Introduction to the proceedings of the Fifth International Scientific Symposium on Tea and Human Health1–4 Jeffrey B Blumberg account for w35% of their fresh weight. Most of the putative health benefits of tea have been attributed to the flavonoids in tea, although caffeine and L-theanine, a nonproteinic amino acid found only in tea, have also been suggested to contribute to some of these outcomes. Numerous research studies suggest that regular consumption of tea is associated with an array of health benefits, including impacts on chronic conditions such as cancer, diabetes, heart disease, neurodegenerative diseases, and obesity. However, in the context of research, descriptions of tea and its constituents can be confusing due to an absence of standards in reporting, different analytic methods for measuring flavonoids, and other limitations. In this supplement issue, Dwyer and Peterson (5) point out that tea and flavonoid research needs not only to be expanded but also enhanced through an improved quality of phytochemical databases and dietary assessment tools that more accurately and completely determine intake. Furthermore, they stress the need for a deeper understanding of the bioavailability and metabolism of tea to better inform the design of human studies. Future clinical studies should also incorporate validated intermediary biomarkers of chronic disease and establish a safety profile for tea consumption. General guidance is needed in this area so as to create more robust evidence on the relation between tea and tea bioactives and health. The absorption, metabolism, and excretion of tea polyphenols, particularly of tea flavanols, have been the subject of many studies. The flavanol monomers appear to be absorbed quickly, with maximal plasma concentrations achieved within a couple hours. Gallated and nongallated compounds are differentially metabolized, with limited additional conjugation or extensive methylation, sulfation, and/or glucuronidation, respectively. Gallate-ester flavanols are eliminated principally via the bile, 1
From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA. 2 Presented at the conference “Fifth International Scientific Symposium on Tea and Human Health,” held at the US Department of Agriculture, Washington, DC, 19 September 2012. 3 The Fifth International Scientific Symposium on Tea and Human Health was underwritten by the Tea Council of the USA. 4 Address correspondence to JB Blumberg, Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: jeffrey.blumberg@tufts. edu. First published online October 30, 2013; doi: 10.3945/ajcn.113.060186.
Am J Clin Nutr 2013;98(suppl):1607S–10S. Printed in USA. Ó 2013 American Society for Nutrition
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The Fifth International Scientific Symposium on Tea and Human Health was held 19 September 2012 at the US Department of Agriculture in Washington, DC. The conference was organized by a steering committee that included representatives from each of the symposium cosponsors: the American Cancer Society (Marji McCullough), the American College of Nutrition (Harry Preuss), the American Institute for Cancer Research (Susan Higginbotham), the American Medical Women’s Association (Mary Guinan), the American Society for Nutrition (Sharon Donovan), the Food and Agriculture Organization of the United Nations (Kaison Chang), and the Linus Pauling Institute (Balz Frei). Jonathan Hodgson (University of Western Australia) and Richard Draijer (Unilever Discover Vlaardingen) also served on the steering committee, which was chaired by Jeffrey Blumberg (Tufts University). The symposium was underwritten by the Tea Council of the USA, a nonprofit association of tea packers, importers, and allied industries within the United States and major tea-producing countries. Two primary objectives of the tea council are the dissemination of key scientific findings about tea via support of scientific meetings and working with health organizations to disseminate information about the potential health effects of tea consumption. A review of the proceedings of the first 4 symposia show both a broadening of the scope of research on tea and health and a deepening investigation into the molecular mechanisms that appear to underlie this relation (1–4). The instigation for this fifth symposium was based largely on the number of new studies, averaging 400– 500 per year, published since the fourth symposium was held in 2007. Tea is the most widely consumed beverage in the world after water and is a major source of dietary flavonoids. All tea is derived from Camellia sinensis, an evergreen shrub of the Theaceae family. Postharvest processing of white and green tea leaves includes drying (withering) and rolling (crushing). Further processing by partial or complete fermentation allows polyphenol oxidase to generate high-molecular-weight oligomers and polymers (theaflavins and thearubigins), which result in oolong and black tea, respectively. Although any C sinensis variety can be used to make any kind of tea, the varietal sinensis is most often used for green tea, whereas the varietal assamica is mostly used for black tea due to the taste characteristics arising from their different flavonoid composition profiles. Whereas tea leaves are composed of an array of compounds, including amino acids, cellulose, lignans, organic acids, mono- and polysaccharides, proteins, and xanthines, the flavonoids and related polyphenols
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of endothelial function associated with the risk of stroke and coronary heart disease (11). More detail about our knowledge of tea and its actions on the vascular endothelium, derived from intervention studies, is provided here by Grassi et al (12). Tea flavonoids appear to affect flow-mediated vasodilation through improving the bioactivity of the endothelium-derived vasodilator nitric oxide (NO) by enhancing NO synthesis and/or by decreasing superoxide-mediated NO breakdown. Because reduced NO bioavailability with endothelial dysfunction is considered one of the earliest steps in atherogenesis and is directly improved by tea intake, this relation provides an important (although not the only) mechanistic explanation for the association between tea and heart health and offers a relevant biomarker that should be included in more clinical studies. There is a considerable and still growing body of data derived from laboratory animal model and human intervention studies suggesting the cancer-preventive effects of tea and tea constituents. Both the polyphenolic components as well as caffeine have been implicated in cancer chemoprevention. Lambert (13) discusses a number of potential molecular mechanisms, including modulation of the cellular redox milieu, enhanced expression of phase II metabolic pathways, and inhibition of growth factor signaling, that may underlie an effect of tea alone or in combination with drugs on some forms of cancer. However, he notes the absence of much information regarding the biological activity of the metabolites of the tea polyphenols and recommends further in vitro and in vivo research on this issue. Yuan (14) extends the discussion of tea and cancer to the many observational studies that have been published from cohorts in Asia, North America, and Europe. A number of these studies have shown an inverse association between high consumption of green tea and risk of oral-digestive tract and lung cancers, with inconsistent results being obtained for breast, liver, and prostate cancers. Intervention studies undertaken with green tea extracts in patients with premalignant lesions in the oral cavity or prostate and at risk of liver cancer are showing promising results. Critical advances in examining the effect of tea on cancer outcomes require nutrigenomic approaches, such as have been conducted recently on the role of O-methylation by catechol-O-methyltransferase in the conjugation reaction of tea flavanols. Yuan (14) notes the discrepancy between the comparatively consistent and strong evidence of a chemopreventive action of tea in animal experiments and the results from observational data. This discordance may be due partly to the low doses of tea consumed in some cohorts compared with the high doses used in animal models but also to potential confounding by added ingredients and the effect modification of tea type and temperature as well as how the tea is assessed; other confounders include lifestyle factors such as smoking and alcohol consumption. Like Dwyer and Peterson (5), Yuan (14) recommends the development and validation of biomarkers of the uptake and metabolism of tea polyphenols to overcome some of the limitations in exposure measurement inherent in observational studies that rely on self-reports with common dietary assessment tools. Recent meta-analyses of clinical trials suggest that oral administration of tea flavanol-caffeine mixtures increases energy expenditure and fat oxidation and may be associated with modest reductions in BMI, body weight, and/or waist circumference (15– 17). Hursel and Westerterp-Plantenga (18) review these data in the context of goals for weight loss and weight maintenance.
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whereas the nongallated forms are excreted in the urine. In contrast, the bioavailability of tea flavonol glycosides have received limited attention, perhaps because of their relatively low concentration in tea; however, tea remains a major source of dietary flavonols, so more research on this topic is warranted. Clifford et al (6) describe the many variables that influence the bioavailability of flavonoids, including the food matrix, dose, and action of gut microbiota. They summarize some of the new insights into tea bioavailability achieved via technological advancements in analytic detection, including HPLC–mass spectrometryn and nuclear magnetic resonance, and propose that metabolites of tea polyphenols such as the valerolactones and urolithins as well as simple phenolic and aromatic acids may contribute importantly to the potential health benefits associated with tea consumption. Although most attention in this area has been focused on green tea, van Duynhoven et al (7) discuss the recently investigated bioconversion by gut microbiota of black tea polyphenols, particularly the dominant theaflavins and thearubigins, by using novel metabolomics platforms coupled with de novo identification. The use of nutrikinetic modeling is proving to be important in defining nutritional phenotypes related to gut microbial bioconversion capacity. The bioactivity of these circulating metabolites is still poorly understood but is now the subject of ongoing investigations. Research studies using in vitro and animal model approaches indicate a great many potential molecular targets for tea polyphenols and their metabolites that are related to the potential cardiovascular, chemopreventive, and neuroprotective effects of tea. Lorenz (8) presents evidence that green tea catechins and black tea theaflavins and thearubigins can each contribute to the effects of tea in vitro via modulation of protein kinases, growth factors, and transcription factors. Some of this bioactivity may be mediated indirectly by modification of intracellular signaling by activation at cellular receptors or directly by action on intracellular targets. As with other polyphenols, it is also noted that the earlier emphasis on tea flavonoids acting as classical antioxidants to quench free radical reactions now appears to be misdirected. Further research is still necessary to elucidate the likely interactions and synergies that exist between different tea polyphenols and other tea bioactives such as caffeine and theobromine. Of all the available evidence on its potential benefits to human health, the effect of tea on many types of cardiovascular disease appears to be the most promising. The global burden of cardiovascular disease continues to be the number one cause of death, with predictions that this mortality figure will increase to 23.3 million by 2030 (9). The westernization and urbanization of countries such as China and India are projected to bear an increasing proportion of this burden. The principle that a modest but real beneficial effect on a common disease can have a substantial impact on public health may apply to tea. Arab et al (10) have undertaken a systematic literature review of the consistency and strength of the effect of tea on cardiovascular diseases based on published observational studies and meta-analyses regarding tea or tea flavonoids and cardiovascular disease risk. They summarize 5 meta-analyses and found a consistent, dose-dependent protective effect of tea consumption on stroke incidence and mortality. This important observation is consistent with another meta-analysis of controlled clinical trials on the effect of tea on flow-mediated vasodilation of the brachial artery, a measurement
INTRODUCTION
dyslipidemia, impaired immune responsiveness, and neurodegeneration. Despite the promise of this research showing an inverse association between tea and the risk of chronic disease, it is worth emphasizing that tea is also a healthy choice for hydration. Proper hydration is essential to the maintenance of a constant water and mineral balance. However, there is a common myth that because tea contains caffeine, a diuretic agent, it acts to increase fluid loss relative to the amount of fluid consumed in the tea, which contains .99% of water and can be a significant contributor to total water intake. Thus, it is important that clinical studies have now shown that tea is as good a source of hydration as water (and both contain no calories), except when daily consumption of caffeine exceeds 300 mg/d, an amount present in w8 cups (1600 mL) of tea (30, 31). Thus, tea should continue to be ranked highly as a beverage of choice for its hydration qualities as well as its phytochemical profile as suggested by Popkin et al (32) and the current dietary guidelines in Germany and Japan that explicitly recommend tea for hydration. JBB received an honorarium and travel support from the Tea Council of the USA for speaking at the Fifth International Scientific Symposium on Tea and Human Health and for editorial services provided for this supplement publication. He declared no competing financial interests.
REFERENCES 1. Weisburger JH, ed. Proceedings of the First International Symposium on Tea and Health. Prev Med 1992;21:503–53. Available from: http:// www.sciencedirect.com/science/journal/00917435/21/4. 2. Weisburger JH, ed. Second International Symposium on Tea and Human Health. Proc Soc Exp Biol Med 1999;220:193–4. 3. Blumberg J, Katan M, eds. Third International Scientific Symposium on Tea and Human Health: role of flavonoids in the diet. J Nutr 2003; 133(suppl):3244S–6S. 4. Arab L, Blumberg JB, eds. Fourth International Scientific Symposium on Tea and Human Health: role of flavonoids in the diet. J Nutr 2008; 138(suppl):1526S–8S. 5. Dwyer JT, Peterson J. Tea and flavonoids: where we are, where to go next. Am J Clin Nutr 2013;98(suppl):1611S–8S. 6. Clifford MN, van der Hooft JJJ, Crozier A. Human studies on the absorption, distribution, metabolism, and excretion of tea polyphenols. Am J Clin Nutr 2013;98(suppl):1619S–30S. 7. van Duynhoven J, Vaughan EE, van Dorsten F, Gomez-Roldan V, de Vos R, Vervoort J, van der Hooft JJJ, Roger L, Draijer R, Jacobs DM. Interactions of black tea polyphenols with human gut microbiota: implications for gut and cardiovascular health. Am J Clin Nutr 2013;98 (suppl):1631S–41S. 8. Lorenz M. Cellular targets for the beneficial actions of tea polyphenols. Am J Clin Nutr 2013;98(suppl):1642S–50S. 9. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:e442. 10. Arab L, Khan F, Lam H. Tea consumption and cardiovascular disease risk. Am J Clin Nutr 2013;98(suppl):1651S–9S. 11. Ras TR, Zock PL, Draijer R. Tea consumption enhances endothelialdependent vasodilation: a meta-analysis. PLoS ONE. 2011;6:e16974. 12. Grassi D, Desideri G, Di Giosia P, De Feo M, Fellini E, Cheli P, Ferri L, Ferri C. Tea, flavonoids, and cardiovascular health: endothelial protection. Am J Clin Nutr 2013;98(suppl):1660S–6S. 13. Lambert JD. Does tea prevent cancer? Evidence from laboratory and human intervention studies. Am J Clin Nutr 2013;98(suppl):1667S–75S. 14. Yuan J-M. Cancer prevention by green tea: evidence from epidemiologic studies. Am J Clin Nutr 2013;98(suppl):1676S–81S. 15. Phung OJ, Baker WL, Matthews LJ, Lanosa M, Thorne A, Coleman CI. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. Am J Clin Nutr 2010;91:73–81. 16. Hursel R, Viechtbauer W, Dulloo AG, Tremblay A, Tappy L, Rumpler W, Westerterp-Plantenga MS. The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis. Obes Rev 2011; 12:e573–81.
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The modest effect size of tea on these outcomes suggests that it might have the greatest impact in helping to support weight maintenance with (like all such efforts) the full compliance of the individual to other aspects of diet and physical activity. In this regard, further research is warranted on those factors that may modify the effect of tea on energy metabolism, eg, habitual caffeine intake, food matrices, flavanol dose and profile, and ethnicity and other genetic predispositions. However, it is worth noting that the research that indicates tea flavanols in combination with caffeine may improve central adiposity also suggests a benefit on additional components of the metabolic syndrome, including dyslipidemia, insulin, and glucose (19–22). With the aging of the world’s population, the prevalence of osteoporosis has become a major health issue. Shen et al (23) summarize the evidence from in vitro and animal model studies showing that green tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis via antiinflammatory and antioxidant pathways and thereby promote greater bone mass and bone strength. Whereas animal studies have largely tested long bones rather than hip and spine, the sites of frequent fractures in humans, evidence from observational studies of tea and osteoporosis is consistent with the experimental evidence, albeit quite limited. However, recent results from a randomized clinical trial are promising in showing that green tea polyphenols may favor bone formation, increase muscle strength, and reduce oxidative stress in osteopenic women, particularly when combined with exercise. Observational evidence continues to emerge that tea may act to improve cognitive function (24, 25), and a recent clinical trial using fMRI shows that green tea increases brain activation in a key area that mediates working memory processing (26). The literature suggesting that tea polyphenols may be useful for the prevention or treatment of various neurodegenerative diseases has also stimulated experimental work in mice, which shows that the tea flavanol (2)-epigallocatechin-3-gallate promotes adult neurogenesis in hippocampal cells in vitro and improves spatial cognition in vivo via sonic hedgehog pathway activation (27). Although tea drinking has long been associated with positive psychological effects on alertness, mood, and stress, until recently few scientific studies have directly addressed these potential benefits. Eino¨ther and Martens (28) review the evidence indicating that tea, through its content of caffeine and L-theanine, can significantly, albeit modestly, affect attention and mood. They note several studies showing a consistent effect of tea on alertness, attention, and arousal, but found little research examining outcomes such as hedonic tone and relaxation. It is worth noting that the psychological benefits of tea and tea ingredients have now been extended to some real-life areas such as driving, creativity, and work performance. Based on archeological evidence, the consumption of tea appears to have first occurred w5000 y ago during the Paleolithic period, predating the legend of its discovery by the mythical Chinese emperor, Shen Nung. However, it is clear that by the fourth century, tea was an important part of Chinese life because of its perceived value as a medicine for the treatment of a variety of ailments, including poor vision, fatigue, rheumatic pain, and problems of the kidneys and lungs (29). Modern research has suggested an array of other potential benefits of tea that were not covered at the Fifth International Scientific Symposium on Tea and Health, including antibacterial and antiviral activity, arthritis, dental caries, type 2 diabetes mellitus,
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BLUMBERG 25. Ng TP, Feng L, Niti M, Kua EH, Yap KB. Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr 2008;88:224–31. 26. Borgwardt S, Harmmann F, Scheffler K, Kreuter M, Drewe J, Beglinger C. Neural effects of green tea extract on dorsolateral prefrontal cortex. Eur J Clin Nutr 2012;66:1187–92. 27. Wang Y, Li M, Xu X, Song M, Tao H, Bai Y. Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Mol Nutr Food Res 2012;56:1292–303. 28. Eino¨ther SJ, Martens VE. Acute effects of tea consumption on attention and mood. Am J Clin Nutr 2013;98(suppl):1700S–8S. 29. MacFarlane A, MacFarlane I. The empire of tea: the remarkable history of the plant that took over the world. Woodstock, NY: The Overlook Press, 2003. 30. Chang C-Q, Chen Y-B, Chen Z-M, Zhang L-T. Effects of acarbohydrate-electrolyte beverage on blood viscosity after dehydration in healthy adults. Chin Med J (Engl) 2010;123:3220–5. 31. Ruxton CH, Hart VA. Black tea is not significantly different from water in the maintenance of normal hydration in human subjects: results from a randomised controlled trial. Br J Nutr 2011;106:588–95. 32. Popkin BM, Armstrong LE, Bray GM, Caballero B, Frei B, Willett WC. A new proposed guidance system for beverage consumption in the United States. Am J Clin Nutr 2006;83:529–42.
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17. Jurgens TM, Whelan AM, Killian L, Doucette S, Kirk S, Foy E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane Database Syst Rev 2012;12:CD008650. 18. Hursel R, Westerterp-Plantenga MS. Catechin- and caffeine-rich teas for control of body weight in humans. Am J Clin Nutr 2013;98(suppl): 1682S–93S. 19. Zheng X-X, Xu Y-L, Li S-H, Hui R, Huang X-H. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. Am J Clin Nutr 2011;94:601–10. 20. Vernarelli JA, Lambert JD. Tea consumption is inversely associated with weight status and other markers for metabolic syndrome in US adults. Eur J Nutr 2013;52:1039–48. 21. Vieira Senger AE, Schwanke CHA, Gomes I, Balle Gottlieb MG. Effect of green tea (Camellia sinensis) consumption on the components of metabolic syndrome in elderly. J Nutr Health Aging 2012;16:738–42. 22. Liu K, Zhou R, Wang B, Chen K, Shi L-Y, Zhu J-D, Mi M-T. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr 2013;98:340–8. 23. Shen C-L, Chyu M-C, Wang J-S. Tea and bone health: steps forward in translational nutrition. Am J Clin Nutr 2013;98(suppl):1694S–9S. 24. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr 2006;83:355–61.
From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA. 2 Presented at the conference “Fifth International Scientific Symposium on Tea and Human Health,” held at the US Department of Agriculture, Washington, DC, 19 September 2012. 3 The Fifth International Scientific Symposium on Tea and Human Health was underwritten by the Tea Council of the USA. 4 Address correspondence to JB Blumberg, Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: jeffrey.blumberg@tufts. edu. First published online October 30, 2013; doi: 10.3945/ajcn.113.060186.
Am J Clin Nutr 2013;98(suppl):1607S–10S. Printed in USA. Ó 2013 American Society for Nutrition
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The Fifth International Scientific Symposium on Tea and Human Health was held 19 September 2012 at the US Department of Agriculture in Washington, DC. The conference was organized by a steering committee that included representatives from each of the symposium cosponsors: the American Cancer Society (Marji McCullough), the American College of Nutrition (Harry Preuss), the American Institute for Cancer Research (Susan Higginbotham), the American Medical Women’s Association (Mary Guinan), the American Society for Nutrition (Sharon Donovan), the Food and Agriculture Organization of the United Nations (Kaison Chang), and the Linus Pauling Institute (Balz Frei). Jonathan Hodgson (University of Western Australia) and Richard Draijer (Unilever Discover Vlaardingen) also served on the steering committee, which was chaired by Jeffrey Blumberg (Tufts University). The symposium was underwritten by the Tea Council of the USA, a nonprofit association of tea packers, importers, and allied industries within the United States and major tea-producing countries. Two primary objectives of the tea council are the dissemination of key scientific findings about tea via support of scientific meetings and working with health organizations to disseminate information about the potential health effects of tea consumption. A review of the proceedings of the first 4 symposia show both a broadening of the scope of research on tea and health and a deepening investigation into the molecular mechanisms that appear to underlie this relation (1–4). The instigation for this fifth symposium was based largely on the number of new studies, averaging 400– 500 per year, published since the fourth symposium was held in 2007. Tea is the most widely consumed beverage in the world after water and is a major source of dietary flavonoids. All tea is derived from Camellia sinensis, an evergreen shrub of the Theaceae family. Postharvest processing of white and green tea leaves includes drying (withering) and rolling (crushing). Further processing by partial or complete fermentation allows polyphenol oxidase to generate high-molecular-weight oligomers and polymers (theaflavins and thearubigins), which result in oolong and black tea, respectively. Although any C sinensis variety can be used to make any kind of tea, the varietal sinensis is most often used for green tea, whereas the varietal assamica is mostly used for black tea due to the taste characteristics arising from their different flavonoid composition profiles. Whereas tea leaves are composed of an array of compounds, including amino acids, cellulose, lignans, organic acids, mono- and polysaccharides, proteins, and xanthines, the flavonoids and related polyphenols
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of endothelial function associated with the risk of stroke and coronary heart disease (11). More detail about our knowledge of tea and its actions on the vascular endothelium, derived from intervention studies, is provided here by Grassi et al (12). Tea flavonoids appear to affect flow-mediated vasodilation through improving the bioactivity of the endothelium-derived vasodilator nitric oxide (NO) by enhancing NO synthesis and/or by decreasing superoxide-mediated NO breakdown. Because reduced NO bioavailability with endothelial dysfunction is considered one of the earliest steps in atherogenesis and is directly improved by tea intake, this relation provides an important (although not the only) mechanistic explanation for the association between tea and heart health and offers a relevant biomarker that should be included in more clinical studies. There is a considerable and still growing body of data derived from laboratory animal model and human intervention studies suggesting the cancer-preventive effects of tea and tea constituents. Both the polyphenolic components as well as caffeine have been implicated in cancer chemoprevention. Lambert (13) discusses a number of potential molecular mechanisms, including modulation of the cellular redox milieu, enhanced expression of phase II metabolic pathways, and inhibition of growth factor signaling, that may underlie an effect of tea alone or in combination with drugs on some forms of cancer. However, he notes the absence of much information regarding the biological activity of the metabolites of the tea polyphenols and recommends further in vitro and in vivo research on this issue. Yuan (14) extends the discussion of tea and cancer to the many observational studies that have been published from cohorts in Asia, North America, and Europe. A number of these studies have shown an inverse association between high consumption of green tea and risk of oral-digestive tract and lung cancers, with inconsistent results being obtained for breast, liver, and prostate cancers. Intervention studies undertaken with green tea extracts in patients with premalignant lesions in the oral cavity or prostate and at risk of liver cancer are showing promising results. Critical advances in examining the effect of tea on cancer outcomes require nutrigenomic approaches, such as have been conducted recently on the role of O-methylation by catechol-O-methyltransferase in the conjugation reaction of tea flavanols. Yuan (14) notes the discrepancy between the comparatively consistent and strong evidence of a chemopreventive action of tea in animal experiments and the results from observational data. This discordance may be due partly to the low doses of tea consumed in some cohorts compared with the high doses used in animal models but also to potential confounding by added ingredients and the effect modification of tea type and temperature as well as how the tea is assessed; other confounders include lifestyle factors such as smoking and alcohol consumption. Like Dwyer and Peterson (5), Yuan (14) recommends the development and validation of biomarkers of the uptake and metabolism of tea polyphenols to overcome some of the limitations in exposure measurement inherent in observational studies that rely on self-reports with common dietary assessment tools. Recent meta-analyses of clinical trials suggest that oral administration of tea flavanol-caffeine mixtures increases energy expenditure and fat oxidation and may be associated with modest reductions in BMI, body weight, and/or waist circumference (15– 17). Hursel and Westerterp-Plantenga (18) review these data in the context of goals for weight loss and weight maintenance.
Downloaded from ajcn.nutrition.org at UNIVERSITY OF ILLINOIS URBANA on March 10, 2015
whereas the nongallated forms are excreted in the urine. In contrast, the bioavailability of tea flavonol glycosides have received limited attention, perhaps because of their relatively low concentration in tea; however, tea remains a major source of dietary flavonols, so more research on this topic is warranted. Clifford et al (6) describe the many variables that influence the bioavailability of flavonoids, including the food matrix, dose, and action of gut microbiota. They summarize some of the new insights into tea bioavailability achieved via technological advancements in analytic detection, including HPLC–mass spectrometryn and nuclear magnetic resonance, and propose that metabolites of tea polyphenols such as the valerolactones and urolithins as well as simple phenolic and aromatic acids may contribute importantly to the potential health benefits associated with tea consumption. Although most attention in this area has been focused on green tea, van Duynhoven et al (7) discuss the recently investigated bioconversion by gut microbiota of black tea polyphenols, particularly the dominant theaflavins and thearubigins, by using novel metabolomics platforms coupled with de novo identification. The use of nutrikinetic modeling is proving to be important in defining nutritional phenotypes related to gut microbial bioconversion capacity. The bioactivity of these circulating metabolites is still poorly understood but is now the subject of ongoing investigations. Research studies using in vitro and animal model approaches indicate a great many potential molecular targets for tea polyphenols and their metabolites that are related to the potential cardiovascular, chemopreventive, and neuroprotective effects of tea. Lorenz (8) presents evidence that green tea catechins and black tea theaflavins and thearubigins can each contribute to the effects of tea in vitro via modulation of protein kinases, growth factors, and transcription factors. Some of this bioactivity may be mediated indirectly by modification of intracellular signaling by activation at cellular receptors or directly by action on intracellular targets. As with other polyphenols, it is also noted that the earlier emphasis on tea flavonoids acting as classical antioxidants to quench free radical reactions now appears to be misdirected. Further research is still necessary to elucidate the likely interactions and synergies that exist between different tea polyphenols and other tea bioactives such as caffeine and theobromine. Of all the available evidence on its potential benefits to human health, the effect of tea on many types of cardiovascular disease appears to be the most promising. The global burden of cardiovascular disease continues to be the number one cause of death, with predictions that this mortality figure will increase to 23.3 million by 2030 (9). The westernization and urbanization of countries such as China and India are projected to bear an increasing proportion of this burden. The principle that a modest but real beneficial effect on a common disease can have a substantial impact on public health may apply to tea. Arab et al (10) have undertaken a systematic literature review of the consistency and strength of the effect of tea on cardiovascular diseases based on published observational studies and meta-analyses regarding tea or tea flavonoids and cardiovascular disease risk. They summarize 5 meta-analyses and found a consistent, dose-dependent protective effect of tea consumption on stroke incidence and mortality. This important observation is consistent with another meta-analysis of controlled clinical trials on the effect of tea on flow-mediated vasodilation of the brachial artery, a measurement
INTRODUCTION
dyslipidemia, impaired immune responsiveness, and neurodegeneration. Despite the promise of this research showing an inverse association between tea and the risk of chronic disease, it is worth emphasizing that tea is also a healthy choice for hydration. Proper hydration is essential to the maintenance of a constant water and mineral balance. However, there is a common myth that because tea contains caffeine, a diuretic agent, it acts to increase fluid loss relative to the amount of fluid consumed in the tea, which contains .99% of water and can be a significant contributor to total water intake. Thus, it is important that clinical studies have now shown that tea is as good a source of hydration as water (and both contain no calories), except when daily consumption of caffeine exceeds 300 mg/d, an amount present in w8 cups (1600 mL) of tea (30, 31). Thus, tea should continue to be ranked highly as a beverage of choice for its hydration qualities as well as its phytochemical profile as suggested by Popkin et al (32) and the current dietary guidelines in Germany and Japan that explicitly recommend tea for hydration. JBB received an honorarium and travel support from the Tea Council of the USA for speaking at the Fifth International Scientific Symposium on Tea and Human Health and for editorial services provided for this supplement publication. He declared no competing financial interests.
REFERENCES 1. Weisburger JH, ed. Proceedings of the First International Symposium on Tea and Health. Prev Med 1992;21:503–53. Available from: http:// www.sciencedirect.com/science/journal/00917435/21/4. 2. Weisburger JH, ed. Second International Symposium on Tea and Human Health. Proc Soc Exp Biol Med 1999;220:193–4. 3. Blumberg J, Katan M, eds. Third International Scientific Symposium on Tea and Human Health: role of flavonoids in the diet. J Nutr 2003; 133(suppl):3244S–6S. 4. Arab L, Blumberg JB, eds. Fourth International Scientific Symposium on Tea and Human Health: role of flavonoids in the diet. J Nutr 2008; 138(suppl):1526S–8S. 5. Dwyer JT, Peterson J. Tea and flavonoids: where we are, where to go next. Am J Clin Nutr 2013;98(suppl):1611S–8S. 6. Clifford MN, van der Hooft JJJ, Crozier A. Human studies on the absorption, distribution, metabolism, and excretion of tea polyphenols. Am J Clin Nutr 2013;98(suppl):1619S–30S. 7. van Duynhoven J, Vaughan EE, van Dorsten F, Gomez-Roldan V, de Vos R, Vervoort J, van der Hooft JJJ, Roger L, Draijer R, Jacobs DM. Interactions of black tea polyphenols with human gut microbiota: implications for gut and cardiovascular health. Am J Clin Nutr 2013;98 (suppl):1631S–41S. 8. Lorenz M. Cellular targets for the beneficial actions of tea polyphenols. Am J Clin Nutr 2013;98(suppl):1642S–50S. 9. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006;3:e442. 10. Arab L, Khan F, Lam H. Tea consumption and cardiovascular disease risk. Am J Clin Nutr 2013;98(suppl):1651S–9S. 11. Ras TR, Zock PL, Draijer R. Tea consumption enhances endothelialdependent vasodilation: a meta-analysis. PLoS ONE. 2011;6:e16974. 12. Grassi D, Desideri G, Di Giosia P, De Feo M, Fellini E, Cheli P, Ferri L, Ferri C. Tea, flavonoids, and cardiovascular health: endothelial protection. Am J Clin Nutr 2013;98(suppl):1660S–6S. 13. Lambert JD. Does tea prevent cancer? Evidence from laboratory and human intervention studies. Am J Clin Nutr 2013;98(suppl):1667S–75S. 14. Yuan J-M. Cancer prevention by green tea: evidence from epidemiologic studies. Am J Clin Nutr 2013;98(suppl):1676S–81S. 15. Phung OJ, Baker WL, Matthews LJ, Lanosa M, Thorne A, Coleman CI. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. Am J Clin Nutr 2010;91:73–81. 16. Hursel R, Viechtbauer W, Dulloo AG, Tremblay A, Tappy L, Rumpler W, Westerterp-Plantenga MS. The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis. Obes Rev 2011; 12:e573–81.
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The modest effect size of tea on these outcomes suggests that it might have the greatest impact in helping to support weight maintenance with (like all such efforts) the full compliance of the individual to other aspects of diet and physical activity. In this regard, further research is warranted on those factors that may modify the effect of tea on energy metabolism, eg, habitual caffeine intake, food matrices, flavanol dose and profile, and ethnicity and other genetic predispositions. However, it is worth noting that the research that indicates tea flavanols in combination with caffeine may improve central adiposity also suggests a benefit on additional components of the metabolic syndrome, including dyslipidemia, insulin, and glucose (19–22). With the aging of the world’s population, the prevalence of osteoporosis has become a major health issue. Shen et al (23) summarize the evidence from in vitro and animal model studies showing that green tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis via antiinflammatory and antioxidant pathways and thereby promote greater bone mass and bone strength. Whereas animal studies have largely tested long bones rather than hip and spine, the sites of frequent fractures in humans, evidence from observational studies of tea and osteoporosis is consistent with the experimental evidence, albeit quite limited. However, recent results from a randomized clinical trial are promising in showing that green tea polyphenols may favor bone formation, increase muscle strength, and reduce oxidative stress in osteopenic women, particularly when combined with exercise. Observational evidence continues to emerge that tea may act to improve cognitive function (24, 25), and a recent clinical trial using fMRI shows that green tea increases brain activation in a key area that mediates working memory processing (26). The literature suggesting that tea polyphenols may be useful for the prevention or treatment of various neurodegenerative diseases has also stimulated experimental work in mice, which shows that the tea flavanol (2)-epigallocatechin-3-gallate promotes adult neurogenesis in hippocampal cells in vitro and improves spatial cognition in vivo via sonic hedgehog pathway activation (27). Although tea drinking has long been associated with positive psychological effects on alertness, mood, and stress, until recently few scientific studies have directly addressed these potential benefits. Eino¨ther and Martens (28) review the evidence indicating that tea, through its content of caffeine and L-theanine, can significantly, albeit modestly, affect attention and mood. They note several studies showing a consistent effect of tea on alertness, attention, and arousal, but found little research examining outcomes such as hedonic tone and relaxation. It is worth noting that the psychological benefits of tea and tea ingredients have now been extended to some real-life areas such as driving, creativity, and work performance. Based on archeological evidence, the consumption of tea appears to have first occurred w5000 y ago during the Paleolithic period, predating the legend of its discovery by the mythical Chinese emperor, Shen Nung. However, it is clear that by the fourth century, tea was an important part of Chinese life because of its perceived value as a medicine for the treatment of a variety of ailments, including poor vision, fatigue, rheumatic pain, and problems of the kidneys and lungs (29). Modern research has suggested an array of other potential benefits of tea that were not covered at the Fifth International Scientific Symposium on Tea and Health, including antibacterial and antiviral activity, arthritis, dental caries, type 2 diabetes mellitus,
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BLUMBERG 25. Ng TP, Feng L, Niti M, Kua EH, Yap KB. Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr 2008;88:224–31. 26. Borgwardt S, Harmmann F, Scheffler K, Kreuter M, Drewe J, Beglinger C. Neural effects of green tea extract on dorsolateral prefrontal cortex. Eur J Clin Nutr 2012;66:1187–92. 27. Wang Y, Li M, Xu X, Song M, Tao H, Bai Y. Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Mol Nutr Food Res 2012;56:1292–303. 28. Eino¨ther SJ, Martens VE. Acute effects of tea consumption on attention and mood. Am J Clin Nutr 2013;98(suppl):1700S–8S. 29. MacFarlane A, MacFarlane I. The empire of tea: the remarkable history of the plant that took over the world. Woodstock, NY: The Overlook Press, 2003. 30. Chang C-Q, Chen Y-B, Chen Z-M, Zhang L-T. Effects of acarbohydrate-electrolyte beverage on blood viscosity after dehydration in healthy adults. Chin Med J (Engl) 2010;123:3220–5. 31. Ruxton CH, Hart VA. Black tea is not significantly different from water in the maintenance of normal hydration in human subjects: results from a randomised controlled trial. Br J Nutr 2011;106:588–95. 32. Popkin BM, Armstrong LE, Bray GM, Caballero B, Frei B, Willett WC. A new proposed guidance system for beverage consumption in the United States. Am J Clin Nutr 2006;83:529–42.
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17. Jurgens TM, Whelan AM, Killian L, Doucette S, Kirk S, Foy E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane Database Syst Rev 2012;12:CD008650. 18. Hursel R, Westerterp-Plantenga MS. Catechin- and caffeine-rich teas for control of body weight in humans. Am J Clin Nutr 2013;98(suppl): 1682S–93S. 19. Zheng X-X, Xu Y-L, Li S-H, Hui R, Huang X-H. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. Am J Clin Nutr 2011;94:601–10. 20. Vernarelli JA, Lambert JD. Tea consumption is inversely associated with weight status and other markers for metabolic syndrome in US adults. Eur J Nutr 2013;52:1039–48. 21. Vieira Senger AE, Schwanke CHA, Gomes I, Balle Gottlieb MG. Effect of green tea (Camellia sinensis) consumption on the components of metabolic syndrome in elderly. J Nutr Health Aging 2012;16:738–42. 22. Liu K, Zhou R, Wang B, Chen K, Shi L-Y, Zhu J-D, Mi M-T. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr 2013;98:340–8. 23. Shen C-L, Chyu M-C, Wang J-S. Tea and bone health: steps forward in translational nutrition. Am J Clin Nutr 2013;98(suppl):1694S–9S. 24. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr 2006;83:355–61.
