Chow HH, Hakim IA, Crowell JA, Ranger-moore J, Chew WM, Celaya CA et al.. Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of polyphenon E in healthy individuals. Clin Cancer Res 11, 4627-4633

Arizona Cancer Center, The University of Arizona, Tucson, Arizona 85724, USA.
Clinical Cancer Research (Impact Factor: 8.72). 06/2005; 11(12):4627-33. DOI: 10.1158/1078-0432.CCR-04-2549
Source: PubMed

ABSTRACT Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its consumption has been associated with decreased risk of certain types of cancers in humans. The oral bioavailability of the major green tea constituents, green tea catechins, is low, resulting in systemic catechin levels in humans many fold less than the effective concentrations determined in in vitro systems. We conducted this clinical study to test the hypothesis that the oral bioavailability of green tea catechins can be enhanced when consumed in the absence of food. Experimental Designs: Thirty healthy volunteers were randomly assigned to one of the following doses of Polyphenon E (a decaffeinated and defined green tea catechin mixture): 400, 800, or 1,200 mg, based on the epigallocatechin gallate content (10 subjects per dose group). After an overnight fast, study participants took a single dose of Polyphenon E with or without a light breakfast, which consisted of one or two 4-oz muffins and a glass of water. Following a 1-week wash-out period, subjects were crossed over to take the same dose of Polyphenon E under the opposite fasting/fed condition. Tea catechin concentrations in plasma and urine samples collected after dosing were determined by high-pressure liquid chromatography analysis.
Consistent with previous reports, epigallocatechin gallate and epicatechin gallate were present in plasma mostly as the free form, whereas epicatechin and epigallocatechin were mostly present as the glucuronide and sulfate conjugates. There was >3.5-fold increase in the average maximum plasma concentration of free epigallocatechin gallate when Polyphenon E was taken in the fasting condition than when taken with food. The dosing condition led to a similar change in plasma-free epigallocatechin and epicatechin gallate levels. Taking Polyphenon E in the fasting state did not have a significant effect on the plasma levels of total (free and conjugated) epigallocatechin, but resulted in lower plasma levels of total epicatechin. Urinary epigallocatechin gallate and epicatechin gallate levels were very low or undetectable following Polyphenon E administration with either dosing condition. Taking Polyphenon E under the fasting state resulted in a significant decrease in the urinary recovery of total epigallocatechin and epicatechin. Polyphenon E administered as a single dose over the dose range studied was generally well-tolerated by the study participants. Mild and transient nausea was noted in some of the study participants and was seen most often at the highest study agent dose (1,200 mg epigallocatechin gallate) and in the fasting condition.
We conclude that greater oral bioavailability of free catechins can be achieved by taking the Polyphenon E capsules on an empty stomach after an overnight fast. Polyphenon E up to a dose that contains 800 mg epigallocatechin gallate is well-tolerated when taken under the fasting condition. This dosing condition is also expected to optimize the biological effects of tea catechins.

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    • "Studies have shown that EGCG mediates its anti-cancer effect by regulating cancer cell angiogenesis and metastasis [1, 2, 8]. Another important characteristic of EGCG is its relatively low systemic toxicity [9, 10]. Thus, EGCG has been proposed to merit possible use as an adjuvant or immunostimulant in cancer therapy [11]. "
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    ABSTRACT: Background Cancer immunotherapy requires proper manipulation of the immune system, lymphocytes in particular, in order to identify and destroy the cancer cells as non-self. In this study we investigated the effect of the flavonoid present in green tea, namely epigallocatechin-3-gallate (EGCG), on the proliferation of, and IFN-γ production by, peripheral blood mononuclear cells (PBMC) from breast cancer patients stimulated with a mitogen, anti-CD3 and the common breast cancer peptides Her-2/neu, and p53. Methods Blood samples were collected from 25 patients with breast cancer at the Kuwait Cancer Control Centre (KCCC). The patients were newly diagnosed, and had not undergone any treatment or surgery at the time of sample collection. The control group consisted of 25 healthy women age-matched (±5 years) to the patients. PBMC were isolated from the patients and controls, and were cultured separately with the mitogen PHA, anti-CD3 antibodies, and Her-2/neu and p53 in the presence or absence of standardized doses of EGCG. The degree of proliferation and interferon-γ [IFN-γ) release were then analyzed. Results EGCG significantly suppressed the proliferation of PBMC in response to stimulation separately with (i) the mitogen, (ii) anti-CD3, and (iii) the cancer antigen peptides. IFN-γ production was also significantly suppressed by EGCG in vitro. Conclusions EGCG appears to have an immunosuppressive effect on the proliferation of PBMC, indicating that EGCG is worth exploring for immunomodulatory effects in autoimmune diseases and tissue transplantation.
    BMC Complementary and Alternative Medicine 08/2014; 14(1):322. DOI:10.1186/1472-6882-14-322 · 2.02 Impact Factor
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    • "The predominantly centrolobular damage can be assigned to Rappaport Zone 3, which is the hepatolobular area most susceptible to toxic substances due to its low oxygen supply, limiting regeneration of cellular antioxidants and impairing various other cellular damage control mechanisms. It has been reported that the postprandial ingestion of green tea extracts may limit the adverse side effects observed in animal fasting studies, since bioavailability of free catechins is increased under these conditions (Chow et al., 2005; Isbrucker et al., 2006). Furthermore, physical constitution, gender and genetic factors like variability in enzyme expression or activities could be important in modulating a patient's susceptibility to green tea (Stewart et al., 2010; Lucena et al., 2011; Masubuchi et al., 2011). "
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    ABSTRACT: Unlabelled: ETNOPHARMACOLOGICAL RELEVANCE: The popularity of concentrated green tea extracts as dietary supplements for a wide range of applications is increasing due to their health-promoting effects attributed to the high amounts of catechins they contain. The most important of the green tea catechins is (-)-epigallocatechin-3-O-gallate (EGCG). While their beneficiary effects have been studied extensively, a small number of adverse events have been reported in the medical literature. Here we present a typical reversible course of severe hepatitis after green tea consumption. Materials and methods: The case study describes in a 63-year old woman during treatment with green tea-capsules upon recommendation of a cancer support group. Results: The histological finding was consistent with drug induced hepatitis, and other possible causes of hepatitis were excluded. According to the CIOMS/RUCAM score the causality was assessed as "probable". After discontinuation of medication, followed by extracorporal albumin dialysis, rapid and sustained recovery occurred. Pharmaceutically analysis (HPLC) of the green tea capsules did not give evidence for contaminants but revealed the two typical compounds of green tea, namely (-)-epigallocatechin-3-O-gallate (EGCG, 93.2%) and epicatechin (EC, 6.8%) at a very high dose level. Conclusion: The present case highlights the fact that such concentrated herbal extracts from green tea may not be free of adverse effects under certain circumstances. There is still a lack of a uniform European Union-wide surveillance system for adverse drug reactions of herbal products. Therefore this case underlines the importance of public awareness in the potential risks in use of herbal products.
    Journal of Ethnopharmacology 05/2014; 155(1). DOI:10.1016/j.jep.2014.05.015 · 3.00 Impact Factor
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    • "As reported before, green tea and its components are well-tolerable and rapidly absorbed by blood after oral administration in humans. Even after an intake of single high doses like 1.600 mg of epigallocatechingallate, the elimination in the blood plasma occurs after 5 - 6 hours post administration [39,40]. The short half-life of active GTE compounds also guarantees no accumulation risks after multiple administrations [41]. "
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    ABSTRACT: Background Oxidative stress is involved in the pathogenesis of bone diseases such as osteoporosis, which has a high coincidence with fractures in elderly. Several studies showed positive effects of herbal bioactive substances on oxidative stress. This study analyses the effect of green tea extract (GTE) Sunphenon 90LB on primary human osteoblasts differentiation and viability during H2O2-induced oxidative stress. Moreover, it was analyzed, whether GTE acts during the HO-1 signaling pathway. Methods Human osteoblasts were isolated from femoral heads of patients undergoing total hip replacement. Beneficial effects of GTE on osteoblasts were examined in a dose- and time-dependent manner. Furthermore, GTE was given before, simultaneous with and after induction of oxidative stress with 1 mM H2O2 to simulate prophylactic, acute and therapeutic use, respectively. Cell damage was measured by LDH leakage and cell viability by MTT assay. Flow cytometry was applied to measure formation of Reactive Oxygen Species by using 2`7`-dichlorofluorescein-diacetate. The formation of Extracellular Matrix after differentiation with GTE supplementation during oxidative stress was visualized with von Kossa and Alizarin Red staining. Last one was additionally photometrically quantified. To assess the effects of H2O2 and GTE on the osteogenic genes, RT-PCR was performed. To evaluate the intramolecular influence of GTE after the stimulation the protein levels of HO-1 were analyzed. Results Stimulation of primary human osteoblasts with low doses of GTE during oxidative stress over 21 days improved mineralization. Furthermore, GTE supplementation in combination with H2O2 leads to a higher gene expression of osteocalcin and collagen1α1 during osteoblasts differentiation. Both are important for bone quality. Pre-incubation, co-incubation and post-incubation of osteoblasts with high doses of GTE protect the osteoblasts against acute oxidative stress as shown by increased cell viability, decreased LDH leakage, and reduced production of intracellular free radicals. Functional analysis revealed an increased HO-1 protein synthesis after stimulation with GTE. Conclusions Incubation of human primary osteoblasts with GTE significantly reduces oxidative stress and improves cell viability. GTE also has a beneficial effect on ECM production which might improve the bone quality. Our findings suggest that dietary supplementation of GTE might reduce inflammatory events in bone-associated diseases such as osteoporosis.
    Journal of Inflammation 05/2014; 11(1):15. DOI:10.1186/1476-9255-11-15 · 2.02 Impact Factor
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