Toxicology Letters Tea and Human Health: the Dark Shadows

Home , Camellia sinensis, Fermented tea, Oolong, Tea bag, White tea

Toxicology Letters 220 (2013) 82–87

Contents lists available at SciVerse ScienceDirect

Toxicology Letters

jou rnal homepage: www.elsevier.com/locate/toxlet

Mini review

Tea and human health: The dark shadows

a,b a,b a b a,∗

Aditi Jain , Chanchal Manghani , Shrey Kohli , Darshika Nigam , Vibha Rani

Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida 201307, Uttar Pradesh, India

Department of Biochemistry, School of Life Sciences, Dr. B.R. Ambedkar University, Agra 282004, India

h i g h l i g h t s

•

Different varieties of tea.

•

The major polyphenols present in tea.

•

The toxic effects of Green, Black, White, Oolong, Pu-erh Tea.

a r t i c l e i n f o a b s t r a c t

Article history: Tea is one of the most popularly consumed beverage. Depending on the manufacturing process, different

Received 26 February 2013

varieties of tea can be produced. The antioxidative and antimutagenic potential of tea in cardiovascular

Received in revised form 11 April 2013

diseases, cancer and obesity have long been studied. These therapeutic and nutritional beneﬁts of tea

Accepted 15 April 2013

can be attributed to the presence of ﬂavanoids. However, these ﬂavanoids also have certain detrimental

Available online 21 April 2013

effects on human health when their consumption exceeds certain limits. The toxicity of these ﬂavanoids

can be attributed to the formation of reactive oxygen species in the body which causes damage to the

Keywords:

DNA, lipid membranes etc. The aim of this review is to summarize brieﬂy, the less studied evidences of

Flavanoids

Black Tea

Oolong Tea

Pu-er Tea

Contents

1. Introduction ...... 83

2. Varieties of tea derived from C. sinensis ...... 83

3. Polyphenols in tea: the key players...... 83

4. Toxic effects of tea ...... 84

5. Green Tea...... 84

6. Black Tea ...... 84

7. White Tea ...... 85

8. Oolong Tea ...... 85

9. Pu-erh Tea ...... 85

10. Conclusion ...... 85

Conﬂict of interest ...... 85

Acknowledgement ...... 86

References ...... 86

∗

Corresponding author. Tel.: +91 120 2594210; fax: +91 120 2400986.

E-mail address: [email protected] (V. Rani).

A. Jain et al. / Toxicology Letters 220 (2013) 82–87 83

1. Introduction Seraﬁni et al., 1996), reduction of cardiovascular diseases by revers-

ing endothelial vasomotor dysfunction in patients (Duffy et al.,

The long history of tea as a beverage is remarkable and it is 2001), antimutagenicity (Yen and Chen, 1995) and prevention of

grown in many different places of the world. However, all true teas the onset of ischemic stroke (Arab et al., 2009).

are derived from the leaves of Camellia sinensis which is indige- White Tea is another common variety of tea derived from the

nous to China (Chen et al., 2007). The manufacture and processing buds of C. sinensis which are subjected to withering followed by

steps of tea vary with the variety of tea that is desired (Table 1). The drying. Care is taken to minimize the processing protocols as much

freshly plucked leaves undergo one or more of the processes that as possible to prevent oxidation and to leave delicate white leaf hair

include withering (reduces the moisture content), rolling (exposes intact which makes this tea “White” (Hilal and Engelhardt, 2007).

the sap of leaves to oxygen), oxidation (imparts the characteristic White Tea extract, although less studied, is a natural source that is

◦

ﬂavor to the tea), drying (at temperatures of 85–88 C) and sorting known to effectively inhibit adipogenesis and hence has potential

(on the basis of size of leaf particle) (Martin, 2007). The difference anti-obesity effects (Sohle et al., 2009). Certain varieties of White

in processing to attain different levels of oxidation determines the Tea also exhibit potent antimutagenic activity and act as photo-

variety of tea produced. Whereas Black Tea is produced after com- protective agents to prevent stimulated solar radiation-induced

plete oxidation of tea leaves, no oxidation is required for Green Tea. oxidative DNA damage (Koutelidakis et al., 2009; Camouse et al.,

Over the years, the potential health beneﬁts of different varieties 2009; Santana-Rios et al., 2001).

of tea have been extensively studied. The presence of polyphenolic Oolong Tea is a partially fermented tea and lies between un-

compounds accounts for their health beneﬁts besides imparting the fermented Green Tea and fermented Black Tea. It is produced

tea its characteristic ﬂavor (Yao et al., 2004). However, the detri- through a unique process including withering under the strong

mental effects of tea on human health cannot be overlooked while sun and oxidation before curling and twisting. Oolong Tea shows

considering its health beneﬁts. This review focuses on the deleteri- anti-obesity effects (He et al., 2009) and has role in prevention of

ous effects that different varieties of tea can have on human health diabetes (Yasui et al., 2011).

which will help the researchers in understanding the potential tox- Pu-erh Tea (also known as Pu’er) is prepared from the tender

icities associated with its consumption. leaves of tall and old plants of Tea. It is also prepared by full fer-

mentation, like Black Tea, but it is fermented for a longer duration

hence, it is also called as a “post fermented tea”. The time for which

2. Varieties of tea derived from C. sinensis

fermentation is done is directly proportional to its quality. Pu-erh

Tea has the highest content of caffeine as compared to all the other

The common varieties of tea which are known for their poten-

varieties of tea. In vitro studies have shown the role of Pu-erh Tea in

tial health beneﬁts are derived from the leaves and leaf buds of C.

decreasing levels of cholesterol ester and triglyceride in the plasma

sinensis, a species of ﬂowering plants in the family Theaceae. Var-

of rats (Sano et al., 1986). Aqueous extracts of Pu-erh Tea have also

ious studies have reported the health beneﬁts of tea derived from

shown antimicrobial and antimutagenic activities against strains

this plant which can be attributed to the anti-oxidant activity of the

like gram-positive Staphylcoccus aureus and Bacillus subtilis (Wu

tea ﬂavonoids (Liao et al., 2001; Yang and Landau, 2000).

et al., 2007). Some of the major health beneﬁts of different varieties

Green Tea is a non fermented tea, produced by drying and steam-

of tea have been summarized in Fig. 1.

ing of the fresh tea leaves. It is considered as a prophylactic drink

by Chinese since ancient times. It has a very complex composition

3. Polyphenols in tea: the key players

with maximum of protein content (15–20% dry weight) followed by

soluble carbohydrates (5–7% dry weight), minerals and trace ele-

Polyphenols are the secondary metabolites of plants and have

ments (5% dry weight) and amino acids (1–4% dry weight) (Cabrera

a great potential as an alternative source of treatment of chronic

et al., 2006). Green Tea is widely known for its potential health

diseases. Tea is a promising natural source for these bioactive ingre-

beneﬁts like reduction in the occurrence of cardiovascular dis-

dients which play an important role in different nutritional and

eases (Dogra et al., 2011), inhibition of matrix metalloproteinases

therapeutic effects of tea to delay the onset of risk factors associated

(Demeule et al., 2000), use as stimulant, regulation of body tem-

with the development of diseases like cancer and diabetes (Yang

perature, anti-microbial activity (Kubo et al., 1992), regulation of

et al., 2008). Tea polyphenols have been proposed to have antimu-

blood sugar and promotion of digestion (Samali et al., 2012).

tagenic, antiviral, anti-oxidant and anti-inﬂammatory properties in

Black Tea is fully oxidized during processing steps which

various biological systems (Lampe, 2003).

accounts for its stronger ﬂavor as compared to the other types

The polyphenolic content of tea is mainly attributed to

of teas which are comparatively less oxidized. It is manufactured

flavanoids including flavan-3-ols and flavanols. Catechins, the

as a fermented tea product following withering of the tea leaves

major ﬂavanoids present in Green Tea includes epicatechin

(Frei and Higdon, 2003). There have been reports showing its asso-

(EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and

ciation with attenuation of blood pressure (Negishi et al., 2004;

Table 1

Different varieties of tea and their characteristic features.

Tea variety Preparation Processing Caffeine content (per Steeping time Water temperature

8 oz cup ∼ 250 ml)

Green Tea Mature tea leaves Non fermented, non oxidized 15–35 mg 2–3 min Boil cool 3 min

Black Tea Mature tea leaves Fermented, fully oxidized 50–65 mg 4–5 min Boiling

White Tea Tea buds (immature tea leaves) Lightly oxidized (15–80%), non 10–25 mg 3–6 min Boil cool 4 min

fermented

Oolong Tea Mature tea leaves Partially fermented, semi 15–50 mg 2–3 min Boil cool 2 min

oxidized (15–80%)

Pu-erh Tea Tender tea leaves Post fermented, semi oxidized 60–70 mg 3–6 min Boiling

References Cabrera et al. (2006) and Chan Heiss and Heiss (2007) Lin et al. (2003) Web reference: www.theteaspot.com

and Pong (2006)

8 oz cup (steeping) for Green Tea and Oolong Tea: 1 rounded tsb. of leaves; Black Tea: 1 level tsb. of leaves; White Tea and Pu-erh Tea: 1 heaping tsb. of leaves.

84 A. Jain et al. / Toxicology Letters 220 (2013) 82–87

Fig. 2. Balance between antioxidant and pro-oxidant characteristics of ﬂavonoids:

consumption of tea in high doses leads to an imbalance in pro-oxidant and antioxi-

dant characteristics of ﬂavanoids thus resulting in toxicity.

5. Green Tea

Fig. 1. Health beneﬁts of different varieties of tea: the ﬁgure summarizes the ther-

Most of the harmful effects of Green Tea like hypertension and

apeutic effects of different varieties of tea which can be attributed to the presence

osteoporosis are due to its caffeine content. However, it is impor-

of flavanoids like flavan-3-ols and flavanols.

tant to note that toxicity from Green Tea occurs only at high doses.

The LD50 dose of caffeine in Green Tea is estimated to be 10–14 g

(150–200 mg/kg of Green Tea) (Henning et al., 2003) but certain

−

( )-epigallocatechin-3-gallate (EGCg) (McKay and Blumberg, harmful side effects are observed at lower doses also. However,

2002). Among these, the most abundant and active compound is caffeine may not be the sole factor responsible for Green Tea tox-

EGCg (Murakami et al., 1992). icity as several side-effects like headache, nausea, confusion and

White Tea has been reported to possess higher concentration of muscle pain have also been observed in people consuming decaf-

catechins as compared to Green Tea which is followed by Black Tea feinated tea (Su-Yin, 2009). The hepatotoxic effects of different

and Oolong Tea (Venditti et al., 2010; Rusak et al., 2008; Kanwar components of Green Tea in vitro have been reported, where acute

et al., 2012). Polyphenolic content of Green Tea accounts for half toxicity in rat liver cells was observed with high concentrations

of the dry matter followed by caffeine and amino acid theanine of hydro-alcoholic Green Tea extracts (100–500 ␮g/ml) and EGCg

(Schmidt et al., 2005). In general, catechin content of Green Tea is was found to be responsible for this effect (Schmidt et al., 2005). The

around 30–40% of the total dry weight (Su-Yin, 2009). polyphenols present in Green Tea are also known to have inhibitory

Compounds other than catechins include gallic acid and quinic effects on drug metabolism where the catechins can bind to the

esters of gallic, coumaric, and caffeic acids, purine alkaloids theo- drug molecules and hence reduce their bioavailability by affecting

bromine caffeine, proanthocyanidins and trace levels of ﬂavones their absorption (Yang and Pan, 2012). Due to these reasons, drink-

(Crozier et al., 2009). ing of Green Tea is not recommended to patients taking drugs like

beta blockers, lithium drugs used to treat bipolar disorders, estro-

gens, clozapine etc. (Stammler and Volm, 1997). The catechins also

4. Toxic effects of tea inhibit the enzymatic activity of drug transporters and drug metab-

olizing enzymes or alter their protein levels (Feng, 2007). Dose

Although health beneﬁts of the varieties of tea are extensively limiting side effects of Green Tea extracts have been observed in

studied, analysis of their potential toxicities which may pose harm- central nervous system, stomach and intestine (Chow et al., 2003;

ful effects on human health remains largely ignored. Although the Inoue et al., 2011). However since these effects of Green Tea occur

mechanism of toxicity is not well understood, it is proposed that only at high doses, its consumption should not be allowed to exceed

the phenolics present in tea, which are known for their usual health beyond a certain level.

beneﬁts, can also act as prooxidants in the presence of redox-

active chemicals and lead to the formation of reactive oxygen 6. Black Tea

species which can cause damage to DNA, lipids and other bio-

logical molecules (Decker, 1997). It is the balance between the Black Tea has been reported to possess a high concentration of

pro-oxidant and antioxidant effects of ﬂavanoids that serves to tannins that is about 0.8 mg/ml (Pasha and Reddy, 2005). The pres-

determine the toxicity associated with tea (Fig. 2). Certain vari- ence of tannins contribute to inhibition of absorption of non-heam

eties of tea also elicit severe allergic reactions such as hay fever, iron to a signiﬁcant extent by forming insoluble complexes with the

asthma, nausea, vomiting and neckpain in patients (Subiza et al., ferric ion and subsequently affecting iron absorption in the lumen

1989). Presence of xanthines (like caffeine) in tea is responsible (Disler et al., 1975). However, this characteristic of Black Tea that

for a variety of toxic effects including nervous irritability, convul- leads to reduction of intestinal absorption of dietry iron can be uti-

sions, tachycardia, extrasystoles, and gastric irritation (Brem et al., lized to reduce iron uptake in iron overload syndromes such as

1977). Due to the presence of xanthines, tea ingestion has also been genetic hemochromatosis or refractory anemia (Kaltwasser et al.,

linked to the occurrence of tonic posturing and nervous irritability 1998). The phenolic compounds present in tea may also cause pre-

when given to a seven-week-old infant. Therefore the assessment cipitation of digestive enzymes of the gut and hence inhibit them

of potential dietary ﬂavonoid/phenolic-induced toxicity concerns (Jolyn and Jolyn, 1964). Black Tea is also known to affect some

of different varieties of tea including their pro-oxidant activity and intestinal microﬂoras that contribute to health by metabolizing

mitochondrial toxicity is of prime importance while considering pro-carcinogens, carcinogens and nutrients that reach the colon

their beneﬁcial properties. (Mountzouris et al., 2002). It signiﬁcantly reduces the amounts of

A. Jain et al. / Toxicology Letters 220 (2013) 82–87 85

bacteria present in the intestine which may have health beneﬁts

for an individual (Mai et al., 2004). Although the anti-carcinogenic

effects of the Black Tea have been reported, Black Tea consumption

may also show carcinogenic effects on selected organs like rectum

(Heilbrun et al., 1986). Black Tea has been able to garner unanimous

acceptance given its hygienic packaging in tea bags. However, these

tea bags have been known to have high ﬂuoride content in the range

of 1.15–6.01 mg/L (Cao et al., 2006). According to the 1989 American

Dietry Reference Intake (RDA), the safe upper limit of daily ﬂuoride

intake is 1.5–4.0 mg for adults and 2.5 mg for children. Thus 4 cups

of Black Tea are safe if each tea bag is assumed to contain 2 g of

tea. However in areas affected by drinking water ﬂuoridation and

other ﬂuoride supplements, even lower intake of Black Tea can pose

threats to health (Trivedi et al., 2011). Excessive levels of ﬂuoride

may cause skeletal ﬂuorosis and bone fractures. In fact, the ﬂuo-

ride content of tea has been increasing over the past years due to

water ﬂuoridation. Hence it is of considerable importance to keep

the consumption of Black Tea in safe limits to avoid its associated

side effects on humans.

7. White Tea

Studies show that White Tea reduces iron absorption when con-

sumed in high doses by forming insoluble complexes in the lumen

of gastrointestinal tract without causing any alteration to body

weight, food intake, and food efﬁciency in rats (Hamdaouia et al.,

1997). The apparent iron absorption was signiﬁcantly reduced in

rats at the highest dose of White Tea extract (12 mg of the polyphe-

nols per kilogram body weight per day, equivalent to 9 cups of tea in

Fig. 3. Toxic effects of different varieties of tea: the ﬁgure summarizes potential

humans) for both 3 and 30 days of consumption (Perez-Llamas et al., toxicities associated with the consumption of high dosage of different varieties of

tea.

2011). However, it is suggested that the potential antinutritional

effects of White Tea depend on the length of exposure.

the possible health risks resulting from long-term exposure to

metals contained in the tea needs to be evaluated, as it has been

8. Oolong Tea

shown in a study that the arsenic levels of Pu-erh Tea approaches

the accepted risk levels for the highest exposure group and hence

A cohort study conducted on Japanese male population has

arsenic levels are of great concern (Cao et al., 2010). The toxic effects

shown that long term consumption of Oolong Tea can lead to

of different varieties of tea have been summarized in Fig. 3.

onset of diabetes whereas its short term consumption shows

anti-hyperglycemic effect in diabetic patients (Hayashino et al.,

2011; Hosoda et al., 2003). The polymerized polyphenols isolated 10. Conclusion

from leaves of Oolong Tea such as Oolonghomobisﬂavans A and

B and Oolongtheanine 3 -O-gallate also show inhibitory activities The health beneﬁts associated with different varieties of tea

against pancreatic lipase which affects lipid metabolism in the gut have been extensively studied. However, the toxic effects, which

(Nakai et al., 2005). Some case studies also show the develop- have been overlooked in the past, should be kept in mind while

ment of hypokalemia, atrioventricular block, QT prolongation and considering tea as a healthy beverage. The toxicities associated with

incessant non-sustained ventricular tachycardia because of over different varieties of tea differ in their nature and the extent of

consumption of Oolong Tea (Toshiya et al., 1999). Also, too much damage caused to human body which may also result in severe

of consumption of Oolong Tea can ﬂush out calcium in the urine complications in some cases. Other factors are also associated with

because of its high caffeine content which can lead to osteoporo- the difference in the extent of toxicity of tea such as pesticidal con-

sis by interfering with the absorption of calcium (Heaney, 2002). tamination during the cultivation of tea. This may be the reason

Hence, it should be limited to not more than 3 cups a day. why in some cases toxicity is different and speciﬁc to one particular

population only. The difference in preparation and consumption of

tea in different parts of the world also contributes to these effects.

9. Pu-erh Tea

However, further studies should be conducted to understand the

underlying mechanism responsible for the toxicity of different vari-

The toxicity shown by the Pu-erh Tea is majorly associated with

eties of tea. Moreover, the varieties of tea when consumed in safe

its high caffeine content. Caffeine consumption is directly associ-

amount pose a lot of health beneﬁts. Only when their consumption

ated with several deleterious effects like osteoporosis, high blood

continues for a long period of time or it is taken in high doses, the

pressure, diabetes, sleep problems etc. A study suggests that intake

side effects of tea come to the fore. Hence, a rigorous assessment of

of caffeine in amounts >300 mg/d accelerates bone loss at the spine

the effects of tea in well controlled human trials will be required for

in elderly postmenopausal women (Rapuri et al., 2001). Because

better understanding of the toxic effects of tea on human health.

of its caffeine content, Pu-erh Tea is not advised for consumption

during pregnancies as it may harm the fetus. In a case study, a 16

year old male who ingested an estimated 6–8 g of caffeine reported Conﬂict of interest

many adverse effects including hypokalemia, elevated blood glu-

cose, tachycardia, bigeminy and agitation (Leson et al., 1988). Also, No conﬂict of interest.

86 A. Jain et al. / Toxicology Letters 220 (2013) 82–87

Acknowledgement Kaltwasser, J.P., Werner, E., Schalk, K., Hansen, C., Gottschalk, R., Seidl, C., 1998.

Clinical trial on the effect of regular tea drinking on iron accumulation in genetic

haemochromatosis. Gut 43, 699–704.

We acknowledge Jaypee Institute of Information Technology

Koutelidakis, A.E., Argiri, K., Seraﬁni, M., Proestos, C., Komaitis, M., Pecorari, M., Kap-

(Deemed to be University) for the support. sokefalou, M., 2009. Green tea, white tea and Pelargonium purpureum increase

the antioxidant capacity of plasma and some organs in mice. Nutrition 25, 53–58.

Kubo, I., Muroi, H., Masaki Himejima, M., 1992. Antimicrobial activity of green tea

References ﬂavor components and their combination effects. Journal of Agricultural and

Food Chemistry 19, 245–248.

Arab, L., Liu, W., Elashoff, D., 2009. Green and black tea consumption and risk of Lampe, J.W., 2003. Spicing up a vegetarian diet: chemopreventive effects of phyto-

stroke: a meta-analysis. Stroke 40, 1786–1792. chemicals. American Journal of Clinical Nutrition 78, 579–583.

Brem, A.S., Martin, H., Stern, L., 1977. Toxicity from tea ingestion in an infant: a Leson, C.L., McGuigan, M.A., Bryson, S.M., 1988. Caffeine overdose in an adolescent

computer simulation analysis. Clinical Biochemistry 10, 148–150. male. Clinical Toxicology 26, 407–415.

Cabrera, C., Artacho, R., Gimenez, R., 2006. Beneﬁcial effects of green tea – a review. Liao, S., Kao, Y.H., Hiipakka, R.A., 2001. Green tea: biochemical and biological basis

Journal of the American College of Nutrition 25, 79–99. for health beneﬁts. Vitamins and Hormones 62, 1–94.

Camouse, M.M., Domingo, D.S., Swain, F.R., Conrad, E.P., Matsui, M.S., Maes, D., Lin, Y.S., Tsai, Y.J., Tsay, J.S., Lin, J.K., 2003. Factors affecting the levels of tea polyphe-

Declercq, L., Cooper, K.D., Stevens, S.R., Baron, E.D., 2009. Topical application nols and caffeine in tea leaves. Journal of Agricultural and Food Chemistry 51,

of green and white tea extracts provides protection from solar-simulated ultra- 1864–1873.

violet light in human skin. Experimental Dermatology 18, 522–526. Mai, V., Katki, H.A., Harmsen, H., Gallaher, D., Schatzkin, A., Baer, D.J., Clevi-

Cao, H., Qiao, L., Zhang, H., Chen, J., 2010. Exposure and risk assessment for alu- dence, B., 2004. Effects of a controlled diet and black tea drinking on the

minium and heavy metals in Puerh tea. Science of the Total Environment 408, fecal microﬂora composition and the fecal bile acid proﬁle of human volun-

277727–277784. teers in a double-blinded randomized feeding study. Journal of Nutrition 134,

Cao, J., Zhao, Y., Li, Y., Deng, H.J., Yi, J., Liu, J.W., 2006. Fluoride levels in various 473–478.

black tea commodities: measurement and safety evaluation. Food and Chemical Martin, L.C., 2007. Tea: The Drink That Changed the World. Tuttle Publishings, U.S.A.

Toxicology 44, 1131–1137. McKay, D.L., Blumberg, J.B., 2002. The role of tea in human health: an update. Journal

Chan, Pong, K., 2006. First-Step to Chinese Puerh Tea. WuShing Books Publications of the American College of Nutrition 21, 1–13.

Co. Ltd., Taipei, Taiwan, ISBN 978-957-8964-33-4. Mountzouris, K.C., McCartney, A.L., Gibson, G.R., 2002. Intestinal microﬂora of

Chen, L., Zhou, Z., Yang, Y., 2007. Genetic improvement and breeding of tea plant human infants and current trends for its nutritional modulation. British Journal

(Camellia sinensis) in China: from individual selection to hybridization and of Nutrition 87, 405–420.

molecular breeding. Euphytica 154, 239–248. Murakami, S., Muramatsu, M., Otomo, S., 1992. Gastric H+, K(+)-ATPase inhibition

Chow, H.H., Cai, Y., Hakim, I.A., Crowell, J.A., Shahi, F., Brooks, C.A., Dorr, R.T., Hara, Y., by catechins. Journal of Pharmaceutical Sciences 44, 926–928.

Alberts, D.S., 2003. Pharmacokinetics and safety of green tea polyphenols after Nakai, M., Fukui, Y., Asami, S., Toyoda-Ono, Y., Iwashita, T., Shibata, H., Mitsunaga,

multiple-dose administration of epigallocatechin gallate and polyphenon E in T., Hashimoto, F., Kiso, Y.J., 2005. Inhibitory effects of oolong tea polyphenols

healthy individuals. Clinical Cancer Research 9, 3312–3319. on pancreatic lipase in vitro. Journal of Agricultural and Food Chemistry 53,

Crozier, A., Jaganath, I.B., Clifford, M.N., 2009. Dietary phenolics: chemistry, bioavail- 4593–4598.

ability and effects on health. Natural Products Reports 26, 1001–1043. Negishi, H., Xu, J.W., Ikeda, K., Njelekela, M., Nara, Y., Yamori, Y., 2004. Black and

Decker, E.A., 1997. Phenolics: pro-oxidants or antioxidants? Nutrition Reviews 55, green tea polyphenols attenuate blood pressure increases in stroke-prone spon-

396–407. taneously hypertensive rats. Journal of Nutrition 134, 38–42.

Demeule, M., Brossard, M., Page, M., Gingras, D., Beliveau, R., 2000. Matrix metal- Pasha, C., Reddy, G., 2005. Nutritional and medicinal improvement of black tea by

loproteinase inhibition by green tea catechins. Biochimica et Biophysica Acta yeast fermentation. Food Chemistry 89, 449–453.

1478, 51–60. Perez-Llamas, F., Gonzalez, D., Cabrera, L., Espinosa, C., Lopez, J.A., Larque, E., Alma-

Disler, P.B., Lynch, S.R., Charlton, R.W., Torrance, J.D., Bothwell, T.H., Walker, R.B., jano, M.P., Zamora, S., 2011. White tea consumption slightly reduces iron

Mayet, F., 1975. The effect of tea on iron absorption. Gut 16, 193–200. absorption but not growth, food efﬁciency, protein utilization, or calcium, phos-

Dogra, D., Ahuja, S., Krishnan, S., Kohli, S., Rani, V., 2011. In vitro cardioprotec- phorus, magnesium, and zinc absorption in rats. Journal of Physiology and

tive effect of Indian Camellia sinensis extract against hydrogen peroxide induced Biochemistry 67, 331–337.

hypertrophy. Journal of Pharmacy Research, 4. Rapuri, P.B., Gallagher, J.C., Kinyamu, H.K., Ryschon, K.L., 2001. Caffeine intake

Duffy, S.J., Keaney, J.F., Holbrook, M., Gokce, N., Swerdloff, P.L., Frei, B., Vita, J.A., 2001. increases the rate of bone loss in elderly women and interacts with vita-

Short- and long-term black tea consumption reverses endothelial dysfunction min D receptor genotypes. The American Journal of Clinical Nutrition 74,

in patients with coronary artery disease. Circulation 104, 151–156. 694–700.

Feng, W.Y., 2007. Metabolism of green tea catechins: an overview. Current Drug Rusak, G., Komes, D., Likic, S., Horzic, D., Kovac, M., 2008. Phenolic content and

Metabolism 7, 755–809. antioxidative capacity of green and white tea extracts depending on extraction

Frei, B., Higdon, J.V., 2003. Antioxidant activity of tea polyphenols in vivo: evidence conditions and the solvent used. Food Chemistry 110, 852–858.

from animal studies. Journal of Nutrition 133, 32755–32845. Samali, A., Kirim, R.A., Mustapha, K.B., 2012. Qualitative and quantitative evaluation

Hamdaouia, M.H., Hédhilib, A., Doghric, T., Tritard, B., 1997. Effect of tea decoction of some herbal teas commonly consumed in Nigeria. African Journal of Pharmacy

given to rats ad libitum for a relatively long time on body weight gains and iron, and Pharmacology 6, 384–388.

copper, zinc, magnesium concentrations in blood, liver, duodenum and spleen. Sano, M., Takeuaka, Y., Kojima, R., Saito, S.I., Tomita, I., Katou, H., 1986. Effects of

Annals of Nutrition and Metabolism 41, 196–202. pu-erh tea on lipid metabolism in rats. Chemical and Pharmaceutical Bulletin

Hayashino, Y., Fukuhara, S., Okamura, T., Tanaka, T., Ueshima, H., 2011. High oolong 34, 221–228.

tea consumption predicts future risk of diabetes among Japanese male workers: Santana-Rios, G., Orner, G.A., Amantanaa, A., Provost, C., Wu, S., Dashwood, R.H.,

a prospective cohort study. Diabetic Medicine 28, 805–810. 2001. Potent antimutagenic activity of white tea in comparison with green tea

He, R., Chen, L., Lin, B., Matsui, Y., Yao, X., Kurihara, H., 2009. Beneﬁcial effects in the Salmonella assay. Mutation Research 495, 61–74.

of oolong tea consumptions and diet-induced overweight and obese subjects. Schmidt, M., Schmitz, H.J., Baumgart, A., Guedon, D., Netsch, M.I., Kreuter, M.H.,

Chinese Journal of Integrative Medicine 15, 34–35. Schmidlin, C.B., Schrenk, D., 2005. Toxicity of green tea extracts and their con-

Heaney, R., 2002. Effects of caffeine on bone and calcium economy. Food and Chem- stituents in rat hepatocytes in primary culture. Food and Chemical Toxicology

ical Toxicology 40, 1263–1270. 43, 307–314.

Heilbrun, L.K., Nomura, A., Stemmerman, G.N., 1986. Black tea consumption and Seraﬁni, M., Ghiselli, A., Ferro-Luzzi, A., 1996. In vivo antioxidant effect of green and

cancer risk: a prospective study. British Journal of Cancer 54, 677–683. black tea in man. European Journal of Clinical Nutrition 50, 28–32.

Heiss, M.L., Heiss, R.J., 2007. The Story of Tea: A Cultural History and Drinking Guide, Sohle, J., Knott, A., Holtzmann, U., Siegner, R., Gronniger, E., Schepky, A., Gallinat, S.,

ﬁrst ed. Ten Speed Press, New York, ISBN: 978-1-58008. Wenck, H., Stab, F., Winnefeld, M., 2009. White tea extract induces lipolytic activ-

Henning, M., Fajardo-Lira, C., Lee, H.W., Yousseﬁan, A.A., Go, V.L., Heber, D., 2003. ity and inhibits adipogenesis in human subcutaneous (pre)-adipocytes. Nutri-

Catechin content of 18 teas and a green tea extract supplement correlates with tion and Metabolism (London) 6, 20, http://dx.doi.org/10.1186/1743-7075-6-20.

the antioxidant capacity. Nutrition and Cancer 45, 226–325. Stammler, G., Volm, M., 1997. Green tea catechins (EGCG and EGC) have modulating

Hilal, Y., Engelhardt, U., 2007. Characterisation of white tea – comparison to green effects on the activity of doxorubicin in drug-resistant cell lines. Anti-Cancer

and black tea. Journal für Verbraucherschutz und Lebensmittelsicherheit 2, Drugs 8, 265–268.

414–421. Subiza, J., Subiza, J.L., Hinojosa, M., Garcia, R., Jerez, M., Valdivieso, R., Subiza, E.,

Hosoda, K., Wang, M.F., Liao, M.L., Chuang, C.K., Iha, M., Clevidence, B., Yamamoto, S., 1989. Anaphylactic reaction after the ingestion of chamomile tea: a study of

2003. Antihyperglycemic effect of oolong tea in type 2 diabetes. Diabetes Care cross-reactivity with other composite pollens. Journal of Allergy and Clinical

26, 1714–1718. Immunology 84, 353–358.

Inoue, H., Akiyama, S., Yamamoto, M., Nesumi, A., Tanaka, T., Murakami, A., 2011. Su-Yin, A.N., 2009. Toxicity of green tea extracts used for weight loss. Emergency

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate Medicine 18, 43–48.

sodium-induced colitis mice by down-regulation of antioxidant enzymes and Toshiya, A., Manabu, O., Hideyuki, H., Shingo, K., Kotaro, M., Naoyoshi, A., Kazui,

heat-shock protein expressions. Cell Stress and Chaperones 16, 653–662. S., Takashi, O., Tohru, I., 1999. Hypokalemia with syncope caused by habitual

Jolyn, M.A., Jolyn, L., 1964. Astringency of fruits and fruit products in relation to drinking of oolong tea. Internal Medicine 38, 252–256.

phenolic content. Advances in Food Research 13, 179–217. Trivedi, M.H., Verma, R.J., Sangai, N.P., Chinoy, N.J., 2011. Black tea extract mitigation

Kanwar, J., Taskeen, M., Mohammad, I., Huo, C., Han, T.H., Dou, Q.P., 2012. Recent of NaF-induced lipid peroxidation in different regions of mice brain. Research

advances on tea polyphenols. Frontiers in Bioscience 4, 111–131. Report 44, 243–254.

A. Jain et al. / Toxicology Letters 220 (2013) 82–87 87

Venditti, E., Bacchetti, T., Tiano, L., Carloni, P., Greci, L., Damiani, E., 2010. Hot vs. Yao, L.H., Jiang, Y.M., Shi, J., Tomas-Barberan, F., Datta, A., Singanusong, R., Chen,

cold water steeping of different teas: do they affect antioxidant activity? Food S.S., 2004. Flavonoids in food and their health beneﬁts. Plant Foods for Human

Chemistry 119, 1597–1604. Nutrition 59, 113–122.

Wu, S.C., Yen, G.C., Wang, B.S., Chiu, C.K., Yen, W.J., Chang, L.W., Duh, P.D., 2007. Yasui, K., Miyoshi, N., Tababe, H., Ishigami, Y., Fukutomi, R., Imaai, S., Isemura, M.,

Antimutagenic and antimicrobial activities of pu-erh tea. LWT - Food Science 2011. Effects of oolong tea on gene expression of glucooneogenic enzymes in

and Technology 40, 506–512. the mouse liver and in rat hepatoma H4IIE cells. Journal of Medicinal Food 14,

Yang, C.S., Landau, J.M., 2000. Effects of tea consumption on nutrition and health. 930–938.

Journal of Nutrition 130, 2409–2412. Yen, G., Chen, H., 1995. Antioxidant activity of various tea extracts in relation to

Yang, C.S., Ju, J., Lu, G., 2008. Cancer prevention by tea and tea polyphenols. Asia their antimutagenicity. Journal of Agricultural and Food Chemistry 43, 27–32.

Paciﬁc Journal of Clinical Nutrition 17, 245–248.

Yang, C.S., Pan, E., 2012. The effects of green tea polyphenols on drug metabolism. Web reference

Expert Opinion on Drug Metabolism & Toxicology 8, 677–689. http://theteaspot.com/how-to-brew.html