Complementary and Alternative Medicine for the Treatment of Obesity: A Critical Review

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1 Int J Endocrinol Metb April; 13(2): e Published online 2015 April 20. DOI: /ijem Review Article Complementry nd Alterntive Medicine for the Tretment of Obesity: A Criticl Review Alirez Esteghmti 1,* ; Tin Mzheri 1 ; Mon Vhidi Rd 1 ; Sin Noshd 1 1 Endocrinology nd Metbolism Reserch Center (EMRC), Vli-Asr Hospitl, School of Medicine, Tehrn University of Medicl Sciences, Tehrn, IR Irn *Corresponding uthor: Alirez Esteghmti, Endocrinology nd Metbolism Reserch Center (EMRC), Vli-Asr Hospitl, School of Medicine, Tehrn University of Medicl Sciences, Tehrn, Irn. Fx: , Tel: , E-mil: Received: April 24, 2014; Revised: September 3, 2014; Accepted: December 2, 2014 Context: Obesity nd its ssocited morbidities pose mjor helth hzrd to the public. Despite multiplex of vilble diet nd exercise progrms for losing nd mintining weight, over the pst yers, interest in the use of complementry nd lterntive medicine (CAM) for obesity tretment hs gretly incresed. Evidence Acquisition: We serched PubMed, Google scholr nd the Cochrne dtbses for systemic reviews, review rticles, metnlysis nd rndomized clinicl trils up to December Results: In this review, the efficcy nd sfety of the more commonly used CAM methods for the tretment of obesity, nmely herbl supplements, cupuncture, nd non-invsive body-contouring, re briefly discussed. The evidence supporting the effectiveness nd sfety of these methods is either lcking or point to negligible clinicl benefit, brely surpssing tht of the plcebo. Furthermore, severl limittions re observed in the vilble scientific literture. These shortcomings include, without being limited to, uncontrolled tril designs, non-rndom lloction of subjects to tretment rms, smll number of ptients enrolled, short durtions of follow-up, nd mbiguous clinicl nd lbortory endpoints. Conclusions: Further investigtions re necessry to ccurtely determine the efficcy, sfety, stndrd dosge/procedure, nd potentil side effects of the vrious CAM methods currently in use. Keywords:Weight Loss; Obesity; Biliopncretic Diversion; Complementry Therpies; Dietry Supplements; Acupuncture Therpy; Lser Therpy; Tretment Outcome 1. Context According to the World Helth Orgniztion (WHO) 2010 globl report on non-communicble diseses, overweight/obesity is climing 2.8 million lives nnully (1). The plgue of obesity hs reched epidemic proportions nd is spreding t n unprecedented pce, prticulrly in urbn res of low nd middle income countries (2, 3). However, this globl clmity is not only confined to the developing world (3, 4), s bout 60% of the dults in the United Sttes re currently either obese or overweight (5). Obesity, defined by WHO s body mss index (BMI) equl to or greter thn 30 kg/m 2, hs been linked to wide rry of illnesses nd disbilities, including type 2 dibetes, crdiovsculr diseses, chronic kidney disese, sleep pne nd its resultnt chronic ftigue nd poor ttention, rthritis, lung disese, nd severl forms of cncer (e.g. brest nd prostte) (6-10). Obese individuls re lso t n incresed risk of premture deth (9, 11). Overweight/obesity is ssumed to be product of imblnced cloric intke nd expenditure. Therefore, incresed physicl ctivity, coupled with clorie-restricted diet, remins the minsty of tretment in obese/ overweight individuls. Physicl ctivity lowers the risk of dibetes, hypertension, stroke, ischemic hert disese nd severl types of cncers (12-14). The prevlence of insufficient physicl ctivity is rising globlly. According to WHO report, 48% of women nd 41% of men hve insufficient physicl ctivity in high-income countries nd lmost 3.2 million deths ech yer re ttributed to physicl inctivity (1). Adherence to unhelthy diets, high in simple crbohydrtes nd sturted ftty cids, hs lso been rising, especilly in low- nd middle-income countries. Collectively, pproximtely 80% of coronry hert disese nd cerebrovsculr disese re ttributble to behviorl risk fctors, such s indequte physicl ctivity, nd dherence to unhelthy dietry ptterns (15). Busy schedules, sedentry lifestyle, incresed utomtion of work, nd decresed trnsport-relted physicl ctivity in modern societies, ll contribute to the incresing physicl inctivity trend. It is suggested tht, s long s culture nd environment support unhelthy life style ptterns, especilly through medi, modifying lifestyle would be unttinble (16). Consequently, lterntive methods, with little or no scientific evidence supporting them, hve ttrcted the interest of individuls t risk Copyright 2015, Reserch Institute For Endocrine Sciences nd Irn Endocrine Society. This is n open-ccess rticle distributed under the terms of the Cretive Commons Attribution-NonCommercil 4.0 Interntionl License ( which permits copy nd redistribute the mteril just in noncommercil usges, provided the originl work is properly cited.

2 Esteghmti A et l. nd hve replced the stndrd weight-lowering methods, with proven efficcy. Complementry nd lterntive medicine (CAM) is defined by the Ntionl Center for Complementry nd Alterntive Medicine (NCCAM) s group of vried medicl nd helthcre systems, prctices, nd products tht re not considered to be prt of ny current Western helth cre system (17). Incresed public wreness regrding obesity-relted helth problems, long with the socil pressure concerning the body imge nd desire to hve slim body, hs enormously given wy to CAM during the recent yers. However, up to present, there re insufficient reserches regrding the effectiveness of CAM therpies for weight loss nd much of the existing literture hve fundmentl methodologicl problems (18). The present review provides summry of the more commonly used CAM methods for the tretment of overweight/obesity. In ech section, fter brief introductory pssge, the body of evidence endorsing or dispproving the method, s weight-lowering strtegy, is discussed. 2. Evidence Acquisition We serched PubMed, Google scholr nd the Cochrne review dtbse for relted publictions written in English lnguge (Abstrct nd/or full-text). Systemtic reviews, review rticles, met-nlyses nd rndomized clinicl trils, conducted nd published up to December 1st, 2013, were considered. Studies published from 2000 nd fterwrds were given high priority. The combintion of keywords used for our reserch ws s follows: obesity tretment, weight loss, herbl supplements, chinese herbl medicine, Grcini cmbogi (G. cmbogi), Cmelli sinensis (C. sinensis), chromium picolinte, conjugted linoleic cid (CLA), Hoodi gordonii (H. gordonii), Cynnchum uricultum (C. uricultum), chitosn, cupuncture, non-invsive body contouring, including high intensity focused ultrsound (HIFU), lser therpy, cryolipolysis nd rdiofrequency (RF). A list of keywords ws derived initilly. Authors then performed independent literture reviews nd the findings were shred in designted rticle dtbse. To increse the inclusiveness of our serch strtegy, uthors lso reviewed the texts to find other relevnt mnuscripts cited tht were not retrieved in the initil serch. Given the nrrtive nture of the review, no forml qulity ssessment ws performed. 3. Results Avilble evidence on the CAM methods used for the tretment of obesity re summrized in Tble 1. Tble 1. Summry of the Avilble Evidence on Complementry nd Alterntive Medicine Methods Used for the Tretment of Overweight/Obesity Methods Nme Min Mechnism of Action Strength of Publiction Effect Size Possible Side Effects Herbl Supplements Grcini cmbogi Cmelli sinensis Chromium picolinte Conjugted linoleic cid Hoodi gordonii Cynnchum uricultum Chitosn Inhibition of citrte lyse enzyme, inducing stiety 1. Stimultion of sympthetic nervous system, leding to increse in energy consumption2. Ft oxidtion Stimultion of neurotrnsmitters responsible for eting behviors Not fully understood Inhibiting ppetite by ltering the neuropeptide pthwys of the centrl nervous system Appetite inhibiting effects, similr to Hoodi gordonii Reducing nutritionl ft bsorption Observtionl Studies/ Non- Rndomized Trils Rndomized Clinicl Trils Systemtic Review Met-Anlysis 95% CI: kg _ Minor (e.g. rhinitis, joint pin) Non-specific nd well tolerted (e.g: nuse, wtery stools, wekness, dizziness) 95% CI: kg Mild gstrointestinl complints n/ b n/ b 95% CI: kg Mild gstrointestinl complints (e.g. nuse, bloting, indigestion, bdominl pin), comprble to plcebo 2 Int J Endocrinol Metb. 2015;13(2):e19678

3 Esteghmti A et l. Gmbisn Inhibiting dipogenesis? (not yet confirmed) n/ b Acupuncture Acupuncture 1. Regulting obesity-relted neuropeptides, 2. Regulting Hypothlmus-pituitry-drenl cortex nd symptheticdrenl cortex, 3. Lipid lowering effects 95% CI: kg (compred with shm); (compred with lifestyle control) Mild locl rections t the site of needle insertion Non-invsive Body Contouring High intensity focused ultrsound Low level lser therpy Cryolipolysis Rdiofrequency 1. Hyperthermi, 2. Cvittion formtion Forming temporry pores in dipocytes membrne Incresing tissue temperture Mild loclized dverse events, e.g: erythem. No dverse events reported Loclized edem nd erythem, decresed cutneous senstion Mild nd loclized side-effects Denotes the type of evidence vilble for ech method. b n/, no dt vilble or no side effects hve been reported Herbl Supplements Welcomed by the public t lrge, one of the fstest burgeoning methods for weight loss is the use of medicinl plnt extrcts. Despite the long history of their trditionl use for purposes of chronic disese prevention nd cure, the effectiveness of these products, which consist of dietry phytochemicl constituents, remins to be scertined (19). The recent interest in how suitble these nturl supplements re in treting obesity, on long-term bsis, hs led to rft of reserch. Nonetheless, there is need for further investigtion into their efficcy, long-term sfety, optimum dosge, possible side-effects, nd mechnisms of ction. Two other spects of these weight loss ids, which pose significnt problem to the dietry supplement industry, re their overhype, despite indequte supporting proof nd incompetent qulity control, resulting, t times, in incorrect lbel informtion (20). There is flurry of herbl plnts mrketed over the counter, climing nti-obesity effects. The most frequently mentioned ones re reviewed next Grcini Cmbogi Extrcted from the dehydrted fruit rind of G. cmbogi, hydroxycitric cid is one such dietry supplement, which is populr cooking ingredient in Southern Indi. Its mechnism of ction consists of preventing the ctivity of the ATP-dependent citrte lyse enzyme, which stimultes the brekdown of citrte into oxlocette nd cetyl-coa, thus either inducing sense of stiety or lessening the ppetite (21, 22). Consumed for centuries on regulr or supplementl bsis, G. cmbogi is climed to be free of dverse or side effects (22). Experiments on rts nd humns indicte tht dministering hydroxycitric cid indeed contributes to feeling of stiety nd subsequent weight reduction (23). Conversely, number of humn trils hve produced unconvincing evidence, supporting tht no significnt difference ws found between the effects of this supplement nd those of the plcebo (24-27). The results of met-nlysis, which pooled the dt from nine clinicl trils, evluting the effectiveness of hydroxycitric cid in weight reduction, indicted tht hydroxycitric cid is reltively more effective thn the plcebo (men difference: kg; 95% confidence intervl (CI): kg). Collectively, reserch trils point to the fct tht G. cmbogi extrcts cn positively ct s weight loss gents, on short-term bsis. Nonetheless, their effect is limited nd their clinicl relevnce is yet to be determined (28). In conclusion, given the fct tht most humn trils hve been conducted on short-term bsis nd on smll ptient smples, there is no proof supporting the effectiveness of G. cmbogi for length of time longer thn 12 weeks of dministrtion Cmelli Sinensis Used for vriety of resons over centuries, the green te produced from the leves of C. sinensis is nother populr remedy for obesity (19). Commonly referred to s ctechins, the most bioctive constituent of green te re the polyphenols (29). The mechnism of ction of green te cn be outlined s influencing the sympthetic nervous system, thereby incresing energy consumption nd triggering the oxidtion of ft. Reduced nutrient bsorption, ppetite prevention, nd up-regultion of enzymes responsible for heptic ft oxidtion my lso be enumerted s lterntive mechnisms (30). Int J Endocrinol Metb. 2015;13(2):e

4 Esteghmti A et l. According to recent review of three studies on weight mintennce nd fifteen weight loss trils, which involved 1945 humn subjects, consumption of green te, over minimum period of 12 weeks, ws unlikely to be cliniclly effective (30). A further conclusion ws tht the mintennce of weight loss is not considerbly ffected by green te, either. No informtion concerning costs, ptient stisfction or illnesses, s consequence of green te preprtion, ws included in these studies (31). Severl studies hve ttempted, lthough they ultimtely filed, to vlidte the curtive effect of C. sinensis on ppetite reduction or energy consumption, s observed in nd compred between the experimentl nd the plcebo group (32-35). Overll, lthough there is scnt proof, which cn substntite the role of C. sinensis, s n ppetite inhibitor, most studies conclude tht C. sinensis functions through mechnisms other thn ppetite suppression (e.g. incresed energy expenditure), which my indeed help reduce body weight (32, 34, 36, 37) Chromium Picolinte Sold s over-the-counter slimming id throughout the USA nd Europe, (11) chromium picolinte stimultes the neurotrnsmitters responsible for the regultion of food crvings, mood nd eting behvior (38). Chromium supplementtion lso boosts glucose metbolism, body composition, nd insulin sensitivity, to modest extent, in humn trils (39). A systemtic review of nine trils ccounting for 622 subjects (experimentl group = 346; control group = 276) ws conducted on the use of chromium picolinte for weight loss. The subjects in the experimentl group, who were given four different doses of chromium picolinte (200 µg, 400 µg, 500 µg, 1,000 µg) were reported to hve lost 1 kg more thn those receiving plcebo (Men Difference: 1.1 kg, 95% CI: ; P = 0.001). Furthermore, the sfety nd long-term effects of chromium picolinte could not be determined due to the reltively short length (mximum of 24 weeks) of the studies reviewed. This pucity of evidence, therefore, prevented the reviewers from reching ny conclusions regrding the effectiveness nd sfety of this dietry supplementtion in overweight nd obese dults (40) Conjugted Linoleic Acid Conjugted linoleic cid refers to set of isomers in the cis-9, trns-11 form or the cis-12, trns-10 form (41). It is hypothesized tht certin doses of CLA ( g/dy) cn help increse the ft-free mss nd reduce ft mss (42, 43). Currently, number of dietry supplements, with CLA content for the purposes of weight loss, re being dvertised, even though not ll studies hve reported positive results (44, 45). According to met-nlysis from 2012, four out of seven clinicl trils were methodologiclly flwed (46). Overll, the CLA ws fvored over the plcebo due to smll difference in the mount of ft loss (men kg: 1.33 kg; 95%CI: ; I2 = 54%; the I2 sttistics were used to evlute sttisticl heterogeneity between studies, demonstrting low, medium, nd high sttisticl heterogeneity, with vlues of 25, 50, nd 75%, respectively). However, since the mgnitude of the positive effects ws smll nd no p vlues were documented, the evidence ws concluded to be unconvincing nd therefore, the long-term effects of the CLA on body composition cnnot be decisively considered of clinicl importnce (46) Hoodi Gordonii Widely consumed for its lleged weight loss effect (47), H. gordonii, which is member of the Asclepidcee (the milkweed fmily), hs been trditionlly used s n ppetite (both food nd wter) suppressnt during hunting expeditions by the Khoi-Sn tribe, in South Americ (48). Although little is known bout its mechnism of ction, it seems tht its bioctive element, steroidl glycosides P57, which is ssocited with ppetite inhibition, lters the neuropeptide-medited pthwys of the centrl nervous system (47). Bsed on niml studies, the injection of P57 into the centrl nervous system of mice leds to reduced food intke over the following 24 hours (49). Humn trils hve displyed positive results s well. According to press relese from Phytophrm (Huntingdon, UK), reporting phse I/II rndomized tril, fter 15 dys, sttisticlly significnt reduction ws documented in the verge clorie consumption nd body ft content of the group receiving P57, compred to the plcebo group (P = nd P = 0.035, respectively). According to review of the commercil importnce of H. gordonii, there re very few scientificlly-bsed studies on chief fetures (bioctivity of its chemicl ingredients, clinicl relevnce, in vivo biophrmceutics, nd sfety) of this nti-obesity plnt. Obviously, this hs brought bout considerble concern, s H. gordonii is mong the most populr orgnic nti-obesity products (48) Cynnchum Auricultum Ntive to Chin, C. uricultum (Royle ex Wight) is plnt species of which the roots, ccording to Chinese trditionl medicine, enhnce immunity nd espouse longevity (50). Pregnne glycosides nd bishouwubenzophenone hve been found to exist in C. uricultum (51). The similrity in the structure of pregnne nd tht of P57 (found in H. gordonii) shows tht C. uricultum could be n lterntive to H. gordonii in developing ntiobesity dietry supplementtion (51). Wilfoside K1N is the most widely known pregnne glycoside, which bers gret structurl resemblnce to P57 (51). An niml tril, involving rts, hs demonstrted tht Wilfoside K1N cn produce considerble ppetite-inhibiting effect (51). The efficcy nd sfety of pregnne glycosides need to be further investigted, especilly becuse, unlike H. gordonii, which my soon become n endngered species, C. uricultum is n bundnt plnt source (50, 52). 4 Int J Endocrinol Metb. 2015;13(2):e19678

5 Esteghmti A et l Chitosn Chitosn is polyscchride extrctble through the prtil decetyltion of chitin (53). A non-toxic dietry supplement, Chitosn hs been shown to bring bout nti-obesity effects (54, 55) nd is widely believed to be sfe compound (56). Its nti-obesity effects hve been generlly ttributed to its ft-binding qulity, which restricts the bsorption of nutritionl ft from the gstrointestinl trct (57). In vivo studies on mice indicte tht the consumption of chitosn cn led to reduced food intke (58, 59). The effect of chitosn on obesity ws evluted through review of fifteen rndomized trils, with totl of 1219 subjects. Although initil nlyses scribed considerble weight loss to the use of chitosn preprtions (men loss: 1.7 kg; 95%CI: kg, P < ), high qulity trils, conducted lter, reveled tht the nti-obesity effect of chitosn ws not nerly s lrge s the previous subliminl trils climed. In fct, the nti-obesity effect of chitosn ws deemed miniml t best nd therefore cliniclly irrelevnt (60) Gmbisn Gmbisn is newly developed extrct formul which ws designted s HH911G t Kyung Hee University nd Koren Medicine Hospitl, Seoul, South Kore (60). In spite of the fct tht its mechnism of ction is yet to be understood, Gmbisn hs been cliniclly used s populr supplement, with over prescribed doses from 2010 to Indeed, Gmbisn my be ble to offer n effective method of weight loss, though more in vivo investigtions nd clinicl trils re required before ny indisputble conclusions re to be drwn, concerning the sfety, effectiveness, nd the mechnisms of ction of Gmbisn (61-63). In conclusion, herbl supplements re widely mrketed nd commercilized, yet the evidence in support of their effectiveness is either non-existent or point to negligible effect. This should be viewed in light of their possible side effects nd lck of proof of their long-term sfety Acupuncture A longstnding orientl prctice, cupuncture consists of the insertion of needles into certin points on the skin, clled cupoints (64). Over the recent yers, this technique hs come to be incresingly regrded s n lterntive tretment for obesity. Although there is evidence fvoring electrocupuncture over its mnul vritions, in terms of effectiveness, there is less consensus over the optiml frequency for the procedure (65). Studies on nimls nd humns indicte number of possible mechnisms, by which cupuncture contributes to weight reduction. First, it is suggested tht cupuncture cn regulte obesity-relted neuropeptides in the centrl nervous system, s well s ft depot derived dipokines (66, 67). Second, cupuncture my be involved in the regultion of hypothlmus-pituitry-drenl cortex nd sympthetic-drenl cortex xis (68). Third, number of studies hve observed reduction in triglycerides (69, 70), LDL (70, 71), nd totl cholesterol (69, 70) with cupuncture nd thereby might exert lipid lowering effects. Fourth, since high levels of bcteroides hve been observed in obese ptients (72), one of the weight loss mechnisms of bdominl cupuncture my involve the reduction of bcteroides. According to systemtic review nd met-nlysis including 29 rndomized controlled trils, cupuncture ws illustrted to be more effective thn conventionl mediction both in terms of body weight reduction (men reduction = 1.90 kg; 95%CI: kg) nd obesity tretment (reltive risk = 1.13; ) (73). Despite these promising results, becuse of the poor methodologicl qulity of the trils reviewed, the reviewers concluded tht to determine the efficcy of cupuncture in treting obesity, it ws urgent tht more orgnized nd long-term studies need to be conducted (73). Another systemtic review of eight clinicl trils, including 1017 prticipnts, tht evluted the effectiveness of cupuncture, reveled tht cupuncture ws sfe complementry tretment for simple obesity, defined s n imblnce between cloric intke nd energy expenditure. Yet, owing to the limited quntity of conducted rndomized trils nd their poor methodologicl qulity, further investigtions re necessry before cupuncture cn be conclusively certified s n effective solution to obesity (74). In more recent systemtic review of Chinese medicine nd cupuncture, totl of 44 rndomized clinicl trils were exmined (11). According to the pooled nlysis, lifestyle modifiction nd plcebo were found to be less effective thn cupuncture in terms of weight nd BMI reduction (11). Compred to nti-obesity drugs (Orlistt nd Sibutrmine), moreover, cupuncture displyed eqully positive results, with reduced number of side effects nd relpses (11). Nonetheless, the smll size of the smple nd substndrd methodologicl rigor limits the vlidity of the conclusions (11). In summry, the shortcomings observed in the vilble literture on cupuncture re mnifold. To begin, severl studies drw their conclusions from uncontrolled trils. Additionlly, studies with controlled tril designs re riddled with flws, s they suffer from methodologicl weknesses, such s limited durtions of follow up, bsence of plcebo control groups, loosely observed protocols, nd rbitrry selection of cupoints, in terms of the precise loction, s well s the correct depth, ngle nd direction of insertion (11, 73, 74). If conclusive result is to be chieved, concerning the effectiveness of cupuncture, future studies need to mp the cupuncture site on the body nd determine fctors, such s depth nd ngle, s well (75) Non-invsive Body Contouring Invsive body-contouring refers to the surgicl removl of loclized res of diposity from under the skin (76). Int J Endocrinol Metb. 2015;13(2):e

6 Esteghmti A et l. Liposuction is the most common cosmetic plstic surgery procedure used round the world (77). However, this populr method still rises serious concerns bout the sfety of its invsive nture. Possible complictions, resulting from the invsive procedure, rnge in severity from prolonged swelling, bruising, nd numbness, to thrombophlebitis nd pulmonry embolism (78). A pressing need for sfer procedures, with fster recovery time, s well s smller number of side effects, therefore, mkes non-invsive body contouring techniques perhps severl of the most ppeling nd fstest growing extents of esthetic surgery tody (77, 79). Focused ultrsound, cryolipolysis nd low level lser therpy re mong these non-invsive methods, which hve gined populrity over the lst decde High Intensity Focused Ultrsound High Intensity Focused Ultrsound is non-invsive technique used for the bltion of subcutneous ft tissue. Mechnisms by which HIFU ffects the ft depot include (1) hyperthermi, whereby cogultive necrosis of certin res is brought bout with no hrm to djcent res (80, 81), nd cvittion formtion (2), which exerts high degrees of het nd pressure in the microenvironment, therefore subjecting the dipose tissue to mechnicl dmge (82). Avilble evidence suggests ptients with BMI lower thn 30 kg/m 2 show the optiml results to HIFU (83). A 12-week study of 137 prticipnts, nlyzing the effects of focused ultrsound tretment, reveled positive results. Within 2 weeks of tretment, the men reduction in the circumference of the tretment re nd the skin ft thickness were reported to be pproximtely 2 cm nd 2.9 mm, respectively (84) Low Level Lser Therpy Developed nd populrized over the pst decde, Low Level Lser Therpy (LLLT) is nother non-invsive body contouring method, which hs yielded successful results in ft reduction of loclized res, such s the hips, wist, thighs, nd upper rms (85, 86). The mechnism of ction of LLLT is open to investigtion. According to one nrrtive, by forming temporry pores in the dipocytes membrne, LLLT triggers the relese of intrcellulr lipid for dditionl metboliztion (87). In double-blind study of 67 rndomized subjects, ged yers old, with BMI kg/m 2, LLLT resulted in reduction of totl circumference of the wists, hips nd bilterl thighs (88). Despite these preliminry findings, suggestive of the efficcy of the method, further reserch into LLLT is required to fully pprecite its cellulr nd systemic effects, nd to scertin tretment protocols, which llow the highest degree of sfety nd effectiveness possible Cryolipolysis Regrded s n efficcious method for subcutneous ft reduction, cryolipolysis is n emergent technology which trgets ft selectively through controlled cooling. A number of studies hve ssessed the sfety nd effectiveness of cryolipolysis. According to retrospective study on 518 prticipnts, the bdomen, bck nd flnk res were most effectively treted by mens of cryolipolysis. Three months follow-up of the ptients, moreover, displyed no significnt dverse events or side effects (88). Apprising the findings of preclinicl nd clinicl studies on the use of cryolipolysis for nimls nd humns, 2009 review of four clinicl studies concluded tht there ws sufficient evidence to support the efficcy nd sfety of cryolipolysis, s noninvsive ft reduction procedure, even though its mechnism of ction is yet to be explined (89) Rdiofrequency Rdiofrequency is yet nother non-invsive technique used for body contouring (90). The mechnism of ction of RF is bsed on therml ltertion of the derml/ hypoderml lyers. Incresing tissue temperture rises vsculr perfusion, resulting in lipid turnover secondry to the incresed oxygen content. Incresed lipid turnover eventully leds to ft cell shrinkge, nd circumferentil reduction (79). Brightmn nd collegues (91) evluted nineteen prticipnts who underwent five weekly tretments of the upper rms nd 10 ptients received four weekly tretments of bdomen nd flnk, with Vel Shpe (Syneron Medicl Ltd., Irvine, CA, USA) RF energy device tht hs FDA pprovl for both circumference reduction nd cellulitis. Reductions of both rm nd bdomen circumference were sttisticlly significnt, with men loss off cm nd 1.82 cm, respectively t 3 months of follow up. At present, the non-invsive reduction of ft is the most common use of RF-bsed devices nd there re mny rticles to support the clinicl efficcy nd sfety of using RF (79, 91, 92). Non-invsive body contouring techniques re generlly regrded s sfe. By fr, the most criticl issue concerning these methods is ptient disstisfction. Non-invsive body contouring only results in moderte reductions of 2 to 4 cm in limb or wist circumference. Therefore, their efficcy in morbidly obese ptients is firly limited (79). At present, there re no systemtic evlutions of the non-invsive methods used in body contouring or subcutneous ft reduction, in terms of efficcy, sfety, nd ptient stisfction. Crrying out more sophisticted outcome studies, in the form of systemtic reviews nd met-nlyses, is essentil to offer proof of the vlue of non-invsive body contouring. 4. Conclusions Complementry nd lterntive medicine is n umbrell term used to describe wide rry of tretment strtegies tht, by definition, do not conform to the principles nd ides of western medicine. This lleged mrginliz- 6 Int J Endocrinol Metb. 2015;13(2):e19678

7 Esteghmti A et l. tion, by no mens hs ffected their populrity. Tody, more thn ever, ptients re seeking lterntive wys to lose weight nd get len nd this vehemence hs been welcomed by the industry, s well s medi outlets, nd sizble proportion of helthcre prctitioners. Despite their widespred commerciliztion nd n ever incresing demnd from the public, scientific evidence supporting their efficcy nd sfety is strikingly limited nd in sense, non-existent. Herbl supplements re widely mrketed. However, t present, vilble dt supporting their long-term usge nd sfety for obesity tretment is scrce nd, t best, conflictul. Clinicl studies hve often reported negligible effects for herbl supplements brely exceeding tht of the plcebo. Studies investigting the puttive role of cupuncture in weight loss nd mngement hve been positive, yet, given the low qulity of the studies conducted nd extreme diversity in site, depth, nd ngle of needle insertion, cution should be prcticed in interpreting the findings. Preliminry studies, investigting tretment outcomes, with non-invsive body contouring methods, hve been promising. However, since these techniques only cuse mild to moderte mount of weight loss in ptients with resonble BMI rnge, their widespred ppliction in other ptient groups remins to be elucidted. Although promising results hve been obtined by britric surgery techniques, the procedure is invsive, costly, nd is ssocited with long-term morbidity nd complictions nd thus, is only reserved for select popultion of obese ptients, with very high BMI, who do not respond well to lifestyle interventions (93). To the present moment, phrmcotherpy for obesity hs not yielded stisfctory results due to its numerous shortcomings. Most of nti-obesity drugs hve been withdrwn from the mrket, s result of their substntil side effects. Orlistt (Roche Holding AG, Bsel, Switzerlnd), the FDA pproved nti-obesity drug, cnnot be well tolerted becuse of its gstrointestinl dverse effects (94). The most ltely pproved nti-obesity drugs, including lorcserin, nd topirmte/phentermine re definitely requiring post pprovl clinicl trils to crefully ssess their long-term efficcy nd sfety (95). Considerble dverse effects, limited efficcy nd lrms over the sfety of medictions, long with utilizing nti-obesity drugs in combintion with low clorie diet in clinicl trils (95), remind the fct tht the key to effective weight reduction is still low-clorie diet, ccompnied by physicl exercise. Putting together lrger, more crefully designed clinicl trils, with long durtion of follow up nd strict protocols, for registering side effects nd dverse events, is mndtory to offer proof of the vlue of herbl supplements, cupuncture nd non-invsive body contouring in overweight/obese individuls. Until concrete evidence, with regrd to effectiveness nd long-term sfety of CAM weight loss techniques, is vilble, combintion of helthy nutrition nd physicl ctivity should be the tretment strtegy offered to overweight nd obese individuls. Authors Contributions Literture review: Tin Mzheri, Mon Vhidi Rd; Drfting the mnuscript: Alirez Esteghmti, Tin Mzheri, Mon Vhidi Rd, Sin Noshd; Criticl revision of the mnuscript for importnt intellectul content: Alirez Esteghmti, Sin Noshd; Study supervision: Alirez Esteghmti. References 1. Alwn A. Globl sttus report on noncommunicble diseses 2010.Genev: World Helth Orgniztion; Mokdd AH, Bowmn BA, Ford ES, Vinicor F, Mrks JS, Kopln JP. The continuing epidemics of obesity nd dibetes in the United Sttes. Jm. 2001;286(10). 3. Chndrsekrn C, Vijylkshmi M, Prksh K, Bnsl V, Meenkshi J, Amit A. Review Article: Herbl Approch for Obesity Mngement. Am J Plnt Sci. 2013;3. 4. Obesity: The Prevention, Identifiction, Assessment nd Mngement of Overweight nd Obesity in Adults nd Children.London: Ntionl Institute for Helth nd Clinicl Excellence: Guidnce; Hurt RT, Kulisek C, Buchnn LA, McClve SA. The obesity epidemic: chllenges, helth inititives, nd implictions for gstroenterologists. Gstroenterol Heptol (N Y). 2010;6(12): Clle EE, Rodriguez C, Wlker-Thurmond K, Thun MJ. Overweight, obesity, nd mortlity from cncer in prospectively studied cohort of U.S. dults. N Engl J Med. 2003;348(17): Field AE, Cokley EH, Must A, Spdno JL, Lird N, Dietz WH, et l. Impct of overweight on the risk of developing common chronic diseses during 10-yer period. Arch Intern Med. 2001;161(13): Knnel WB, Adrienne Cupples L, Rmswmi R, Stokes III J, Kreger BE, Higgins M. Regionl obesity nd risk of crdiovsculr disese; the Frminghm Study. clinicl epidemiology J. 1991;44(2): Knowler WC, Brrett-Connor E, Fowler SE, Hmmn RF, Lchin JM, Wlker EA, et l. Reduction in the incidence of type 2 dibetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6): Mrmot M, Atinmo T, Byers T, Chen J, Hiroht T, Jckson A, et l. Food, nutrition, physicl ctivity, nd the prevention of cncer: globl perspective. UCL Discovery Sui Y, Zho HL, Wong VC, Brown N, Li XL, Kwn AK, et l. A systemtic review on use of Chinese medicine nd cupuncture for tretment of obesity. Obes Rev. 2012;13(5): Mthers CD, Loncr D. Projections of globl mortlity nd burden of disese from 2002 to PLoS Med. 2006;3(11). 13. Orgniztion WH. Switzerlnd: Globl helth risks: mortlity nd burden of disese ttributble to selected mjor risks. 14. Orgniztion WH. Switzerlnd: Globl recommendtions on physicl ctivity for helth. 15. Ezzti M, Orgniztion WH.. Comprtive Quntifiction of Helth Risks: Globl nd Regionl Burden of Disese Attributble to Selected Mjor Risk Fctors.Genev: World Helth Orgniztion. 16. Mitchell NS, Ctencci VA, Wytt HR, Hill JO. Obesity: overview of n epidemic. Psychitr Clin North Am. 2011;34(4): Helth NIo Helth NIo. Complementry, Alterntive, or Integrtive Helth: Wht s In Nme? Shrpe PA, Blnck HM, Willims JE, Ainsworth BE, Conwy JM. Use of complementry nd lterntive medicine for weight control in the United Sttes. J Altern Complement Med. 2007;13(2): Astell KJ, Mthi ML, Su XQ. A Review on Botnicl Species nd Chemicl Compounds with Appetite Suppressing Properties for Body Weight Control. Plnt Foods for Humn Nutrition. 2013;68(3): Int J Endocrinol Metb. 2015;13(2):e

8 Esteghmti A et l. 20. Hller CA, Dun M, Benowitz NL, Jcob P3. Concentrtions of ephedr lkloids nd cffeine in commercil dietry supplements. J Anl Toxicol. 2004;28(3): Triscri J, Sullivn AC. Anti-obesity ctivity of novel lipid synthesis inhibitor. Int J Obes. 1984;8 Suppl 1: Mrquez F, Bbio N, Bullo M, Sls-Slvdo J. Evlution of the sfety nd efficcy of hydroxycitric cid or Grcini cmbogi extrcts in humns. Crit Rev Food Sci Nutr. 2012;52(7): Preuss HG, Ro CV, Gris R, Brmble JD, Ohi SE, Bgchi M, et l. An overview of the sfety nd efficcy of novel, nturl(-)-hydroxycitric cid extrct (HCA-SX) for weight mngement. J Med. 2004;35(1-6): Heymsfield SB, Allison DB, Vsselli JR, Pietrobelli A, Greenfield D, Nunez C. Grcini cmbogi (hydroxycitric cid) s potentil ntiobesity gent: rndomized controlled tril. JAMA. 1998;280(18): Kovcs EM, Westerterp-Plnteng MS, de Vries M, Brouns F, Sris WH. Effects of 2-week ingestion of (-)-hydroxycitrte nd (-)-hydroxycitrte combined with medium-chin triglycerides on stiety nd food intke. Physiol Behv. 2001;74(4-5): Mttes RD, Bormnn L. Effects of (-)-hydroxycitric cid on ppetitive vribles. Physiol Behv. 2000;71(1-2): Vsques CA, Rossetto S, Hlmenschlger G, Linden R, Heckler E, Fernndez MS, et l. Evlution of the phrmcotherpeutic efficcy of Grcini cmbogi plus Amorphophllus konjc for the tretment of obesity. Phytother Res. 2008;22(9): Onkpoy I, Hung SK, Perry R, Wider B, Ernst E. The Use of Grcini Extrct (Hydroxycitric Acid) s Weight loss Supplement: A Systemtic Review nd Met-Anlysis of Rndomised Clinicl Trils. J Obes. 2011;2011: Wolfrm S, Wng Y, Thielecke F. Anti-obesity effects of green te: from bedside to bench. Mol Nutr Food Res. 2006;50(2): Rins TM, Agrwl S, Mki KC. Antiobesity effects of green te ctechins: mechnistic review. J Nutr Biochem. 2011;22(1): Jurgens TM, Wheln AM, Killin L, Doucette S, Kirk S, Foy E. Green te for weight loss nd weight mintennce in overweight or obese dults. Cochrne Dtbse Syst Rev. 2012;12:CD Gregersen NT, Bitz C, Krog-Mikkelsen I, Hels O, Kovcs EM, Rycroft JA, et l. Effect of moderte intkes of different te ctechins nd cffeine on cute mesures of energy metbolism under sedentry conditions. Br J Nutr. 2009;102(8): Kovcs EM, Lejeune MP, Nijs I, Westerterp-Plnteng MS. Effects of green te on weight mintennce fter body-weight loss. Br J Nutr. 2004;91(3): Ngo T, Hse T, Tokimitsu I. A green te extrct high in ctechins reduces body ft nd crdiovsculr risks in humns. Obesity (Silver Spring). 2007;15(6): Wng H, Wen Y, Du Y, Yn X, Guo H, Rycroft JA, et l. Effects of ctechin enriched green te on body composition. Obesity (Silver Spring). 2010;18(4): Mki KC, Reeves MS, Frmer M, Ysung K, Mtsuo N, Ktsurgi Y, et l. Green te ctechin consumption enhnces exercise-induced bdominl ft loss in overweight nd obese dults. J Nutr. 2009;139(2): Auvichypt P, Prpochnung M, Tunkmnerdthi O, Sripnidkulchi B, Auvichypt N, Thinkhmrop B, et l. Effectiveness of green te on weight reduction in obese This: A rndomized, controlled tril. Physiology & Behvior. 2008;93(3): Docherty JP, Sck DA, Roffmn M, Finch M, Komorowski JR. A double-blind, plcebo-controlled, explortory tril of chromium picolinte in typicl depression: effect on crbohydrte crving. J Psychitr Prct. 2005;11(5): Drke TC, Rudser KD, Sequist ER, Seed A. Chromium infusion in hospitlized ptients with severe insulin resistnce: retrospective nlysis. Endocr Prct. 2012;18(3): Tin H, Guo X, Wng X, He Z, Sun R, Ge S, et l. Chromium picolinte supplementtion for overweight or obese dults. Cochrne Dtbse Syst Rev. 2013;11:CD Riner L, Heiss CJ. Conjugted linoleic cid: helth implictions nd effects on body composition. J Am Diet Assoc. 2004;104(6): Priz MW, Prk Y, Cook ME. The biologiclly ctive isomers of conjugted linoleic cid. Prog Lipid Res. 2001;40(4): Gullier JM, Hlse J, Hoye K, Kristinsen K, Fgertun H, Vik H, et l. Conjugted linoleic cid supplementtion for 1 y reduces body ft mss in helthy overweight humns. Am J Clin Nutr. 2004;79(6): Kmphuis MM, Lejeune MP, Sris WH, Westerterp-Plnteng MS. The effect of conjugted linoleic cid supplementtion fter weight loss on body weight regin, body composition, nd resting metbolic rte in overweight subjects. Int J Obes Relt Metb Disord. 2003;27(7): Zmbell KL, Keim NL, Vn Lon MD, Gle B, Benito P, Kelley DS, et l. Conjugted linoleic cid supplementtion in humns: effects on body composition nd energy expenditure. Lipids. 2000;35(7): Onkpoy IJ, Posdzki PP, Wtson LK, Dvies LA, Ernst E. The efficcy of long-term conjugted linoleic cid (CLA) supplementtion on body composition in overweight nd obese individuls: systemtic review nd met-nlysis of rndomized clinicl trils. Eur J Nutr. 2012;51(2): Lee RA, Blick MJ. Indigenous use of Hoodi gordonii nd ppetite suppression. Explore (NY). 2007;3(4): Vermk I, Hmmn JH, Viljoen AM. Hoodi gordonii: n upto-dte review of commercilly importnt nti-obesity plnt. Plnt Med. 2011;77(11): McLen DB, Luo LG. Incresed ATP content/production in the hypothlmus my be signl for energy-sensing of stiety: studies of the norectic mechnism of plnt steroidl glycoside. Brin Res. 2004;1020(1-2): Lu Y, Teng HL, Yng GZ, Mei ZN. Three New Steroidl Glycosides from the Roots of Cynnchum uricultum. Molecules. 2011;16(12): Gu XJ, Yo N, Qin SH, Li YB, Li P. Four New C21Steroidl Glycosides from the Roots ofcynnchum uricultum. Helvetic Chimic Act. 2009;92(1): Liu S, Chen Z, Wu J, Wng L, Wng H, Zho W. Appetite suppressing pregnne glycosides from the roots of Cynnchum uricultum. Phytochemistry. 2013;93: Bldrick P. The sfety of chitosn s phrmceuticl excipient. Regul Toxicol Phrmcol. 2010;56(3): Hn LK, Kimur Y, Okud H. Reduction in ft storge during chitin-chitosn tretment in mice fed high-ft diet. Int J Obes Relt Metb Disord. 1999;23(2): Sumiyoshi M, Kimur Y. Low moleculr weight chitosn inhibits obesity induced by feeding high-ft diet long-term in mice. J Phrm Phrmcol. 2006;58(2): Thnou M, Verhoef JC, Junginger HE. Orl drug bsorption enhncement by chitosn nd its derivtives. Adv Drug Deliv Rev. 2001;52(2): Zhng J, Liu J, Li L, Xi W. Dietry chitosn improves hypercholesterolemi in rts fed high-ft diets. Nutr Res. 2008;28(6): Kumr SG, Rhmn MA, Lee SH, Hwng HS, Kim HA, Yun JW. Plsm proteome nlysis for nti-obesity nd nti-dibetic potentils of chitosn oligoscchrides in ob/ob mice. Proteomics. 2009;9(8): Rhmn M, Kumr SG, Yun JW. Proteome nlysis in dipose tissue of ob/ob mice in response to chitosn oligoscchrides tretment. Biotechnology nd Bioprocess Engineering. 2010;15(4): Ni Mhurchu C, Dunshe-Mooij CAE, Bennett D, Rodgers A, Ni Mhurchu C. Chitosn for overweight or obesity Hsni-Rnjbr S, Nyebi N, Lrijni B, Abdollhi M. A systemtic review of the efficcy nd sfety of herbl medicines used in the tretment of obesity. World J Gstroenterol. 2009;15(25): Joyl SV. A perspective on the current strtegies for the tretment of obesity. Curr Drug Trgets CNS Neurol Disord. 2004;3(5): Kng JW, Nm D, Kim KH, Huh JE, Lee JD. Effect of Gmbisn on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes. Evid Bsed Complement Alternt Med. 2013;2013: NIH Consensus Conference. Acupuncture. JAMA. 1998;280(17): Belivni M, Dimitroul C, Ktsiki N, Apostolopoulou M, Cummings M, Htzitolios AI. Acupuncture in the tretment of obesity: nrrtive review of the literture. Acupunct Med. 2013;31(1): Cbioglu MT, Ergene N. Chnges in serum leptin nd bet en- 8 Int J Endocrinol Metb. 2015;13(2):e19678

9 Esteghmti A et l. dorphin levels with weight loss by electrocupuncture nd diet restriction in obesity tretment. Am J Chin Med. 2006;34(1): Gucel F, Bhr B, Demirts C, Mit S, Cevik C. Influence of cupuncture on leptin, ghrelin, insulin nd cholecystokinin in obese women: rndomised, shm-controlled preliminry tril. Acupunct Med. 2012;30(3): Yin S, Lin-shn Z. Therpeutic ide nd pproches to obesity with cupuncture. Journl of Acupuncture nd Tuin Science. 2005;3(4): Sun Q, Xu Y. Simple obesity nd obesity hyperlipemi treted with otocupoint pellet pressure nd body cupuncture. J Trdit Chin Med. 1993;13(1): Tuǧrul Cbıoǧlu M, Ergene N. Electrocupuncture Therpy for Weight Loss Reduces Serum Totl Cholesterol, Triglycerides, nd LDL Cholesterol Levels in Obese Women. The Americn Journl of Chinese Medicine. 2005;33(04): Abdi H, Zho B, Drbndi M, Ghyour-Mobrhn M, Tvllie S, Rhsepr AA, et l. The effects of body cupuncture on obesity: nthropometric prmeters, lipid profile, nd inflmmtory nd immunologic mrkers. ScientificWorldJournl. 2012;2012: Abdllh Ismil N, Rgb SH, Abd Elbky A, Shoeib AR, Alhosry Y, Fekry D. Frequency of Firmicutes nd Bcteroidetes in gut microbiot in obese nd norml weight Egyptin children nd dults. Arch Med Sci. 2011;7(3): Cho SH, Lee JS, Thbne L, Lee J. Acupuncture for obesity: systemtic review nd met-nlysis. Int J Obes (Lond). 2009;33(2): Lin XM, Li B, Du YH, Xiong J, Sun P. [Systemtic evlution of therpeutic effect of cupuncture for tretment of simple obesity]. Zhongguo Zhen Jiu. 2009;29(10): Ling F, Koy D. Acupuncture: is it effective for tretment of insulin resistnce? Dibetes Obes Metb. 2010;12(7): Khn R, Ahmed A, Ismil FW, Abid S, Awn S, Shh H, et l. Perception nd knowledge bout dietry intke in ptients with liver cirrhosis nd its reltionship with the level of eduction. J Coll Physicins Surg Pk. 2012;22(7): Shping B, Reduction C. Technology Prolifertion Driven by Demnd.Aliso Viejo, CA: Medicl Insight, Inc; Bernstein G, Hnke CW. Sfety of liposuction: review of 9478 cses performed by dermtologists. J Dermtol Surg Oncol. 1988;14(10): Mulhollnd RS, Pul MD, Chlfoun C. Noninvsive body contouring with rdiofrequency, ultrsound, cryolipolysis, nd low-level lser therpy. Clin Plst Surg. 2011;38(3): Sedi N, Kminer M. New wves for ft reduction: high-intensity focused ultrsound. Semin Cutn Med Surg. 2013;32(1): Shlom A, Wiser I, Brwer S, Azhri H. Sfety nd Tolerbility of Focused Ultrsound Device for Tretment of Adipose Tissue in Subjects Undergoing Abdominoplsty: A Plcebo-Control Pilot Study. Dermtologic Surgery. 2013;39(5): Zhou YF. High intensity focused ultrsound in clinicl tumor bltion. World J Clin Oncol. 2011;2(1): Stephn PJ, Kenkel JM. Updtes nd dvnces in liposuction. Aesthet Surg J. 2010;30(1): Teitelbum SA, Burns JL, Kubot J, Mtsud H, Otto MJ, Shirkbe Y, et l. Noninvsive body contouring by focused ultrsound: sfety nd efficcy of the Contour I device in multicenter, controlled, clinicl study. Plst Reconstr Surg. 2007;120(3): Nestor MS, Newburger J, Zrrg MB. Body contouring using 635- nm low level lser therpy. Semin Cutn Med Surg. 2013;32(1): Jckson RF, Stern FA, Neir R, Ortiz-Neir CL, Mloney J. Appliction of low-level lser therpy for noninvsive body contouring. Lsers Surg Med. 2012;44(3): Avci P, Nyme TT, Gupt GK, Sdsivm M, Hmblin MR. Low-level lser therpy for ft lyer reduction: comprehensive review. Lsers Surg Med. 2013;45(6): Jckson RF, Dedo DD, Roche GC, Turok DI, Mloney RJ. Low-level lser therpy s non-invsive pproch for body contouring: rndomized, controlled study. Lsers Surg Med. 2009;41(10): Jlin HR, Avrm MM. Cryolipolysis: historicl perspective nd current clinicl prctice. Semin Cutn Med Surg. 2013;32(1): Weiss RA. Noninvsive rdio frequency for skin tightening nd body contouring. Semin Cutn Med Surg. 2013;32(1): Brightmn L, Weiss E, Chps AM, Kren J, Hle E, Bernstein L, et l. Improvement in rm nd post-prtum bdominl nd flnk subcutneous ft deposits nd skin lxity using bipolr rdiofrequency, infrred, vcuum nd mechnicl mssge device. Lsers in Surgery nd Medicine. 2009;41(10): Winter ML. Post-pregnncy body contouring using combined rdiofrequency, infrred light nd tissue mnipultion device. J Cosmet Lser Ther. 2009;11(4): Buchwld H, Avidor Y, Brunwld E, Jensen MD, Pories W, Fhrbch K, et l. Britric surgery: systemtic review nd metnlysis. JAMA. 2004;292(14): Bry GA, Ryn DH. Drug tretment of the overweight ptient. Gstroenterology. 2007;132(6): Cheung BM, Cheung TT, Smrnyke NR. Sfety of ntiobesity drugs. Ther Adv Drug Sf. 2013;4(4): Int J Endocrinol Metb. 2015;13(2):e

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