statins and myoglobin

7/23/2019 Statins and Myoglobin

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Statins and Myoglobin:

How Muscle Pain and Weakness Progress

toHeart, Lung and Kidney Failure

by Stephanie Seneff

[email protected] 28, 2010.

Translation into Danish by Daniela Milton

Slovenian translationcourtesy of as!er "ali!ovich

Translation into Macedonian by #etra $lasic%a&

! "ntroduction

Statin dru' use has steadily increased over the last several decades, due to the (ides!read

belief that cholesterol reduction is an im!ortant ste! in !reventin' heart disease. )t isundeniable that statins are effective* they can decrease serum cholesterol levels from over +00db%ml to (ell (ithin the normal ran'e in a matter of (ees. -or a !erson (ho already hasnormal cholesterol levels, statins can drive their cholesterol do(n to levels not seen in nature.Statins have also been sho(n to reduce the relative ris of heart attacs in men in their 0/s

by as much as +0, but, because heart attacs are relatively rare for this se'ment of the!o!ulation, the absolute ris reduction is only on the order of 2, a !oint that is often missedby the !erson bein' treated.

ll dru's have !otential side effects, and (ith any dru' it/s a matter of (ei'hin' theris%benefit factors to decide (hether the dru' is (arranted. Statin dru's have a remarablydiverse set of side effects, includin' co'nitive and memory im!airment, reduced libido, andmuscle !ain and (eaness. The dru' manufacturers claim that the incidence of side effects isrelatively rare, but often side effects don/t a!!ear until after several months or even years intotreatment. )n many of these cases, it may not be obvious that the statin dru' is the cause ofthe !roblem. This is es!ecially true because these side effects can easily be attributed toincreasin' a'e. )n fact, as ) (ill sho( later, statin side effects can best be inter!reted as anacceleration of the a'in' !rocess.

)n my vie(, statin dru's are never (orth the ris of their side effects. holesterol is a vitalnutrient, (ithout (hich mammalian cells can not survive, and it is inconceivable to me that
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cri!!lin' the body/s ability to synthesi3e cholesterol can ever be a 'ood idea. )n an e4cellentand hi'hly informative revie( article !ublished in 2005, 6ain(ri'ht et al. 7+9 develo!ed astron' ar'ument that statin dru's, by de!letin' cholesterol, lead to a destabili3ation of cellmembranes :from head to toe.: This !roblem, in turn, increases ris to a lon' list of serioushealth conditions and diseases, includin' diabetes, multi!le sclerosis, co'nitive !roblems,

hemorrha'ic stroe, cancer, and even ;S revie(ed ?ournal !ublications. ) have ar'ued in !revious essays that statins may increase theris to l3heimer/s disease, as (ell as tose!sis, cancer, and heart failure.

The most commonly re!orted side effects to statin thera!y are muscle !ain and (eaness. )fleft uncheced, these sym!toms can !ro'ress to rhabdomyolysis


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to a hu'e list of !otential health !roblems. G4actly ho( an individual res!onds de!ends u!ontheir 'enetic mae>u!* faced (ith a deficiency, the body (ill decide to sacrifice certain cellty!es in order to safe'uard certain other cell ty!es. So, one !erson may develo! l3heimer/s

because the brain/s neurons are sacrificed, (hile another succumbs to heart failure orrhabdomyolysis oen3yme . Several more ste!s !roduce cholesterol from mevalonate. Mevalonate is alsothe !recursor to a lar'e number of other biolo'ically active molecules that are im!ortant for

!ro!er cell function. These include the antio4idants, coen3yme F10 and the dolichols, assho(n in the fi'ure to theri'ht.

The so>called :bad:cholesterol, ;D;, deliverscholesterol, fats, andantio4idants from the liver toall the cells of the body. llcells need both fats andcholesterol to maintain healthymembranes, not only in theouter cell (all, but also in themembranes encasin' thenucleus, the mitochondria


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final (ay that statins can dama'e cells is throu'h their entry mechanism. Statins belon' toa class of dru's called :am!hi!hilic: dru's 729 that mana'e to brea throu'h the cell (all ins!ite of bein' relatively lar'e. They act lie a soa! by essentially dissolvin' a section of thecell membrane. This leaves behind a hole in the (all, (hich needs to be !atched u!, as (ellas debris (hich must be cleaned u! and recycled by the lysosomes. To !atch the hole reAuires

ne( sources of both fats and cholesterol, (hich come from the ;D; !articles, (hose su!!lyis 'reatly reduced due to the statin dru'. So it becomes increasin'ly difficult over time for thecell to re!air all the holes introduced by the statin dru' molecules. s the cell (all becomesmore !ermeable due to !revious e4!osure to an am!hi!hilic dru', the amount of dru' thatsuccessfully enters the cell steadily increases over time, leadin' to ever 'reater internalconcentrations of the dru'.

(! Statins, Muscle Pain and Weakness, and )habdo&yolysis

Muscle cells have tremendous ener'y needs, !articularly if the !erson has been !ut on ane4ercise re'imen as !art of their treatment !ro'ram. The heart, in !articular, never rests. )thas to ee! on beatin' 24 at the rate of at least once every second. "ence the heart ises!ecially de!endent on coen3yme F10 to re!lenish the T# consumed every time itcontracts and !ushes blood from one chamber to another and out the aorta.

The !harmaceutical industry readily admits that statin thera!y may cause muscle !ain and%ormuscle (eaness in some cases, but they claim that the incidence of these side effects issmall, on the order of 2. "o(ever, observational studies have sho(n that at least 10 to1 of statin users com!lain of muscle !ain 7C9709. The actual number (ho e4!erience !ainor (eaness is liely to be much lar'er, ho(ever, because many !eo!le are una(are that thisis a !otential side effect. -urthermore, it sometimes taes several years of cumulative statin

dama'e before the sym!toms become intolerable. #eo!le are often (illin' to believe thattheir aches and !ains and 'enerally (eaenin' condition are sim!ly due to 'ettin' older.

The reaction by the 'eneral community to a relatively beni'narticle !osted by 6ebMD onmuscle !ain su''ests that the !roblem is much (orse than is 'enerally acno(led'ed. ver200 often len'thy comments describe many very sad stories often the doctor (as alsomisinformed, and denied that the !ain could be due to the statin dru'. case in !oint isdescribed in thisKe( Lor Times article. (oman in Iansas had been tain' a statin foryears to reduce her cholesterol. ver that same time !eriod, she e4!erienced chronic muscle

!ain (hich neither she nor her doctor attributed to the statin thera!y. )t even led to a uselessshoulder o!eration. "er !roblem eventually escalated into sin lesions caused by a reaction to

to4ic !rotein by>!roducts released by her disinte'ratin' muscles. She (as 'iven an antifun'alto treat the sin lesions, another misdia'nosis. But the antifun'al interacted (ith the statins729 to further increase the severity of her muscle disorders. Three months later, she could

barely stand, and her !ulmonary muscles (ere so (ea she couldn/t breathe. She died shortlythereafter.

Hhabdomyolysis is a condition (here the muscles ra!idly disinte'rate due to an in?ury, often,for e4am!le, !hysical trauma follo(in' an accident. But Hhabdomyolysis is also a rare sideeffect of statins >> essentially (here the muscle !ain and (eaness are e4treme. Some !eo!lereact immediately to statin thera!y (ith severe rhabdomyolysis, and it is often fatal, due toacute renal failure > there is even a no(n case (here a sin'le
http://blogs.webmd.com/cholesterol-management/2008/02/statins-and-muscle-pain.htmlhttp://blogs.webmd.com/cholesterol-management/2008/02/statins-and-muscle-pain.htmlhttp://blogs.webmd.com/cholesterol-management/2008/02/statins-and-muscle-pain.htmlhttp://web.mit.edu/mwpstr/www/brody/http://blogs.webmd.com/cholesterol-management/2008/02/statins-and-muscle-pain.htmlhttp://blogs.webmd.com/cholesterol-management/2008/02/statins-and-muscle-pain.htmlhttp://web.mit.edu/mwpstr/www/brody/


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statin dose caused rhabdomyolysis 7219. ne of the statins, Baycol, (as abru!tly taen off themaret in 2001, after +1 !eo!le died from subseAuent rhabdomyolysis.

*! How Muscles Maintain their +nergy Supply

)n this section and the ne4t, ) (ill describe the metabolic !ath(ays involved in assurin' thatmuscle cells have enou'h ener'y to contract. 6hen o4y'en is available, and (hen it can besafely e4!loited, the muscle can decom!ose food sources into carbon dio4ide and (ater, byconsumin' the o4y'en. But o4y'en, (hile life>'ivin', is also a very dan'erous substance, andif the !rocess is not orchestrated e4actly accordin' to !lan, there can be a lot of collateraldama'e due to the (ron' substances reactin' (ith the o4y'en. s you (ill see later,myo'lobin, (hich is res!onsible for bufferin' o4y'en and deliverin' it from the cell (all tothe mitochondria, !ics u! a lot of the collateral dama'e. This aerobic metabolic !rocess istermed res!iration, and it taes !lace inside s!ecial or'anelles called mitochondria, (hosesole res!onsibility is to di'est foods and 'enerate ener'y for the cell.

6henever o4y'en is in short su!!ly, or if the mitochondria are dysfunctional, the cell hasalternative (ays to 'enerate ener'y reAuirin'= !rocesses that are seAuestered(ithin s!ecial ener'y>'eneratin' subre'ions of the cell called mitochondria. This aerobicmetabolic !rocess is hi'hly efficient, 'eneratin' as many as +0 units of T#


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nfortunately, the !rocess ofmetaboli3in' food sources forener'y is Auite com!le4. ) havefound t(o ima'es (hich de!ictfood metabolism in

com!lementary (ays, (hereone


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The smallfi'ure to theleft sho(s aschematic of amitochondrion,

and the lar'erfi'ure belo(sho(s a moredetailede4!lanation ofthe electrontrans!ort chain

!rocess thattaes !lace

alon' the (all enclosin' the mitochondrion, 'eneratin' a lar'e !ercenta'e of the cell/s ener'yneeds in the !rocess. The electron trans!ort chain in?ects !rotons & "2 at the ri'ht of the fi'ure=, since the chain of eventsis held u! at the :F: !osition. $arious hi'hly to4ic char'ed ions containin' o4y'en, such as>", "22


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! Managing +nergy -eeds 'uring +.tre&e +.ercise

6henever a healthy !erson e4!eriences e4treme e4ercise, such as runnin' a 00 meter dash,the muscles are challen'ed to come u! (ith sufficient T# to satisfy their ener'y needs. Botho4y'en and 'lucose can become de!leted. To com!ensate for these deficiencies, muscle cells

have devised a com!le4 set of strate'ies, (hich o!erate in the cyto!lasm instead of in themitochondria. They involve a number of en3ymes that (ill resurface later in our story, sincethey are the en3ymes that are monitored to determine (hether statin dru's are dama'in'muscles and%or the liver.

s you/ve already seen, one o!tion is to 'enerate lactic acid anaerobically called 'lucose>alaninecycle. The alanine, derived from muscle !rotein, is released into the blood and shi!!ed to theliver to be utili3ed for ener'y 'eneration, as sho(n in the accom!anyin' fi'ure. The liver canthen 'enerate more 'lucose from the alanine throu'h 'luconeo'enesis, (hile e4!ortin' the(aste !roduct, urea, to the idneys for e4cretion. This also allo(s the liver to re'eneratesome T# to hel! satisfy its o(n ener'y needs, (hich are very lar'e durin' such stressfulconditions. The 'lucose is shi!!ed throu'h the blood stream to the muscle cell, (hich ea'erlytaes it u! to 'enerate more T# for itself. The anaerobic !rocessin' of 'lucose yields

!yruvate (hich can also be turned into alanine, but it needs yet another en3yme to (or.Thus, (henever !yruvate can/t be sent to the mitochondria because of insufficient o4y'en, it

can instead be converted to alanine (ith the hel! of an en3yme, ;T


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)n the above discussion,several en3ymes have beenidentified that must be !resentfor these cyto!lasmic ener'y>'eneratin' !rocesses to

function. These includecreatine inase, lactatedehydro'enase, and ;T. Theso>called liver en3yme test thatis conducted routinely (ithstatin users measures theconcentration of ;T in the

blood. Muscle en3yme testsdetect creatine inase andlactate dehydro'enaseconcentrations in the blood. So

these tests are all measurin'these !articular en3ymes

because they si'nal thatmuscles are !referentially

!rocessin' 'lucoseanaerobically in the cyto!lasminstead of aerobically in themitochondria i.e., themitochondria are not (orin'

!ro!erly. Lou should ee! this!oint in mind as (e (ill revisitit later on.

/! +.tre&e +.ercise can lead to )habdo&yolysis

6hen !eo!le en'a'e in e4treme e4ercise such as lon' distance marathon runnin' or (ei'ht>bearin' e4ercises, they run the ris of causin' serious dama'e, both to their muscles and totheir idneys, due to the stress im!osed on their system in tryin' to maintain adeAuate ener'yto fuel the muscles. )t has become common !ractice to measure the levels of creatine inasein the blood as a no(n indicator of !otential dama'e 79. !erson (hose creatine inaselevel 'ets alarmin'ly hi'h (ill liely need immediate medical attention to avoid renal

7idney9 failure.

The cause of the idney failure is most liely myo'lobin that has been dum!ed into the bloodstream by com!romised or dead muscle cells, due to rhabdomyolysis. )f too much myo'lobinis released, !articularly (ith inadeAuate (ater su!!ly, the myo'lobin can bloc the renalfiltration system causin' a condition no(n as :acute tubular necrosis.: The !roblem can beeasily detected by observin' the color of the urine, (hich (ill be dar bro(n. study

!ublished in 2005 sho(ed that, in rhabdomyolysis, the dama'e to the idneys involves directinteraction bet(een myo'lobin and the mitochondria in the idney cells 7++9. The resultin'o4idation of the mitochondrial membranes leads to res!iratory failure and subseAuent celldeath.


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Myo'lobinuria is the term used to describe the !resence of myo'lobin in the urine, usuallydue to rhabdomyolysis. ccordin' to 7+9, 1 of !atients (ith severe myo'lobinuriadevelo! acute renal failure, and it is associated (ith hi'h mortality rates. Dialysis orintravenous fluids must be introduced fast enou'h, or the !erson (ill not be able to recover.

s early as 1551, a 'rou! of Ja!anese researchers 7+89 demonstrated that coen3yme F10could be administered orally to !rotect rats from muscle dama'e due to strenuous e4ercise.They also noticed that rats that (ere administered coen3yme F10 did not have elevated levelsof creatine inase and lactate dehydro'enase, (hereas the control rats did.

0! Myoglobin: $he 1ood, $he %ad, and the 2gly

Myo'lobin is a uniAue !rotein s!ecially ada!ted for muscle cells to hel! them (ith theirenormous needs for o4y'en. )ts !hysical structure is schemati3ed in the fi'ure on the ri'ht. )tresembles hemo'lobin in that it contains a central heme element


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'enerate ener'y is confined to the mitochondria in order to !rotect the constituents in thecyto!lasm as much as !ossible. But myo'lobin is tased (ith trans!ortin' o4y'en from thecell (all throu'h the cyto!lasm to the mitochondria. )t can/t avoid o4y'en e4!osure, and(hen it delivers the o4y'en, it necessarily has to come in contact (ith these to4icintermediate !roducts of the !rocess that ultimately converts o4y'en to (ater. ne of the

most im!ortant roles of coen3yme F10 in the muscle cells is to neutrali3e the dama'e tomyo'lobin caused by these o4idative a'ents.

6hen a !erson suffers from a heart attac


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n article !ublished in 2005by Iucera et al. 7229 nicelysums u! several no(n rolesof cholesterol in membranes*:holesterol is found in all

animal cell membranes and isreAuired for !ro!er membrane

!ermeability and fluidity. )t isalso needed for buildin' andmaintainin' cell membranes,and may act as an antio4idant.Hecently, cholesterol has also

been im!licated in cellsi'nalin' !rocesses, and issu''ested to enable li!id raftformation in the !lasma

membrane.: 7)bid, !. 1C+89The article 'oes on to describeho( cholesterol is able toorient itself (ithin themembrane either vertically


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Ty!ically in merica, if a !erson fails a stress test or suffers from a heart attac and then isfound to have a bloced coronary artery, a stent (ill be introduced to correct the !roblem andhi'h>dose statin thera!y (ill be initiated, (ith the e4!ectation that the dru' (ill be needed forthe rest of their life. The acce!ted belief today is that, no matter (hether their cholesterol isalready lo(, hi'h>dose statin thera!y (ill yield sufficient benefit to offset any side effects it

mi'ht cause. t the same time, these !atients are encoura'ed to s!end u! to an hour a daye4ercisin' on a treadmill, since e4ercise has been sho(n to be hi'hly beneficial to heartdisease !ro'nosis. The e4ercise, in con?unction (ith the metabolic deficiencies induced bythe statin dru', are a !otentially lethal combination.

Ty!ically, also, the !atient is not alerted that a common side effect of statin dru's is muscle!ain and muscle (eaness. )t is often the case that such sym!toms don/t a!!ear immediately.)n fact, it can sometimes be years before statin thera!y leads to enou'h dama'e to causeobvious sym!toms. By that time, the !erson may (ell believe that the !ain and (eaness aresim!ly a conseAuence of 'ettin' older.

)t has been (idely claimed, and statin users seem to have embraced this conce!t, that, as lon'as you monitor your en3yme levels, you can sim!ly terminate statin thera!y if the en3ymes'et too hi'h, and all (ill be (ell. "o(ever, ?ud'in' from some of the sad stories that aresho(in' u! in comment !a'es all over the (eb, this has turned out not to be the case forsome !eo!le.

n article !ublished in July, 2005 729 investi'ated the association bet(een !hysical muscledama'e and !atients/ com!laints of muscle (eaness or !ain. #atients (ho re!orted (eanesssaid, for e4am!le, that it (as difficult to 'et u! from a seated !osition (ithout arm su!!ort.Those (ho re!orted !ain 'enerally said that it (as (orse after !hysical e4ercise. nly oneout of !atients e4amined develo!ed overt rhabdomyolysis, (ith the serum level of themuscle en3yme creatine inase measured at ,C %;. This !atient reAuired hos!italtreatment for mana'ement of his !ain.

The authors (ere interested in investi'atin' the e4tent to (hich muscle dama'e could be seenthrou'h muscle bio!sy for these !atients. They com!ared them (ith 20 !atients (ho hadnever taen a statin dru'. T(enty five of the !atients tain' statins had clear muscledama'e. Kone of the 20 controls had any evidence of dama'e. ther than the one !atient (ithovert rhabdomyolysis, none of the others had muscle en3yme levels above the cut>offconsidered the u!!er level of :normal.: -or those !atients (ith in?uries, on avera'e 10 oftheir fibers (ere in?ured. The authors concluded that the lac of elevated levels of creatine

inase does not rule out structural muscle in?ury.

7! Statins and Heart Failure

!a!er titled sim!ly :;ovastatin decreases coen3yme F levels in humans: 71C9 statesuneAuivocally in the abstract* :)t is established that oen3yme F10 is indis!ensable forcardiac function.: The heart is a muscle, and hence it is sub?ect to all the same la(s of

!hysics as the seletal muscles. )t faces the same !roblem of fuel deficiency due to thevarious effects statins have on metabolism discussed above. "eart muscle cells (ould alsohave to cannibali3e themselves to 'et enou'h fuel, and (ould also suffer dama'e to their cellmembranes due to e4!osure to -erryl myo'lobin.


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n article !ublished in 200 729 !rovides a !lausible theory for the !rocess by (hich musclecells in the heart become dysfunctional (ith old a'e, leadin' ultimately to heart failure. Thear'ument blends !erfectly (ith the lo'ical deductions associated (ith the mechanism by(hich statins dama'e cells, and leads to the unavoidable conclusion that statins mae you a'eat an accelerated !ace. The !rocess involves a do(n(ard s!iral caused by deficiencies in both

the mitochondria and the lysosomes. Hecall that the mitochondria are res!onsible for!rovidin' fuel to the cell, and the lysosomes are res!onsible for di'estin' and decom!osin'residues of (aste !roducts. The article claims that the do(n(ard s!iral is caused by:continuous !hysiolo'ical o4idative stress.: 4idative stress is 'reatly enhanced by statins,

because they de!lete the su!!ly of both antio4idants lie coen3yme F10 and fresh!hos!holi!ids and cholesterol to rebuild dama'ed cell (alls. Debris from dama'ed!hos!holi!ids in the cell (all, the mitochondrial (alls, and the lysosome (alls must be taenu! by the lysosomes, di'ested, and dis!osed of. nder normal circumstances the lysosomes(ould easily brea them do(n in their hi'hly acidic environment, usin' their !o(erfuldi'estive en3ymes.

6hen the lysosomes are unable to di'est the debris that accumulates from dama'ed cell(alls, the residue that remains is called :li!ofuscin.: ;i!ofuscin is considered to be asi'nature of old a'e, accumulatin' in the liver, idney, heart muscle, and nerve cells as (e 'etolder. ;i!ofuscin is believed to be the !roduct of o4idation of unsaturated fatty acids, and isindicative of membrane dama'e, (hether to the cell/s outer (all or to the (alls of thelysosomes and mitochondria 719.

-or lon'>term statin users, li!ofuscin almost certainly accumulates, because their lysosomesare dysfunctional. This condition (ould arise not ?ust in the heart, but in all the cells of the

body. s ) mentioned earlier, statins cri!!le the !roduction of the dolichols, antio4idants that!lay a crucial role in !rotectin' the lysosomesfrom hydro'en ion leaa'e. ;ysosomes alsode!end u!on cholesterolin their membranes to !rovide additional insulation a'ainst char'edissi!ation. 6ith a constant leaa'e out(ard of "Nions, lysosomes can not maintain their !"at a sufficiently acidic level to allo( their en3ymes to (or. s a conseAuence, unde'radabledebris, i.e., li!ofuscin, accumulates (ithin the lysosomes, and the cell has no bacu! re!airsystem to salva'e the disaster. The last sentence in the abstract of 729 says* :This interrelatedmitochondrial and lysosomal dama'e eventually results in functional failure and death ofcardiac myocytes Pheart muscle cells9.:

Doctor #eter ;an's?oehn believes that statins are inducin' an e!idemic rise in the incidenceof heart failure. "e (rote* :)n my !ractice of 1 years in Tyler, Te4as, ) have seen a

fri'htenin' increase in heart failure secondary to statin usa'e, /statin cardiomyo!athy./ verthe !ast five years, statins have become more !otent, are bein' !rescribed in hi'her doses,and are bein' used (ith recless abandon in the elderly and in !atients (ith /normal/cholesterol levels. 6e are in the midst of a "- e!idemic in the S (ith a dramatic increaseover the !ast decade. re (e causin' this e!idemic throu'h our 3ealous use of statinsE )nlar'e !art ) thin the ans(er is yes. :


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very recent study called :interstitial lun' disease:


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miodarone is a !otent antidysrhythmic a'ent, i.e., a dru' used to try to correct an irre'ularheart beat durin' heart failure or !ost>o!erative. )t has numerous side effects, but !robablythe most serious side effect is interstitial lun' disease. n article (ritten in 2001 7+9 e4!loredthe liely mechanism of !ulmonary dama'e. The authors conducted in vitro e4!eriments oncells in lun' tissue e4tracted from hamsters. They noted that e4!osure to the dru' decreased

the mitochondrial membrane !otential


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)n addition to the above defects in the cell membrane, im!aired function of the mitochondriain the beta cells has also been clearly im!licated in diabetes, in studies involvin' diabeticmice (ith defective mitochondrial 'enes 7+59. These mice e4hibited reduced insulin secretion(hen they (ere only five (ees old, and their mitochondria (ere abnormal in a!!earanceand (ere unable to maintain an adeAuate char'e 'radient across their membranes. )n other

(ords, they e4hibited defects that are similar to (hat (ould be e4!ected (ith reducedcoen3yme F10 as a conseAuence of statin e4!osure. lder mice (ith the same defect (ereseverely deficient in insulin !roduction, as many of their !ancreatic beta cells had died off.

)nsulin su!!resses the release of fats from both the fat cells and the liver, and therefore there(ill be a fat shorta'e in the blood su!!ly subseAuent to insulin release, unless abundant fatsare already !resent. Thus, it is a 'ood strate'y, biolo'ically, for the beta cells to be sure fatsand cholesterol are (ell su!!lied before in?ectin' insulin into the blood stream. ) have

!reviously (ritten e4tensively on this sub?ect'eneratin' factory (ere functionin' !ro!erly. Let the reduced insulin ismain' it harder to 'et enou'h 'lucose in. This (ill force the cell into the starvation modethat leads to cannibali3ation of its internal muscle !rotein. The !erceived result over time (ill

be e4treme muscle (eaness.

(! 4onclusion

)f you live in the nited States, and your doctor has identified that you are at hi'h ris toheart attacs, he has liely !rescribed a hi'h dose statin even if your cholesterol levels are nothi'h. Lou have liely also been !ut on a lo(>fat, lo( saturated fat diet, and you have been

encoura'ed to (or out on a treadmill every day.

My research indicates that, if you ri'orously follo( all of your doctor/s advice, you (ill befacin' severe muscle dama'e sooner or later. The statin dru'/s im!act on the mitochondriaand on the cell (alls of the muscle cells is such that even modest e4ercise can lead torhabdomyolysis. -or some it (ill be obvious ri'ht a(ay that the side effects are too dama'in'and the statin thera!y must be terminated. -or others, the dama'e (ill ha!!en moreinsidiously, and (ill not become a!!arent until years after statin thera!y (as initiated. Butoften !atients (ill find that the sym!toms remain after the dru' is sto!!ed >> it (ill be too lateto re!air the muscle dama'e. r, (orse, they (ill develo! idney failure or heart failure as aconseAuence.
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Statin dru's have many adverse side effects, but !robably the most freAuent com!laintsconcern muscle !ain and muscle (eaness. )n this essay, ) have develo!ed a !hysiolo'icale4!lanation for the mechanism res!onsible for this side effect. )t is due to the fact that statinsinterfere (ith the synthesis of not only cholesterol, but also coen3yme F10 and the dolichols.Statins also reduce the bioavailability to the cells of both fatty acids and all dietary

antio4idants, due to the shar! reduction in serum levels of ;D;, (hich delivers theseessential nutrients to the cells.

6ithout sufficient coen3yme F10, muscle cells suffer from an im!aired ability to 'enerateener'y to fuel their contractions. They are forced to cannibali3e their o(n !roteins to survive.t the same time, !o(erful o4idative a'ents are 'enerated (hich dama'e the myo'lobin inthe cell, renderin' it both ineffective to trans!ort o4y'en and to4ic to the cell (all. Theo4idi3ed myo'lobin, no(n as :-erryl myo'lobin: is to4ic to the fatty acids that are the maincom!onent of the cell (all. 6ith insufficient cholesterol in the cell (all, the cell can/t hold achar'e, and this also causes it to (aste ener'y. The lysosomes are unable to di'est debris

because they can/t maintain a sufficiently acidic environment. The !roblem is further

com!ounded by !rofound shorta'es of cholesterol, (hich (ould have offered further!rotection a'ainst o4idative dama'e to the fatty acids and ion leaa'e in the cell (all, themitochondrial (all, and the lysosome (all. Gventually the cell disinte'rates and themyo'lobin is released into the blood stream. )t maes its (ay to the idneys, (hich try todis!ose of it. But the -erryl myo'lobin is also to4ic to the idneys, (hich leads to severeidney disease.

The lo(>fat diet and the e4ercise re'ime (ill both increase the lielihood that the statin dru'(ill cause !roblems. $i'orous e4ercise increases the ener'y needs of the muscles, (hile thelo(>fat diet reduces even further the bioavailability of fatty acids to re!lace dama'ed cell(alls. -urthermore, cell (alls com!osed of unsaturated fats are more vulnerable to attac bythe -erryl myo'lobin than those com!osed of saturated fats.

Because the heart is also a muscle, it also suffers from dama'e due to e4!osure to statins.This leads to a reduced lielihood of recoverin' from a diastolic heart attac, and anincreased chance of develo!in' heart failure. Dama'ed cells of the res!iratory system lead toan increased ris of both !neumonia and interstitial lun' disease, both of (hich are verydan'erous for someone (ith a (ea heart.

The J#)TGH trial revealed that the treatment 'rou! had a 2 increased ris for diabetes,and ) have e4!lained above (hy this (ould be true. Diabetes is a si'nificant ris factor for

heart disease, so this outcome is disturbin', and one (onders (hether the trial (as terminatedearly to avoid main' this number even (orse. Dr. 6illiam Davis, a cardiolo'ist (hobelieves that statins should be a last resort in treatin' heart disease, has this to say about theJ#)TGH trial* :) vie( the foistin' of restor via the J#)TGH ar'ument on the !ublic astain' full advanta'e of the hel!less situation many mericans find themselves in* Heduce fatintae, eat more healthy (hole 'rains and . . . cholesterol and H# syrocetR /Lou needrestorR See, ) told you it (as 'enetic,/ says the doctor after attendin' the nice straeneca>s!onsored dru' dinner.:< Dr. Davis/ Blo' #ost on J#)TGH=

The ne(s has ?ust come out that even children are no( bein' tested for hi'h cholesterol, andit is bein' su''ested that they should be !ut on a statin dru' if they can not control their

cholesterol levels


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no idea (hat ne'ative conseAuences statin dru's mi'ht have on the develo!in' nervoussystem of a child. "o(ever, it has been sho(n that statins can com!letely destroy the nervoussystem of an embryo 71+9.

remarable recent!ublication by Jeff ablere!orted adverse effects of statin thera!y by !atients. lthou'h the re!orts covered a(ide ran'e of no(n side effects of statins, includin' co'nitive im!airment, muscle !ain and(eaness, sin !roblems and se4ual dysfunction, (hat (as most disturbin' (as the lar'enumber of re!orts of severe neurolo'ical dama'e. Most distressin' (as the fact that there(ere a total of 1 re!orts of ;S (ith 2 additional re!orts related to motor neurondeterioration, (hich he counts to'ether as 1 to 'ive a total of 18. )n ;S, nerve cells (astea(ay or die, and can no lon'er send messa'es to muscles. This eventually leads to muscle(eaenin', t(itchin', and ultimately !aralysis. s the disease !ro'resses, s(allo(in' and

breathin' become difficult. Most victims die (ithin five years of dia'nosis.

The author/s comments related to neurolo'ical disorders and ;S are Auoted here* :ne

fra'ment of information that (as 'ained from the !atient accounts is the a!!arent incidenceof ma?or neurode'enerative diseases (hich may (ell have been !reci!itated by statin thera!y.... The rarest of these conditions is ;S and yet in ?ust +1 re!orts there (ere enou'h cases tohave made the !rediction > a study of the -D/s adverse event re!orts 7109 as (ell as a study sho(in' that hi'hcholesterol !rotects a'ainst ;S 7159. My ne4t essay (ill be on the sub?ect of statin dru's/liely adverse effects on the nervous system* ) (ill ar'ue that statins increase ris not ?ust to;S but to multi!le sclerosis, #arinson/s disease, and l3heimer/s.

8cknowledge&ents

) (ould lie to than lyn 6ain(ri'ht for !ointin' me to both his o(n e4cellent revie(!a!er and the very informative and fascinatin' article by "aines 7209 on !roton and sodiumleas throu'h li!id bilayers, (hich !layed a crucial role in my ar'uments for statin dama'e to

muscles.

)eferences

719 rduini, ;. Gddy, and #. "ochstein, :Detection of ferryl myo'lobin in the isolatedischemic rat heart,:Free-adic-!iol-Med"+.729 M. Baciu, S.. Sebai, . es, . Mulet, J.. lare, .. Shearman, and H.$. ;a(,Tem!ler H", #lisson , #arer , ee . :De'radative trans!ort of cationic am!hi!hilicdru's across !hos!holi!id bilayers.:#hilos Transact A Math #hys $ng %ci"Desethylamiodaronein )nitiation of miodarone>)nduced #ulmonary ytoto4icity,:$T


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$ol. 258, Ko. +, !!. 1280>1285.79 S.;. Bontin', #.J. van Breu'el, -.J. Daemen, :)nfluence of the li!id environment of the

!ro!erties of rhodo!sin in the !hotorece!tor membrane,:Adv" $xp" Med" !iol"85.79 #. Brancaccio, K. Maffulli, and -.M. ;imon'elli, :reatine inase monitorin' in s!ort

medicine:!ritish Medical !ulletin82. Ko. 1, !!. 205>2+0doi*10.105+%bmb%ldm017C9 G. Brucert, . "ayem, S. De?a'er, et al. :Mild to moderate muscular sym!toms (ithhi'h>dosa'e statin thera!y in hy!erli!idemic !atients >> the #H)M study.: Cardiovasc

'rugs Ther1.79 J. able, :dverse Gvents of Statins >> n )nformal )nternet>based Study,:&()M


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studies revealin' a deficiency of KD">cytochrome b reductase activity.:&" /eurol" %ci"0*1>1+, 1581.729 S. ;antue?oul, G. Brambilla, . Brambilla, and . Devouassou4, :Statin>induced -ibrotic

Kons!ecific )nterstitial #neumonia,:$ur espir &"80.729 H.S. ;ees and .M. ;ees, :Hhabdomyolysis from the oadministration of ;ovastatin

and the ntifun'al 'ent )tracona3ole,:/$&MCC.72C9 S.H. Ma?umdar, -.. Mclister, D.T. Gurich, H.S. #ad(al, and T.J. Marrie, :Statins andoutcomes in !atients admitted to hos!ital (ith community acAuired !neumonia* !o!ulation

based !ros!ective cohort study,:!M&induced myo'lobin o4idation,:Free adical

!iology and Medicine150doi*10.101C%?.freeradbiomed.200.02.018.7+09 D. #a!ahad?o!oulosa :KaN>INdiscrimination by VBR"induced muscular in?ury.:!iochem !iophys es Commun"


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;arsson, :)m!aired insulin secretion and beta>cell loss in tissue>s!ecific nocout mice (ithmitochondrial diabetes:/at 6enet"0.709 ". Sin3in'er, H. 6olfram, and B.. #esar, :Muscular side effects of statins,:&Cardiovasc #harmacol1.719 H. Suhi?a, MD, S.#raya'a, MD, M. Marashdeh, MD, . Bursac, #hD, M#", #. Iaar,

MD, D. Bansal MD, H. Sachdeva, MD, S.". Iesan, MD, and J.;. Mehta, MD, #hD, :Gffectof Statins on -astin' #lasma lucose in Diabetic and Kondiabetic #atients:&ournal of

)nvestigative Medicine55 doi*10.2+1%J)M.0b01+e+1815ec8b729 . Termana and .T. Brun :The 'in' Myocardium* Holes of Mitochondrial Dama'eand ;ysosomal De'radation,:*eart, 1ung and Circulation11 doi*10.101C%?.hlc.200.12.02+7+9 . 6ain(ri'ht, ;. Mascitelli, and M.H. oldstein, :holesterol>lo(erin' Thera!y andell Membranes. Stable #laAue at the G4!ense of nstable MembranesE:Arch" Med" %ci"25.79 T. 6aler, J. Mcaffery and . Steinfort, :#otential lin bet(een "M>o reductase

inhibitor ated alcium hannel-unction in #ancreatic Beta>ells,:$ndocrinology1.79 H.. a'er and I.M. Burhart, :Differential effects of 'lutathione and cysteine on -e2N,-e+N, "22 and myo'lobin>induced !ro4imal tubular cell attac,:Kidney )nernational1C2. doi*10.10C%?.12+>1.1558.00515.4

Statins and Myo'lobin* "o( Muscle #ain and 6eaness #ro'ress to "eart, ;un' and Iidney-ailure by Ste!hanie Seneffis licensed under a reative ommons ttribution +.0 nitedStates ;icense.
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statins and myoglobin

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