Tea and Its Consumption: Benefits and Risks

Abstract

ABSTRACT The recent convention of introducing phytochemicals to support the immune system or combat diseases is a centuries' old tradition. Nutritional support is an emerging advancement in the domain of diet-based therapies; tea and its constituents are one of the significant components of these strategies to maintain the health and reduce the risk of various malignancies. Tea is the most frequently consumed beverage worldwide, besides water. All the three most popular types of tea, green (unfermented), black (fully fermented), and oolong (semi-fermented), are manufactured from the leaves of the plant Camellia sinensis. Tea possesses significant antioxidative, anti-inflammatory, antimicrobial, anticarcinogenic, antihypertensive, neuroprotective, cholesterol-lowering and thermogenic properties. Several research investigations, epidemiological studies, and meta-analyses suggest that tea and its bioactive polyphenolic constituents have numerous beneficial effects on health, including the prevention of many diseases such as cancer, diabetes, arthritis, cardiovascular disease, stroke, genital warts and obesity. Controversies regarding benefits and risks of tea consumption still exist but the limitless health-promoting benefits of tea outclass its few reported toxic effects. However, with significant rise in the scientific investigation of role of tea in human life, this review is intended to highlight the beneficial effects and risks associated with tea consumption.

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TEA AND ITS CONSUMPTION: BENEFITS AND RISKS
Khizar Hayat a b , Hira Iqbal b , Uzma Malik b , Uzma Bilal b & Sobia Mushtaq b
a Department of Chemistry, COMSATS Institute of Information Technology , Abbottabad ,
22060 , Pakistan
b Department of Biochemistry, Faculty of Biological Sciences , Quaid-i-Azam University ,
Islamabad , 45320 , Pakistan
Accepted author version posted online: 20 Sep 2013.
To cite this article: Critical Reviews in Food Science and Nutrition (2013): TEA AND ITS CONSUMPTION: BENEFITS AND RISKS,
Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2012.678949
To link to this article: http://dx.doi.org/10.1080/10408398.2012.678949
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TEA AND ITS CONSUMPTION: BENEFITS AND RISKS
Khizar Hayat a,b,*, Hira Iqbal b, Uzma Malik b, Uzma Bilal b, Sobia Mushtaq b
a Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060,
Pakistan
b Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University,
Islamabad 45320, Pakistan
*Corresponding author: Tel: +92-992-383591-6; Fax: +92-992-383441;
E-mail: khizaraura@hotmail.com
ABSTRACT
The recent convention of introducing phytochemicals to support the immune system or
combat diseases is a centuries’ old tradition. Nutritional support is an emerging advancement in
the domain of diet-based therapies; tea and its constituents are one of the significant components
of these strategies to maintain the health and reduce the risk of various malignancies. Tea is the
most frequently consumed beverage worldwide, besides water. All the three most popular types
of tea, green (unfermented), black (fully fermented), and oolong (semi-fermented), are
manufactured from the leaves of the plant Camellia sinensis. Tea possesses significant
antioxidative, anti-inflammatory, antimicrobial, anticarcinogenic, antihypertensive,
neuroprotective, cholesterol-lowering and thermogenic properties. Several research
investigations, epidemiological studies, and meta-analyses suggest that tea and its bioactive
polyphenolic constituents have numerous beneficial effects on health, including the prevention of
many diseases such as cancer, diabetes, arthritis, cardiovascular disease, stroke, genital warts and
obesity. Controversies regarding benefits and risks of tea consumption still exist but the limitless
health-promoting benefits of tea outclass its few reported toxic effects. However, with significant
rise in the scientific investigation of role of tea in human life, this review is intended to highlight
the beneficial effects and risks associated with tea consumption.
Keywords: Tea consumption, Health effects, Risks, Cardiovascular health, Black tea, Green tea.
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INTRODUCTION
The term functional food was first time introduced in 1980 in Japan. Functional foods are
defined as "any substance containing ingredients which in addition to fulfill basic nutrition
requirements provides physiological benefits". Functional foods are being derived from plant as
well as animal sources. Tea is one of the most important functional foods.
Tea holds second position in consumption among all beverages. Tea has been obtained
from leaves of plant Camellia sinensis for almost 50 centuries ago. The plant of tea was
originated from Southeast Asia and is now being cultivated in more than 30 countries. About
three billion kilograms of tea is produced and consumed yearly. Tea has been categorized into
three main types on the basis of processing during manufacturing. Of the tea produced
worldwide, 78% is black tea, which is usually consumed in the Western countries, 20% is green
tea, which is commonly consumed in Asian countries, and 2% is oolong tea which is produced
(by partial fermentation) mainly in southern China (Mukhtar and Ahmad, 2000; Cabrera et al.,
2006; Khan and Mukhtar, 2007; Butt and Sultan, 2009).
Three main types of tea i.e. green, black and oolong tea differ in manufacturing
processes. For the production of green tea, freshly harvested leaves are rapidly steamed or pan-
fried to inactivate enzyme polyphenol oxidase, thereby preventing fermentation and producing a
dry, stable product. To produce black and oolong teas, the fresh leaves are allowed to wither
until their moisture content is reduced to <55% of the original leaf weight, which results in the
concentration of polyphenols (PPs) in the leaves. The withered leaves are then rolled and
crushed, initiating fermentation of the PPs. During these processes the catechins (a group of
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natural polyphenols in green tea, accounting for its characteristic color and flavor) are converted
to polymeric compounds, theaflavins (TFs) and thearubigins, consequently decreasing the
catechin content. Oolong tea is prepared by firing the leaves shortly after rolling to terminate the
oxidation and drying the leaves. Normal oolong tea is considered to be nearly half as fermented
as black tea. The fermentation process causes oxidation of simple polyphenols to more complex
condensed polyphenols which give black and oolong teas their characteristic colors and flavors.
The extended fermentation lowers the polyphenol content and elevates the caffeine content.
Black tea has 2-3 times more caffeine as compared to the green tea (Adak and Gabar, 2011). Fig.
1 summarizes the principal differences between green and black tea processing.
The tea composition depends on a variety of factors, including horticultural practices,
climate, season, the type and age of the plant. The important constituents of green tea are PPs
particularly flavonoids. The main flavonoids present in green tea include catechins (flavan-3-
ols), which account for 6-16% of the dry green tea leaves. The four major catechins are (–)-
epigallocatechin-3-gallate (EGCG), that represents approximately 59% of the total of catechins;
(–)-epigallocatechin (EGC) (19% approximately); (–)-epicatechin-3-gallate (ECG) (13.6%
approximately); and (–)-epicatechin (EC) (6.4% approximately). Another group of polyphenol
pigments found in both black and oolong teas are TFs. These are formed from polymerization of
catechins at the fermentation or semi-fermentation stage during the manufacture of black or
oolong tea respectively. TFs contribute to the characteristic bright orange-red color of black tea
and account for approximately 2g/100g of the dried water extract of black tea. The major TFs in
both black and oolong tea are theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3´-gallate
(TF2B) and theaflavin-3,3´-digallate (TF3) (Leung et al., 2001; Cabrera et al., 2006).
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The limitless benefits of tea have been evidenced by in vitro animal and in vivo studies in
the last few decades. Beneficial health effects have been attributed to the presence of PPs. Many
papers have discussed its role against cancer, cardiovascular diseases (CVDs), congenital
impairments, neurodegenerative diseases, depression and many other diseases. Because little has
been debated about the risk factors associated with tea, the purpose of this review is to focus
primarily on the potential of tea for adverse effects along with benefits and to raise awareness of
the rare, yet underappreciated risks. Fig. 2 shows the botanical classification and morphology of
Camellia sinensis.
BENEFITS OF TEA CONSUMPTION
Cardiovascular Health and Tea
Cardiovascular diseases (CVDs) are the leading cause of death all over the world. Several
intrinsic and extrinsic factors play an important role in the onset and pathogenesis of CVDs. The
American Heart Association (AHA) has categorized high cholesterol, high homocysteine level,
atherosclerosis, arterial calcification, and several other factors as a risk for CVDs (Ramaa et al.,
2006). There is increasing evidence from human, animal and cell culture models which suggests
that green tea catechins, specifically EGCG, have a positive impact on endothelial and overall
vascular functions (Moore et al., 2009).
The relationship between tea consumption and CVD risk has been investigated in a
number of epidemiological studies. Negishi et al. (2004) concluded that both black and green tea
PPs attenuate the development of hypertension (HTN), through their antioxidant properties, in
stroke-prone spontaneously hypertensive rats. Because the amounts of PPs used in this
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experiment correspond approximately to those in 1 liter of tea, the regular consumption of black
and green tea by humans may also provide some protection against HTN. Similarly, Yang et al.
(2004) conducted a cross-sectional study and observed that habitual moderate strength green tea
or oolong tea consumption, 120 mL/day or more for 1 year significantly lowers the risk of
developing HTN in the Chinese population.
Compelling evidence from chronic and acute human intervention studies has
established a positive correlation between the consumption of tea and protection against
CVD. A more recent meta-analysis demonstrated that individuals consuming ≥3 cups of tea
(green or black) per day had a 21% lower risk of ischemic stroke than those consuming <1 cup
per day (Arab et al., 2009). These studies explained that drinking black tea may result in
beneficial cardiovascular health effects comparable to those of green tea.
Many cohort and case-control studies demonstrate an inverse association between tea
consumption and risk of stroke and coronary heart disease (CHD) but the results are inconsistent
owing to the relation of tea consumption with certain other factors that influence the
cardiovascular disease (CVD) risk. Certain animal and acute human studies signify tea to reduce
aggregation of platelets (associated with pro-inflammatory activity) and as beneficial for
endothelial functions but the studies involving persistent tea administration show indecisive
results.
The effects of chronic tea intake on CVD factors, examined through a randomized,
placebo-controlled study, showed favorable outcome regarding platelet activation. In comparison
with the placebo beverage, 6 weeks of tea consumption significantly lowered all the three
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markers of CHD risk (platelet-monocyte aggregates, platelet-neutrophil aggregates and total
platelet-leukocyte aggregates) with a difference of 9%. Black tea PPs reduce the platelet
activation in vitro whereas arachidonic acid induced inhibitory effect of peroxinitrite on platelet
aggregation is eradicated by EGCG, another component of black tea. Hence anti-inflammatory
effects of black tea are responsible for guarding against CVD development (Steptoe et al., 2007).
Atherosclerosis
The relationship between tea or flavonoid intake and atherosclerosis has been
investigated in few human studies. Debette et al. (2008) reported that carotid plaques were less
frequent with increasing tea consumption in women. Mursu et al. (2007) showed that decreased
carotid atherosclerosis was associated with high intake of flavonoids in middle-aged Finnish
men. In contrast there is a significant literature describing studies using animal models to explore
the relationship between flavonoid-rich foods or extracts and the development of atherosclerosis.
The apolipoprotein E (ApoE) deficient mouse and hamsters have been used to study the effects
of flavonoid-rich foods or extracts on the development of atherosclerosis (Hodgson and Croft,
2006). In the ApoE deficient mouse, which develops human-like atherosclerotic plaques,
inhibition of atherosclerotic lesion development has been demonstrated with tea and tea-derived
flavonoids, red wine-derived PPs, isolated quercetin or catechin, and a pure phenolic acid
derivative from honey. More recently, Loke et al. (2010) concluded that isolated quercetin (a
flavonol found in both green and black tea) and theaflavin (a dimeric catechin from black tea)
can reduce atherosclerotic lesion formation in the ApoE-/- gene-knockout mouse by alleviating
inflammation, improving nitric oxide (NO) bioavailability, and inducing heme oxygenase-1.
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Overall, the results of studies using animal models clearly show that flavonoids present in tea can
attenuate the risk of atherosclerosis development. However, further human studies are needed.
Endothelial function
The endothelium, the inner lining of all blood vessels, functions as a selectively
permeable barrier between blood and tissues. It plays a crucial role in regulating vasomotor tone,
platelet activity, leukocyte adhesion and vascular smooth muscle cell proliferation through
release of several factors including NO, which is one of the most important molecules released
by the endothelium and an important regulator of arterial wall tone. Endothelial dysfunction
develops by the loss of normal endothelium-dependent and NO-mediated vasodilation in the
artery. The development of endothelial dysfunction is considered as an early biomarker for the
development of CVD and cardiovascular events.
Endothelial function may be estimated in a number of ways. Isolated vessels from
animals have been used to assess the effects of potentially vasoactive substances in vitro. The
results of several in vitro studies indicate that tea and tea flavonoids cause NO and endothelium-
dependent vasorelaxation of rat aortic rings. In humans, ultrasonography has been used to
measure flow-mediated dilatation (FMD) of the brachial artery. FMD is a non-invasive technique
which measures NO-dependent vasodilation of the artery in response to shear stress induced by
increased blood flow.
A number of studies have examined the effects of black or green tea, or tea flavonoids on
FMD of the brachial artery. Recent studies have demonstrated a significant improvement in FMD
after consumption of black and green tea, and both teas appeared to have similar effects
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(Hodgson and Croft, 2006). Jochmann et al. (2008) assessed the endothelial function in response
to black and green tea in bovine aortic endothelial cells (BAEC) and rat aortic rings. To explain
whether these findings are also applicable to humans, FMD and nitro-mediated dilation (NMD)
were quantified by ultrasound in twenty-one healthy women before and 2h after consumption of
both teas (2h of FMD and NMD), in comparison with control (water). In BAEC, both teas
significantly increased endothelial NO synthase (eNOS) activity to the same extent and induced
comparable endothelial-dependent vasodilation in rat aortic rings. In human subjects, intake of
green and black tea led to significant increases in FMD: from 5.4% to 10.2% and from 5% to
9.1% between baseline and 2h after consumption of 500ml green tea and black tea, respectively;
no FMD effect was found with hot water. Between any of the groups, NMD did not vary. A
recent population study found that FMD-assessed endothelial function increased from 4.4% to
8.1% after 450ml (6g of green tea) beverage, with no significant effects shown with the caffeine
or water controls (Alexopoulos et al., 2008).
Experimental studies have also reported that isolated flavonoids found in tea can augment
NO status. A recent randomized, placebo-controlled, crossover trial in healthy men conducted by
Loke et al. (2008) showed that oral administration of dietary flavonoids present in green tea,
including quercetin and (–)-epicatechin, could boost NO status-a potent vasodilator and reduce
endothelin-1 (ET-1) concentrations-a potent vasoconstrictor. A double blind, placebo-controlled,
crossover design study by Widlansky et al. (2007) also demonstrated that acute EGCG
supplementation (a single 300 mg dose of EGCG) can improve brachial artery FMD in humans
with coronary artery disease (CAD).
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Therefore, from consistent randomized controlled trials, there is evidence that
consumption of black and green tea, and specific flavonoids present in tea, can significantly
improve endothelial function.
Antioxidant Properties of Tea
The antioxidative property of tea PPs in part ascribes to the potential health benefits
related with tea consumption. Tea preparations entrap the reactive oxygen species, such as
radicals of superoxide, hydroxyl and peroxyl, singlet oxygen, nitric oxide, nitrogen dioxide and
peroxynitrite, and thus reduce their damage to lipid membranes, proteins and nucleic acids in
cell-free systems. EGCG is the most effective tea catechin which reacts with most reactive
oxygen species. In vitro studies have shown that green and black tea inhibit the oxidation of
lipoproteins induced by Cu2+ and thus have been proposed to contribute to prevent
atherosclerosis and other cardiovascular diseases. A number of clinical trials have demonstrated
that plasma antioxidant capacity of healthy adults is improved within 30 to 60 min after taking a
single dose of tea. Another study verified that biomarkers of oxidative status are decreased by the
repeated consumption of tea and encapsulated tea extracts for one to four weeks (Khan and
Mukhtar, 2007).
Antioxidant property of green tea is higher than black tea. Erba et al. (2005) described
that tea phenols improve antioxidant ability in overall balanced food and also protect against
damage reactive oxygen species. The underlying mechanism is that reactive oxygen species
(ROS) such as peroxyl radical, singlet oxygen, hydroxyl radical are trapped by tea phenols and
thus provide protection against ROS mediated damage to lipid membranes, protein and DNA in
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cell free environment. The vicinal dihydroxy or trihydroxy structure can chelate metal ions and
prevent the generation of free radical and accounts for the antioxidant activities of catechins.
High reactivity to quench free radicals is also enhanced by electron delocalization of this
structure. Reactions of EGCG and other catechins with peroxyl radicals lead to the formation of
anthocyanin-like compounds as well as seven-membered B ring anhydride dimers and
ringfission compounds. The trihydroxyphenyl B ring in EGCG and EGC appears to be the
principal site of antioxidant reactions (Kondo et al., 1999).
Absence of Toxicity
Since 2000 years, Pu-erh black tea, a kind of black tea attained by drying and fermenting
crude green tea leaves, has been used as beneficial health beverage in China, Japan and Taiwan.
A study conducted on Sprague-Dawley (SD) rats for evaluating the toxicity of tea extracts did
not show any treatment related effect for its dietary administration, suggesting a safety profile for
high intake black tea extract (BTE) as dietary supplement for both animals as well as humans
(Wang et al., 2011).
Anti-inflammatory Effect
Tea and its extracts are known to assist health in chemopreventive effects on cancers,
cardiovascular diseases, and inflammation. Various epidemiological studies associated the
elevated levels of uric acid (UA) and C-reactive protein (CRP) with cardiovascular risk.
According to a study, varying levels of the risk were significantly reduced with tea
supplementation that decreased the UA and CRP levels owing to the synergistic effects of tea
phenolics. This could be substantial from public health viewpoint as inflammation is involved in
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every disease progression, including diabetes, arthritis, heart disease, cancer and obesity
(Bahoruna et al., 2010).
Cancer and Tea
The widespread consumption of tea throughout the world has aroused interest in the
possibility of its use in chemoprevention of carcinogenesis and its related phenomenon,
mutagenesis. Several population-based studies confirm about the cancer protective effects of tea
(Vasisht et al., 2003). Cancer is usually caused by oxidative damage resulting from cigarette
smoking. Researchers claim that tea PPs are powerful anti-oxidants that induce phase-2
detoxification enzymes which in turn reduce the risk of cancer by reducing damage of DNA in
the cell and activation of cancer leading to malignancy (Shim et al., 1995; Beltz et al., 2006;
Sharangi, 2009). The anti-carcinogenic and anti-mutagenic activities of green tea have been
reviewed by Butt et al. (2009) suggesting that it can reduce the prevalence of cancer and even
provide protection. Yang et al. (2000) also supported the fact that tea is not toxic and its
consumption is suggested to prevent carcinogenesis. Both green and black teas have significant
antimutagenic and anticlastogenic effects. Compared to green tea, reports on black tea are
relatively less. Green tea was found to have no mutational toxicity but was able to inhibit
mutagenesis, at concentration levels equivalent to daily human consumption. A few reports on
thearubigins, which are present in black tea, indicate that it has significant antimutagenic and
anticlastogenic effects similar to TFs (Gupta et al., 2002).
Inhibitory effects of BTE and TFs on selenoprotein thioredoxin reductase 1 (TrxR1), high
levels of which in cells are associated with enhanced resistance of the cells to anti-cancer drugs
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that induce oxidative stress, have been demonstrated by Smart et al. (2004). The inhibitory effect
of BTE and TFs on TrxR1 means that they could have roles in reducing cancer risk. TFs are
major components for black tea to inhibit TrxR1 because TFs account for 3-6% of the water-
extractable materials from black tea but TFs are contributed to near 50% inhibitory effects of
BTE on TrxR1 (Gardner et al., 2007).
Prostate cancer inhibition
Prostate cancer (PCA), the second most important cause of cancer related mortality in
US, is the most recurrently analyzed non-cutaneous cancer (Siddiqui et al., 2005). Studies show
that androgen sensitive human prostate carcinoma cells can be inhibited by tea extracts and TFs
(Lyn-cook et al., 1999).
Various studies suggest a key role for the oxidative stress induced by reactive oxygen
species (ROS) in the process of prostate carcinogenesis (Sun, 1990). A strong association exists
between androgen hormone and PCA risk but the underlying mechanism of action is unclear. In
Wistar rats, antioxidant enzymes level was altered by androgen administration (Siddiqui et al.,
2005). Androgen concentration transfers the prostate prooxidant-antioxidant balance towards
increased oxidative stress thereby modulating the gene expression and causing prostate tumors
(Ripple et al., 1997). In a dose-dependent manner, aqueous tea extracts (ATE) restored eminent
amounts of antioxidant enzymes (Siddiqui et al., 2005).
Another study demonstrated an ATE based successful inhibition of oxidative stress
induced by testosterone which is a vital cause of PCA development (Siddiqui et al., 2005).
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Skin cancer
Extensive studies have shown the activity of tea and tea PPs on the inhibition of skin
tumorigenesis. Growth of well-established skin tumors is inhibited or, in some cases, regressed
by the oral administration of green tea, black tea or EGCG. Papilloma-bearing mice even showed
complete regression (Conney et al., 1999). Feeding tumor-bearing mice with black tea
significantly decreased the growth of nonmalignant tumors, squamous cell carcinomas and tumor
volume. In addition, DNA synthesis was inhibited and apoptosis was enhanced (Khan and
Mukhtar, 2007).
In a study, oral administration of black tea for 11 weeks in female mice, which were
allowed to develop tumors by being treated with UVB light, noticeably reduced the number and
volume of nonmalignant and malignant tumors (by 54% to 84%). In another study, oral
administration of black tea for 11 to 15 weeks inhibited the growth of established papillomas (by
35% to 48%) in mice, but inconsistent results were obtained for decaffeinated black tea (Lu et
al., 1997). A case-control study conducted in Italy showed protective effect of tea consumption
on cutaneous malignant melanoma (Naldi et al., 2004). In a population-based case-control study,
a considerable decrease in the SCC development was reported for the subjects consuming hot
black tea (Khan and Mukhtar, 2007). Green tea extract EGCG like many other applications
provides protection against skin carcinogenesis (Katiyar et al., 2007).
Lung cancer
Studies regarding the effects of green and black tea on lung cancer development in mice
can yield promising implications for humans. In mice 4-(methylnitrosamino)-1-(3-pyridyl)-1-
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butanone or nicotine-derived nitrosamine ketone (NNK)-induced pulmonary hyperproliferation
and tumorigenesis initiated with NNK can be protected by brewed black tea and TFs,
particularly, oral administration of brewed black tea inhibits the development of adenoma to
adenocarcinoma in mice with already developed lung adenomas (Yang et al., 1997).
Reports have shown that in mice with benzo-alpha-pyrene-induced lung carcinogenesis,
black tea suppresses cell proliferation and induce apoptosis (Banerjee et al., 2005). In mice, the
spontaneous formation of lung tumors and rhabdomyosarcomas has been shown to be inhibited
by black tea and green tea infusions. 60 weeks of treatment with black or green tea notably
reduced the prevalence of lung cancer from 52–27%, multiplicity from 0.72–0.33 tumors/mouse
and volume from 38.3–4.27 mm3. In addition, the tea-treated groups of mice had significantly
lower body weights, particularly the body fat weights, as compared to the control group (Landau
et al., 1998).
Examining the effects of black tea and caffeine administration on NNK induced lung
tumorigenesis in rats, it was found that total lung tumor (adenomas, adenocarcinomas, and
adenosquamous carcinomas) incidence was significantly reduced from 47–19% by black tea and
from 47–10% by caffeine treatment. This implies that caffeine in black tea might actually
account for its inhibitory activity (Khan and Mukhtar, 2007).
A case control study conducted in Uruguay demonstrated an association between tea
drinking and reduced risk of lung cancer in male cigarette smokers (Khan and Mukhtar, 2007).
Regular tea drinking reduces the likelihood of lung cancer among nonsmoking women. This fact
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has been supported by Zhong and his colleagues in 2001 by large population-based case-control
study among women inhabitants of Shanghai, China (Zhong et al., 2001).
Liver cancer
It has been reported that administration of 2% black tea significantly reduced the
incidence of NNK-induced liver tumors (from 34–12%) in rats. Studies have demonstrated
inhibitory effects of individual tea catechins, black tea extract, and oolong tea extract (0.05 or
0.1%) on the formation of hepatic preneoplastic glutathione-S transferase (GST)-positive foci in
rats treated with a single dose of N-nitrosodiethylamine (NDEA) and then phenobarbital for 6
weeks in the drinking water (Khan and Mukhtar, 2007).
Breast cancer
The occurrence of late-onset breast cancer has been mounting in the United States since
1980’s. It is estimated that known risk factors, such as genetic modifications, account for
approximately 5-10% of breast cancer cases. Moreover, dietary habits may be responsible for the
risk as well as prevention of breast cancer. Recently, Wnt signaling in invasive breast cancer
cells was found to be suppressed by EGCG (Khan and Mukhtar, 2007). Leong et al. (2008) also
studied that black tea has its potential use as a breast cancer chemopreventive agent. Laboratory
studies have provided evidence that GTE inhibits breast cancer growth by a direct anti-
proliferative effect on the tumor cells, as well as by indirect suppressive effects on the tumor-
associated endothelial cells (Sartippour et al., 2006).
Stomach Ulceration
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Stomach ulceration induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is a
major medical problem, ranking fourth in terms of causing morbidity and mortality (Hawkey,
1990). Several plants and herbs are used in traditional medicine to treat GI disorders. Regular
intake of black tea may reduce the risk of stomach ulceration (Adhikary et al., 2011).
Prevention of Pancreatitis
About 80% of pancreatitis cases occur due to alcohol abuse. Although the underlying
mechanism is unknown, evidence shows that ethanol (EtOH) not only directly targets the
pancreatic acinar cells by its toxic effects but even sensitize them to intracellular zymogen
proteolysis stimulated by cholecystokinin (CCK). Combined stimulation by EtOH+CCK results
in acute pancreatitis (Das et al., 2006).
BTE provides surplus health benefits through its PPs collectively known as tea
flavonoids. The antioxidant properties of tea flavonoids make them a protective dietary
component that significantly increases the plasma antioxidant activity and thus reduce various
cancer risks. BTE effectively blunted the significantly increased levels of amylase and lipase
(biomarkers for pancreatitis) and pancreatic levels of malondialdehyde (MDA) and nitric oxide
(NO), the biomarkers of oxidative stress in an EtOH+CCK induced pancreatitis rat model. BTE
also normalized the suppressed activities of other antioxidative enzymes, blunted the
histopathological and inflammatory changes and diminished the increased DNA fragmentation
and damage. Thus BTE effectively averted the toxic activity in EtOH+CCK induced pancreatitis
rats (Das et al., 2006).
Neurological and Psychological Effects
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Various reports indicate that neurologic and psychologic functions can be improved by
tea. Recently, in a broad array of cellular and animal models of neurological diseases, it has been
reported that tea catechins penetrate the brain barrier and protect neuronal death by its divalent
metal chelating, antioxidant and anti-inflammatory activities. In order to evaluate the effect of
acute and chronic administration of green or black tea, mice with experimentally induced
convulsions were analyzed. It was found that tea not only accelerates the onset of convulsion, but
also increases the duration and mortality. Possibly, tea acts on Ca2+ channels and not through
gamma-aminobutyric acid (GABA) in brain (Khan and Mukhtar, 2007).
A cross-sectional study in 1058 community-dwelling elderly Japanese individuals aged
≥70 has been carried out by Niu et al. (2009). This study showed a positive association between
green tea consumption and lower prevalence of depressive symptoms.
In future, the availability of effective brain permeable, iron-chelatable/radical scavenger
neuroprotective drugs that would avert the progression of neurodegeneration can be a promising
treatment for neurodegenerative diseases and aging (Khan and Mukhtar, 2007).
Role in Neurotrasnsmission
It is believed that green tea induced relaxation is due to the presence of amino acid
theanine which is also responsible for its exotic taste. Juneja et al. (1999) experimented that L-
theanine accessed rat brain in 30 minutes without any metabolic change when administered
peritonealy. Theanine reduced blood pressure in hypertensive rats and performed the function of
a neurotransmitter. After oral administration of L-theanine it reached the brain within 40 minutes
of oral administration and generated α-waves (an index of relaxation) in human volunteers. L-
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theanine is being produced industrially and supplied under the trade name of Suntheanine™. It is
used for designing medical foods targeting relaxation and the reduction of stress.
Reduced Cognitive Impairment
Approximately 30 percent of eukaryotic proteomes remain unfolded and account for
many neurodegenerative diseases. For example, tau and amyloid-β (Aβ) in Alzheimer’s disease
(AD) and α-synuclein (α-syn) in Parkinson’s disease (PD) all seem to transition from a highly
dynamic, natively unfolded state through heterogeneous molten, oligomers to the generic ‘cross-
β’ form of amyloid fibers. EGCG inhibits tau, Aβ, α-syn (by traping Aβ and α-syn in monomeric
and oligomeric forms with diminished ability to participate in amyloidogenesis) and
polyglutamine fibrillization in vitro and antagonizes polyglutamine aggregation and toxicity in
both yeast and fly models of Huntington’s disease (Roberts and Shorter, 2008).
Treatment of Diabetes
Population based studies suggest that green tea consumption is associated with reduced
risk of several human malignancies such as cancer and diabetes (Shankar et al., 2007). In a
laboratory study published in 2009, scientists discovered that compounds extracted from black
tea were more effective at slowing the absorption of blood sugar than those extracted from green
tea and oolong tea. Additionally, a 2009 population study of 1,040 elderly adults found that long-
term intake of black tea was associated with lower prevalence of diabetes (Panagiotakos et al.,
2009).
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Heavy consumption (6-10 cups/day) of black tea brew is frequently advised by Sri
Lankan physicians for pre-diabetics and mild diabetics owing to the glucose lowering potential
and anti-diabetic activity of tea infusion. Sri Lankan Broken Orange Pekoe Fannings (BOPF)
grade black tea (a grade containing medium size leaf particles) possesses striking
hypoglycaemic, antihyperglycaemic and antidiabetic activities, the former two being dose
dependent (Abeywickramaa et al., 2011).
Various components of black tea, including catechins, TFs, anthocyanines, gallic acid,
some polysaccharides and PPs, contribute to the impairment of carbohydrate digestion by
inhibiting the carbohydrate-hydrolyzing enzymes: alpha-glucosidase and alpha-amylase.
Black tea infusion (BTI) increases the insulin/glucose ratio by its TFs and EGCG,
resulting in insulin sensitizing action or enhancement of insulin activity. Black tea PPs possess
insulinomimetic activity; suppressing the blood glucose level in streptozotocin-induced diabetic
rats. The antioxidant activity of BTI assists in reducing the blood glucose level by scavenging
ROS which are concerned with the pathogenesis of diabetes mellitus.
Different studies have claimed flavonol and myricetin present in BTI to lower the blood
glucose levels by various mechanisms, including high uptake of glucose via cell membranes in
adipocytes, enhanced glucose metabolism in cells, high release of insulin upon stimulating action
of pancreatic cells and augmented lipogenesis. All these findings are essential as BOPF grade
black tea is an everyday natural beverage consumed globally having beneficial effects regarding
the regulation of dysglycemia (Abeywickramaa et al., 2011).
Obesity
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Reports have shown that feedings of oolong, black, and green tea leaves to rats
significantly reduces their body weights and plasma triglyceride, cholesterol and LDL-
cholesterol (Murase et al., 2002; Zheng et al., 2004; Kuo et al., 2005; Lin and Lin-Shiau, 2006).
In mice supplemented with tea catechins, there was a significant reduction in body weight gain
induced by high-fat diet, accumulation of visceral and liver fat, and the development of
hyperinsulinemia and hyperleptinemia (Khan and Mukhtar, 2007).
Black tea extract and caffeine is beneficial for the suppression of high-fat diet-induced
obesity, and that their effects may be attributed to the inhibition of adipose tissue formation and
reduction of adipose tissue mass. Moreover, better results can be achieved by combination of
different compounds. BTE and caffeine to render the most effective anti-obesity action and
sufficient supply of BTE and CF may prevent obesity and possibly reduce the risk of associated
diseases, such as coronary heart disease (Huang et al., 2009).
Anti Arthritis Effect
Green tea protects against rheumatoid arthritis by modulating arthritis-related immune
responses. It suppresses both cytokine IL-17 (an inflammatory substance) and antibodies to
Bhsp65 (arthritis inducing protein), and increases cytokine IL-10 (an anti-inflammatory
substance) (Kim et al., 2008).
Bone mineral density (BMD) may be influenced by chemical compounds in tea such as
caffeine, fluoride and phytoestrogens. Black tea consumption had a moderately positive effect on
BMD, particularly in older women. There was a significant increase in BMD with higher levels
of tea consumption (four or more cups per day) (Chen et al., 2003). Black tea was also emerged
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as an independent protective factor for the risk of hip fractures in men in the Mediterranean
Osteoporosis Study (Kanis et al., 1999). Johnell et al. (1995); Kanis et al. (1999) and Hegarty et
al. (2000) reported that this effect was independent of the addition of milk to tea. In the UK,
black tea consumption increased the overall calcium intake of women almost 3% of the
Reference Nutrient Intake due to the routine addition of milk (Gardner et al., 2007).
Antihistaminic Effect
Antihistaminic effect is exhibited by green tea extract (GTE) EGCG. Histamine is
released from mast cells in allergic responses, particularly inflammation, dermatis, urticaria,
mastocytosis and asthma, triggered by environment antigens. Tea extract, beside its anti-
inflammatory properties, also exhibits an antihistaminic effect on rat peritoneal mast cells and
inhibits hyaluronidase activity. Histamine release can be inhibited up to 90% in rat cell culture
by EGCG. This inhibitory effect of the histamine release is supposed to be related to the
triphenol moiety of the molecule. Quercetin flavonoid produces an anti-inflammatory activity in
antigen activated cells and causes a concentration-dependant inhibition of histamine release
(Toyoda et al., 1997; Alexis et al., 1999).
Antibacterial, Antiviral and Probiotic Effects
Screening of methanolic extract of tea leaves for antimicrobial property against 111
bacteria comprising 2 genera of Gram positive and 7 genera of Gram negative bacteria resulted
in the inhibition of most of these strains. The protection of Swiss strain of white mice challenged
with different dosages of Salmonella typhimurium confirmed the antibacterial activity of tea
extract in vivo (Bandyopadhyay et al., 2005). Lately, EGCG was found to have an effect on the
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inhibition of HIV infection and Staphylococcus aureus infections (Nance and Shearer, 2003).
Drinking tea not only reduces enterobacteria (which produce ammonia and other harmful
amines), but also causes a beneficial increase in the level of lactobacilli and bifidobacteria
(which produce organic acids) and lower the pH of intestine (Weisburger, 1999). The beneficial
effect of tea against viral infection cannot be overlooked. Strong inhibition of rotavirus
propagation in monkey cell culture and influenza A virus in animal cell culture was achieved
through tea PPs (Khan and Mukhtar, 2007). Several flavonoids including EGCG and ECG have
been reported to inhibit the propagation of retrovirus human immunodeficiency virus (HIV) by
restraining reverse transcriptase, the enzyme responsible for the establishment of the virus in host
cells (Yamamoto et al., 1997), so it can be suggested as a complementary therapy for HIV. But it
still needs a lot of work to be done because experiment has been carried out in vitro and in
previous studies many substances which proved to be effective against HIV in vitro cannot show
the same results in vivo. So it can be used in combination with conventional medicines
(Williamson et al., 2006).
Anogenital Wart Suppression
Sinecatechins, a defined green tea extract, was shown to be effective in the treatment of
external genital and perianal warts in a randomized, double-blind, vehicle-controlled trial
involving 502 male and female patients aged 18 years and older, with 2-30 anogenital warts
ranging from 12 to 600 mm² total wart area. Patients applied a topical ointment containing either
sinecatechins or vehicle (placebo) to the affected area for up to 4 months, followed by a 3
months treatment-free follow-up to assess recurrence. More than half of the patients (57%) in the
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treatment group experienced a complete resolution of their warts, compared with 34% in the
control group. 78% of the patients in the treatment group experienced partial improvement (at
least 50%) in their warts. It was observed that topical sinecatechins ointments 15% and 10%
were effective and well-tolerated in the treatment of anogenital warts, with relatively few side-
effects (Tatti et al., 2008).
LACKLUSTER OF TEA CONSUMPTION
No doubt, the benefits associated with the consumption of black and green tea are
overwhelming but still need attention in order to explain its detrimental effects on human health.
Harmful effects of tea over consumption (black or green) are primarily due to three main factors:
(1) its caffeine content, (2) presence of aluminum, and (3) the effects of tea PPs (TPP) on iron
bioavailability. Various compounds present in tea may have deleterious effects at
pharmacological concentrations, in certain vulnerable populations, and in certain disease or
polypharmaceutical contexts. A day-long consumption of green tea (which contains less
caffeine) improved the psychomotor and cognitive performance of healthy adults in a manner
similar to coffee, but it is less likely than coffee to disrupt sleep quality at night. The caffeine
content in the same type of tea, but manufactured by different fermentation processes, has been
presented by the following order: black tea > oolong tea > green tea > fresh tea leaf. Although
green tea caffeine content is low, its consumption is not recommended in cases of special
sensitiveness to xanthic bases (Cabrera et al., 2006; Lambert et al., 2007). The reported negative
effects produced by caffeine present in many tea products are nervousness, restlessness, tremors,
palpitations, sleep disorders, vomiting, diarrhea, headaches, epigastric pain and tachycardia.
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However, research on the effects of caffeine in children is limited (Higdon and Frei, 2006).
Negative effects of theophylline (member of the xanthine family of stimulants) are similar to
those of caffeine, but they only occur with high quantities intake. Thus, green tea should be
avoided by the patients suffering from heart conditions or major cardiovascular problems.
Pregnant and breast feeding women should drink not more than 1–2 cups/day, since it can
augment the heart rhythm. It is also suggested to control the concomitant consumption of green
tea and some drugs, due to its diuretic effects (Cabrera et al., 2006).
Tea is "Generally Recognized As Safe" (GRAS) by the US Food and Drug
Administration (FDA). Safety studies have looked at the consumption of up to 1200 mg of
EGCG (as supplement) in healthy adults over 1-4week time periods. The adverse effects reported
in these studies included excess intestinal gas, nausea, heartburn, stomach ache, abdominal pain,
dizziness, and muscle pain (Chow et al., 2003; Chow et al., 2005). Fig. 3 summarizes some
potentially detrimental effects associated with concentrated GTE.
Drug Antagonism
Green tea is considered as a significant source of vitamin K, which can antagonize the
effect of anticoagulant drugs, such as warfarin. A case report of 44-year-old white man
demonstrated that warfarin produces anticoagulation by inhibiting the production of vitamin K-
dependent clotting factors (i.e., factors II, VII, IX, X). The exogenous administration of vitamin
K limits the effect of warfarin and reduces the patient's degree of anticoagulation (Taylor and
Wilt, 1999).
Hepatic and Gastrointestinal Toxicities of Green Tea Polyphenols (GTPP)
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Mazzanti et al. (2009) reviewed the current literature on suspected green tea-related
hepatic reactions and described 2 new cases reported within the framework of the Italian
surveillance system of natural health products. This analysis suggests a causal association
between green tea and liver damage. The hepatotoxicity is probably due to EGCG or its
metabolites which can induce hepatic oxidative stress. In a few cases, concomitant medications
related toxicity could also be involved. Unfortunately, some reports of adverse effects (mainly
hepatitis) associated with the consumption of green tea preparations have been published. In
April 2003, the manufacturer of Exolise (Arkopharma, Carros, France), a GTE containing high
EGCG levels and marketed as a weight loss supplement, suspended the sale of this product and
withdraw it from the market after 13 reported cases of liver damage due to its consumption. The
same product was also removed from the Spanish market due to other hepatotoxicity cases in
humans. Since then, much attention has been given to the possible hepatotoxicity from green tea.
Despite the removal of Exolise from the market, other green tea-based herbal supplements have
been marketed; therefore reports of hepatotoxicity from green tea are increasing.
Despite several human studies that reported no toxicity of tea polyphenol preparations
and that the major harmful effects associated with consumption of high doses of tea preparations
are due to gastrointestinal (GI) irritation, there are a number of recent case reports of
hepatotoxicity related to the consumption of high doses (10–29 mg/kg/day, po) of tea-based
dietary supplements (Bonkovsky, 2006). In nearly all cases (eight out of nine), patients displayed
elevated serum alanine aminotransferase (ALT) and bilirubin levels. In two out of nine cases,
periportal and portal inflammation were noticed. All cases resolved after cessation of supplement
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consumption, suggested by the fact that reinjury was reported following rechallenge with the
same preparations.
Laboratory studies in animals (particularly rodents and dogs) have supported the potential
toxic effects of high doses of GTEs (Galati et al., 2006; Isbrucker et al., 2006) Oral
administration (po) of TeavigoTM (a green tea polyphenol preparation containing 90% EGCG) or
Polyphenon E® (a decaffeinated extract of green tea containing 60% EGCG) for 13 or 9 weeks,
respectively, to Beagle dogs caused dose-dependent toxicity and death. Vomiting and diarrhea
were noticed throughout both studies. In addition, TeavigoTM (500 mg/kg, po) caused proximal
tubule necrosis and elevated serum bilirubin in all treated dogs. Serum aspartate
aminotransferase (AST) levels in most male dogs (2/3) were found to be elevated. Female dogs
(2/3), but not male dogs, manifested liver necrosis. Oral (po) and intragastric administration (ig)
of TeavigoTM (2000 mg/kg) to rats caused lethality in 80% of animals treated (Isbrucker et al.,
2006).
Experiments performed in rat hepatocytes showed that high concentrations of GTEs and
of single tea phenolics are toxic. This cytotoxicity seemed to be related to the gallic acid unit,
and the order of cytotoxic effectiveness found was EGCG (the most abundant tea phenolic) >
propyl gallate > ECG (also a food additive) > GA, EGC > EC. The major cytotoxic mechanism
found with rat hepatocytes was GTEs (particularly EGCG) induced mitochondrial membrane
potential collapse or toxicity and ROS formation (prooxidant activity). Hemorrhagic lesions in
the stomach and intestine were revealed by histological analysis. Intraperitoneal (ip)
administration of EGCG to mice resulted in dose-dependent lethality (associated with increases
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in serum ALT levels) beginning at 150 mg/kg and thus suggested the involvement of
hepatotoxicity. EGCG was also found to be the most cytotoxic to isolated rat hepatocytes and
hepatotoxic to mice in vivo (Galati et al., 2006).
These data suggest that high doses of EGCG can produce toxicity in the liver, kidneys,
and intestine. Hepatic and renal toxicity appears to be correlated with the bioavailability of
EGCG. In the rat (low bioavailability), toxicity is limited to the GI tract following oral
administration. In the dog (much higher bioavailability), hepatotoxicity, nephrotoxicity, and
intestinal toxicity were reported. Toxicity was much higher in fasted, than in prefed, dogs
(Isbrucker et al., 2006). Recent studies in humans have also proved that fasting increases the
bioavailability of EGCG. Since there have been no reports of toxicity in human volunteers
enrolled in intervention studies, therefore careful monitoring of liver and kidney function is
needed until the risk of toxic events associated with tea catechins is established in humans.
A 9-month chronic study was conducted in fasted dogs to take advantage of the reported
increased catechin bioavailability with fasting. Kapetanovic et al. (2009) evaluated standardized
GTE (i. e., Polyphenon E®; PPE) for exposure and toxicity in Beagle dogs following oral dosing
by capsules. Extensive morbidity, mortality, and pathology of many major organs led to early
termination of the study at 6.5 months and hindered identification of the toxicity mechanisms. A
follow-up 13-week study investigated the exposure to and toxicity of PPE. In general, toxicities
were less severe when compared to the chronic study during the same interval. Dosing in a fed
state resulted in considerably lower and less variable exposure than observed under fasted
conditions. PPE-treated dogs manifested adverse events like diarrhea, emesis, and excessive
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salivation. In addition, a multitude of PPE-induced toxicities were observed including
hematology (decreases in red blood cells, hemoglobin, and hematocrit, increases in white blood
cells, neutrophils, monocytes, platelet count), gross pathology (lesions in GI tract, lymph nodes,
liver, kidney, lung, heart and tonsils), histopathology (epithelial necrosis in GI tract, liver
inflammation including centrilobular necrosis and congestion, renal tubular necrosis, atrophy of
reproductive organs, and atrophy and necrosis of hematopoietic tissues) as well as abnormalities
in clinical chemistry, coagulation and urinalysis parameters.
Recently, Lambert et al. (2010) investigated the hepatotoxic effects of high doses of the
GTPP (particularly EGCG) in male CF-1 mice. A single dose of EGCG (1500 mg/kg, ig) raised
plasma ALT levels (marker of liver damage) by 138-fold, reduced survival by 85% and
increased hepatotoxic response. Plasma ALT levels were raised 184-fold following two once-
daily doses of EGCG (750 mg/kg, ig). Moderate to severe liver necrosis was observed following
EGCG treatment. EGCG hepatotoxicity was appeared to be related with oxidative stress
including increased hepatic lipid peroxidation (LPO), plasma 8-isoprostane and increased hepatic
metallothionein and γ-histone 2AX protein expression. In addition, EGCG also increased plasma
interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1).
On the basis of these results, it can be concluded that the suspected hepatic reactions from
green tea can likely be attributed to catechins, specifically to EGCG. After oral administration,
the bioavailability of catechins is low; however, under fasting and after repeated administration,
catechin plasma levels can rise up to toxic levels. Thus, the hepatotoxicity can be ascribed to the
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capability of EGCG or its metabolites to induce oxidative stress in the liver (Mazzanti et al.,
2009).
The experience of Molinari et al. (2006) complemented previous reports of acute liver
toxicity observed in individuals consuming supplements containing GTE. After review of the
literature and reporting a case of acute liver dysfunction caused by consumption of GTE
supplements, it was concluded that many herbal medicines and dietary supplements were
associated with severe adverse events, including hepatotoxicity and even fulminant liver failure.
Green Tea-Induced Asthma
Shirai et al. (1994) described green tea dust induced asthma and nasal symptoms in 3
patients working in green tea factories. It was found that all 3 patients displayed an immediate
skin and bronchial response to EGCG. Prausnitz-Küstner (immunologic) test with EGCG was
also positive. The asthmatic and healthy controls did not show any positive reaction. These
results indicated that EGCG is a causative agent of green tea-induced asthma and suggested that
an IgE-mediated response may be responsible for causing this type of occupational asthma.
Dietary Flavonoids, Effects on DNA, and Fetal Leukemia Risk
In 1994, Ross and colleagues hypothesized that maternal consumption of dietary
topoisomerase inhibitors II (including flavonoids) could increase the risk of leukemia in
offspring. A subsequent epidemiological study suggested the existence of a link between
maternal intake of these compounds and acute myeloid leukemia (AML). A statistically
significant positive association between AML and increasing the consumption of DNA
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topoisomerase II inhibitor-containing foods has been reported. No such association was observed
between maternal flavonoid consumption and acute lymphocytic leukemia (ALL). Cell line
studies with purified flavonoids (including quercetin, luteolin, fisetin, and kaempferol) have
suggested that the mechanistic basis for the increased risk of leukemia is inhibition of
topoisomerase II activity in the fetus, which causes chromosomal translocation at chromosome
11q23 involving the mixed-lineage leukemia (MLL) gene. Quercetin and fisetin were found to be
the most potent DNA topoisomerase II inhibitors (Lambert et al., 2007).
Risk of Pre-eclampsia
Recently, although promising beneficial effects have been demonstrated by tea in various
vascular diseases, yet no uniformity is seen regarding its effects in the human clinical and
epidemiological studies. A pregnancy-specific vascular disease, Pre-eclampsia, is concerned with
3% and 10% of all pregnancies worldwide accounting for about 8,370,000 cases annually.
It has been proposed that pregnant mothers consuming tea persistently may be highly
associated with any degree of pre-eclampsia risk. Different constituents of tea influence this risk
by numerous probable mechanisms like pathways related to oxidative stress or modulation of
pre-eclampsia angiogenic factors (Wei et al., 2009).
Polycyclic Aromatic Hydrocarbons (PAHs) Risk
Polycyclic aromatic hydrocarbons (PAHs) are a renowned class of carcinogens,
consisting of more than two fused aromatic rings, can be a threat to human health. Due to higher
surface area of tea leaves, contact with air can get PAHs to be accumulated. Another way PAHs
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absorption could occur is while drying the leaves in presence of combustion gases during the
production process (Lin et al., 2005).
While studying release of PAHs in tea liquor, black tea is found to contain the highest
level of all PAHs. Although the toxic 5-6 rings PAHs fail to be detected in the infusion yet 91.2-
97.2% of ΣPAHs are accounted by the milder 2-3 rings PAHs. The rate of PAHs release in tea
varies with the infusion time (Lin et al., 2005).
Due to PAHs being less soluble in water, they are not a threat to human health. However
solubility of these contaminants increases till 50% (NA) of the actual concentration in tea
infusion. The amount of essential oil in tea liquor (which serves as a co-solvent for numerous
lipophilic compounds) may account for increasing solubility of the PAHs in water. So
consuming liquor formed by tea contaminated with PAHs could pose a health risk. Sanitary
Standards are required for tea to check for health risks from PAHs in the tea (Lin et al., 2005).
Fluoride and Metal Risk
As per studies conducted by South and East Asian countries, tea contains certain
elements e.g. arsenic, aluminum, barium, cobalt, cadmium, copper, nickel, manganese, zinc and
strontium, which could adversely affect the human health (Gulati et al., 1993; Cao et al., 1996;
Wong et al., 1998; Fung et al., 1999; Lung et al., 2003; Nookabkaew et al., 2006).
The risk of dental flourosis due to intake of fluoride from the instant tea bags is not
significant. Yet recently an American patient was diagnosed with skeletal flourosis (SF) due to
long term use of instant tea bags (Whyte et al., 2005). Environmental risk assessment considers
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one in million (10-6) as the acceptable risk level for carcinogenic (Kavcar et al., 2006). With
respect to Alzheimer’s disease, the level of non-carcinogenic risk stayed in control while being
exposed to the 10 metals including aluminum. Environmental policies may affect the
acceptability levels raising it as much as 10-4 for arsenic concentrations. A study by Sofuoglu et
al. (2008) showed the arsenic concentrations to be at levels corresponding to moderately high
carcinogenic risk.
Reduced Absorption of Iron
Owing to tannins present in black tea, its consumption with meal reduces the absorption
of non-heme iron (Fe). For a meal comprising of hamburger the absorption reduces to 0.12 from
0.32 mg. It was found that on consuming tea the negative balance of iron increased for black and
decaffeinated black tea consumption than for consuming no tea (Prystai et al., 1999).
Several studies have demonstrated that black tea appears to inhibit the bioavailability of
non-heme iron by 79%–94% when both are consumed concomitantly; the impact of this
interaction depends on the Fe intake and Fe status of the individual. Similarly, green tea
catechins may have an affinity for Fe, and green tea infusions can significantly decrease the Fe
bioavailability from the diet. These studies affirmed that tea should not be consumed by patients
suffering from anaemia. For example, Fe-deficiency anaemia among children in Saudi Arabia
and the United Kingdom may be aggravated by the regular consumption of tea with meals. It is
proposed that the interaction between tea and Fe can be alleviated by the addition of lemon or
consuming tea between meals (Cabrera et al., 2006).
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The authors of a systematic review of 35 studies on the effect of black tea drinking on Fe
status in the UK concluded that tea drinking reduced the absorption of non-heme Fe from the diet
and statistically significant relationships were observed between tea drinking and poor Fe status
among preschool children (Nelson and Poulter, 2004).
Gastrointestinal Tract Cancer Risk
Cancers of upper gastrointestinal tracts pose a significant health threat to humans and
account for nearly 18% of unexampled cases of cancer worldwide e.g. oral, hypo- and oro-
pharyngeal, oesophageal, gastric and laryngeal cancers (Parkin et al., 2005).
In an experiment, consuming hot tea in large amounts was found inversely related to the
risk of pharyngeal cancer. The hazard ratio (95% confidence limits) found when compared with
individuals who did not consume hot tea to ones that consumed 1-6 cups was 0.52 and 0.37 for
those that took over 1 cup a day (Ren et al., 2010). The results showed consistency with the
findings of Southern Brazil which reported a 69% decrease of the risk of pharyngeal cancer in
hot tea drinkers over the non-drinkers (Pintos et al., 1994). However, a case study conducted in
India showed opposite results (Notani and Jayant, 1987). An increase in the risk for pharyngeal
cancer was observed for individuals who drank over 3-5 cups per day in contrast to the ones
consuming 2 or less cups of hot tea in a day (Vecchia et al., 1992; Mashberg et al., 1993; Tavani
et al., 2003; La Ide et al., 2007). Other studies conducted prove that there is no link between
consumption of hot tea and pharyngeal, oral cavity tumors or the remaining 5 upper
gastrointestinal cancer sites (Ren et al., 2010).
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Tea’s effect for prevention of cancer has been researched a lot in the past few years
(Yang et al., 2008). The tea PPs are believed to affect a number of carcinogenesis areas e.g.
growth of cancer cells, metastasis and apoptosis (Beltz et al., 2006). However, chronic thermal
injuries caused due to drinking beverages that are too hot could lead to carcinogenesis in some of
the UGI sites (Castellsague et al., 2000; Islami et al., 2009a; Islami et al., 2009b). Furthermore,
on processing black tea, carcinogenesis contaminations may be acquired in form of mycotoxins
or benzo[α]pyrene (BαP) (Martins et al., 2001; Lin and Zhu, 2004).
Hot tea was found to affect positively for the oesophageal squamous cell carcinoma
(ESCC) risk (Ren et al., 2010). In three other case control studies, green tea was found to protect
against oesophageal cancer (Gao et al., 1994; Mu et al., 2003; Wang et al., 2007). On the other
hand, intake of green tea was found to be linked to oesophageal cancer in men in two studies
(Hara et al., 1984; Ishikawa et al., 2006). A recent case control study in Iran revealed existence
of no relation of black tea with ESCC (Islami et al., 2009b). While, a case control hospital based
study involving 1248 cases of ESCC and 1248 controls, in China reported an inverse association
between Chinese black tea, called Congou tea and the ESCC risk (Ke et al., 2002). Furthermore,
after an analysis of 13 epidemiological studies, a noticeable inverse relation was found between
consumption of green tea and the risk of stomach cancer (Myung et al., 2009). Recently, a case
control study in Italy involving 999 gastric cancer patients and 2628 controls reported an
implausible association between black tea consumption and the gastric cancer (Ren et al., 2010).
Islami et al. (2009b) investigated the association between tea drinking habits in Golestan
province, northern Iran, and risk of oesophageal squamous cell carcinoma in a population based
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case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk
were measured in a cohort study of healthy participants. The results of the case-control study
showed that drinking hot or very hot tea was strongly associated with a higher risk of
oesophageal cancer, compared to that of drinking luke warm or warm tea. The interval between
tea being poured and drunk was inversely associated with risk of oesophageal squamous cell
carcinoma. Similarly, compared with drinking tea 4 or more minutes after being poured, drinking
tea 2-3 minutes or less than 2 minutes after pouring was associated with a significantly increased
risk. A previous study reported a significantly higher tea drinking temperature among 7
participants with oesophageal disorders (62°C) than among 50 controls (56°C) (Pearson and
McCloy, 1989).
Colorectal Cancer Risk
The association of black tea to colorectal cancer when studied for men and women
brought forward certain facts. In women black tea showed a protecting effect on colorectal
cancer while mild risk enhancement was noted for men. A few studies and reports have
established an association of colorectal carcinogenesis protection with the sex hormones (Sun et
al., 2006). A population-based case-control study in Moscow showed an inverse association of
tea consumption with rectal cancer in women. In men, no such association was evident due to
high levels of alcohol consumption which not only is a risk for the disease but also reduces the
protective effect of tea (Il'yasova et al., 2003).
Although the nonhuman in vivo and in vitro studies support the chemo-preventive effect
of black and green tea on colorectal carcinogenesis, yet the information from epidemiologic
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studies is not sufficient to prove the preventive effect of tea on human colorectal cancer (Sun et
al., 2006).
Osteomalacia and Alzheimer’s disease Risk
Some studies have revealed the high capacity of tea plant to accumulate aluminum (Al), a
neurotoxic element. This aspect is important for the individuals with renal failure because
accumulation of Al by the body can result in neurological diseases; therefore it is necessary to
control the intake of food with high amounts of this metal. Studies have found concentrations of
Al (which is naturally taken up from soil) in green and black teas (as infusions) that range from
14-27 μg/L to 431-2239 μg/L. One study reported that black tea contains approximately six-fold
more Al than green tea, and the extraction of Al in black teas was higher than in the green teas;
the Al concentrations in the tea infusions remained constant after 5 min of extraction. The
variations in Al content may be due to different soil conditions, different harvesting periods, and
the influence of the water quality. The possible connection between elevated tissue Al content
and problems such as osteomalacia and neurodegenerative disorders (i.e., Alzheimer’s disease)
has enlightened interest in Al intake via diet. Several studies reported that in order to avoid
potentially toxic levels Al dietary intake must not exceed 6 mg/day. Several authors consider that
Al is poorly absorbed by the body, so future studies are necessary to accurately assess the
presence and bioavailability of Al in green tea leaves (Cabrera et al., 2006).
Parkinson’s disease Risk
Parkinson’s disease (PD) may be attributed to the complex interactions of both genetic
and environmental factors. Studies regarding the association of caffeine-containing beverage
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such as tea and PD risk show conflicting results. Tea consumption was shown to be a risk factor
for PD in a case-control study in France. Contrastingly, a cohort study in Singapore Chinese
Health study showed an inverse relation of black tea with PD risk but this association was
independent of caffeine intake; other components of black tea accounted for this protective
effect. Green tea, however, didn’t show any effect (Tanaka et al., 2011).
CONCLUSION AND FUTURE DIRECTIONS
According to the recent research in last 30 years, tea has been identified as a Nature's
reward for promoting human health. There is a continuous increase in the amount of
experimental evidence filing the properties of tea and its constituents. Subsequently, both
endogenous and exogenous factors that influence the incidence and development of many
chronic diseases are being defined and understood in a better way. Evidence shows that the tea is
a source of a large variety of phytochemicals that are digested, absorbed and metabolized by the
body, and that the effects of tea constituents are exerted at the cellular level. Status of tea as a
functional food provides credibility to the beliefs of tea drinkers for centuries.
Debate still persists to conclude that whether tea is beneficial or somewhat troublesome
for human health. Because of its wide-spread and long use, it is considered to be safe and
effective against various cancers, cardiovascular diseases as well as diabetes mellitus.
Nevertheless, several cases of hepatotoxicity, neurodegenerative disorders and other adverse
effects following the consumption of large amounts or concentrated preparations of C. sinensis
have been reported.
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Future research needs to outline the actual extent of health benefits, ascertain the secure
range of tea consumption associated with these benefits and clarify probable mechanisms of
action. New experimental systems must be developed in order to further evaluate the effects of
tea on humans. Development of methods which are more specific and sensitive with more
models of representation together with the development of good predictive biomarkers will
enable a better understanding of the interaction of tea with endogenous systems and other
exogenous factors. Being one of the most popular beverages worldwide, further studies on tea
regarding the assessment of its consumption and polyphenol status should be directed to
enumerate its role in the primary and secondary prevention of chronic diseases.
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Figure 1. Principal differences between green and black tea processing and its influence on the
final polyphenols content. (Source: Cabrera et al., 2006)
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Figure 2
BOTANICAL CLASSIFICATION
Kingdom: Plantae
Division: Magnoliophyta
Class: Magnoliopsida
Order: Theales
Family: Theaceae
Genus: Camellia
Species: sinensis
Figure 2. Morphology of Camellia sinensis (Source: Ravindranath et al., 2006)
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Figure 3
Figure 3. Potentially detrimental effects of concentrated green tea extract (GTE). (Source:
Schönthal, 2011)
Liver damage
(rare)
Interactions with other
natural supplements
Interference with
transmembrane drug
efflux pumps
Interactions with medications:
 reduced absorption
 limited bioavailability
 direct inhibition of activity
Interference with
metabolic enzyme
activity
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