Original Article
Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis Guowei Li a, Yuan Zhang a, Lehana Thabane a,b, Lawrence Mbuagbaw a, Aiping Liu c, Mitchell A.H. Levine a,b, and Anne Holbrook a,b
Background: Emerging randomized controlled trials (RCTs) investigating the effect of green tea or green tea extract (GTE) supplementation on blood pressure (BP) among overweight and obese adults reported inconsistent findings. Objective: To conduct a systematic review and metaanalysis to clarify the efficacy of green tea or GTE on BP among overweight and obese adults. Methods: Electronic databases, conference proceedings and gray literature were searched systematically to include parallel and cross-over RCTs examining the efficacy of green tea or GTE on BP compared with placebo. Data were meta-analyzed using a randomeffects model, to compare the mean difference of the change in BP from baseline in the intervention and the placebo groups. Results: Fourteen RCTs with 971 participants (47% women) were pooled for analysis. Green tea or GTE produced a significant effect on both SBP (mean difference 1.42 mmHg, 95% confidence interval 2.47 to 0.36, P ¼ 0.008; I2 ¼ 52%, P ¼ 0.01 for heterogeneity) and DBP (mean difference 1.25 mmHg, 95% confidence interval 2.32 to 0.19, P ¼ 0.02; I2 ¼ 74%, P < 0.001 for heterogeneity), compared with placebo. The quality of evidence across studies was low. Similar results were found in subgroup and sensitivity analyses. Conclusion: Among overweight and obese adults, green tea or GTE supplementation is found to cause a small but significant reduction in BP. More high-quality RCTs with large sample sizes are needed to further confirm the efficacy on BP and make strong recommendations for green tea or GTE supplementation among the overweight and obese adults. Keywords: blood pressure, green tea, obesity, overweight, systematic review Abbreviations: BP, blood pressure; CI, confidence interval; EGCG, epigallocatechingallate; GTE, green tea extract; PRISMA, preferred reporting items for systematic reviews and meta-analyses; RCT, randomized controlled trial
INTRODUCTION
O
verweight and obesity are a highly prevalent public health problem globally. In adults aged 20 years and older, the prevalence of overweight and obesity has doubled since 1980, with an estimation of 35 and 11% in 2008 worldwide for overweight and obesity, respectively [1]. Obesity is well known as one of the most important risk factors for the development of hypertension. Obese individuals have a more than three-fold increased likelihood of developing hypertension [2,3], and approximately 70% of the hypertensive adults are overweight or obese [4,5]. Furthermore, it has been estimated at least twothirds of the prevalence of hypertension can be directly attributed to obesity [2,6]. In the United States, possibly related to the increased prevalence of obesity, the prevalence of hypertension increased from 25.0 to 30.9% between 1988–1991 and 2005–2008 [7–9]. This epidemic of obesity and obesity-related hypertension is paralleled by an astonishing increase in the incidence of diabetes mellitus, chronic kidney disease, and cardiovascular morbidity and mortality [10–13]. Tea is one of the most consumed beverages in the world [14,15]. Green tea is rich in antioxidant polyphenols such as catechins and flavonols [14,16,17], and the green tea extract (GTE) has been shown to engender a vasodilator effect [18–20], both of which can benefit cardiovascular health [21–23]. Green tea or GTE may also protect humans against endothelial dysfunction and hyperlipidemia [24,25]. The physiological effects of green tea on the risk factors for cardiovascular disease, including blood pressure (BP), are therefore promising and of interest. On the basis of Whelton et al.’s [26] findings, a reduction in SBP of 5 mmHg would
Journal of Hypertension 2015, 33:243–254 a Department of Clinical Epidemiology and Biostatistics, bSt Joseph’s Hospital, McMaster University, Hamilton, Ontario, Canada and cDepartment of Social Medicine and Health Education, Health Science Center, Peking University, Beijing, China
Correspondence to Guowei Li, MD, MSc, PhD(c), Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada. Tel: +1 905 962 1068; fax: +1 905 308 7386; e-mail: [email protected] Received 26 May 2014 Revised 17 September 2014 Accepted 17 September 2014 J Hypertens 33:243–254 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000000426
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Li et al.
result in a 7, 9 and 14% overall reduction in mortality due to all causes, coronary heart disease and stroke, respectively. In animal studies, green tea supplementation and epigallocatechingallate (EGCG) as the major catechin species in green tea have been reported to prevent BP increases [27,28]. However, whereas findings from observational studies suggest a significant inverse relationship between green tea intake and cardiovascular diseases [29–31], systematic reviews or meta-analyses of randomized controlled trials (RCTs) report an inconclusive effect of green tea on BP [32–35]. Furthermore, none of the reviews investigated the effect of green tea among the overweight and obese population. Mounting evidence from RCTs among overweight and obese adults yielded inconsistent results – with some suggesting significant reduction in BP [36–38], whereas others showing no associations between green tea and BP [39–41]. Therefore, in order to clarify the efficacy of green tea or GTE supplementation in preventing the development of hypertension or treating hypertension among overweight and obese adults, we aimed to conduct a systematic review to summarize the evidence from RCTs. Our primary objective was to assess the effect of oral green tea or GTE supplementation compared to placebo on the change in BP from baseline (i.e. postintervention BP minus baseline BP) among overweight and obese adults. Our secondary objectives were to determine the effect on quality of life, adverse events and treatment discontinuation rates.
METHODS The study was conducted according to guidance from the Cochrane Handbook of Systematic Reviews and was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations [42,43]. The methods have been described in detail in our protocol [44].
Search strategy Briefly, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov (up to January 2014). An additional search of PubMed (up to 10 April 2014) was also conducted to retrieve relevant studies. Unpublished studies were identified by searching the abstract books or websites of three major conference proceedings (up to March 2014): the International Society of Hypertension, the Nutrition and Health Conference, and the World Congress of Nutrition and Health. Furthermore, we tried to contact the authors of the included studies to obtain additional data that may either be informally published or unpublished or ongoing, and which are associated with efficacy of green tea or GTE on BP. In our searches, descriptors that included synonyms for green tea, BP and RCTs in various combinations were used, for example, ‘tea or green tea or green tea extract or Camellia sinensis or catechin or epigallocatechin gallate’ and ‘BP or hypertension or cardiovascular or cerebrovascular’ and ‘RCT or placebo or clinical trial or intervention’ [44].
Study selection Parallel and cross-over RCTs investigating the efficacy of green tea or GTE in BP in adults aged 18 or older and with 244
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BMI of 25 kg/m2 and more [1], were eligible for inclusion in this systematic review. Since there may be different cut-off points of BMI to define overweight and obesity in the trials from the WHO definition, we also accepted varied BMI values to include overweight and obese participants based on the authors’ definition. If the cut-off points were unclear, we contacted the authors for clarification [44]. We aimed to isolate the intervention effect due to green tea and obtain its efficacy by direct comparison with placebo in the absence of any other hypertension intervention [45]. At least one of the intervention arms had to include oral intake of green tea or GTE as a mono-intervention in the included studies. Only trials using placebos in their control groups were included. However, to retrieve all potential eligible evidence in our systematic review, we also included studies with co-interventions, if the nonstudy co-interventions were the same in both the intervention and the placebo groups [44]. We excluded the trials with the intervention duration no longer than 1 week, because the acute effect of green tea or GTE on BP was not clinically relevant from the perspective of public health [34]. Furthermore, if no data on SBP and DBP were reported, then the studies were also excluded.
Outcomes The primary outcome was the change in BP from baseline after intervention, comparing green tea or GTE with placebo. The secondary outcomes included quality of life, adverse events associated with green tea, and treatment discontinuation rates.
Data extraction Two review authors (G.L. and Y.Z.) independently screened and selected studies for possible inclusion in the systematic review. Agreement between review authors was quantified using the Kappa statistic [46]. Data were extracted by two review authors (G.L. and Y.Z.) independently using specially developed data extraction forms. Information was collected on details of participants, intervention and outcome measures [44].
Statistical analysis A random-effects meta-analysis was performed to synthesize the data by pooling the results of the included studies. We analyzed the data using Review Manager (RevMan) version 5.2 for Windows (the Nordic Cochrane Center, the Cochrane Collaboration, Copenhagen, Denmark). We calculated and pooled the mean difference of the change in BP from baseline between the intervention and the placebo groups, presenting the pooled results with 95% confidence intervals (CIs) [43]. We first assessed clinical heterogeneity by determining whether the included studies were similar enough to pool. If the studies could not be pooled because they had heterogeneous populations, interventions and outcome measures, then narrative summaries would be reported by synthesizing the qualitative evidence [43]. If the studies could be meta-analyzed, the statistical heterogeneity was evaluated using the I2 statistic, with a value of I2 above 50% or P value less than 0.1 taken as implying significant Volume 33 Number 2 February 2015
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Green tea and blood pressure among overweight and obese adults
heterogeneity [47,48]. To explore heterogeneity, the results were stratified by the following a priori subgroup analyses: high versus low doses of green tea or GTE: the cut-off point was chosen as 5 cups per day (1 cup ¼ 237 ml) in green tea supplementation [49], or equivalently 450 mg catechins or 250 mg EGCG per day in GTE approximately [50–52]; different intervention durations: that is, the RCTs with duration periods of at least 3 months versus those with duration of less than 3 months; different geographic regions: that is, Asia, Europe and others; overweight versus obese participants; and participants with versus without change in body weight after intervention. Since there may be effect of green tea on weight loss in overweight and obese adults [53], and a concurrent decrease in body weight may reduce BP [33,54], a subgroup analysis was conducted to explore whether the effect on BP was different in participants with versus without significant weight loss (in kg) [44]. Moreover, meta-regression analyses were also performed to examine the relationship between mean weight loss or mean BMI change after intervention and the change in BP from baseline [43]. We also carried out predefined sensitivity analyses by excluding studies classified as having high risk of bias and using a fixed-effects model. Furthermore, we pooled the mean difference for the postintervention BP between the intervention and the placebo groups in all the included trials. Another sensitivity analysis was conducted by excluding the trials with nonstudy co-interventions, to examine the robustness of the results [44]. A funnel plot was constructed to investigate the potential for publication bias for the primary outcome, by means of visual inspection for signs of asymmetry, Begg’s rank correlation and Egger’s regression tests [43].
Quality assessment For each included RCT, the review authors (G.L. and Y.Z.) rated each domain as having low, high or unclear risk of bias independently, using the Cochrane Collaboration ‘Risk of bias’ assessment tool [43]. The quality of evidence across studies in this systematic review was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool [55], with GRADEprofiler (GRADEpro) version 3.6 software [43].
RESULTS Study identification We identified 2468 citations in total. After removing 251 duplicates, 2217 citations remained for title and abstract screening, from which 102 studies were retrieved for fulltext screening. We excluded six trials with intervention duration no longer than 1 week (i.e. four with less than or equal to 3-day duration [56–59], and two with 7-day intervention [60,61]). One study [62] reported data only on mean arterial pressure, rather than SBP and DBP, and therefore was excluded. Two studies [63,64] using overweight and obese participants were also excluded because no data on BP were reported. There were three discrepancies resolved by discussion between the review authors (kappa ¼ 0.89, 95% CI 0.76–1.00). Fourteen studies [36,38,39,41,65–74] met the inclusion criteria and were Journal of Hypertension
included in the meta-analyses. No study was identified from unpublished or gray literature. eFig. 1 (http://links. lww.com/HJH/A428) shows the study selection process for this systematic review.
Characteristics of included studies Among the fourteen studies (Table 1), five were conducted in Asia (including two Japanese [71,72] and three Chinese [69,73,74] trials), six in Europe (three in UK [36,39,67], two in Poland [38,41], and one in Netherlands [66]), two in USA [65,70] and one in Australia [68]. There were 1021 participants randomized in the 14 studies; however, data were only reported and analyzed from a total of 971 participants (47% women, n ¼ 454) in the included trials. The mean ages varied from 29 [70] to 54 [73] years approximately, and the mean BMIs were from 25 [70] to 35 kg/m2 [65]. All studies were published between 2006 and 2014. The baseline SBP and DBP ranged from 124 [68] to 148 mmHg [69], and from 70 [68] to 89 mmHg [38], respectively. There were only three articles reporting the baseline comorbidities, that is, Basu et al.’s [65] study participants were with metabolic syndrome, whereas Liu et al.’s [73] and Hsu et al.’s [69] study participants were with type 2 diabetes. Three studies [65,71,72] used green tea beverage as intervention, whereas the other 11 studies [36,38,39,41,66 – 70,73,74] applied GTE capsules. There were two trials using the same nonstudy co-intervention in both the intervention and the control groups, that is, Diepvens et al.’ study [66] administered a low-energy diet and Hill et al.’s [68] trial used the same exercise in the GTE and placebo groups. The duration of green tea or GTE supplementation ranged from 3 [67] to 16 weeks [69,73]. The daily EGCG contained in the green tea or GTE varied from 133 [72] to 857 mg [69,73], whereas the daily catechins were from 320 [70] to 1207 mg [66]. Six RCTs [39,65,69,70,72,73] chose decaffeinated green tea or GTE, whereas Frank et al.’s [67] study capsules contained 114 mg caffeine per day in both the intervention and the placebo groups. However, no ascertained information on the caffeine status of green tea or GTE could be extracted from the five trials [36,38,41,68,71]. Assessment of the risk of bias showed high risk of bias in nine trials [36,65,67–71,73,74], unclear risk of bias in four studies [38,39,66,72] and low risk of bias in only one RCT [41] (see eFigs. 2 and 3, http://links.lww.com/HJH/A428 for risk of bias summary and graph, respectively). The principal reason for high risk of bias was due to no intention-to-treat (ITT) analysis used to address the dropouts and incomplete outcome data [36,65,67–71,73,74]. The four RCTs were rated as unclear risk of bias, mainly because their allocation concealment [38,66,72] and the influence of funding [39,66,72] were unclear.
Effect of green tea or green tea extract on blood pressure among the overweight and obese adults The point estimate of efficacy of green tea or GTE in SBP and DBP among the overweight and obese adults and the meta-analysis result for the green tea or GTE versus placebo are shown in Figs 1 and 2, respectively. There was a www.jhypertension.com
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245
246
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Netherlands 46 Females
UK
Australia
China
China
China
Diepvens, 2006d
Frank, 2009e
Hill, 2007f
Hsu, 2008g
Hsu, 2011h
Liu 2014i
Poland
UK
Brown, 2011c
Suliburska, 2012
UK
Brown, 2009b
USA
Poland
Bogdanski, 2012
Nantz, 2009j
35 (8, 23%)
USA
Basu, 2011a
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
46 (23, 50%)
Baseline BMI (SD)
Not reported
Placebo-41.6 (10.0) GTE- 41.0 (9.5)
Placebo- 52.2 (9.1) GTE- 55.0 (6.6)
Placebo- 43.9 (12.6) GTE- 50.5 (9.2)
GTE- 43.0 (11.1)
Placebo- 52.26 (7.71)
Placebo- 30.3 (11.2) GTE- 48.56 (8.81) Not reported
Not reported
With type 2 diabetes
With type 2 diabetes
Not reported
Not reported
31.4 (2.6) 27.7 (1.8)
Not reported
Placebo-49.4 (5.6) GTE- 41.7 (8.6)
Placebo- 40.8 (9.5) Ranged from 45 to 70 years
31.0 (2.5) 31.7 (2.7)
Placebo-50.57 (6.48) GTE- 49.5 (5.6) Not reported
33.45 (2.65)
24.3 (5.99) 32.07 (2.41)
26.4 (4.6) 25.4 (4.45)
29.2 (3.6) 26.2 (4.2)
30.5 (4.6) 30.3 (4.3)
25.4 (3.4) GTE- 30.65 (0.59) Placebo-31.39 (0.73) 31.2 (3.5)
27.7 (1.8) 26.7 (3.3)
33.9 (2.3) 31.2 (2.8)
Not reported
Placebo-51.5 (7.4) GTE-52.15 (6.43)
36.4 (2.8) 32.5 (3.3)
Not reported
With metabolic 34.6 (1.5) syndrome
Comorbidity
Placebo-44.6 (3.2) GTE-49.2 (8.8)
GT-42.8 (2.6)
Age (SD)
Placebo- 53.5 (7.0) 111 (55, 58%) GTE- 28.9 (8.0)
77 (45, 58%)
68 (44, 65%)
78 Females
38 Females
33Males
83 Males
88 Males
56 (28, 50%)
n (n and % for females)
Source – first author, year Country
Participants
TABLE 1. Characteristics of included randomized controlled trials
80.0 (2.1) 88 (4)
83.0 (2.2)
Baseline DBP (SD)
One placebo capsule/day containing pure micro crystalline cellulose
4 cups (946 ml) water/day
Comparison used
Two placebo capsules/day containing; 1900 mg lactose
Two capsules/day decaffeinated GTE containing 320 mg catechins and 180 mg EGCG
Three decaffeinated GTE capsules/day containing 857 mg EGCG
Three decaffeinated GTE capsules/day containing 857 mg EGCG
Three caffeinated GTE capsules/day containing 377 mg EGCG and 27.3 mg caffeine
Two GTE capsules/day containg 300 mg EGCG
Six GTE capsules/day containing 714 mg polyphe nols, 150 mg EGCG and 114 mg caffeine
12 weeks
6 weeks
8 weeks
3 months
8 weeks
Intervention duration
12 weeks
One placebo capsule/day containing pure micro crystalline cellulose
Two placebo capsules/day containing microcrystal line cellulose, dextrose, dicalcium phosphate, magnesium stearate, sili con dioxide, and FD&C red #40, yellow #6, and blue #1
3 months
3 months
Three placebo capsules/day 16 weeks containing 1500 mg microcrystalline cellulose
Three placebo capsules/day 16 weeks containing 1500 mg microcrystalline cellulose
Three placebo capsules/day 12 weeks containing 1200 mg microcrystalline cellulose and 0 mg caffeine
Two placebo (lactose) capsules/day
3 weeks Six placebo capsules/day containing 2214 mg maltodextrin and 114 mg caffeine
Nine GTE capsules/day con- Nine placebo capsules/day containing 2790 mg taining 1207 mg catemaltodextrin and 0 mg chins, 674 mg EGCG and caffeine 236.7 mg caffeine
Two decaffeinated GTE capsules/day containing 800 mg catechins and 430 mg EGCG
Two GTE capsules/day con- Two placebo capsules/day taining; 800 mg EGCG containing; 800 mg lactose
One GTE capsule/day containing 379 mg of GTE (including 208 mg EGCG).
4 cups (946 ml) of decaffeinated GT/d containing 440 mg EGCG
Type and dose for GT or GTE
129 (6.0) 78 (3.7) 130.72 (6.95) 85.10 (12.47) One GTE capsule/day containing 208 mg EGCG 129.58 (7.88) 84.21 (3.32)
133.3 (16.7) 84.5 (15.3) 131 (6.3) 80 (4.2)
150 (17.6) 87.6 (2.7) 133.4 (18.6) 78.9 (10.8)
135.4 (20.0) 81.6 (11.5) 147 (20.6) 88.6 (12.7)
134.9 (16.2) 82.9 (9.3)
122.6 (3.28) 69.5 (1.73)
126 (16) 79 (11) 125.2 (2.96) 70.9 (1.35)
122.5 (13.2) 78.6 (8.9) 125 (10) 78 (8)
127.7 (8.3) 79.5 (5.9) 127.3 (11.8) 80.0 (12.0)
138.2 (18.2) 87.2 (9.2) 127.1 (8.7) 79.1 (6.1)
146 (10) 89 (3) 136.2 (13.0) 86.7 (7.3)
130.0 (2.6) 145 (10)
132.0 (3.5)
Baseline SBP (SD)
Intervention
0.3 (7.2) 0.54 (5.61)
0.8 (1.8) 2.9 (7.2)
2.7 (1.6) 4.9 (5.7)
4.4 (2.1)
Change in SBP (SD)
1.7 (11.7) 3 (3.98)
8 (11.69) 1.9 (16.9)
2.9 (12.3) 1 (13.03)
3.6 (14.9)
0.79 (1.63)
1 (10.48) 0.04 (2.02)
6.6 (7.97) 2 (6.32)
0.09 (1.68) 1.26 (4.73)
0 (3.79) 0.36 (1.49) 2.57 (4.37)
0.1 (0.9) Not reported
0 (2.20) 0.2 (0.6)
0 (0.8) 0.1 (2.72)
0.06 (2.8)
0.16 (0.10)
0.2 (2.10) 0.03 (0.08)
1.5 (1.14) 0 (2.09)
0.24 (5.63) 1.5 (1.32) 10.0 (7.17)
0.058 (0.49) Not reported
0.36 (1.09) 0.0042 (0.49)
0 (0.3) 0.39 (1.02)
0.9 (0.3)
Change in BMI (SD)
Outcome
0.29 (2.33)
2 (2.34) 1.04 (7.82)
4.1 (12.6) 1 (2.66)
1.7 (8.20) 0.7 (11.1)
2.3 (10.4) 0.6 (8.32)
1.2 (10.6)
1.35 (0.99)
2 (6.60) 0.75 (1.45)
1.4 (5.39) 1 (5.06)
0.01 (4.61) 4.0 (7.28)
0.058 (4.9) 0.39 (3.70)
0.6 (3.8) 2.7 (4.9)
0.3 (1.6) 4.7 (3.2)
2.9 (1.5)
Change in DBP (SD)
Li et al.
Volume 33 Number 2 February 2015
2 (9) 2 (10)
Journal of Hypertension
significant effect of green tea or GTE supplementation on the change in BP from baseline, with the mean difference of 1.42 (95% CI 2.47 to 0.36, P ¼ 0.008) and 1.25 (95% CI 2.32 to 0.19, P ¼ 0.02) mmHg for SBP and DBP, respectively. However, there was significant heterogeneity among the included studies for both SBP (I2 ¼ 52%, P ¼ 0.01) and DBP (I2 ¼ 74%, P < 0.001).
Assessment of heterogeneity
82 (9) 132 (12) 28.0 (2.6) Placebo- 41 (9)
GT, green tea; GTE, green tea extract. a Forty-one participants randomized, but data only available for 35 people; data extracted from GT group and placebo group; no Intention-to-treat (ITT) analysis used. b Ninety-four participants randomized, but data only available for 88 people; no ITT analysis used. c Data extracted for the whole cross-over trial, because data for the first half not reported; ITT analysis used. d All participants consumed a same low-energy diet as a co-intervention in both GTE and placebo groups. e Thirty-five participants randomized, but data only available for 33 people; no ITT analysis used. f Forty-two participants randomized, but data only available for 38 people; no ITT analysis used; all participants took the same exercise as a co-intervention in both GTE and placebo groups. g Hundred participants randomized, but data only available for 78 people; no ITT analysis used. h Eighty participants randomized, but data only available for 68 people; no ITT analysis used. i Ninety-two participants randomized, but data only available for 77 people; no ITT analysis used. j One hundred and twenty-four participants randomized, but data only available for 111 people; no ITT analysis used. k One hundred and one participants randomized, but data only available for 89 people; no ITT analysis used.
0.1 (0.5)
2 (6) 2 (10) 12 weeks 500 ml/day decaffeinated placebo drink not containing cathchins, but with similar taste to GT beverage 130 (11) 81 Males Japan Takeshita, 2008
Placebo- 48.0 (5.8) GT- 40 (12)
Not reported
27.8 (2.3)
79 (11) 128 (15) 27.7 (1.6)
80 (9)
500 ml/day decaffeinated GT beverage containing 548 mg catechins and 133 mg EGCG
500 ml/day placebo drink containing0mgcathchins and 0.05) [73].
GT/GTE Placebo Mean SD Total Mean SD Total Weight –0.3 1.56 13 10.8% –2.9 1.51 12 –4.7 3.8 3.2 28 –0.6 28 9.1% 46 –0.058 4.86 42 8.6% –2.68 4.88 69 0.39 66 –0.01 4.61 3.7 10.3% –4 7.28 23 –1.4 5.39 23 5.0% 1 5.06 17 –2 6.6 16 4.5% 19 19 0.75 1.45 1.35 0.99 11.7% –1.2 10.6 41 37 –2.3 10.4 3.7% –0.6 8.32 35 –1.7 8.2 33 4.6% 0.7 11.1 39 –4.1 12.6 38 3.0% 55 56 –1 2.66 2 2.34 11.4% 23 –1.04 7.82 0.29 2.33 23 5.6% 44 –3 8 –2 7 45 6.0% 40 –2 6 –2 9 41 5.6%
Total (95% CI)
489
482
100.0%
Heterogeneity: Tau2 = 1.36; Chi2 = 50.08, df = 13 (P = 0.00001); I2 = 74% Test for overall effect: Z = 2.31 (P = 0.02)
Mean difference IV, random, 95% CI –1.70 [–3.18, –0.22] –4.10 [–6.31, –1.89] –2.59 [–5.60, –0.42] 0.30 [–1.60, –2.20] –3.40 [–7.78, 0.98] –1.00 [–6.95, 4.95] –0.75 [–1.92, 0.42] –0.70 [–6.74, 5.34] 7.00 [1.12, 12.88] 3.60 [–2.88, 10.08] –3.00 [–4.45, –1.55] –1.31 [–3.94, –1.32] –300 [–8.20, 2.20] 0.00 [–4.36, 4.36]
Mean difference IV, random, 95% CI
–1.42 [–2.47, –0.36] –4 –2 0 2 4 Favours [GT or GTE] favours [placebo]
FIGURE 2 Forest plot for the mean difference of the change in DBP comparing green tea or green tea extract with placebo. The size of the data markers (squares) for the MD corresponds to the weight of the study in the meta-analysis; the horizontal lines correspond to the 95% CI values. CI, confidence interval; GT, green tea; GTE, green tea extract; MD, mean difference.
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Green tea and blood pressure among overweight and obese adults TABLE 2. Results of predefined and post-hoc subgroup analyses for mean difference of the change in blood pressure
Change in SBP
Subgroup analyses Predefined subgroup analyses Dose of GT or GTEa High Low Trial duration 3 months
Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis Guowei Li a, Yuan Zhang a, Lehana Thabane a,b, Lawrence Mbuagbaw a, Aiping Liu c, Mitchell A.H. Levine a,b, and Anne Holbrook a,b
Background: Emerging randomized controlled trials (RCTs) investigating the effect of green tea or green tea extract (GTE) supplementation on blood pressure (BP) among overweight and obese adults reported inconsistent findings. Objective: To conduct a systematic review and metaanalysis to clarify the efficacy of green tea or GTE on BP among overweight and obese adults. Methods: Electronic databases, conference proceedings and gray literature were searched systematically to include parallel and cross-over RCTs examining the efficacy of green tea or GTE on BP compared with placebo. Data were meta-analyzed using a randomeffects model, to compare the mean difference of the change in BP from baseline in the intervention and the placebo groups. Results: Fourteen RCTs with 971 participants (47% women) were pooled for analysis. Green tea or GTE produced a significant effect on both SBP (mean difference 1.42 mmHg, 95% confidence interval 2.47 to 0.36, P ¼ 0.008; I2 ¼ 52%, P ¼ 0.01 for heterogeneity) and DBP (mean difference 1.25 mmHg, 95% confidence interval 2.32 to 0.19, P ¼ 0.02; I2 ¼ 74%, P < 0.001 for heterogeneity), compared with placebo. The quality of evidence across studies was low. Similar results were found in subgroup and sensitivity analyses. Conclusion: Among overweight and obese adults, green tea or GTE supplementation is found to cause a small but significant reduction in BP. More high-quality RCTs with large sample sizes are needed to further confirm the efficacy on BP and make strong recommendations for green tea or GTE supplementation among the overweight and obese adults. Keywords: blood pressure, green tea, obesity, overweight, systematic review Abbreviations: BP, blood pressure; CI, confidence interval; EGCG, epigallocatechingallate; GTE, green tea extract; PRISMA, preferred reporting items for systematic reviews and meta-analyses; RCT, randomized controlled trial
INTRODUCTION
O
verweight and obesity are a highly prevalent public health problem globally. In adults aged 20 years and older, the prevalence of overweight and obesity has doubled since 1980, with an estimation of 35 and 11% in 2008 worldwide for overweight and obesity, respectively [1]. Obesity is well known as one of the most important risk factors for the development of hypertension. Obese individuals have a more than three-fold increased likelihood of developing hypertension [2,3], and approximately 70% of the hypertensive adults are overweight or obese [4,5]. Furthermore, it has been estimated at least twothirds of the prevalence of hypertension can be directly attributed to obesity [2,6]. In the United States, possibly related to the increased prevalence of obesity, the prevalence of hypertension increased from 25.0 to 30.9% between 1988–1991 and 2005–2008 [7–9]. This epidemic of obesity and obesity-related hypertension is paralleled by an astonishing increase in the incidence of diabetes mellitus, chronic kidney disease, and cardiovascular morbidity and mortality [10–13]. Tea is one of the most consumed beverages in the world [14,15]. Green tea is rich in antioxidant polyphenols such as catechins and flavonols [14,16,17], and the green tea extract (GTE) has been shown to engender a vasodilator effect [18–20], both of which can benefit cardiovascular health [21–23]. Green tea or GTE may also protect humans against endothelial dysfunction and hyperlipidemia [24,25]. The physiological effects of green tea on the risk factors for cardiovascular disease, including blood pressure (BP), are therefore promising and of interest. On the basis of Whelton et al.’s [26] findings, a reduction in SBP of 5 mmHg would
Journal of Hypertension 2015, 33:243–254 a Department of Clinical Epidemiology and Biostatistics, bSt Joseph’s Hospital, McMaster University, Hamilton, Ontario, Canada and cDepartment of Social Medicine and Health Education, Health Science Center, Peking University, Beijing, China
Correspondence to Guowei Li, MD, MSc, PhD(c), Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada. Tel: +1 905 962 1068; fax: +1 905 308 7386; e-mail: [email protected] Received 26 May 2014 Revised 17 September 2014 Accepted 17 September 2014 J Hypertens 33:243–254 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000000426
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Li et al.
result in a 7, 9 and 14% overall reduction in mortality due to all causes, coronary heart disease and stroke, respectively. In animal studies, green tea supplementation and epigallocatechingallate (EGCG) as the major catechin species in green tea have been reported to prevent BP increases [27,28]. However, whereas findings from observational studies suggest a significant inverse relationship between green tea intake and cardiovascular diseases [29–31], systematic reviews or meta-analyses of randomized controlled trials (RCTs) report an inconclusive effect of green tea on BP [32–35]. Furthermore, none of the reviews investigated the effect of green tea among the overweight and obese population. Mounting evidence from RCTs among overweight and obese adults yielded inconsistent results – with some suggesting significant reduction in BP [36–38], whereas others showing no associations between green tea and BP [39–41]. Therefore, in order to clarify the efficacy of green tea or GTE supplementation in preventing the development of hypertension or treating hypertension among overweight and obese adults, we aimed to conduct a systematic review to summarize the evidence from RCTs. Our primary objective was to assess the effect of oral green tea or GTE supplementation compared to placebo on the change in BP from baseline (i.e. postintervention BP minus baseline BP) among overweight and obese adults. Our secondary objectives were to determine the effect on quality of life, adverse events and treatment discontinuation rates.
METHODS The study was conducted according to guidance from the Cochrane Handbook of Systematic Reviews and was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations [42,43]. The methods have been described in detail in our protocol [44].
Search strategy Briefly, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov (up to January 2014). An additional search of PubMed (up to 10 April 2014) was also conducted to retrieve relevant studies. Unpublished studies were identified by searching the abstract books or websites of three major conference proceedings (up to March 2014): the International Society of Hypertension, the Nutrition and Health Conference, and the World Congress of Nutrition and Health. Furthermore, we tried to contact the authors of the included studies to obtain additional data that may either be informally published or unpublished or ongoing, and which are associated with efficacy of green tea or GTE on BP. In our searches, descriptors that included synonyms for green tea, BP and RCTs in various combinations were used, for example, ‘tea or green tea or green tea extract or Camellia sinensis or catechin or epigallocatechin gallate’ and ‘BP or hypertension or cardiovascular or cerebrovascular’ and ‘RCT or placebo or clinical trial or intervention’ [44].
Study selection Parallel and cross-over RCTs investigating the efficacy of green tea or GTE in BP in adults aged 18 or older and with 244
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BMI of 25 kg/m2 and more [1], were eligible for inclusion in this systematic review. Since there may be different cut-off points of BMI to define overweight and obesity in the trials from the WHO definition, we also accepted varied BMI values to include overweight and obese participants based on the authors’ definition. If the cut-off points were unclear, we contacted the authors for clarification [44]. We aimed to isolate the intervention effect due to green tea and obtain its efficacy by direct comparison with placebo in the absence of any other hypertension intervention [45]. At least one of the intervention arms had to include oral intake of green tea or GTE as a mono-intervention in the included studies. Only trials using placebos in their control groups were included. However, to retrieve all potential eligible evidence in our systematic review, we also included studies with co-interventions, if the nonstudy co-interventions were the same in both the intervention and the placebo groups [44]. We excluded the trials with the intervention duration no longer than 1 week, because the acute effect of green tea or GTE on BP was not clinically relevant from the perspective of public health [34]. Furthermore, if no data on SBP and DBP were reported, then the studies were also excluded.
Outcomes The primary outcome was the change in BP from baseline after intervention, comparing green tea or GTE with placebo. The secondary outcomes included quality of life, adverse events associated with green tea, and treatment discontinuation rates.
Data extraction Two review authors (G.L. and Y.Z.) independently screened and selected studies for possible inclusion in the systematic review. Agreement between review authors was quantified using the Kappa statistic [46]. Data were extracted by two review authors (G.L. and Y.Z.) independently using specially developed data extraction forms. Information was collected on details of participants, intervention and outcome measures [44].
Statistical analysis A random-effects meta-analysis was performed to synthesize the data by pooling the results of the included studies. We analyzed the data using Review Manager (RevMan) version 5.2 for Windows (the Nordic Cochrane Center, the Cochrane Collaboration, Copenhagen, Denmark). We calculated and pooled the mean difference of the change in BP from baseline between the intervention and the placebo groups, presenting the pooled results with 95% confidence intervals (CIs) [43]. We first assessed clinical heterogeneity by determining whether the included studies were similar enough to pool. If the studies could not be pooled because they had heterogeneous populations, interventions and outcome measures, then narrative summaries would be reported by synthesizing the qualitative evidence [43]. If the studies could be meta-analyzed, the statistical heterogeneity was evaluated using the I2 statistic, with a value of I2 above 50% or P value less than 0.1 taken as implying significant Volume 33 Number 2 February 2015
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Green tea and blood pressure among overweight and obese adults
heterogeneity [47,48]. To explore heterogeneity, the results were stratified by the following a priori subgroup analyses: high versus low doses of green tea or GTE: the cut-off point was chosen as 5 cups per day (1 cup ¼ 237 ml) in green tea supplementation [49], or equivalently 450 mg catechins or 250 mg EGCG per day in GTE approximately [50–52]; different intervention durations: that is, the RCTs with duration periods of at least 3 months versus those with duration of less than 3 months; different geographic regions: that is, Asia, Europe and others; overweight versus obese participants; and participants with versus without change in body weight after intervention. Since there may be effect of green tea on weight loss in overweight and obese adults [53], and a concurrent decrease in body weight may reduce BP [33,54], a subgroup analysis was conducted to explore whether the effect on BP was different in participants with versus without significant weight loss (in kg) [44]. Moreover, meta-regression analyses were also performed to examine the relationship between mean weight loss or mean BMI change after intervention and the change in BP from baseline [43]. We also carried out predefined sensitivity analyses by excluding studies classified as having high risk of bias and using a fixed-effects model. Furthermore, we pooled the mean difference for the postintervention BP between the intervention and the placebo groups in all the included trials. Another sensitivity analysis was conducted by excluding the trials with nonstudy co-interventions, to examine the robustness of the results [44]. A funnel plot was constructed to investigate the potential for publication bias for the primary outcome, by means of visual inspection for signs of asymmetry, Begg’s rank correlation and Egger’s regression tests [43].
Quality assessment For each included RCT, the review authors (G.L. and Y.Z.) rated each domain as having low, high or unclear risk of bias independently, using the Cochrane Collaboration ‘Risk of bias’ assessment tool [43]. The quality of evidence across studies in this systematic review was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool [55], with GRADEprofiler (GRADEpro) version 3.6 software [43].
RESULTS Study identification We identified 2468 citations in total. After removing 251 duplicates, 2217 citations remained for title and abstract screening, from which 102 studies were retrieved for fulltext screening. We excluded six trials with intervention duration no longer than 1 week (i.e. four with less than or equal to 3-day duration [56–59], and two with 7-day intervention [60,61]). One study [62] reported data only on mean arterial pressure, rather than SBP and DBP, and therefore was excluded. Two studies [63,64] using overweight and obese participants were also excluded because no data on BP were reported. There were three discrepancies resolved by discussion between the review authors (kappa ¼ 0.89, 95% CI 0.76–1.00). Fourteen studies [36,38,39,41,65–74] met the inclusion criteria and were Journal of Hypertension
included in the meta-analyses. No study was identified from unpublished or gray literature. eFig. 1 (http://links. lww.com/HJH/A428) shows the study selection process for this systematic review.
Characteristics of included studies Among the fourteen studies (Table 1), five were conducted in Asia (including two Japanese [71,72] and three Chinese [69,73,74] trials), six in Europe (three in UK [36,39,67], two in Poland [38,41], and one in Netherlands [66]), two in USA [65,70] and one in Australia [68]. There were 1021 participants randomized in the 14 studies; however, data were only reported and analyzed from a total of 971 participants (47% women, n ¼ 454) in the included trials. The mean ages varied from 29 [70] to 54 [73] years approximately, and the mean BMIs were from 25 [70] to 35 kg/m2 [65]. All studies were published between 2006 and 2014. The baseline SBP and DBP ranged from 124 [68] to 148 mmHg [69], and from 70 [68] to 89 mmHg [38], respectively. There were only three articles reporting the baseline comorbidities, that is, Basu et al.’s [65] study participants were with metabolic syndrome, whereas Liu et al.’s [73] and Hsu et al.’s [69] study participants were with type 2 diabetes. Three studies [65,71,72] used green tea beverage as intervention, whereas the other 11 studies [36,38,39,41,66 – 70,73,74] applied GTE capsules. There were two trials using the same nonstudy co-intervention in both the intervention and the control groups, that is, Diepvens et al.’ study [66] administered a low-energy diet and Hill et al.’s [68] trial used the same exercise in the GTE and placebo groups. The duration of green tea or GTE supplementation ranged from 3 [67] to 16 weeks [69,73]. The daily EGCG contained in the green tea or GTE varied from 133 [72] to 857 mg [69,73], whereas the daily catechins were from 320 [70] to 1207 mg [66]. Six RCTs [39,65,69,70,72,73] chose decaffeinated green tea or GTE, whereas Frank et al.’s [67] study capsules contained 114 mg caffeine per day in both the intervention and the placebo groups. However, no ascertained information on the caffeine status of green tea or GTE could be extracted from the five trials [36,38,41,68,71]. Assessment of the risk of bias showed high risk of bias in nine trials [36,65,67–71,73,74], unclear risk of bias in four studies [38,39,66,72] and low risk of bias in only one RCT [41] (see eFigs. 2 and 3, http://links.lww.com/HJH/A428 for risk of bias summary and graph, respectively). The principal reason for high risk of bias was due to no intention-to-treat (ITT) analysis used to address the dropouts and incomplete outcome data [36,65,67–71,73,74]. The four RCTs were rated as unclear risk of bias, mainly because their allocation concealment [38,66,72] and the influence of funding [39,66,72] were unclear.
Effect of green tea or green tea extract on blood pressure among the overweight and obese adults The point estimate of efficacy of green tea or GTE in SBP and DBP among the overweight and obese adults and the meta-analysis result for the green tea or GTE versus placebo are shown in Figs 1 and 2, respectively. There was a www.jhypertension.com
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245
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Netherlands 46 Females
UK
Australia
China
China
China
Diepvens, 2006d
Frank, 2009e
Hill, 2007f
Hsu, 2008g
Hsu, 2011h
Liu 2014i
Poland
UK
Brown, 2011c
Suliburska, 2012
UK
Brown, 2009b
USA
Poland
Bogdanski, 2012
Nantz, 2009j
35 (8, 23%)
USA
Basu, 2011a
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
46 (23, 50%)
Baseline BMI (SD)
Not reported
Placebo-41.6 (10.0) GTE- 41.0 (9.5)
Placebo- 52.2 (9.1) GTE- 55.0 (6.6)
Placebo- 43.9 (12.6) GTE- 50.5 (9.2)
GTE- 43.0 (11.1)
Placebo- 52.26 (7.71)
Placebo- 30.3 (11.2) GTE- 48.56 (8.81) Not reported
Not reported
With type 2 diabetes
With type 2 diabetes
Not reported
Not reported
31.4 (2.6) 27.7 (1.8)
Not reported
Placebo-49.4 (5.6) GTE- 41.7 (8.6)
Placebo- 40.8 (9.5) Ranged from 45 to 70 years
31.0 (2.5) 31.7 (2.7)
Placebo-50.57 (6.48) GTE- 49.5 (5.6) Not reported
33.45 (2.65)
24.3 (5.99) 32.07 (2.41)
26.4 (4.6) 25.4 (4.45)
29.2 (3.6) 26.2 (4.2)
30.5 (4.6) 30.3 (4.3)
25.4 (3.4) GTE- 30.65 (0.59) Placebo-31.39 (0.73) 31.2 (3.5)
27.7 (1.8) 26.7 (3.3)
33.9 (2.3) 31.2 (2.8)
Not reported
Placebo-51.5 (7.4) GTE-52.15 (6.43)
36.4 (2.8) 32.5 (3.3)
Not reported
With metabolic 34.6 (1.5) syndrome
Comorbidity
Placebo-44.6 (3.2) GTE-49.2 (8.8)
GT-42.8 (2.6)
Age (SD)
Placebo- 53.5 (7.0) 111 (55, 58%) GTE- 28.9 (8.0)
77 (45, 58%)
68 (44, 65%)
78 Females
38 Females
33Males
83 Males
88 Males
56 (28, 50%)
n (n and % for females)
Source – first author, year Country
Participants
TABLE 1. Characteristics of included randomized controlled trials
80.0 (2.1) 88 (4)
83.0 (2.2)
Baseline DBP (SD)
One placebo capsule/day containing pure micro crystalline cellulose
4 cups (946 ml) water/day
Comparison used
Two placebo capsules/day containing; 1900 mg lactose
Two capsules/day decaffeinated GTE containing 320 mg catechins and 180 mg EGCG
Three decaffeinated GTE capsules/day containing 857 mg EGCG
Three decaffeinated GTE capsules/day containing 857 mg EGCG
Three caffeinated GTE capsules/day containing 377 mg EGCG and 27.3 mg caffeine
Two GTE capsules/day containg 300 mg EGCG
Six GTE capsules/day containing 714 mg polyphe nols, 150 mg EGCG and 114 mg caffeine
12 weeks
6 weeks
8 weeks
3 months
8 weeks
Intervention duration
12 weeks
One placebo capsule/day containing pure micro crystalline cellulose
Two placebo capsules/day containing microcrystal line cellulose, dextrose, dicalcium phosphate, magnesium stearate, sili con dioxide, and FD&C red #40, yellow #6, and blue #1
3 months
3 months
Three placebo capsules/day 16 weeks containing 1500 mg microcrystalline cellulose
Three placebo capsules/day 16 weeks containing 1500 mg microcrystalline cellulose
Three placebo capsules/day 12 weeks containing 1200 mg microcrystalline cellulose and 0 mg caffeine
Two placebo (lactose) capsules/day
3 weeks Six placebo capsules/day containing 2214 mg maltodextrin and 114 mg caffeine
Nine GTE capsules/day con- Nine placebo capsules/day containing 2790 mg taining 1207 mg catemaltodextrin and 0 mg chins, 674 mg EGCG and caffeine 236.7 mg caffeine
Two decaffeinated GTE capsules/day containing 800 mg catechins and 430 mg EGCG
Two GTE capsules/day con- Two placebo capsules/day taining; 800 mg EGCG containing; 800 mg lactose
One GTE capsule/day containing 379 mg of GTE (including 208 mg EGCG).
4 cups (946 ml) of decaffeinated GT/d containing 440 mg EGCG
Type and dose for GT or GTE
129 (6.0) 78 (3.7) 130.72 (6.95) 85.10 (12.47) One GTE capsule/day containing 208 mg EGCG 129.58 (7.88) 84.21 (3.32)
133.3 (16.7) 84.5 (15.3) 131 (6.3) 80 (4.2)
150 (17.6) 87.6 (2.7) 133.4 (18.6) 78.9 (10.8)
135.4 (20.0) 81.6 (11.5) 147 (20.6) 88.6 (12.7)
134.9 (16.2) 82.9 (9.3)
122.6 (3.28) 69.5 (1.73)
126 (16) 79 (11) 125.2 (2.96) 70.9 (1.35)
122.5 (13.2) 78.6 (8.9) 125 (10) 78 (8)
127.7 (8.3) 79.5 (5.9) 127.3 (11.8) 80.0 (12.0)
138.2 (18.2) 87.2 (9.2) 127.1 (8.7) 79.1 (6.1)
146 (10) 89 (3) 136.2 (13.0) 86.7 (7.3)
130.0 (2.6) 145 (10)
132.0 (3.5)
Baseline SBP (SD)
Intervention
0.3 (7.2) 0.54 (5.61)
0.8 (1.8) 2.9 (7.2)
2.7 (1.6) 4.9 (5.7)
4.4 (2.1)
Change in SBP (SD)
1.7 (11.7) 3 (3.98)
8 (11.69) 1.9 (16.9)
2.9 (12.3) 1 (13.03)
3.6 (14.9)
0.79 (1.63)
1 (10.48) 0.04 (2.02)
6.6 (7.97) 2 (6.32)
0.09 (1.68) 1.26 (4.73)
0 (3.79) 0.36 (1.49) 2.57 (4.37)
0.1 (0.9) Not reported
0 (2.20) 0.2 (0.6)
0 (0.8) 0.1 (2.72)
0.06 (2.8)
0.16 (0.10)
0.2 (2.10) 0.03 (0.08)
1.5 (1.14) 0 (2.09)
0.24 (5.63) 1.5 (1.32) 10.0 (7.17)
0.058 (0.49) Not reported
0.36 (1.09) 0.0042 (0.49)
0 (0.3) 0.39 (1.02)
0.9 (0.3)
Change in BMI (SD)
Outcome
0.29 (2.33)
2 (2.34) 1.04 (7.82)
4.1 (12.6) 1 (2.66)
1.7 (8.20) 0.7 (11.1)
2.3 (10.4) 0.6 (8.32)
1.2 (10.6)
1.35 (0.99)
2 (6.60) 0.75 (1.45)
1.4 (5.39) 1 (5.06)
0.01 (4.61) 4.0 (7.28)
0.058 (4.9) 0.39 (3.70)
0.6 (3.8) 2.7 (4.9)
0.3 (1.6) 4.7 (3.2)
2.9 (1.5)
Change in DBP (SD)
Li et al.
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2 (9) 2 (10)
Journal of Hypertension
significant effect of green tea or GTE supplementation on the change in BP from baseline, with the mean difference of 1.42 (95% CI 2.47 to 0.36, P ¼ 0.008) and 1.25 (95% CI 2.32 to 0.19, P ¼ 0.02) mmHg for SBP and DBP, respectively. However, there was significant heterogeneity among the included studies for both SBP (I2 ¼ 52%, P ¼ 0.01) and DBP (I2 ¼ 74%, P < 0.001).
Assessment of heterogeneity
82 (9) 132 (12) 28.0 (2.6) Placebo- 41 (9)
GT, green tea; GTE, green tea extract. a Forty-one participants randomized, but data only available for 35 people; data extracted from GT group and placebo group; no Intention-to-treat (ITT) analysis used. b Ninety-four participants randomized, but data only available for 88 people; no ITT analysis used. c Data extracted for the whole cross-over trial, because data for the first half not reported; ITT analysis used. d All participants consumed a same low-energy diet as a co-intervention in both GTE and placebo groups. e Thirty-five participants randomized, but data only available for 33 people; no ITT analysis used. f Forty-two participants randomized, but data only available for 38 people; no ITT analysis used; all participants took the same exercise as a co-intervention in both GTE and placebo groups. g Hundred participants randomized, but data only available for 78 people; no ITT analysis used. h Eighty participants randomized, but data only available for 68 people; no ITT analysis used. i Ninety-two participants randomized, but data only available for 77 people; no ITT analysis used. j One hundred and twenty-four participants randomized, but data only available for 111 people; no ITT analysis used. k One hundred and one participants randomized, but data only available for 89 people; no ITT analysis used.
0.1 (0.5)
2 (6) 2 (10) 12 weeks 500 ml/day decaffeinated placebo drink not containing cathchins, but with similar taste to GT beverage 130 (11) 81 Males Japan Takeshita, 2008
Placebo- 48.0 (5.8) GT- 40 (12)
Not reported
27.8 (2.3)
79 (11) 128 (15) 27.7 (1.6)
80 (9)
500 ml/day decaffeinated GT beverage containing 548 mg catechins and 133 mg EGCG
500 ml/day placebo drink containing0mgcathchins and 0.05) [73].
GT/GTE Placebo Mean SD Total Mean SD Total Weight –0.3 1.56 13 10.8% –2.9 1.51 12 –4.7 3.8 3.2 28 –0.6 28 9.1% 46 –0.058 4.86 42 8.6% –2.68 4.88 69 0.39 66 –0.01 4.61 3.7 10.3% –4 7.28 23 –1.4 5.39 23 5.0% 1 5.06 17 –2 6.6 16 4.5% 19 19 0.75 1.45 1.35 0.99 11.7% –1.2 10.6 41 37 –2.3 10.4 3.7% –0.6 8.32 35 –1.7 8.2 33 4.6% 0.7 11.1 39 –4.1 12.6 38 3.0% 55 56 –1 2.66 2 2.34 11.4% 23 –1.04 7.82 0.29 2.33 23 5.6% 44 –3 8 –2 7 45 6.0% 40 –2 6 –2 9 41 5.6%
Total (95% CI)
489
482
100.0%
Heterogeneity: Tau2 = 1.36; Chi2 = 50.08, df = 13 (P = 0.00001); I2 = 74% Test for overall effect: Z = 2.31 (P = 0.02)
Mean difference IV, random, 95% CI –1.70 [–3.18, –0.22] –4.10 [–6.31, –1.89] –2.59 [–5.60, –0.42] 0.30 [–1.60, –2.20] –3.40 [–7.78, 0.98] –1.00 [–6.95, 4.95] –0.75 [–1.92, 0.42] –0.70 [–6.74, 5.34] 7.00 [1.12, 12.88] 3.60 [–2.88, 10.08] –3.00 [–4.45, –1.55] –1.31 [–3.94, –1.32] –300 [–8.20, 2.20] 0.00 [–4.36, 4.36]
Mean difference IV, random, 95% CI
–1.42 [–2.47, –0.36] –4 –2 0 2 4 Favours [GT or GTE] favours [placebo]
FIGURE 2 Forest plot for the mean difference of the change in DBP comparing green tea or green tea extract with placebo. The size of the data markers (squares) for the MD corresponds to the weight of the study in the meta-analysis; the horizontal lines correspond to the 95% CI values. CI, confidence interval; GT, green tea; GTE, green tea extract; MD, mean difference.
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Green tea and blood pressure among overweight and obese adults TABLE 2. Results of predefined and post-hoc subgroup analyses for mean difference of the change in blood pressure
Change in SBP
Subgroup analyses Predefined subgroup analyses Dose of GT or GTEa High Low Trial duration 3 months
