review article effects of commercially available dietary...

Review ArticleEffects of Commercially Available Dietary Supplements onResting Energy Expenditure A Brief Report

Roger A Vaughan123 Carole A Conn3 and Christine M Mermier1

1 Department of Health Exercise and Sports Science University of New Mexico USA2Department of Biochemistry and Molecular Biology University of New Mexico Health Sciences Center USA3Department of IFCE Nutrition University of New Mexico USA

Correspondence should be addressed to Roger A Vaughan vaughanrunmedu

Received 18 September 2013 Accepted 10 October 2013 Published 2 January 2014

Academic Editors H Schroder C Soulage and M Tesauro

Copyright copy 2014 Roger A Vaughan et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Commercially available dietary products advertised to promote weight loss are an underresearched but heavily purchasedcommodity in the United States Despite only limited evidence interest in dietary supplements continues to increase This workuniquely summarizes the current evidence evaluating the efficacy of several over-the-counter thermogenic products for theireffects on resting energy expenditure Currently there is some evidence suggesting dietary products containing select ingredientscan increase energy expenditure in healthy young people immediately following consumption (within 6 hours) It is unclearif supplement-induced increases in metabolic rate provide additional benefit beyond that provided by dietary constituents thatcontain similar ingredients It is also unclear if dietary supplements are effective for weight loss in humans

1 Introduction

Obesity has rapidly become a leading cause of deathwithout aforeseeable resolution in the near future Most clinicians be-lieve the combination of food overconsumption with seden-tary lifestyle synergistically promote weight gain and obesityThe importance of restrictive dietary practices in combina-tion with physical activity are of undeniable importance forweight loss and general health [1 2] however the role of gen-omics and corresponding interactions with dietary and exer-cise practice still remain largely ill-defined as the field is stillin its infancy [3] A variety of therapies are currently availableto combat obesity however recent trends in obesity preva-lence provide strong evidence that current interventions areinsufficient to effectively slow the development of obesity andrelated comorbidities [1ndash3]

The role which food chemicals and dietary componentsmay play in obesity therapeutics is increasing interest In obe-sity research several classes of chemicals including methylx-anthines polyphenols capsaicin (capsaicinoidscapsinoids)polyunsaturated fats and many other components found infood have shown some promise in promoting a metabolic

advantage forweight loss [4 5] As a result of preliminary datasupporting some of the aforementioned ingredients produc-ers of commercially available dietary supplements often in-clude one or many of these components in their products [5]Dietary supplements are sold for a variety of purposesincluding weight loss and many ingredients are promotedspecific benefits such as increased thermogenesis

Dietary supplements are unique because unlike pharma-ceutical agents they do not require close regulation of con-tent function or safety prior to consumption by humans [6]and are generally not recommended by healthcare profes-sionals [7] Because of limited regulation it is not uncommonfor single ingredients to be promoted for a promiscuousvariety of unsubstantiated functions and health benefitsAlthough subjected to limited regulation it is mandated thatall dietary supplements be marked with a disclaimer statingthe lack of support by the FDA for all claims Supplementssold as thermogenic products for weight loss andor energyaugmenters are often promoted to cause rapid weight lossoften times independent of calorie restriction or physicalactivity Despite resistance from healthcare professionalsconsumer interest in dietary supplements continues to surge

Hindawi Publishing CorporationISRN NutritionVolume 2014 Article ID 650264 7 pageshttpdxdoiorg1011552014650264

2 ISRN Nutrition

[8] According to NHANES questionnaire data from roughly12000 participants approximately 50 of those surveyedused dietary supplements in the past 30 days [8] Use wasmost common among 20ndash30-year-old participants andmorecommon inwomen than inmen [8] Interestinglywhen askedto select the motivating factor for supplement consumptionldquoweight lossrdquo or ldquoget more energyrdquo were reported as the mot-ivation for approximately 14 of participants both of whichwere also more common in women participants [8] Thiswork seeks to summarize current research evaluating com-mercially available dietary supplements sold as stimulators ofthermogenesis and increasedmetabolic rate leading toweightloss

2 Individual Ingredients asMetabolic Stimulators

21 Caffeine and Xanthine Metabolites Of the available die-tary supplements marketed for weight loss many contain ablend of ingredients that includes caffeine Caffeine has pre-viously been shown to dose-dependently heighten restingenergy expenditure in adult humans both normal and over-weight [5 9ndash14] Despite some conflicting data it is generallyaccepted that caffeine effectively stimulates the central ner-vous system and increases metabolic rate in humans [14ndash16]Caffeine functions through inhibition of phosphodiesterase(PDE) and through stimulation of adenosine receptors lead-ing to accumulation of intracellular 35-cyclic-adenosinemonophosphate (cAMP) which is metabolically excitatoryfor cells [11 12 14]

22 1205732-Adrenergic Receptor Agonists Like caffeine stimula-

tors of 1205732-adrenergic receptors such as ephedraephedrine

have been another primary component found in supplemen-tal thermogenic products [9 11 14] Following the restrictionof ephedra use similar chemical analogs such as synephrinefrom bitter orange extract became widely accepted replace-ments [17ndash20] 120573

2-adrenergic receptor agonists work to in-

crease cAMP biosynthesis while caffeine inhibits the break-down of cAMP by PDE [14] Additionally salicylates inhibitprostaglandins further allowing the accumulation of cAMP[14] Taken together caffeine 120573

2-adrenergic receptor agonists

and salicylates function to synergistically increase cAMPaccumulation and metabolic rate [14]

23 Green Tea Extract Polyphenols Several other dietarystimulators of metabolism are thought to function by aug-menting the accumulation of cAMP [14] Green tea extract isrich in polyphenols and is heavily promoted for health bene-fits including increased metabolism [4 12ndash14 21ndash28] Epigal-locatechin gallate (EGCG) epigallocatechin (EGC) epicate-chin gallate (ECG) and epicatechin (EC) are believed to causemost of green tearsquos beneficial effects [5] Other teas such asblack tea thearubigins and theaflavins share similar effects tothose found in green tea [4 29] Green tea extract appears tooffer some thermogenic effect when coupled with caffeineresulting in increased energy expenditure [14 22 30] In con-trast isolated green tea polyphenol ingestion independent

of caffeine does not appear to increase metabolic rate how-ever it does increase indicators of fat metabolism in somepopulations [14 22 30]

Green tea is purported to function by inhibiting thedegradation of 120573

2-adrenergic receptor agonists such as nore-

pinephrine by the enzyme catechol O-methyltransferase(COMT) thereby increasing intracellular cAMP [4 12]Again the combination of green tea polyphenols with caf-feine cause a synergistic effect further increasing cAMP Re-cently the effects and mechanisms of green tea extract inhuman metabolism were reviewed and it was suggested thatthe mechanism of COMT inhibition is possibly a product ofin vitro experimental conditions because COMT inhibitionexperiments have yet to identify a specific catechin inhibitoror determine if the active polyphenol is an inhibitor a sub-strate of COMT or a combination [31] Additionally themechanisms of the hypothesized downstream effect ofCOMT inhibition resulting in heightened fat metabolismhave yet to be elucidated experimentally [31] In addition toCOMT inhibition it is theorized that effects of green teaextract are also a function of metabolic gene activation Spe-cifically green tea may function to inhibit adipogenic genessuch as peroxisome proliferator-activated receptor (PPAR120574)and sterol regulatory element binding protein-1c (SREBP-1c)and increase the expression of genes that increase energyexpenditure and mitochondrial biogenesis including nuclearrespiratory factors (NRF) mitochondrial uncoupling pro-tein-3 (UCP3) peroxisome proliferator-activated receptor(PPAR120572) and peroxisome proliferator-activated receptor 120574coactivator-1120572 (PGC-1120572) leading to increased oxidative andmetabolic capacities [31]

24 Capsaicinoids and Capsinoids Another common constituent of thermogenic products is the capsaicinoidscapsinoids components found in spicy foods such as chilipepper and cayenne [32 33] Available data suggests that sup-plemental capsaicinoidscapsinoids effectively increase rest-ing energy expenditure although findings have been incon-sistent [32ndash34] Capsaicinoids are believed to function byincreasing catecholamine release heightening sensitivity tocirculating catecholamines or a combination thereof [33]Figure 1 summarizes the proposed mechanisms of the above-mentioned individual ingredients commonly found in com-mercially available thermogenic products

3 Propriety and Commercially AvailableThermogenic Products

31 Proprietary Products Several previous investigationshave identified that commercially available products increaseresting energy expenditure in a variety of subjects most fre-quently using young healthy subjects (Table 1) Most com-monly these products contain several of the following caffe-ine green tea capsaicin and catecholamine-like compounds(synephrine) In general most investigations evaluated chan-ges in energy expenditure within 6 hours of consumptionWhile the magnitude of the individual supplementrsquos effect on

ISRN Nutrition 3

EGCG

COMT

Salicylate PG

NE G-CPR

AC

cAMP

AMP

PDE Caffeinexanthine metabolites

AMPKCREBPKA

Gene transcription

Increased energy expenditure and fatty acid oxidation

ATP

Capsaicin

Figure 1 Summary of proposedmechanisms of common ingredients in thermogenic products adenylate cyclase (AC) adenosinemonophos-phate (AMP) 35-cyclic-adenosine monophosphate (cAMP) 51015840adenosine monophosphate-activated protein kinase (AMPK) adenosinetriphosphate (ATP) catechol O-methyltransferase (COMT) cAMP-related element binding protein (CREB) epigallocatechin gallate(EGCG) G-coupled protein receptor (G-CPR) prostaglandin (PG) protein kinase A (PKA) norepinephrine (NE) and phosphodiesterase(PDE)

energy expenditure seems to vary depending on the ingredi-ents consumed the increase in energy expenditure is similarto previous observations using individual ingredients such ascaffeine ranging from 50 to 200 k cals per hour immediatelyfollowing ingestion Although this increase is experimentallysignificant it must be stressed that the effect is time-depend-ent and energy expenditure appears to return to basal levels6 hours following consumption Previous acute (24 hours orless) investigations with caffeine alone or green tea with caffe-ine showed approximately a 4 increase in 24 hourmetabolicrate [5 10 12 14] which approximates the increases seen withselected thermogenic products Extended treatment for up to8 weeks has also shown increased resting energy expendituresuggesting that regular green tea consumption with selectstimulants can continuously cause an increase in metabolism[35 36]

Despite evidence that several of the single ingredients pre-viously described have been shown to increasemetabolic ratethere is some question about the efficacy of advertised diet-ary products for weight reduction Hasani-Ranjbar and col-leagues selectively identified dozens of studies which impli-cate natural products in the reduction of body weight in hu-mans [6] The investigations reviewed ingredients frequentlyfound in dietary supplements including caffeine ephedraand a variety of herbal agents many of which function in partas antioxidants [6] These studies included experimental

designs lasting from as little as 4 weeks to up to 9 monthswithout controlling for exercise andor concurrent energy re-striction In general there appears to be some evidence thatthermogenic products may partially aid in weight lossalthough it is difficult to identify the magnitude because ofbetween-study variables

4 Limitations to Current Observations

41 Individual Ingredients One possible contributor to dis-crepancies within the literature regarding efficacy of indi-vidual ingredients is experimental variability Multiple con-founds exist in energy expenditure measurements such asduration of measurement type of analytical and measure-ment software duration of measurement after ingestion ofstimulant and the amount of purportedmetabolic stimulatorconsumed An additional issue is that much of the originalmeasurements were conducted several decades ago More-over significant biological differences between demographicsmay also contribute to varied response across similar studies

42 Commercial Products Proprietary blends found withindietary supplements have numerous issues that are not en-countered when testing pharmaceutical grade single chemi-cals (such as caffeine) For example dietary supplements may

4 ISRN Nutrition

Table 1 Investigations evaluating the effects of thermogenic products on resting energy expenditure (REE) following acute (24 hours or less)and extended (longer than 24 hours)

Subjects Ingredients Findings AuthorEffects of acute consumption of dietary supplements on energy expenditure

Obese men(119873 = 19)

Green tea extract 750mg L-tyrosine 609mg caffeine151mg cayenne 225mg calcium 1965mg

Supplement containingbioactive food ingredientsincreased daily REE by200 kJ or 2 (48 kcal)

Belza and Jessen2005 [34]

Healthy menand women(119873 = 20)

Caffeine anhydrous toothed clubmoss (Huperziaserrata) yerba mate (Llex paraguariensis) 31015840-51015840-CAMP(31015840-51015840-cyclic adenosine monophosphate) synephrineHCL R-beta-methylphenylethylamineN-Methyl-B-phenylethylamine yohimbeMethyl-hordenine

Increased REE 59 plusmn 26kcalsdot6 hrs serumepinephrinenorepinephrine glycerolsystolic and diastolic BP

Bloomer et al 2009[37]


Caffeine anhydrous toothed clubmoss (Huperziaserrata) yerba mate (Llex Paraguariensis) 31015840-51015840-CAMP(31015840-51015840-cyclic adenosine monophosphate) synephrineHCL R-beta-methylphenylethylamineN-mehtyl-B-phenylethylamine yohimbeMethyl-hordenine

Increased REE increasedHR no change in BP

Hoffman et al2009 [38]


Caffeine anhydrous toothed clubmoss (Huperziaserrata) yerba mate (Llex paraguariensis) 31015840-51015840-CAMP(31015840-51015840-cyclic adenosine monophosphate) synephrineHCL R-beta-methylphenylethylamineN-mehtyl-B-phenylethylamine yohimbeMethyl-hordenine

Increased REE 45 60 120minutes after ingestionwith no change in HR or BP

Jitomir et al 2008[39]


Caffeine anhydrous guarana yerba mate green teaextract L-carnitine L-tartrate pathothenic acidchromium picolinate proprietary blends containinsAssuriTea green tea extract Salvia sclarea raspberryketones and Capsicum annum extract plus l-tyrosineSalix alba Zingiber officinale fucus vesiculosus Panaxginseng bioperineW

Increased REE 60 120 180240 minutes after ingestion

Outlaw et al 2013[40]


Supplement caffeine 200mg capsicum extract3334mg Niacin 20mg Bioperine 5mg

Increased REE 50 minutesafter consumption withelevated HR and BP

Ryan et al 2009[32]

40 male and40 femalehealthyyoungsubjects

1mg capsinoids in 199mg of rapeseed oil andmedium-chain triglycerides

No change in REE orweight but increased fatoxidation

Snitker et al 2009[41]

10 healthysubjects pertreatment

600mg naringin 50mg p-synephrine100mg hesperidin 50mg p-synephrine 600mgnaringin1000mg hesperidin 50mg p-synephrine 600mgnaringin

Increased REE 129 kcalIncreased REE 183 kcalIncreased REE 79 kcal

Stohs et al 2011 [17]

8 male and 10femalehealthyyoungsubjects

442mg of a proprietary 100mg of caffeine 230mg ofgreen tea extract L-tyrosine L-taurine chocaminewhite willow extract yohimbine-HCl vinpocetine

Increased REE 60 120 180minutes after ingestion

Wilborn et al 2009[42]


Caffeine citrus aurantium garcinia cambogia andchromium polynicotinate

Significantly increased REEat 60 120 180min

Dalbo et al 2008[43]

ISRN Nutrition 5

Table 1 Continued

Subjects Ingredients Findings Author

18 healthyyoung men

15mg capsinoids in 199 mg of rapeseed oil andmedium-chain triglycerides

EE increased by 152 kJh(BAT+) (5 kcalshour)groups 1 hours afteringestion

Yoneshiro et al2012 [44]

Effects of extended consumption of dietary supplements on energy expenditure


pantothenic acid 40mg green tea leaf extract 200mgguarana extract (198mg of caffeine) 550mg bitterorange (9mg of synephrine) 150mg white willow barkextract (75mg of salicin) 50mg ginger root 10mgproprietary blend (L-tyrosine L-carnitine naringin)375mg phenylephrine (20mg)

Increased REE withincreased body weight

Greenway et al2006 [36]

Obesesubjects(119873 = 80)

Green tea extract 750mg L-tyrosine 609mg caffeine151mg Cayenne 225mg calcium 1965mg

Supplement increased REEby 873 kJ (21 kcal) sustainedfor 8 weeks with reducedbody fat mass

Belza et al 2007[35]

vary in content from one lot to the next suggesting somebatches function better than others Additionally supple-ments are not required to third-party test products for purityand content which allows for the possibility that nonlistedingredients are included and ingredients that are purportedlyincluded are missing Such inconsistencies would likely infl-ate the variability of experimentalmeasurement contributingto inconsistencies in the reported effects of dietary supple-ments Perhaps the most significant limitation to commer-cially available dietary supplements is the near-complete abs-ence of scholarly evidence supporting individual productsafety and efficacy Another interesting and significant vari-able worth discussing is the matter of funding for research ondietary supplementsMultiple articles disclose that funding iscontributed by the companies which market the product forretail purposes This is not surprising because cost of biolog-ical research continues to increase while funding opportun-ities remain limited therefore it is logical that select compa-nies have outsourced primary research opportunities to theuniversity setting Surprisingly many dietary supplementsadvertise one or multiple nonbiased studies illustrating effi-cacy of their product however often times these studies havenot been systematically peer-reviewed or readily shared withthe scientific community making the original research dif-ficult to locate In addition identification and tracking ofadverse events with the majority of studies would not meetrequirements for similar pharmaceutical agents [6] Of theknown adverse effects dry mouth insomnia nervousnesspalpitations headache hypertension arrhythmias myocar-dial infarction stroke and seizures have been linked to con-sumption of ingredients such as caffeine and ephedra sug-gesting a major need for further safety evaluation prior toconsumption [6 7] Lastly along with limited evidence ofwhole-body efficacy and safety there is inadequate evaluationof themolecular effects of commercially available dietary sup-plements Our lab previously demonstrated that select dietarysupplements containing a variety of ingredients could effec-tively increase skeletalmusclemetabolism andmitochondrialcontent in vitro however additional information is required

to adequately describe cell- and tissue-specific effects of ther-mogenic products [45 46]

5 Concluding Remarks

Increasing obesity prevalence and consumer interest in ther-mogenic dietary supplements support the need for further re-search of these and other supplement ingredients From theavailable evidence it appears that commercially availabledietary supplements advertised to stimulate metabolism havethe propensity to increase metabolic rate Despite significantincreases in resting energy expenditure it is doubtful thatcommercially available thermogenic products stimulatemetabolism more than consumption of food products con-taining equivocal content of caffeinestimulants andor poly-phenols Moreover it should be mentioned that increases inmetabolism induced by food or dietary supplement are smallcontributing only subtly to metabolic rate Additional re-search is necessary to identify the precise mechanisms bywhich commonly consumed ingredients function to alterenergy expenditure andwhat correspondingmolecular adap-tations may develop

Abbreviations

AC Adenylate cyclaseAMP Adenosine monophosphateAMPK 51015840Adenosine monophosphate-activated

protein kinaseATP Adenosine triphosphatecAMP 35-cyclic-adenosine monophosphateCOMT Catechol O-methyltransferaseCREB cAMP-related element binding proteinEGCG Epigallocatechin gallateEGC EpigallocatechinECG Epicatechin gallateEC EpicatechinG-CPR G-Coupled protein recepetorPG Prostaglandin

6 ISRN Nutrition

PKA Protein kinase ANE NorepinephrineNRF Nuclear respiratory factorsPGC-1120572 Peroxisome proliferator-activated receptor

120574 coactivator-1120572PPAR120572 Peroxisome proliferator-activated

receptor 120572PPAR120574 Peroxisome proliferator-activated

receptor 120574PDE PhosphodiesteraseSREBP-1c Sterol regulatory element binding

protein-1cUCP3 Mitochondrial uncoupling protein-3

Conflict of Interests

The authors declare no conflict of interests No funding wasreceived for this work

References

[1] S R Bird and J A Hawley ldquoExercise and type 2 diabetes newprescription for an old problemrdquo Maturitas vol 72 no 4 pp311ndash316 2012

[2] T Church ldquoExercise in obesity metabolic syndrome and dia-betesrdquo Progress in Cardiovascular Diseases vol 53 no 6 pp412ndash418 2011

[3] C A Conn R A Vaughan and W S Sherman ldquoNutritionalgenetics and energy metabolism in human obesityrdquo CurrentNutrition Reports vol 2 no 3 pp 142ndash150 2013

[4] R Hursel W Viechtbauer and M S Westerterp-PlantengaldquoThe effects of green tea onweight loss andweightmaintenancea meta-analysisrdquo International Journal of Obesity vol 33 no 9pp 956ndash961 2009

[5] RHurselWViechtbauer AGDulloo et al ldquoThe effects of cat-echin rich teas and caffeine on energy expenditure and fat oxi-dation ameta-analysisrdquoObesity Reviews vol 12 no 7 pp e573ndashe581 2011

[6] S Hasani-Ranjbar N Nayebi B Larijani and M Abdollahi ldquoAsystematic review of the efficacy and safety of herbal medicinesused in the treatment of obesityrdquoWorld Journal of Gastroenterol-ogy vol 15 no 25 pp 3073ndash3085 2009

[7] R B Saper D M Eisenberg and R S Phillips ldquoCommon diet-ary supplements for weight lossrdquo American Family Physicianvol 70 no 9 pp 1731ndash1738 2004

[8] R L Bailey J J Gahche P E Miller P R Thomas and J TDwyer ldquoWhyUS adults use dietary supplementsrdquo Jama InternalMedicine vol 173 no 5 pp 355ndash361 2013

[9] P A Daly D R Krieger A G Dulloo and J B Young ldquoEphed-rine caffeine and aspirin safety and efficacy for treatment of hu-man obesityrdquo International Journal of Obesity vol 17 no 1 ppS73ndashS78 1993

[10] A G Dulloo C A Geissler A Collins and D S Miller ldquoNor-mal caffeine consumption influence on thermogenesis anddaily energy expenditure in lean and postobese human volun-teersrdquo American Journal of Clinical Nutrition vol 49 no 1 pp44ndash50 1989

[11] A G Dulloo ldquoEphedrine xanthines and prostaglandin-inhi-bitors actions and interactions in the stimulation of thermoge-nesisrdquo International Journal of Obesity vol 17 no 1 pp S35ndashS401993

[12] A G Dulloo C Duret D Rohrer et al ldquoEfficacy of a green teaextract rich in catechin polyphenols and caffeine in increasing24-h energy expenditure and fat oxidation in humansrdquo Ameri-can Journal of Clinical Nutrition vol 70 no 6 pp 1040ndash10451999

[13] A G Dulloo J Seydoux L Girardier P Chantre and J Vand-ermander ldquoGreen tea and thermogenesis interactions betweencatechin-polyphenols caffeine and sympathetic activityrdquo Inter-national Journal of Obesity vol 24 no 2 pp 252ndash258 2000

[14] A G Dulloo ldquoThe search for compounds that stimulate ther-mogenesis in obesity management from pharmaceuticals tofunctional food ingredientsrdquoObesity Reviews vol 12 no 10 pp866ndash883 2011

[15] K J Acheson B Zahorska-Markiewicz and P P Pittet PhldquoCaffeine and coffee their influence on metabolic rate and sub-strate utilization in normal weight and obese individualsrdquoAmerican Journal of Clinical Nutrition vol 33 no 5 pp 989ndash997 1980

[16] K J Acheson GGremaud IMeirim et al ldquoMetabolic effects ofcaffeine in humans lipid oxidation or futile cyclingrdquo AmericanJournal of Clinical Nutrition vol 79 no 1 pp 40ndash46 2004

[17] S J Stohs H G Preuss S C Keith P L Keith HMiller and GR Kaats ldquoEffects of p-synephrine alone and in combinationwith selected bioflavo-noids on restingmetabolism blood pres-sure heart rate and self-reported mood changesrdquo InternationalJournal of Medical Sciences vol 8 no 4 pp 295ndash301 2011

[18] S J Stohs H G Preuss and M Shara ldquoThe safety of Citrusaurantium (bitter orange) and its primary protoalkaloid p-syn-ephrinerdquo Phytotherapy Research vol 25 no 10 pp 1421ndash14282011

[19] S J Stohs H G Preuss and M Shara ldquoA review of the humanclinical studies involving Citrus aurantium (bitter orange)extract and its primary protoalkaloid p-synephrinerdquo Interna-tional Journal of Medical Sciences vol 9 no 7 pp 527ndash538 2012

[20] S Haaz K R Fontaine G Cutter N Limdi S Perumean-Chaney and D B Allison ldquoCitrus aurantium and synephrinealkaloids in the treatment of overweight and obesity an updaterdquoObesity Reviews vol 7 no 1 pp 79ndash88 2006

[21] A Basu and E A Lucas ldquoMechanisms and effects of green teaon cardiovascular healthrdquo Nutrition Reviews vol 65 no 8 pp361ndash375 2007

[22] A Belza S Toubro and A Astrup ldquoThe effect of caffeine greentea and tyrosine on thermogenesis and energy intakerdquoEuropeanJournal of Clinical Nutrition vol 63 no 1 pp 57ndash64 2009

[23] C-H Hsu T-H Tsai Y-H Kao K-C Hwang T-Y Tseng andP Chou ldquoEffect of green tea extract on obese women a rand-omized double-blind placebo-controlled clinical trialrdquoClinicalNutrition vol 27 no 3 pp 363ndash370 2008

[24] Y-H Kao R A Hiipakka and S Liao ldquoModulation of endo-crine systems and food intake by green tea epigallocatechin gall-aterdquo Endocrinology vol 141 no 3 pp 980ndash987 2000

[25] M A Potenza F L Marasciulo M Tarquinio et al ldquoEpigallo-catechin gallate (EGCG) a green tea polyphenol reduces bloodpressure improves insulin sensitivity and protects againstmyo-cardial IschemiaReperfusion (IR) injury in SpontaneouslyHypertensive Rats (SHR)rdquo Diabetes vol 55 pp A126ndashA1262006

ISRN Nutrition 7

[26] D N Sarma M L Barrett M L Chavez et al ldquoSafety of greentea extracts a systematic review by theUS PharmacopeiardquoDrugSafety vol 31 no 6 pp 469ndash484 2008

[27] N P Seeram S M Henning Y Niu R Lee H S Scheuller andD Heber ldquoCatechin and caffeine content of green tea dietarysupplements and correlation with antioxidant capacityrdquo Journalof Agricultural and Food Chemistry vol 54 no 5 pp 1599ndash16032006

[28] V R Sinija and H N Mishra ldquoGreen tea health benefitsrdquo Jour-nal of Nutritional amp Environmental Medicine vol 17 no 4 pp232ndash242 2008

[29] S Wolfram Y Wang and F Thielecke ldquoAnti-obesity effects ofgreen tea from bedside to benchrdquoMolecular Nutrition and FoodResearch vol 50 no 2 pp 176ndash187 2006

[30] M C Lonac J C Richards MM Schweder T K Johnson andC Bell ldquoInfluence of short-term consumption of the caffeine-free epigallocatechin-3-gallate supplement teavigo on restingmetabolism and the thermic effect of feedingrdquo Obesity vol 19no 2 pp 298ndash304 2011

[31] A B Hodgson R K Randell and A E Jeukendrup ldquoThe effectof green tea extract on fat oxidation at rest and during exerciseevidence of efficacy and proposed mechanismsrdquo Advances inNutrition vol 4 pp 129ndash140 2013

[32] E D Ryan T W Beck T J Herda et al ldquoAcute effects of a ther-mogenic nutritional supplement on energy expenditure andcardiovascular function at rest during low-intensity exerciseand recovery from exerciserdquo Journal of Strength and Condition-ing Research vol 23 no 3 pp 807ndash817 2009

[33] K Diepvens K RWesterterp andM SWesterterp-PlantengaldquoObesity and thermogenesis related to the consumption of caf-feine ephedrine capsaicin and green teardquo American Journal ofPhysiology Regulatory Integrative and Comparative Physiologyvol 292 no 1 pp R77ndashR85 2007

[34] A Belza and A B Jessen ldquoBioactive food stimulants of sym-pathetic activity effect on 24-h energy expenditure and fat oxid-ationrdquo European Journal of Clinical Nutrition vol 59 no 6 pp733ndash741 2005

[35] A Belza E Frandsen and J Kondrup ldquoBody fat loss achievedby stimulation of thermogenesis by a combination of bioactivefood ingredients a placebo-controlled double-blind 8-weekintervention in obese subjectsrdquo International Journal of Obesityvol 31 no 1 pp 121ndash130 2007

[36] F Greenway L de Jonge-Levitan C Martin A Roberts IGrundy and C Parker ldquoDietary herbal supplements with phe-nylephrine for weight lossrdquo Journal ofMedicinal Food vol 9 no4 pp 572ndash578 2006

[37] R J Bloomer R E Canale M M Blankenship K G Ham-mond K H Fisher-Wellman and B K Schilling ldquoEffect of thedietary supplement Meltdown on catecholamine secretionmarkers of lipolysis and metabolic rate in men and womena randomized placebo controlled cross-over studyrdquo Lipids inHealth and Disease vol 8 article 32 2009

[38] J RHoffman J KangNA Ratamess S L Rashti C P Tranch-ina and A D Faigenbaum ldquoThermogenic effect of an acuteingestion of a weight loss supplementrdquo Journal of the Interna-tional Society of Sports Nutrition vol 6 article 1 2009

[39] J Jitomir E Nassar J Culbertson et al ldquoThe acute effects of thethermogenic supplement Meltdown on energy expenditure fatoxidation and hemodynamic responses in young healthymalesrdquo Journal of the International Society of Sports Nutritionvol 5 article 23 2008

[40] J Outlaw C Wilborn A Smith et al ldquoEffects of ingestion of acommercially available thermogenic dietary supplement onresting energy expenditure mood state and cardiovascularmeasuresrdquo Journal of the International Society of Sports Nutri-tion vol 10 article 25 2013

[41] S Snitker Y Fujishima H Shen et al ldquoEffects of novel capsi-noid treatment on fatness and energy metabolism in humanspossible pharmacogenetic implicationsrdquo American Journal ofClinical Nutrition vol 89 no 1 pp 45ndash50 2009

[42] CWilborn L Taylor C Poole et al ldquoEffects of ingesting a com-mercial thermogenic product on hemodynamic function andenergy expenditure at rest in males and femalesrdquo Applied Phys-iology Nutrition and Metabolism vol 34 no 6 pp 1073ndash10782009

[43] V J DalboMD Roberts J R Stout andCMKerksick ldquoAcuteeffects of ingesting a commercial thermogenic drink on changesin energy expenditure and markers of lipolysisrdquo Journal of theInternational Society of Sports Nutrition vol 5 article 6 2008

[44] T Yoneshiro S Aita Y Kawai T Iwanaga and M Saito ldquoNon-pungent capsaicin analogs (capsinoids) increase energy expen-diture through the activation of brown adipose tissue inhumansrdquo American Journal of Clinical Nutrition vol 95 no 4pp 845ndash850 2012

[45] R A Vaughan R Garcia-Smith M Bisoffi C A Conn and KA Trujillo ldquoConjugated linoleic acid or omega 3 fatty acids in-crease mitochondrial biosynthesis and metabolism in skeletalmuscle cellsrdquo Lipids in Health and Disease vol 11 article 1422012

[46] RAVaughan RGarcia-SmithM BisoffiKA Trujillo andCA Conn ldquoTreatment of human muscle cells with popular diet-ary supplements increase mitochondrial function and metab-olic raterdquo vol 9 no 1 article 101 2012

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

2 ISRN Nutrition

[8] According to NHANES questionnaire data from roughly12000 participants approximately 50 of those surveyedused dietary supplements in the past 30 days [8] Use wasmost common among 20ndash30-year-old participants andmorecommon inwomen than inmen [8] Interestinglywhen askedto select the motivating factor for supplement consumptionldquoweight lossrdquo or ldquoget more energyrdquo were reported as the mot-ivation for approximately 14 of participants both of whichwere also more common in women participants [8] Thiswork seeks to summarize current research evaluating com-mercially available dietary supplements sold as stimulators ofthermogenesis and increasedmetabolic rate leading toweightloss

2 Individual Ingredients asMetabolic Stimulators

21 Caffeine and Xanthine Metabolites Of the available die-tary supplements marketed for weight loss many contain ablend of ingredients that includes caffeine Caffeine has pre-viously been shown to dose-dependently heighten restingenergy expenditure in adult humans both normal and over-weight [5 9ndash14] Despite some conflicting data it is generallyaccepted that caffeine effectively stimulates the central ner-vous system and increases metabolic rate in humans [14ndash16]Caffeine functions through inhibition of phosphodiesterase(PDE) and through stimulation of adenosine receptors lead-ing to accumulation of intracellular 35-cyclic-adenosinemonophosphate (cAMP) which is metabolically excitatoryfor cells [11 12 14]

22 1205732-Adrenergic Receptor Agonists Like caffeine stimula-

tors of 1205732-adrenergic receptors such as ephedraephedrine

have been another primary component found in supplemen-tal thermogenic products [9 11 14] Following the restrictionof ephedra use similar chemical analogs such as synephrinefrom bitter orange extract became widely accepted replace-ments [17ndash20] 120573

2-adrenergic receptor agonists work to in-

crease cAMP biosynthesis while caffeine inhibits the break-down of cAMP by PDE [14] Additionally salicylates inhibitprostaglandins further allowing the accumulation of cAMP[14] Taken together caffeine 120573

2-adrenergic receptor agonists

and salicylates function to synergistically increase cAMPaccumulation and metabolic rate [14]

23 Green Tea Extract Polyphenols Several other dietarystimulators of metabolism are thought to function by aug-menting the accumulation of cAMP [14] Green tea extract isrich in polyphenols and is heavily promoted for health bene-fits including increased metabolism [4 12ndash14 21ndash28] Epigal-locatechin gallate (EGCG) epigallocatechin (EGC) epicate-chin gallate (ECG) and epicatechin (EC) are believed to causemost of green tearsquos beneficial effects [5] Other teas such asblack tea thearubigins and theaflavins share similar effects tothose found in green tea [4 29] Green tea extract appears tooffer some thermogenic effect when coupled with caffeineresulting in increased energy expenditure [14 22 30] In con-trast isolated green tea polyphenol ingestion independent

of caffeine does not appear to increase metabolic rate how-ever it does increase indicators of fat metabolism in somepopulations [14 22 30]

Green tea is purported to function by inhibiting thedegradation of 120573

2-adrenergic receptor agonists such as nore-

pinephrine by the enzyme catechol O-methyltransferase(COMT) thereby increasing intracellular cAMP [4 12]Again the combination of green tea polyphenols with caf-feine cause a synergistic effect further increasing cAMP Re-cently the effects and mechanisms of green tea extract inhuman metabolism were reviewed and it was suggested thatthe mechanism of COMT inhibition is possibly a product ofin vitro experimental conditions because COMT inhibitionexperiments have yet to identify a specific catechin inhibitoror determine if the active polyphenol is an inhibitor a sub-strate of COMT or a combination [31] Additionally themechanisms of the hypothesized downstream effect ofCOMT inhibition resulting in heightened fat metabolismhave yet to be elucidated experimentally [31] In addition toCOMT inhibition it is theorized that effects of green teaextract are also a function of metabolic gene activation Spe-cifically green tea may function to inhibit adipogenic genessuch as peroxisome proliferator-activated receptor (PPAR120574)and sterol regulatory element binding protein-1c (SREBP-1c)and increase the expression of genes that increase energyexpenditure and mitochondrial biogenesis including nuclearrespiratory factors (NRF) mitochondrial uncoupling pro-tein-3 (UCP3) peroxisome proliferator-activated receptor(PPAR120572) and peroxisome proliferator-activated receptor 120574coactivator-1120572 (PGC-1120572) leading to increased oxidative andmetabolic capacities [31]

24 Capsaicinoids and Capsinoids Another common constituent of thermogenic products is the capsaicinoidscapsinoids components found in spicy foods such as chilipepper and cayenne [32 33] Available data suggests that sup-plemental capsaicinoidscapsinoids effectively increase rest-ing energy expenditure although findings have been incon-sistent [32ndash34] Capsaicinoids are believed to function byincreasing catecholamine release heightening sensitivity tocirculating catecholamines or a combination thereof [33]Figure 1 summarizes the proposed mechanisms of the above-mentioned individual ingredients commonly found in com-mercially available thermogenic products

3 Propriety and Commercially AvailableThermogenic Products

31 Proprietary Products Several previous investigationshave identified that commercially available products increaseresting energy expenditure in a variety of subjects most fre-quently using young healthy subjects (Table 1) Most com-monly these products contain several of the following caffe-ine green tea capsaicin and catecholamine-like compounds(synephrine) In general most investigations evaluated chan-ges in energy expenditure within 6 hours of consumptionWhile the magnitude of the individual supplementrsquos effect on

ISRN Nutrition 3

EGCG

COMT

Salicylate PG

NE G-CPR

AC

cAMP

AMP


AMPKCREBPKA

Gene transcription


ATP

Capsaicin








4 ISRN Nutrition



Obese men(119873 = 19)























Ryan et al 2009[32]

















ISRN Nutrition 5

Table 1 Continued


18 healthyyoung men

















Abbreviations



6 ISRN Nutrition








References


























ISRN Nutrition 7



























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















ISRN Nutrition 3

EGCG

COMT

Salicylate PG

NE G-CPR

AC

cAMP

AMP


AMPKCREBPKA

Gene transcription


ATP

Capsaicin








4 ISRN Nutrition



Obese men(119873 = 19)























Ryan et al 2009[32]

















ISRN Nutrition 5

Table 1 Continued


18 healthyyoung men

















Abbreviations



6 ISRN Nutrition








References


























ISRN Nutrition 7



























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















4 ISRN Nutrition



Obese men(119873 = 19)























Ryan et al 2009[32]

















ISRN Nutrition 5

Table 1 Continued


18 healthyyoung men

















Abbreviations



6 ISRN Nutrition








References


























ISRN Nutrition 7



























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















ISRN Nutrition 5

Table 1 Continued


18 healthyyoung men

















Abbreviations



6 ISRN Nutrition








References


























ISRN Nutrition 7



























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















6 ISRN Nutrition








References


























ISRN Nutrition 7



























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















ISRN Nutrition 7



























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















review article effects of commercially available dietary...

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