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CoenzymeQ10(Ubiquinone):ImplicationsinClinicalPractice
DeepakLangade*,PratibhaTarapure#,AbhayJagtap**,PreetiArora***,SanjeevAnand***

INTRODUCTION
Coenzyme Q10 (CoQ10) is a lipophilic compound naturally found throughout the body. It is an endogenously
synthesizedprovitaminthatservesasalipidsolubleelectroncarrierinthemitochondrialelectrontransport.1The
alternativenamesubidecarenoneandubiquinone,meaningubiquitousquinone,alludetothepresenceofCoQ10
inallcells.2ThecellulareffectsofCoQ10maybeimportantinpatientswithcardiacdiseasesespeciallycoronary
artery disease and congestive cardiac failure. It has been used as an adjunctive therapy for various
cardiovascularconditionsandinsomecountriesitisavailableasoverthecounternutritionalsupplement.
CoenzymeQ exists in several forms and can be found in microorganisms, plants and mammals including
humans.Coenzymesq6,q7,q8arefoundinyeastandbacteriawhereascoenzymeq9isfoundinratsandmice.
CoQ10 is prevalent in humans, with high endogenous concentration found in the heart, liver, kidney and
pancreas.CurrentCoQ10supplementsaremanufacturedbythefermentationofbeetsandsugarcane.

ItcanbesynthesizedinthebodythereforeCoQ10isnotconsideredtobeanessentialnutrient.Itispresentin
foodssuchasbeef,poultryandbroccoli.3OthersourcesofCoQ10aresoyoil,fishoils,peanuts,sardinesand
mackerel.DietaryintakeofCoQ10is25mgperday,whichisalwaysinadequatetoprovidelevelsinthebody
requiredtobebeneficialinpathologicalstates.ThetotalbodycontentofCoQ10is0.4to1.5gm..
Chemistry
Chemically CoQ10 is 2, 3 dimethoxy 5 methyl 6 decaprenyl benzoquinones. It is a naturally occurring fat
solublequinoneubiquitousineukaryoticcells.(Fig.1).
Synthesis
CoQ10 is synthesized in almost all tissues in the body from the amino acid Tyrosine. The biosynthesisofthe
compound is multifold, with the isoprenyl side chain deriving from mevolonate, the benzoquinone ringstructure
fromtyrosine,andcondensationofthesestructuresthroughpolyprenyltransferaseenzymeactivity.4Theprimary
regulation of CoQ10 biosynthesis is the 3 hydroxymethylglutarylcoenzymea,(HMGCOA)reductasereaction
thatissimilarincholesterolsynthesis.(Fig.2).
History
CoQ10 was first isolated from beef heart mitochondria by
Dr. Frederick Crane of University of Wisconsin, USA in
1957, Professor Morton introduced the name ubiquinone,
meaning the ubiquitous quinone.1 In 1958, professor Karl
Folkers and coworkers determined the precise chemical
tructureofCoQ10as2,3,dimethoxy5methyl6decaprenyl
benzoquinonessynthesizedandwerethefirsttoproduceit

byfermentation.
In1960,professorYamamuraofJapanbecamethefirstin
the world to use coenzyme q7 a related Compound in the
treatmentofhumandiseasesviz.congestiveheartfailure.
In 1978, Peter Mitchell received the Noble prize for his
contribution to the understanding of biological energy
transferthroughtheformulationofthechemiosmotictheory,
which includes the vital proton motive role of CoQ10 in
energytransfersystems.

MechanismofAction
CoQ10isalipidsolublebenzoquinonewitha10isoprenylunitsidechain,isstructurallysimilartovitaminK5.Itis
an essential component in the synthesis of ATP and exhibits both antioxidants and membrane stabilizing
property. CoQ10 acts as a redox link between flavoproteins and cytochromes that are needed for oxidative
phosphorylation and synthesis of ATP. It serves as an electron transport carrier during the processes of
respirationandoxidativephosphorylation.Thus,itisinvolvedinthemanufactureofATP.CoQ10directlyregulates
NADHand succinate dehyrogenase, enabling reversiblereactionsbetweentheseenzymesinthemitochondrial
electron transport chain. CoQ10 must be reduced to ubiquinol to wield its antioxidative function, and
supplementationwithCoQ10mayinhibitlipidoxidizability.
CoenzymeQparticipatesintheelectrontransportinsidethemitochondriaofthecell,thuseitherhydrogenionsor
electrons are gained or lost by CoQ10. It serves as an electron acceptor for one group of enzymes and as an
electron donor to the next group of enzymes in the electron transport chain. It helps transport electron from
complexitocomplexiiandfromcomplexiitocomplexiii.The[H]+accumulatedintheintermembranespaceof
mitochondriaisdrivenbackintothemitochondriamatrixviaATPsyntheses(complexv)withformationofATP.
Other mechanisms of action may include stabilization of calcium dependent slow channels, inhibition of
intracellularphospholipases,andalterationofprostaglandinmetabolism.5

PhysiologicalroleofCoQ10
I.CoQ10asEnergizer
CoQ10participatesintheelectrontransportinsidethemitochondriaofthecell,thuseitherH+orearegainedor
lostbyCoQ10.Itservesasanelectronacceptorforonegroupofenzymesandasanelectrondonortothenext
groupofenzymesintheelectrontransportchain.
ATP synthase is like a turbine where higher concentrations of H+ leads to more energy trapping and ATP
formationandviceversa.CoQ10istheimportantcoenzymeresponsiblefortakingupelectronsandpushingH+
intotheintermembranespace.
Thus, CoQ10 is an essential component in the ATP synthesis in the mitochondria and high concentrations of
CoQ10 can increase the total utilization of energy released by the metabolic processes in the body whereas
deficiencyofwhichmayleadtolossofenergygeneratedduringthemetabolicprocessesintheformofheat.
It is a central ratelimiting constituent of the mitochondrial respiratory chain, which generates most of the ATP
withinthecell.ThusCoQ10actsasanenergizerwhereitimprovestheefficiencyofthecellstoutilizeallavailable
energyfromitssources.

II.AntioxidanteffectsofCoQ10
It is well known that free radicals cause oxidative damage in various chronic disease states like atherosclerotic
heart disease, hypertension, congestive heart failure, diabetes mellitus, ischaemia reperfusion injury,
dyslipidaemiaandmanyotherconditions.
Free radicals are the substances, which have one or more unpaired electrons. These unpaired electrons can
easilyreactwithcellcomponentstocausefreeradicalsinjuryoroxidativedamage.Theunutilizedoxygeninthe
bodycanleadtotheformationoffreeoxygenradicalsviz.Suproxideanion(O2),Hydroxylradicals(OH).
Various drugs, chemicals, pesticides, industrial pollutants, tobacco smoke, sunlight and ionizing radiation can
generatefree radicals whereas in the body they are being constantly formed in the lysosomes, peroxisomes,
endoplasmic reticulum, plasma membrane and the cytoplasm. Free radicals bring about modulation of
inflammatoryprocessbyregulatingprostaglandinsynthesis.

FreeradicalshavehighpropensitytodamagecellularDNAleadingtoactivationofcarcinogenesis.Theyalsolead
tofattyacidperoxidationanddamagetothecellarchitectureandfunction.Theyalsodamagethevariouscellular
metabolicprocessesandinterferewithionchannelslocatedonthecells.
CoQ10actsasanantioxidantbydecreasingformationoffreeradicals.Itimprovesthetransportofelectrons(e)
and protons (H+) and thus prevents the formation of superoxide radicals that would otherwise form from the
releasedO2.Ititselfisastrongdirectlyactingendogenousantioxidant.Itactsasasubstrateforfreeradicalsand
accepts the free electrons from free radicals gets converted to reduced CoQ (Ubiquinol), thus rendering free
radicalsintoharmlesscompounds.ReducedCoQ10thengivesupelectronsandgetsreactivatedagainforfurther
activity.CoQ10isfoundtoregeneratetheoxidizedVitaminEthusconvertingitintoastrongantioxidant.

III.OtherpossiblerolesofCoQ
ItmaybeinvolvedinmaintenanceofcellmembraneintegrityofRBCsandmaintainsoptimumbloodviscosity.It
stabilizes the calcium channels and may promote apoptosis in malignant cells and may improve the immune
statusofpatients.
Pharmacokinetics
Absorption
In animal studies CoQ10 has an oral bioavailability of 23%. With high doses of dietary CoQ10, the blood
concentration in both rats and humans can be increased about 2 to 4fold. Following ingestion of 100 mg of
CoQ10,peakplasmalevelsoccurbetween5and10hours.Tmaxisapproximately6.5hours,whichindicatesslow
absorpitonfromtheGItractpossiblyduetothehighmolecularweightandlowwatersolubilityofCoQ10.2Uptake
ofdietaryCoQ10intheliverdoesnotaffectthesynthesisofendogenousCoQ10.
Distribution
Themeanplasmalevelsafterasingle100mgoraldoseofCoQ10inhumansubjectsis1.0040.37mg/ml.In
humans,CoQ10isfoundinrelativelyhighconcentrationsintheheart,liver,kidney,andpancreas.6Theplasma
halflife of CoQ10 in different tissues varies between 49125 hours.7 Following absorption from the GI tract,
CoQ10istakenupbychylomicrons.ThemajorportionofanexogenousdoseofCoQ10isdepositedintheliver
andpackagedintoVLDLlipoprotein.
MetabolismandExcretion
It is assumed that metabolism and excretion of exogenous CoQ10 is analogous to endogenously produced
CoQ10.TheexcretionofCoQ10predominantlyoccursviathebiliarytract.

Roleinpathologicalconditions
RoleinCHF
CoenzymeQ10supplementationasanadjuncttoCHFstandardtherapyisreportedtohavepositiveoutcomes,
especially in patients with deficient levels of the provitamin. Heart failure often is characterized by an energy
depletionstatus that has been associated with low endogenous CoQ10 levels. The possible usefulness of the
CoQ10 in the treatment of CHF may be related to its ability to increase ATP synthesis and enhancement of
myocardialcontractility.5
Aswithothermuscletypes,cardiacmusclefibresrequirecalciumforcontractionandrelaxation,andmoreenergy
isrequiredforrelaxation.Thesecellsrelyheavilyonfatsourcesofenergyandhencecontainmoremitochondria.
Sinceenergysynthesis(ATPSynthesis)fromfatsrequiresahigheroxygenconcentration,mitochondriafunction
inthecardiacmyocytescanbesignificantlyimpairedindeficiencyofCoQ10.Therefore,administrationofCoQ10
increases the energy synthesis in the mitochondria and significantly improves the cardiac function (contraction
andrelaxation),decreasesenddiastolicventricularpressureandimprovestheejectionfractioninCHF.
Thus, therapy with CoQ10 may be considered to be an efficacious aid in the traditional treatment of chronic
congestiveheart failure along with other agents used in CHF. CoQ10 administration has shown to reduce the
signs and symptoms of CHF like oedema, pulmonary rales, cyanosis, hepatomegaly and breathlessness on
exertion.
CoQ10 is also useful in patients with hypertension, cardiac transplantation, cardiac bypass surgery,
cardiomyopathiesandischaemicheartdisease.Inpatientsofdyslipidaemiawhoareonstatins,whichdecrease
cholesterolsynthesisbyHMGCoAreductaseinhibition,thereisanapparentdeficiencyofCoQ10andconcurrent
CoQ10administrationinsuchpatientssignificantlyimprovesthecellularfunctionandreducesthecomplications
of dyslipidaemia. CoQ10 also reduces the ischaemiareperfusion injury seen in patients recovering from
myocardialischaemia.Itsantioxidantpropertiescontributetopreventionoflipidperoxidation,whichalleviatesthe
oxidativestressinherentinCHF.PatientswithsevereCHF,i.e.NYHAclassIIIandIVtendtohavelowerlevelsof
endogenousCoQ10thanthatofpatientswithNYHAclassICHForhealthysubjects.5Thus,patientswithsevere
diseasesmaybemorelikelytoattainafavourableclinicalresponsetoCoQ10supplementation.
Studies reported clinical benefits from shortterm (14 wks) and longterm (3 months 6 yrs) therapy with oral
CoQ10supplements,50100mg/day,addedtoconventionaltherapyinpatientswithsevereCHF(NYHAclassIII
and IV).4,5,811 Two large multicenter, openlabel studies evaluated the efficacy and safety of CoQ10 as
adjuvanttherapy in CHF. The two studies examined a total of more than4000patientswithvaryingseverityof
CHF(i.e.patientswithNYHAclassIIandIIIandclassIIIandIVCHF)whoexperiencedclinicalimprovementin

signsandsymptomssuchascyanosis,oedema,pulmonaryrales,dyspnoea,andpalpitations.12,13
Roleinangina
The mechanism for improved exercise tolerance in patients with stable angina may be due to ischaemic
myocardialprotectionbyCoQ10,allowingtissuetoreachhigherlevelsofenergyexpenditure.5Possibleactivities
ofthecoenzymeinthemaintenanceofoxidativephosphorylation,enhancementofATPsynthesis,orreductionof
free radicals formation create distinctions between the antianginal effects of CoQ10 and the effects of other
agentssuchasnitrates,calciumchannelblockers,orbadrenergicblockers.TheabilityofexogenousCoQ10to
protecttheischaemicmyocardiumandreduceordelaysignsandsymptomsofanginaissuggestedbysixsmall
randomized,doubleblind,placebocontrolledstudiesinvolvingpatientswithstableanginapectoris.14,1519Allof
these studies determined that CoQ10 dosages of 60600 mg/day significantly prolonged exercise duration,
reduced exerciseinduced ischaemic STsegment depression, and delayed the onset of stable angina pectoris
whencomparedwithplacebo.
Roleinhypertension
These effect of CoQ10 to decrease blood pressure is attributed to the correction of endogenous provitamin
deficiency.20,21Inastudyofhypertensiverats,adeficiencyintheactivityofsuccinatedehydrogenaseCoQ10
reductaseinleucocyteswasfound.DeficientactivityofthisenzymecanresultindecreasedlevelsofCoQ10.22
Having identified same deficiency in human subject with chronic hypertension, investigators conducted a pilot
studyinwhichtheyconcludedthatincreasedsuccinatedehydrogenaseCoQ10reductaseactivityandsubsequent
increasedCoQ10 level leadto decreases in systolic and diastolic blood pressures.20,23 Statistically significant
decreases in systolic and diastolic blood pressure were observed with CoQ10 dosages ranging from 30360
mg/dayinpatientswithhypertensionbuttheseresultsarenotconsistentamongthetrials.20,21,2429
Maleinfertility
Threeimportantparametersininfertilityarecount,morphologyandmotilityofspermcells.Thespermcountand
morphology may be adversely affected due to damage by free radicals. The reduced sperm motility is the
consequence of decrease in energy production ATP. CoQ10 has been found to be useful in idiopathic
asthenozoospermia,whichislossordecreaseofspermmotilityinsemen.InJan2004astudywasconductedto
evaluateroleofCoQ10inmaleinfertility.Inthisstudysubjectswithhistoryofprimaryinfertilityreceived200mg
twice daily of CoQ10 for 6 months. At the end of study period CoQ10 levels in seminal plasma and
phosphatidylcholineincreasedsignificantly.Motilityofspermcellsalsoincreasedfrom9.13%to16.34%.
Testicular tissue and sperm viability are particularly vulnerable to peroxidation injury produced by free radicals
and reactive oxygen species. Increased lipid peroxidation of sperm leads to its damage and thereby causing
infertility.The reasons why sperms are vulnerable to damaging effects of these are: wide surface of the sperm
membranes,poorcytoplasmicdefensemechanisms,lackofprotectioninthefemalegenitaltractoncethesperms
areejaculated.Wheneverthereisoligoasthenozoospermia,theavailablespermalsohaveahighchanceofbeing
damagedbyfreeradicals.
AsthenospermiaandATP
Themainconcentrationofmitochondriainthespermisinitsmidpiece.Thespermmotilityisdirectlydictatedby
itsabilitytogenerateATP,whichinturnisdependentonCoQ10production.Themotilityofspermrequiresahigh
energyexpenditure,andhenceoptimalmitochondrialATPgenerationplaysanimportantroleinspermmotility.30
Just before ovulation, the quantity of water and mucus increases in the living cells of the cervix in female. The
water and salt interact with the glycoproteins present in mucus to form crystal. This is called ferning and, asa
result of the latter channels is formed in mucus, which only allows sperms, which are normal, and possess
adequatemotility,tonavigatesuccessfullysoastoreachthe ovum for fertilization in the optimal 69 minutes of
time.CoQ10encouragesbetterspermviabilityduetoprovingprotectionagainstthedamagingeffectsofreactive
oxygenspecies,andalsobyenhancingspermmotility.TheCoQ10concentrationinserumisusually0.0811.066
mmol,andgoodcorrelationhasbeendemonstratedbetweentheselevelsandspermmotility/count.31Duetoits
lipophillic nature. CoQ10 increases the membrane integrity of sperm and increases defense mechanism of the
sperm. Because of its antioxidant and free radical scavenging activity, CoQ10 prevents the sperm from free
radicalinduceddamage.
Afteradministration,CoQ10getsincorporatedinthespermmitochondriaduringtheprocessofspermatogenesis.
SincethecompleteprocessofspermatogenesisrequiresalongtimeCoQ10shouldbeadministeredatleastfora
periodof10to12weeks
Sideeffects
In therapeutic dosages, CoQ10 has proved to be relatively devoid of major side effects. The most common
adverse effects are nausea, epigastric pain, diarrhoea, heartburn, and appetitesuppression. However, the
prevalenceoftheseadverseeffectswaslessthan1%inreportedstudies.3,5GastrointestinaleffectsofCoQ10
may be lessened with a dosage reduction or may subside with continued therapy. Asymptomatic elevations in
serumlactatedehydrogenaseandhepaticenzymeswereobservedandmayoccurwithoraldosagesofCoQ10in
excessof300mg/dayhowever,casesofserioushepatotoxicityhavenotbeenreported.6,35Clinicalrelapsewas
noted on withdrawal of CoQ10, whereas reinstatement of therapy resulted in improvement.3637 In one
withdrawal study, subsequent onset of fatigue and dyspnoea indicating clinical relapse occurred in 88% of 16
patients,yet75%improvedandregainedtheirclinicalstatuswithresumptionofCoQ10.36

Druginteractions
A drug interaction may occur between HMGCoA reductase inhibitors and CoQ10 because the coenzyme is a
byproductofthecholesterolbiosyntheticpathway.UseofHMGCoAreductaseinhibitors(statinsi.e.simvastatin,
pravastatin,lovastatin)mayresultinthediminutionofCoQ10bloodlevelsduetointerruptionofsynthesis.3841
Other antilipidaemic agents such as cholestyramine of fibrate derivatives do not appear to affect CoQ10
concentrations.40
The oral antidiabetic agents (i.e., acetohexamide, glyburide, phenformin, and tolazamide) may inhibit enzymes
(e.g.,NADHandsuccinatedehydrogenase)resultinginreductionsinserumCoQ10levels.42
CoQ10 is structurally related to vitaminK and subsequently possesses procoagulant effects. The potentially
criticalinteractioncanresultasadiminishedresponsetowarfarintherapy.Severalreportsdescribedecreasesin
international normalized ratio (INR) after the addition of CoQ10 in patients previously stabilized with warfarin
therapy.43 The concomitant use of warfarin and CoQ10 should be avoided due to the risk of thrombotic
complications.
Also,reducedinsulinrequirementswereobservedinpatientswith diabetes who were taking CoQ10 because it
exertsfavourableeffectsonATP,whichinturnactsasachemicalenergycarrierinthebiosynthesisofinsulin.42
CoQ10 supplementation in patients with hepatic insufficiency or biliary obstruction may increase serum CoQ10
levelsbecausethismoleculeismetabolizedinliverandexcretedprimarilythroughthebiliarytract.35
Safety profile of CoQ10 during pregnancy and lactation has not been established, and interactions between
CoQ10andfood,herbs,orotherdietarysupplementsarenotknown.

Conclusions
CoQ10administeredorallyhasfavourableactionsinvariouscardiovascularconditionsandappearstobesafe
andwelltoleratedintheadultpopulation.AconservativeapproachtoCoQ10therapyistosupportitsuseas
adjuvanttreatmentforCHF,anginaorhypertension.Itsfavourableeffectsonejectionfraction,exercisetolerance,
cardiacoutput,andstrokevolumeweredemonstratedinCHF.Theseclinicallysignificanteffectsmaybenefit
patientswithNYHAclassII,IIIandIVCHFwhoareusingCoQ10asanadjuvanttotraditionalheartfailure
therapy.PatientswithanginamayseeprolongedexercisedurationandreducedexerciseinducedSTsegment
depressionwithCoQ10.CoQ10maypossiblyfindaplaceinthetherapyofparkinsonism,dyslipidaemia,
migraine,maleinfertility,andatherosclerosisinnearfuture.

Acknowledgement
TheauthorswishtothanktheDean,Dr.MEYeolekar,forgrantinguspermissiontopublishthisreport.

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MICROSCOPICCOLITIS:ONETOLOOKFOR
In a Swedish population with nonbloody diarrhoea, nearly 10% had microscopic colitis found on
colonoscopy,adiagnosismissedinthefirsthistologicalexamination.Theincidenceofmicroscopiccolitis
almostmatchedthat of Crohns disease. The cause of microscopic colitis is unknown. Budesonide and
bismuthsubsalicylatemayworkasinitialtherapy.
BMJ,20042055.

*LecturerinPharmacology,**LucturerinBiochemistry,
***TraineeIntern,GrantMedicalCollegeandSirJJGroupofHospitals,Mumbai
#LecturerinPharmacology,TNMedicalCollegeandBLYNairHospital,Mumbai.