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Publication of the International Union Against Cancer

Int. J. Cancer: 108, 130 –135 (2004)
© 2003 Wiley-Liss, Inc.

Le JIAN1, Li Ping XIE2, Andy H. LEE1* and Colin W. BINNS1
School of Public Health, Curtin University of Technology, Perth, WA, Australia
First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
To investigate whether green tea consumption has an etiological association with prostate cancer, a case-control
study was conducted in Hangzhou, southeast China during
2001–2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The
controls were 274 hospital inpatients without prostate cancer or any other malignant diseases, and matched to the age
of cases. Information on duration, quantity and frequency of
usual tea consumption, as well as the number of new batches
brewed per day, were collected by face-to-face interview
using a structured questionnaire. The risk of prostate cancer
for tea consumption was assessed using multivariate logistic
regression adjusting for age, locality, education, income,
body mass index, physical activity, alcohol consumption, tobacco smoking, total fat intake, marital status, age at marriage, number of children, history of vasectomy and family
history of prostate cancer. Among the cases, 55.4% were tea
drinkers compared to 79.9% for the controls. Almost all the
tea consumed was green tea. The prostate cancer risk declined with increasing frequency, duration and quantity of
green tea consumption. The adjusted odds ratio (OR), relative to non-tea drinkers, were 0.28 (95% CI ⴝ 0.17– 0.47) for
tea drinking, 0.12 (95% CI ⴝ 0.06 – 0.26) for drinking tea over
40 years, 0.09 (95% CI ⴝ 0.04 – 0.21) for those consuming
more than 1.5 kg of tea leaves yearly, and 0.27 (95% CI ⴝ
0.15– 0.48) for those drinking more than 3 cups (1 litre) daily.
The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer.
© 2003 Wiley-Liss, Inc.
Key words: case-control study; green tea; prostate cancer; risk

Prostate cancer accounts for about 200,000 deaths annually
worldwide. It is the most commonly diagnosed and the second
leading cause of male cancer deaths in western countries. The
incidence rate of prostate cancer per 100,000 is 104.33 in the
United States, 75.97 in Australia but only 1.74 in China.1,2 Such
large differences between countries suggest that dietary, lifestyle
and environmental factors may be influential in the etiology of
prostate cancer.3
About 75% of prostate cancer cases worldwide occur in men 65
years of age or older, and both incidence and mortality rates tend
to increase with age.2,4,5 Although there are no dietary risk factors
established currently, a high fat intake may increase the prostate
cancer risk,2,6 whereas diets with relatively high levels of phytoestrogens such as lignins, isoflavones and genistein seem to be
protective.7 Hormones (androgens) play an important role too,8,9
whereas men with family history of prostate cancer are at high-risk
of the disease.10,11 The effects of these variables in low incidence
populations, however, are unclear. A history of vasectomy is also
linked to the risk of prostate cancer in China, although the evidence is not well established in western countries.12
Because prostate cancer has few symptoms during its initial
stages, it is typically diagnosed at an advanced stage in China.
Patients often present with symptoms of urinary outflow obstruction or metastatic tumors in bone, the latter often associated with
chronic pain. PSA testing has become popular in China for diagnosis, but its use in screening is not widespread. Treatment of
prostate cancer is difficult and somewhat controversial.13–15 Therefore, strategies that could enhance primary prevention are invaluable.

There has been considerable interest in the protective effect of
tea, particularly green tea, both in vitro and in vivo.16 –18 In animal
studies of cancers of the skin, esophagus, lung, mammary glands
and colon, intake of green or black tea as the sole drinking fluid has
been shown to lower the incidence, multiplicity, and volume of
induced tumors, compared to animals restricted to water as the
only beverage. Moreover, epidemiological studies have found inverse association between tea and several lifestyle-related cancers,
including cancers of the esophagus, lung, colon, breast, pancreas,
stomach and skin. Current research suggests that tea drinking
should be part of a healthy diet to lower the incidence of certain
cancers.19 –22
China is the second largest producer of tea and has the largest
area in the world for tea cultivation.23 Green tea accounts for 75%
of the tea production and is the most widely consumed beverage by
Chinese residents. Zhejiang Province, located in southeast China,
is the home of the famous green tea Long Jing. The annual output
of green tea from Zhejiang exceeds 138,000 tones, which amounts
to almost 20% of the annual tea production in China.24 Despite the
popularity of tea, there has been no epidemiological study undertaken in China documenting its association with prostate cancer
risk, although the few findings from North America have been
inconsistent.25–27 Furthermore, the effect of quantity of tea leaves
consumed has never been thoroughly investigated, so that the
apparent dose-response relationship cannot be firmly established in
the literature. The present case-control study, conducted during
2001– 02 in Hangzhou, capital of Zhejiang Province, attempts to
ascertain the relationship between tea consumption and prostate

Study design and participants
A hospital based 1:2 case-control design was used to investigate
the association between tea consumption and prostate cancer.
Cases were identified by daily searching of all inpatient records,
including those at the urology wards of the 8 public hospitals in
Hangzhou, between July 2001 and June 2002. Inclusion criteria for
cases were defined to be men over 45 years of age with a confirmed histopathological report of adenocarcinoma of the prostate,
who had been residents of Zhejiang Province for at least 10 years
and were capable of being interviewed (not too ill to participate).
To ensure complete ascertainment of cases, all medical records and
laboratory pathology reports were reviewed. Of the 143 cases
identified during the data collection period, 133 (93%) were interviewed and 10 (7%) refused participation. Three patients were
later excluded because their dates of diagnosis were more than 3
years ago. Most of the final 130 cases (84%) were recent patients
*Correspondence to: School of Public Health, Curtin University of
Technology, GPO Box U 1987, Perth, WA 6845, Australia.
Fax: ⫹61-8-92662958. E-mail:
Received 10 June 2003; Revised 25 July 2003; Accepted 5 August 2003
DOI 10.1002/ijc.11550

marital status.32. a history of stroke. locality (urban or rural areas). hemorrhoid and rectum wards after their diagnoses were confirmed. age at marriage. Crude and adjusted OR and associated 95% CI of prostate cancer risk for tea consumption variables were obtained from fitting separate unconditional multivariate logistic regression models. controls: mean ⫽ 156.2. physical activity MET score (cases: mean ⫽ 157. Intraclass correlation coefficients were found to be high (0. marital and reproductive status. education. SD ⫽ 24. Confidentiality and anonymity issues were also explained.5%) participated in the study. Subjects with a history of stroke were excluded because the effect of stroke on memory was uncertain. Information collected also included demographic characteristics. tea consumption variables. or have been on long-term modifications of diet for medical reasons were excluded. occupation. with non-tea drinking being the reference category. Histopathological records were obtained from the pathology department or retrieved from inpatient medical records of the eight hospitals. and years of regular tea drinking. education.3 g/day. The common method of preparation is to brew dry tea leaves in a cup using hot water without milk and sugar. medical history and family history of prostate cancer. orthopedic and injury wards (19.7%) later withdrew for personal reasons.35 Each quantitative tea consumption variable was subjected to a linear trend test in prostate cancer risk. The two groups were also similar in BMI (cases: mean ⫽ 23. model adequacy was assessed using the Hosmer and Lemeshow goodness-of-fit statistic.6. Although calendars were used to assist the participants to recall their tea exposure along with other data 5 years ago. Measurement of tea exposure Questions on habitual tea consumption were taken from our previous ovarian cancer study28 and the Arizona skin cancer study. see Table III. number of children. Frequency of liquid tea consumed was measured by a standard container (350 ml cup) during the interview. SD ⫽ 55. alcohol concentration in beer was set at 5%. SD ⫽ 3. frequency (number of cups consumed per day). never)”. Compared to .2 g/day. usually in the presence of the participant’s next-of-kin to minimize recall bias. with scores 1. B (28).31 These 3 questionnaires have been validated in studies of large multi-ethnic populations including Chinese immigrants whom are comparable to our study population of Chinese men. A reference recall period was set at the year that was 5 years before diagnosis for cases or 5 years before interview for controls.95) for tea consumption variables. The feasibility and validity of the questionnaire used to measure tea exposure was evaluated in a preliminary pilot trial involving 21 Zhejiang residents. Men recruited for controls were matched with cases by age and geographical area. The same exclusion criteria also applied to cases.9). family history of prostate cancer and history of vasectomy. The stage classification for 1 patient was missing. Demographic characteristics and potential risk factors between cases and controls were compared by t-test for continuous variables and chi-square test for categorical variables. family income. There were no significant differences between cases and controls in mean age at interview.2 years SD ⫽ 3. total fat intake (g/day). including 5 asymptomatic cases who were diagnosed initially by PSA test.4.33 In estimating alcohol intake. The use of teapots and small cups in other parts of China is not popular among Zhejiang residents (whose average cup size being 300 – 400 ml). Ethics and interview The study was approved by the Human Research Ethics Committee of the researchers’ institution and by the Zhejiang hospital administration and doctors-in-charge of the relevant wards. The internal reliability and reproducibility of the questionnaire were then assessed by a test–retest study of 40 subjects conducted in Hangzhou. X-ray.7) and age at marriage (cases: mean ⫽ 26. SD ⫽ 59. usual diet and physical activity.1). lifestyle habits such as alcohol drinking and smoking. locality of residence.9. controls: mean ⫽ 56. The pretest led to a few minor modifications of the initial questionnaire. Questionnaire A structured questionnaire that measured consumption of tea and other beverages was used.34 Men consuming more than 25 drinks per week were classified as heavy drinkers. These variables were included in the multivariate models because they were either plausible risk factors of prostate cancer from the literature or potential confounders with tea consumption according to the univariate analysis. The questionnaire was modified from that used in our recent ovarian cancer study.82– 0. Statistical analysis All data were checked for completeness at the end of each interview. alcohol consumption. Potential controls with a diagnosis of Alzheimer’s disease. 8 (2. Each interview usually took an hour to complete. quantity (g) of tea leaves used per batch. family income. 274 (96. they were blinded to the purpose of the study.8%) declined the interview and 2 persons (0. height and weight.0 assigned for sedentary.4. alcohol consumption. marital status. To assess potential survival bias.5. number of new batches brewed each day.28 which in turn had included components from the Hawaii Cancer Research Survey.3%). The distribution of cases by their cancer stage is: A (12). SD ⫽ 20.131 GREEN TEA AND PROSTATE CANCER RISK interviewed within 12 months from diagnosis. tobacco smoking. total fat intake (cases: mean ⫽ 60. controls: mean ⫽ 27. To facilitate analysis. During the same period 274 inpatient controls were recruited from the 8 hospitals and interviewed. were categorized into 3 or 4 levels according to the distributions of controls. data for the 109 cancer patients (interviewed within one year from diagnosis) and data for all cases (interviewed within 3 years from diagnosis) were analyzed separately. C (37) and D (52).1. Each fitted regression equation included terms for adjusting age at interview. These 5 cases were subsequently biopsied and their diagnosis confirmed by histology. except “tea drinking (ever vs.5. 3. The ever-drinkers were then asked for information on usual consumption pattern namely types of tea drank. The data were coded and analyzed using the SPSS package. Of the 284 eligible controls identified. and factors related to hormonal. according to reference values recorded in the Chinese food ingredients database. confirming that it was an appropriate instrument to measure the required habitual information for the target population. moderate and vigorous activities respectively to generate weighted estimates of time spent each week in physical activities.7. whereas wine and rice wine were 12% and liquor 47%. physical activity level. Finally. All 130 cases were histopathologically confirmed. The first author conducted all interviews. Subjects were eligible if they had no prostate cancer or any other diagnosed malignant diseases confirmed by physical examination. quantity (kg) of tea leaves consumed per year. The overall physical activity was measured in terms of metabolic equivalent tasks (MET). and history of vasectomy.0 years SD ⫽ 4. An appointment for face-to-face interview was made after obtaining formal consent from the participants.0 and 6. RESULTS Table I contrasts the sample characteristics of men with and without prostate cancer for tea drinkers and non-drinkers (⬍once per month).29 Australian Health Survey 199530 and the United States food survey 1992.4).21 Participants were first classified as either “ever” or “never” tea drinkers (⬍once per month).3%). controls: mean ⫽ 22. The majority of the eligible controls were recruited from the urology wards (65. SD ⫽ 3. tobacco smoking. body mass index (BMI). operation or histopathological reports within the past 12 months.

8) 58 (86. 55% were classified as tea drinkers compared to 80% of the controls.132 JIAN ET AL.3) 74.4 (57.8) 38 (69.1) 22.09 (0.001 ⬍0.0) 195 (89.6) 10 (18.1 (28.78 (2.8) 16 (22.9) 27.7) 12 (5.05 for differences between cases and controls.8) 21 (29.01 ⬍0.2) 32 (55.6) 10 (17.0) 0 24 (11.0) 9 (16. were not significantly different in the types of tea drank and number of new batches brewed each day.5) 52.5) 28 (38. Table II summarizes the tea consumption patterns for the subset of participants who drank tea. mean (SD) Locality of residence.2 (2.9) 16 (29. .26) 36.383 Consume tea more than once per month.9) 195 (89.9) 27 (37.2) p-value ⬍ 0.2) 17 (23.6 (22.38 (2.4) 67 (93.6) 18 (31.2) 73.7) 51 (23.9) 9 (16.2) 23 (39.0) 24 (11. however.86) 4.3) 10 (18. mean (SD) Age at marriage.031 55 (76.8) 0.1) 5 (6.3) 22 (40.9 (61. 1 2 controls.2) 23 (41.1) 20 (9.5) 57.7) 25.3) 27 (37.4) 28 (38.7) 17 (29.5) 118 (53.2) 28 (38.9) 39 (54.0) 46 (83.1 (20. n (%) Never Moderate Heavy Tobacco smoking.5) 207 (94.3) 15 (25.6) 34 (47.5) 20 (36. n (%) Married Widowed/divorced/separated History of vasectomy. n (%) None Primary Secondary Tertiary Family income per month.7) 4 (6.8) 7 (3.4) 28 (48.1) 8 (11.27 (1.7) 19 (34.1) 71 (98.7 (3.5) 65 (29.2) 11 (19.6) 28 (38.8) 12 (16.0) 50 (90.4) 26 (36.6) 26.6) 169 (77.9) 6 (8.9) 104 (47. Among the 130 prostate cancer patients.2) 1 (1.8) 56 (77.7 (64.9) 5 (9.1) 19 (26.7 (7. n (%) ⱕ500 RMB 501–1000 RMB 1001–2000 RMB ⬎2001 RMB Alcohol consumption. n (%) Urban Rural Education.2) 50 (22.9) 17 (23.1) 10 (4.4) 212 (96.7 (5.4) 2 (3.13 (3.1) 33 (45.2) 54 (98. n (%) ⬍1 1–3 ⬎3 Number of new batches brewed/day.2) 39 (70.5) 26 (47.8) 20 (36.0) 16 (27. mean years (SD) BMI.6) 2 (2.6) 2 (3.7) 3 (5.4) 27 (46.2) 76 (34.0) 23.4) 11 (15.1) 13 (22.2) 18 (31.0) 91 (41.01 ⬍0. On average.8) 88 (40.57) 2.1 (4.7) 56 (25.4 (3.2) 155.54 (1.3) 66 (91.8) 13 (18.4) 15 (27. t-test for continuous variables and ␹-square test for categorical variables.9) 0.6) 14 (24. n (%) Never Former Current Marital status.2) 159.7) 30 (13. The 2 groups of ever tea drinkers.1) 79 (36.1 (2.0) 15 (25.0 (21. It is evident that the 219 controls had longer duration of tea drinking and drank significantly more tea (in terms of frequency and quantity of tea leaves consumed per year and per batch) than the 72 cases.0) 11 (19.88) 1.49) ⬍0.3) 13 (22.2) 154.1) 8 (14.5) 17 (23.4) 40 (18.892 6 (8.9 (52.9) 21 (9.– p-value for differences between cases and controls. n (%) ⱕ2 3–4 ⬎4 1 Controls Tea drinkers (n ⫽ 72) Non-tea drinkers (n ⫽ 58) Tea drinkers (n ⫽ 219) Non-tea drinkers (n ⫽ 55) 71.68 (14.9) 58.9) 47 (81. TABLE I – SELECTED CHARACTERISTICS OF PARTICIPANTS WITH AND WITHOUT PROSTATE CANCER Cases Age at interview.6) 32 (55.1) 62.7) 50 (22.6) 80 (36.9) 22.001 5 (6.9) 70.98) 2.1) 5 (9.3) 168 (76.4) 56 (96.9) 2 (3.7) 53 (91.6) 1 (1.6) 87 (39. mean g/day (SD) MET.9) 26.0 (6.8) 23.35 (12. n (%) Black and green tea Green tea only Cases.2) 48 (21.3) 90 (41.30) 3.7) 27 (49.6 (5. n (%) No Yes Unclear Number of children1.8 (4.9 (7.2) 41 (70.5) 0.9 (3. the cases tended to have slightly more children and had apparent family susceptibility. n (%) 1 ⱖ2 Types of tea drunk.6) 98 (44.1) 158.1) 63 (28.4) 17 (23.62) 1. n (%) No Yes Prostate cancer in first degree relatives1. mean years (SD) Fat. (n ⫽ 72) Controls (n ⫽ 219) p-value2 30.1) 12 (21. the controls consumed a larger quantity of green tea leaves per day than the prostate cancer patients.4) 1 (1.6) 0 9 (16. TABLE II – TEA CONSUMPTION PATTERNS OF TEA DRINKING PARTICIPANTS1 Years of tea drinking Total tea leaves consumed (kg/year) Tea leaves used (g/batch) Quantity of green tea leaves (g/day) Number of cups/day.

promotion.1) 42 (15.50 0.43 0.9) 0.98 (p-value ⫽ 0.9 3–4.00 0.79 0.26–0.9) 62 (22.53 0. physical activity (MET. the relationship between tea drinking and human prostate cancer remains unclear. education (none. vasectomy (no.18–0.5) 39 (30.4) 1.7) 15 (11.29 1.59 0.14 1.8) 9 (6.24–0.00 0. tertiary).6) 72 (55. continuous).51 58 (44. former.19–0. continuous).20–0.9) 55 (20. with significant dose-response relationships. age at marriage (years.36 0. and particularly across all levels of green tea consumption.15–0.21–0.07–0.41 0.6) 55 (47.10 0.01 0.8) 79 (28.00 0. 1001–2000. ⱕ500.00 0.98 0.15 1.7) 1.26–0.05–0.7) 80 (29.48 0.27–0. A lack of detailed and specific information on tea consumption has limited the conclusion drawn by previous studies.09–0.30 36.8) 72 (26. black and Oolong tea are not commonly consumed by Zhejiang residents. respectively. BMI (5 years ago.4) 48 (17.2) 118 (43.06–0.07–0. 501–1000.3–1.28 0. The risk of prostate cancer tended to decline with increasing frequency and duration of tea drinking.00 0.65 0.78 0.26–0.37 0. primary.6) 32 (24. It should be remarked that for the 291 participants that drank tea. continuous).1) 68 (24.1) 108 (39. indicating no lack of fit for the logistic regression models.55 0. we documented in detail the quantitative effects of green tea consumption with respect to prostate cancer risk for Chinese men.6) 34 (26. Moreover.2) 55 (20. Unlike green tea.16 Despite the inhibitory effects of tea against carcinogenesis have been consistently demonstrated in laboratory experiments. Finally.50 0.1) 1.2) 1.06 – 0. The adjusted OR was 0.26 58 (44.59 0.32 0.21 58 (44.17–0.36 –38 In addition.19–0.17 1.24 0. secondary. Inverse associations were also observed for quantity of tea leaves consumed per year and per batch.94 0. total fat intake (g/day.23 0.53 0.00 0.43 0. compared to never or seldom tea-drinkers.04–0.11–0.14 0.06–0. continuous). tobacco smoking (never.00 0.29 63 (48.12 0.09 0.– 2p-value ⬍ 0.49 25.49 0.28 0. yes.23 (pvalue ⫽ 0.162 0.3) 1.212 0.01. epigallocatechin gallate. heavy).14–0.31 0.33 0. number of children (continuous).72 0.2) 23 (17.64 0.28 (95% CI ⫽ 0.00 0.9) 38 (29.0) 28 (21.47) for tea-drinkers relative to nondrinkers. Results from the 109 recent patients were also similar and omitted for brevity.11–0.31 0. the effect of different tea types on prostate cancer risk cannot be further analyzed owing to the small number of participants involved in drinking black tea.852 0. blocking signal transduction and nuclear oncogene expression.6) 86 (31. family history of prostate cancer (no.5) 63 (23.45 0.48 58 (44.86) and 11.23–0. current).12 (95% CI ⫽ 0.17–0.25–1.1) 219 (79. Therefore.5) 13 (10.79 0. moderate.60 0.5 ␹2 for trend Tea leaves used (g/batch) 0 0.44 0.1) 169 (61.17–0.26) for those drinking more than 3 cups per day and over 40 years.9) 55 (20. rural).50 0.3) 17 (13.802 0.48) and 0.24–0.26 31.9 ⱖ5 ␹2 for trend Cases (%) Controls (%) Crude OR 95% CI Adjusted OR1 95% CI 58 (44. with adjusted OR ⫽ 0.5) 76 (27. trapping of ultimate carcinogens.00 0. the Hosmer and Lemeshow goodness-of-fit statistic ranged between 3.9) 76 (27.53 0. widowed or divorced or separated).472 1 Estimates from separate logistic regression models include terms for age at interview (years.80 0.26 0.9 2–3 ⬎3 ␹2 for trend Number of cups/day ⬍1 1–3 ⬎3 2 ␹ for trend Number of new batches brewed/day 0 1 ⱖ2 ␹2 for trend Quantity of green tea leaves (g/day) 0 0. and inducing apoptosis and cell cycle arrest.30–0.17– 0.15– 0. increasing the number of new batches brewed per day to 2 or more was associated with a 76% reduced risk of prostate cancer.12 1.13–0. Some progress has been made recently in elucidating the molecular mechanisms of cancer chemo-prevention by tea and tea polyphenols.32 36.28 0. The principle active constituent of tea polyphenols. marital status (married.1) 55 (20.27 (95% CI ⫽ 0. ⱖ2001). they all consumed green tea but 18 of them (6 cases and 12 controls) drank both green tea and black tea.6) 22 (16.31 38.32 1.19). family income (RMB.0) 9 (6.632 0.4) 55 (20.1) 71 (25.35 0. alcohol consumption (never. yes).3) 101 (36.5 ⬎1.27 0.17–0.24 0.7) 50 (18. unclear).6) 31 (23.61 0. because of its antioxidant properties against free radicals.2) 12 (9. can offer protection against all stages of carcinogenesis (tumor initiation.94 0.17–0.63 18.04–0. continuous).72 0.00 0.0) 1. DISCUSSION In this epidemiological study.6) 50 (38.5) 55 (20. locality (urban.21–0. The corresponding linear trend was significant.133 GREEN TEA AND PROSTATE CANCER RISK TABLE III – CRUDE AND ADJUSTED OR AND ASSOCIATED 95% CI OF PROSTATE CANCER RISK FOR TEA DRINKING Drink tea No Yes Years of tea drinking 0 1–19 20–40 40 ␹2 for trend Total tea leaves consumed (kg/year) 0 ⬍1 1–1. and progression) by suppressing tumor promotion and inflammation.35–0.45 0. Table III presents the results from separate multivariate logistic regression fits for each tea consumption measure. it can repress the transcription of the androgen receptor gene and thus inhibit androgen action.00 0. .47 58 (44.00 0.3–2.

Hankin J. Kong X. Although a case-control design for the present study was appropriate due to the low incidence of prostate cancer in China. Anderson KM. especially older men.28 so that the participants recruited would be representative of the Zhejiang population. GLOBOCAN 2000: cancer incidence. Cohen RJ. Kestin L. McRae CU. IARC CancerBase. Prostate cancer in relation to diet. BJU Int 1999. 2. whites. Kolonel LN. Kleihues P. a reference recall period (5 years before diagnosis for cases and 5 years before interview for controls) was adopted to avoid possible change in tea exposure since the onset of the disease. Stamey T. Miles B. Wang X. 5. Lancet Oncol 2002. but its level can be substantially decreased in the third cup.39 It has also been reported that most of the antioxidants in tea can enter the liquid phase within 5 min of brewing. the present study of Chinese men suggests that increasing the frequency. To minimize recall bias. REFERENCES 1. 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It is known that the first 2 cups brewed from a new batch of tea contain almost equal amounts of epigallocatechin gallate. which in turn can reduce the intake of active compounds.

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