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(Circulation. 2001;104:151.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Short- and Long-Term Black Tea Consumption Reverses Endothelial Dysfunction in Patients With Coronary Artery Disease
From Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass, and Linus Pauling Institute, Oregon State University, Corvallis (B.F.).
Correspondence to J.A. Vita, MD, Cardiology, Boston University Medical Center, 88 E Newton St, Boston, MA 02118. E-mail jvita{at}bu.edu
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Abstract |
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Background—— Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids.
Methods and Results—— To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption.
Conclusions—— Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.
Key Words: antioxidants • tea • flavonoids • endothelium • nitric oxide • coronary disease
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Introduction |
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Apart from water, tea is the most widely consumed beverage worldwide. 1 Recent epidemiological studies suggest an inverse relationship between tea consumption and cardiovascular disease, 2–5 with one notable exception.6 There is also convincing evidence that dietary intake of antioxidant flavonoids from tea and other sources (eg, onions, apples, red wine, and broccoli) is associated with reduced cardiovascular risk.2–5,7–9 The benefit of high flavonoid intake may be greater for individuals with established coronary artery disease (CAD), 2,10 although favorable effects have also been demonstrated in people without evidence of atherosclerosis.5,8,9
One proposed mechanism for the benefit of dietary flavonoids is their antioxidant properties. These polyphenols are effective scavengers of reactive oxygen species11 and can inhibit lipid peroxidation through chelation of transition metal ions12 or their action as chain-breaking antioxidants.13 These properties suggest that flavonoids might prevent LDL oxidation, a key early event in the development of atherosclerosis.14 However, although several flavonoids exert this antioxidant activity in vitro, they do not prevent ex vivo LDL oxidation,15,16 and their cumulative concentration in LDL particles with regular tea ingestion is low.16
Recent experimental evidence also suggests that flavonoids may favorably affect endothelial function.17,18 Normal endothelium regulates vasomotor tone, platelet activity, leukocyte adhesion, and vascular smooth muscle proliferation via release of several paracrine factors, including nitric oxide (NO).19 These endothelial functions are impaired with atherosclerosis and its risk factors.14,20 Indeed, endothelial dysfunction may contribute to the pathogenesis of atherosclerosis both in the early stages of lesion formation and late in the disease process when patients develop clinical symptoms.19 Recent studies have also linked coronary endothelial dysfunction with future cardiovascular disease events.21
Endothelial dysfunction in atherosclerosis is associated with increased oxidative stress and may be reversed by antioxidant treatment.14 To test the hypothesis that tea consumption would improve endothelial function in patients with CAD, we performed a randomized, placebo-controlled, crossover study of short- and long-term black tea consumption for its effect on brachial artery flow-mediated dilation.
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Methods |
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Volunteers
Boston Medical Center patients with CAD (history of revascularization or
1 coronary stenosis >70% on angiography) were eligible. Exclusion criteria included uncontrolled hypertension, heart failure, recent acute coronary syndrome (<3 months), or intake of antioxidant vitamin supplements in doses greater than the recommended daily allowance. The Institutional Review Board approved the study. Volunteers provided written, informed consent.
Study Design
Patients made 3 visits, each 4 weeks apart. Patients fasted overnight and did not smoke for 24 hours. Vasoactive medications were withheld for 12 hours, and long-acting vasoactive drugs were withheld for 24 hours. Patients maintained their usual diet but excluded red wine and other tea consumption during the study. Baseline dietary flavonoid intake was estimated by a 1-week food-frequency questionnaire. This included major dietary sources of flavonols (quercetin, kaempferol, and myricetin) and flavanols (the various catechins but not proanthocyanidins), which were quantified through the use of food flavonoid content charts.22
Patients consumed tea or water first (Figure 1) according to computer-generated randomization numbers. Endothelial function was assessed at 6 time points: (1) baseline; (2) 2 hours after consumption of 450 mL freshly brewed black tea (short-term tea); (3) after consumption of 900 mL (freeze-dried) black tea daily for 4 weeks but none the morning of study (long-term tea); (4) 2 hours later that day after 450 mL freshly brewed tea (short–on–long-term tea); (5) after 900 mL fresh water daily for 4 weeks (long-term water); and (6) 2 hours after 450 mL water (short-term water). Short-term tea effects were examined after 2 hours, coincident with maximal flavonoid bioavailability.16,23 For short-term studies, 9.7 g fresh tea leaf (World Blend, provided by Tea Trade Health Research Association, London, England) was brewed in a standard brewer (Bunn-O-Matic Corporation) for 5 minutes with 1 L fresh water. Freeze-dried tea was prepared from the same tea leaf by Lipton, Inc. Tea composition is detailed in Table 1. To increase compliance and mimic usual practice, participants added sugar, lemon, or milk as desired.16,23 Compliance was confirmed by direct questioning and counting of empty tea packets. At all 6 time points, blood was collected and vital signs were measured after 10 minutes of semirecumbent rest with an automated monitor,24 and the average of 3 measurements was recorded.
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To investigate whether tea effects were related to caffeine, endothelial function and blood pressure were assessed in separate patients before and 2 hours after a 200-mg oral dose of caffeine, which matched the caffeine content of 450 mL brewed tea (Table 1).
Vascular Function Assessment
Endothelium-dependent flow-mediated dilation, endothelium-independent nitroglycerin-mediated vasodilation (0.4 mg), and hyperemic flow of the conduit brachial artery were determined by use of high-resolution vascular ultrasound and an upper-arm occlusive cuff as previously described.24–26 To avoid confounding effects, nitroglycerin was administered last at each visit. Nitroglycerin was omitted if systolic blood pressure was <100 mm Hg or if there was a previous adverse reaction. Ultrasound images were digitized online and stored. "Blinded" analysis was performed with commercially available software (Brachial Analyzer, Medical Imaging Applications).
We assessed reproducibility of our analysis system in 20 studies. Intraobserver and interobserver correlation coefficients were 0.99 and 0.99, respectively, for diameter determination and 0.93 and 0.89 for flow-mediated dilation. The average differences between 2 determinations by the same individual were 0.03±0.03 mm for diameter and 0.93± 0.66% for flow-mediated dilation. The average differences between determinations by 2 different individuals were 0.04±0.05 mm for diameter and 1.01±0.92% for flow-mediated dilation. Reproducibility of flow-mediated dilation over 1 month in our laboratory was documented in 25 volunteers from the present cohort by comparing baseline to the long-term water-phase flow-mediated dilation. The mean±SD difference was 1.96±1.16 percentage points.
Biochemical Analyses
Serum total cholesterol, HDL, triglycerides, and glucose were measured by automated analyzer (Hitachi-917). LDL cholesterol was calculated with the Friedewald formula. Plasma catechins (important tea flavonoids)27 and ascorbic acid24–26 were measured with high-performance liquid chromatography as previously described. The total antioxidant capacity of plasma was determined with Trolox, an aqueous analog of 
-tocopherol, as reference antioxidant. The protein-independent oxygen-radical absorbance capacity of plasma (ORAC) was measured with the method of Cao and colleagues.28 The ferric-reducing ability of plasma (FRAP), a measure of the ability to donate electrons, was measured with the method of Benzie and Strain.29 Results for both are expressed in micromole of Trolox activity per liter of plasma.
Statistical Analysis
Data are mean±SD, except in the figures (mean±SE). Baseline characteristics were compared with unpaired t, 
2, or Fisher’s exact tests as appropriate. The effects of treatment and treatment order were compared by 2-way repeated-measures ANOVA, with post hoc Student-Newman-Keuls comparison. Univariate clinical and biochemical predictors of flow-mediated dilation were determined by linear regression. To identify independent predictors of flow-mediated dilation, all clinical variables with univariate P<0.10 were entered into a stepwise multivariate regression model. Statistical significance was accepted at P<0.05.
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Results |
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Baseline Characteristics
We enrolled 66 patients. Eight withdrew, and 8 had
1 ultrasounds that were technically unsuitable for analysis. These 16 patients were excluded before data analysis, leaving 50 participants. Eleven patients were treated with caffeine tablets. Clinical characteristics are displayed in Table 2. Other than body mass index, there were no differences in baseline characteristics among groups.
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Concurrent cardiac medications were aspirin in 50 patients (100%), ß-blockers in 45 (90%), calcium channel blockers in 17 (34%), nitrates in 14 (28%), and ACE inhibitors in 8 (16%). Estimated mean dietary flavonoid intake at baseline was 61.1±60.1 mg/d (median, 43.8 mg/d), of which flavonols contributed 42.3±33.4 mg/d and flavanols contributed 18.8±39.4 mg/d. Flavanol intake correlated with baseline total plasma catechin levels (r=0.37, P=0.022).
Brachial Artery Responses
Baseline brachial artery flow-mediated dilation was comparable in the water- and tea-first groups (5.2±2.9% versus 6.8±3.7%, P=0.10). With traditional risk factors and baseline dietary flavonoid intake used as independent variables, the univariate predictors of baseline flow-mediated dilation were flavonoid intake (r=0.31, P=0.026), diastolic blood pressure (r=-0.27, P=0.056), and fasting glucose (r=-0.26, P =0.064). The only independent predictor of baseline flow-mediated dilation was dietary flavonoid intake (adjusted R2=0.16, P=0.012).
Both short- and long-term tea consumption improved brachial artery flow-mediated dilation, whereas water had no effect (Figure 2). There was no interaction between beverage order and treatment effects (P=0.93). When the results of patients randomized to tea first and water first were combined, flow-mediated dilation was 6.0±3.4% at baseline, 5.7±3.9% after short-term water, 6.1±4.3% after long-term water, 9.4±3.9% after short-term tea, 9.5±3.6% after long-term tea, and 10.8±4.4% after short–on–long-term tea. Overall, beverage significantly affected flow-mediated dilation (P<0.001). By post hoc analysis, flow-mediated dilation was greater after short- and long-term tea consumption compared with baseline and water consumption (P<0.001). Furthermore, consumption of short-term tea after 4 weeks of tea (short–on–long term) produced further improvement compared with long-term tea (P<0.02).
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Tea had no effect on baseline arterial diameter, maximal hyperemia, diastolic blood pressure, or heart rate (Table 3). Short-term tea ingestion increased systolic blood pressure by 
5 mm Hg (P=0.015); however, this effect was not evident after long-term tea consumption. Neither short-term nor short-on -long-term tea consumption affected nitroglycerin-induced endothelium-independent vasodilation (n=44, P=0.85; Figure 3).
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Baseline flow-mediated dilation was comparable in the caffeine and tea groups (7.8±5.2% versus 6.0±3.4%, respectively; P=0.16). Flow-mediated dilation remained similar 2 hours after caffeine treatment (7.8±5.2% versus 7.7±4.3%, P=0.86), suggesting that the short-term effects of tea are not attributable to caffeine. Caffeine treatment tended to increase systolic blood pressure to an extent similar to that of tea, from 142±24 to 148±21 mm Hg (P=0.153). Diastolic blood pressure (78±10 versus 80±5 mm Hg, P=0.38) and heart rate (60±7 versus 59±6 bpm, P=0.39) were unaffected by caffeine.
Biochemical Parameters
Long-term water or tea consumption had no effect on fasting lipid, glucose, or ascorbic acid levels (Table 4). However, short- and long-term tea consumption increased total plasma catechins. Total plasma catechin concentrations were 25.5±17.1 ng/mL at baseline, 21.5±12.6 ng/mL after short-term water, 25.1±13.0 ng/mL after long-term water, 32.8±22.4 ng/mL after short-term tea, 34.6±20.1 ng/mL after long-term tea, and 33.7±17.2 ng/mL after short-on-long-term tea (n=39, P<0.001). By post hoc analysis, total plasma catechins were greater after short-term, long-term, and short-on-long-term tea consumption compared with baseline and water consumption (P<0.05). Long-term tea consumption also tended to increase total antioxidant capacity of plasma measured as ORAC or FRAP (P=0.09), although only 21 patients had complete data (Table 4).
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Discussion |
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This study demonstrates that short- and long-term consumption of black tea improves brachial artery flow-mediated dilation in patients with CAD. This improvement was associated with increased total plasma catechins. Tea consumption had no effect on baseline diameter, extent of reactive hyperemia, or nitroglycerin-induced vasodilation, suggesting that tea acted to improve endothelial vasomotor function rather than acting to alter resting vascular tone, increase the stimulus for dilation, or improve vascular smooth muscle function. Baseline flow-mediated dilation in the present population was comparable to that in prior studies of patients with CAD and blunted compared with that of healthy control subjects.24–26,30 Flow-mediated dilation with short–on–long-term tea consumption was comparable to that of healthy volunteers in our laboratory (11.2±5.7%).24 These findings suggest that tea consumption reverses endothelial vasomotor dysfunction in patients with CAD and are comparable to our recent findings with the antioxidant ascorbic acid.26
No previous study has examined the effects of tea on vascular function. However, our findings concur with experimental studies17,18 and with 2 smaller clinical studies that examined the effects of grape-derived flavonoids.31,32 Stein and colleagues 31 demonstrated that purple grape juice consumption for 14 days improved brachial artery flow-mediated dilation and decreased LDL oxidizability in 15 patients with CAD. That study was limited by lack of a control group. In contrast to the present study, nitroglycerin-induced vasodilation was also improved, and lipid and insulin levels changed with treatment. Possible reasons for these apparently discrepant results include differences in flavonoid composition of grapes versus tea, the additional carbohydrate load, and differences in study populations. In a recent randomized, crossover study, Agewall et al32 demonstrated improved brachial artery flow-mediated dilation <1 hour after ingestion of dealcoholized red wine but not after red wine with alcohol in 12 healthy volunteers. That study did not examine nitroglycerin responses and lacked a placebo group, but it supports our finding that short-term tea flavonoid intake improves endothelial function.
An interesting finding of the present study is the significant relation between dietary flavonoid intake and baseline endothelial function. Estimated daily flavonoid intake was comparable to that of some population studies,2,3,9,10 albeit at the upper end of the observed range for flavonols,3 which may limit generalization of the observed correlation. Our cohort’s relatively high flavonoid intake is partly explained by inclusion of flavanol plus flavonol intake, because previous studies did not quantify dietary flavanol.2,3,9,10 Flavanols are particularly important if tea or red wine is regularly consumed,16,22 and flavanols represented one third of our cohort’s baseline dietary flavonoids. These dietary questionnaire results lend further support to our conclusion that dietary flavonoids importantly affect vascular function.
The precise mechanism by which tea improves endothelial function was not determined. However, our findings do provide some insights. Tea consumption did not influence traditional atherosclerotic risk factors, consistent with previous randomized studies.15 Indeed, endothelial function improved after short-term tea despite modestly increasing systolic blood pressure. This increase in blood pressure was not observed after long-term tea consumption and is likely due to caffeine, because oral caffeine had a similar effect.
Several lines of evidence suggest that the observed benefit relates to antioxidant flavonoids in tea. First, baseline dietary flavonoids correlated with flow-mediated dilation, as noted above. Second, tea consumption increased plasma catechins, consistent with prior data.16 Like other phenolic compounds, flavonoids can accumulate in tissues with long-term consumption33 and might favorably affect tissue redox status. Third, short-term tea consumption can increase plasma antioxidant activity in vivo in healthy volunteers,23 findings that are consistent with our data. However, tea flavonoids do not appear to affect ex vivo LDL oxidizability.15,16 Finally, there is experimental evidence that purified antioxidant flavonoids improve endothelium-derived NO bioactivity.17,18 Interestingly, this effect may be mediated by enhanced NO synthesis rather than by decreased superoxide-mediated NO breakdown,18 similar to our recent findings with ascorbic acid.34
Regarding potential limitations, one issue is the relevance of peripheral artery endothelial function for coronary events, although prior studies have shown a close relation between vasomotor responses in these 2 vascular beds.30 A second limitation is the use of water as placebo, preventing us from blinding volunteers to treatment. Unfortunately, prior experience indicates that it is not possible to produce a placebo beverage that convincingly tastes like tea but lacks tea flavonoids (personal communication, Douglas Balentine, Lipton, Inc, April 1998). Third, this study used caffeinated tea. Although caffeine alone had no short-term effect, we cannot exclude the possibility that caffeine influenced our long-term results. Importantly, studies of other caffeinated beverages have failed to demonstrate health benefits similar to those of tea.5 Fourth, it is conceivable that concurrent medications could have confounded our results, although the crossover design minimizes this concern. Fifth, it is noted that the 16 excluded volunteers were significantly more overweight than those included in the study, possibly reflecting the difficulty in imaging the brachial artery in these patients. Finally, although the benefit of tea was sustained for 4 weeks, the longer-term effects remain unknown.
The present study has important clinical implications. There is growing evidence that endothelial dysfunction is important for the pathogenesis and clinical expression of cardiovascular disease.19,21 Furthermore, recent studies support the concept that reversing endothelial dysfunction may partly explain the beneficial effects of other interventions proven to reduce cardiovascular risk, such as lipid lowering, ACE inhibitors, and exercise.35 The present study represents a relatively large and well-controlled study demonstrating a beneficial effect of short- and long-term black tea consumption on endothelial function. Thus, it provides a plausible biological mechanism in humans to explain the inverse relation between black tea consumption and cardiovascular disease.2–5 The findings fit well with the growing appreciation that diet and lifestyle modifications are important approaches to the prevention and treatment of atherosclerotic vascular disease. Further prospective, randomized studies of tea consumption appear warranted.
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Acknowledgments |
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This work was supported by a grant and tea supplies from the North America Tea Trade Health Research Association. Dr Duffy is supported by the National Health and Medical Research Council of Australia Neil Hamilton Fairley Fellowship (007139). Dr Gokce is supported by a National Research Service Award from the NIH (HL-0989401). Drs Keaney and Vita are recipients of Established Investigator Awards from the AHA. Lipton, Inc, used the leaf tea to prepare freeze-dried tea for long-term consumption and completed tea composition analyses. Plasma catechin analysis was completed by Beverly Warden, PhD, Analytical Sciences, Inc, Durham, NC. We are grateful for the superb technical assistance of Vadim Ivanov, Ross Germani, Michael Hollywood, Judson Russell, and Warren Shepherd. We are also extremely grateful for the advice and support provided by Douglas Balentine, PhD, of Lipton.
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Footnotes |
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Drs Vita and Frei serve as consultants to Lipton, Inc.
Received February 7, 2001; revision received April 18, 2001; accepted April 20, 2001.
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 M. Lorenz, K. Stangl, and V. Stangl Addition of milk prevents vascular protective effects of tea: reply Eur. Heart J., May 2, 2007; 28(10): 1266 - 1267. [Full Text] [PDF]
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 M. A. Potenza, F. L. Marasciulo, M. Tarquinio, E. Tiravanti, G. Colantuono, A. Federici, J.-a Kim, M. J. Quon, and M. Montagnani EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1378 - E1387. [Abstract] [Full Text] [PDF]
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 D. Taubert, R. Roesen, and E. Schomig Effect of Cocoa and Tea Intake on Blood Pressure: A Meta-analysis Arch Intern Med, April 9, 2007; 167(7): 626 - 634. [Abstract] [Full Text] [PDF]
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M. E. Widlansky, N. M. Hamburg, E. Anter, M. Holbrook, D. F. Kahn, J. G. Elliott, J. F. Keaney Jr., and J. A. Vita Acute EGCG Supplementation Reverses Endothelial Dysfunction in Patients with Coronary Artery Disease J. Am. Coll. Nutr., April 1, 2007; 26(2): 95 - 102. [Abstract] [Full Text] [PDF]
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L. J. Ignarro, M. L. Balestrieri, and C. Napoli Nutrition, physical activity, and cardiovascular disease: An update Cardiovasc Res, January 15, 2007; 73(2): 326 - 340. [Abstract] [Full Text] [PDF]
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V. Stangl, H. Dreger, K. Stangl, and M. Lorenz Molecular targets of tea polyphenols in the cardiovascular system Cardiovasc Res, January 15, 2007; 73(2): 348 - 358. [Abstract] [Full Text] [PDF]
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F. de Nigris, S. Williams-Ignarro, V. Sica, L. O. Lerman, F. P. D'Armiento, R. E. Byrns, A. Casamassimi, D. Carpentiero, C. Schiano, D. Sumi, et al. Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis Cardiovasc Res, January 15, 2007; 73(2): 414 - 423. [Abstract] [Full Text] [PDF]
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C. Vlachopoulos, N. Alexopoulos, I. Dima, K. Aznaouridis, I. Andreadou, and C. Stefanadis Acute Effect of Black and Green Tea on Aortic Stiffness and Wave Reflections J. Am. Coll. Nutr., June 1, 2006; 25(3): 216 - 223. [Abstract] [Full Text] [PDF]
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C. Cabrera, R. Artacho, and R. Gimenez Beneficial effects of green tea--a review. J. Am. Coll. Nutr., April 1, 2006; 25(2): 79 - 99. [Abstract] [Full Text] [PDF]
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B. M Popkin, L. E Armstrong, G. M Bray, B. Caballero, B. Frei, and W. C Willett A new proposed guidance system for beverage consumption in the United States Am. J. Clinical Nutrition, March 1, 2006; 83(3): 529 - 542. [Abstract] [Full Text] [PDF]
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 H. Schroeter, C. Heiss, J. Balzer, P. Kleinbongard, C. L. Keen, N. K. Hollenberg, H. Sies, C. Kwik-Uribe, H. H. Schmitz, and M. Kelm (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans PNAS, January 24, 2006; 103(4): 1024 - 1029. [Abstract] [Full Text] [PDF]
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 C. Heiss, P. Kleinbongard, A. Dejam, S. Perre, H. Schroeter, H. Sies, and M. Kelm Acute Consumption of Flavanol-Rich Cocoa and the Reversal of Endothelial Dysfunction in Smokers J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1276 - 1283. [Abstract] [Full Text] [PDF]
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 D. Grassi, S. Necozione, C. Lippi, G. Croce, L. Valeri, P. Pasqualetti, G. Desideri, J. B. Blumberg, and C. Ferri Cocoa Reduces Blood Pressure and Insulin Resistance and Improves Endothelium-Dependent Vasodilation in Hypertensives Hypertension, August 1, 2005; 46(2): 398 - 405. [Abstract] [Full Text] [PDF]
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J. H.K. Vogel, S. F. Bolling, R. B. Costello, E. M. Guarneri, M. W. Krucoff, J. C. Longhurst, B. Olshansky, K. R. Pelletier, C. M. Tracy, R. A. Vogel, et al. Integrating Complementary Medicine Into Cardiovascular Medicine: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Writing Committee to Develop an Expert Consensus Document on Complementary and Integrative Medicine) J. Am. Coll. Cardiol., July 5, 2005; 46(1): 184 - 221. [Full Text] [PDF]
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 E. Anter, K. Chen, O. M. Shapira, R. H. Karas, and J. F. Keaney Jr p38 Mitogen-Activated Protein Kinase Activates eNOS in Endothelial Cells by an Estrogen Receptor {alpha}-Dependent Pathway in Response to Black Tea Polyphenols Circ. Res., May 27, 2005; 96(10): 1072 - 1078. [Abstract] [Full Text] [PDF]
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H. Sies, W. Stahl, and A. Sevanian Nutritional, Dietary and Postprandial Oxidative Stress J. Nutr., May 1, 2005; 135(5): 969 - 972. [Abstract] [Full Text] [PDF]
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F. de Nigris, S. Williams-Ignarro, L. O. Lerman, E. Crimi, C. Botti, G. Mansueto, F. P. D'Armiento, G. De Rosa, V. Sica, L. J. Ignarro, et al. Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress PNAS, March 29, 2005; 102(13): 4896 - 4901. [Abstract] [Full Text] [PDF]
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M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response Eur. Heart J., February 2, 2005; 26(4): 363 - 368. [Abstract] [Full Text] [PDF]
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G. Williamson and C. Manach Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies Am. J. Clinical Nutrition, January 1, 2005; 81(1): 243S - 255S. [Abstract] [Full Text] [PDF]
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J. A Vita Polyphenols and cardiovascular disease: effects on endothelial and platelet function Am. J. Clinical Nutrition, January 1, 2005; 81(1): 292S - 297S. [Abstract] [Full Text] [PDF]
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C. L Keen, R. R Holt, P. I Oteiza, C. G Fraga, and H. H Schmitz Cocoa antioxidants and cardiovascular health Am. J. Clinical Nutrition, January 1, 2005; 81(1): 298S - 303S. [Abstract] [Full Text] [PDF]
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H. Sies, T. Schewe, C. Heiss, and M. Kelm Cocoa polyphenols and inflammatory mediators Am. J. Clinical Nutrition, January 1, 2005; 81(1): 304S - 312S. [Abstract] [Full Text] [PDF]
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 N Nagaya, H Yamamoto, M Uematsu, T Itoh, K Nakagawa, T Miyazawa, K Kangawa, and K Miyatake Green tea reverses endothelial dysfunction in healthy smokers Heart, December 1, 2004; 90(12): 1485 - 1486. [Full Text] [PDF]
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E. Anter, S. R. Thomas, E. Schulz, O. M. Shapira, J. A. Vita, and J. F. Keaney Jr. Activation of Endothelial Nitric-oxide Synthase by the p38 MAPK in Response to Black Tea Polyphenols J. Biol. Chem., November 5, 2004; 279(45): 46637 - 46643. [Abstract] [Full Text] [PDF]
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 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
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Y.-C. Yang, F.-H. Lu, J.-S. Wu, C.-H. Wu, and C.-J. Chang The Protective Effect of Habitual Tea Consumption on Hypertension Arch Intern Med, July 26, 2004; 164(14): 1534 - 1540. [Abstract] [Full Text] [PDF]
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L. I. Mennen, D. Sapinho, A. de Bree, N. Arnault, S. Bertrais, P. Galan, and S. Hercberg Consumption of Foods Rich in Flavonoids Is Related to a Decreased Cardiovascular Risk in Apparently Healthy French Women J. Nutr., April 1, 2004; 134(4): 923 - 926. [Abstract] [Full Text] [PDF]
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M. Lorenz, S. Wessler, E. Follmann, W. Michaelis, T. Dusterhoft, G. Baumann, K. Stangl, and V. Stangl A Constituent of Green Tea, Epigallocatechin-3-gallate, Activates Endothelial Nitric Oxide Synthase by a Phosphatidylinositol-3-OH-kinase-, cAMP-dependent Protein Kinase-, and Akt-dependent Pathway and Leads to Endothelial-dependent Vasorelaxation J. Biol. Chem., February 13, 2004; 279(7): 6190 - 6195. [Abstract] [Full Text] [PDF]
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 J. H. O'Keefe Jr and L. Cordain Cardiovascular Disease Resulting From a Diet and Lifestyle at Odds With Our Paleolithic Genome: How to Become a 21st-Century Hunter-Gatherer Mayo Clin. Proc., January 1, 2004; 79(1): 101 - 108. [Abstract] [PDF]
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M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita The clinical implications of endothelial dysfunction J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160. [Abstract] [Full Text] [PDF]
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A. Rietveld and S. Wiseman Antioxidant Effects of Tea: Evidence from Human Clinical Trials J. Nutr., October 1, 2003; 133(10): 3285S - 3292. [Abstract] [Full Text] [PDF]
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J. A. Vita Tea Consumption and Cardiovascular Disease: Effects on Endothelial Function J. Nutr., October 1, 2003; 133(10): 3293S - 3297. [Abstract] [Full Text] [PDF]
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J. M Hodgson, A. Devine, I. B. Puddey, S. Y. Chan, L. J. Beilin, and R. L. Prince Tea Intake Is Inversely Related to Blood Pressure in Older Women J. Nutr., September 1, 2003; 133(9): 2883 - 2886. [Abstract] [Full Text] [PDF]
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M. E. Widlansky, D. T. Price, N. Gokce, R. T. Eberhardt, S. J. Duffy, M. Holbrook, C. Maxwell, J. Palmisano, J. F. Keaney Jr, J. D. Morrow, et al. Short- and Long-Term COX-2 Inhibition Reverses Endothelial Dysfunction in Patients With Hypertension Hypertension, September 1, 2003; 42(3): 310 - 315. [Abstract] [Full Text] [PDF]
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 H. D Sesso, R. S Paffenbarger Jr, Y. Oguma, and I-M. Lee Lack of association between tea and cardiovascular disease in college alumni Int. J. Epidemiol., August 1, 2003; 32(4): 527 - 533. [Abstract] [Full Text] [PDF]
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S. Amar, N. Gokce, S. Morgan, M. Loukideli, T. E. Van Dyke, and J. A. Vita Periodontal Disease Is Associated With Brachial Artery Endothelial Dysfunction and Systemic Inflammation Arterioscler. Thromb. Vasc. Biol., July 1, 2003; 23(7): 1245 - 1249. [Abstract] [Full Text] [PDF]
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D. J. Maron, G. P. Lu, N. S. Cai, Z. G. Wu, Y. H. Li, H. Chen, J. Q. Zhu, X. J. Jin, B. C. Wouters, and J. Zhao Cholesterol-Lowering Effect of a Theaflavin-Enriched Green Tea Extract: A Randomized Controlled Trial Arch Intern Med, June 23, 2003; 163(12): 1448 - 1453. [Abstract] [Full Text] [PDF]
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J. M Hodgson, V. Burke, L. J Beilin, K. D Croft, and I. B Puddey Can black tea influence plasma total homocysteine concentrations? Am. J. Clinical Nutrition, April 1, 2003; 77(4): 907 - 911. [Abstract] [Full Text] [PDF]
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 T.K. Mao, J. Van De Water, C.L. Keen, H.H. Schmitz, and M.E. Gershwin Cocoa Flavonols and Procyanidins Promote Transforming Growth Factor-{beta}1 Homeostasis in Peripheral Blood Mononuclear Cells Experimental Biology and Medicine, January 1, 2003; 228(1): 93 - 99. [Abstract] [Full Text] [PDF]
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N. Gokce, M. Holbrook, L. M. Hunter, J. Palmisano, E. Vigalok, J. F. Keaney Jr, and J. A. Vita Acute effects of vasoactive drug treatment on brachial artery reactivity J. Am. Coll. Cardiol., August 21, 2002; 40(4): 761 - 765. [Abstract] [Full Text] [PDF]
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K. J. Mukamal, M. Maclure, J. E. Muller, J. B. Sherwood, and M. A. Mittleman Tea Consumption and Mortality After Acute Myocardial Infarction Circulation, May 28, 2002; 105(21): 2476 - 2481. [Abstract] [Full Text] [PDF]
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J. M Geleijnse, L. J Launer, D. A. van der Kuip, A. Hofman, and J. C. Witteman Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study Am. J. Clinical Nutrition, May 1, 2002; 75(5): 880 - 886. [Abstract] [Full Text] [PDF]
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Q. Y. Zhu, R. R. Holt, S. A. Lazarus, T. J. Orozco, and C. L. Keen Inhibitory Effects of Cocoa Flavanols and Procyanidin Oligomers on Free Radical-Induced Erythrocyte Hemolysis Experimental Biology and Medicine, May 1, 2002; 227(5): 321 - 329. [Abstract] [Full Text] [PDF]
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 R. R. Holt, D. D. Schramm, C. L. Keen, S. A. Lazarus, and H. H. Schmitz Chocolate Consumption and Platelet Function JAMA, May 1, 2002; 287(17): 2212 - 2213. [Full Text] [PDF]
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D. L. McKay and J. B. Blumberg The Role of Tea in Human Health: An Update J. Am. Coll. Nutr., February 1, 2002; 21(1): 1 - 13. [Abstract] [Full Text] [PDF]
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 R. J. Gordon A Toast to Tea Complementary Health Practice Review, December 1, 2001; 7(2): 83 - 84. [PDF]
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