Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols

This paper reviews recent human studies on the bioavailability of chlorogenic acids in coffee and green tea flavan-3-ols in which the identification of metabolites, catabolites and parent compounds in plasma, urine and ileal fluid was based on mass spectrometric methodology. Both the chlorogenic acids and the flavan-3-ols are absorbed in the small intestine and appear in the circulatory system predominantly as glucuronide, sulfate and methylated metabolites. Even when absorption occurs in the small intestine, feeding studies with ileostomists reveal that substantial amounts of the parent compounds and some of their metabolites appear in ileal fluid indicating that in volunteers with a functioning colon these compounds will pass to the large intestine where they are subjected to the action of the colonic microflora. A diversity of colonic-derived catabolites are absorbed into the bloodstream and pass through the body prior to excretion in urine. There is growing evidence that these compounds, which were little investigated until recently, are produced in quantity in the colon and form a key part of the bioavailability equation of flavonoids and related compounds that occur in fruits, vegetables and beverages. Recent evidence indicates that some colon-derived phenolic acids have in vitro anti-inflammatory activity.     

Bioavailability of polyphenon E flavan-3-ols in humans with an ileostomy

To investigate the degree of absorption of flavan-3-ols in the small intestine, human subjects with an ileostomy ingested 200 mg of Polyphenon E, a green tea extract, after which ileal fluid and urine, collected over a 24-h period, were analyzed by high-performance liquid chromatography with photodiode array and mass spectrometric detection. The data obtained indicated that although approximately 40% of flavan-3-ol intake is recovered in ileal fluid, substantial quantities are absorbed in the small intestine. Moreover, 14 urinary metabolites, comprising sulfates, glucuronide, and methylated derivatives, were identified and quantified. All were metabolites of (epi)catechin or (epi)gallocatechin, representing 47 +/- 2% and 26 +/- 9%, respectively, of the ingested parent compound. These high recoveries indicate that these flavan-3-ols absorbed in the small intestine are much more bioavailable than most dietary flavonoids. No 3-O-galloylated flavan-3-ols or their metabolites were detected in urine. The absence of urinary flavan-3-ol metabolites after ingestion of 200 mg of (-)-epigallocatechin gallate indicates that there is no removal of the 3-O-galloyl group in vivo, and hence, this does not account for the high urinary recovery of (epi)gallocatechin metabolites after ingestion of Polyphenon E. Increasing the intake of Polyphenon E, by feeding doses of 200, 500, and 1500 mg, led to increased urinary excretion of (epi)catechin metabolites but not metabolites of (epi)gallocatechin. Coingestion of 200 mg of Polyphenon E with bread, cheese, or glucose did not significantly modify the absorption, metabolism, and excretion of flavan-3-ols. It does not necessarily follow, however, that the same would occur when flavan-3-ols are ingested with more complex food matrices.     

Antioxidant activity and polyphenol content of green tea flavan-3-ols and oligomeric proanthocyanidins

The antioxidant activity and total phenolics content (TPC) of freshly prepared green tea extract (GTE) as affected by time, temperature and stirring were determined using the ferric reducing antioxidant power (FRAP) and Folin-Ciocalteu assays, respectively. Acetone-water fractions of GTE containing flavan-3-ols and oligomeric proanthocyanidins were evaluated at concentrations between 25 and 500 μg/ml. Increasing the extraction time from 3 min to 10 min resulted in a significant increase in both the FRAP values and TPC. Increasing the extraction time from 10 min to 30 min was without any significant effects on both FRAP and TPC values. Moreover, the FRAP values were correlated with the TPC. GTE fractions had widely different FRAP values that were well correlated with the TPC of the fraction. It was concluded that brewing conditions such as extraction temperature, period of extraction, ratio of tea leaves to extracting water, and stirring are important factors for determining the FRAP values and TPC in GTE. These factors should be taken into consideration during preparation for nutritional benefits during usual consumption of this beverage. Elevated FRAP and TPC values corresponded to those GTE fractions with a higher amount of phenolic compounds, which have stronger antioxidant activities.     

Antioxidant activity and polyphenol content of green tea flavan-3-ols and oligomeric proanthocyanidins

The antioxidant activity and total phenolics content (TPC) of freshly prepared green tea extract (GTE) as affected by time, temperature and stirring were determined using the ferric reducing antioxidant power (FRAP) and Folin–Ciocalteu assays, respectively. Acetone–water fractions of GTE containing flavan-3-ols and oligomeric proanthocyanidins were evaluated at concentrations between 25 and 500 µg/ml. Increasing the extraction time from 3 min to 10 min resulted in a significant increase in both the FRAP values and TPC. Increasing the extraction time from 10 min to 30 min was without any significant effects on both FRAP and TPC values. Moreover, the FRAP values were correlated with the TPC. GTE fractions had widely different FRAP values that were well correlated with the TPC of the fraction. It was concluded that brewing conditions such as extraction temperature, period of extraction, ratio of tea leaves to extracting water, and stirring are important factors for determining the FRAP values and TPC in GTE. These factors should be taken into consideration during preparation for nutritional benefits during usual consumption of this beverage. Elevated FRAP and TPC values corresponded to those GTE fractions with a higher amount of phenolic compounds, which have stronger antioxidant activities.     

Nongallated compared with gallated flavan-3-ols in green and black tea are more bioavailable

Green tea and black tea (BT) contain gallated [(-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate] and nongallated [(-)-epicatechin, (-)-epigallocatechin (EGC)] tea polyphenols (PP). During BT production, PP undergo oxidation and form larger polymers such as theaflavins (THE) and thearubigins, which contribute to the health benefit of BT. This article gives an overview of the role of chemical characteristics and endogenous metabolism of tea PP and their bioavailability in humans and describes attempts to increase their bioavailability. At pH close to neutral, EGCG and EGC form homo- and heterodimers generating hydrogen peroxide. To confirm the pH instability of EGCG, EGC, and THE in cell culture medium, their antiproliferative activity was determined in the presence and absence of catalase. The antiproliferative activity in LNCaP prostate cancer cells was decreased when incubated with catalase prior to EGCG, EGC, and THE treatment. In addition, new findings demonstrated that the formation of methyl-EGC increased the stability at neutral pH compared with EGC. Approaches to increase the bioavailability of flavan-3-ols are reviewed, which include the administration of tea in combination with fruit juices, coadministration with piperine, and peracetylation of EGCG. Future intervention studies will need to focus on the bioactivity not only of green tea and BT PP but also of their metabolites and biotransformation products.     

Dietary flavan-3-ols intake and metabolic syndrome risk in Korean adults

Flavan-3-ols are a subclass of flavonoids found in a variety of foods including teas. The effects of flavan-3-ols on the risk of metabolic syndrome (MetS) have been investigated, generally focusing on tea catechins or individual flavan-3-ol rich foods, but there is little information on dietary flavan-3-ols intake and risk of MetS in population-based studies. In this cross-sectional study, we examined the association between dietary flavan-3-ols intake and the risk of MetS in Korean adults. Subjects comprised 1,827 men and 2,918 women aged 20-69 years whose data was included in the 2008 Korean National Health and Nutrition Examination Survey. This survey was conducted between January 2008 and December 2008. Total flavan-3-ols intakes were calculated from 24-hour dietary recalls using a flavonoids database. Thirty percent of the male subjects and 24% of the female subjects were reported as having MetS. In the female subjects, flavan3-ols intake was inversely associated with the risk of MetS after adjusting for potential confounders (5th vs. 1st quintile, OR = 0.64, 95% CI = 0.45-0.91, P for trend = 0.384). The main food source of flavan-3-ols was green tea followed by apples and grapes. Among MetS components, flavan3-ols intake was inversely associated with the risk of high blood pressure after adjusting for potential confounders (5th vs. 1st quintile, OR = 0.64, 95% CI = 0.45-0.90, P for trend = 0.005). No significant association between flavan-3-ols intake and risk of MetS was found in the male subjects. After stratified analysis by obesity (BMI ≥ 25 or BMI < 25), however, flavan3-ols intake was inversely related to the risk of hypertension in non-obese men. These results suggest that dietary flavan-3-ols intake may have beneficial effects on MetS risk by reducing the risk of hypertension. The effects of flavan-3-ols intake dependent on obesity need further investigation.     

Tea flavan-3-ols as modulating factors in endoplasmic reticulum function

Regular green tea consumption has been shown to reduce the risk of cancer and diabetes mellitus. These effects are attributed to tea flavan-3-ols, especially to epigallocatechin gallate; however, the molecular targets and mechanisms of action are still subject of extensive research. The special roles of the endoplasmic reticulum (ER) in biotransformation, protein synthesis, calcium homeostasis, and glucose production make this organelle a potential target of the antitumor and antidiabetic effects of tea flavan-3-ols. The purpose of this review is to present evidence for the biologic actions of tea flavan-3-ols on specific ER targets associated with normal function and disease. Reactivation of chemical carcinogens can be reduced by tea flavan-3-ols through inhibition of glucuronide transport across the ER membrane. Catechins modulate Ca²⁺ release from the ER lumen and interfere with glycoprotein maturation, which can lead to decreased viability and increased drug sensitivity of tumor cells. Epigallocatechin gallate inhibits glucose transport across the ER membrane, which can underlie the reduction of hepatic glucose production by tea flavan-3-ols. These mechanisms likely contribute to the chemopreventive and glucose-lowering effects of tea catechins. Investigating the effects of flavan-3-ols on ER functions is a promising field of medical and biochemical research to understand disease and improve health.     

Dietary fiber and flavan-3-ols in shortbread biscuits enriched with barley flours co-products

The coarse fraction obtained by air classification of barley flour, rich in dietary fiber and flavan-3-ols, was utilized to develop functional biscuits. The flavan-3-ol content, antioxidant activity and oxidative stability of biscuits were measured during storage under retail conditions for 1 year. The replacement of 60% (w/w) refined wheat flour with barley coarse fraction increased the ash, fiber and flavan-3-ol contents significantly. Biscuit samples enriched with barley coarse fraction had a significantly higher amount of fiber compared with the control sample (six times higher). The β-glucan content in enriched samples was 15 times higher than control samples. The flavan-3-ol loss in biscuits after baking was about 67%. The initial content of flavan-3-ols increased from 0.6 to 4.3 mg/100 g in biscuits formulated with barley coarse fraction and showed improved antioxidant properties. Lipid oxidation increased during the shelf-life; the enriched biscuit showed the higher lipid oxidation status, but the level reached during the shelf-life was lower than the limit of acceptance reported for bakery products and, for this reason, does not compromise the safety.     

Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement

BACKGROUND: Green and black tea polyphenols have been extensively studied as cancer chemopreventive agents. Many in vitro experiments have supported their strong antioxidant activity. Additional in vivo studies are needed to examine the pharmacokinetic relation of absorption and antioxidant activity of tea polyphenols administered in the form of green or black tea or tea extract supplements. OBJECTIVE: The purpose of this study was to compare the pharmacokinetic disposition of tea polyphenols and their effect on the antioxidant capacity in plasma 8 h after a bolus consumption of either green tea, black tea, or a green tea extract supplement. DESIGN: Thirty healthy subjects were randomly assigned to 3 different sequences of green tea, black tea, or a green tea extract supplement in a 3 x 3 crossover design with a 1-wk washout period in between treatments. RESULTS: Flavanol absorption was enhanced when tea polyphenols were administered as a green tea supplement in capsule form and led to a small but significant increase in plasma antioxidant activity compared with when tea polyphenols were consumed as black tea or green tea. All 3 interventions provided similar amounts of (-)-epigallocatechin-3-gallate. CONCLUSIONS: Our observations suggest that green tea extract supplements retain the beneficial effects of green and black tea and may be used in future chemoprevention studies to provide a large dose of tea polyphenols without the side effects of caffeine associated with green and black tea beverages.     

Dietary fiber and flavan-3-ols in shortbread biscuits enriched with barley flours co-products

The coarse fraction obtained by air classification of barley flour, rich in dietary fiber and flavan-3-ols, was utilized to develop functional biscuits. The flavan-3-ol content, antioxidant activity and oxidative stability of biscuits were measured during storage under retail conditions for 1 year. The replacement of 60% (w/w) refined wheat flour with barley coarse fraction increased the ash, fiber and flavan-3-ol contents significantly. Biscuit samples enriched with barley coarse fraction had a significantly higher amount of fiber compared with the control sample (six times higher). The β-glucan content in enriched samples was 15 times higher than control samples. The flavan-3-ol loss in biscuits after baking was about 67%. The initial content of flavan-3-ols increased from 0.6 to 4.3 mg/100 g in biscuits formulated with barley coarse fraction and showed improved antioxidant properties. Lipid oxidation increased during the shelf-life; the enriched biscuit showed the higher lipid oxidation status, but the level reached during the shelf-life was lower than the limit of acceptance reported for bakery products and, for this reason, does not compromise the safety.     

Flavonols and flavan-3-ols as modulators of xanthine oxidase and manganese superoxide dismutase activity

Experiments were performed to assess the dose-dependent effects of quercetin, kaempferol, (+) catechin, and (?) epicatechin on superoxide radical production through the modulation of manganese superoxide dismutase and xanthine oxidase activities. The experiments were carried out at flavanoid concentrations ranging from 1?µM to 100?µM. This investigation highlighted that flavonols induced opposite effects on superoxide radical production at different doses, i.e. pro-oxidant at the highest concentration (100?µM) and anti-oxidant at the lowest concentration (1?µM). Similar behaviors were observed for xanthine oxidase with flavan-3ols. The diastereoisomer (the catechin) acted as a stronger radical scavenger than the epicatechin. However, flavan-3ols were less pro-oxidant than flavonols: in fact, the addition of the superoxide dismutase enzyme was able to cancel the flavan-3ols’ pro-oxidant effect. This study also shows that the absence of the 4-carbonyl group conjugated with the 2–3 double bonds in the heterocyclic ring cancelled the pro-oxidant effect of flavan-3ols. The opposite dose-dependent effects of flavonols suggest that they may be used as either a pro-oxidant or antioxidant.     

Effect of the growing area on the methylxanthines and flavan-3-ols content in cocoa beans from Ecuador

Nacional is a worldwide recognized Ecuadorian cocoa variety. However, little is known regarding its phytochemical profile and how the production area influences its nutritional quality. The contents of methylxanthines (caffeine and theobromine), total polyphenols, flavan-3-ols monomers (catechin and epicatechin) and main proanthocyanidins (procyanidins B2 and C1) in beans of Nacional cocoa were evaluated. A comprehensive sampling was carried out along Ecuador, including 85 farms from three different geographical levels (region, province, and canton). Theobromine and caffeine contents were higher in cocoas from the Amazonian region. According to the caffeine/theobromine ratio, all samples were classified as Trinitario cocoa. The flavan-3-ols amount was not clearly associated to a geographical area. However, when principal component analysis was applied, common patterns were found for some provinces. These results may be useful to further characterize the composition of cocoa beans for quality and authenticity purposes and the development of chocolate products rich in bioactives.     

The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats

Rats were fed a grape seed extract (GSE) containing (+)-catechin, (-)-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a 24 h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to a greater extent the ileum 1 h after ingestion, and into the caecum after 2 h with relatively small amounts being detected in the colon after 3 h. The GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols. Plasma contained exclusively catechin glucuronides and methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B1, B2, B3 and B4 as well as the trimer C2 and an unknown GSE trimer. The amounts of (+)-catechin and (-)-epicatechin metabolites excreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding (-)-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidin oligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.     

Consumption of green tea causes rapid increase in plasma antioxidant power in humans.

Green tea contains polyphenolic antioxidants that have shown anticarcinogenic properties in animal and in vitro experimental studies. Current data regarding absorption and bioavailability of tea antioxidants in humans, however, are conflicting. In this study, plasma and urine antioxidant power after ingestion of green tea was measured using the ferric reducing/antioxidant power (FRAP) assay (US patent pending) to assess absorption, systemic distribution, and renal excretion of green tea antioxidants in healthy adults. Results showed that absorption of green tea antioxidants was rapid, with peak increase in plasma FRAP of around 4% at 40 minutes after ingestion: mean increase was 44 +/- 9 (SE) mumol/l. Excretion of polyphenolic antioxidants was also fast, peaking at 60-90 minutes, with significant correlation between urinary FRAP values and urinary total phenolic concentrations (r = 0.845, p < 0.001). In control studies, no increase in plasma or urine FRAP values was seen after intake of water. Although the amount of antioxidants absorbed was relatively small and the increase in plasma antioxidant power was of short duration, results demonstrate that some potentially anticarcinogenic polyphenolic antioxidants in green tea enter the systemic circulation soon after ingestion and cause a significant increase in plasma antioxidant status. This increase may, in turn, lower oxidative damage to DNA and so decrease risk of cancer.     

Bioavailability of catechins from ready-to-drink tea

ObjectiveBecause consumption of teas may be associated with potential health benefits due to its content in polyphenols and in Western countries the consumption of tea is equally divided between the hot and the ready-to-drink (RTD) cold versions of this typical beverage, the aim of this work was to study the absorption and metabolism of flavan-3-ols in human volunteers after the ingestion of a commercial RTD tea.MethodsA feeding study was carried out in 20 healthy human volunteers and urine samples were collected for 24 h after tea ingestion. Flavan-3-ols–derived molecules were identified and quantified in urine samples by high-performance liquid chromatography with tandem mass spectrometric detection.ResultsEight relevant metabolites were identified in urine, all modified flavan-3-ols with the exception of unmetabolized gallic acid. The urinary excretion of flavan-3-ols was equal to 7.2% of the intake with tea. Gallic acid, which was abundant in the RTD tea used in this study, reached a 4.5% of the drunken amount.ConclusionsThe bioavailability values observed are in agreement with previous reports, although the dosage of polyphenols ingested in this study is remarkably lower. Moreover, the use of a group of 20 volunteers, more than the average number of subjects used for usual human acute-feeding studies involving polyphenols, provides additional credibility to the results. After drinking the RTD ice tea used in this study, the internal compartments are exposed to non-marginal doses of flavanols and flavanol metabolites up to 24 h.     

Systematic review of green tea epigallocatechin gallate in reducing low-density lipoprotein cholesterol levels of humans

We conducted a systematic review of the literature for the ability of green tea epigallocatechin gallate (EGCG) to lower low-density lipoprotein cholesterol (LDL-C). Study subjects were limited to healthy individuals and randomized, controlled trials on human serum lipid levels, especially LDL-C, conducted. A total of 17 trials (n?=?1356) met all of the inclusion criteria. According to weighted mean differences for changes from baseline with 95% confidence intervals (CI), 107–856?mg/d of EGCG for 4 to 14 weeks reduced LDL-C by ?9.29?mg/dl (95% CI, ?12.27 to ?6.31). Sub-analysis was performed to compare the EGCG lowering effect on LDL-C between non-obese and obese subjects, EGCG dose, baseline of LDL-C levels, or BMI. We concluded that consumption of green tea EGCG resulted in a significant reduction of LDL-C at any baseline level and any dose between 107 and 856?mg/d, and the effect size was slightly dependent on the baseline lipid level of the subjects.     

Simultaneous ingestion of dietary proteins reduces the bioavailability of galloylated catechins from green tea in humans

Purpose

To investigate the influence of dietary proteins (casein, soy protein) and skimmed milk on the plasma kinetics of green tea (GT) catechins.

Methods

In a randomized cross-over design with one-week intervals, 24 healthy normal-weight women consumed a test drink containing 1.75 g GT extract with or without the addition of different proteins. Treatments were GT (control), GT with skimmed milk (GT + M), GT with caseinate (GT + CS), or GT with soy protein (GT + S). Venous blood samples were taken before and several times during a period of 4.5 h after consumption of the test drink. Plasma concentrations of catechins were analyzed by HPLC with electrochemical detection.

Results

Compared to control, consumption of GT with milk, caseinate, or soy protein significantly reduced the bioavailability (mean area under the plasma concentration–time curve) of total catechins (means ± SEM; GT + M, 87 ± 5%; GT + CS, 79 ± 5%; GT + S, 88 ± 4%), epigallocatechin gallate (GT + M, 68 ± 4%; GT + CS, 63 ± 5%; GT + S, 76 ± 5%), and epicatechin gallate (GT + M, 68 ± 5%; GT + CS, 66 ± 6%; GT + S, 77 ± 6%), while the bioavailability of non-galloylated catechins such as epigallocatechin (GT + M, 134 ± 9%; GT + CS, 118 ± 9 %; GT + S, 123 ± 8%) and epicatechin (GT + M, 125 ± 10%; GT + CS, 114 ± 11%; GT + S, 110 ± 8%) significantly increased. No significant differences in bioavailability of GT catechins were observed between the treatments GT + M, GT + CS, or GT + S.

Conclusion

Simultaneous ingestion of dietary proteins reduces the bioavailability of galloylated catechins from GT in humans.     

Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption

Green and black tea have shown promise in the chemoprevention of prostate cancer. The objective of this study was to determine the bioavailability and bioactivity of tea polyphenols (PP) and theaflavins in human serum and human and mouse tissues. A decaffeinated black tea diet was administered to C57BL/6 mice. PPs and theaflavins were found in the small and large intestine, liver, and prostate in conjugated and free forms. The relative prostate bioavailability of theaflavin was 70% higher than that of epigallocatechin gallate (EGCG). In the second mouse study, a green tea (GT) diet was administered followed by the control diet for 1-5 d. Epicatechin (EC), EGCG, and epicatechin gallate (ECG) concentrations in prostate tissue were significantly decreased after 1 d of consuming the control diet. Epigallocatechin gallate (EGC), however, did not decrease significantly. For the human study, 20 men scheduled for surgical prostatectomy were randomly assigned to consume 1.42 L daily of GT, BT, or a caffeine-matched soda control (SC) for 5 d before radical prostatectomy. Tea PPs were greater in prostate samples from men consuming BT and GT than in men consuming SC (P = 0.0025). Although tea PP were not detectable in serum, ex vivo LNCaP prostate cancer cell proliferation was less when cells were grown in media containing patient serum collected after BT (P < 0.001) and GT (P = 0.025) consumption relative to baseline serum This is the first human study to show that tea polyphenols and theaflavins are bioavailable in the prostate where they may be active in the prevention of prostate cancer.