = atorvastatin,cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatinMore to come: FAQs with published medical research on other aspects ofstatin adverse effects.
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