The black tea bioactivity: An overview

Abstract

Tea is one of the most popular beverages in many countries and is the second, after the pure water, most consumed drink in the world, but consumption habit varies between different countries. Incidence of different diseases varies widely across the world and many investigators relate these differences to diet including habitual tea drinking. It is consumed mostly as green tea and black tea where other forms such oolong; red or white teas are less popular. Green tea was extensively investigated on its health benefits but black tea is only now catching the serious attention of scientific community. Compounds contained in black tea such as theaflavins and thearubigens contribute to black tea dark color and distinctive flavor. They also provide health benefits originally attributed solely to green tea. This review summarizes available information on bioactive ingredients of tea, their bioactivity and relation to diseases, bioavailability with special attention to health benefits of black tea.

Full text

Central European Journal of Immunology 2011; 36(4)
284
Review paper
The black tea bioactivity: an overview
MAGDALENA SKOTNICKA1,2, JOANNA CHOROSTOWSKA-WYNIMKO3, JERZY JANKUN1,4,5,
EWA SKRZYPCZAK-JANKUN1
1Urology Research Center, Department of Urology, The University of Toledo – Health Science Campus, Toledo, USA
2Department of Chemistry, Biochemistry, Ecology and Food Commodity, Gdañsk Medical University, Gdañsk, Poland
3Laboratory of Molecular Diagnostics and Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
4Department of Clinical Nutrition, Medical University of Gdañsk, Gdañsk, Poland
5Protein Research Chair, College of Sciences, King Saud University, Riyadh, Saudi Arabia
Correspondence: Jerzy Jankun, D.Sc., PhD, Prof., Director Urology Research Center, Department of Urology, Mail Stop 1091, Health Science
Campus, The University of Toledo, 3000 Arlington, Toledo, OH 43614-2598, phone number (419) 383-3691; fax number (419) 383-3785,
e-mail: Jerzy.Jankun@utoledo.edu
Tea is the second, after the pure water, most consumed
drink in the world. It is one of the most well-liked bever-
ages in many countries. Among other popular drinks it con-
tains the highest concentrations of minerals and antioxi-
dants. The real teas are produced from the same species of
the plant Camellia sinensis. There are four types of basic
teas: unfermented green tea, fully fermented black tea, red
tea which is partially fermented oolong tea and white tea
from tea leaf buds. Approximately 20% of the world’s con-
sumption is in the form of green tea, and other 80% are
black and oolong teas [1]. Tea is grown in about 30 coun-
tries but as a popular drink it is mostly consumed in Asia
and Europe, less in North America and North Africa (main-
ly Morocco). Green tea is popular in whole Asia while
oolong is mostly drank in China and Taiwan [2].
Bioactive ingredients of fresh leaves and
green tea
Fresh leaves of tea contain on average: 36% polyphe-
nolic compounds, 25% carbohydrates (pectins, glucose,
fructose, cellulose), 15% proteins, 6.5% lignin, 5% miner-
als and trace elements (magnesium, chromium, iron, cop-
per, zinc, sodium, cobalt, potassium, etc.), 4% amino acids
(such as theanine [5-N-ethyl-glutamine], glutamic acid,
tryptophan, aspartic acid) 2% lipids, 1.5% organic acids,
0.5% chlorophyll as well as carotenoids and ethereal sub-
stances below 0.1%, vitamins (B, C, E) [3]. Green tea leaves
are pan-fried or steamed, which prevents different bioac-
tive compounds, like many polyphenolic flavonoids, from
being oxidized. An average serving of green tea is brewed
of 2 g of leaves in ~200 ml of hot water and contains
approximately 600-900 mg of water extractable solids
including tea catechins (30-40% by weight). The rich con-
tent of catechins representing approximately 90% of the
polyphenolic fraction in green tea (considerably more than
in black tea) is believed to generate its pro-health effects
(Table 1). Tea catechins appear as isomers trans-catechins
and cis-catechins depending on the stereochemical config-
uration of the 3’,4’-dihydroxyphenyl and hydroxyl groups
at the 2- and 3-positions of the C-ring [4]. Main catechins
found in green tea are: catechin (C), gallocatechin (GC),
Abstract
Tea is one of the most popular beverages in many countries and is the second, after the pure water,
most consumed drink in the world, but consumption habit varies between different countries. Incidence
of different diseases varies widely across the world and many investigators relate these differences to
diet including habitual tea drinking. It is consumed mostly as green tea and black tea where other forms
such oolong; red or white teas are less popular. Green tea was extensively investigated on its health
benefits but black tea is only now catching the serious attention of scientific community. Compounds
contained in black tea such as theaflavins and thearubigens contribute to black tea dark color and
distinctive flavor. They also provide health benefits originally attributed solely to green tea. This review
summarizes available information on bioactive ingredients of tea, their bioactivity and relation to diseases,
bioavailability with special attention to health benefits of black tea.
Key words: black tea, polyphenols, bioavailability, cancer, cardiovascular.
(Centr Eur J Immunol 2011; 36 (4): 284-292)
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Central European Journal of Immunology 2011; 36(4) 285
epicatechin (EC), epigallocatechin (EGC), epicatechin gal-
late (ECG), epigallocatechin gallate (EGCG). In addition,
green tea contains alkaloids (caffeine) and other flavonoids
such as quercetin, kaempherol, and myricetin [5-7]. Epi-
gallocatechin gallate was the most extensively studied active
component of green tea and is known for its anti-cancer
properties and potent antioxidative effect. It is a stronger
antioxidant than either vitamin C or E.
Bioactive ingredients of black tea
There are various types of black tea, mostly named after
the geographical region they came from. Assam tea is
named after Assam, the region in India. It brews as bur-
gundy red with rich aroma and a strong, malty taste. Yun-
nan tea is produced in Yunnan region of China. It is char-
Table 1. Content of different polyphenols in green and black
tea (µg/ml) [13]
Compound Green tea Black tea
(µg/ml) (µg/ml)
catechin (C)
(–)-epicatechin (EC)
(–)-epicatechin-3-gallate (ECG)
(–)-epigallocatechin (EGC)
(–)-epigallocatechin-3-gallate (EGCG)
Total catechins
theaflavin (TF1)
theaflavin-3-gallate (TF2a)
theaflavin-3’-gallate (TF2b)
theaflavin-3,3’-digallate (TF3)
Total theaflavins
21
98
90
411
444
1064
0
0
0
0
0
20
37
73
42
128
300
22
20
13
9
64
(+)-C-catechin R1 = H, R2 = OH, R3 = H
(–)-EC-epicatechin R1 = OH, R2 = H, R3 = H
(–)-ECG-epicatechin gallate R1 = galloyl, R3 = H
(–)-EGC-epigallocatechin R1 = OH, R2 = H, R3 = OH
(–)-EGCG epigallocatechin gallate R1 = galloyl; R2 = H; R3 = OH
polyphenol
oxidase + O2quinones +
catechins
+ O2
–CO2
HO
R1
R2
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
HO HO
HO
HO
R1 R1
HO
HO
R2 R2
R3
OH
OH
further
oxidation
Thearubigin R1, R2 = galloyl
Theaflavin R1 = OH, R2 = OH
Theaflavin-3-gallate R1 = galloyl, R2 = OH
Theaflavin-3’-gallate R1 = OH, R2 = galloyl
Theaflavin-3,3’-gallate R1, R2 = galloyl
Fig. 1. Conversion of catechins of green tea to theaflavins and thearubigins of black tea [1]
O
O
O
OO
O
O
O
O
COOH
COOH
The black tea bioactivity: an overview
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Central European Journal of Immunology 2011; 36(4)
286
acterized by malty and peppery flavor. Darjeeling tea com-
ing from the Darjeeling region in West Bengal, India is
famous for its it light-color floral aroma with tannic char-
acteristics.
Nilgiri tea grows in the hills of the Nilgiri district of
Tamil Nadu in India. It is very aromatic with a distinct
briskness and a tantalizing flavor. Ceylon tea is cultivated
in Sri Lanka (formerly Ceylon). It is known for its citrus
taste and therefore is available in pure but also blended form
[8, 9].
The tea fermentation process allows the leaves to under-
go enzymatic oxidation when polyphenol oxidase causes
polymerization of flavan-3-ols to catechin oligomers – bis-
flavanols, theaflavins, thearubigins and others. As a result
only ~15% catechins from green tea remain unchanged, the
rest is transformed to theaflavins and thearubigins [1] – see
Fig. 1. Hence, in contrast to green tea with yellowish-green-
ish hues, fully fermented black tea has a dark brown hue
and a sweet aroma of malt sugar.
The typical black tea brew is composed of number of
small molecules, mostly alkaloids (e.g. theobromine and
caffeine), carbohydrates and aminoacids (including thea-
nine) as well as glycosylated flavonoids, together account-
ing for 30-40% of the dry weight. The remaining 60-70%
consists of poorly characterized polyphenolic fermentation
products, in that number oxytheotannins further subdivid-
ed into theaflavins and thearubigins. Theaflavins (a mix-
ture of [theaflavin-3-gallate, theaflavin-3’-gallate and
theaflavin-3,3’-digallate] posses benzotropolone rings with
dihydroxy or trihydroxy aromatic moieties as substituents
and a characteristic yellow-orange color [10]. The red-
brown or dark brown thearubigins consist of more than
5000 individual compounds retaining chiral properties of
flavanols and theaflavins while prone to aggregation in
aqueous solution. Their structures and bioavailability are
still not well characterized [11]. Theaflavins and thearubi-
gins account for 3-6% and 12-18% of dry weight of black
tea and contribute to its strong, bitter flavor and character-
istic dark color [12]. Comparison of a content of the basic
compounds in crude black and green tea extract is given in
Table 1 [13].
During the production process as much as 75% of cat-
echins from tea leaves undergo oxidation and partial poly-
merization due to the enzymatic processing by polyphenol
oxidase and other endogenous enzymes. Therefore, the final
black tea composition considerably depends on the pro-
cessing technology.
In average expected composition of black tea solid
extract includes: catechins (10-12%), flavonols (6-8%),
theaflavins (3-6%), thearubigins (12-18%), phenolic acids
(10-12%), amino acids (13-15%), methylxanthines (8-11%),
carbohydrates (15%), proteins (1%), and minerals (10%).
The most important flavonols in black tea are myricetin,
quercetin, kaempferol and ruthin, similar as in green tea.
Black tea also contains phenolic acids, caffeine (about one
third the amount typical for coffee) and amino acids includ-
ing theanine (5-N-ethyl-glutamine) which occurs only in
the tea leaves [3].
Theanine (γ-glutamylethylamine) is a compound unique
for tea accounting for almost 50% of its aminoacid content
as well as unique “brothy” taste. It is known for consider-
able neuroprotective effects and cognition enhancing prop-
erties, assists in brain function development i.e. central nerv-
ous system maturation [14]. Theanine was also shown to
act as an neurotransmitter, modulator of serotonine and
dopamine levels enhancing memory and learning abilities
[15]. Importantly enough theanine plays its positive role in
attentional processing in synergy with caffeine [16].
Black tea bioactivity – known facts
The impact of green tea, in particular its flavonoids
and catechins, on the oxidant-antioxidant balance has been
extensively studied. Their antioxidative properties are rec-
ognized and mostly attributed to the ability to inhibit free
radical generation or biological activity activity as well as
to chelate transition metal ions, mainly Fe and Cu catalyz-
ing the free radical reactions.
On the other hand little is known about more complex
compounds formed from catechins during natural fermen-
tation in the process of black tea production [2, 17]. While
catechins repreFsent ~90% of phenolic fraction in green
tea, in black tea brew only ~15% of them remains not oxi-
dized. Still, black tea is a valuable source of polyphenols,
majority of them belonging to oxytheotannins, represent-
ed by theaflavins and thearubigins. Rechner et al. have
shown that a cup of black tea delivers on average ~260 mg
of polyphenols of which ~220 mg stand for theaflavins and
thearubigins. Authors researched seven different brands of
black tea marketed in England showing that each contained
similar combination of polyphenols dominated by thearu-
bigins (75-82% of total phenolics) and followed in
a decreasing order by theaflavins, flavan-3-ols, flavonols,
gallic acids and hydroxycinnamates [18]. Among them epi-
gallocatechin gallate, four theaflavins, epicatechin gallate,
quercetin-3-rutinoside, 4-caffeoylquinic acid were clearly
and theogallin tentatively identified, with the total of 20
polyphenols as quantified by HPLC analysis. The antioxi-
dant activity was assessed independently by three different
methods (Trolox Equivalent Antioxidant Capacity – TEAC,
Oxygen Radical Absorbence Capacity – ORAC, Ferric Ion
Reducing Antioxidant Power – FRAP) showing good cor-
relation in-between the methods as well as corresponding
with previously published studies that characterized
oxytheotannins as effective scavengers of free oxygen
(superoxide anions, singlet oxygen) and nitric (nitric oxide,
peroxynitrite) reactive oxygen species (ROS). Interesting-
ly, theaflavins being dimers contain more hydroxyl (OH)
groups than catechins, and this structural detail is pivotal
for radical scavenging abilities. As a result, some
Magdalena Skotnicka et al.
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Central European Journal of Immunology 2011; 36(4) 287
theaflavins, like TF3 reveal higher antioxidative activity
than EGCG, the strongest antioxidant among catechins.
Also, it was demonstrated that theflavins react over 10 times
faster with superoxide radical than EGCG [3].
Beside free radicals scavenging theaflavins antioxidant
properties are attributed to their ability to inhibit pro-oxi-
dant enzymes and form stable complexes with iron or cop-
per ions, therefore preventing free radical generation and
lipid peroxidation. Yet, the concentration of black tea
polyphenols in human blood even after considerable tea
ingestion is 100-1000 times lower than the circulating
amounts of other physiological antioxidants, like ascorbic
acid or glutathione. That fact provokes the question about
the practical meaning of the abovementioned antioxidant
activity of black tea. Does it really induce any meaningful
effects in vivo?
The increased antioxidant activity has been observed
in laboratory animals exposed to the prolonged black tea
enriched diet. In humans however, results were somewhat
diverse. The ex vivo studies clearly confirmed the scav-
enging properties of black tea and catechins towards human
cells. Interestingly, black tea extract in comparison to cat-
echins exerted higher protective effect towards various types
of oxidative stress [3, 19]. The ion chelating activity of tea
polyphenols is a well proven fact. They avidly interact with
iron ions forming the insoluble complexes, black tea more
than the non-fermented green tea. This process inhibits
haem absorption in the gastrointestinal tract, though
involves the non-haem iron only and might be reversed in
the presence of the ascorbic acid. It is not clear to what
extend this phenomenon is responsible for the antioxidant
activity of black tea in the real-life setting, however defi-
nitely affects the balanced iron turnover.
However, good quality data on the comparison of the
antioxidative capacity of black and green tea are somewhat
contradictory concluding that black tea activity is higher,
on par or diminished in relation to green. Prior and Cao
compared eighteen green and black tea brands from differ-
ent sources demonstrating that an average antioxidative
capacity (ORAC) and total phenolic content for the black
tea is clearly higher than for green one [20]. Alternatively,
Benzie and Szeto evaluated 25 blends of local Hong Kong
tea by FRAP method concluding that green had the high-
est antioxidant potential while black and oolong tea were
similar and less potent in that respect [21]. Still, when green
tea was evaluated against black tea of the same brand
(Assam from India) thus eliminating possible discrepancies
due to the different plants, environmental factors and pro-
duction site, no considerable differences in TEAC poten-
tial were observed [22]. Consequently, it should be accept-
ed that ROS scavenging potential of black tea differs for
different commercial brands, solidly depending on geog-
raphy and technology of production. Thus, results from any
clinical studies in humans strongly depend on local cir-
cumstances. Positive impact of black tea polyphenols on
consumer health seriously depends on people overall metab-
olism but also bioavailability of their metabolites [18].
Xie et al. signalized that flavanols and other constituents
of black tea in a pure form are not only strong antioxidants
but also the effective lipoxygenase inhibitors [23]. It is
worth noticing that human oxygenases are responsible for
fatty acids peroxidation in a submembrane environment of
cells, clearly related to ROS, ubiquitous in the body and
implicated in many human diseases (inflammatory, car-
diovascular, cancers, neurological disorders). Halder and
Bhaduri studied black tea extract as possible preventative
of oxidative stress provoked in human blood by different
inducers. They have found that black tea or its chosen com-
ponents could avert lipid peroxidation, degradation of mem-
brane proteins and reverse membrane fluidity to full restora-
tion of its architecture. In their experiments black tea extract
was performing better than individual catechins proving
that theaflavins and thearubigins which dominate in black
tea brew are just as effective or better than smaller and sim-
pler catechins [19].
Bioavailability of black tea components:
problems and promises
Extensive data indicate that bioactive components of
black tea might be quite important for prevention of con-
siderable number of disorders. While abovementioned stud-
ies on black tea components seem to strongly support that
view, their bioavailability analysis points at its possible
flaws. The relatively high molecular weight, low internal
activity, poor absorption, high rate of metabolisms, and rap-
id inactivation of metabolism products are considered the
most important reasons for rather low bioavailability of
black tea polyphenols. It is also affected by the fact that
phenolic OH group tends to form large hydration shells
[24]. On the other hand Rechner et al. elegantly proved that
incubation of the black tea brew with the simulated gastric
acids significantly increased content of the theaflavins
(140%). It was attributed to the cleavage of the thearubi-
gins at low pH into smaller and therefore more readily
absorbed theaflavins [18]. Some authors have also sug-
gested the possibility of the prolonged colonic metabolism
of black tea polyphenols, theaflavins and thearubigins [25].
Warden et al. quantitatively evaluated bioavailability
of black tea catechins in healthy volunteers demonstrating
their peak in the plasma 5 hours after ingestion, with only
1.68% of their total intake present in the blood, urine and
feces [26]. Catechins were present in the blood for 24 hrs
after single intake of tea. Interestingly, several studies
demonstrated different bioavailability of gallated and non-
gallated forms, but their conclusions were contradictory
[26-28]. In our opinion methodological issues and diffi-
culties in exact theaflavin metabolites estimation might be
responsible for those discrepancies. Detection of theaflavin
metabolites with the modified Aand C ring only, could not
The black tea bioactivity: an overview
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288
be considered adequate and reliable measure of their
bioavailability [28, 29].
However, Leenen et al. have shown that antioxidative
potential of plasma after black tea ingestion was not dif-
ferent to that observed after green tea, irrespective of the
dissimilar catechin levels, confirming the suggestion of their
rapid absorption from the gastrointestinal tract [30]. Simi-
larly, the theaflavin and thearubigin fractions of black tea
strongly inhibited human recombinant sulfotransferase
SULT1A1 and SULT1A3 isoforms representing liver and
intestinal enzymatic activity therefore affecting mechanisms
regulating absorption [31].
Still, the bioavailability of theaflavins and thearubigins
and understanding of their metabolism and resulting
metabolites is unclear and needs further cautious evalua-
tion. Besides, little is known about possible effects of diet
on the bioavailability of tea constituents. Immense differ-
ences in regional dietary habits are rarely considered where-
as might be of considerable importance, responsible for
example for varying result observed in clinical studies on
the health effects of long-term ingestion of black tea. Sim-
ilarly, the effect of milk added to the tea brew as it is cus-
tomary in UK and other Commonwealth countries should
be accounted for. While milk proteins bind directly and eas-
ily to black tea catechins and flavonols, Hertog et al.
demonstrated that beneficial effect of black tea consump-
tion on the risk of coronary heart disease was not observed
in subjects consuming tea with milk [32]. It is still unclear
what mechanism is responsible for this effect. Both ex vivo
and in vivo studies are equivocal at best.
Consequently, any studies evaluating the in vivo bioac-
tivity of black tea or its constituents should strictly define
the studied group according to demographic (race) as well
as geographic criteria. Both strongly imply critical differ-
ences in tea content (black vs. green, brands of black tea)
as well as consumption habits (with milk pre-boiled or
fresh, with lemon, habitual diet) that might considerably
affect the outcomes. This particular fallacy is unfortunate-
ly quite common. If black tea undeniable bioactivity is to
be evaluated properly and relevantly exploited in humans
more well designed studies are needed.
Medicinal effects of black tea
Bioactive components of the black tea brew have been
attracting much attention with regard to human health.
While in vitro data demonstrate quite convincingly their
considerable biological activity, animal and clinical stud-
ies have been less conclusive regarding to their effective-
ness and potential applicability in disease prevention or
therapy (supplementary role). Still, some data provide
intriguing evidence on their beneficial effects, in particu-
lar in chronic pathologies characterized by high oxidative
stress.
Atherosclerosis and cardiovascular
diseases
The mechanism of atherosclerosis and consequently
cardiovascular diseases (CVD) involves chronic inflam-
mation, endothelial dysfunction and metabolic imbalance.
Animal studies showed that black tea consumption reduces
cholesterol liver synthesis and its serum levels thrice more
effective than green tea [33, 34]. Similar effect was demon-
strated by placebo-controlled randomized study in humans
with five servings of black tea resulting in slight drop of
total and LDL cholesterol in serum of mildly hipercholes-
terolemic patients [35]. Vermeer et al. proved as well that
black tea theaflavins, in particular theaflavin-3-gallate,
might interfere with intestinal cholesterol absorption [10].
In contrast, data on the low density lipoprotein (LDL) oxi-
dation are unequivocal. Some authors observed no protec-
tive effect of black tea [36]. Others, as Ishikawa, docu-
mented that catechins, especially EGCG, and theaflavins
strongly delay LDL oxidation i.e. atherosclerosis develop-
ment and progression [37]. And finally some suggested that
black tea might have greater impact on the ex vivo lipopro-
tein oxidation that green tea [38]. As described before black
tea components, like flavonoids, are reducing agents capa-
ble to effectively chelate metals involved in cellular oxi-
dation reactions. Hence their preventive/ameliorating effect
on the oxidative stress within endothelial barrier support-
ing the normalization of endogenous vasodilators produc-
tion, restoration of physiological endothelial barrier per-
meability as well as down-regulation of inflammatory
markers and mediators expressed by endothelial cells.
Jochmann et al. proven that beneficial effects of black tea
on the endothelial function, both ex vivo and in patients,
were comparable to green tea [39]. Also, catechins are able
to incuce cell-cycle arrest and interact with growth factor
to inhibit vascular smooth muscle proliferation, a key event
in the development and progression of atherosclerosis [40].
In addition, considerable effect of black tea on the meta-
bolic and inflammatory markers represented by uric acid
(UA) and C-reactive protein (CRP) was observed in con-
trolled studies [41].
Still, epidemiological studies attempting to analyze the
link between black tea consumption and risk of cardiovas-
cular death are inconclusive. Meta-analysis of ten cohort
studies and seven case-control studies performed by Peters
et al. in 2001 demonstrated considerable heterogeneity pre-
venting reliable estimation of black tea effect on the stroke
and coronary heart disease incidence. Still, occurrence of
myocardial infarction has been shown to decrease by 11%
(relative risk = 0.89) providing that at least three cups of
black tea were consumed per day [42]. Heterogeneity of
evaluated data revealed by this analysis was consistent with
size of the analyzed studies (smaller tending toward sig-
nificant effects) and their geographical origin. On the oth-
er hand, Huxley et al. in their meta-analysis of prospective
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Central European Journal of Immunology 2011; 36(4) 289
cohort studies observed a 20% risk reduction in coronary
artery disease mortality in participants within a top tertile
of flavonoid intake However, subsequent large cohort proj-
ects performed in European Welsh (n= 17 228) and Japan-
ese groups (n= 76 979) demonstrated no significant asso-
ciation between black tea consumption and the risk of CVD
incidence both in men and women [43, 44].
Some authors suggested that black tea polyphenols
might exert positive effects in patients already treated due
to CVD [45]. Duffy et al. analyzed both short- and long-
term effects of black tea on the endothelial dysfunction in
50 patients with confirmed coronary artery disease and
showed significant endothelium-dependent flow-mediated
arterial dilation [46]. Similar effect was described in healthy
volunteers [47]. Also, Hirata et al. have shown improved
coronary flow velocity reserve as assessed by transthoracic
Doppler echocardiography following acute black tea con-
sumption [48].
Acute and chronic inflammation
Considerable evidence points at the anti-inflammatory
bioactivity of the black tea polyphenols. It is warranted not
only by their anti-oxidant properties. Tea polyphenols and
EGCG in particular are able to selectively affect the pro-
duction and/or bioactivity of pro-inflammatory cytokines
(IL-1β, TNF-α, IL-6, IL-8) and mediators (iNOS, COX),
mostly by modulating cellular signaling processes (NF-κB)
[15]. Moreover, both black tea extract and three major black
tea-derived catechins: epicatechin gallate, epigallocatechin
and epigallocatechin gallate, were shown not only to sup-
press production of IL-1βby human leukocytes, but also
to enhance synthesis of well-known anti-inflammatory
cytokine IL-10 [49]. In the animal models of paw oedema
black tea extracts significantly inhibited acute inflamma-
tory response induced by number of physiological media-
tors (histamine, serotonin, prostaglandin) [50]. It has been
repeatedly suggested that chronic persistent inflammation
both low-grade as in atherosclerosis and more severe as
chronic arthritis are to certain extend down-regulated by
the black tea constituents. However, it should be empha-
sized that these effects were observed mainly at catechins
concentrations hardly achievable in human plasma in vivo.
Therefore the average black tea consumption is quite unlike-
ly to exert considerable protective anti-inflammatory effect.
The beneficial effect of black tea on the caries development
and progression seems to be the exception. Black tea brew
in standard, customary quantities appears to suppress sali-
vary amylase activity, decrease tooth surface pH and there-
fore reduce the growth and virulence of periodontal
microorganisms [24, 51]. Moreover, regular consumption
of black tea affects dental bone density due to the higher
fluoride content as the tea plant tends to accumulate fluo-
ride from soil as well as due to other chemical tea com-
pounds, caffeine and phytoestrogens, influence [52].
Cancer
There is a vast literature suggesting beneficial effects
of regular green tea intake on the malignancies incidence
in humans including: liver, lung, stomach, pancreatic, colon,
breast, oral and prostate cancer [53-58]. Still, the thorough
Cochrane meta-analysis of 51 studies with more than 1.6
million participants did not provide any firm conclusions.
On the contrary, it was implied that data were insufficient
and inconsistent. Still, in some types of neoplastic disease
as prostate or lung cancer there was moderate evidence of
risk reduction shown, while in others as gastric or urinary
bladder cancer no effect was observed [1]. Recent
exploratory meta-analysis of 13 observational studies con-
firmed borderline significant association between high green
tea consumption and lower prostate cancer risk, with sig-
nificant ameliorating effect observed in case-control stud-
ies (OR = 0.43) [59]. Still, it should be emphasized that reg-
ulatory authorities in Europe and USA are not as yet
satisfied with abovementioned evidence. Green tea is not
registered or officially recommended as an effective bioac-
tive medicinal substance.
Epidemiological data concerning black tea effects are
even more scant and generally suggest much weaker effect
if any. In the citied meta-analysis no statistically significant
association was observed between black tea consumption
and cancer risk [59]. Numbers of studies provide data on
the use of green tea or green tea polyphenols to enhance the
effectiveness of chemo/radiotherapy. For black tea no com-
pelling data are available [60]. While results of epidemio-
logical analyses are irregular, research data provide quite
persuasive evidence supporting chemo preventive effect of
teas, though much stronger for green than for black tea.
There are multiple and quite divergent mechanisms pro-
posed to explain anti-cancerous tea effects including antiox-
idant, anti-proliferative, anti-inflammatory, antibacterici-
dal and antiviral activity. Many of them are attributed to the
polyphenols bioactivity, EGCG in particular. Strong radi-
cal scavengers and metal chelators exert ameliorating effect
on the oxidative stress, one of the driving processes in can-
cerogenesis [3]. Interestingly, polyphenols induce also pro-
duction of endogenous anti-oxidant molecules and enzymes
enhancing physiological defense mechanisms [61]. Gutier-
rez-Orozco et al. showed that both, green and black tea
extracts exerted down-regulatory effect on the IL-8 pro-
duction and secretion by IL-1βstimulated gastric cancer
cells [62]. Therefore, it was demonstrated that both teas
possess anti-inflammatory activity, also toward persistent-
ly acute inflammation. Observed effect was irrespective of
their different catechin profiles and mediated via inhibition
of intracellular transcription factor NF-κB [62]. In this con-
text, anti-bacterial and anti-viral properties of green and
black tea flavonoids should be recalled as they provide addi-
tional defensive anti-inflammatory mechanism potentially
important in the real-life setting [24]. An excellent exam-
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290
ple might be the abovementioned protective influence on
caries as well as oral cancer cells development and pro-
gression [51, 63].
Tea extracts and constituents are also known for they
ability to directly affect mutagenesis as well as cancer
growth. The antimutagenic effect is well documented for
the green but also black tea polyphenols, in particular
theaflavins and thearubigins and attributed both to the inhi-
bition of the oxidative DNA damage as well as modulation
of xenobiotic-metabolizing enzymes [63, 64]. Also, con-
siderable literature demonstrates their inhibitory effect on
the tumor cell proliferation both in vitro and in vivo in ani-
mal models. Lyn-Cook et al. showed that green and black
tea polyphenols, black tea theaflavins and pure EGCG
decreased down to 10% proliferative rate of pancreatic
(HPAC) and prostate tumor (LNCaP) cells [65]. Similar
effect of black tea theaflavins was observed in the mice
model of lung cancer [66]. It was also proven that tea
polyphenols considerably suppress production and reac-
tivity of cytokines regulating tumor cells growth, like
VEGF, PDGF or protein kinases, like MAP kinase or IkB
kinase. Also, Zhao et al. demonstrated that black tea aque-
ous extract, predominantly theabrownins, not only signifi-
cantly decreased gastric cells viability, but also induced cell
cycle arrest in S phase. Interestingly, normal gastric cells
were not affected [67]. In addition, considerable effect on
the cancer cells apoptosis was shown, though considerably
stronger for green tea most probably due to the higher cat-
echin content. It was suggested that tea polyphenols effec-
tively affect these processes as well mainly via regulation
of nuclear factor κB, Akt and p53 [68, 69]. Hibasami et al.
shown that black tea theaflavins can induce apoptosis and
inhibit the growth of human stomach cancer cells in a time
and dose dependent manner [70]. Finally, green and black
tea extracts proved to suppress cancer cells invasiveness
and ability to metastasize via inhibition of angiogenesis,
proteases and cytokines production [71].
Still, irrespective of numerous studies analyzing in
detail the mechanism of tea biological activity, there is con-
siderable inconsistency between epidemiological and exper-
imental data. Several factors might be responsive for that
including inadequate average tea consumption (to low
intake of bioactive tea constituents to exert positive effect).
However, human genetic heterogeneity together with cul-
tural and life-style differences are most probably the key
reasons. Described dissimilarities between European and
Asian cohort studies strongly support that suggestion.
Other disorders
It was implied that antioxidant and anti-inflammatory
effects of tea consumption might be useful to support phar-
macological therapy of neurodegenerative Parkinson’s and
Alzheimer’s disorders by attenuating the degeneration of
dopamine neurons and promote neurons survival [72, 73].
In recent years number of experimental and observational
studies in humans provided strong evidence for the posi-
tive effect of green and black teas on weight control in
obese subjects [73-77]. Most likely, the underlying mech-
anism is very complex and still not very well understood.
Still, the significant reduction of serum cholesterol both in
experimental animals and humans was observed [78].
Uchiyama et al. have shown that irrespective of metabo-
lism modification black tea polyphenols interfere with intes-
tinal lipids absorption [79]. Meanwhile, Chen et al. sug-
gested their positive effect on metabolic gene expression,
glucose tolerance and body composition in animals fed
a high-fat diet [74]. Still, human interventional studies are
positive for green tea only and mostly its extracts. Inter-
estingly, positive interaction between tea and physical exer-
cise in abdominal fat and serum lipids control has been sug-
gested [75].
In summary, available epidemiologic and experimental
studies showed the positive relationship between black tea
consumption and prevention or possible cure of variety of
diseases. However, more dose-response and mechanistic
studies are needed to understand the effects of tea con-
sumption on human ailments. Furthermore, appropriate
strategies are warranted for future clinical trials transliter-
ating animal data and small human experiments to fully
proven nutraceutical.
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