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Population nutrikinetics of green tea extract.
Scholl, C, Lepper, A, Lehr, T, Hanke, N, Schneider, KL, Brockmöller, J, Seufferlein, T, Stingl, JC
PloS one. 2018;(2):e0193074
Abstract
UNLABELLED Green tea polyphenols may contribute to the prevention of cancer and other diseases. To learn more about the pharmacokinetics and interindividual variation of green tea polyphenols after oral intake in humans we performed a population nutrikinetic study of standardized green tea extract. 84 healthy participants took green tea extract capsules standardized to 150 mg epigallocatechin-gallate (EGCG) twice a day for 5 days. On day 5 catechin plasma concentrations were analyzed using non-compartmental and population pharmacokinetic methods. A strong between-subject variability in catechin pharmacokinetics was found with maximum plasma concentrations varying more than 6-fold. The AUCs of EGCG, EGC and ECG were 877.9 (360.8-1576.5), 35.1 (8.0-87.4), and 183.6 (55.5-364.6) h*μg/L respectively, and the elimination half lives were 2.6 (1.8-3.8), 3.9 (0.9-10.7) and 1.8 (0.8-2.9) h, respectively. Genetic polymorphisms in genes of the drug transporters MRP2 and OATP1B1 could at least partly explain the high variability in pharmacokinetic parameters. The observed variability in catechin plasma levels might contribute to interindividual variation in benefical and adverse effects of green tea polyphenols. Our data could help to gain a better understanding of the causes of variability of green tea effects and to improve the design of studies on the effects of green tea polyphenols in different health conditions. TRIAL REGISTRATION ClinicalTrials.gov: NCT01360320.
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Effect of green tea catechins in patients with high-grade prostatic intraepithelial neoplasia: Results of a short-term double-blind placebo controlled phase II clinical trial.
Micali, S, Territo, A, Pirola, GM, Ferrari, N, Sighinolfi, MC, Martorana, E, Navarra, M, Bianchi, G
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2017;(3):197-202
Abstract
BACKGROUND AND STUDY OBJECTIVE Several studies suggest a protective role of green tea catechins against prostate cancer (PCa). In order to evaluate the efficacy of green tea catechins for chemoprevention of PCa in patients with high-grade prostate intraepithelial neoplasia (HG-PIN) we performed a phase II clinical trial. METHODS Sixty volunteers with HG-PIN were enrolled to carry out a double-blind randomized placebo-controlled phase II clinical trial. Treated group took daily 600 mg of green tea catechins (Categ Plus®) for 1 year. Patients were screened at 6 and 12 months through prostatic biopsy and measurements of prostate-specific antigen (PSA). RESULTS Despite the statistically significant reduction of PSA observed in subjects who received green tea catechins for 6 and 12 months, we did not find any statistical difference in PCa incidence between the experimental groups neither after 6 nor after 12 months. However, throughout the one-year follow- up we observed very limited adverse effects induced by green tea catechins and a not significant improvement in lower urinary tract symptoms and quality of life. CONCLUSIONS Although the small number of patients enrolled in our study and the relatively short duration of intervention, our findings seems to deny the efficacy of green tea catechins. However, results of our clinical study, mainly for its low statistical strength, suggest that the effectiveness of green tea catechins should be evaluated in both a larger cohort of men and longer trial.
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Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States.
Yu, Z, Samavat, H, Dostal, AM, Wang, R, Torkelson, CJ, Yang, CS, Butler, LM, Kensler, TW, Wu, AH, Kurzer, MS, et al
Cancer prevention research (Philadelphia, Pa.). 2017;(10):571-579
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Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The current analysis examined the effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI), 3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI, 2.5-5.1), which were significantly higher than those among women in the placebo arm (both P < 0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an OR of 7.0 (95% CI, 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations. Cancer Prev Res; 10(10); 571-9. ©2017 AACR.
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Identification of Targets of a New Nutritional Mixture for Osteoarthritis Management Composed by Curcuminoids Extract, Hydrolyzed Collagen and Green Tea Extract.
Comblain, F, Dubuc, JE, Lambert, C, Sanchez, C, Lesponne, I, Serisier, S, Henrotin, Y
PloS one. 2016;(6):e0156902
Abstract
OBJECTIVE We have previously demonstrated that a mixture of curcuminoids extract, hydrolyzed collagen and green tea extract (COT) inhibited inflammatory and catabolic mediator's synthesis by osteoarthritic human chondrocytes. The objective of this study was to identify new targets of COT using genomic and proteomic approaches. DESIGN Cartilage specimens were obtained from 12 patients with knee osteoarthritis. Primary human chondrocytes were cultured in monolayer until confluence and then incubated for 24 or 48 hours in the absence or in the presence of human interleukin(IL)-1β (10-11M) and with or without COT, each compound at the concentration of 4 μg/ml. Microarray gene expression profiling between control, COT, IL-1β and COT IL-1β conditions was performed. Immunoassays were used to confirm the effect of COT at the protein level. RESULTS More than 4000 genes were differentially expressed between conditions. The key regulated pathways were related to inflammation, cartilage metabolism and angiogenesis. The IL-1β stimulated chemokine ligand 6, matrix metalloproteinase-13, bone morphogenetic protein-2 and stanniocalcin1 gene expressions and protein productions were down-regulated by COT. COT significantly decreased stanniocalcin1 production in basal condition. Serpin E1 gene expression and protein production were down-regulated by IL-1β. COT reversed the inhibitory effect of IL-1β. Serpin E1 gene expression was up-regulated by COT in control condition. CONCLUSION The COT mixture has beneficial effect on osteoarthritis physiopathology by regulating the synthesis of key catabolic, inflammatory and angiogenesis factors. These findings give a scientific rationale for the use of these natural ingredients in the management of osteoarthritis.
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Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy.
Henning, SM, Wang, P, Said, JW, Huang, M, Grogan, T, Elashoff, D, Carpenter, CL, Heber, D, Aronson, WJ
The Prostate. 2015;(5):550-9
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BACKGROUND Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. METHODS In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation (nuclear and cytoplasmic nuclear factor kappa B [NFκB]) and oxidation (8-hydroxydeoxy-guanosine [8OHdG]). Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. RESULTS Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFκB was significantly decreased in RP tissue of men consuming GT (P = 0.013) but not BT (P = 0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (P = 0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (P = 0.04). CONCLUSION Given the GT-induced changes in NFκB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis.
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'Benifuuki' green tea containing o-methylated catechin reduces symptoms of Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.
Masuda, S, Maeda-Yamamoto, M, Usui, S, Fujisawa, T
Allergology international : official journal of the Japanese Society of Allergology. 2014;(2):211-7
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BACKGROUND Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). METHODS The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. RESULTS Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. CONCLUSIONS 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.
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Green tea halts progression of cardiac transthyretin amyloidosis: an observational report.
Kristen, AV, Lehrke, S, Buss, S, Mereles, D, Steen, H, Ehlermann, P, Hardt, S, Giannitsis, E, Schreiner, R, Haberkorn, U, et al
Clinical research in cardiology : official journal of the German Cardiac Society. 2012;(10):805-13
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BACKGROUND Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy. METHODS 19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI (n = 9) before and after consumption of GT and/or green tea extracts (GTE) for 12 months. RESULTS Five patients were not followed up for reasons of death (n = 2), discontinuation of GT/GTE consumption (n = 2), and heart transplantation (n = 1). After 12 months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (-12.5 %) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 ± 8.9 vs. 172.7 ± 9.4 mg/dL; p < 0.01) and LDL cholesterol (105.8 ± 7.6 vs. 89.5 ± 8.0 mg/dL; p < 0.01) decreased significantly during the observational period. No serious adverse effects were reported by any of the participants. CONCLUSIONS Our observation suggests an inhibitory effect of GT and/or GTE on the progression of cardiac amyloidosis. We propose a randomized placebo-controlled investigation to confirm our observation.
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Bioavailability and catabolism of green tea flavan-3-ols in humans.
Del Rio, D, Calani, L, Cordero, C, Salvatore, S, Pellegrini, N, Brighenti, F
Nutrition (Burbank, Los Angeles County, Calif.). 2010;(11-12):1110-6
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OBJECTIVE The aim of this study was to investigate green tea flavan-3-ol catabolism and plasma pharmacokinetic and urinary excretion by high-performance liquid chromatography with tandem mass spectrometry to evaluate their absolute bioavailability by taking into account all known and some unknown catabolites deriving from their interaction with the gastrointestinal tract and its host microflora. METHODS A feeding study was carried out in 20 healthy human volunteers who ingested 400 mL of a ready-to-drink green tea containing approximately 400 μmol of flavan-3-ols. Urine and plasma were collected for 4 and 24h, respectively, and 39 relevant catabolites were identified in these biological fluids by tandem mass spectrometry. RESULTS In biological fluids, 39 relevant flavan-3-ol catabolites were identified. In plasma, (-)-epigallocatechin-3-gallate was the only unmetabolized compound and the highest in absolute concentration compared with (-)-epigallocatechin and (-)-epicatechin conjugates. Colonic microflora-derived polyhydroxyphenyl-γ-valerolactones were by far the main urinary catabolites, averaging 10 times greater concentratin than flavan-3-ol conjugates. The calculated bioavailability was equal to 39% and it is interesting to notice the great variability in urinary excretion of colonic metabolites among participants, probably related to differences in their own colonic microflora. CONCLUSION This study demonstrates that green tea catechins are more bioavailable than previously observed when colonic ring fission metabolites are taken into consideration. Regular consumption of ready-to-drink green tea containing flavan-3-ols allows a non-marginal exposure of the human body to these catabolites, somehow justifying the numerous beneficial actions described as linked to green tea intake.
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Effect of ground green tea drinking for 2 weeks on the susceptibility of plasma and LDL to the oxidation ex vivo in healthy volunteers.
Gomikawa, S, Ishikawa, Y, Hayase, W, Haratake, Y, Hirano, N, Matuura, H, Mizowaki, A, Murakami, A, Yamamoto, M
The Kobe journal of medical sciences. 2008;(1):E62-72
Abstract
Catechins in green tea have been shown to reduce a risk of coronary heart disease in epidemiological studies. Also, it has been reported catechins have hypolipidemic and antioxidant effects. Then, we investigated the effects of ground green tea drinking on the susceptibility of plasma and low-density lipoprotein (LDL) to the oxidation by CuSO4 ex vivo, and also evaluated daily food consumption using semiquantitative questionnaire. Five healthy female subjects consumed ground green tea (1.5 g/3 times/day) for 2 weeks after a washout period of 1 week, when they drank water instead of tea. After 2-week tea drinking, the subjects drank water again. They also filled food and drink-frequency questionnaires during 4 weeks to assess daily foods consumption to estimate the oxidizability of plasma and LDL. We measured the lag time of conjugated dienes formation of plasma and LDL to oxidation by CuSO4. The lag time of conjugated dienes formation are increased in all subjects after ground green tea consumption from 67+/-19 to 118+/-42 min in plasma and from 47+/-6 to 66+/-10 min in LDL. The cholesterol contents in plasma and LDL decreased 10 mg/dl after ground green tea consumption. The beta-carotene, alpha-tocopherol, vitamin C and uric acid contents in plasma did not change after ground green tea consumption. The superoxide dismutase (SOD) activity in plasma also remained unchanged during this study periods. These findings indicated that ground green tea consumption decreased susceptibility of plasma and LDL to oxidation and also modulated cholesterol metabolism and might prevent initiation and progression of atherosclerosis.
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HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking.
Sonoda, J, Koriyama, C, Yamamoto, S, Kozako, T, Li, HC, Lema, C, Yashiki, S, Fujiyoshi, T, Yoshinaga, M, Nagata, Y, et al
Cancer science. 2004;(7):596-601
Abstract
Human T-cell lymphotropic virus type 1 (HTLV-1) is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV-1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV-1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34-40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV-1-infected T-cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV-1 provirus load in peripheral blood lymphocytes on HTLV-1 carriers. We recruited 83 asymptomatic HTLV-1 carriers to examine HTLV-1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty-seven subjects were followed up for 5 months by measuring HTLV-1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real-time PCR quantification of HTLV-1 DNA revealed a wide range of variation of HTLV-1 provirus load among asymptomatic HTLV-1 carriers (0.2-200.2 copies of HTLV-1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV-1 provirus load as compared with the controls (P = 0.031). These results suggest that green tea drinking suppresses proliferation of HTLV-1-infected lymphocytes in vivo.