Green tea: the human in vivo studies collected!!!

Big'r · Nov 2, 2005

For this post i collected as much human in vivo studies as i could. All positive and negative studies were collected to be able to show a relevant overview.
Note that there's probably an effective difference in tea and green tea.
Since there is such an amount of these human in vivo studies, i believe the animal- and in vitro studies are absolutely not significant any more, except for domains not yet investigated in humans-in vivo!
Please send me a pm if you have an interesting study to add, so i can integrate it into the overview.

TOPICS:
1 Effect on cholesterol
2 Effect on heart
3 Green tea and cancer
4 Effect on loss of body fat
5 Antioxidant properties
6 Bio-availability
7 Side effects
Possible interesting properties

1 EFFECT ON CHOLESTEROL

Green tea seems to reduce LDL(bad)-cholesterol.

Extra theaflavins boost green tea's health benefits
240 adults, on a low-fat diet, with mild to moderate hypercholesterolaemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks.
After 12 weeks, total cholesterol and LDL-cholesterol were reduced by 11 per cent and 16 per cent respectively in the tea extract group. HDL-cholesterol and triglyceride levels were up 2.3 per cent and 2.6 per cent respectively (E105).

Green tea polyphenols (flavan 3-ols) prevent oxidative modification of low density lipoproteins: an ex vivo study in humans.
300 mg polyphenols supplementation for 2 weeks to 22 men did not change plasma concentrations of lipids, ascorbate, alpha-tocopherol, and lipid peroxides but beta-carotene was higher in the tea group.
LDL (0.1 mg/mL) was incubated with 5 microM Cu(2+) and the oxidation was measured by absorbance at 234 nm. These results suggest that daily consumption of seven to eight cups (approximately 100 mL each cup) of green tea may increase resistance of LDL to in vivo oxidation, leading to reduction in the risk of cardiovascular diseases (E106).

Green tea consumption and serum lipid profiles: a cross-sectional study in northern Kyushu, Japan.
For 1,306 men serum total cholesterol levels were found to be inversely related to the consumption of green tea while no association was noted with serum triglycerides and high-density lipoprotein cholesterol. Adjusted mean concentrations of total cholesterol were 8 mg/dl lower in men drinking nine cups or more per day than in those consuming zero to two cups per day. Serum cholesterol levels were inversely associated with traditional Japanese dietary habits (intake of rice and soy bean paste soup) and positively associated with Westernized habits (E107).

2 EFFECT ON HEART

All studies so far show a significant positive effect of green tea on the heart.

Drink tea and live longer, heart attack victims told
1,900 people, mainly in their 60s, who had suffered a heart attack were followed up almost four years later, by which time 313 had died, mainly from heart disease. The researchers found that the less tea the patients drank the more likely they were to have died during the period.
Those who consumed less than 15 cups a week had a 28 per cent lower rate of dying. And those who drank more than 14 cups of tea a day had a 44 per cent lower death rate than non-tea drinkers (E204).

Black tea may lower heart disease risk
Researchers from the University of Arizona in the US and King Saud University in Saudi Arabia interviewed 3,430 Saudis aged from 30 to 70.those who drank more than six cups of tea daily (about 20 per cent of those interviewed) had a 50 per cent lower risk of heart disease than those who did not drink tea (E205).

Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.
18 healthy men ingested 254 mg of total catechins/subject.
The plasma phosphatidylcholine hydroperoxide (PCOOH) levels attenuated from 73.7 pmol/mL in the control to 44.6 pmol/mL in catechin-treated subjects, being correlated inversely with the increase in plasma EGCg level. The results suggested that drinking green tea contributes to prevent cardiovascular disease by increasing plasma antioxidant capacity in humans (E206).

Black tea increases the resistance of human plasma to lipid peroxidation in vitro, but not ex vivo.
Despite antioxidant efficacy in vitro, black tea does not protect plasma from lipid peroxidation in vivo. The striking discrepancy between the in vitro and ex vivo data is most likely explained by the insufficient bioavailability of tea polyphenols in humans (E207).

Dietary polyphenols and the prevention of diseases.
Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of fruits, vegetables, cereals, dry legumes, chocolate, and beverages, such as tea, coffee, or wine.
Epidemiological studies have repeatedly shown an inverse association between the risk of myocardial infarction and the consumption of tea and wine or the intake level of some particular flavonoids, but no clear associations have been found between cancer risk and polyphenol consumption (E208).

Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.
Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine.
Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88).
Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker (E209).

Effects of green tea intake on the development of coronary artery disease.
Green tea consumption was significantly higher in patients without coronary artery disease (CAD) than in those with CAD (5.9+/-0.5 vs 3.5+/-0.3 cups/day; p<0.001). An inverse relationship between the intake of green tea and the incidence of CAD was observed (p<0.001) (E210).

Black and Green Tea Polyphenols Attenuate Blood Pressure Increases in Stroke-Prone Spontaneously Hypertensive Rats
Epidemiologic studies indicated that tea consumption slightly reduces blood pressure.
Both black and green tea polyphenols attenuate blood pressure increases through their antioxidant properties in stroke-prone spontaneously hypertensive rats. Furthermore, because the amounts of polyphenols used in this experiment correspond to those in ~1 L of tea, the regular consumption of black and green tea may also provide some protection against hypertension in humans (E211).

3 GREEN TEA AND CANCER

A)Studies showing no relation between tea and cancer
Studies (E758), (E773), (E779) and (E780) probably were not green tea specific.

Green tea fails to help prostate cancer patients
In a green tea study of 42 patients with advanced androgen-independent prostate cancer, only one patient showed a short-term drop in his prostate-specific antigen (PSA) levels (a marker for prostate cancer) (E755).

Dietary flavonols and flavonol-rich foods intake and the risk of breast cancer.
We computed flavonol intakes from dietary data collected by validated food frequency questionnaires in 1991 and 1995 from 90,630 women in the Nurses Health Study II. We evaluated the association of flavonol intake with breast cancer risk in women who were premenopausal and aged between 26 and 46 years at baseline in 1991. During 8 years of follow-up, we documented 710 cases of invasive breast cancer.
There were no associations seen between individual flavonols such as kaempferol, quercetin and myricetin and breast cancer risk. Among the major food sources of flavonols, we found a significant inverse association with intake of beans or lentils but not with tea, onions, apples, string beans, broccoli, green pepper and blueberries (E758).

Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan.
In a pooled analysis of two prospective studies with 35004 Japanese women, green-tea intake was not associated with a lower risk of breast cancer (222 cases), the multivariate relative risk for women drinking >or=5 cups compared with <1 cup per day being 0.84 (95% confidence interval 0.57-1.24, Trend P=0.69) (E769).

Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women.
In 59,036 swedish women (40-76 y) drinking 4 or more cups of coffee/day had a covariate-adjusted hazard ratio of breast cancer of 0.94 [95% confidence interval (CI) 0.75-1.28] compared to women who reported drinking 1 cup a week or less. The corresponding hazard ratio for tea consumption was 1.13 (95% CI 0.91-1.40). In this large cohort of Swedish women, consumption of coffee, tea, and caffeine was not associated with breast cancer incidence (E773).

The relationship between diet and breast cancer in men (United States).
Possible relationships of dietary factors to risk of breast cancer in men were assessed.
No trends in risk were observed with increasing intakes of specific foods, except for an increase in risk with citrus fruits. No increase in risk with increasing amounts of specific fats, vitamins, or minerals or with amounts of protein, fiber, carbohydrate, starches, nitrites, or alcohol consumed was observed, except for an increase in risk with dietary vitamin C consumption. A decreasing trend in risk with dietary niacin and with coffee and an increasing trend in risk with tea consumption were observed. No associations were found with use of any dietary supplements, including vitamin C (E779).

Coffee consumption and the risk of breast cancer.
Cases were 5,984 women, below age 75, with histologically confirmed breast cancer, and controls were 5,504 women.
No relationship was observed between coffee intake and the risk of breast cancer. Tea consumption was also not associated with the risk of breast cancer (OR 0.94, 95% CI 0.85-1.03) (E780).

B)Studies showing a possitive relation between tea and cancer

Cancer therapy and prevention by green tea: role of ornithine decarboxylase.
Polyphenolic compounds account for 30% of the dry weight of the leaves.
Epidemiological studies revealed that the incidences of stomach and prostate cancers are the lowest in the world among a population that consumes green tea on a regular basis. It has also been reported that the quantity of green tea consumed, plays an important role in reducing cancer risk and in delaying cancer outbreak and recurrence (E752).

Green tea reduces prostate risk
After a year's oral administration of green tea catechins (GTCs), only one man in a group of 32 at high risk for prostate cancer developed the disease, compared to nine out of 30 in a control. The 600 mg-per-day dosage of caffeine-free, total catechins (50 percent of which is EGCG) given to participants in the study was one or two times the amount of green tea consumed daily in China, where 10 to 20 cups a day is normal, said the scientists (E754).

The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis.
The effects of green tea consumption on incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis.
To date, the epidemiological data indicates that consumption of 5 or more cups of green tea a day shows a non-statistically significant trend towards the prevention of breast cancer development. Evidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage (I and II) cancers (E757).

Green tea and cancer chemoprevention.
A case-control study on breast cancer patients revealed that high daily consumption of green tea was associated with a lower recurrence rate among Stages I and II patients (E760).

Cancer inhibition by green tea.
Cancer onset of patients who had consumed over 10 cups of green tea per day was 8.7 years later among females and 3.0 years later among males, compared with patients who had consumed under three cups per day (E761).

Inhibitory effects and toxicity of green tea polyphenols for gastrointestinal carcinogenesis.
Recently, and epidemiologic study showed a lower risk of gastrointestinal carcinogenesis in green tea drinkers. It was determined that 1 g per day of GTE might be an effective dose. GTE was not toxic and no harmful effect was found during its clinical use (E762).

Antimutagenic and anticarcinogenic activity of tea polyphenols.
In Japan, an epidemiological study showed an inverse relationship between habitual green tea drinking and the standardized mortality rates for cancer. Some cohort studies on Chanoyu (Japanese tea ceremony) women teachers also showed that their mortality ratio including deaths caused by malignant neoplasms were surprisingly low (E764).

Influence of drinking green tea on breast cancer malignancy among Japanese patients.
Increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones.
increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer (E765).

Clinical trials in cancer prevention: current results and perspectives for the future.
Among the promising bioactive food components being investigated at the National Cancer Institute in prevention clinical trials to reduce breast cancer risk are indole-3-carbinol, sulforaphanes, phytoestrogen isoflavones, perillyl alcohol, and green tea polyphenols. Prostate cancer prevention trials have focused on hormone modulation with the 5-alpha-reductase inhibitor finasteride and bioactive food components such as selenium and vitamin E. Soy isoflavones, green tea polyphenols, and doxercalciferol also are being investigated for prostate cancer prevention (E768).

[A case-control study on the risk of female breast cancer in Wuhan area]
A case-control study was conducted on 213 cases with histopathological diagnosis and 430 matched controls, using conditional logistic regression analysis. 28 factors were associated with breast cancer risk in one-way variance model.
Factors as later menarche, lactate longer, soybean food, fruit, drink tea habit were protective factors for breast cancer. Further breakdown of data showed some difference between premenopausal and postmenopausal women. Risks in premenopausal women were associated with history of benign breast disease, age of menarche, soybean food intake, whereas risks in postmenopausal women were related to age of menopausal, BMI, waist-hip ratio and fruit intake (E770).

Green tea and risk of breast cancer in Asian Americans.
epidemiologic data obtained from mainly Western populations are not supportive of a protective role of tea, mainly black tea, in the etiology of breast cancer. Much less is known about the relationship between green tea and breast cancer risk. During 1995-1998, we conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County and successfully interviewed 501 breast cancer patients and 594 control subjects.
Risk of breast cancer was not related to black tea consumption. In contrast, green tea drinkers showed a significantly reduced risk of breast cancer, and this was maintained after adjusting for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of menopausal hormones, body size and intake of total calories and black tea. Compared to women who did not drink green tea regularly (i.e., less than once a month), there was a significant trend of decreasing risk with increasing amount of green tea intake, adjusted odds ratios being 1.00, 0.71 (95% confidence interval [CI] 0.51-0.99) and 0.53 (95% CI 0.35-0.78), respectively, in association with no, 0-85.7 and >85.7 ml of green tea per day.
Both green tea and soy intake had significant, independent protective effects on breast cancer risk (E772).

Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan.
A decreased HR (hazard ration) for recurrence adjusted for stage was observed with consumption of three or more daily cups of green tea (HR=0.69, 95% confidence interval (95%CI)=0.47-1.00). Particularly in stage I, the HR was decreased statistically significantly (HR=0.43, 95%CI=0.22-0.84). A similar tendency was observed for stage II subjects, but was not present among more advanced stages (E774).

Serum Enterolactone and Risk of Breast Cancer
A Case-Control Study in Eastern Finland
Phytoestrogens have been linked to a risk of breast cancer. The main phytoestrogens in the Finnish diet are lignans, and enterolactone is quantitatively the most important circulating lignan.
This analysis concerns 194 breast cancer cases (68 premenopausal and 126 postmenopausal) who entered the study before diagnosis and 208 community-based controls.
The odds ratio in the highest quintile of enterolactone values adjusted for all of the known risk factors for breast cancer was 0.38 (95% confidence interval,0.18-0.77; P for trend, 0.03). High enterolactone level was associated with higher consumption of rye products and tea and higher intake of dietary fiber and vitamin E compared with those with low serum enterolactone values (E775).

Food sources of phytoestrogens and breast cancer risk in Mexican women.
A total of 198 women with BC, aged 21-79 years, were individually age matched to an identical number of women with no breast disease.
The adjusted odds ratio for the consumption of more than one slice of onion per day and BC was 0.27 (95% confidence interval = 0.16-0.47), with a statistically significant trend (p < 0.001). Among premenopausal women, there was also a protective and significant effect due to the intake of lettuce and spinach and nonsignificant protective effects for the consumption of apples and herbal tea (E777).

Two stages of cancer prevention with green tea.
a prospective cohort study with over 8000 individuals in Saitama Prefecture revealed that the daily consumption of at least ten Japanese-size cups of green tea resulted in delayed cancer onset, and a follow-up study of breast cancer patients conducted at our Hospital found that stages I and II breast cancer patients consuming over five cups per day experienced a lower recurrence rate and longer disease-free period than those consuming fewer than four cups per day (E778).

Tea and cancer: a review of the epidemiological evidence.
Studies around the world were reviewed to evaluate whether there is a consensus of epidemiologic evidence on the relation of tea drinking to cancer overall or to specific cancers. Ecological data suggest at most a modest benefit.
More relevant case-control and cohort studies show mixed results.
Nevertheless, several investigations point to the possibility of lowered risks of digestive tract cancers among tea drinkers, especially those consuming green tea (E781).

C)Effect of green tea on cancer may be a genetical question

Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore.
A nested case-control study involving 297 incident breast cancer cases and 665 control subjects within the Singapore Chinese Health Study showed no association between intake frequencies of green tea and risk of breast cancer among all women or those with low-activity ACE genotype.
Among women with high-activity ACE genotype, however, intake frequency of green tea was associated with a statistically significant decrease in risk of breast cancer (P for trend=0.039); the odds ratio (95% confidence interval) was 0.33 (0.13-0.82) for women drinking green tea at least monthly and 0.29 (0.10-0.79) for those drinking green tea at least weekly compared with non-drinkers.
Black tea intake was unrelated to breast cancer risk irrespective of the ACE genotype (E756).

Tea Intake, COMT Genotype, and Breast Cancer in Asian-American Women
In a case-control study conducted among Asian-American women in Los Angeles County, we reported a significant inverse relationship between intake of green tea and risk of breast cancer. We examined the interrelationships between tea intake, COMT genotype, and breast cancer risk in 589 incident cases and 563 population-based controls in Chinese-, Japanese-, and Filipino-American women.
Risk of breast cancer was influenced significantly by intake of tea, particularly green tea intake. However, the inverse association between tea intake and breast cancer risk was observed only among individuals who possessed at least one low-activity COMT allele.This risk reduction was observed in relation to both green tea and black tea intake (E759).

THE FOLLOWING STUDIES ARE IN ANIMALS OR IN VITRO, BUT SHOW SOME POSSIBLE INTERESTING SYNERGISTIC EFFECTS WHEN (MOSTLY NATURAL) SUBSTANCES ARE COMBINED

Innovative agents in cancer prevention.
Only a few drugs have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. Indole-3-carbinol (I3C), epigallocatechin gallate (EGCG), curcumin and resveratrol, all have a number of different molecular targets, impinging on several signalling pathways (E730).

Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancer cells.
Low concentrations of catechins are cytotoxic to ERalpha- human breast cancer cells, and the combination of EGCG and tamoxifen elicits synergistic cytotoxicity in MDA-MB-231 cells (E737).

Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro.
Seven phytoestrogens were screened for estrogen receptor binding and growth inhibition of androgen-insensitive (PC-3) and androgen-sensitive (LNCaP) human prostate tumor cells.
Quercetin, baicalein, genistein, epigallocatechin gallate (EGCG), and curcumin displaced > 85% of estradiol binding, whereas apigenin and resveratrol displaced > 40%. From growth inhibition studies in LNCaP cells, apigenin and curcumin were the most potent inhibitors of cell growth, and EGCG and baicalein were the least potent. In PC-3 cells, curcumin was the most potent inhibitor of cell growth, and EGCG was the least potent. In both cell lines, significant arrest of the cell cycle in S phase was induced by resveratrol and EGCG and in G2M phase by quercetin, baicalein, apigenin, genistein, and curcumin. Induction of apoptosis was induced by all of the 7 compounds in the 2 cell lines. Androgen responsiveness of the cell lines did not correlate with cellular response to the phytoestrogens. In conclusion, these 7 phytoestrogens, through different mechanisms, are effective inhibitors of prostate tumor cell growth (E747).

Inhibition of liver cancer cell proliferation and migration by a combination of (-)-epigallocatechin-3-gallate and ascorbic acid.
The combination of EGCG and ascorbic acid can strongly suppress the proliferation and metastasis of liver cancer cells. A mixture of EGCG and ascorbic acid exhibited 73.2% inhibition of SMMC-7721 cell proliferation in, which was much higher than EGCG (40.4%) or ascorbic acid (12.4%) alone. In the cell migration assay, the mixture also significantly suppressed the migration of SMMC-7721 cells by 65.9% while EGCG and/or ascorbic acid did by 28.9% and 18.7%, respectively (E748).

Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells.
Similar to silymarin, genistein and EGCG also inhibit mitogenic signaling pathway(s) and alter cell cycle regulators, albeit at different levels, leading to growth inhibition and death of advanced and androgen-independent prostate carcinoma cells (E753).

In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline, ascorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and MCF-7.
A mix of lysine, proline, arginine, ascorbic acid, and EGCG significantly suppressed tumor growth of breast cancer cells in female athymic nude mice and significantly inhibited MMP expression, angiogenesis, and invasion in breast cancer cells, in vitro (E767).

Combined inhibition of estrogen-dependent human breast carcinoma by soy and tea bioactive components in mice.
Green Tea (GT) infusion at 1.5 g tealeaf/100 mL water produced significant (p < 0.05) reductions of 56% in final tumor weight of androgen-dependent human breast tumor in female SCID mice. GT plus Soy Phytochemical Concentrate (SPC) at 0.1% of the diet further reduced final tumor weight by 72% (p < 0.005). Analysis of serum and tumor biomarkers showed that the combined effects of SPC and GT inhibited tumor angiogenesis, and reduced estrogen receptor (ER)-alpha and serum levels of insulin-like growth factor (IGF)-I (E771).

Cancer prevention with food factors: alone and in combination.
EGCG has been shown to increase the endotoxin-induced production of proinflammatory mediators such as prostaglandin E(2) and tumor necrosis factor-alpha in RAW264.7 macrophages, whereas the soybean isoflavonoid genistein compensated for these inverse properties of EGCG, leading to marked suppression in combination (E813).

4 EFFECT ON LOSS OF BODY FAT

Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men.
690 mg catechins for healthy japanes men for 12 weeks decreases body weight, BMI, waist circumference, body fat mass, and subcutaneous fat area. Changes in the concentrations of malondialdehyde-modified LDL were positively associated with changes in body fat mass and total fat area (E108).

Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men.
A mixture of green tea (90, 200, 300 or 400 mg) and guarana extracts (200 mg caffeine) 3 x/day 30 min. before meal increases 24 h energy expenditure by 750 kJ. No effect of the EGCG-caffeine mixture was observed for lipid oxidation. Systolic and diastolic blood pressure increased by about 7 and 5 mmHg (E528).

Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity.
The green tea extract AR25 is an 80% ethanolic dry extract standardized at 25% catechins expressed as EGCG. In an open study, the effects of extract AR25 were evaluated in moderately obese patients. After 3 months, body weight was decreased by 4.6% and waist circumference by 4.48%. These results suggest the green tea extract AR25 to be a natural product for the treatment of obesity, which exerts its activity by several ways: inhibition of lipases and stimulation of thermogenesis (E529).

5 ANTIOXIDANT PROPERTIES

Relationship between rate and extent of catechin absorption and plasma antioxidant status.
Human volunteers were supplemented with single doses of green tea catechins in free (Greenselect) or phospholipid complex form (Greenselect Phytosome) equivalent to 400 mg epigallocatechingallate (EGCg).
Green tea catechins were absorbed more extensively when administered as phospholipid complex rather than as free catechins. Single dose intake of both forms of catechins produced a transient decrease (10-20%) of plasma ascorbate and total glutathione and an increase of plasma TRAP (16-19%). These variations were consistent with the plasmatic levels of EGCg, ascorbate and total glutathione (E533).

)[Effect of tea polyphenols on oxidative metabolism of polymorphonulear neutrophils in healthy and obese people]
Consuming red tea for 14 obese women revealed alteration in reactive oxygen species generation; the relative decrease of RFT was greater after 5 months than that after 1 month of treatment. A decrease in ROS generation after red tea consumption was accompanied by the decrease of ROS in response to tested compounds in normal cells. EGCG and TF (theaflavins) showed similar potency in antioxidative activities. Tea polyphenols were not found to modulate CRP level in obese women. Tea may thus represent an important source of dietary antioxidants (E534).

Effectiveness of moderate green tea consumption on antioxidative status and plasma lipid profile in humans.
Adding 2 cups of green tea to a controlled diet of healthy volunteers for 42 days caused a significant increase in plasma total antioxidant activity [from 1.79 to 1.98 mumol Trolox equivalent (TE)/ml, P<.001], significant decreases in plasma peroxides level (from 412 to 288 Carr U, P<.05) and induced DNA oxidative damage in lymphocytes (from 14.2% to 10.1% of DNA in tail, P<.05), a moderate although significant decrease in LDL cholesterol (from 119.9 to 106.6 mg/dL, P<.05) with respect to control (E535).

Dose-dependent incorporation of tea catechins, (-)-epigallocatechin-3-gallate and (-)-epigallocatechin, into human plasma.
Catechin intake had no effect on the basal level of endogenous antioxidants (alpha-tocopherol, beta-carotene, and lycopene) or of lipids in plasma.
These results suggested that drinking green tea daily would contribute to maintain plasma catechin levels sufficient to exert antioxidant activity against oxidative modification of lipoproteins in blood circulation systems (E824).

6 BIO-AVAILABILITY

Pharmacokinetics of the green tea derivative, EGCG, by the topical route of administration in mouse and human skin.
EGCG was administered topically to human skin achieved high concentrations in skin but negligible systemic availability (E763).

Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers.
Orally administered EGCG is rapidly absorbed from the gut. After repeated dosing (day 10) dose linearity was applied between the 200 mg and 400 mg group. Dose escalation to 800 mg was more than dose-proportional in rate and extent, and statistically different from the 200 mg and 400 mg group. An increase in elimination half-life (t1/2.z) and in the accumulation factor (R) in the 800 mg dosage group indicates dose-dependent saturation of capacity-limited excretion routes or an increase of hepato-duodenal re-circulation (E805).

Comparison of antioxidant activity and bioavailability of tea epicatechins with their epimers.
The epimerisation reaction occurring in manufacturing canned and bottled tea drinks would not significantly affect antioxidant activity and bioavailability of total tea polyphenols (E807).

Medulloblastoma cell invasion is inhibited by green tea (-)epigallocatechin-3-gallate.
EGCG) can reach the brain following oral intake and could thus act as an anti-tumoral agent targeting several key steps of brain cancer cells invasive activity (E814).

Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers.
200, 400 or 800 mg EGCG/day for 10 days in 36 healthy men is rapidly absorbed from the gut.
Dose linearity was applied for single-dose application (day 1). After repeated dosing (day 10) dose linearity was applied between the 200 mg and 400 mg group. Dose escalation to 800 mg was more than dose-proportional in rate and extent, and statistically different from the 200 mg and 400 mg group. An increase in elimination half-life (t1/2.z) and in the accumulation factor (R) in the 800 mg dosage group indicates dose-dependent saturation of capacity-limited excretion routes or an increase of hepato-duodenal re-circulation (E817)

Pharmacokinetics of Tea Catechins after Ingestion of Green Tea and (-)-Epigallocatechin-3-gallate by Humans
The pharmacokinetic parameters of EGCG), EGC, and EC were analyzed after administration of a single oral dose of green tea or decaffeinated green tea (20 mg tea solids/kg) or EGCG (2 mg/kg) to eight subjects.
The time needed to reach the peak concentrations was in the range of 1.3-1.6 h. The elimination half-lives were 3.4 +/- 0.3, 1.7 +/- 0.4, and 2.0 +/- 0.4 h, respectively (E819).

Plasma concentrations of individual tea catechins after a single oral dose in humans.
1. Ten healthy volunteers ingested 1.5 mmole ECg, EGC or EGCg.
2. The catechin levels in plasma after ingestion were significantly different: EGC rose quickly with a short elimination half-life (t1/2 elim = 1.7 h), ECg was intermediate in rise but slowest in decline (t1/2 elim = 6.9h), EGCg was slowest in rise but intermediate in decline (t1/2 elim = 3.9h). At 24h, EGC and EGCg had returned to base levels, but ECg was still elevated.
3. Very limited interconversion (ECg-->epicatechin, EGCg-->EGC) occurred indicating that degallation is not required for uptake.
5. EGC and ECg produced an increase in antioxidant activity in plasma, but with EGCg, no statistically significant effect was found (E820).

Catechins Are Bioavailable in Men and Women Drinking Black Tea throughout the Day
Following a black tea preparation plasma concentrations of EGC, EC and EGCG increased significantly relative to baseline (P < 0.05). Plasma EGC, EC and EGCG peaked after 5 h, whereas ECG peaked at 24 h.
Approximately 1.68% of ingested catechins were present in the plasma, urine and feces, and the apparent bioavailability of the gallated catechins was lower than the nongallated forms. Thus, catechins were bioavailable. However, unless they are rapidly metabolized or sequestered, the catechins appeared to be absorbed in amounts that were small relative to intake (E821).

Phase I Pharmacokinetic Study of Tea Polyphenols following Single-dose Administration of Epigallocatechin Gallate and Polyphenon E
20 healthy subjects were assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). The AUC and maximum plasma concentration (Cmax) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose. The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin formulations resulted in similar plasma EGCG levels (E822).

Dose-dependent incorporation of tea catechins, (-)-epigallocatechin-3-gallate and (-)-epigallocatechin, into human plasma.
225, 375 and 525 mg EGCG + 7.5, 12.5, and 17.5 mg EGC significantly and dose-dependently increases plasma levels (E824).

Effects of Dosing Condition on the Oral Bioavailability of Green Tea Catechins after Single-Dose Administration of Polyphenon E in Healthy Individuals
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.
After an onvernight fast 30 healthy volunteers took a single dose of Polhyphenon E with or without breakfast. 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 (E826).

Sorry. Had to add this animal study:

Piperine Enhances the Bioavailability of the Tea Polyphenol (–)-Epigallocatechin-3-gallate in Mice
Piperine (an alkaloid derived from black pepper), enhanced the bioavailability of EGCG in mice by 1.3-fold compared to mice treated with EGCG only. EGCG appearance in the colon and the feces of piperine-cotreated mice was slower than in mice treated with EGCG alone. Coadministration of piperine and curcumin to humans and rats enhanced the bioavailability of curcumin by 2000% and 154%, respectively (E810).

7 SIDE EFFECTS

Epigallocatechin gallate (EGCG) (TEAVIGO) does not impair nonhaem-iron absorption in man.
The doses of EGCG in supplements, which will be lower than those used in this study, are not expected to have any health relevant effects on iron absorption in subjects with normal iron stores (E804).

Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers.
10 days' repeated administration of oral doses of EGCG of up to 800 mg per day to healthy men were found to be safe and very well tolerated (E805).

Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose Administration of Epigallocatechin Gallate and Polyphenon E in Healthy Individuals
40 healthy subjects with Fitzpatric skin type II or III supplemented for 4 weeks with: 800 mg EGCG once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo once/day (8 subjects/group).
Adverse events reported during the 4-week treatment period include excess gas, upset stomach, nausea, heartburn, stomach ache, abdominal pain, dizziness, headache, and muscle pain. All of the reported events were rated as mild events. For most events, the incidence reported in the polyphenol-treated groups was not more than that reported in the placebo group.
No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea polyphenol products.
There was no protection against UV-induced erythema.
it is safe for healthy individuals to take green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily) (E816).

Plasma-kinetic characteristics of purified and isolated green tea catechin epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers.
Ten days' repeated administration of oral doses of EGCG of up to 800 mg per day were found to be safe and very well tolerated (E817).

A single ascending dose study of epigallocatechin gallate in healthy volunteers.
Single supplementation of 50-1600 mg EGCG under fasting conditions in 60 healthy men was safe and very well tolerated (E818).]

Epigallocatechin gallate (EGCG) (TEAVIGO) does not impair nonhaem-iron absorption in man.
150 or 300 mg EGCG for 8 days in 30 healthy women showed a relative nonhaem iron absorption reduction of 14% with 150mg EGCG and 27% for 300mg EGCG treatment compared to placebo.
In this study the magnitude of the inhibitory action of EGCG on nonhaem iron absorption was found to be much lower than that reported in the literature for black tea and similar compounds (E825).

POSSIBLE INTERESTING PROPERTIES

Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.
200 mg poly E or EGCG/day for 12 weeks in 51 subjects effectively treated human papilloma virus (HPV) infected cervical lesions in 69% (35/51) (E525).

Green tea lulls brain into quality sleep
200 mg L-theanine (an amino acid found in green tea) 1 h before bedtime was supplemented for 6 days to 22 young men. All subjects reported a significant absence of feeling exhausted and a reduced need for sleep when administered with the L-theanine, compared to the placebo.
Seven of the 10 students had improved sleep efficiency and these same subjects reported a superior mental state prior to sleep and a decreased occurrence of nightmares. Total sleeping time did not alter between the two groups (E526).

Cutaneous photoprotection from ultraviolet injury by green tea polyphenols.
Areas of skin of normal volunteers were treated with an extract of green tea or one of its constituents. Thirty minutes later, the treated sites were exposed to a 2 minimal erythema dose solar simulated radiation.
Polyphenolic extracts of green tea are effective chemopreventive agents for many of the adverse effects of sunlight on human health and may thus serve as natural alternatives for photoprotection (E530).

Green tea polyphenol (–)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress
In this study we have investigated the effects of topical application of EGCG, the major polyphenol present in green tea, to human skin before UV irradiation on UV-induced markers of oxidative stress and antioxidant enzymes.
Pretreatment with EGCG was found to restore the UV-induced decrease in GSH level and afforded protection to the antioxidant enzyme GPx (E531).

Tea and circulating estrogen levels in postmenopausal Chinese women in Singapore.
The relationship between tea intake, and plasma estrogen and androstenedione levels in 130 healthy postmenopausal women showed 13% lower plasma estrone levels in regular green tea drinkers, and 19% higher in regular black tea drinkers. A similar pattern of differences between tea intake, and plasma levels of estradiol (P = 0.08) and androstenedione (P = 0.14) were found (E906).

Green tea: the human in vivo studies collected!!!

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