1 Efficacy of Tea in Human Health Isao Tomita* University of Shizuoka, Shizuoka, Japan Abstract Recent scientific findings on the effects of teaCamellia ( sinensis) on human health are reviewed. Some mechanistic explanations are discussed in relation to the special nature of (-)-epigallocatechin-3-gallate which works not only as an antioxidant but also as pro-oxidant. Though there are still some discrepan- cies between the results in animal models and those of epidemiological studies, the reasons will be uncovered in the near future. Keywords: antioxidant, chronic disease prevention, health effects, pro-oxidant, tea catechins 1.1 How the Physiological distribution which are soluble in hot water and show Effects Caused by Tea Drinking special physiological functions, such as Attracted Humans stimulation of the central nervous system. It is also well known that the tea leaves There are many legends whichfor told us to ex- contain a large amount of catechins (8–20% plain why the people in ancient China began of the dry weight) of which the major one is to drink tea. One of the stories told is about (-)-epigallocatechin-3-gallate (EGCG) (Fig.1.1). Wan Tu, the ancient Chinese emperor. He Tea catechins are oxidized to various was banished to a remote southern part of dimerization products, theaflavins, theasin- China (Yunnan province) due to his cruel ensins, and proantocyanidins and further to and tyrannizingNot governance. One day, he polymerization products, thearubigins, in the was sitting in the shade of a large bush in the process of tea preparation (Fig. 1.1). The taste area where Camellia sinensis grew and drank of tea is very unique: bitter, and astringent be- hot water. There, he found that some leaves cause of the presence of the above sub- were floating in the hot water. After he drank stances. It may be worth knowing that their the brewed tea with the leaves, he felt excited contents are quite different depending on and freed from fatigue (Wild, 1994). the species of Camellia leaves. The leaves of It is now known that the leaves of tea C. sinensis, Camellia taliensis, and Camellia (C. sinensis) contain caffeine (2–4% in dry irrawadiensis are all known to contain caf- leaves) and theobromine (~0.1%) both of feine, theobromine, and catechins, but other *[email protected] © CAB International 2017. Health Benefits of Green Tea: An Evidence-based Approach (eds Y. Hara et al.) 1 2 Isao Tomita OH OR 2 OH O HO O OH HO HO OH O OH OR 2 OH OH O OR2 OR2 Theaflavins OH OH HO O OH R O OH O OH 2 R O 2 OH R 1 O R HO O OH 1 OH O OH R1 OH OH HO OH OR OH 2 OH HO HO OH OH O HO O R1 R1 Catechins OR OR OH 2 2 OH OH OH HO O OR Theasinensins 1 OH OR O OH 2 Gal: C OH OH OH OH Assumed structure of thearubigins HO O R1 R =H or OH, R =H or Gal R , R = H: Epicatechin (EC) 1 2 1 2 OH OR R1 =H, R2 = Gal: Epicatechin gallate 2 (ECG) OH OH R1 =OH, R2 = H: Epigallocatechin HO O (EGC) R1 R =OH, R =Gal: Epigallocatechin gallate 1 2 OR (EGCG) 2 OH Proantocyanidins R1 =H or OH, R2 =H or Gal Fig. 1.1. Chemical structures of catechin and its related compounds. AIDS, acquired immune deficiency syndrome; RNS, reactive nitrogen species; ROS, reactivedistribution oxygen species; UV, ultraviolet. species such as Camellia furfuraceae and at this time that it was found that oxygen Camellia sasanqua have no such components radicals, such as the superoxide anion rad- – (Nagata and Sakai, 1984, 1985). Tea leaves ical (·O2 ) and the hydroxyl radical (·OH) are also known to contain the specialfor amino formed from “various stimulants”, could acid, theanine (0.5–3%) which is rarely found cause degenerative disease and even aging. in the plant kingdom. The term “oxidant stress” has become popu- lar, and it was believed to be a main cause in developing diseases such as cancer, athero- Not sclerosis, stroke, coronary heart disease, dia- 1.2 Strong Antioxidant Properties betes, and so on. The negative correlation of Tea and its Relation to Disease between the mortality of such chronic dis- Prevention eases and the consumption of common vegetables and fruits containing various fla- Since tea drinking has a long history of more vonoids as antioxidants seemed to accelerate than 3000 years, there have been many sci- this area of research (Hertog, 1996). entific research studies on the nature of the Cao et al. (1997) reported that tea has a components. These include isolation of the very strong antioxidant activity compared responsible substances for their characteristic with those of common vegetables in their taste, color, aroma, and physiological func- ORAC (oxygen radical absorbing capacity) tions. However, it was not until the late 20th assay. We also recognized that the tea extracts century that the research on tea as a “func- as well as its main constituent, EGCG and tional food (beverage)” was carried out. It was its metabolites, exerted strong antioxidant Efficacy ofTea in Human Health 3 activities in rats (Tomita et al., 1998). The most common and acceptable beverage to development of evaluating methods for avoid or decrease the risk of various diseases detection of antioxidant activities using (Fig. 1.2). TBARS (thiobarbituric acid reacting sub- However, now, we have to respond to the stances), 15-isoprostane F2t and 8-hydroxy- question: Why are the antioxidant effects of 2′- deoxyguanosine as biomarkers contrib- tea catechins and their related compounds uted greatly to this area of research. so powerful despite their limited absorption In another area of study at that time, a into the body? Their absorption is less than convenient method using microorganisms 2–3% of the intake, and the maximum con- such as Salmonella typhimurium TA and centration in blood is only 0.03–0.38 μmole/l Escherichia coli WP2 to detect mutagenic for EGCG (T1/2 = 2.5–5.1 h) and it is far too and antimutagenic substances was employed, low to expect direct antioxidant activity. and pioneering works on the antimutagenic properties of tea extracts were reported in 1984–1985 (Kuroda and Hara, 1999). Their anticarcinogenic effects in various assay 1.3 How Do Catechins Exert their systems at the stage of anti-initiation and Various Effects on Lifestyle-related anti-promotion were also demonstrated and Diseases? reported (Nakamura et al., 1997). General mechanisms of antimutagenesis and anticar- In order to discuss the mechanistic explan- cinogenesis were discussed in detail in the ation of tea catechins as the bio-antioxidant First International Conference which was in connection to disease prevention, recent held at the University of Kansas, USA in findings by several researchers on the effects October 1985. The presentation on the effects of tea catechins for cell signaling or gene of tea (extracts) seemed to attract successive expression must be considered. research in different and diverse fields. Tea It is known that tea catechins as well research done in the last 30 years has revealed as other flavonoids work as pro-oxidants that green as well as black tea will be thedistribution (not only as an antioxidants) under some Dental caries and halitosis Free radical induced peroxidation oxidative stress (ROS, RNS) Infection and food poisoning for UV- and chemical-induced mutagenesis (bacteria and toxins) Chemical-induced carcinogenesis (digestive tract, Intestinal bacteria colon, pancreas, mammary gland, lung, skin) Hyperlipidemia Liver damage (blood cholesterolNot level) Infection (influenza and AIDS virus) Atherosclerosis Platelet aggregation Brain and cognitive function Hypertension and stroke Diabetes mellitus (blood glucose level) Obesity (body and liver fat) Aging Allergy (Immunity) Metabolic syndrome Fig. 1.2. Possible effects of tea on health. AIDS, acquired immune deficiency syndrome; RNS, reactive nitrogen species; ROS, reactive oxygen species; UV, ultraviolet. 4 Isao Tomita experimental conditions and produce hydro- et al., 2013), the failure might be due not only gen peroxide (H2O2) in vitro and in vivo (Cao to the amount of EGCG consumed, but also to et al., 1997; Miura et al., 1998; Lambert and the amount of the substances that coexisted Elias, 2010). H2O2 is now known to be an in its dietary supplements. A recent report by important second messenger, transducing the Isomura et al. (2016), based on their work of oxidative signal into biological responses randomized controlled trials in humans (odds through post-translational protein modifica- ratio as the result of four principal reports of tion (Forman et al., 2004). In the case of excess 800–1600 mg of EGCG intake was 2.1), sug- H2O2 production, however, it might deteri- gests that liver-related adverse effects upon orate vascular functions, for example promot- intake of GTE or EGCG would be not so ser- ing vascular diseases through multiple path- ious as long as they are not consumed exces- ways (Shimokawa and Satoh, 2015). Adverse sively. Anyway, we should be careful not to effects may occur by intake of a high amount have excessive intake of GTE or EGCG, even of green tea extracts (GTE) containing EGCG, if they are believed to be an excellent natural possibly due to the suppression of the activ- medicine. It has been said that “the last drop ities of antioxidant enzymes such as catalase makes the cup run over”. The potential hep- and peroxidase in vivo (Fig. 1.3). atotoxicity of GTE or EGCG is also discussed The problems on EGCG-triggered hep- in Chapter 20. atotoxicity and the safety of green tea drinking In contrast to the above discussion on or intake as a dietary supplement have been the induction of hepatic failure in humans, extensively discussed (Sarma et al., 2008; beneficial effects of EGCG or GTE for not only Navarro et al., 2013, 2017; Mazzanti et al., viral hepatitis, but also non-alcoholic fatty 2015; Teschke and Andrade, 2016).