Advertisement

A comprehensive overview on the effects of green tea on anthropometric measures, blood pressure, glycemic and lipidemic status: An umbrella review and meta meta-analysis study

  • Tirang R. Neyestani
    Affiliations
    Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Bahareh Nikooyeh
    Correspondence
    Corresponding author. Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran 198161957, Iran
    Affiliations
    Laboratory of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    Search for articles by this author

      Highlights

      • Green tea and its bioactive constituents have beneficial effects on body weight, blood pressure, blood glucose and lipids.
      • These compounds are, at least in part, responsible for GT health benefits including decrease in cardiometabolic risk factors.
      • Regular consumption of GT and probably its bioactive constituents as supplements have beneficial effects on different health aspects including body weight, blood pressure, blood glucose and lipids.
      • Effects might be influenced by the amount of consumption, health/disease condition, dietary habits and physical activity.

      Abstract

      Aim

      The aim of this meta-review was to establish the effects of green tea (GT) intake on some cardiometabolic risk factors including anthropometric measures, blood pressure as well as blood glucose and lipids using evidence from previous systematic reviews and meta-analyses.

      Data synthesis

      Articles were identified via searches in PubMed, Embase, and the Cochrane Library, Web of Knowledge database from the index date of each database through January 31, 2021. A total of 13 meta-analyses were finally included in the synthesis. Meta-meta-analysis revealed significant effects of GT on weight and waist circumference with weighted mean difference (WMD) of −0.89 (95% CI -1.43 to −0.34, p < 0.001) and −1.01 (95% CI -1.63 to −0.39, p < 0.001), systolic and diastolic blood pressure, with WMDs of −1.17 (95% CI -2.18 to −0.16) and −1.24 (95% CI -2.07 to −0.4), respectively. There was similar effect on fasting blood glucose (WMD, −1.3, 95% CI -2.09 to −0.51, p < 0.001) but not on other glycemic indicators. The findings also revealed a significant effect size of total cholesterol and LDL-C (WMD -4.93; 95% CI -6.41 to −3.46, p < 0.001, WMD -4.31; 95% CI -6.55 to −2.07, p < 0.001, respectively).

      Conclusion

      Regular consumption of GT and probably its bioactive constituents as supplements have beneficial effects on different health aspects including weight, blood pressure, blood glucose and lipids. However, these effects might be influenced by several factors such as the amount and frequency of consumption, health/disease condition and life style including dietary habits and physical activity.

      Keywords

      1. Introduction

      Different varieties of tea including non-fermented green tea; semi-fermented oolong tea; and fully fermented black tea are among the widely consumed beverages around the world. Green tea (GT) is not just a refreshing drink since it contains large amounts of bioactive compounds such as flavonoid-like polyphenols, proteins, including enzymes, antioxidants, minerals, and vitamins [
      • He H.-F.
      • Wei K.
      • Yin J.
      • Ye Y.
      Insight into tea flavonoids: composition and chemistry.
      ]. Polyphenolic compounds representing 36% of dry weight of GT, exert a variety of physiological actions. The main polyphenolic secondary metabolites (flavonoids) present in GT are catechins, which include epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG), gallocatechin (GC), catechin gallate (CG), and gallocatechin gallate (GCG) [
      • Henning S.M.
      • Fajardo-Lira C.
      • Lee H.W.
      • Youssefian A.A.
      • Go V.L.
      • Heber D.
      Catechin content of 18 teas and a green tea extract supplement correlates with the antioxidant capacity.
      ]. These compounds are, at least in part, responsible for GT health benefits including decrease in cardiovascular disease (CVD) risk [
      • Stangl V.
      • Lorenz M.
      • Stangl K.
      The role of tea and tea flavonoids in cardiovascular health.
      ,
      • Balentine D.A.
      • Wiseman S.A.
      • Bouwens L.C.
      The chemistry of tea flavonoids.
      ]. A community study showed that subjects who were drinking three to five cups of GT a day had a 41% lower CVD mortality compared with GT non-drinkers [
      • Mineharu Y.
      • Koizumi A.
      • Wada Y.
      • Iso H.
      • Watanabe Y.
      • Date C.
      • et al.
      Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women.
      ]. These findings were further supported by recent studies indicating that tea polyphenols including EGCG may lower CVD risk [
      • Dludla P.V.
      • Nkambule B.B.
      • Mazibuko-Mbeje S.E.
      • Nyambuya T.M.
      • Orlando P.
      • Silvestri S.
      • et al.
      Tea consumption and its effects on primary and secondary prevention of coronary artery disease: qualitative synthesis of evidence from randomized controlled trials.
      ,
      • Keller A.
      • Wallace T.C.
      Tea intake and cardiovascular disease: an umbrella review.
      ,
      • Abe S.K.
      • Inoue M.
      Green tea and cancer and cardiometabolic diseases: a review of the current epidemiological evidence.
      ] via multiple mechanisms including inhibition of oxidation, vascular inflammation, thrombogenesis, improvement in blood lipid profile and also alteration of the gut microbiota [
      • Xing L.
      • Zhang H.
      • Qi R.
      • Tsao R.
      • Mine Y.
      Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols.
      ,
      • Meng Q.
      • Li S.
      • Huang J.
      • Wei C.-C.
      • Wan X.
      • Sang S.
      • et al.
      Importance of the nucleophilic property of tea polyphenols.
      ,
      • Zhang Y.
      • Cheng L.
      • Liu Y.
      • Zhang R.
      • Wu Z.
      • Cheng K.
      • et al.
      Omics analyses of intestinal microbiota and hypothalamus clock genes in circadian disturbance model mice fed with green tea polyphenols.
      ].
      CVD is a leading cause of global morbidity, mortality and disability and will continue to dominate mortality trends in the future [
      • Roth G.A.
      • Mensah G.A.
      • Johnson C.O.
      • Addolorato G.
      • Ammirati E.
      • Baddour L.M.
      • et al.
      Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study.
      ]. Hypertension, dyslipidemia, diabetes, obesity, sedentary lifestyle and poor dietary habits are major modifiable risk factors linked to detrimental changes in cardiometabolic health [
      • Yusuf S.
      • Joseph P.
      • Rangarajan S.
      • Islam S.
      • Mente A.
      • Hystad P.
      • et al.
      Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.
      ]. Most public health actions have targeted modifiable risk factors to reduce the burden of CVD, as preventing or treating major modifiable risk factors has proven to be effective in reducing mortality from CVD [
      • Lagerweij G.R.
      • de Wit G.A.
      • Moons K.G.
      • van der Schouw Y.T.
      • Verschuren W.M.
      • Dorresteijn J.A.
      • et al.
      A new selection method to increase the health benefits of CVD prevention strategies.
      ]. Considering the beneficial role of GT consumption in reducing the risk of these risk factors (hypertension, dyslipidemia, diabetes obesity) and high consumption of this beverage in all communities even small effects in humans could have large implications for public health [
      • Chieng D.
      • Kistler P.M.
      Coffee and tea on cardiovascular disease (CVD) prevention.
      ]. Several systematic review and meta-analysis (SRM) studies have reported the effects of GT consumption on CVD risk factors to date. However, with increasing number of these reports, the information end-users (service providers and policymakers) would be overwhelmed with too many of them. Umbrella reviews summarize the existing systematic reviews relevant to a question so that decision makers do not need to integrate the results of multiple systematic reviews by themselves [
      ]. Thus, the aim of this meta-review was to establish the effects of GT intake on some cardiometabolic risk factors (lipid profile, blood pressure, glycemic and anthropometric markers) using evidence from previous systematic reviews and meta-analyses.

      1.1 Objectives

      The objectives of this study were to summarize evidence from systematic reviews and meta-analyses of GT consumption on (i) anthropometric measures including weight, body mass index (BMI) and waist circumference (WC); (ii) systolic blood pressure (SBP) and diastolic blood pressure (DBP); (iii) glycemic outcomes including fasting blood glucose (FBG), fasting serum insulin, hemoglobin (Hb) A1c and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR); and blood lipid profile including total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) and triglycerides.

      2. Methods

      This overview was conducted using methods presented in The Cochrane Handbook for Systematic Reviews of Interventions [
      ]. Also, recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed. The protocol of the study was registered at PROSPERO 2021: CRD42021253230. An umbrella review and meta-meta-analysis were conducted to identify the effect of GT on cardiometabolic risk factors. Umbrella reviews (also called overview of systematic reviews) represent an effective way of SRM reports on a specific research topic.

      2.1 Criteria for selecting reviews for inclusion

      In this overview of systematic reviews (SRs), we included SRs and meta-analyses containing randomized controlled trials (RCTs) and/or controlled clinical trials (CCTs) that assessed the effects of GT intake on cardiometabolic risk factors as a primary or secondary outcome of the review.

      2.2 Types of participants

      From the eligible SRs, we included results from trials that contained adults only.

      2.3 Types of interventions

      We included reviews comparing the intake of GT as beverage or supplement with placebo or no intervention.

      2.4 Types of outcome measures

      The primary outcomes were cardiometabolic risk factors including (i) anthropometric measures (weight, BMI, waist circumference), (ii) blood pressure (systolic, diastolic), (iii) glycemic indicators (fasting blood sugar, fasting insulin, HOMA-IR, HbA1c), and (iv) lipid profile (triglycerides, TC, LDL-C, HDL-C).

      2.5 Search methods for identification of reviews

      Relevant English language articles were identified via searches in PubMed, Embase, and the Cochrane Library, Web of Knowledge database from the index date of each database through January 31, 2021 and reference lists of relevant articles using the text keywords (“systematic review” OR “meta-analysis”) and (“green tea”) and (“fasting blood sugar” OR “insulin” OR “HbA1c” OR “HOMA” OR “triglyceride” OR “cholesterol” OR “LDL” OR “HDL” OR “systolic blood pressure” OR “weight” OR “BMI” OR “waist circumference”). Articles were initially screened on the basis of title and abstract reading. The full texts of potentially eligible articles were then independently scrutinized by two investigators (BN, TN).

      2.6 Data collection and analysis

      The methodology for data collection and analysis is based on Chapter 22, ‘Overviews of Reviews' in the Cochrane Handbook of Systematic Reviews of Interventions [
      ].

      2.7 Selection of reviews

      Two overview authors independently assessed all systematic reviews for potential inclusion. Titles and abstracts were screened. Full texts of all potentially relevant documents were retrieved and then methods section of reviews were assessed to ensure those with the appropriate population and pre-specified outcome were selected.

      2.8 Data extraction and management

      Data extraction was performed independently by two investigators. Any existing discrepancies were resolved in consensus meetings. The following data were extracted: (i) descriptive characteristics of SRs, (ii) the number of trials in the review, (iii) risk of bias of the included trials, (iv) interventions and comparisons, and (v) the outcome data. In cases where data were not available, we accessed the original published papers of the studies for further details.

      2.9 Data synthesis

      The quantitative and qualitative approaches were used to summarize the estimates of the included SRs. Stata version 16.0 software (StataCorp, TX USA) was applied for the quantitative analyses. Data were summarized using effect size (EF), 95% confidence intervals (CIs), and numbers of studies and participants contributing data to each pooled effect from comparisons and for the outcome relevant to this overview.
      For all pooled effect estimates, the accompanying I2 values were reported and represent the degree of statistical heterogeneity between the trials. Degree of heterogeneity was classified into low (I2<25%), moderate (25%≤ I2<50%) and large (50%≤ I2) [
      ]. Fixed-effects models were used if the level of heterogeneity was <50%. Otherwise, the pooled estimates were calculated using the random-effects model. Egger's test was used to evaluate publication bias and small-study effect, and a p value < 0.1 in the test confirmed the bias and small-study effect.
      To evaluate the impact of the overlap in the inclusion of the same primary studies, the degree of overlap between reviews was measured to generate a citation matrix and also to calculate the corrected cover area (CCA), a metric that provides a percentage of overlap of the primary studies. A CCA value lower than five indicates slight overlap, whereas values greater than or equal to 15 can be considered as a very high [
      • Pieper D.
      • Antoine S.-L.
      • Mathes T.
      • Neugebauer E.A.
      • Eikermann M.
      Systematic review finds overlapping reviews were not mentioned in every other overview.
      ].
      The results from meta-analyses with CCA <15, but no shared authorship team, were reported and compared as separate reviews. In the case of very high overlap in primary study, the most recent meta-analysis or best quality was considered (Table 2, Table 3, Table 4, Table 5).

      2.10 Quality of included reviews

      Two reviewers independently assessed the methodological quality of included reviews using the validated AMSTAR2 (A Measurement Tool to Assess Systematic Reviews 2) instrument [
      • Shea B.J.
      • Grimshaw J.M.
      • Wells G.A.
      • Boers M.
      • Andersson N.
      • Hamel C.
      • et al.
      Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews.
      ,
      • Shea B.J.
      • Bouter L.M.
      • Peterson J.
      • Boers M.
      • Andersson N.
      • Ortiz Z.
      • et al.
      External validation of a measurement tool to assess systematic reviews (AMSTAR).
      ] and disagreements were resolved through consensus. AMSTAR assessments are presented in the results and tables. AMSTAR2 includes the following critical areas: registered protocol; adequacy of literature search; rationalization for excluded studies; risk of bias for included studies; appropriateness of meta-analytic methods; consideration of risk of bias when interpreting results; and assessing of publication bias. The tool provides guidance to rate the overall confidence in the results of a review (high, moderate, low or critically low depending on the number of critical flaws and/or non-critical weaknesses).

      2.11 Risk of bias of primary studies included in the reviews

      The risk of bias of included studies during reviews was not re-assessed but reported study risk of bias according to the review's authors' assessment was considered, instead.

      2.12 Quality of evidence in included reviews

      An overall assessment of the quality of evidence for each intervention of interest was performed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The GRADEpro includes five criteria: risk of bias, consistency, directness, imprecision and publication bias [
      • Guyatt G.H.
      • Oxman A.D.
      • Vist G.E.
      • Kunz R.
      • Falck-Ytter Y.
      • Alonso-Coello P.
      • et al.
      GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
      ]. Assessing and combining these components determined evidence quality as: high: further research is very unlikely to change confidence in the estimate of the effect; moderate: further research is likely to have an important impact on confidence in the estimate of effects and may change the estimate; low: further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate; or very low: any estimate of the effect is very uncertain.
      Also, the signs were used to link the estimated effects of review and our confidence in the available data as follows:
      • Clear evidence of benefit (moderate- or high-quality evidence with confidence intervals (CIs) not crossing line of no effect): ✓
      • Clear evidence of harm (moderate- or high-quality evidence with CIs not crossing line of no effect): ×
      • Clear evidence of no effect or equivalence (moderate- or high quality evidence with narrow CIs crossing the line of no effect):=
      • Possible benefit (low-quality evidence with clear benefit, or moderate- or high-quality evidence with wide CIs crossing the line of no effect): +
      • Possible harm (low-quality evidence with clear harm, or moderate- or high-quality evidence with wide CIs crossing the line of no effect):
      • Unknown benefit or harm (low-quality evidence with wide CIs crossing the line of no effect or very low-quality evidence): ?

      2.13 Ethical consideration

      The present study was done using data extracted from published studies. Hence, no study participants’ consent or ethical approval was required.

      3. Results

      The database search provided a total of 1204 articles, of which 259 were excluded because of having narrative design not meta-analysis that was the main inclusion criterion of the present study. After screening the titles and reviewing the abstracts and full-texts, a total of 19 studies were included in the qualitative synthesis of current umbrella review (Fig. 1). Due to the requirement of CCA> 15, six additional meta-analyses were excluded so that 13 meta-analyses were finally included in the quantitative synthesis.
      Fig. 1
      Fig. 1PRISMA flow diagram for studies included in and excluded from the meta-meta-analysis.

      3.1 Description of the included reviews

      All included systematic reviews comprised randomized clinical trials on the effect of GT as beverage or supplement vs. placebo and were published between 2009 and 2020. Studies that were included in this overview had focused on glycemic indicators (n = 5), lipid profiles (n = 6), blood pressure (n = 5) and anthropometric measurements (n = 5). They included a total of 317 studies, providing a total sample of 24,482 adults. The range of number of studies per SRM were from seven [
      • Asbaghi O.
      • Fouladvand F.
      • Moradi S.
      • Ashtary-Larky D.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea extract on lipid profile in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ,
      • Wang X.
      • Tian J.
      • Jiang J.
      • Li L.
      • Ying X.
      • Tian H.
      • et al.
      Effects of green tea or green tea extract on insulin sensitivity and glycaemic control in populations at risk of type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials.
      ] to 31 [
      • Xu R.
      • Yang K.
      • Li S.
      • Dai M.
      • Chen G.
      Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.
      ]. The number of participants in the included reviews ranged from 480 [
      • Asbaghi O.
      • Fouladvand F.
      • Moradi S.
      • Ashtary-Larky D.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea extract on lipid profile in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ] to 3321 [
      • Xu R.
      • Yang K.
      • Li S.
      • Dai M.
      • Chen G.
      Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.
      ]. Further details of the included reviews can be found in Table 1.
      Table 1Characteristics of included reviews.
      First author,

      Year
      participantsNumber of studies (number of subjects)Intervention vs. placeboOutcomeEffect size (95%CI) MDCredibility

      Assessment
      Effect on outcomesubgroupsAMSTAR2 score
      Asbaghi, 2020atype 2 diabetes14 (879)green tea and green tea extract vs. placeboFBG, FBI,

      Hb A1c,

      HOMA-IR.
      FBG: 1.79 (−7.89, 4.31)

      FBI: 0.27 (−0.51, 1.04)

      HbA1c: 0.14 (−0.38, 0.1)

      HOMA: 0.16 (−0.17, 0.49)
      Low

      Low

      Low

      Low
      ?

      ?

      ?

      ?
      Duration, Catechins dose,14/16

      Moderate
      Asbaghi, 2020btype 2 diabetes7 (480)green tea and green tea extract vs. placeboTC, LDL, HDL, TGTC (mg/dL): 6.81 (−15.13, 1.52)

      LDL (mg/dL): 0.37 (−4.13, 3.4)

      HDL (mg/dL): 3.1 (−10.16, 3.95)

      TG (mg/dL): 12.79 (−24.71, −0.84)
      Low

      Moderate

      Very low

      Low
      ?

      ?

      ?

      ?
      Dose, duration14/16

      Moderately
      Asbaghi, 2020ctype 2 diabetes11 (687)green tea and green tea extract vs. placeboWt, BMI, WC, BFWt (kg): 0.4 (−0.64, −0.16)

      BMI: 0.05 (−0.1, −0)

      WC (cm): 1.22 (−2.81, 0.36)

      BF (%): 0.56 (−0.73, 0.38)
      Moderate

      Moderate

      Moderate

      Moderate


      ?

      =

      =
      Duration, dose, overweight,14/16

      Moderate
      Hursel, 2009adults11 (1226)green tea and green tea extract vs. placeboWtWt (kg): 1.31 (−2.05, −0.57)Low+Ethnicity, habitual caffeine intake12/16 low
      Jurgens, 2012overweight or obese adults14 (1562)green tea and green tea extract vs. placeboWt, BMI, WC, WHRWt (kg): 0.95 (−1.76, −0.14)

      BMI: 0.2 (−0.5, 0.1)

      WC (cm): 0.99 (−1.76, −0.22)

      WHR: 0 (−0.02, 0.01)
      Moderate

      Moderate

      Moderate

      Moderate


      =



      =
      with or without caffeine,16/16

      High
      Kim, 2011Adults20 (1415)green tea and green tea extract vs. placeboTC, LDL, HDL, TGTC (mg/dL): 5.46 (−9.59, −1.32)

      LDL (mg/dL): 5.3 (−9.99, −0.62)

      HDL (mg/dL): 0.27 (−1.62, 1.09)

      TG (mg/dL): 3.0 (−2.73, 8.73)
      High

      High

      Moderate

      Moderate




       = 

      +
      Beverage/capsule

      Dose, hyperlipidemia/healthy
      16/16 high
      Khalesi, 2014Adults13 (768)green tea and green tea extract vs. placeboSBP, DBP, TC, TG, LDL, HDL, FBG, BMISBP (mmHg): 2.05 (−3.06, −1.05)

      DBP (mmHg): 1.71 (−2.86, −0.56)

      TC: 5.8 (−10.44, −0.77)

      TG: 8.8 (−11.5, 28.34)

      LDL: 6.18 (−8.5, −3.48)

      HDL: 0.38 (−1.93, 2.32)

      FBG: 0.14 (−0.37, 0.09)

      BMI: 0.06 (−0.43, 0.31)
      Moderate

      Moderate

      Moderate

      Very Low

      Moderate

      Low

      Very Low

      Low




      +

      ?

      +

      ?

      ?

      ?
      Beverage/capsule

      Dose, SBP <130/<130 mmHg, BMI >30/<30
      13/16 low
      Li, 2015overweight and obese adults14 (971)green tea and green tea extract vs. placeboSBP, DPBSBP (mmHg): 1.42 (−2.47, −0.36)

      DBP(mmHg): 1.42 (−2.47, −0.36)
      High

      Moderate


      Dose, duration, overweight/obese, sex, with or without comorbidity, with or without hypertension, with or without caffeine,14/16

      Moderate
      Liu, 2013Adults17 (1133)green tea and green tea extract vs. placeboFBG, FBI,

      Hb A1c,

      HOMA-IR.
      FBG (mmol/L): 0.09 (−0.15, −0.03)

      FBI (μIU/mL): 0.4 (−1.27, 0.46)

      HbA1c (%): 0.3 (−0.37, −0.22)

      HOMA: 0.04 (−0.67, 0.59)
      High

      Moderate

      High

      Moderate


      =



      =
      Metabolic syndrome risk/healthy, with or without caffeine, Duration, Catechins dose14/16

      Moderate
      Lin, 2020adults22 (2357)green tea and green tea extract vs. placeboWt, BMI, WCWt (kg): 1.78 (−2.8, −0.76)

      BMI: 0.65 (−1.05, −0.25)

      WC: 1.5 (−3.19, 0.19)
      Moderate

      Moderate

      Low
      =

      =

      ?
      Overweight or obese, dose, duration14/16

      Moderate
      Onakpoya, 2014adults20 (1536)green tea supplement vs. placebosSBP, DBP, TC, LDL, HDL, TGSBP (mmHg): 1.94 (−2.95, −0.93)

      DBP (mmHg): 0.98 (−2.14, 0.18)

      TC (mmol/L): 0.13 (−0.2, −0.07)

      LDL (mmol/L): 0.19 (−0.3, −0.09)

      HDL (mmol/L): 0.01 (−0.08, 0.06)

      TG (mmol/L): 0.02 (−0.16, 0.12)
      Moderate

      Moderate

      Moderate

      Moderate

      Moderate

      Moderate


      ?





      ?

      ?
      Men of women, with or without dyslipidemia,13/16

      Low
      Peng, 2014adults13 (1367)green tea and green tea extract vs. placeboSBP, DBPSBP (mmHg): 1.98 (−2.94, −1.01)

      DBP (mmHg): 1.92 (−3.17, −0.68)
      Moderate

      Moderate


      +
      Stage 1 hypertension or prehypertension, with or without caffeine, duration, dose13/16 low
      Phung, 2011adults15 (1243)green tea and green tea extract vs. placeboWt, BMI, WC, WHRWt (kg): 0.14 (−1.45, 1.16)

      BMI: 0.06 (−0.54, 0.42)

      WC (cm): 0.31 (−2.1, 2.72)

      WHR: 0.01 (−0.11, 0.13)
      High

      High

      High

      High
      ?

       = 

      ?

      ?
      with or without caffeine,14/16

      Moderate
      Wang, 2014type 2 diabetes/at risk of type 2 diabetes7 (510)green tea or green tea extract or EGCG vs. placeboFBG, FBI,

      Hb A1c,

      HOMA-IR.
      FBG: 0.04 (−0.15, 0.24)

      FBI: 0.09 (−0.3, 0.11)

      HbA1c (%): 0.01 (−0.13, 0.33)

      HOMA: 0.06 (−0.35, 0.23)
      Low

      Moderate

      Very low

      Moderate
      ?

      ?

      ?

      ?
      With or without diabetes,13/16

      Low
      Xu, 2020aadult27 (2194)green tea or green tea extract vs. placeboFBG, FBI,

      Hb A1c,

      HOMA-IR.
      FBG (mg/dL): 1.44 (−2.26, −0.62)

      FBI (μIU/mL): 0.46 (−1.1, 0.17)

      Hb A1c (%): 0.06 (−0.12, 0.01)

      HOMA: 0.15 (−0.39, 0.10)
      High

      Moderate

      High

      High


      =

      =

      =
      Beverage/capsule

      Duration

      Catechins dose with or without caffeine, Fasting blood glucose
      14/16

      Moderately
      Xu, 2020bAdults31 (3321)green tea and green tea extract vs. placeboTC, LDL, HDL, TGTC (mg/dL): 4.66 (−6.36, −2.96)

      LDL (mg/dL): 4.55 (−6.31, −2.8)

      HDL (mg/dL): 3.77 (−8.9, 1.37)

      TG (mg/dL): 3.77 (−8.9, 1.37)
      High

      High

      Moderate

      High




      =

      =
      Beverage/capsule

      Dose, duration, with or without caffeine, overweight, obese/normal
      15/16

      Moderately
      Xu, 2020cadults24 (1697)green tea and green tea extract vs. placeboSBP, DBPSBP (mmHg): 1.17 (−2.18, −0.16)

      DBP (mmHg): 1.24 (−2.07, −0.4)
      High

      High


      Beverage/capsule, duration, dose, with or without caffeine, with or without cardiovascular, hypertension or healthy14/16 moderate
      Zheng, 2011Adults15 (1136)green tea and green tea extract vs. placeboTC, LDL, HDLTC (mg/dL): 7.2 (−8.19, −6.21)

      LDL (mg/dL): 2.19 (−3.16, −1.21)

      HDL (mg/dL): 0.25 (−0.73, 1.23)
      High

      High

      High




      =
      Beverage/capsule

      Dose, With cardiovascular risks/healthy, duration,
      14/16

      Moderately
      Zheng, 2013Adults22 (1584)GTCs with or without caffeine vs. placeboFBG, FBI,

      Hb A1c,

      HOMA-IR.
      FBG (mg/dL): 1.48 (−2.57, −0.4)

      FBI (μIU/mL): 0.04 (−0.36, 0.45)

      Hb A1c (%): 0.04 (−0.15, 0.08)

      HOMA: 0.05 (−0.37, 0.26)
      High

      Moderate

      Moderate

      Moderate


      =

      =

      =
      Duration, Ethnicity, Catechin dose, with or without caffeine, BMI, Baseline glucose concentration13/16

      Low

      3.2 Quality of the included reviews

      We assessed the quality of the systematic reviews through the use of the AMSTAR2 questionnaire (Table 1). The range of scores was from 12 [
      • Hursel R.
      • Viechtbauer W.
      • Westerterp-Plantenga M.S.
      The effects of green tea on weight loss and weight maintenance: a meta-analysis.
      ,
      • Khalesi S.
      • Sun J.
      • Buys N.
      • Jamshidi A.
      • Nikbakht-Nasrabadi E.
      • Khosravi-Boroujeni H.
      Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.
      ] to 16 [
      • Kim A.
      • Chiu A.
      • Barone M.K.
      • Avino D.
      • Wang F.
      • Coleman C.I.
      • et al.
      Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis.
      ,
      • Jurgens T.M.
      • Whelan A.M.
      • Killian L.
      • Doucette S.
      • Kirk S.
      • Foy E.
      Green tea for weight loss and weight maintenance in overweight or obese adults.
      ] out of a maximum score of 16. All reviews presented a comprehensive literature search and a list of included studies. Also, in most reviews, two or more independent reviewers were involved in the study selection and data extraction. The majority of reviews included the components of PICO in their research questions as well. Only two reviews lacked detail on publication bias [
      • Hursel R.
      • Viechtbauer W.
      • Westerterp-Plantenga M.S.
      The effects of green tea on weight loss and weight maintenance: a meta-analysis.
      ,
      • Khalesi S.
      • Sun J.
      • Buys N.
      • Jamshidi A.
      • Nikbakht-Nasrabadi E.
      • Khosravi-Boroujeni H.
      Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.
      ]. All reviews explained the methods used to combine findings. Only two reviews reported details on funding of included studies [
      • Kim A.
      • Chiu A.
      • Barone M.K.
      • Avino D.
      • Wang F.
      • Coleman C.I.
      • et al.
      Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis.
      ,
      • Jurgens T.M.
      • Whelan A.M.
      • Killian L.
      • Doucette S.
      • Kirk S.
      • Foy E.
      Green tea for weight loss and weight maintenance in overweight or obese adults.
      ].

      3.3 Effects of interventions

      3.3.1 Anthropometric measures

      Of the 5 reviews that assessed the effect of GT on anthropometric measures, one reported data in overweight/obese adults [
      • Asbaghi O.
      • Fouladvand F.
      • Gonzalez M.J.
      • Aghamohammadi V.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea on anthropometric indices and body composition in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ] and one included subjects with T2D [
      • Jurgens T.M.
      • Whelan A.M.
      • Killian L.
      • Doucette S.
      • Kirk S.
      • Foy E.
      Green tea for weight loss and weight maintenance in overweight or obese adults.
      ]. All studies (four high/moderate and one low quality evidence) suggested that GT intake might decrease body weight significantly [
      • Jurgens T.M.
      • Whelan A.M.
      • Killian L.
      • Doucette S.
      • Kirk S.
      • Foy E.
      Green tea for weight loss and weight maintenance in overweight or obese adults.
      ,
      • Asbaghi O.
      • Fouladvand F.
      • Gonzalez M.J.
      • Aghamohammadi V.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea on anthropometric indices and body composition in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ,
      • Lin Y.
      • Shi D.
      • Su B.
      • Wei J.
      • Găman M.A.
      • Sedanur Macit M.
      • et al.
      The effect of green tea supplementation on obesity: a systematic review and dose-response meta-analysis of randomized controlled trials.
      ,
      • Phung O.J.
      • Baker W.L.
      • Matthews L.J.
      • Lanosa M.
      • Thorne A.
      • Coleman C.I.
      Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis.
      ].
      Considering low overlapping among the reviews (Table 5), we included all reviews in quantitative analysis and showed a significant effect on weight, with WMD of −0.89 (95% CI -1.43 to −0.34, p < 0.001). There was similar results on waist circumference with WMD of −1.01 (95% CI -1.63 to −0.39, p < 0.001) (Table 6).

      3.3.2 Blood pressure

      In order to evaluate the effect of GT on BP, we found five reviews of which one had reported results of overweight/obese adults [
      • Li G.
      • Zhang Y.
      • Thabane L.
      • Mbuagbaw L.
      • Liu A.
      • Levine M.A.
      • et al.
      Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis.
      ]. All reviews that regarded as high or moderate quality demonstrated a positive effect of GT consumption on systolic and diastolic blood pressure. Due to very high overlapping among the reviews, we included only most recent reviews in quantitative analysis (Table 4). To do this, we applied citation matrix in subsets and one by one comparison of the reviews. Consequently, we identified 24 trials, covering more than 1697 participants and succeeded to detect a significant effect on SBP and DBP, with WMDs of −1.17 (95% CI -2.18 to −0.16) and −1.24 (95% CI -2.07 to −0.4), respectively (Table 6).

      3.3.3 Glycemic outcomes

      Data for the effect of GT on glycemic status (overall effect) obtained from five meta-analyses, of which two studies included patients with type 2 diabetes (T2D)/at risk of diabetes. Three reviews showed that the intervention produced a statistically significant benefit, as compared with control, on FBG, all of which had a high quality [
      • Liu K.
      • Zhou R.
      • Wang B.
      • Chen K.
      • Shi L.Y.
      • Zhu J.D.
      • et al.
      Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials.
      ,
      • Xu R.
      • Bai Y.
      • Yang K.
      • Chen G.
      Effects of green tea consumption on glycemic control: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Hui R.
      • Wu Y.J.
      • Huang X.H.
      Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.
      ]. However, two moderate and low quality evidence that included patients with T2D showed no significant effect on FBG [
      • Wang X.
      • Tian J.
      • Jiang J.
      • Li L.
      • Ying X.
      • Tian H.
      • et al.
      Effects of green tea or green tea extract on insulin sensitivity and glycaemic control in populations at risk of type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials.
      ,
      • Asbaghi O.
      • Fouladvand F.
      • Gonzalez M.J.
      • Ashtary-Larky D.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea on glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ]. Only one review reported statistical significant effect on HbA1c [
      • Liu K.
      • Zhou R.
      • Wang B.
      • Chen K.
      • Shi L.Y.
      • Zhu J.D.
      • et al.
      Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials.
      ].
      Table 2 shows that overall CCA among reviews was very high (28%). Due to the requirement of CCA <15, using citation matrix in subsets and comparison of two individual reviews, two meta-analyses were excluded [
      • Liu K.
      • Zhou R.
      • Wang B.
      • Chen K.
      • Shi L.Y.
      • Zhu J.D.
      • et al.
      Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Hui R.
      • Wu Y.J.
      • Huang X.H.
      Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.
      ] so that three meta-analyses were finally included in the quantitative analysis (Table 2).
      Table 2Matrix and corrected covered area (CCA) to examine overlap for subsets of glycemic markers.
      Asbaghi, 2020Zheng, 2013Liu, 2013Wang, 2014Xu, 2020
      1Fukino, 2005
      2Fukino, 2008
      3Mirzaei, 2009
      4Mohammadi, 2020
      5Hsu, 2011
      6Mousavi, 2013
      7Lasaite, 2014
      8Liu, 2014
      9Borges, 2016
      10Zandi DarehGharibi, 2018
      11Sobhani, 2019
      12Quezada-Fernandez, 2019
      13Hosseini, 2018
      14Basu, 2011
      15Brown, 2009
      16Brown, 2011
      17Chan, 2006
      18Diepven, 2006
      19Frank, 2009
      20Hase, 2001
      21Hill, 2007
      22Hsu, 2008
      23Hursel, 2009
      24Kovacs, 2004
      25Nagao, 2005
      26Ryu, 2006
      27Sone, 2011
      28Stendell-Hollis, 2010
      29Tsuchida, 2002
      30Westerterp, 2005
      31Nagao, 2009
      32Wu, 2012
      33Bogdanski, 2012
      34Suliburska, 2012
      35Nantz, 2009
      36Chen, 2016
      37Dostal, 2016
      38Frank, 2009
      39Lu, 2016
      40Mielgo-Ayuso, 2014
      41Miyazaki, 2013
      42Tadayon, 2018
      NrcCCA
      Overall874250.26
      Asbaghi, 2020 vs. Zheng, 2013363020.2
      Asbaghi, 2020 vs. Liu, 201320.24
      Asbaghi, 2020 vs. Wang, 201420.10
      Asbaghi, 2020 vs. Xu, 202020.2
      Zheng, 2013 vs. Liu, 201320.56
      Zheng, 2013 vs. Wang, 201420.38
      Zheng, 2013 vs. Xu, 202020.48
      Liu, 2013 vs. Wang, 201420.14
      Liu, 2013 vs. Xu, 202020.57
      Wang, 2014 vs. Xu, 202020.17
      Meta-meta-analysis revealed statistically significant effect of GT on FBG (WMD, −1.3, 95% CI -2.09 to −0.51, p < 0.001) but not in other glycemic indicators (HbA1c: WMD, −0, 95% CI -0.17 to 0.17, p = 1.0, HOMA: WMD, −0,04, 95% CI -0.22 to 0.14, p = 0.66, FBI: WMD, −0.28% CI -0.76 to 0.19, p = 0.24) (Table 6).

      3.3.4 Lipid profile

      Lipid profile was the primary outcome of interest in six out of 13 reviews. Only one study included subjects with T2D [
      • Asbaghi O.
      • Fouladvand F.
      • Moradi S.
      • Ashtary-Larky D.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea extract on lipid profile in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ]. Most reviews (five out of six) with high/moderate quality reported that GT might improve serum TC and LDL-C concentrations [
      • Xu R.
      • Yang K.
      • Li S.
      • Dai M.
      • Chen G.
      Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Khalesi S.
      • Sun J.
      • Buys N.
      • Jamshidi A.
      • Nikbakht-Nasrabadi E.
      • Khosravi-Boroujeni H.
      Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.
      ,
      • Kim A.
      • Chiu A.
      • Barone M.K.
      • Avino D.
      • Wang F.
      • Coleman C.I.
      • et al.
      Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Liu X.X.
      • Hui R.
      • Huang X.H.
      Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.
      ,
      • Onakpoya I.
      • Spencer E.
      • Heneghan C.
      • Thompson M.
      The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials.
      ]. However, only one review reported that GT might decrease serum TG concentration in the subjects with T2D [
      • Asbaghi O.
      • Fouladvand F.
      • Moradi S.
      • Ashtary-Larky D.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea extract on lipid profile in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ].
      After excluding two reviews due to high overlap (Table 3), four reviews were included in quantitative analysis and meta-meta-analysis on effect of GT on serum TC and LDL-C concentrations. The findings revealed a statistically significant effect size (WMD -4.93; 95% CI -6.41 to −3.46, p < 0.001, WMD -4.31; 95% CI -6.55 to −2.07, p < 0.001, respectively). However, there was no significant effect on circulating HDL-C (WMD 0.13; 95% CI -0.46 to 0.71, p = 0.67) and TG (WMD -1.96; 95% CI -8.94 to 5.02, p = 0.58) concentrations (Table 6).
      Table 3Matrix and corrected covered area (CCA) to examine overlap for subsets of lipid.
      Asbaghi, 2020Zheng, 2011Kim, 2011Xu, 2020Khalesi, 2014Onakpoya, 2014
      1Fukino, 2008
      2Mohammadi, 2010
      3Hsu, 2011
      4Mousavi, 2013
      5Liu, 2014
      6Sobhani, 2019
      7Quezada-Fernandez, 2019
      8Basu, 2011
      9Brown, 2009
      10Brown, 2011
      11Chan, 2006
      12Diepven, 2006
      13Frank, 2009
      14Hsu, 2008
      15Nagao, 2005
      16Ryu, 2006
      17Nagao, 2009
      18Wu, 2012
      19Bogdanski, 2012
      20Suliburska, 2012
      21Nantz, 2009
      22Chen, 2016
      23Lu, 2016
      24Mielgo-Ayuso, 2014
      25Miyazaki, 2013
      26Tadayon, 2018
      27Batista, 2009
      28Diplerro, 2009
      29Elchenberger, 2009
      30Makl, 2009
      31Bertipaglia de Santana, 2008
      32Matsuyama
      33Nagao, 2008
      34Akeshita, 2008
      35Inami, 2007
      36Nagao, 2007
      37Erba, 2005
      38Maron, 2003
      39Princen, 1998
      40Van het Hof, 1997
      41Freese, 1999
      42Huang, 2018
      43Kafeshani, 2017
      44Lee, 2016
      45Samvat, 2016
      46Venkatakrishnan, 2018
      47Fukino, 2008
      48Mohammadi, 2010
      49Hsu, 2011
      50Mousavi, 2013
      51Liu, 2014
      52Sone, 2011
      53Vieira Senger, 2005
      54Kajimoto, 2003
      55Takase,2008
      56Widlansky,2007
      NrcCCA
      overall1025160.20
      Asbaghi, 2020 vs. Zheng, 2011211920.1
      Asbaghi, 2020 vs. Kim, 2011272620.03
      Asbaghi, 2020 vs. Xu, 2020383420.10
      Asbaghi, 2020 vs Khalesi, 2014181620.12
      Asbaghi, 2020 vs Onakpoya, 2014262320.13
      Zheng, 2011 vs. Kim, 2011342520.36
      Zheng, 2011 vs. Xu, 2020453320.36
      Zheng, 2011 vs. Khalesi, 2014252020.25
      Zheng, 2011 vs. Onakpoya, 2014332520.32
      Kim, 2011 vs. Xu, 2020514220.21
      Kim, 2011 vs. Khalesi, 2014312820.10
      Kim, 2011 vs. Onakpoya, 2014393020.3
      Xu, 2020 vs. Khalesi, 201443320.27
      Xu, 2020 vs. Onakpoya, 2014503820.31
      Khalesi, 2014 vs. Onakpoya, 2014302120.42
      Table 4Matrix and corrected covered area (CCA) to examine overlap for subsets of BP.
      Khalesi, 2014Li, 2015Onakpoya, 2014Peng, 2014Xu, 2020
      1Fukino, 2008
      2Fukino, 2005
      3Hsu, 2011
      4Liu, 2014
      5Basu, 2011
      6Brown, 2009
      7Brown, 2011
      8Diepven, 2006
      9Frank, 2009
      10Hsu, 2008
      11Nagao, 2009
      12Bogdanski, 2012
      13Suliburska, 2012
      14Nantz, 2009
      15Chen, 2015
      16Miyazaki, 2013
      17Batista, 2009
      18Matsuyama
      19Nagao, 2007
      20Kafeshani, 2017
      21Maki, 2009
      22Sone, 2011
      23Vieira Senger, 2005
      24Hill, 2007
      25Takase, 2008
      26Takeshita, 2008
      27Kajimoto, 2003
      28Widlansky, 2007
      29Basu, 2010
      30Liu, 2016
      31Maeda-Yamamoto, 2018
      32Nogueira, 2016
      33Takahashi, 2014
      34NrcCCA
      Overall843350.38
      Khalesi, 2014 vs. Li, 2015271920.42
      Khalesi, 2014 vs. Onakpoya, 2014332220.5
      Khalesi, 2014 vs. Peng, 2014261720.52
      Khalesi, 2014 vs. Xu, 2020372520.48
      Li, 2015 vs. Onakpoya, 2014342320.47
      Li, 2015 vs. Peng, 2014271920.42
      Li, 2015 vs. Xu, 2020382620.46
      Onakpoya, 2014 vs. Peng, 2014443120.41
      Onakpoya, 2014 vs. Xu, 2020372520.48
      Table 5Matrix and corrected covered area (CCA) to examine overlap for subsets of Anthropometric measurements.
      Asbaghi, 2020Hursel, 2009Jurgens, 2012Lin, 2019Phung, 2011
      1Fukino, 2005
      2Fukino, 2008
      3Mirzaei, 2009
      4Mohammadi, 2010
      5Hsu, 2011
      6Mousavi, 2013
      7Lasaite, 2014
      8Liu, 2014
      9Borges, 2016
      10Zandi DarehGharibi, 2018
      11Quezada-Fernandez, 2019
      12Basu, 2011
      13Chan, 2006
      14Diepven, 2006
      15Frank, 2009
      16Hase, 2001
      17Hill, 2007
      18Hsu, 2008
      19Hursel, 2009
      20Kovacs, 2004
      21Nagao, 2005
      22Tsuchida, 2002
      23Westerterp-Plantenga, 2005
      24Nagao, 2009
      25Bogdanski, 2012
      26Suliburska, 2011
      27Nagao, 2001
      28Kozuma, 2005
      29Nagao, 2007
      30Auvichayapat, 2008
      31Wang, 2008
      32Kajimoto, 2005
      33Kataoka, 2004
      34Maki, 2009
      35Suzuki, 2009
      36Takese, 2008
      37Takashima, 2004
      38Takeshita, 2008
      39Wang, 2010
      40Amozade, 2018
      41Naderi Nabi, 2018
      42Venkatakrishnan, 2018
      43Rostamian, 2017
      44Tabatabaee,2017
      45Mombaini, 2017
      46Soeizi, 2017
      47Afzalpour, 2016
      48Hovanloo, 2016
      49Janssens,2015
      50Al-Naggar, 2013
      51Toolsee, 2013
      52Aparecida Cardoso, 2012
      53Vieira Senger, 2012
      54Hsu, 2012
      55Di Pierro, 2009
      56Matsuyama, 2008
      NrcCCA
      Overall785850.08
      Asbaghi, 2020 vs. Hursel, 2009222220
      Asbaghi, 2020 vs. Jurgens, 2012272720
      Asbaghi, 2020 vs. Lin, 2019343420
      Asbaghi, 2020 vs. Phung, 2011262420.08
      Hursel, 2009 vs. Jurgens, 2012271920.42
      Hursel, 2009 vs. Lin, 2019363020.2
      Hursel, 2009 vs. Phung, 2011262120.23
      Jurgens, 2012 vs. Lin, 2019413520.17
      Jurgens, 2012 vs. Phung, 2011312420.29
      Lin, 2019 vs. Phung, 2011403420.17
      Table 6The cardiometabolic risk factors studied in the included reviews.
      Cardiometabolic risk factorIncluded meta-analysisNumber of Meta-analysis (number of subjects)Effect size

      95% CI
      I2
      Glycemic markersFBSAsbaghi, 2020a

      Wang, 2014

      Xu, 2020a
      3 (3583)−1.3 (−2.09 to −0.51)1.11
      HbA1cAsbaghi, 2020a

      Wang, 2014

      Xu, 2020a
      3 (3583)−0 (−0.17 to 0.17)84.3
      HOMA-IRAsbaghi, 2020a

      Wang, 2014

      Xu, 2020a
      3 (3583)−0.04 (−0.22 to 0.14)8.54
      Fasting serum insulinAsbaghi, 2020a

      Wang, 2014

      Xu, 2020a
      3 (3583)−0.28 (−0.76 to 0.19)37.16
      Lipid profileTGAsbaghi, 2020b

      Kim, 2011

      Xu, 2020b

      Khalesi, 2014
      4 (5984)−1.96 (−8.94 to 5.02)62.7
      TCAsbaghi, 2020b

      Kim, 2011

      Xu, 2020b

      Khalesi, 2014
      4 (5984)−4.93 (−6.41 to −3.46)0
      LDL-CAsbaghi, 2020b

      Kim, 2011

      Xu, 2020b

      Khalesi, 2014
      4 (5984)−4.31 (−6.55 to −2.07)57.4
      HDL-CAsbaghi, 2020b

      Kim, 2011

      Xu, 2020b

      Khalesi, 2014
      4 (5984)0.13 (−0.46 to 0.71)0
      Blood pressureSBPXu, 2020c1 (1694)−1.17 (−2.18 to −0.16)43
      DBPXu, 2020c1 (1694)−1.24 (−2.07 to −0.4)57
      AnthropometryWeightAsbaghi, 2020c

      Hursel, 2009

      Jurgens, 2012

      Lin, 2019

      Phung, 2011
      5 (7075)−0.89 (−1.43 to −0.34)64.4
      BMIKhalesi, 2014

      Asbaghi, 2020c

      Jurgens, 2012

      Lin, 2019

      Phung, 2011
      5 (6617)−0.24 (−0.49, −0.0)72.7
      WCAsbaghi, 2020c

      Jurgens, 2012

      Lin, 2019

      Phung, 2011
      4 (5849)−1.01 (−1.63 to −0.39)0.0

      4. Discussion

      4.1 Summary of the main results

      To evaluate the effects of GT consumption on cardiometabolic risk factors as the primary or secondary outcome, this study included 19 reviews comprising 317 randomized controlled trials and 24,482 adults. The estimates of effects and certainty of the estimates for different outcomes varied. Summary of the main findings are as follows:
      • 1.
        GT consumption has beneficial effects on body weight and waist circumference;
      • 2.
        GT consumption has beneficial effect on at least one outcome of glycemic status, i.e. FBG, especially in healthy subjects;
      • 3.
        GT consumption has ameliorating effects on circulating TC and LDL-C concentrations;
      • 4.
        None of the reviews found evidence for any harm due to GT consumption (defined as a clear increase in the risk of cardiovascular factors);

      4.2 Overall completeness and applicability of the evidence

      There was broad evidence for the effects of GT on cardiometabolic risk factors. However, there were limited data on subgroups including subjects with diabetes or overweight/obesity. It was, therefore, difficult to draw generalizable conclusions regarding the applicability of the findings to these subgroups.
      Evidence of the effects of GT on some other outcomes like body fat was not considered in this overview since eligible systematic reviews were not found. Likewise, there were limited studies that examined the costs and cost-effectiveness of the intervention with GT.

      4.3 Quality of the evidence

      The quality of the included reviews, as evaluated by AMSTAR tool, was considered “relatively good”. All included reviews had assessed the risk of bias for the included randomized trials. However, the quality of the trials covered within individual reviews was variable. In general, recent trials tended to report their methodology in more detail.

      4.4 Anthropometric measures

      The overview found high and moderate quality evidence of the efficacy of GT on body weight.
      The overview found high quality evidence of the efficacy of GT consumption on waist circumference.
      High and moderate-quality evidence suggested a benefit of GT intake on weight and waist circumference that was confirmed by the results of the meta-meta-analysis.
      Subgroup analysis in high and moderate quality evidence [
      • Jurgens T.M.
      • Whelan A.M.
      • Killian L.
      • Doucette S.
      • Kirk S.
      • Foy E.
      Green tea for weight loss and weight maintenance in overweight or obese adults.
      ,
      • Phung O.J.
      • Baker W.L.
      • Matthews L.J.
      • Lanosa M.
      • Thorne A.
      • Coleman C.I.
      Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis.
      ] showed that GT is effective on body weight independent of the caffeine content. Two moderate quality reviews reported that GT intake was more effective in overweight/obese subjects. Nonetheless, more evidence is needed.

      4.5 Blood pressure

      The overview found moderate quality evidence of the efficacy of GT on SBP and DBP. Moderate and low-quality evidence suggested beneficial effect of GT intake on SBP and DBP.
      A low-quality evidence showed the benefit of GT either as beverage or extract only in subjects with baseline SBP> 130 mmHg. Notwithstanding, the moderate quality evidence suggested similar effect in both hypertensive and healthy participants.

      4.6 Glycemic status

      The overview found moderate quality evidence for effectiveness of the intervention on FBG. No decisive conclusions are possible: low quality evidence, moderate-quality evidence showed no clear difference or provided insufficient evidence to comment on the efficacy of GT intake on fasting serum insulin, HbA1c and HOMA-IR.
      Moderate-quality evidence suggested beneficial effect of GT intake on FBG that was confirmed by results of the meta-meta-analysis.
      It is noteworthy that the beneficial effects of GT consumption on FBG were not reported in those reviews that included participants with T2D/at risk of diabetes [
      • Wang X.
      • Tian J.
      • Jiang J.
      • Li L.
      • Ying X.
      • Tian H.
      • et al.
      Effects of green tea or green tea extract on insulin sensitivity and glycaemic control in populations at risk of type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials.
      ,
      • Asbaghi O.
      • Fouladvand F.
      • Gonzalez M.J.
      • Ashtary-Larky D.
      • Choghakhori R.
      • Abbasnezhad A.
      Effect of green tea on glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
      ]. Interestingly, subgroup analysis in moderate quality evidence showed that GT was effective in lowering FBG just in the subjects with normal FBG at baseline [
      • Liu K.
      • Zhou R.
      • Wang B.
      • Chen K.
      • Shi L.Y.
      • Zhu J.D.
      • et al.
      Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials.
      ,
      • Xu R.
      • Bai Y.
      • Yang K.
      • Chen G.
      Effects of green tea consumption on glycemic control: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Hui R.
      • Wu Y.J.
      • Huang X.H.
      Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.
      ]. In addition, subgroup analysis in most recent and qualified evidence demonstrated that GT intake was beneficial when consumed with caffeine [
      • Xu R.
      • Bai Y.
      • Yang K.
      • Chen G.
      Effects of green tea consumption on glycemic control: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Hui R.
      • Wu Y.J.
      • Huang X.H.
      Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.
      ] or in a dose of catechin above 450 mg/day [
      • Liu K.
      • Zhou R.
      • Wang B.
      • Chen K.
      • Shi L.Y.
      • Zhu J.D.
      • et al.
      Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Hui R.
      • Wu Y.J.
      • Huang X.H.
      Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.
      ].
      Moderate evidence showed no beneficial effect of GT consumption on circulating insulin, HbA1c and HOMA-IR compared with placebo.

      4.7 Lipid profile

      The overview found moderate quality evidence supporting the efficacy of GT on serum TC and LDL-C concentrations. No decisive conclusions were possible: low quality evidence, moderate-quality evidence showed no clear difference or provided insufficient evidence to comment on the efficacy of GT intake on serum TG and HDL-C concentrations.
      High and moderate-quality evidence suggested beneficial effects of GT intake on TC and LDL-C that was confirmed by the results of the meta-meta-analysis.
      Subgroup analysis in moderate quality evidence [
      • Xu R.
      • Yang K.
      • Li S.
      • Dai M.
      • Chen G.
      Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.
      ,
      • Zheng X.X.
      • Xu Y.L.
      • Li S.H.
      • Liu X.X.
      • Hui R.
      • Huang X.H.
      Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.
      ] showed that GT, apart from its catechin content, is effective in lowering serum TC and LDL-C concentrations.

      5. Authors’ conclusions

      Regular consumption of GT and probably its bioactive constituents as supplements have beneficial effects on different health aspects including weight, blood pressure, blood glucose and lipids. However, these effects might be influenced by several factors such as the amount and frequency of consumption, health/disease condition and life style including dietary habits and physical activity.

      5.1 Implication for practice

      Prevention of CVD involves modification of life style including healthy diet, weight control and physical activity [
      • Visseren F.L.J.
      • Mach F.
      • Smulders Y.M.
      • Carballo D.
      • Koskinas K.C.
      • Bäck M.
      • et al.
      ESC Guidelines on cardiovascular disease prevention in clinical practice.
      ]. Nonetheless, encouragement of the subjects with CVD risk factors, CVD patients and also general population to consume moderate amounts of GT, as a part of healthy diet, may synergistically help lower CVD risk of morbidity and mortality.

      5.2 Implication for research

      Further high quality studies are needed to evaluate the efficacy of GT on cardiometabolic risk factors in a dose-response manner.

      Contributors

      TN and BN were involved in each of the following points:
      1. Design.
      2. Data collection.
      3. Analysis.
      4. Writing manuscript.

      Role of the funding source

      This research was performed independently of any funding, as part of the institutional activity of the investigators. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit it for publication.

      Research involving human participants and/or animals

      This article does not contain any studies with human participants or animals performed by any of the authors.

      Authorship

      BN with the intellectual aid of TN designed the study. BN and TN performed the searches and data extraction. All statistically analyses were done by BN and the results were interpreted by TN and BN. The preliminary manuscript was written by BN and finalized by TN. All authors read and approved the final manuscript.

      Declaration of competing interest

      On behalf of all authors, the corresponding author states that there is no conflict of interest.

      Acknowledgements

      Not applicable.

      References

        • He H.-F.
        • Wei K.
        • Yin J.
        • Ye Y.
        Insight into tea flavonoids: composition and chemistry.
        Food Rev Int. 2021; 37: 812-823
        • Henning S.M.
        • Fajardo-Lira C.
        • Lee H.W.
        • Youssefian A.A.
        • Go V.L.
        • Heber D.
        Catechin content of 18 teas and a green tea extract supplement correlates with the antioxidant capacity.
        Nutr Cancer. 2003; 45: 226-235
        • Stangl V.
        • Lorenz M.
        • Stangl K.
        The role of tea and tea flavonoids in cardiovascular health.
        Mol Nutr Food Res. 2006; 50: 218-228
        • Balentine D.A.
        • Wiseman S.A.
        • Bouwens L.C.
        The chemistry of tea flavonoids.
        Crit Rev Food Sci Nutr. 1997; 37: 693-704
        • Mineharu Y.
        • Koizumi A.
        • Wada Y.
        • Iso H.
        • Watanabe Y.
        • Date C.
        • et al.
        Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women.
        J Epidemiol Community Health. 2011; 65: 230-240
        • Dludla P.V.
        • Nkambule B.B.
        • Mazibuko-Mbeje S.E.
        • Nyambuya T.M.
        • Orlando P.
        • Silvestri S.
        • et al.
        Tea consumption and its effects on primary and secondary prevention of coronary artery disease: qualitative synthesis of evidence from randomized controlled trials.
        Clin Nutr ESPEN. 2021; 41: 77-87
        • Keller A.
        • Wallace T.C.
        Tea intake and cardiovascular disease: an umbrella review.
        Ann Med. 2021; 53: 929-944
        • Abe S.K.
        • Inoue M.
        Green tea and cancer and cardiometabolic diseases: a review of the current epidemiological evidence.
        Eur J Clin Nutr. 2021; 75: 865-876
        • Xing L.
        • Zhang H.
        • Qi R.
        • Tsao R.
        • Mine Y.
        Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols.
        J Agric Food Chem. 2019; 67: 1029-1043
        • Meng Q.
        • Li S.
        • Huang J.
        • Wei C.-C.
        • Wan X.
        • Sang S.
        • et al.
        Importance of the nucleophilic property of tea polyphenols.
        J Agric Food Chem. 2018; 67: 5379-5383
        • Zhang Y.
        • Cheng L.
        • Liu Y.
        • Zhang R.
        • Wu Z.
        • Cheng K.
        • et al.
        Omics analyses of intestinal microbiota and hypothalamus clock genes in circadian disturbance model mice fed with green tea polyphenols.
        J Agric Food Chem. 2022; 70: 1890-1901
        • Roth G.A.
        • Mensah G.A.
        • Johnson C.O.
        • Addolorato G.
        • Ammirati E.
        • Baddour L.M.
        • et al.
        Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study.
        J Am Coll Cardiol. 2020; 76: 2982-3021
        • Yusuf S.
        • Joseph P.
        • Rangarajan S.
        • Islam S.
        • Mente A.
        • Hystad P.
        • et al.
        Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.
        Lancet. 2020; 395: 795-808
        • Lagerweij G.R.
        • de Wit G.A.
        • Moons K.G.
        • van der Schouw Y.T.
        • Verschuren W.M.
        • Dorresteijn J.A.
        • et al.
        A new selection method to increase the health benefits of CVD prevention strategies.
        Eur J Prev Cardiology. 2020; 25: 642-650
        • Chieng D.
        • Kistler P.M.
        Coffee and tea on cardiovascular disease (CVD) prevention.
        Trends Cardiovasc Med. 2021; (Online ahead of print)
      1. Higgins J.P.T. Thomas J. Chandler J. Cumpston M. Li T. Page M.J. Welch V.A. Cochrane handbook for systematic reviews of interventions version 6.2 (updated February 2021). Cochrane. 2021 (Available from:)
      2. ([updated September 2009])Higgins J. Higgins J.P.T. Green S. Cochrane handbook for systematic reviews of interventions, version 5.0. 2. Cochrane Collaboration, London (GB)2009
        • Pieper D.
        • Antoine S.-L.
        • Mathes T.
        • Neugebauer E.A.
        • Eikermann M.
        Systematic review finds overlapping reviews were not mentioned in every other overview.
        J Clin Epidemiol. 2014; 67: 368-375
        • Shea B.J.
        • Grimshaw J.M.
        • Wells G.A.
        • Boers M.
        • Andersson N.
        • Hamel C.
        • et al.
        Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews.
        BMC Med Res Methodol. 2007; 7: 10
        • Shea B.J.
        • Bouter L.M.
        • Peterson J.
        • Boers M.
        • Andersson N.
        • Ortiz Z.
        • et al.
        External validation of a measurement tool to assess systematic reviews (AMSTAR).
        PLoS One. 2007; 2e1350
        • Guyatt G.H.
        • Oxman A.D.
        • Vist G.E.
        • Kunz R.
        • Falck-Ytter Y.
        • Alonso-Coello P.
        • et al.
        GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
        Br Med J. 2008; 336: 924-926
        • Asbaghi O.
        • Fouladvand F.
        • Moradi S.
        • Ashtary-Larky D.
        • Choghakhori R.
        • Abbasnezhad A.
        Effect of green tea extract on lipid profile in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
        Diabetes Metab Syndr. 2020; 14: 293-301
        • Wang X.
        • Tian J.
        • Jiang J.
        • Li L.
        • Ying X.
        • Tian H.
        • et al.
        Effects of green tea or green tea extract on insulin sensitivity and glycaemic control in populations at risk of type 2 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials.
        J Hum Nutr Diet. 2014; 27: 501-512
        • Xu R.
        • Yang K.
        • Li S.
        • Dai M.
        • Chen G.
        Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.
        Nutr J. 2020; 19: 48
        • Hursel R.
        • Viechtbauer W.
        • Westerterp-Plantenga M.S.
        The effects of green tea on weight loss and weight maintenance: a meta-analysis.
        Int J Obes. 2009; 33: 956-961
        • Khalesi S.
        • Sun J.
        • Buys N.
        • Jamshidi A.
        • Nikbakht-Nasrabadi E.
        • Khosravi-Boroujeni H.
        Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.
        Eur J Nutr. 2014; 53: 1299-1311
        • Kim A.
        • Chiu A.
        • Barone M.K.
        • Avino D.
        • Wang F.
        • Coleman C.I.
        • et al.
        Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis.
        J Am Diet Assoc. 2011; 111: 1720-1729
        • Jurgens T.M.
        • Whelan A.M.
        • Killian L.
        • Doucette S.
        • Kirk S.
        • Foy E.
        Green tea for weight loss and weight maintenance in overweight or obese adults.
        Cochrane Database Syst Rev. 2012; 12Cd008650
        • Asbaghi O.
        • Fouladvand F.
        • Gonzalez M.J.
        • Aghamohammadi V.
        • Choghakhori R.
        • Abbasnezhad A.
        Effect of green tea on anthropometric indices and body composition in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
        Complement Med Res. 2020; : 1-8
        • Lin Y.
        • Shi D.
        • Su B.
        • Wei J.
        • Găman M.A.
        • Sedanur Macit M.
        • et al.
        The effect of green tea supplementation on obesity: a systematic review and dose-response meta-analysis of randomized controlled trials.
        Phytother Res. 2020; 34: 2459-2470
        • Phung O.J.
        • Baker W.L.
        • Matthews L.J.
        • Lanosa M.
        • Thorne A.
        • Coleman C.I.
        Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis.
        Am J Clin Nutr. 2010; 91: 73-81
        • Li G.
        • Zhang Y.
        • Thabane L.
        • Mbuagbaw L.
        • Liu A.
        • Levine M.A.
        • et al.
        Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis.
        J Hypertens. 2015; 33: 243-254
        • Liu K.
        • Zhou R.
        • Wang B.
        • Chen K.
        • Shi L.Y.
        • Zhu J.D.
        • et al.
        Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials.
        Am J Clin Nutr. 2013; 98: 340-348
        • Xu R.
        • Bai Y.
        • Yang K.
        • Chen G.
        Effects of green tea consumption on glycemic control: a systematic review and meta-analysis of randomized controlled trials.
        Nutr Metab. 2020; 17: 56
        • Zheng X.X.
        • Xu Y.L.
        • Li S.H.
        • Hui R.
        • Wu Y.J.
        • Huang X.H.
        Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.
        Am J Clin Nutr. 2013; 97: 750-762
        • Asbaghi O.
        • Fouladvand F.
        • Gonzalez M.J.
        • Ashtary-Larky D.
        • Choghakhori R.
        • Abbasnezhad A.
        Effect of green tea on glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
        Diabetes Metab Syndr. 2020; 15: 23-31
        • Zheng X.X.
        • Xu Y.L.
        • Li S.H.
        • Liu X.X.
        • Hui R.
        • Huang X.H.
        Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.
        Am J Clin Nutr. 2011; 94: 601-610
        • Onakpoya I.
        • Spencer E.
        • Heneghan C.
        • Thompson M.
        The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials.
        Nutr Metabol Cardiovasc Dis. 2014; 24: 823-836
        • Visseren F.L.J.
        • Mach F.
        • Smulders Y.M.
        • Carballo D.
        • Koskinas K.C.
        • Bäck M.
        • et al.
        ESC Guidelines on cardiovascular disease prevention in clinical practice.
        Eur Heart J. 2021; 42 (2021): 3227-3337