Potencial terapêutico da suplementação de Creatina na reabilitação de pacientes com doença...

8/13/2019 Potencial teraputico da suplementao de Creatina na reabilitao de pacientes com doena arterial perifrica.

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ABSTRACTCrea ne (Cr) Supplementa on has been e cient and safely used as a therapeu c aid in manyhealth and sickness condi ons including muscle weakness, atrophy and metabolic disturbances.In Peripheral arterial obstruc ve disease (PAOD), chronic ischemia leads to muscle ber atrophyand denerva on, nega ve muscle metabolism altera ons, thus reducing strength and endurance,impairing general physical tness. Adding the studied bene ts of Cr supplementa on and theclinical frame of PAOD, it presents Cr Supplementa on as a poten al therapeu c aid to beconsidered. Objec ve: To make a systema c review in scien c literature, searching for studiesinvolving Cr supplementa on in PAOD individuals. Method: A search for Portuguese and English

wri en ar cles, published over the last ten years, including terms related to PAOD and Crsupplementa on, was conducted on PubMed SciELO, and LILACS. Results: Only one study evaluatedthe in uence of Cr supplementa on in the desired sample (PAOD), describing posi ve e ects inwalking distance and blood proper es. Due to lack of scien c data, the use Cr supplementa onin PAOD popula on, including metabolic, func onal and structural considera ons was discussed.Conclusion: Despite the presented discussion for using Cr supplementa on in PAOD as a poten altherapeu c aid, only one previous study could verify its bene ts. Therefore, it s ll has a gap inscien c literature, leaving several possibili es for future studies researching for possible bene tsto counteract the loss of func onal tness and impairments in musculoskeletal structure andmetabolism of diseased individuals.

Keywords: Crea ne, Peripheral Arterial Disease/rehabilita on, Intermi ent Claudica on

Creatine supplementation as a potentialtherapeutic aid in peripheral arterial obstructivedisease rehabilitation

Lucas Caseri Cmara 1 , Erika Magalhes Suzigan 2 , Marcelo Andrade Starling 1

1 Mdico Residente em Medicina Fsicae Reabilitao, Universidade Federal deSo Paulo - (UNIFESP-EPM).2 Mdica Fisiatra, Assistente do Servio deReabilitao da Santa Casa de Misericrdia de

So Paulo.

Mailing address:Lucas Caseri CmaraRua Pascal, 1622, Campo BeloSo Paulo - SPCEP 04616-005E-mail: [email protected]

Received on November 16, 2012.Accepted on July 26, 2013.

DOI: 10.5935/0104-7795.20130025

Suplementao de creatina como potencial agente teraputicona reabilitao da doena arterial obstrutiva perifrica

RESUMOSuplementao de Crea na (Cr) tm sido u lizada de forma segura e e caz em diversas condiesde sade e doena, incluindo fraqueza, atro a e distrbios metablicos musculares. Na Doenaarterial obstru va perifrica (DAOP), a isquemia crnica promove atro a, denervao e prejuzosmetablicos musculares, reduzindo a fora e resistncia, prejudicando a ap do sica geral.Tomando em conjunto, os bene cios conhecidos da suplementao de Cr e a apresentaoclnica da DAOP, apresentam a suplementao de Cr como potencial agente terapu co a serconsiderado. Obje vo: Realizar uma reviso sistem ca da literatura cien ca procurando porestudos envolvendo a suplementao de Cr em portadores de DAOP, publicados nos l mos dezanos. Mtodo: Uma pesquisa por ar gos escritos em portugus e ingls no perodo descrito,incluindo o cruzamento de termos relacionados a DAOP e a suplementao de Cr foi realizada noPubMed, SciELO, e LILACS. Resultados: Um nico estudo avaliou a in uncia da suplementaode Cr na amostra desejada (DAOP), descrevendo efeitos posi vos na distncia de caminhada e empropriedades sanguneas. Devido escassez de dados sobre o tema, o potencial uso da Cr na DAOP

incluindo consideraes metablicas, funcionais e estruturais foi discu do. Concluso: Apesar dasapresentadas consideraes para a u lizao da Cr como potencial agente terapu co na DAOP,apenas um estudo prvio veri cou bene cios. Assim ainda h uma grande lacuna na literaturacien ca, deixando campo aberto para futuros estudos na procura de possveis bene cios nocombate a perda funcional, prejuzo da estrutura e metabolismo muscular de indivduos doentes.

Palavras-chave: Crea na, Doena Arterial Obstru va Perifrica/reabilitao, Claudicao Intermitente


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Acta Fisiatr. 2013;20(3):152-156 Cmara LC, Suzigan EM, Starling MACreatine supplementation as a potential therapeutic aid in peripheral arterial obstructive

disease rehabilitation

INTRODUCTION

Over the last two decades an increasingof evidences iden ed the nutri onalsupplement crea ne (Cr) as the most e ec veergogenic aid to improve exercise tolerance,muscle strength and lean body mass. 1,2

The undeniable documented bene tsassociated with an excellent safety pro le of itsuse, lead researches to explore Cr as a therapeu caid in many health and sickness condi ons, 3 asrecent reviewed by Gualano et al. 4,5

In this context, Cr supplementa on canpossibly counteract the nal result of manydegenera ve diseases, like muscle weakness,atrophy and metabolic disturbances. 4,5

In peripheral arterial obstruc ve disease(PAOD), the chronic obstruc on in blood ow todistal territories due to atherosclero c process,and its consequence and constant mismatchbetween oxygen delivery and demand, lead toa progressive disability cycle involving muscle

ber atrophy and denerva on, nega ve musclemetabolism altera ons, reduced strength andendurance, impairing general physical tnesscapacity, specially walking capacity, in diseasedindividuals. 6-9

Cost-e ec veness strategies 10 to counteractmuscle, nerve and metabolism impairments, andto reduce the loss of physical tness capacity,like exercise training have been previouslyproposed 11,12 and studied. 13-17

Therefore, adding up the cost-e ec ve-

ness and the safety pro le of studied bene tsof Cr supplementa on 18,19 and the clinicalframe of PAOD, the use of Cr rises as a poten-

al therapeu c aid to be considered.

OBJECTIVE

So, the goal of this study was to make asystema c review in scien c literature, sear-ching for studies involving Cr supplementa on inPAOD individuals, published in the last ten years.

METHODA search in the last ten years for Portu-

guese and English wri en ar cles includingand incluiding terms related to PAOD and Crsupplementa on was conducted on PubMed,SciELO, and LILACS.

Included terms: 1) PAOD: a) English - Periphe-ral Arterial Disease and Intermi ent Claudica on;b) Portuguese - Doena Arterial Perifrica, Obstru-o Arterial Perifrica e Claudicao Intermi ente.2) Cr Supplementa on: a) English - Crea ne,

Crea ne Monohydrate and Crea ne Supplemen-ta on; b) Portuguese - Crea na, Crea na Mono-hidratada, Suplementao de Crea na.

All included terms found in the ar cleswere individually selected by the tle andabstract to be included in this review. A erthe selec on, the ar cles were taken from twoopen access libraries (University of So Pauloand Federal University of So Paulo).

RESULTS

A er our research, only on Pubmed,ar cles related to the subject were found.Relevant studies (3 studies) were selecteda er matching Intermi ent Claudica on xCrea ne (29 searched, 3 selected), and fromPeripheral Arterial Disease x Crea ne (85searched, 13 selected).

Studies were excluded if they were notabout inves ga ons concerning the subject(ie. Crea ne supplementa on, or peripheralarterial disease). Ar cles that scope periphe-ral arterial disease metabolism, includingATP-PCr, were selected, even if they were notspeci c, and they were men oned along thisstudy.

One important detail to point out is thatthe previous period planned (last ten years)was extended to 15 years due to limited data.

Only one study 20 from Cardiology Centerof Moscow (Russia), in fact, evaluated the in-

uence of Cr supplementa on in the desiredsample (PAOD), describing posi ve in uen-ce not only in maximal walking distance,but as well as on platelet aggrega on, bloodrheology, coagula on and brinoly c system.

DISCUSSION

Despite the presented discussion of Crsupplementa on as a poten al therapeu caid in PAOD popula on, we could only nd onestudy published in 1994 from Russian resear-chers. Panchenko et al. 20 studied the in uence

of daily 10g supplementa on of Cr in 37 PAODpa ents, versus non-diseased paired samplemen, with symptoms of intermi ent claudi-ca on, with diagnosis con rmed by angio-graphy or ultrasound technique. Comparingpa ents with control group (before and a erthis interven on), the diseased supplementedgroup signi cantly increased maximal walkingdistance. The authors a ributed this improve-ment on walking due to posi ve in uences onplatelet aggrega on, blood rheology, coagula-

on and brinoly c system. 20

Surprisingly, the described method inthe present research, no other studies wereconducted un l now (con rming or refu ng theresults), despite the clinical bene ts observedand documented in the PAOD popula on ofPanchenko et al. 20 study.

Due the lack of scien c data evalua ngthis subject, we believe it will be interes ngto be er discuss the poten al use of Crsupplementa on in PAOD popula on,including metabolic, func onal and structuralconsidera ons:

MetabolicIn PAOD, due to chronic atherosclero c

process, the reduced blood ow leads to im-paired oxygen delivery in peripheral territoriesdistal to obstruc on 6. Therefore, every methe peripheral demand to oxygen increases,for example during repeated muscular con-trac ons (eg. Walking), there is a mismatchbetween delivery and demand of oxygen,increasing the dependence of anaerobicenergy supply, leading to increase in localacidosis and consequent fa gue. 21-24

The peripheral metabolic fa gue can beobserved clinically by ischemia symptoms (in-termi ent claudica on), commonly describedas pain while walking, that prevented the pa-

ent to con nue. 6 Moreover, not only in theacute increase of demand of oxygen by ac vemuscles (eg walking), 23,24 evidence suggeststhat this chronic ischemic process leads to

more permanent decreases in energy storages(ATP-PCr, glycogen, lipids), reduced glycoli cand oxida ve enzymes, and decreased mito-chondrial func on. 21-24 Adding up, the citedaltera ons impairs ATP synthesis and rege-nera on. In fact, previous studies using Phos-phorus-31 magne c resonance spectroscopyfound a perturba on in oxida ve ATP synthe-sis rate and a delayed PCr recovery me inPAOD pa ents. 21-23 PCr recovery me was thestrongest inversely correlated factor togetherwith walking capacity, 22 and predictor of latefollow up requirements for surgical limb inter-ven ons and mortality. 23 One can argue that

once blood ow can be restored (eg angio-plasty, revasculariza on surgery), the meta-bolic impairments could reverse, but Pipinoset al. 25 could not nd improvement of clinicalperformance a er surgical procedure, sugges-

ng that blood ow restric on is not the onlyfactor implying in walking impairment in PAODpa ents.

Wolosker et al. 26 found a very low pre-dic ve value of the ankle-brachial index inthe evalua on of walking capacity in pa entswith intermi ent claudica on. According to


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it, many exercise interven on studies coulddocument signi cant gain in many spheres ofphysical tness without a signi cant improve-ment in blood ow, con rming the data aboutan important metabolic contribu on leadingto func on. 15-17

Even in non diseased (normal blood ow)persons (eg athletes), an increase on metabo-lic func on is capable to improve performan-ce, as seen in studies with Cr supplementa-

on, corrobora ng the data. 27,28 The inges onof 20g/day of Cr for 5 days can lead to increasemore than 20% of muscle Cr content, of whi-ch approximately 20% can be a ributable toPCr form. 1 As reviewed previously by Rawsonand Persky 27 (2007), in the context of exerci-se performance, Cr supplementa on can actas an ergogenic aid through some mechanis-ms, mainly: a) increased storages of glycogenand PCr pre-exercise; b) reduced me to PCrresynthesys; c) reduced post exercise mus-cle damage and in amma on; d) increasedtraining intensity, volume, and sensi vity ofcontrac le muscle bers to Ca++; e) acts inoxida ve stress preven on via direct and in-direct an oxidant ac on; f) maintains the ATP/ADP ra o and maintains cellular pH via H+ bu-

ering; and g) provide ac va on of glycolysisand glycogenolysis through Pi release therebyintegra ng the carbohydrate and Cr degrada-

on to provide energy at the early stage ofexercises.

Finally, due to metabolic altera on

seen in PAOD and the Cr supplementa onbene ts mapped un l now, there is a largeand extensive eld of possibili es for originalresearches, un l this moment only one studywas done. 20 With a plausible applica on of thisnutri onal supplement (based on clinical rea-soning), Crea ne can act as a therapeu c aidaiming to restore the metabolic impairmentsof PAOD.

FunctionalPerformance in daily living regarding

general physical e orts, with special consi-dera on to walking capacity, is impaired in

PAOD individuals. 6 The worsening of arterialobstruc on and consequent disease evolu o-nal stage was previously correlated with theseimpairments. 14,15,29 In fact, studies made withambulatory measurements and subjec veques onnaires to analyze physical func on,observed decreasing levels of physical ac vityin more severe diseased pa ents. 14,15,29,30

This scenario of reduced physical capacitydue to PAOD, increases the levels of a more

sedentary lifestyle, which provokes in enda progressive disability cycle of physicalfunc on. 31 In this eld, scien c literaturehas been previously documented reducedvalues of strength, power and endurance inpa ents when compared with non diseasedcontrols. 7-9,16,17,30,32-34

Once muscular strength could be stronglycorrelated with walking capacity (mostaccessed measure of tness capacity) in PAODpa ents by Regensteiner et al. 34 and Gerdleet al. 32 interven ons (resistance training) tocounteract this condi on has been propo-sed 11,12 and studied with documented posi vebene ts. 13-17

Addi onal to resistance training, asa bene cial exercise type prescrip on innon diseased popula on, 35 associa on ofCr supplementa on has been studied andproposed as a more e ec ve interven on toimprovements muscular strength. 36 In fact tworecent meta-analysis 37,38 documented that Crsupplementa on can signi cantly increasemuscular capacity to generate strength.

In this context, despite of documentedposi ve bene ts, there is s ll a gap in actualknowledge about if Cr supplementa on canincrease strength per se or due to consequentposi ve adapta ons in training capacity,but this discussion is beyond of scope ofour present considera ons and has beenfashionably reviewed before by Lemon et al. 39 and Gualano et al. 40

To our knowledge, no previous studiesincluding strength training in combina on withCr supplementa on was conducted yet in PAODpa ents, leaving a large, open and a poten ala rac ve eld to original inves ga ons.

StructuralSigni cant morphological changes in

skeletal muscle are presented by PAODpa ents, including atrophy (sarcopenia),modi ca on in the pa erns of ber typedistribu on, disturbance in neural func on,and these changes have been associated withimpaired walking capacity. 34,41-43

Askew et al. 42 and Regensteiner et al. 34 using muscular biopsy, found a reduc on inskeletal muscle cross sec onal area, and areduc on in size of bers type I and IIa, com-paring PAOD pa ents with their paired healthycontrols.

Mc Guigan et al. 41 documented a signi-cant increase in muscular capillary density

due the chronic ischemic process, and also anincrease in expression of myosin heavy chain

(MHC) IIx, besides a reduc on in MHC I. Asmen oned before, 34,42 this study also veri eda reduc on in cross sec onal area of berstype I and IIa.

Mc Dermo et al. 43 showed a reduc onin neural func on, due to impairments inmotoneuron, as measured by a reduc on innerve conduc on velocity presented in elec-troneuromyography of 109 older Italian com-munity-dwelling PAOD pa ents.

Gualano et al. 44 conducted a recent reviewabout posi ve in uence of Cr supplementa-

on in enhancement of muscular hypertrophyand strength in healthy persons. The authorsconclusion was a sugges on that the gains ob-tained was not due water reten on, but geneexpression and protein transla on e ciencyrelated to hypertrophy, and prolifera on andac va on of satellite cels.

Again, a bene cial combina on of resis-tance training and Cr supplementa on is capa-ble to bene t pa ents with neuropathies 45 andseveral other nervous system condi ons. 46-48

In conclusion Cr supplementa on can actas a main poten al counter-actor of degenera-

ve muscle and nervous impairments conse-quent to chronic PAOD, but unfortunately nostudies were conducted before to corroborateor refute our present hypothesis.

Other ConsiderationsTaking into account, that the prevalence of

PAOD increases with age, 49-51 is important to

consider that the impairments exclusively dueto disease occurs, most of the me, associatedwith the loss of physical func on of normalsedentary aging process. 52-56 It is reasonableto conclude that the morphological and me-tabolic changes in skeletal muscle, as wellas reduc on in physical tness derived fromnormal aging, can be empowered in PAODpa ents. 41-43 Dalbo et al. 57 recently publisheda detailed manuscript about the bene ts ofCr supplementa on in promo ng bene ciale ects on many aspects of physical tness lossdue to aging.

Comorbidi es as dyslipidemia, diabetes

mellitus , chronic kidney disease, hypertension,pro-in ammatory status, cardiac dysfunc ons(e.g. hearth failure), chronic obstruc ve pul-monary disease (due to high smoke prevalen-ce) are frequently presented in the diseasedpacients. 6

As presented by Gualano et al. 4,5 Crsupplementa on have already been studiedshowing bene ts undoing some of theunfavorable changes for the majority of those


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comorbidi es. In the end, Cr monohydrate hasbeen the most studied supplement applied onsports performance enhancement and severalhealth condi ons. 4,5,58

CONCLUSION

Despite the presented discussion of Cr su-pplementa on in PAOD pa ents as a poten altherapeu c aid, to our knowledge, only oneprevious study could verify its bene ts. The-re is a large and extensive eld of possibili esfor future studies, which are encouraged bythe authors. These surveys should focus onthe possible bene ts to counteract the loss offunc onal tness and impairments in muscu-loskeletal structure and metabolism of agingdiseased individuals.

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