Critical Reviews in Food Science and Nutrition

ISSN: 1040-8398 (Print) 1549-7852 (Online) Journal homepage: http://www.tandfonline.com/loi/bfsn20

Black tea: Phytochemicals, cancer

chemoprevention, and clinical studies

Brahma N. Singh, Prateeksha, A. K. S. Rawat, R. M. Bhagat & B. R. Singh

To cite this article: Brahma N. Singh, Prateeksha, A. K. S. Rawat, R. M. Bhagat & B. R. Singh
(2017) Black tea: Phytochemicals, cancer chemoprevention, and clinical studies, Critical Reviews in
Food Science and Nutrition, 57:7, 1394-1410, DOI: 10.1080/10408398.2014.994700

To link to this article: http://dx.doi.org/10.1080/10408398.2014.994700

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Nov 2015.
Published online: 11 Nov 2015.

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 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2017, VOL. 57, NO. 7, 1394–1410
http://dx.doi.org/10.1080/10408398.2014.994700

Black tea: Phytochemicals, cancer chemoprevention, and clinical studies

Brahma N. Singha,b, Prateeksha a, A. K. S. Rawata, R. M. Bhagatc, and B. R. Singhd
a
Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Lucknow, UP, India; bBiochemistry Department, Tocklai
Experimental Station, Tea Research Association, Jorhat, Assam, India; cSoil Department, Tocklai Experimental Station, Tea Research Association, Jorhat,
Assam, India; dCenter of Excellence in Materials Science (Nanomaterials), Z. H. College of Engineering & Technology, Aligarh Muslim University, Aligarh,
UP, India

ABSTRACT KEYWORDS
Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed Black tea; phytochemistry;
by two-thirds of the world’s population. Black tea leaves are reported to contain thousands of bioactive antioxidant; cancer
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constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of prevention; anti-mutagenic
promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of
various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of
mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked
to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-kB, Bcl-xL,
caspases, p53, FOXO1, TNFa, PARP, and MAPK, which may be the basis of how dose of black tea prevents and
cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in
human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its
anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity,
and clinical applications of black tea to reveal its anti-cancer effect.

Abbreviations: AMPK, AMP-activated protein kinase; AOM, Azoxymethane; AP-1, Activated protein-1; B(a)P, Benzo
[a] pyrene; Bcl2, B-cell lymphoma-2; Bcl-xL, B-cell lymphoma-extra large; CAT, Catalase; CI, Confidence interval;
COX-2, Cyclooxygenase-2; CP, Cyclophosphamide; CYP, Cytochrome; DMBA, 7,12 Dimethyl benz(a) anthracene;
DMH, 1,2-Dimethyl hydrazine; EAC, Ehrlich’s ascites carcinoma; EC, (¡)-Epicatechin; ECG, (¡)-Epicatechin gallate;
EGC, (¡)-Epigallocatechin; EGCG, (¡)-Epigallocatechin gallate; EGFR, Epidermal growth factor receptor; FRs, Free
radicals; GC, (C)-Gallocatechin; GPx, Glutathione peroxidase; GR, Glutathione reductase; GSH, Glutathione; GST,
Glutathione-S-transferase; HAAs, Heterocyclic aromatic amines; HUVECs, Human vascular endothelial cells; IGF-1,
Insulin-like growth factor-1; IL-6, Interleukin-6; IQ, 2-Amino 3-methyl imidazo (4, 5-f) quinoline; JNK, c-Jun N-termi-
nal kinase; LOX, Lipoxygenase; LPO, Lipid peroxidation; MAPK, Mitogen-activated protein kinases; MeIQx, 2-Amino-
3,8-dimethylimidazo [4,5-f] quinoxaline; MNNG, N-Methyl-N’-nitro-N-nitrosoguanidine; mTOR, Mammalian target of
rapamycin; NDEA, N-Dinitroso-diethyl amine; NF-kB, Nuclear factor-kappa B; PARP, Poly(ADP-ribose) polymerase;
PhIP, 2-Amino1-methyl-6-phenylimidazo[4,5-b]pyridine; PI3K, Phosphoinositide 3-kinase; PO, Peroxidase; PPO, Poly-
phenol oxidase; PTP1B, Protein tyrosine phosphatase 1B; RR, Relative risks; SOD, Superoxide dismutase; STAT, Signal
transducer and activator of transcription; TF1, Theaflavin; TF2, Theaflavin 3-O-gallate; TF3, Theaflavin 30 -O-gallate;
TF4, Theaflavin 3,30 -O,O-digallate; TRs, Thearubigins

Introduction Polyphenols, particularly catechins, such as (¡)-epicatechin

Tea (Camellia sinensis L.) is the second most consumed flavored, (EC), (¡)-epicatechin gallate (ECG), (¡)-epigallocatechin
functional, and therapeutic non-alcoholic beverage in the world, (EGC), and (¡)-epigallocatechin gallate (EGCG), determine
next to the water (Singh et al., 2011b; Hayat et al., 2013). The har- the quality of green tea leaves (Sharma and Rao, 2009; Singh
vested shoots comprise an apical bud and two to three tender leaves et al., 2011b; Singh and Katiyar, 2013). Biotransformation of
containing 10–30% polyphenolic compounds (Li et al., 2013). The catechins during processing of leaves is usually divided into
simple act of putting tea leaves into hot water has provided ancient three basic types: black (fully oxidized), oolong (semi-oxidized),
societies with a tasty beverage associated with the observation of and green (non-oxidized). Of the total amount of tea produced
certain medicinal effects. Strong antioxidant activity of tea can be and consumed in the world, 78% is black, 20% is green, and
attributed to polyphenolic compounds (Gardner et al., 2007; Butt <2% is oolong tea. Black tea is consumed primarily in Western
et al., 2014), which neutralize free radicals (FRs) that can damage countries and in some Asian countries, whereas green tea is
the body’s cells, leading to disease development (Chen et al., 2004; consumed primarily in India, China, Japan, and a few countries
Singh et al., 2009c). of North Africa and Middle East. During the mechanical

CONTACT Dr. Brahma N. Singh brahmasingh99@gmail.com Pharmacognosy & Ethnopharmacology Division, CSIR-National Botanical Research Institute, Luck-
now, UP, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/bfsn.
© 2017 Taylor & Francis Group, LLC
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1395

maceration of green tea leaves, the oxidative polymerization (TF2), TF-30 -O-gallate (TF3), and TF-3,30 -O,O-digallate (TF4)
and condensation of catechins into theaflavins (TFs) and thear- formed from catechins (Li et al., 2013; Butt et al., 2014). The benzo-
ubigins (TRs) takes place by the action of polyphenol oxidase tropolone (core of TF) is formed by the reaction of catechol and
(PPO) and peroxidase (PO) (Li et al., 2013). TFs and TRs could pyrogallol. The reaction between a catechol and a pyrogallolyl
be the chemical entities not only responsible for the color of group on a gallate occurs at a slow rate and yields only small
black tea brew but also accountable for a range of health bene- amounts of other TF isomers.
fits (Blot et al., 1997; Sharma and Rao, 2009). Isomers of TFs, such as iso-TF, neo-TF, theaflavate A¡B,
Epidemiologic studies have also shown that black tea or its iso-TF-30 -O-gallate, neotheaflavate-3-O-gallate, theaflavic
chemical constituents inhibit the growth of established cancers at acids, theaflagallins, and methylated TFs, have also been iso-
various organ sites such as prostate, pancreas, liver, colon, and oral lated from black tea (Table 1; Fig. 1). The coupling between EC
(Blot et al., 1997; Beltz et al., 2006). Black tea contains various and (C)-gallocatechin (GC) forms iso-TF. Due to the trace
groups of chemicals, including flavonoids (TFs, TRs, and cate- amount of GC in green tea, the total concentration of iso-TF in
chins), phenolic acids (gallic, cauramic, caffeic, and chlorogenic black tea is normally not detectable and has not been reported
acids), amino acids (theanine), methylxanthines (caffeine), pro- to have any contribution to pharmacological activities. Simi-
teins, lipids, carbohydrates, volatile compounds fluoride, b-caro- larly, iso-TF-30 -O-gallate was formed through reaction between
tene, and traces of vitamins A, K, C, and folate (Hayat et al., 2013; ECG and GC and characterized in green tea (Li et al., 2013).
Li et al., 2013). A myriad of scientific data have shown that the Neo-TF-3-O-gallate has been isolated from black tea extract,
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pharmacological effects of black tea are mainly attributed to its and structurally identified by nuclear magnetic resonance
polyphenolic compounds (Butt et al., 2014). Among them, TFs and (NMR) and mass spectrometry (MS). The structural difference
TRs are the major polyphenols that appear to be the most potential between iso-TF and neo-TF is the orientation of benzotropo-
antioxidants with respect to regulating aging, cell proliferation, and lone core, which is reversed. Theaflagallins are enzymatic oxi-
apoptosis in human cancer cell lines (Beltz et al., 2006; Henning dative products of the reaction between catechins and
et al., 2011; Li et al., 2013). In addition to therapeutic effects, TRs, pyrogallol (Sharma and Rao, 2009). The pyrogallol mainly
TFs, and theanine are prime quality attributes of black tea, and con- comes from gallic acid in green tea or ester cleavage of gallates
tribute color and taste. Apart from green tea, black tea is currently a during the oxidation process. However, other authors con-
hot topic worldwide in both nutritional and therapeutic research firmed that theaflagallins are theaflagallin and epitheaflagallin-
because of the presence of key therapeutic TFs and TRs that are 3-O-gallate. Theaflavic acids and theaflavates have been found
more bio-stable and direct-acting than those found in other plants in some black tea infusions or extracts. In a model study of tea
(Li et al., 2013). The activities of these compounds are so all pervad- fermentation, epitheaflavic acid and epitheaflavic acid-3-Ogal-
ing that they are virtually broad spectrum in their actions. This late were formed and identified. There is possibility of their
paper provides a critical review on phytochemical constituents, presence in industrial black tea manufacturing, because epicate-
anticancer property, and clinical applications of black tea and its chin and gallic acid are their precursors existing in green tea
bioactive compounds. leaves (Li et al., 2013). However, these TF isomers, namely iso-
TFs, neo-TFs, theaflagallins, theaflavates, and theaflavic acids,
are usually trace components of black tea (Hayat et al., 2013).
Chemical constituents Recently, Chen et al. (2012) identified TF trigallate and tetragal-
late in black tea extract by liquid chromatography (LC)/electro-
Polyphenolic compounds
spray ionization mass spectrometry.
Both green tea and black tea have similar chemical compositions, Theaflavins are orange-yellow pigments that constitute ~0.5–
the basic difference between the two being the chemical changes 2.0% of dry weight, depending upon the type of manufacture of
that take place during their production. Polyphenols in tea mainly black tea. Yet, TFs and TRs have more difficult to be identified
include the following six groups of compounds: flavanols, than catechins, but they exhibit strong antiradical property. Black
hydroxyl-4-flavanols, anthocyanins, flavones, flavonols, and phe- tea is equal to green tea in terms of antioxidant potential (Sharma
nolic acids (Drynan et al., 2010a; Hayat et al., 2013). Polyphenols and Rao, 2009). The uptake of TFs is relatively low compared
contribute to the overall significant bitterness, astringency, and with catechins, but this may be masked by imprecise methodol-
sweet taste, and constitute 16¡30% of green tea, 3¡10% of black ogies that do not detect all of the TF metabolites (Hayat et al.,
tea, and 8¡20% of oolong tea (Li et al., 2013). The main bioactive 2013). The drinking of three cups of tea per day for two weeks
constituents of black tea belong to the polyphenol group account- (@ 2-g dry tea/cup) enhanced the concentration of flavonoids
ing for 25–35% on the dry weight basis (Table 1). Black tea, as typi- in the blood by 25%. The gallated flavonols are related to astrin-
cally brewed in India, contains about 200-mg flavonoids per cup. gency and bitterness of black tea, while the non-gallated tea fla-
Clinical investigations have documented a significant association vonols are associated with bitterness. Among the TFs,
between regular intake of black tea (>3 cups/day) and a reduced theoflavin is less astringent. The contribution of astringency by
risk of diseases. It was associated with the presence of polyphenols TF4 and TF3 was reported to be 6.4 and 2.2 times, respectively,
(Li et al., 2013). TFs, TRs, theaflavinic acids, and TF isomers attri- to that of TF. The attractive color of tea infusion is also due to
bute taste, color tone, and body to the brew. Figure 1 illustrates the the presence of TFs, and it emerges as an important quality
formation of TFs. The basic skeleton of TFs is benzotropolone, a index of black tea.
bicyclic ring containing the tropolone structure. In contrast to the On other hand, TRs are orange-brown colored compounds
theoretical eight or more TFs that can be produced proportionally, constituting about 6–18% of dry weight (Table 1). TR pigments
usually there are four major TFs, including TF1, TF-3-O-gallate contribute around 35% of the total color and provide brown
 1396 B. N. SINGH ET AL.

Table 1. Composition of tea and their impact on taste and color of brew.

% Dry weight

Molecular Molecular Green Black Taste threshold Color of

Chemical constituents formula weight tea tea Taste level (mol/L) brew

Total polyphenols 30–40 25–30

Simple polyphenols 2 3
Oxidized polyphenols 4–6 23–25
Flavanols 20–30 Small amount Astringent and bitter Light yellow
(¡)-Epicatechin (EC) C15H14O6 290 1–3
(¡)-Epicatechin gallate (ECG) C22H18O10 442 3–6
(¡)-Epigallocatechin (EG) C15H14O7 306 3–6
(¡)-Epigallocatechin gallate (EGCG) C22H18O11 458 9–13 0.5–0.9 190
(C)-Catechin C15H14O6 290 1–2 Puckering astringent 410
Flavonols and flavonol glucosides Velvety astringent, mouth
drying/ coating
Quercetin C15H10O7 302 Trace Trace
Kaempferol C15H10O6 286 Trace Trace
Quercetin 3-rhamnoglucoside (Rutin) C27H30O16 610 0.9–1.0 Trace 0.001 Light yellow
Kaempferol 3-rhamnoglucoside C27H30O15 594 Trace Trace 0.25
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Quercetin 3-rhamnodiglucoside C33H40O21 772 Trace Trace 1.36

Kaempferol 3-rhamnodiglucoside C33H40O21 756 Trace Trace 0.67
Phenolic acids Astringent
Theogallin C14H15O10 343 1.0 1.0
Ellagic acid C14H6O8 302 Trace Trace
Gallic acid C7H6O5 170 0.5 0.5
Quinic acid C7H12O6 192 2.0 2.0
Chlorogenic acid C16H18O9 354 Trace Trace
p-Coumarylquinic C16H18O8 338 Trace Trace
Theaflavins (TFs) 3–6 Mouth drying, rough Yellowish
astringent brown
Theaflavin (TF) C29H24O12 564 Trace
Isotheflavin C29H24O12 564 Trace
Neotheaflavin C29H24O12 564 Trace
Theaflavin-3-monogallate (TF1) C36H28O16 716 Trace
Theaflavin-30 -monogallate (TF2) C36H28O16 716 Trace
Theaflavin-3,30 -gallate (TF3) C43H32O20 868 Trace
Theaflavic acid C21H16O10 428 Trace
Epitheaflavic acid C21H16O10 428 Trace
Epitheaflavic acid gallate C28H20O14 580 Trace
Thearubigins (TRs) 12–18 Ashy and slight astringent Reddish brown
Thearubigin-1 (TR1) Trace
Thearubigin-2 (TR2) Trace
Thearubigin-3 (TR3) Trace
Others
Bisflavanol A C44H34O22 914 Small amount Astringent and
bitter
Bisflavanol B C37H30O18 762 Trace
Bisflavanol C C30H26O14 610 Trace
Tricetinidin C15H11O6 287 Trace
Purpurogallin-6-carboxylic acid C12H8O7 264 Trace
Categallin C20H16O8 384 Trace
Pyrogallin C20H16O9 400 Trace
Carotenoids Yellow
b-carotene C40H56 537 0.006 0.006
Lutein C40H56O2 569 0.008 0.007
Violaxanthin C40H56O4 601 0.002 0.001
Neoxanthin C40H56O4 601 0.003 0.003
Theanine C7H14N2O3 174 3 3 Brothy
Caffeine C8H10N4O2 194 3–6 3–6 Bitter and creamy
Pectin 3 3
Proteins 6–15 5–15
Amino acids 6 6 Brothy
Ash 5 5
Cellulose (C6H10O5) 5–7 5–7
n
Carbohydrates 10–15 10–15
Lignin 6.0 4–6
Lipids/organic acid 2–8 2–8
Volatile compounds 0.01 0.01

appearance to make tea black. It is notable that the lower the and continues up to the drying stage of the black tea processing.
amount of TRs, the poorer the creaming characteristic of brew During the rolling and fermentation stages of black tea manu-
(Drynan et al., 2010a). The formation of TRs begins at plucking facture, TRs increase steadily, while catechins, gallocatechins,
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1397
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Figure 1. Chemical structure of tea bioactive phytochemicals and formation of TFs from catechins.

and their gallates along with flavonol glycosides decrease TFs are formed, and with the progress of oxidation and fall of
throughout this period. It has been also observed that during pH, PO activity supports the generation of TRs. In water defi-
rolling the leaves, the PPO activity predominates, and favoring cient conditions (withered leaves), the concentration of PO is
 1398 B. N. SINGH ET AL.

considerable, facilitating the formation of TRs, but in a water- oxide, phenyl ethyl alcohol, a-terpineol, cis-geraniol, indole,
rich reaction medium, its action is hindered, but the PPO activ- geranyl acetate, b-ionone, dihydroactinidiolide, nerolidol,
ity enhances, resulting in more formation of TFs. Table 1 shows and phytol (Table 2 and Fig. 2). Among these, linalool is
the list of phenolics and color formed during the rolling oxida- the main essence in black tea. Moreover, the degraded
tion stage of black tea. Different ratios of TFs and TRs contrib- products of amino acids, carotenoids, and linoleic acid are
ute to different shades of black tea (Mahanta, 1988). also responsible for brew’s flavor. Primeverosides, such as
Moreover, the yellow color of brew is mainly due to the 4-O-b-D-glucopyranosides and 6-O-dxylopyranosyl-O-D-
presence of water-soluble flavonols (kaempferol, quercetine, gluco-pyranosides, act as key aroma precursors developed
isoquercetin, myricetin, myricitrin, rutin, and kaempferitrin), during the rolling of tea leaves. In addition, vicianosides,
flavones (apigenin, isovitexin, vitexin, saponarin, and vicenin- acuminosides, aglycons of (Z)-3-hexenol, geraniol, linalool,
2), and their glycosides. Of these, quercetin-3-O-(6-O-a-l- linalool oxides, benzyl alcohol, 2-phenyl ethanol, and
rhamnopyranosyl)-b-D-glucopyranoside (rutin) has a very low methyl salicylate are other primeverosides, bio-transformed
taste threshold level and is therefore important in determining into their VFCs (Li et al., 2013).
the tea taste (Park and Dong, 2003; Drynan et al., 2010b; Butt
et al., 2014).
Methyl xanthines
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Amino acids Methyl xanthines are present as caffeine (1, 3, 7-trimethyl

xanthine) and small amounts of theophylline and theobromine.
Black tea contains numerous amino acids, but L-theanine
Caffeine is a derivative of purine and the richest alkaloid among
(g-glutamylethylamide) is a unique amino acid accounting for
xanthine molecules, constituting 3–4% of the dry weight of tea
1–2% of dry weight, which makes 50% of the total amino acids
leaves (Table 1). It is the most stable molecule and remains
(Table 1). It appears to occur in only one mushroom species
unchanged during all the processes that it undergoes. Synergis-
and two other species of the Camellia genus. The degradation
tic effects of caffeine and polyphenols are required for the
of theanine is greatly involved in the biogenesis of aroma and
development of reasonable amounts of tangy astringency and
taste of tea (Mahanta, 1988). It is synthesized in the roots, and
creamy property of brew. According to Ulrich et al. (2000),
transports to the leaves, where sunlight converts theanine into
decaffeination may change the nature of astringency from
polyphenols. Because of this, some tea cultivators grow their
tangy to non-tangy-type. The content of caffeine in a cup of tea
plants out of direct sunlight to preserve theanine content, and
beverage depends on several factors such as variety, processing
thus the flavor. Some amino acids, such as arginine and alanine,
method, brewing time, amount of tea powder, and the quantity
contribute the bitterness of tea infusion. Moreover, lysine, glu-
of water used (Feng et al., 2002), although the amount of caf-
tamine, aspartic acid, threonine, glutamic acid, glycine, a-ala-
feine is higher in tea leaves than roasted coffee beans. Theobro-
nine, arginine, valine, methionine, isoleucine, leucine, tyrosine,
mine has been associated to enhance the rate of metabolism,
phenylalanine, histidine, asparagine, and tryptophan are also
while theophylline has been reported to be a bronchodilator in
detected in black tea. During processing, some of these amino
pure form. The amounts of theophylline and theobromine vary
acids are transformed into volatile aroma compounds (Sharma
dramatically in tea products to have possible health promoting
and Rao, 2009). For example, valine, methionine, isoleucine,
effects (Sharma and Rao, 2009).
leucine, and phenylalanine transform into isobutyraldehyde,
methional, 2-methyl butanal, isovaleraldehyde, and phenyl
acetaldehyde, respectively. During the heating process, amino
Miscellaneous constituents
acids interact with polyphenols to yield colored compounds,
while amadori is formed when amino acids interact with glu- The main shade of color in the infused leaf of black tea can
cose, which improves the flavor of brew (Li et al., 2013). be quantified by measuring the ratio of chlorophyll a (dark
green) and chlorophyll b (yellowish-green). The chlorophyl-
lase-dependent bio-transformation of chlorophyll into pheo-
Volatile flavor compounds
phytin and pheophorbide under high temperature and
The popularity of tea as a universal beverage depends upon humidity may cause the tea color to become darker. Carote-
its soothing flavor together with its stimulating effects. The noids, lipids, and anthocyanins are not only the major con-
principle bioactive constituents, which influence the flavor, stituents present in a black tea brew but they also
include volatile flavor compounds (VFCs). These volatiles contribute the therapeutic effects to tea and are responsible
become recognizable only when tea leaves have withered, for the development of aroma and color (Table 1). Carbo-
rolled, oxidized, and fired (Li et al., 2013). Volatile fractions hydrates, such as glucose, fructose, sucrose, raffinose, sta-
of tea leaves have been studied in detail, and more than chyose, maltose (in Assam tea), and rhamnose (in China
600 different compounds have been identified (Sang et al., tea), are associated to produce heterocyclic flavor com-
2011). Major VFCs characterized in black tea are linalool, pounds (Mahanta, 1988). Several minerals, such as fluorine,
benzyl alcohol, nonanal, phenyl acetaldehyde, n-hexanal, potassium, aluminum, iodine, selenium, nickel, and manga-
methyl salicylate, E-2-hexenal, Z-3-hexenol, 2-hexenol, nese, comprise about 4 to 9% of inorganic matter of tea.
n-hexanol, n-heptanal, benzaldehyde, (E,Z)-2,4-heptadienal, Other chemical compounds such as phytoestrogens and
(E,E)-2,4-heptadienal, cis-linalool oxide, trans-linalool vitamin C are also detected in black tea (Li et al., 2013).
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1399

Table 2. Volatile compounds responsible for aroma and flavor of tea.

Compound Molecular formula Molecular weight Flavor Found in Characteristic MS data (m/e)

Alkanals/alkenals
3-Methyl butanal C5H10O 86 Sweet, stimulus B, F 57, 29, 41, 58
Z-3-pentenal C5H10O 84 Green notes B 55, 29, 27, 41
2-Methyl pentanal C6H12O 100 B 43, 58, 41, 71
3-Methyl pentanal C6H12O 100 DB 56, 41, 43, 44
Hexanal C6H12O 100 Green notes B 44, 56, 41, 43
E-2-Haxenal C6H10O 98 Green notes B, G, F, P 41, 55, 69, 83
Z-3-Hexenal C6H10O 98 Leafy odour F 41, 55, 69, 83
E-2-Z-4-Hexadienal C6H8O 96 Green notes B 81, 39, 41, 96
2,4-Dimethyl-2,4-hetadienal C9H14O 138 B 109, 41, 67, 138
E-2-Z-4-Heptadienal C7H10O 110 Green notes B 81, 39, 53, 67
E-2-Z-4-Octadienal C8H12O 124 Green notes B 81, 39, 41, 67
E-2-Z-4-Non-adienal C9H14O 138 Fresh woody note B 67, 81, 95, 109
E-2-Z-4-Decadienal C10H16O 152 Fresh woody note B 67, 81, 95, 109
C5H10O
Alkanones/alkenones
3-hydroxy-2-butanone C4H8O2 88 B 45, 43, 88, 42
2,3,-butadione C4H6O2 86 Buttery, nutty B 43, 15, 86, 42
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1-Penten-3-one C5H8O 84 B 55, 84, 56, 57

3-hydroxy-pentan-2-one C5H10O 86 B 59, 43, 41, 58
2-Heptanone C7H14O 114 B 43, 58, 71, 59
2-Methyl-2-hepten-6-one C8H14O 126 B, P 43, 41, 69, 55
E-3-E-5-Octadien-2-one C8H12O 124 B, G, F 43, 95, 81, 53
2-Octanone C8H16O 128 B 43, 58, 59, 71
Alkanols/Alkenol
Pentan-2-ol C5H12O 88 Green notes B 45, 41, 43, 73
1-Penten-3-ol C5H10O 86 Green notes B, G, F, P 57, 29, 27, 31
Hexanol C6H14O 102 Hay-like notes B, G, F 56, 43, 55, 42
1-Hexen-3-ol C6H12O 100 B 57, 43, 72, 41
Z-3-Hexen-1-ol C6H12O 100 Green sweet notes B, G, F, P 41, 67, 55, 82
E-2-Hexen-1-ol C6H12O 100 Green notes B, G 31, 41, 57, 67
2-Heptanol C7H16O 116 DB 45, 43, 55, 41
1-Octen-3-ol C8H16O 128 B 57, 72, 85, 81
1,5-Octadien-3-ol C8H14O 126 DB 57, 70, 55, 41
1-Octanol C8H18O 130 B, G, F 31, 42, 56, 70
1-Nonanol C9H20O 144 DB 69, 41, 87, 43
Acids
Butanoic C4H8O2 88 Fatty notes B, G, F, P 60, 73, 27, 41
2-Methyl butanoic C5H10O2 102 Fatty notes B 74, 57, 29, 41
Pentanoic C5H10O2 102 Fatty notes B, G, F 60, 73, 41, 43
Hexanoic C6H12O2 116 Fatty notes B, G, F, P 60, 73, 41, 27
Z-3-Hexenoic C6H10O2 114 Fatty notes B, G, F 41, 39, 68, 73
Benzoic C7H6O2 122 B, G 100, 122, 78, 51
Phenyl acetic C8H8O2 136 Floral B 91, 136, 92, 65
Geranoic C10H16O2 168 Green floral B 69, 41, 39, 100
Esters
1-Hydroxy-2-propan acetate C5H8O4 132 DB 43, 87, 42, 44
Butyl acetate C6H12O2 116 B 43, 94, 58, 82
E-2-Hexenyl formate C7H12O2 128 B 67, 41, 57, 82
Methyl hexanoate C7H14O2 130 B, F 74, 87, 59, 99
E-3-Hexenyl acetate C8H14O2 142 B, F 43, 67, 82, 41
Phenyl acetate C8H8O2 136 DB 43, 94, 58, 42
Ethyl benzoate C9H10O2 150 DB 105, 77, 51, 122
Benzyl benzoate C13H10O2 198 DB 105, 91, 77, 51
Methyl tetradecanoate C15H30O2 242 DB 74, 87, 43, 41
Methyl heptadecanoate C18H36O2 284 DB 74, 87, 43, 55
Methyl palmitate C17H34O2 270 G 74, 43, 87, 41
Ethyl palmitate C18H36O2 284 G 88, 101, 43, 41
Lactones
2-Methyl-4-butanolide C5H8O2 100 Nut-like DB 41, 56, 42, 100
Methyl-4-butanolide C8H14O2 142 B 85, 41, 55, 42
5-Octanolide C8H14O2 142 Sweet creamy B 42, 99, 71, 55
5-Nonanolide C9H16O2 156 Nut-like odour DB 42, 99, 41, 43
5-Decanolide C10H18O2 170 Typical musky B 85, 128, 29, 41
Coumarin C9H6O2 146 B, G, P 146, 117, 90, 89
Dihydroactinidiolide C11H16O2 180 Peach-like B, G, F, P 111, 43, 67, 41
Cis-Jasmone (7) (3-methyl-2- (Pent-2-en) C11H16O 164 B, G, F, P 164, 110, 149, 79
cyclopent-2-en-1-one)
Furfural C5H4O2 96 Caramel, nutty B, G 39, 96, 95, 67
2-Ethylfuran C6H8O2 96 B 81, 96, 53, 39
2,5-Furandione C4H2O3 98 B 54, 53, 98, 41
2-Pentylfuran C9H14O 138 Beany grassy B 81, 53, 138, 39
(Continued on next page)
 1400 B. N. SINGH ET AL.

Table 2. (Continued ).
Compound Molecular formula Molecular weight Flavor Found in Characteristic MS data (m/e)

2,6,6-Trimethyl-2-vinyl tetrahydropyran C10H18O 154 DB 68, 67, 110, 43

Toluene C7H8 92 Solvent-like B 92, 93, 91, 66
O-xylene C8H10 106 Caramel, toffee-like B 91, 106, 105, 65
Benzaldehyde C7H6O 106 Fruity B, G, F, P 77, 105, 106, 43
Phenyl acetaldehyde C8H8O 120 Floral B, P 91, 120, 92, 65
Guaicol (O-methoxyphenol) C7H8O2 124 Smoky note B 109, 119, 81, 42
Thymol C10H14O 150 B 135, 150, 91, 117
Methyl salicylate C8H8O3 152 Winter green B, G, F 39, 65, 92, 120
Naphthalene C10H8 128 G 128, 129, 127, 51
2-Methylnaphthalene C11H10 142 DB 156, 141, 155, 157
1,7-Dimethylnaphalene C12H12 156 DB 156, 141, 155, 157
2-Furfuryl methyl ketone C7H6O2 122 DB 43, 81, 82, 53
1-Indanone C9H8O 132 DB 132, 104, 78, 42
Benzyl alcohol C7H8O 108 B, G, F, P 79, 108, 107, 77
2-Phenyl ethanol C8H10O 122 B, G, F, P 91, 92, 122, 65
2-Butyl furan C8H12O 124 DB 91, 124, 82, 53
Terpenoids/Hydrocarbons
Limonene C10H16 136 Sweet and floral B, G, F 68, 79, 93, 107
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E-b-Ocimene C10H16 136 Pleasant B, G 93, 80, 79, 77

Camphene C10H18 138 DB 93, 41, 79, 121
b-Myrecene C10H16 136 Pleasant B 41, 69, 93, 79
D-3-Carene C10H16 136 DB 93, 41, 91, 77
p-Cymene C10H14 134 B 119, 91, 134, 117
a-Cubene C15H24 204 G 161, 119, 105, 81
a-Cadinene C15H24 204 G 161, 119, 105, 93
b-Elemene C15H24 204 B 121, 93, 41, 79
L-Humulene C15H24 204 Slightly pappery B, G 93, 41, 69, 80
Caryophyllene C15H24 Woody, Spicy G, P 41, 69, 93, 133
Alcohols
Linaool C10H18O 154 Sweet B, G, F, P 71, 93, 41, 43
E-Furan-linalool oxide C15H18O2 170 Sweet B, G, F 59, 43, 94, 111
Z-Furan-linalool oxide C10H18O2 170 Sweet B, G, F 59, 43, 94, 121
E-Pyran-linalool oxide C10H18O2 170 Sweet B, G, F, P 110, 95, 152, 67
Z-Pyran-linalool oxide C10H18O2 170 Sweet B, G, F, P 110, 95, 152, 67
Myrtenol C10H18O 154 DB 79, 91, 41, 43
Nerol C10H18O 154 Rosy B, G, P 69, 41, 39, 93
Fenchyl alcohol C10H18O 154 B 81, 80, 69, 82
Geraniol C10H18O 154 Rosy notes B, G, F, P 69, 41, 39, 64
Carveol C10H16O 152 Spicy note DB 119, 91, 13, 92
a-Terpineol C10H18O 154 Fine, delicate odour B, G, F, P 59, 93, 43, 81
Citronellol C10H20 156 Rosy B 41, 69, 55, 67
Nerolidol C15H26O 222 Woody floral B, G, F, P 69, 41, 93, 43
Cedrol C15H26O 222 B, G 95, 150, 81, 43
b-Eudesmol C15H26O 222 Sweet woody DB, G 59, 109, 149, 189
Phytol C20H40O 296 B 71, 43, 57, 41
Ketones
2,6,6-Trimethyl cyclohex-2-en-1-one C9H14O 130 B 82, 54, 138, 39
2,6,6-Trimethyl cyclohexanone C9H16O 140 B 82, 56, 69, 55
2,6,6-Trimethyl cyclohex-2-en, 1,4-dione C9H12O2 152 B, G 68, 96, 40, 152
2,6,6-Trimethyl-4-hydroxycyclo hex-1-one C9H16O2 156 B, G 83, 57, 41, 69
5-(Methylethyl)-E-3-hepten-2-one C6H12O 154 DB 43, 97, 112, 55
3,3-Dimethyl-2,7-octadione C10H18O 168 B 43, 69, 109, 86
Fenchone C10H16O 152 Harsh fennel odour B 81, 68, 51, 152
Damascenone C13H18O 190 Floral B 69, 121, 41, 105
a-Damascenone C13H20O 192 Floral B 69, 123, 81, 41
b-Damascenone C13H20O 192 Floral B 177, 69, 41, 121
1,5,5,9-Tetramethyl bicycle(4–3–0)non-8en-7-one C13H20O 192 Floral B 110, 123, 177, 41
a-Ionone C13H20O 192 Floral B, G, P 43, 121, 93, 136
b-Ionone C13H20O 192 Warm woody B, G 177, 43, 41, 93
Geranyl acetone C13H22O 194 B 43, 69, 93, 125
4-Oxo-b-ionone C13H18O2 206 B 43, 163, 121, 206
5,6-Epoxy-b-ionone C13H20O2 208 B, P 123, 43, 135, 109
Dehydro vomifoliol-(10 -hydroxy 40 -oxo-a-ionone) C13H20O2 208 B 124, 43, 166, 95
Z-Theaspirane C13H22O 194 B 138, 82, 96, 83
Z-Dihydrotheaspirene C13H22O2 210 B 43, 126, 154, 55
Z-6-Hydroxy dihydrotheaspirane C13H24O2 212 B 85, 43, 126, 86
b-Cyclocitral C10H16O 152 Warm woody B 41, 81, 109, 123
Geranyl formate C11H18O2 182 Green rosy B 69, 41, 39, 68
Methyl-E-dihydro jasmonate C13H22O3 224 Sweet floral B, G 83, 156, 153, 82
2,5-Dimethyl pyrrole C6H8O 94 B 94, 95, 42, 80
2-Formyl purrole C6H5NO 95 Smoky note B 109, 108, 53, 80
Pyridene C5H5N 79 B 79, 52, 51, 50
(Continued on next page)
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1401

Table 2. (Continued ).
Compound Molecular formula Molecular weight Flavor Found in Characteristic MS data (m/e)

2-Ethyl pyridine C7H9N 107 B 104, 105, 79, 80

Methyl pyridine C5H6N2 94 Pungent odour R 94, 67, 39, 40
2,6-Dimethyl pyrazine C6H8N2 108 Pungent odour B, R 43, 108, 39, 40
2-Acetyl pyrazine C6H6N2O 122 B 43, 52, 53, 94
Indole C8H7N 117 B, G, F, P 117, 90, 91, 63
3-Methyl indole C9H9N 131 DB, G 130, 131, 43, 42
Dimethyl sulphide C2H6S 62 B, G 47, 62, 45, 46

B: Black tea; G: Green tea; DB: Darjeeling black tea; F: Fresh leaves tea; P: Pouchong tea; R: Roasted green tea.

Chemopreventive properties 2011b; Shukla et al., 2014; Singh et al., 2014). Antioxidants
such as flavonoids and phenolic acids are found in various
Antioxidant activity
plants (Singh et al., 2009b). They have been found to reduce
Overproduction of FRs causes oxidative damage to biomole- the access of the most damaging FRs due to their ability to
cules, resulting in the development of numerous diseases, scavenge oxygen–nitrogen-derived FRs by donating hydro-
including cancer, cardiovascular, atherosclerosis, inflamma- gen atom or an electron, chelating metal catalysts, activating
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tory injury, aging, and neurodegenerative diseases (Singh antioxidant enzymes, and inhibiting oxidases (Prakash et al.,
et al., 2009a, 2009b, 2009c, 2011a). In recent years, increas- 2007; Singh et al., 2009c). Based on accumulative evidence,
ing attention has been paid to the role of diet in human in recent decades, tremendous interest has considerably
health. Several epidemiological studies have indicated that a increased in finding natural antioxidants present to replace
high intake of fruits, vegetables, spices, and medicinal plants synthetic antioxidants, which are being restricted due to their
is associated with a reduced risk of cancer (Aggarwal and side effects. On the other hand, flavonoids, used as natural
Shishodia, 2004, 2006; Aggarwal et al., 2008; Singh et al., antioxidants, are gaining importance due to their range of

Figure 2. Flavor-related volatile constituents of tea.

 1402 B. N. SINGH ET AL.

biological activities, decreasing the risk of various cancers endogenous antioxidants, including SOD, CAT, GR, GPx, GST,
(Katiyar and Mukhtar, 1997b; Singh et al., 2009c). GSH, and total thiol. These enzymatic proteins are known to
Certain bioactive constituents present in black tea possess efficiently quench oxidative burden by minimizing damage to
antiradical activity. Thus, tea drinking elicits the endogenous cells. This study suggests that black tea can help in the revival
antioxidant gene pool and reduces the risk of various types of of endogenous antioxidant system. Among the polyphenols of
cancers (Katiyar and Mukhtar, 1997b). Black tea contributes black tea, TFs are the main activity-modulating components
60–84% of dietary flavonoids in Western populations, and it (Katiyar and Mukhtar, 1997b; Feng et al., 2002).
has been reported that consumption of flavonoids by tea Studies have cleared that a group of TFs in black tea, specifi-
drinkers is 20 times more than by non-consumers of tea (Song cally TF-3 and TF-4, showed strong antioxidant activity, which
and Chun, 2008). Polyphenols such as TFs, TRs, and gallic acid was similar to EGCG of green tea. Therefore, these TFs inhibit
present in black tea are reported to be responsible for its strong inflammation, clastogenesis, and several types of cancers
antioxidant activity. A plethora of evidence suggests that the (Sharma and Rao, 2009). Interestingly, EGCG alone was found
black tea polyphenols can protect cells from FR-mediated oxi- to considerably affect LPO in jarkut cells; however, along with
dative damage (Fig. 3). Luo and co-workers (2012) observed black tea extract, no protective effect was observed. Authors
that oxidative stress, inflammation, and hepatocyte apoptosis concluded that some components of black tea might be respon-
increased in steatotic liver compared with a normal liver. How- sible for loss of antioxidant effect of EGCG. At 5 mg/mL, black
ever, administration of TF1 was found to significantly decrease tea extract showed radioprotection in normal lymphocytes. TFs
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the levels of these changes. In LPS-stimulated RAW264.7 cells, blocked LPO in erythrocyte membrane ghosts and microsomes.
the decreased production of reactive oxygen species (ROS) and This antioxidant effect was related to FR scavenging of galloyl
TNF-a by TF1 is also examined. moiety of TFs. Alcohol intake causes oxidative stress by gener-
Numerous studies have shown that black tea consumption ating FRs in the cells, resulting in the depletion of antioxidant
has equal antioxidant and FR scavenging effects as to those system. TFs were found to significantly protect against alcohol-
drinking green tea. Black tea TFs and TRs possess at least the induced oxidative damage and partial protection to the brain
same antioxidant potential as catechins present in green tea cells. The maximum antioxidant level was examined in the liver
(Feng et al., 2002; Erba et al., 2003; Singh et al., 2011b). Oxida- of mice (Luczaj and Skrzydlewska, 2004).
tive damage to lipoproteins is related to atherogenesis. Flavo- The antioxidant potential of hot water extract of black tea
noids present in black tea inhibited the oxidation of lipids, was studied by evaluating radioprotection conferred to pBR322
thereby preventing atherosclerosis (Sharma and Rao, 2009). DNA, calf thymus DNA, and normal lymphocytes during
Pretreatment of black tea was found to inhibit the frequency of gamma irradiation (Fig. 3). The highest protection was
chloropyriphos and cypermethrin-induced LPO in mice liver. observed in pBR322 DNA followed by calf thymus with IC50
This protective effect was associated with the upregulation of with 182 mg/mL. Oxidative DNA damage generates 8-hydroxy-
2-deoxyguanosine, which is used as a plasma or urinary marker
for exposure to chemical carcinogens or radiation (Ghosh et al.,
2012). TFs were recorded to decrease DNA damage and muta-
genesis by enhancing antioxidant function and suppressing
cytochrome P450 1A1 in the normal liver epithelium RL-34
cells of rat. Protective effect of polyphenols was found to be in
the following order: TF4 > TF3 > TF2 (Feng et al., 2002).
Serafini and colleagues tried to compare antioxidant activity of
phenol-rich beverages such as black tea, green tea, red wine,
and white wine. The antioxidant capacity of red wine was
found to be higher than in the tea using low-density lipoprotein
(LDL) oxidation assay, an in vitro system. The phenolic content
and the antioxidant activity were reported in the following
order: red wine > green tea > black tea > white wine. Unex-
pectedly, under the in vivo model system, black tea showed
higher antioxidant activity than green tea and red wine. This
occurred due to changes in the structure of polyphenols during
digestion and assimilation. A number of human studies sup-
Figure 3. Mechanistic representation of antioxidant, anti-mutagenic, and chemo- ported this interpretation. However, work on animals showed
preventive properties of black tea. Several environmental factors, including UV that the black tea extract improves plasma lipid profiles and
light, ozone, tobacco smoke, different xenobiotics, ionizing radiation herbicides,
and pesticides, generate ROS in excess amount. These ROS are generated during reduces the oxidation of LDL and very low density lipoprotein
the bio-transformation of mutagens into pre-carcinogens, thereby inducing DNA (VLDL), followed by a high cholesterol diet (Sharma and Rao,
damage, protein aggregation, and lipid peroxidation. COX-2, 5-LOX, TNFa, IL-6, 2009). Inhibitory effect of black tea on LDL oxidation and fatty
and excessive and prolonged NO generation are linked with inflammation and
tumorigenesis. Apoptosis is a well-orchestrated process controlled by multiple pro- acid synthase suggests a key role in the prevention of cardiovas-
apoptotic and anti-apoptotic genes, particularly the Bcl-2 gene family. Antioxidant cular diseases. Black tea consumption provided protection
polyphenols of black tea prevent cancer by scavenging ROS, inhibiting inflamma- against nitrous oxide and superoxide (O2¡) in murine perito-
tion-inducing enzymes, and by controlling cell proliferation through induction of
apoptotic protein expression (Bax, PARP, and caspases). The various protective neal macrophages (Sharma and Rao, 2009). Many researchers
mechanisms are marked with a blunt headline. also documented that TFs are the most effective compounds in
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1403

down-regulating oxidative stress and found a better chemo- study conducted by Davies et al. (2003), in which improvement
preventive agent than green tea. in coronary heart disease (CHD) risk factors was examined, but
Pre-Treatment with black tea extract inhibited carbon tetra- no noticeable changes in antioxidant status were determined. A
chloride-induced LPO by 49% and 37% in the liver of female considerable body of observational evidence revealed that the
and male rats, respectively. Similar protective effect was also intake of black tea and its flavonoids improve heart health and
observed in the kidneys and testes of rats. This effect was regulate the process of carcinogenesis, diabetes, inflammation,
related with the scavenging of FRs induced by carbon tetrachlo- thrombosis, and endothelial function by enhancing endogenous
ride (Fadhel and Amran, 2002). Flavonoid-rich black tea antioxidant system (Sharma and Rao, 2009).
extract also inhibited blue sprat-mediated oxidation of linoleic
acid. Its aqueous extract was also found to prevent cross-linking
of proteins, and inhibited oxidative DNA strands breakage.
Anti-mutagenic activity
Moreover, the reduced oxidative stress induced by cigarette
smoking was also observed in the black tea extract-treated ani- Both intracellular and extracellular mechanisms seem to be
mals (Sharma and Rao, 2009). Within first 5 min of brewing, involved in the anti-mutagenic activity of black tea (Table 3).
approximately 84% antioxidant activity was solubilized, while These include modulation of metabolism, DNA replication and
an additional 13% activity was extracted when tea was brewed repair effects, and promotion of invasion and metastasis
for another 5 min. (Fig. 3). Not only green tea flavonoids but black tea polyphe-
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In a randomized study, Henning et al. (2004) approached 30 nols have also been reported to bring benefits in lowering oxi-
healthy subjects for consuming a single bolus of black or green dative stress and exerting anti-mutagenic effect (Sharma and
tea, and observed maximum antioxidant status of plasma at 2 h Rao, 2009). TFs cause dose-dependent inhibition of Cd-
after their consumption. It was analyzed by Oxygen Radical induced DNA damage in rat testis and enhance the levels of
Absorbance Capacity assay (Prior and Cao, 1999) that black tea serum testosterone and sperm characteristics. TFs also reduce
had a mean antioxidant capacity of 761.1 mmol Trolox equiva- LPO and Cd concentration in urine, feces, liver, testis, and
lent to per gram dry matter. Rietveld and Wiseman (2003) blood (Wang et al., 2012b). TFs also suppress H2O2-induced
examined the powerful antioxidant activity of black tea flavo- mutagenicity in Salmonella typhimurium TA104. Exposure of
noids in in vitro; however, no activity was found in in vivo sys- Escherichia coli to black tea extract was observed to
tems. Improvement in human vascular function was observed inhibit the mutagenicity of N-Methyl-N’-nitro-N-nitrosoguani-
when drinking flavonoid-rich black tea (450 mL/day) for four dine (MNNG) because it contained low molecular weight tan-
days (Widlansky et al., 2005). This study was supported by a nins, including gallic acid (Roy et al., 2001).

Table 3. Anti-mutagenic activity of black tea.

Responsible
Mutagen components Bio-activity Mode of action Experimental model Reference

B(a)P TFs Antimutagenic Inhibition of CyP450-1A1 Hep G2 cells Feng et al., 2002
Prevention of DNA damage
Cyclophosphamide TFs and TRs Anticlastogenic Mouse bone marrow cells Gupta et al., 2001
and DMBA
Mitomycin Green, black tea and tannin Antimutagenic Mouse bone marrow cells Imanishi et al., 1991
Hydrogen peroxide TF2, T3, and TF4 Antimutagenic Mazumdar et al., 2013
Mutant H ras gene Black and green tea Antimutagenic Inhibition of AP-1 activity. Epidermal JB-6 cell line Krishnan and Maru,
polyphenols Inhibition of cell proliferation 2004
HAA Black and green tea extract Antimutagenic S. typhimurium Stavric et al., 1996
Mitomycin and UV Black tea extract Antimutagenic Co-mutagenic effect as such, but Imanishi et al., 1991
antimutagenic in presence
of liver enzymes
9AA, MNNG and Galic acid Antimutagenic Blocking the membrane Roy et al., 2001
Folpet transporters of the mutagen
MeIQX Black tea extract Antimutagenic S. typhimurium Apostolides et al., 1996
4 NQO and UV, Tannic acid Antimutagenic Activation of excision repair system E. coli (WP2) Sharma and Rao, 2009
Gamma rays
B(a)P Black tea extract Antimutagenic Prevention of DNA damage Swiss albino mice Imanishi et al., 1991
to germ cells
PHIP Caffeine Antimutagenic Competitive inhibition of Cyp450 Apostolides et al., 1996
through non-covalent
interactions
MNNG Black and green tea extract Antimutagenic E. coli (WP2) Sharma and Rao, 2009
IQ Caffeine Antimutagenic Inhibition of CyP450 isozymes, Rats McArdle et al., 1999
quenching free radicals and
electrophiles
B(a)P Black tea polyphenols Antimutagenic Inhibition of CyP450 isozymes Prevention of DNA adduct Krishnan and Maru,
formation 2004
PHIP Black and green tea extract Antimutagenic Promotion of DNA excision repair Chinese hamster cells Kuroda and Hara, 1999
system activity
B(a)P TFs and TRs Antimutagenic, Mouse bone marrow cells Krishnan and Maru,
anti-clastogenic and S. typhimurium 2004
 1404 B. N. SINGH ET AL.

Heterocyclic aromatic amines (HAAs) are well-known marrow micronuclei by TFs and TRs. Moreover, black tea was
mutagens found in meat during heat processing. Black tea has also found to inhibit tumor invasion and cell proliferation.
been shown to inhibit the mutagenic effects of HAAs in S. These data suggest strong inhibition of cancer development at
typhimurium (Stavric et al., 1996). On the other hand, it has different stages by administration of black tea. However, this
been also reported that black tea extract at low concentration potential of black tea was not always related to a lower inci-
enhances the mutagenicity of 2-amino-3,4,7,8-tetra methyl 3H dence of cancer in epidemiological investigations. On the other
imidazo (4,5-f) quinoxaline and 3-amino-1-methyl-5H-pyrido hand, black tea did not appear as a cancer-promoting agent.
(4,3-b) indole (Trp-P2) (Weisburger et al., 1996). Caffeine, a Aflatoxin belongs to the class of naturally occurring myco-
constituent of black tea, decreases the mutagenic potential of toxins and food contaminants having potential carcinogenicity.
benzo(a) pyrene, 1,2-dibromoethane and 2-nitropropane in rat The oral administration of aflatoxin caused reduction in the
liver. However, no inhibitory effects were observed against 1- contents of DNA, RNA, protein, and glycogen, while the levels
nitropyrene and 2-chloro,4-methyl thiobutanoic acid (Jolivette of cholesterol and phosphorylase activity were significantly
et al., 1998). Black and green tea extracts have been reported to increased in mice liver. Co-treatment with black tea extract was
possess a strong anti-mutagenic activity against food mutagens found to reverse these changes (Jha et al., 2012). Growth of
such as 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline human prostate carcinoma cells was recorded to inhibit when
(MeIQX) and 2-amino 3-methyl imidazo (4,5-f) quinoline (IQ) treated with TR plus genistein in the ratio of 1:40. However, TR
(Krul et al., 2001). McArdle and colleagues (1999) showed that alone did not show any significant inhibitory effect on cell
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caffeine inhibited the mutagenicity of IQ. Later on, Yoxall et al. growth. A reduced mammary gland tumor burden was
(2004) reported the anti-mutagenic activity of black tea on IQ observed in DMBA-treated female Sprague Dawley rats fed
due to induction of hepatic Cyp1a2 (cytochrome 450 enzyme) with a fat-rich diet (Gupta et al., 2001). However, this effect dis-
activity. They also observed the inhibition of colonic crypt foci appeared in rats fed with the AIN-76A diet. TFs were found to
formation induced by heterocyclic amine. inhibit the proliferation of prostate cancer LNCaP cells, and
Exposure of Chinese hamster cells to tea tannins in the pres- this inhibitory effect varied in the following order: TF4 > TF3
ence of S9 mix (liver enzymes) resulted in decreasing chromo- > TF2 > EGCG > TF1. TF4 suppresses 5a-R1 activity that
somal aberrations induced by mitomycin and ultraviolet (UV) leads to the growth inhibition of androgens sensitive LNCaP
radiation mediated via promotion of DNA excision repair cells. TFs and TRs also quench the FRs generated by testoster-
activity (Imanishi et al., 1991). Black tea extract, TFs, and TRs one, a promoter of prostate cancer.
exhibit anti-clastogenic activity against cyclophosphamide (CP) Black tea has been found to reduce the mitotic index by
and dimethyl-benz(a)anthracene (DMBA) in mouse bone mar- three-fold (Sharma and Rao, 2009). Treatment of DMH (1,2-
row (Gupta et al., 2001). Shukla and Taneja (2001) observed dimethyl hydrazine)-treated F-3-4-4 rats with black tea extract
that black tea extract prevented B(a)P-induced DNA damage enhanced the activity of GST and reduced quinone reductase
in Swiss albino mice germ cells. TFs and gallated catechins activity in colorectal epithelium. The drinking of black tea
strongly inhibited the activity of cytochrome P450 as compared causes inhibition of nitrosomethyl benzamine-induced esoph-
with catechins (Apostolides et al., 1996). Addition of black tea ageal tumors by 70% in male Sprague Dawley rats (Wang et al.,
extract was observed to inhibit the formation of heterocyclic 1995). A single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-
amines, including 2-amino1-methyl-6-phenylimidazo[4,5-b] butanone (103 mg/kg body weight) causes rapid proliferation
pyridine (PhIP) and MelQx, important food-borne pro-carci- in bronchiolar cells and tumor formation in the lungs of female
nogens produced during frying or broiling of meat and fish. A/J mice. However, treatment with 0.1% and 0.3% solutions of
Interestingly, decaffeinated tea was less effective than normal TFs inhibited these events (Sharma and Rao, 2009). Treatment
tea because of inhibitory effect of caffeine on cytochrome P450 with TFs also reduces the damage of homocysteine-injured
system (Kuroda and Hara, 1999). Black tea selectively activates human vascular endothelial cells (HUVECs) and inhibits
cytochrome P450 isoforms such as CYP1A2, CYP4A, and homocysteine-induced oxidative DNA damage induced by
CYP2B in rat liver (Bu-Abbas et al., 1999). These activated quenching the FRs (Wang et al., 2012a). Black tea inhibited
cytochrome P450 isoforms enhance the bio-activation of pro- inflammation induced by 12-O-tetradecanoyl phorbol-13-ace-
carcinogens. Lin and co-workers have demonstrated that black tate in the SENCAR mouse skin carcinogenesis model (Katiyar
tea prevents DNA fragmentation formation by inhibiting direct and Mukhtar, 1997a).
reduction of PhIP (Kuroda and Hara, 1999). Numerous investigations have pointed out the contradictory
results reported in the research concerning the drinking of
black tea. Chronic treatment by black tea was not found to
Anti-cancer activity
affect the progression of Peyer’s patch carcinomas in colon
A number of studies have shown that the black tea phytochem- induced by azoxymethane (AOM). Black tea has not shown
icals exert their chemopreventive effects directly or indirectly any effect on the incidence and multiplication of colon cancers,
through the inhibition of tumor promoters. In the hamster buc- and rather it was found to stimulate the growth of exophytic
cal pouch carcinogenesis model, black tea extract showed che- carcinomas (Weisburger et al., 1998). Some studies indicated
mopreventive effect by inhibiting DMBA-induced that tea drinking increases the risk of bladder cancer (Lu et al.,
carcinogenesis (Chandra Mohan et al., 2005). Authors have 1999). Later on, Zeegers and coworkers (2001) mentioned in
also documented that this effect is associated with the inhibi- their review that tea drinking inhibits bladder cancer and its
tion of oxidative stress, formation of neoplastic lesions, activity proliferation. However, there are several in vitro and in vivo
of carcinogen metabolizing enzymes, and the incidence of bone studies in which potent anti-cancer effects of black tea have
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1405

been reported. Administration of black tea extract suppresses

intestine cancer in male F-3-4-4 rats. Black tea also increases
the apoptotic index of tumors from 2.92§0.25 in controls to
4.13§0.46 in rats. After decaffeination, black tea extract was
observed to reduce the number of lung tumors in NDEA-
treated male C3H mice. Aqueous extract (4%) of black tea
inhibited the development of pulmonary tumors in Swiss
albino mice induced by NDEA (Sharma and Rao, 2009).
Black tea and green tea are potent antioxidants that demon-
strate anti-cancer effects. Exposure of hepatoma AH109A and
L929 tumor cells to TF1 and their gallates reduce their prolifer-
ation and invasion, while normal cells were found as unaffected
(Zhang et al., 2001). Addition of EDTA, a chelator of antioxi-
dants’ anticancer effect of black tea disappeared, which suggests
its strong antioxidant property (Zhang et al., 2001). Aqueous
extract of black tea was also examined as an effective inhibitor
of skin cancer induced by 7,12-dimethyl benz(a) anthracene in Figure 4. Oncogenic signaling pathways regulated by black tea polyphenols for
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female CD-1 mice by inducing cell death and apoptosis (Kalra prevention and therapy of cancer. Most human cancers are driven by chromosomal
translocations or other genetic alterations that directly affect the functioning of cell
et al., 2005). Similarly, drinking of black tea was associated to cycle regulating proteins. Cell signaling pathways such as JAK, AKT/PI3K/mTOR,
inhibit the growth of papilloma by 35–40%. Treatment with MAPK, EGFR, STAT, AP-1, FOXO, p50, and p65 contribute cell survival and prolifera-
decaffeinated tea has been shown to decrease papilloma growth tion. Black tea polyphenols are reported to inhibit deregulated cellular prolifera-
tion, de-differentiation, and progression by controlling cell proliferative pathways
in one case, and increase it in two others. Black tea treatment and by inducing apoptotic cell death. Blunt headlines indicate the inhibition of
was shown to suppress the 70% growth of skin cancer induced molecular targets by black tea polyphenols. The purpose of this mechanism is to
by 30 mJ/cm2 of UV-B light in SKH-1 female mice (Sharma present an appraisal of the current level of knowledge regarding the chemo-
preventive potential of black tea polyphenols via an understanding of their mecha-
and Rao, 2009). Black tea extract in a concentrated form ranged nism of action at the level of cell cycle regulation.
from 0.1–0.2 mg/mL and inhibited tumorigenesis in NDEA-
treated male C3H mice by decreasing the number of hepatic
tumors. Moreover, chemopreventive effect of black tea was highest affinity with quadruplex DNA reported than reported
shown to result from reduced DNA replication in HT rat hepa- by other phytochemicals so far. This study indicates the chemo-
toma cells (Lea et al., 1993). preventive effect of black tea against cancer and its possible role
Inhibition of DNA replication and cell proliferation was as “life span essential.”
observed in mouse erythroleukemia DS19 cells when treated Growth factors, including insulin like growth factor (IGF),
with ethyl acetate extract of black tea. Treatment of JB-6 mouse epidermal growth factor (EGF), and platelet-derived growth
epidermal cells with TFs has been shown to inhibit UVB-medi- factor (PDGF), are proteins that bind to receptors on the cell
ated activation of AP-1 (Nomura et al., 2000). Pre-treatment surface, thereby activating cellular proliferation. Aberrant
with black tea extract also decreased the number of skin papil- expression of IGF-1 leads to increased cell proliferation, sup-
lomas induced by UV ACB light in hairless mice. The effect of pression of apoptotic signals, and invasion contributing to
black tea was higher than green tea (Record and Dreosti, 1998). metastasis (Sharma and Rao, 2009). Black tea and its TFs
Exploiting the anticancer property of black tea, plenty of prepa- inhibit IGF-1-induced progression of cells into S phase of cell
rations have been formulated. For example, a medicinal formu- cycle in prostate carcinoma DU145 cells, indicating that it has
lation having rhubarb, Fangdou tea, Dragon’s bone, and potential to disrupt the autocrine loops that are examined in
premium black tea treats burns and scalds (Sharma and Rao, several advanced cancers (Klein and Fischer, 2002). TFs also
2009). Therefore, tea can be used for preparing anti-cancer tea, reduce mitochondrial membrane potential and induce ROS
powder, pill, capsule, anti-cancer-medicated wine, anti-cancer generation, p53 expression, Bax/Bcl-2 ratio, cytochrome-c
beer, liquid medicine, sweets, and anti-cancer biscuits (Sharma release, cleavage of procaspase-3 and procaspase-9, and poly
and Rao, 2009). (ADP-ribose) polymerase (PARP) (Singh et al., 2011c). TF
treatment suppressed the activation of AKT and NF-kB by sup-
pressing phosphorylation, cyclooxygenase-2 (COX-2), and deg-
Molecular targets for cancer prevention
radation of inhibitor of kBa and kBb subunits. In addition,
Intake of black tea has been reported to prevent various types of cyclin D1 expression (a transcriptional target of NF-kB) was
cancers. Extensive research in the last two decades has docu- also significantly down-regulated by TF.
mented that black tea contains cancer preventive phytochemi- Apoptosis is a normal physiological process that allows the
cals that modulate various cellular signaling pathways that can removal of abnormal cells engaged in sustaining homeostasis in
potentially be used not only for the prevention but also for the a living system (Singh et al., 2011b, 2012). Consequently, regu-
treatment of cancer (Fig. 4; Mikutis et al., 2013). TFs have been lating apoptosis may prove to be a useful approach for preven-
shown to display affinity to all of the selected cell nuclear struc- tion and therapy of cancer. Apoptosis-dependent inhibitory
tures such as histone proteins, double stranded DNA, and action of tea polyphenols has been found to suppress the
quadruplex DNA, thereby demonstrating a degree of unex- growth of rat hepatoma, mouse erythroleukemia, and the
pected molecular promiscuity. Most notably, TF4 exhibited the growth of several human cancer cell lines, including MCF-7
 1406 B. N. SINGH ET AL.

breast carcinoma, HT-29 colon carcinoma, A-427 lung carci- 8/caspase-3 pathway via inhibition of Ras/Raf/ERK. Black tea
noma, and UACC-375 melanoma (Katiyar and Mukhtar, extract and TFs treatment of KATO III human stomach cancer
1997b). Anandhan et al. (2013) found that oral treatment of cells resulted in the induction of DNA fragmentation, a classic
TF1 (10 mg/kg) attenuated 1 methyl,4 phenyl–1,2,3,6-tetrahy- sign of apoptosis. In leukemic cancer cell lines (HL-60 and K-
dropyridine-induced neuro-inflammation and apoptosis 562), black tea has been shown to inhibit cell growth and
through regulation of IL-1b, IL-6, TNFa, IL-10, glial fibrillary induce apoptosis (Kundu et al., 2005). These effects were
acidic protein, Bax, and Bcl-2. These authors also reported that accompanied by increased expressions of caspases and Bax.
the effect of black tea was found to be at par with that of green Katiyar and Mukhtar (1997b) also reported cancer preventive
tea. Pre-exposure to black tea extract significantly decreased potential of black tea via inhibition of tumor promoters, includ-
radiation-induced loss of cell viability, generation of ROS, ing ornithine decarboxylase, COX, LOX, and FR production.
mitochondrial dysfunction, activation of caspase-3, and apo- TF4 causes concentration-dependent inhibition of proliferation
ptosis in normal lymphocytes compared with K562 cells. Black of A431 cells and mouse NIH3T3 fibroblasts. This effect was
tea extract also regulates the activity of endogenous antioxidant associated with the inhibition of mitogenic signal transduction,
enzymes. Changes in the mRNA expression of Bax, Bcl2, p53, NF-kB activation, NO production, and auto-phosphorylation
and Nrf2 were also followed to assess regulation of radiation- of epidermal growth factor receptor (EGFR) (Liang et al.,
induced apoptosis by black tea extract (Ghosh et al., 2014). 1999). TF1 has also inhibited the expressions of IL-6, monocyte
TUNEL and DNA fragmentation assays indicated induction of chemo-attractant protein-1, and intercellular adhesion mole-
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apoptosis by hydro-methanolic and black tea in oral squamous cule-1 in bone marrow-derived macrophages through inhibi-
cell carcinoma KB cells (Aghbali et al., 2014). tion of NF-kB/MAPK pathways.
Activated AKT induces cell proliferation by regulating the Black tea extract prevents formation of DNA adducts by
downstream targets such as Wnt/b-catenin, cyclin D1, fork- inhibiting activity of CYP450 isozymes, namely CYP1A1,
head transcription factor 1 (FOXO1), cylcin-dependent kinase CYP1A2, and CYP2B1 (Krishnan and Maru, 2004). Feng et al.
(CDK), p19, p21, and p27. Halder et al. (2012) found that TF1 (2002) also found out that black tea decreased CYP450 1A1
and TR abrogated the activation of AKT pathway and its down- activity in human hepatoma Hep G2 cells. TF treatment blocks
stream targets. The increased expressions of p19, p21, and p27 GSH-Benzo(a) pyrene conjugation via enhancing GST level,
and decreased levels of CDK2, CDK4, CDK6, and cyclin D1 thereby resulting in decreasing DNA adducts formation in
were also observed. Cyclooxygenases, lipoxyenases (LO), and tumor cells (Sharma and Rao, 2009). The down-regulation of
CYP450 regulate the metabolism of arachidonic acid, which is AP-1, the transcription factor which is an association of the
a well acceptable phenomena to reduce the risk of colorectal products of proto-oncogenes, such as fos and jun, is therefore
cancer (Fig. 3). Prostaglandin G2 (PGG2) formed by the action considered to be a sound therapeutic target against cancer
of COX-2 is involved in rapid cell proliferation in tumors, (Singh et al., 2011b). Black tea and green tea decreases AP-1-
mitogenesis, invasiveness, and angiogenesis. COX-2 has been dependent cell proliferation in the mouse epidermal H ras
shown to be over-expressed in colorectal cancer cells. Interest- mutant JB 6 cells, thereby inhibiting JNK1 (Chung et al., 1999).
ingly, TFs were found to increase PGE2 formation by stimulat- Suppression of EGF- or 12-O-tetradecanoyl-phorbol-13-ace-
ing the COX-2 activity; however, catechins reduced the tate-induced transformation was observed when mouse epider-
activities of both COX-1 and COX-2, and thus catechins had mal cells were treated with TFs and EGCG. This effect was
anticancer activity (Sharma and Rao, 2009). Numerous studies associated with the inhibition of AP-1 transcriptional activity
have reported that TFs exert anti-cancer effects by reducing cell and DNA binding affinity by tea phenols (Dong et al., 1997).
survival and inducing apoptosis in different human cancers (Lu Anti-metastatic effect of black tea extracts system was studied
et al., 2000; Yang et al., 2000). These include 33 BES, 21 BES, in oral squamous SCC-4 cells (Chang et al., 2012). The com-
SV40-WI 38, and Caco-2. Of these, TF3 (25 mM) had very plete inhibition of invasion of cells was observed via the sup-
strong anticancer effect through down-regulation of phosphor- pression of levels of p-FAK, p-paxillin, MMP-2, and uPA. In
ylation of c-jun, which lowers AP-1 activity and suppresses the addition to these effects on gene expression, black tea extract
growth of cancer cells. Co-treatment of TF2 and TF3 sup- also inhibited tumor growth in xenografted nude mice.
presses the growth of colon cancer cells by inhibiting the COX-
2 activity and inducing apoptotic cell death.
Clinical studies
Ehrlich’s ascites carcinoma (EAC) affects the host’s immune
system by reducing the number of splenic lymphocytes. Black Limited number of human intervention studies done on regular
tea extract has been shown to induce p53-dependent apoptosis intake of black tea demonstrate its chemopreventive potential,
and inhibit Bcl2, thereby increasing the Bcl2/Bax ratio. TFs and while a substantial number of clinical investigations with green
EGCG induction of apoptosis has been repeatedly reported to tea are documented. In vitro and preclinical studies support
be accompanied by enhanced hydrogen peroxide production in anti-cancer activity of black tea; however, its effect in human
H661 cells. Mazumdar et al. (2013) have very recently reported trails is uncertain. Two large prospective cohort studies of men
that TFs successfully induce apoptosis in human medullary and women found no association between the consumption of
thyroid carcinoma (MTC) cell line by inversely modulating two caffeine-rich tea and colon or rectal cancer (Gardner et al.,
molecular pathways: (i) stalling PI3K/AKT/Bad pathway that 2007). Ganmaa et al. (2008) also observed similar effect
resulted in mitochondrial transmembrane potential (MTP) between drinking of black tea and breast cancer. This supports
loss, cytochrome-c release, and activation of executioners cas- a previous meta-analysis, which analyzed eight breast cancer
pase-9 and caspase-3, and (ii) upholding p38 MAPK/caspase- studies and recorded no steady association with intake of black
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1407

tea (Gardner et al., 2007; Nie et al., 2014). Of the three newer studies designate a number of possible mechanisms to elucidate
investigations on ovarian cancer, only one study showed a sig- how black tea and its bioactive phytochemicals could help to pre-
nificant protective association with tea drinking with intake of vent cancer, further research from long-term human studies is
two or more cups per day (Baker et al., 2007). One case control needed to determine real life relationships with routine black tea
study of 770 subjects with renal cell cancer found no relation- drinking and incidence of cancer (Gardner et al., 2007).
ship with tea consumption.
Studies on endometrial and skin cancer were also examined,
Bioavailability and bioactivity
and outcomes revealed significant inverse association between
drinking two cups of black tea per day and cancer risk. In a Subsequently, natural products differ in their bioavailability
cross-sectional study of postmenopausal Chinese women, the and bioactivity; these are most critical issues when assessing
effect of drinking black tea was observed on the levels of estro- them for the development of functional foods, biopharmaceuti-
gen and endostenedione in plasma. Higher levels are associated cals, and nutraceuticals. Certainly, some sources demonstrating
with a higher risk of breast cancer. The oestrone level was antioxidant properties in in vitro system may have no effect
found to be 13% lower in green tea drinkers, compared with when consumed. This can be due to differences in the size of
non-tea drinkers. However, in black tea drinkers, the levels bioactive phyto-molecules, which influences the absorption of
were found to be 19% higher (Gardner et al., 2007). The phytochemicals in the gut, and how different phytochemicals
authors concluded that this observation needs further study, are processed in the body after absorption. However, intake
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because the number of participants involved was very low. also plays a key role in evaluating health value, with the fre-
Recent epidemiologic studies, especially cohort and case- quently taken black tea potentially making a greater contribu-
control studies, have yielded inconsistent findings regarding tion to health beneficial phytochemical status among tea-
association between tea consumption and risk of lung cancer. drinking populations than the more bioavailable, however
Consumption of black tea was associated with lower incidence irregularly taken green tea. An added consideration for black
of rectal cancer in the population of Moscow. A pooled analysis tea is that the processing readily oxidizes the absorbed cate-
of 13 prospective studies of renal cell cancer (n D 1480 cases) chins into potentially less bioavailable TFs and TRs. Widlansky
was carried out. The effect of black tea was observed more in et al. (2005) recorded the higher levels of catechin (33%) in
women than men, possibly because of high alcohol intake by plasma after consuming 450 mL of black tea per day. However,
men. Black tea drinking and the incidence of rectal cancer were after intake of 900-mL black tea per day for four weeks, cate-
inversely correlated in a dose-dependent manner, and a mini- chins level in plasma was 29% more compared with baseline,
mum consumption level of about 80 g/month was required to indicating that the chronic consumption has no impact on the
have any significant effect. (Gardner et al., 2007). In contrast to bioavailability of catechins.
the findings of the case control study mentioned above, taking Lack of a precise analytical technique to assess the presence
three cups of black tea per day was associated with a 15% of TRs and TFs in vivo can also make an underestimation of
reduction in cancer risk as compared with drinking less than the bioactivity of black tea compared with green tea. However,
one cup per day. Very recently, Cassidy et al. (2014) selected since green tea and black tea display equal antioxidant activity
171,940 Nurses’ Health Study and Nurses’ Health Study II par- in vivo in spite of containing different classes of flavonoids, it is
ticipants to examine associations between intake of total flavo- supposed that at least some of the TFs and TRs are absorbed. A
noids and their subclasses and risk of ovarian cancer by using very limited evidence from clinical investigations exists suggest-
Cox proportional hazards models. They concluded that the ing that the flavonoids, namely TFs and TRs, in black tea are
higher intake of flavonols and flavanones as well as black tea sufficiently bioavailable to stimulate the anticancer and anti-
consumption reduce the risk of ovarian cancer. A meta-analysis mutagenic effects described previously. The effects of food
of case-control and cohort studies showed both green tea (RR: matrix on the bioavailability of anti-mutagenic compound of
0.75; 95% CI: 0.62–0.91) and black tea (RR: 0.82; 95% CI: 0.71– black tea were studied, and reduced activity was observed when
0.94) significantly associated with reduced lung cancer risk milk was added to them (Widlansky et al., 2005). Maximum
(Wang et al., 2014). The overall odds ratio (ORs) for coffee, inhibition of 22, 42, and 78% was recorded in the presence of
green tea, and black tea intake examined recently by Bai et al. whole milk, semi-skimmed milk, and skimmed milk, respec-
(2014) were 1.17 (95% CI: 1.03–1.33), 0.76 (95% CI: 0.66–0.95), tively. A homogenized breakfast added together with black tea
and 0.80 (95% CI: 0.65–0.97), respectively. They suggested that extract completely escaped the anti-mutagenic potential of
greater consumption of fluid might have a protective effect on black tea. This was due to the precipitation of milk components
bladder cancer in Asian people. with tea polyphenols. The capacity of tea flavonoids to reach
A meta-analysis of lung cancer risk observed in 22 studies key tissues was estimated by Henning and colleagues, who ran-
found no overall significant association with black tea drinking domly assigned men awaiting a prostatectomy to consume
(Tang et al., 2009). No significant anti-cancer effect of black tea 1.421 per day of black tea, green tea, or a soft drink for five
was observed on stomach, colorectal, lung, and breast cancers in days. Analysis of prostate samples after surgery indicated that
a cohort study conducted in the Netherlands (Gardner et al., the concentration of tea flavonoids was higher in men given to
2007). A systematic review proposed that black tea has a small tea. There has been some discussion about whether the addition
beneficial effect on lung cancer risk in those who had never of milk to tea affects the bioavailability of flavonoids (Kyle et al.,
smoked. However, a meta-analysis of studies (n D 25) docu- 2007). Plasma levels of catechins, quercetin, and kaempferol
mented reported no significant relationship between black tea increased significantly after tea drinking, but were unaffected
intake and colorectal cancer risk. In conclusion, although in vitro by the addition of milk.
 1408 B. N. SINGH ET AL.

Acknowledgment and black tea polyphenols in H-ras-transformed cells: Structure–activ-

ity relationship and mechanisms involved. Cancer Res. 59:4610–4617.
Authors acknowledge Council of Scientific and Industrial Research (BSC- Davies, M. J., Judd, J. T., Baer, D. J., Clevidence, B. A., Paul, D. R., Edwards,
0106) and (OLP-089) and Department of Science & Technology (GAP A. J., Wiseman, S. A., Muesing, R. A. and Chen, S. C. (2003). Black tea
3325), New Delhi. Authors also thankful to Dr. C. S. Nautiyal, Director consumption reduces total and LDL cholesterol in mildly hypercholes-
CSIR–NBRI, Lucknow and Dr. N. Muraleedharan, Director, TRA, Tocklai terolemic adults. J. Nutr. 133:3298S–3302S.
Experimental Station, Jorhat, Assam, for their encouragement. Dong, Z., Ma, W., Huang, C. and Yang, C. S. (1997). Inhibition of tumor
promoter-induced activator protein 1 activation and cell transforma-
tion by tea polyphenols, (¡)-epigallocatechin gallate, and theaflavins.
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