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Ahn, Lee, Lee, Choi, and Lee: A Review of Combination Effects and Adverse Effects of Yerba Mate (Ilex paraguariensis) on the Treatment of Obesity
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The aim of this study is to review the combination effects and adverse effects of Yerba Mate (Ilex paraguariensis) on the treatment of obesity


Four databases were searched, including Pubmed National assembly library, RISS4u, and NDSL, for studies published before March 31, 2016 using the keywords ‘yerba mate’, ‘Ilex paraguariensis’, and those related to ‘obesity’, Clinical trials, and both in vivo and in vitro studies were classified according to the following categories: publication year, nationality, types and composition of test compounds, combination effects, adverse effects, and safety.


A total of 16 articles (14 clinical trials, one in vivo, one in vitro) were included in the analysis. Combination effects were reported from six YGD (Yerba Mate, Guarana, Damiana, Zotrim), five Meltdown, one Shred-matrix, one DBX (DymaBurn Xtreme), one XSIII research study, and adverse effects were reported from two YGD (Zotrim), four Meltdown, one Shred-matrix and one MetEF research study. YGD and Shred-matrix increased satiety while YGD and MetEF had adverse gastrointestinal effects potentially due to guarana. Meltdown and Shred-matrix increased energy expenditure and fat oxidation and had the adverse effects of increased heart rate and blood pressure due to the thermogenic effect of caffeine and yohimbine. DBX increased resting energy expenditure but no difference was observed in respiratory exchange ratio. XSIII reduced body weight gain and food intake more than each of the extracts did on their own.


Taken together, the combination effects and adverse effects differed according to the composition of test compounds and the ratio of ingredients. Multicomponent approaches should be used for treating multifactorial diseases such as obesity. As a general conclusion, there is a place for a combination of herbal components including yerba mate, based on the principle of Kun-Shin-Choa-Sa for the treatment of obesity.

Fig. 1
Flowchart of study selection process
Fig. 2
The number of researches of yerba mate compound for the purpose of treatment of obesity analyzed by year
Fig. 3
Number of test compounds containing each component
Table 1
Composition of Test Compounds
Test compound Capacity of YM* Combined materials
YGD (Zotrim) 112 mg Guarana(95 mg)., Damiana(36 mg)
Meltdown n.r Anhydrous caffeine+alpha-methyl TTA+cAMP (317 mg) Yohimbine (9 mg) Synephrine HCl(20 mg)
R-BMPEA§+N-methyl-beta-PEA(138mg) Methyl-hordenine HCl(20 mg)
Shred-matrix n.r Anhydrous caffeine(50 mg). Guarana(100 mg). Green Tea(70 mg).
Yohimbine HCI. Cayenne Pepper Fo-Ti. Eleuthero root.
Anhydrous caffeine. Guarana. Green tea.
Black pepper. Chromium picolinate(100 mg).
DymaBurn Xtreme(DBX) n.r L-carnitine L-tartrate(200 mg), Pathothenic acid (17 mg). Salvia sclarea.
Raspberry ketones. Capsicum Annum. L-tyrosine plus. Salix alba. Ginger. Fucus vesiculosus. Panax ginseng.
XSIII 0.5 mg Green tea(5.33 mg). Coleus forskohlii(0.17 mg). Betula alba(0.5 mg)
MetEF n.r** Proprietary blend(1132 mg) of caffeine, guarana, green tea, garcinia cambogia etc.
Chromium picolinate(150 μg). Potassium(30 mg). Calcium(50 mg). Sodium(60 mg).

* YM: Yerba Mate.

TTA: tetradecylthioacetic acid.

cAMP: Cyclic Adenosine Monophosphate.

§ BMPEA: beta-methylphenylethylamine.

PEA: phenylethylamine.

MetEF: Metabolife Ephdra Free.

** n.r: not reported.

Table 2
Effects of Weight Loss Supplements including Yerba Mate on Obesity: in vitro
Study Experimental materials Concentrations Cell lines Comparison Significantly decreased in Oil red O assay Significantly decreased in TG* content Down-regulation of pro-adipogenic genes Up-regulation of anti-adipogenic genes
Santos et al (2014, Brazil) 22) Yerba Mate 50, 75, 100, (150), 200, 300 μg/mL 150, 200, 300 μg/mL (p<0.05) 150, 200 (p<0.05) 300 (p<0.01) Adig (Adipogenin), Axin (Axin 1), Cebpa (CCAAT/enhancer binding protein (C/EBP) alpha), Fgf10 (Fibroblast growth factor 10), Lep (Leptin), Lpl (Lipoprotein lipase), Pparγ2 (Peroxisome proliferator-activated receptor, gamma 2).(7 genes) Dlk-1 (Delta-like 1 homolog), Klf2 (Kruppel-like factor 2), and Ucp1(Uncoupling protein 1). (3 genes)
YGD 50, 75, (100), 150, 200, 300 μg/mL 100, 150, 200, 300 μg/mL (p<0.05) 50, 100 (p<0.05) 75, 150, 200, 300 (p<0.01) Down-regulated genes by Yerba Mate + Bmp2 (Bone morphogenetic protein 2), Ccnd1 (Cyclin D1), Fasn (Fatty acid synthase), Srebf1 (Sterol regulatory element binding transcription factor 1 (11 genes)
Resveratrol (10), 20, 30 μg/mL 3T3-L1 cells no 10, 20, 30 μg/mL (p<0.01) 10, 20 (p<0 01) 30 (p<0.05) Adig, Bmp2, Ccnd1, C/EBPα, Fasn, Fgf10, Lep, Lpl, Pparγ2.
Cebpb (CCAAT/enhancer binding protein(C/EBP),beta), Cdk4 (Cyclin-dependent kinase 4), Fgf2 (Fibroblast growth factor 2), Klf15(Kruppel-like factor 15). (13 genes)
Klf2, Ucp1, Ddit3(DNA-damage in-ducible transcript 3), Foxo1 (Forkhead box O1), Sirt1 (Sirtuin 1), Sirt2(Sirtuin 2) (6 genes)
YM + Resveratrol (150:10) or 200:10 μg/mL 150:10, 200:10 (p<0.01) 150:10 (p<0 01), 200:10 (p<0.05) Above all Above all
YGD + Resveratrol (100:10) or 150:10 μg/mL 100:10, 150:10 (p<0 01) 100:10, 150:10 (p<0 01) Above all Above all

* TG: Triglyceride

The regulation of gene expression involving in adipogenesis was examined at the parenthesized concentration

Table 3
Effects of Weight Loss Supplements including Yerba Mate on Obesity: in vivo
Study Species Sex Age Number of animals Intervention Comparison Duration Outcome Result
Krotkiewsk i (2008, Poland)23) Wistar rats Female 8 weeks 12/group 1)XSIII 6.5mg (oral) per 24h 2)Green tea 5.33 mg
3)Coleus forskohlii 0.17 mg
4)Yerba Mate 0.5 mg
5)Betula alba 0.5 mg (oral) per 24h
12 weeks 1)Weight gain(%) XSIII vs Green tea vs Coleus forskohlii vs Yerba Mate vs Betula alba: 32.12 % vs 45.54 % (p=0 0228) vs 44.68 % (p<0.0001) vs 42.22 % (p = 0.0753) vs 43.98 % (p=0.0004)
2)Food intake(g) Food intake was significantly lower than Green tea (p=0.1798) Coleus forskohlii (p =0.0036) Yerba Mate (p = 0.0058) Betula alba
Table 4
Effects of Weight Loss Supplements including Yerba Mate on Obesity: Clinical Trials
Study Design Participants Intervention Comparison Duration Outcome measures Result
Andersen (2001, Denmark)11) 1) N=7 (1/6) normal weight YGD 3Ca PLCb 3C Once each 1)Gastric emptying time YGD: 58 ± 15 min (53 % increase) (p=0 025) PLC: 38 ± 7.6 min
DBc PLC-controlled 2) N=47 (15/23) overweight (BMId 25.8–30.4) YGD 3C tide N=24 PLC 3C tid (N=23) 10, 45Df 2)WRg (kg) YGD vs PLC: 0.8 ± 0.05 vs 0.3 ± 0.03 (after 10 days)
YGD vs PLC: 5.1 ± 0.5 vs 0.3 ± 0.08 (after 45days)
Uncontrolled 3) N=22 (12/10) N=22 N = 0 12Mh 3) Weight maintenance 73 kg → 72.5 kg (after 12 months)
Ruxton (2004, UK24) Consumer survey N=48 (11/37) BMI > 20 Zotrim 2Ti tid No 4 weeks 1)WR 2.3 kg
2)QDj 83 % reported feeling fuller, 75 % believed they ate less, 69 % ate snacks less frequently than usual.
Ruxton et al (2005, UK)25) Consumer study N=61 (0/61) overweight(BMI 25–35) aged 18–70 years Zotrim 2T tid for 1 week and 3T tid for next 3 weeks No 4 weeks 1)WR (kg) 0.7(week 1) (p<0.0001) → 1.79(week4) (p<0.0001)
2)BRk (kg/m2) 0.27(week 1) (p<0.0001) → 0.68(week 4) (p<0.0001)
3)WCl (cm) −1.8(week 1) (p<0.001) → −4.3(week4) (p<0.0001)
4)HCm (cm) −1.3(week 1) (p<0.001) → −3.2cm(week 4) (p<0.0001)
5)QD Fullness: higher(week 1) (p<0 005) → higher(week 4) (p<0 05)
Hunger: lower(week 1) (p<0 0001) → lower(week4) (p<0.0001)
Ruxton, et al. (2007, UK)26) Consumer study N=73 overweight nurses (WC ≥ 94 cm(men) ≥ 80 cm(women) aged 18–70 years Zotrim 2T tid for 1 week and 3T tid for next 5 weeks. 12 subjects continued Zotrim after 6 weeks. No 6 weeks 1)Weight (kg) 84.4 → 82.1(week 6) (p<0.001) → 81.5(week 10) (p<0.001)
2)BMI (kg/m2) 30.8 → 30.0(week 6) → 29.6(week 10) (p<0.001)
3)WC (cm) 97.8 → 94.2(week 6) (p<0.001) → 92.6(week 10) (p<0.001)
4)HC (cm) 112.2 →108.5(week 6) (p<0.001) → 108.4(week 10) (p<0.001)
5)QD Fullness: higher(week 6) (p<0 005) → lower(week 10)
Hunger: lower(week 6) (p<0.05) → higher(week 10)
Week 10 compared with week 6
Harrold et al (2013, UK)27) DB PLC-controlled crossover N=58 (0/58) normal to slightly overweight (BMI 18.5–29.9) aged 18–65 years 1)YGD 3T+5g of SFFn bid 2)YGD 3T bid + water 3)SFF+ PLC 3T bid 4)Control (water+ PLC 3T bid) 1 day 1)Test meal intake reduction YGD present: 59.5 g(16.3 %), 112.4 kcal(17.3 %) (p<0.001)
SFF present: 31.9 g(9.1 %), 80 kcal(11.7 %) (p=0.001) compared with conditions when they were absent
2)Food choice YGD: reduced intake of HFSVo(p=0 03) and HFSWp (p=0 038) compared to control
YGD+SFF: reduced intake of HFSV(p<0 01) HFSW (p<0 001) LFSWq(p = 0 05) compared to control and LFSVr compared to YGD(p=0.032) and SFF(p = 0.019)
3)Appetite YGD+SFF lowered subjective ratings of hunger(p=0 027) and desire to eat(p=0.038) compared with control.
Jitomir et al (2008, USA)28) DB random PLC-controlled crossover N=12 (12/0) Aged 23.67 ± 466 years, height: 175.05 ± 7.16 cm Weight: 79.89 ± 18.01 kg healthy, recreationally active, mild caffeine users (80 mg/day) Meltdown 3C (500 mg) PLC 3C Two sessions 1)REEs (kcal/min) Meltdown vs PLC
1.44 ± 0 25 vs 1.28 ± 0.23 (45 min post-ingestion) (p=0.003)
1 49 ± 0 28 vs 1 30 ± 0 22 (60 min post-ingestion) (p=0.025)
1.51 ± 0.26 vs 1.33 ± 0.27 (60 min post-exercise) (p=0.014).
2)RERt (VCO2/VO2) 0 84 ± 0 03 vs 0 91 ± 0.04 (30min post-ingestion) (p=0.022)
0 82 ± 0 04 vs 0 89 ± 0.05 (45min post-ingestion) (p=0.042)
0.83 ± 0.05 vs 0.90 ± 0.07 (post-exercise) (p = 0.009)
Hoffman et al (2009,US A)29) DB rando m crossover N=10 (5/5) Aged 20.2 ± 1.2 years, height: 172.2 ± 8.9 cm, weight: 71.5 ± 17.2 kg, body fat: 17.3 ± 2.6 % Meltdown 3C PLC 3C. Two sessions 1)EEu(kcal/min) Meltdown vs PLC: 1.28 ± 0.33 vs 1.00 ± 0.32 (p = 0.01) (29 % increase during 3 hour period)
2)RQv 0.79 ± 0.4 vs 0.86 ± 0.7 (hour 3) (p<0.05)
3)FUw (kcal/min) 0.78 ± 0.23 vs 0.50 ± 0.38 (p = 0.06) (3 hour average)
Bloomer et al (2009 USA)30) DB rando m crossover design N = 10 (10/0) Aged 27 ± 4 years BMI: 25 ± 3 kg/m2 body fat: 9 ± 3 % Meltdown 3C PLC 3C Two sessions 1)NEx 1332 ± 128 vs 100 ± 133 pg/mL/90 min (p = 0.03)
2)Glycerol 44 ± 3 vs. 26 ± 2 μg/mL/90 min (p< 0.0001)
3)FFAy 1.24 ± 0.17 vs 0.88 ± 0.12 mmol/L/90 min (p=0.0003)
4)EPIz 665 ± 16 vs 664 ± 10 pg/mL/90 min (p>0.05)
5)EE(kcal) 35 ± 3 vs 27 ± 2 (30 min) (p = 0.02) 29.6 % increase
Bloomer et al (2009 USA)31) Randomized, placebo controlled crossover N=20 (10/10) Aged 23.7 ± 4.3/21.9 ± 2.4 BMI: 24.8 ± 2.9/22.6 ± 2.8 (men/women) Meltdown 3C PLC 3C Two sessions 1)NE 2345 ± 205 vs 1659 ± 184 pg/mL/6 hr (p=0.02)
2)Glycerol 79 ± 8 vs 59 ± 6 μg/mL/6 hr (p = 0.03)
3)FFA 2.46 ± 0.64 vs 1.57 ± 0.42 mmol/L/6 hr (p = 0.05)
4)EPI 367 ± 58 vs 183 ± 27 pg/mL/6 hr (p=0.01)
5)EE(kcal) 439 ± 26 vs 380 ± 14 kcal/6 hr (p = 0.02)
Rashti (2009,US A)32) DB, random crossover N=10 (0/10) Aged 20.4 ± 0.70 years BMI: 23.9 ± 3.5 kg/m2 Meltdown drink 140 ml PLC 140 ml Two sessions 1)VO2aa increase 13.9 % (hour 2) (p=0.01) → 11.9 % (hour3) (p = 0.03)
2)EE (kcal/min) 1.09 ± 0.10 vs 0.99 ± 0.09 kcal/min (3 hour average) (p=0.03)
3)RQ 0.86 ± 0.05 vs 0.88 ± 0.06 (3 hour average) (p>0.05)
Alkhatib et al (2015 UK)33) DB crossover repeated, controlled N = 12 (7/5) Aged 24 ± 3.8 years, BMI: 22.5 ± 3.85 kg/m2 Shred-matrix 3C(1.5 g) PLC 3C Two sessions 1)FAObb increase FAO increased by 28 % before exercise (p<0 05) and 26 % after 30 min exercise (p>0.05) comparing to PLC.
2)RPEcc Lowered throughout the exercise duration (p<0.001)
3)Satiety Higher satiety score 30 min post-ingestion (p = 0.039)
Outlawetal(2013, USA)34) DB crossover N = 12 (6/6) Aged 22.50 ± 3.22 years Weight: 76.94 ± 14.78 kg DBX 2C PLC 2C Two sessions 1)REE DBX vs PLC: 147.3 ± 3.5 vs 32.1 ± 86.7 (kcal/day)(hour 4) (p = 0.003)
2)RER No significant difference

Data are mean±SD. N=(male/female)

Ca: Capsule. PLCb: Placebo. DBc: Double Blind. BMId: Body Mass Index. tide: three times a day. Df: Days. WRg: Weight Reduction. Mh: Month. Ti: Tablet. QDj: Questionnaire data. BRk: BMI Reduction. WCl: Waist Circumference. HCm: Hip Circumference. SFFn: Soluble Fermentable Fibre. HFSVo: High Fat Savoury. HFSWp: High Fat Sweet. LFSWq: Low Fat Sweet. LFSVr: Low Fat Savoury. REEs: Resting energy expenditure. RERt: Respiratory Exchange Ratio. EEu: Energy Expenditure. RQv: Respiratory quotient. FUw: Fat Utilization. NEx: Norepinephrine. FFAy: Free fatty acids. EPIz: Epinephrine. VO2aa: Resting oxygen consumption. FAObb: Fatty Acid Oxidation. RPEcc: Rate of Perceived Exertion.

Table 5
Adverse effects of Weight Loss Supplements including Yerba Mate on Obesity
Study Design Participants Intervention Comparison Duration Adverse effects
Ruxton et al (2005, UK)25) Consumer study N=61 (0/61) overweight(BMI 25–35) aged 18–70 years Zotrim 2T for 1 week, 3T for next 3 weeks No 4 weeks Feeling unwell, tired, change in bowel habit, sleeplessness, bloating
Ruxton, et al. (2007, UK)26) Consumer study N=73 overweight nurses aged 18–70 years (WC ≥ 94 cm(men) 80 cm(women) Zotrim 2T for 1 week, 3T for next 5 weeks.. No 6 weeks Bloating, nausea, irritability, psoriasis, constipation, sleeplessness
Hoffman et al (2009,USA)29) DB random crossover N=10 (5/5) Aged 20 2 ± 1.2 years height: 172.2 ± 8.9 cm weight: 71.5 ± 17.2 kg body fat: 17.3 ± 2.6 % Meltdown(M) 3C PLC 3C. Two sessions HR(b/min) Meltdown vs PLC: 72.3 ± 9.1 vs 64.8 ± 5.8 (hour 3) (p<0 05)
SBP* (mmHg)Meltdown vs PLC: 119.3 ± 8.9 vs 111.7 ± 7.9 (hour3) (p = 0.002)
Bloomer et al (2009USA)30) DB random crossover N = 10 (10/0) Aged 27 ± 4 years BMI: 25 ± 3 kg/m2 body fat: 9 ± 3 % Meltdown 3C PLC 3C Two sessions SBP(mmHg) Meltdown vs PLC: 122 ± 3 vs 116 ± 1 (90 min) (p = 0.04)
Bloomer et al (2009 SA)31) Random,placebo controlled crossover N=20 (10/10) Aged 237 ± 4.3/21.9 ± 2.4 BMI: 24.8 ± 2.9/22.6 ± 2.8 (men/women) Meltdown 3C PLC 3C Two sessions HR(bpm) 1–9 higher(p = 0.01)
BP(mmHg) both SBP and DBP was 1–16 higher (p<0.0001)
Rashti(2009,US A)40) DB, random crossover N = 10 (0/10) Aged 20.4 ± 0.70 years, BMI: 23.9 ± 3.5 kg/m2 Meltdown drink 140ml PLC 140 ml Two sessions SBP(mmHg) Meltdown vs PLC: 110.0 ± 3.9 vs 107.3 ± 4.4 (3 hour average) (p=0.007)
Buchanan(2015, USA)41) DB, random crossover N=31 (15/16) Aged 18–40 years, Weight: 69.87 ± 15.7 kg Shred-matrix PLC Two sessions Increase: SBP, DBP(due to vascular resistance), arterial pressure, pulse pressure, pulse rate, pulse wave velocity from carotid to radial, from carotid to femoral, from femoral to distal. Decrease: cardiac ejection time, stroke volume, cardiac output, arterial elasticity
Min et al (2005, USA)39) DB, random placebo controlled crossover N=20 (12/8) Age ≥ 18 MetEF 1C PLC 1C Two sessions Headache, gastrointestinal upset, sweating, palpitation, jitteriness

* SBP: Systolic Blood Pressure.

DBP: Diastolic Blood Pressure.

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