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Address reprint requests to: Arpita Basu, PhD, RD, Assistant Professor, Nutritional Sciences, 301 Human Environmental Sciences, Oklahoma State University, Stillwater,
OK. E-mail: arpita.basu@okstate.edu
The authors have no conflicts of interest to report.
The abstract of this manuscript was presented in 2008 at the 49th Annual Meeting of the American College of Nutrition, at Arlington, VA, and received the Best Poster
Award.
Abbreviations: ATP III 5 Adult Treatment Panel III, BMI 5 body mass index, BUN 5 blood urea nitrogen, CV 5 coefficient of variation, EC 5 epicatechin, ECG 5
epicatechin gallate, EGC 5 epigallocatechin, EGCG 5 epigallocatechin-3-gallate, ELISA 5 enzyme-linked immunosorbent assay, GCRC 5 General Clinical Research
Center, Hb 5 hemoglobin, HbA1C 5 glycated hemoglobin, HDL 5 high-density lipoprotein, HNE 5 hydroxynonenals, HOMAIR 5 homeostasis model assessment of
insulin resistance, HPLC 5 high-performance liquid chromatography, IDL 5 intermediate density lipoprotein, IRB 5 institutional review board, LC 5 liquid
chromatography, RD 5 registered dietitian, LDL 5 low-density lipoprotein, MCV 5 mean corpuscular volume, MDA 5 malondialdehyde, MeS 5 metabolic syndrome,
MPO 5 myeloperoxidase, NCEP 5 National Cholesterol Education Program, NMR-LSP 5 nuclear magnetic resonance-determined lipoprotein subclass profile, OSU 5
Oklahoma State University, OUHSC 5 University of Oklahoma Health Science Center, OUMC 5 University of Oklahoma Medical Center, ox-LDL 5 oxidized LDL,
RBC 5 red blood cell, SPSS 5 Statistical Package for the Social Sciences, TSH 5 thyroid-stimulating hormone, UV 5 ultraviolet, VLDL 5 very low density lipoprotein,
WBC 5 white blood cell.
Journal of the American College of Nutrition, Vol. 29, No. 1, 3140 (2010)
Published by the American College of Nutrition
31
INTRODUCTION
Green tea (Camellia sinensis), traditionally used in Chinese
medicine, has gained scientific recognition in recent years for
its cardioprotective and weight loss effects [13]. The
antioxidant and antiobesity effects of green tea have been
associated with its catechin content: epiogallocatechin-3gallate (EGCG ,48%55%), epigallocatechin (EGC ,9%
12%), epicatechin gallate (ECG ,9%12%), and epicatechin
(EC) (5%7%), with EGCG being the most abundant and
pharmacologically active of the catechins [4]. Results of
epidemiologic studies in Asian countries have shown chronic
green tea consumption to be significantly associated with
reduced risks of cardiovascular disease [58]. Mechanistic
studies show that green tea catechins significantly decrease
low-density lipoprotein (LDL) oxidation [9], superoxide
production [10], vascular smooth muscle cell proliferation
[11], cholesterol absorption and serum cholesterol [12,13],
serum glucose [14], aortic lesion formation [15], and systolic
and diastolic blood pressure [16], thus causing an overall
attenuation in risk factors for atherosclerosis and hypertension.
Limited clinical trials have shown green tea intervention to
lower oxidative stress in smokers and healthy subjects [1721]
and to improve insulin resistance and decrease glycated
hemoglobin (HbA1C) levels in patients with prediabetes or
diabetes [22,23]. However, most of these studies were
conducted among habitual green tea drinkers in Asian
countries [17,18,22,23] or had small sample size or short
study duration [1820], or the interventions used green tea in
combination with a low-fat diet [21] or green tea formulations
not commercially available in the United States [2023].
With an alarming rise in the prevalence of obesity and
metabolic syndrome (MeS) in the U.S. population [24,25], use
of alternative nutrition therapies, such as dietary supplements,
to promote weight loss [26] has been increasing. MeS, a
constellation of risk factors, including atherogenic dyslipidemia (low high-density lipoprotein [HDL], high triglyceride),
impaired fasting glucose, hypertension, and central adiposity,
also predisposes to higher risks of oxidative stress, type 2
diabetes, and atherosclerotic cardiovascular disease [27]. Diet
and exercise have been shown to improve oxidative stress,
insulin sensitivity, and atherosclerotic risk factors in subjects
with MeS [28]. Selected clinical trials in overweight and obese
subjects have shown green tea catechins to reduce body fat and
body weight or to maintain weight loss when catechin doses in
the range of 270750 mg are used [29,30], although the effects
of green tea supplementation in the U.S. population with
metabolic syndrome have not been reported.
To examine the hypothesis that commercially available
green tea or extracts will reduce body weight, fasting glucose
and lipids, and oxidative stress in subjects with metabolic risk
factors, we conducted a randomized controlled study in 35 men
and women with MeS. The effects of green tea catechins on
32
Study Design
This was a randomized controlled trial with a single-blind
and permuted block randomization design. To account for the
effects of age and gender on the variables of interest,
participants were recruited into trios matched for age (65 years)
and gender. The age and gender for a trio were determined by
the first participant assigned to that trio. The next consecutive
participant who met the matching criteria of that trio was
assigned as the second participant of that trio, and so on. Each
trio had 1 participant in each of the 3 intervention groups: green
tea (4 cups/d), green tea extracts (2 capsules, 4 cups water/d), or
control (4 cups water/d). Although trios were filled consecutively within the matching parameters, the intervention to which
Green Tea2
(4 cups)
928.0 (100.0)
440.0 (47.4)
220.0 (23.7)
180.0 (19.4)
88.0 (9.5)
8.96
870.0 (100.0)
460.0 (52.8)
240.0 (27.6)
120.0 (13.8)
50.0 (5.8)
3.6
1
Total catechin concentration was defined as the sum of EGCG, EGC, ECG, and
EC values.
2
Percentage of total catechin in parentheses.
EC 5 epicatechin, ECG 5 epicatechin gallate, EGC 5 epigallocatechin, EGCG
5 epigallocatechin gallate.
33
Anthropometrics
Anthropometric measurements were obtained by trained
staff members at the GCRC. Height, weight, blood pressure,
waist circumference, and body fat percentage were measured
at screen and at 4- and 8-week visits. Participants removed
shoes and items in dress pockets and were weighed on a flat,
uncarpeted surface with the SECA 644 Multifunctional Hand
Rail Scale (SECA, Hamburg, Germany); weight was recorded
to the nearest 0.1 kg. Height was measured without shoes by
using the Accustat Genentech Stadiometer (San Francisco,
CA), and height was recorded to the nearest 0.1 cm. Systolic
and diastolic blood pressure was measured in mmHg with the
Spot Vital Signs Device (Welch Allyn, Skaneateles Falls, NY).
The Gulick II Tape Measure (Vital Signs, Gay Mills, WI) was
34
Dietary Analyses
Three-day averages of micronutrient and macronutrient
intakes were analyzed with Nutritionist Pro (version 3.2, 2007;
Axxya Systems, Stafford, TX). All data entry was performed
by registered dietitians (RDs) at GCRC who were trained and
certified in using the software. All dietary data entry was
verified by a second RD as a measure of quality control. If a
participant ate a food that was not in the database, a food with
very similar nutrient composition was chosen. Nutrient
information was also obtained from food labels or recipes
obtained from subjects or online sources or at grocery stores.
Clinical Analyses
Blood samples were collected immediately after each draw
at the GCRC and were transported to the University of
Oklahoma Medical Center (OUMC) Laboratory for analyses of
fasting glucose, insulin, lipid profile (total cholesterol,
triglycerides, LDLs, and HDLs), and other blood variables
(Hb, platelets, WBCs, red blood cells [RBCs], hematocrit,
mean corpuscular volume [MCV], liver enzymes, creatinine,
blood urea nitrogen [BUN], electrolytes, albumin, total protein,
and thyroid-stimulating hormone [TSH]). HbA1C was analyzed
at the GCRC with the use of a DCA 2000+ (Bayer
Corporation, Elkhart, IN). Insulin resistance was evaluated
by homeostasis model assessment (HOMAIR) and was
calculated as follows: Fasting insulin (mU/mL) 3 Fasting
glucose (mmol/L)/22.5.
Nuclear magnetic resonance-determined lipoprotein subclass profile (NMR-LSP) was performed in first-thaw plasma
specimens with a 400-MHz proton NMR analyzer at
LipoScience Incorporated (Raleigh, NC), as described previously [34].
For oxidized LDL (ox-LDL), myeloperoxidase (MPO), and
malondialdehyde and hydroxynonenal (MDA and HNE)
assays, serum and EDTA-plasma samples were collected,
were separated by centrifugation (3000 rpm for 10 minutes at
4uC), and were stored at 280uC for subsequent analyses.
Statistical Analyses
For all measures, descriptive statistics were calculated and
graphs drawn to look for outliers. Outliers due to data errors
were corrected where possible or were removed. Pairwise
differences (green tea versus control and green tea extracts
versus control) between the 3 groups at baseline were assessed
with the use of student t-tests. Changes in measurements over
the 8-week study period were assessed by calculating the
differences between preintervention and postintervention
measurements. Differences calculated for the green tea and
green tea extract groups were then conditioned on their
respective controls; the difference seen in the control
participant was subtracted from the difference seen in each
corresponding green tea and green tea extract participant
within the age- and gender-matched trio. These conditional
differences for the green tea and green tea extract groups were
assessed as being different from zero (no change) with the use
of student t-tests. All statistical tests were 2-tailed with
significance level set at 0.05. Significance levels were not
adjusted for multiple-hypothesis testing, rather the results were
reviewed for consistencies. The Statistical Package for the
Social Sciences (SPSS) for Windows (version 15.0; SPSS
Incorporated, Chicago, IL, 2006) was used for the statistical
calculations.
RESULTS
Baseline Characteristics
35
Control
N
Gender (female/male)
Age (years)
Weight (kg)
Body mass index (kg/m2)
Body fat (%)
Waist circumference (inches)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Glucose (mg/dL)
Hemoglobin A1C (%)
Triglycerides (mg/dL)
Total cholesterol (mg/dL)
LDL-cholesterol (mg/dL)
HDL-cholesterol (mg/dL)
LDL/HDL
HOMAIR
Oxidized LDL (U/L)
Myeloperoxidase (mg/L)
Malondialdehyde and hydroxynonenal (mM)
Catechins (EGC, EGCG, ECG) (mmol/L)
44.6
102.7
36.4
44.0
42.5
130
80.0
90.0
5.6
129
212
144
42.0
3.5
3.0
104
70
1.14
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
Green Tea
12
10/2
3.2 (2563)
6.6 (76154)
2.8 (2561)
3.4 (2363)
2.0 (3555)
2.6 (113141)
2.1 (6990)
4.1 (65113)
0.1 (5.16.3)
21.0 (62271)
10.5 (158264)
9.5 (91206)
2.0 (3452)
0.3 (2.15.3)
0.4 (0.85.6)
10.6 (33186)
4.7 (3298)
0.02 (1.01.3)
ND
42.8
96.4
34.6
42.0
41.3
132
83.0
89.0
5.5
175
193.5
122
40.0
3.1
3.0
104
63.3
1.2
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
13
10/3
2.6 (2859)
4.7 (67123)
1.5 (2845)
2.8 (2453)
1.1 (3547)
3.5 (119161)
2.2 (7195)
3.2 (73112)
0.1 (5.16.3)
25.0 (53404)
11 (143283)
10.4 (84196)
2.1 (2747)
0.3 (1.94.9)
0.4 (1.15.9)
7.2 (42135)
2.8 (5078)
0.04 (1.01.4)
ND
39.5
106.2
38.0
42.0
45.3
128
82.0
85.0
5.5
161
170
100
38.0
3.0
3.2
91
74
1.2
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
10
7/3
3.0 (2752)
7.5 (69138)
2.3 (2546)
2.8 (2553)
2.5 (3758)
3.3 (114150)
1.7 (7591)
2.8 (72104)
0.1 (4.66.1)
26.6 (53314)
15 (108249)*
10.0(54146)*
5.0 (2176)
0.3 (1.25.0)
0.6 (0.66.4)
9.1 (49133)
4.2 (56100)
0.04 (1.11.4)
ND
Table 3. Pairwise Comparisons of Differences in Anthropometrics, Blood Pressure, and Clinical Variables within Ageand Gender-Matched Trios between 0 and 8 Weeks1
Variable
Pairs (n)
Weight (kg)
Body mass index (kg/m2)
Body fat (%)
Waist circumference
(inches)
Systolic blood pressure
(mmHg)
Diastolic blood pressure
(mmHg)
Glucose (mg/dL)
Hemoglobin A1C (%)
Triglycerides (mg/dL)
Total cholesterol (mg/dL)
LDL-cholesterol (mg/dL)
HDL-cholesterol (mg/dL)
LDL/HDL
HOMAIR
Green Tea
versus Control
11
22.5 6 0.7*
20.9 6 0.3*
20.3 6 0.9
7
21.9 6 0.6{
20.7 6 0.2{
0.2 6 1.3
0.4 6 0.9
21.6 6 1.0
0.4 6 4.9
6.0 6 5.6
23.0
1.3
0.3
214.8
20.7
210.4
3.0
20.4
0.2
6
6
6
6
6
6
6
6
6
3.3
7.2
0.2
34.3
5.2
4.9"
1.7l
0.2j
0.6
23.1
22.4
0.2
23.0
211.4
214.7
21.1
20.3
0.7
6
6
6
6
6
6
6
6
6
1.9
9.1
0.1
15.8
9.9
7.2
2.6
0.2
0.7
36
20.1 6 5.5
21.7
4.4
165.4
55.1
85.0
1.1
3.4
21.6
0.1
0.5
0.4
6
6
6
6
6
6
6
6
6
6
6
6.6
13.0
179.5
44.7
266.4
1.3
1.7*
2.4
4.7
0.4
0.3
2.2 6 3.7
20.3
20.4
2177.7
214.0
281.6
20.4
V0.1
6.4
1.2
20.2
20.2
6
6
6
6
6
6
6
6
6
6
6
15.4
11.0
201.3
47.0
383.7
2.5
8.1
4.6
3.7
0.6
0.3
Green Tea
versus Control
11
215.6 6 10.86
224.8 6 16.7
7
10.0 6 14.1
27.4 6 19.2
20.39 6 0.06*
0.09 6 0.008*
20.11 6 0.05
0.088 6 0.01*
1
Data represented as mean 6 standard error.
* Significantly different from control (p , 0.001).
{ Significantly different from control (p , 0.01).
LDL 5 low-density lipoprotein.
DISCUSSION
To our knowledge, the study reported here is the first to
show that green tea beverage and extract supplementation for
8 weeks leads to a significant weight loss in obese subjects
with MeS compared with age- and gender-matched controls.
Our observations are consistent with previous findings in the
Asian population, in which green tea catechin supplementation
was shown to reduce body weight and body fat in overweight
and obese subjects [3537]. However, it should be noted that in
comparison with these studies, subjects in our trial had higher
body weight and BMI, which may explain the fact that a
significant weight loss was observed over a shorter time
(8 weeks) versus previously reported findings in a 12-week
period [3537]. This may suggest that the effects of green tea
may be more pronounced in subjects with clinically significant
obesity (BMI .35) with features of MeS than in healthy or
overweight adults. Studies reported by Hill et al. [38] and Maki
et al. [39] show that green tea catechin supplementation
together with exercise reduces abdominal fat and improves
features of MeS, such as fasting glucose and triglycerides, in
overweight or obese adults. The longer study duration
(12 weeks), the supervised exercise sessions, and the larger
37
Control
Green Tea
11
11
1900.31 6 148.35
1842.76 6 109.09
1911.34 6 247.78
1935.78 6 285.85
1986.82 6 268.93
2088.63 6 320.53
222.21 6 32.65
213.98 6 22.65
218.75 6 34.68
223.08 6 46.13
229.40 6 45.82
220.67 6 42.84
0 week
8 week
71.73 6 15.13
69.82 6 16.21
82.43 6 14.51
79.06 6 8.95
82.51 6 6.40
84.50 6 15.5
81.45 6 13.65
72.44 6 8.13
81.44 6 16.83
84.73 6 13.56
82.0 6 6.63
85.1 6 10.6
24.35 6 4.62
22.66 6 2.54
25.20 6 1.46
27.18 6 4.75
31.0 6 8.1
32.5 6 8.8
20.25 6 4.38
17.04 6 3.52
19.50 6 4.64
16.30 6 3.95
20.31 6 5.50
16.07 6 3.22
12.05 6 2.68
10.49 6 2.14
11.04 6 3.44
10.05 6 4.38
10.82 6 3.67
9.67 6 2.62
17.20 6 3.88
14.80 6 2.27
19.63 6 4.24
15.72 6 3.50
16.40 6 6.60
14.63 6 5.70
2485.65 6 617.85
2851.37 6 583.73
2354.33 6 237.86
2129.65 6 437.93
2635.95 6 249.74
2963.67 6 274.69
43.61 6 16.7
37.84 6 7.32
49.21 6 13.51
44.57 6 15.83
52.75 6 20.8
55.44 6 15.7
2.47 6 0.93
2.20 6 0.58
3.20 6 0.84
4.36 6 0.93
3.25 6 0.93
2.78 6 0.74
N
Calories (kcal)
0 week
8 week
Carbohydrates (g)
0 week
8 week
Proteins (g)
38
ACKNOWLEDGMENTS
The authors wish to thank Kavitha Penugonda for her
technical assistance in plasma catechin analyses, all OUHSC
employees for their participation in the study, and the
Bionutrition staff at GCRC for administration of intervention
and patient follow-up. This work was supported in part by the
University of Oklahoma Health Sciences Center General
Clinical Research Center grant M01-RR14467, National
Center for Research Resources, National Institutes of Health.
It was also supported by the College of Human Environmental
Sciences, Oklahoma State University.
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