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Tea and Health: Indian Scenario
By Dr. Biswajit Bera, Director of Research, Tea Board

Introduction and Importance :
Medicinal values and health aspects of Tea are being increasingly reported and documented in research papers now a days. The various properties of tea as a health drink are being discussed in different forums (symposia, workshop etc.) and being considered important for future in the context of identification of research projects in tea. In the recent past National Tea Research Foundation (NTRF) has funded various projects in the areas of tea and human health to different nationally acclaimed research institutes. Some of the projects were successfully completed and some are being continued as ongoing.

Effects of Tea extracts and chemical compounds in preventing human disease like Cardiac problems, Cancer, Bone degeneration and Gastric disorder etc. are well known. Black tea, the most widely consumed beverage, is a source of compound with antioxidative, antimicrobial, antimutagenic and anticarceinogenic properties.

In a study on the medicinal properties of tea root extracts and its active constituents conducted by one of the famous institute of Kolkata (IICB) stated that triterpinoid saponins in tea root possesses strong activity against human lymphoma and leukemic cells. The findings also suggest that the cytotoxic effect and apoptosis inducing capacity of tea root extract reflects its importance as potential chemo preventive agent and its use in cancer therapy in future.

In another study chemo preventive efficacy of black tea was investigated by scientist from Tata Memorial Centre, Mumbai. It is evident from the study that black tea derived polymeric polyphenols retain the beneficial effect of monomeric green tea polyphenols. The said report also supports the view that use of dietary supplements offers a better chemo preventive strategy. Antioxidant potential of black tea on prostate cancer was investigated by Indian Toxicological Research Institute, Lucknow. This study opens new avenue and noble perspective in cancer chemo prevention. The data generated from the study also imply that antioxidant enzymes can be used for studies on prevention different types of cancer.

Medicinal properties and pharmacological evaluation of Indian black tea was studied recently and it was stated that catechins are the most abandoned polyphenols in green tea, whereas the typical pigments in black tea are theaflavins and thearubigins. Recently, theaflavins are attracted considerable interest because of their potential benefits for human health including antimutagenecity, anti-inflammatory and in cancer. The result suggests that polyphenols especially the flavonoids possesses a high antioxidant power, which can protect cells against the adverse effects of reactive oxygen species. Flavonoids present in tea were found to be several times more potent in comparison to vitamin-C. The scavenging property such polyphenols have been demonstrated against various types of free radicals. The pharmacotheraputic properties of both green and black tea re being attributed to these polyphenols. Green tea catechins have profound effect on the lipid metabolism.

Work done in India ( 2007-2012) :


Tea leaves contain more than 700 chemicals, among which the compounds closely related to human health are polyphenols, flavanoides, amino acids mainly theanine, vitamins (C, E and K), caffeine and polysaccharides. Moreover, tea drinking has recently proven to be associated with cell-mediated immune function of the human body. Tea plays an important role in improving beneficial intestinal microflora, as well as providing immunity against intestinal disorders and in protecting cell membranes from oxidative damage. Tea also prevents dental caries due to the presence of fluorine. The role of tea is well established in normalizing blood pressure, lipid depressing activity, prevention of coronary heart diseases and diabetes by reducing the blood-glucose activity. Tea also possesses germicidal and germistatic activities against various gram-positive and gram negative human pathogenic bacteria. Both green and black tea infusions contain a number of antioxidants, mainly catechins and their oxidized forms that have anti-carcinogenic, anti-mutagenic and anti-tumoric properties.

A. Major thrust areas of Tea & Health Research in India:

Aging & Neurodegenerative Disorder
Gastric Ulcer
Microbial, Viral And Parasitic Infection
Liver Disease
Cardiovascular Disease
Dental/ Oral Healt...etc.

B. Institutes / Universities involved in Tea & Health Research in India

Bose Institute
Calcutta University
CSIR-Indian Institute Of Chemical Biology
Jadavpur University
Chittaranjan National Cancer Institute
Institute of Postgraduate Medical Education & Research
KPC Medical College And Hospital
Bhaba Atomic Research Centre
S.N.Pradhan Institute of Neurosciences
Vivekananda Institute of Medical Sciences

C. Salient Observations of Tea & Health Research in India:


1. Anticarcinogenic and antimutagenic effects of black tea.
Salient findings:
Cancer is one of the most dreaded diseases affecting millions of people worldwide. In this research, the antigenotoxic effects (both antimutagenic and anticarcinogenic) of black tea together with its mechanistic aspects were evaluated in experimental studies. The antigenotoxic activity of balck tea was identified in microbial and mammalian in-vivo systems.

2. An approach to induce selective apoptosis in tumor cells without harming the normal cells of the host by black tea extract.
Salient findings:
Black tea acts as immune function restorer and protects the immune system in the tumor bearing host. These findings are important in formulating future cancer therapy because unlike other means black tea is non-toxic by itself and ameliorates cancer induced toxicity of the host. Therefore its emergence as a harmless cancer drug is very high.

3. Evaluation of the role of Black Tea in the Prevention of Lung Cancer.
Salient findings:
The results strongly suggest that black tea does have a role in prevention of lung cancerioma and two major actrive tea compounds are potential chemopreventive agents. Drinking tea can effectively restrict cellular proliferation and induce apoptosis at the target site.

4. Investigations on chemopreventive efficacy of Black Tea, the popular beverage in India.
Salient findings:
In vivo and In vitro studies with isolated black tea polyphenols established their strong anti-promoting activity against initiation of cancer. Five fractions of polymeric black tea polyphenols, had this anti-initiating effect in varying degrees, but in general, these polymeric polyphenols in their chemopreventive properties are comparable to those shown by monomeric green tea poylyphenols.

5. Modulation of Cytotoxicity and Genotoxicity of Arsenic Compounds in Mammalian cells by Tea extract and its Polyphenols
Salient findings:
Toxicity due to arsenic is a serious problem in different parts of West Bengal. This study reveals that tea extracts like pure tea polyphenols have promising chemo preventive activity as well as enhancing repair activity against environmental arsenic contamination. Black tea and TF are equally effective in combining arsenic toxicity, genotoxicity and clastogenicity.

6. Investigations on chemo preventive efficacy of Black Tea, the popular beverage in India.
Salient findings:
In vivo and In vitro studies with isolated black tea polyphenols established their strong anti-promoting activity against initiation of cancer. Five fractions of polymeric black tea polyphenols, had this anti-initiating effect in varying degrees, but in general, these polymeric polyphenols in their chemo preventive properties are comparable to those shown by monomeric green tea poylyphenols.

7. Antioxidant Potential of Black Tea on Prostrate Cancer - ITRC, Lucknow.
Salient findings:
Tea seems to have a remarkable effect in reducing the intensity of prostrate cancer, mostly by inhibiting the cancer promoting elements in prostrate cancer. At cellular level, these promoters operate by increasing the role of cell cycling, through prior critical cell damage followed by regeneration. Tough these mechanisms tea polyphenols exert a protective and healing effect.

8. Evaluation of pro and antioxidant properties of black tea in relation to regulation of mitochondrial death cascade in cancer and immune cells
Salient findings:
Theflavins of tea initiate the apoptotic cascade in a dosage dependent manner against breast cancer. The pathway of the action basically involves utilization of an enzyme medicated box translocat to mitochondria. It has further been established the programmed death of cancerous cells following exposure to theaflavins is independent of the production of reactive oxygen species.

Black tea as an antidote for cigarette smoke induced oxidative damage of proteins and DNA as well as cancer (II phase)
Salient findings:
Black tea extract has beneficial effects in preventing or reducing cigarette smoke induced cancer in lungs. This study has established the strong efficacy of black tea compounds in preventing the oxidative damage of protein and DNA which otherwise are destructive to lung cells, including the changes deep within the lung i.e. the emphysematous changes damage.

Immunomodulatory activity of Black Tea
Salient findings:
Black tea extract (BTE) displays immunomodulatory as well as immunoprophylatic activities as reflected in increases in lymphocyte counts when subjects were treated with BTE at 25 mg/kg and 50 mg/kg for 7, 15, and 48 days. The adjuvant effects include higher haemaglution titre, but BTE did not produce any significant change in lung macrophage counts.

11. Stress-Hypertension and effect of tea
Salient findings:
The causal pathway to the reduction of stress hypertension in human subjects by following programmed consumption of black tea extract for 12 consecutive weeks was identified. For chronic subjects’ consumption of 450 ml of BTE, equivalent to 7.5 gms of tea leaves, during the said period caused an increase in serotonin level effecting thereby a reduction in stress level.

12. Assessment of Anti-stress and aging defence activities of black tea thearubigins and theaflavins.
Salient findings:
This is a very basic study. By using Drosophila as a model it looks into the mechanism of aging and stress generation, and their gene expressions in the presence and absence of thearubigins. Theorubigins are major components of black tea extract (BTE). Their impact as anti-aging and antistress agents could to a great extent be expropolated from this study to human beings.

13. Study of Genotypic Predisposition to Oral Cancer modified by Tea “A collaborative study on the population of Assam.
Salient Features:
This is one of the first studies with human cohorts to evaluate the potential health benefits of tea. This study took note of the anthropometric aspects of a tribal population of Assam having had various chronic oral diseases following tea dring as a therapeutic agent. It had been established that tea drinking was certainly conducive to overall improvement in the oral pathology of these human subjects, even within the limits of their highly specialized life styles and food habits in a tribal socio-ethlogical ambience.

14. Black Tea Extract (BTE) on obesity - induced liver and bone pathophysiologic changes.
Salient Features:
Using animal models it has been successfully established that liver and bone degeneration caused due to obesity could be greatly reduced by the utilization of black tea extract (BTE). BTE could even prevent decline in bone mass and volume in a characteristic way, apart from reversing functional degradation of liver cells.

15. Green & Black tea extracts on Endocrine system (Thyroid-Gonadal)
Salient findings:
Using specialized models of threshold level of tea flavonoids has been established for the first time. This research shows the effective levels of tea compounds for human physiological distress.

16. Use of black tea in reducing cytotoxic effects of heavy metal pollutants.
Salient findings:
Tea when given alone or with sugar and milk (administered for 7 days) is able to protect significantly against clastogenic activity of sodium arsenite. Protection against arsenic cytotoxicity by prolonged dietary administration of black tea is of importance in view of the widespread exposure of human populations to arsenic through drinking water from tube-wells.

Salient findings:
Based on evidences, black tea extract and the constituent, theaflavins can  be categorized as non-toxic formulations as against the common Indian  myth of purported toxicity with restricted use, for the prevention of  NSAID induced ulceration and other inflammatory diseases by regulating  the cytokines balance and antigenic factor.

18. Therapeutic potential of black tea in various gastrointestinal (GI) disorders: Study with theaflavins and other black tea constituents
Salient findings:
Darjeeling tea has the attributes to inactivate the virulent strains of vibrio cholerae responsible for severe diarrhea. There is evident that oral consumption of tea compounds could effect amelioration to a great extent.

19. Protective role of black tea and mint tea against changes in the  endothelial function in preeclamptic women.
Salient findings:
The present study is the first to report the use of Mint tea ( a mixture of tea and mint)as a source of antioxidants for the treatment of preeclampsia. Both tea and mint are low in cost and are widespread. This enables the use of Mint Tea as a preventive medicine and effective dietary supplementation for the prevention and treatment of preeclampsia.

This study emphasize that tea with concentration of  minimum 2% enhanced with 1.5% mint is adequate to enhance the inbuilt  antioxidant potential to combat with oxidative stress especially in conditions like preeclampsia.

20. Effect of Tea on Oral Mucosal Cells
Salient findings:
Following case study method and clinical studies, it is shown that consumption of black tea, one tea spoon per cup three times a day could, significantly reduce occurrences of leucoplakia. Leucoplakia is precancerous lesion in the oral mucosa and any effect that tea had in reducing its incidence will have a positive impact in reducing the level and degree of growth of cancerous cells in humans.

21. Multicentric Study on Effect of Tea in Cerebrovascular Disease.
Salient findings:
Tea consumption at the level of 4 cups per day reduces the risk of incidence of stroke (66%to 33%) and better control of fasting hyperglycemia and in raising the level of HDL, a good cholesterol.

22. Milk blunt the benefits of black tea
Salient findings:
The Study underpins the protective effects of tea with or without milk against hypertension. Beyond a level milk blunts the effects of black tea. A 2%addition of milk to tea is acceptable from these perspectives.

D. Recent Publications:


Operation 'p53 Hunt' to combat cancer: theaflavins in action. Mohanty S, Adhikary A, Chakrabarty S, Sa G, Das T. Front Biosci (Schol Ed). 2012 Jan 1;4:300-20.

Comparative antimutagenic and anticancer activity of three fractions of black tea polyphenols thearubigins. Bhattacharya U, Mukhopadhyay S, Giri AK. Nutr Cancer. 2011;63(7):1122-32.

Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53. George J, Singh M, Srivastava AK, Bhui K, Roy P, Chaturvedi PK, Shukla Y. PLoS One. 2011;6(8):e23395. Epub 2011 Aug 26.

Synergistic anticancer activity of curcumin and catechin: an in vitro study using human cancer cell lines. Manikandan R, Beulaja M, Arulvasu C, Sellamuthu S, Dinesh D, Prabhu D, Babu G, Vaseeharan B, Prabhu NM. Microsc Res Tech. 2012 Feb;75(2):112-6.doi: 10.1002/jemt.21032.

Tea polyphenols induce apoptosis through mitochondrial pathway and by inhibiting nuclear factor-kappaB and Akt activation in human cervical cancer cells. Singh M, Singh R, Bhui K, Tyagi S, Mahmood Z, Shukla Y. Oncol Res. 2011;19(6):245-57.

Enhancement of cancer chemosensitization potential of cisplatin by tea polyphenols poly(lactide-co-glycolide) nanoparticles. Singh M, Bhatnagar P, Srivastava AK, Kumar P, Shukla Y, Gupta KC. J Biomed Nanotechnol. 2011 Feb;7(1):202.

Role of oxidation-triggered activation of JNK and p38 MAPK in black tea polyphenols induced apoptotic death of A375 cells. Bhattacharya U, Halder B, Mukhopadhyay S, Giri AK. Cancer Sci. 2009 Oct;100(10):1971-8. Epub 2009 Jun 22.

Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols. Singh M, Tyagi S, Bhui K,     Prasad S, Shukla Y. Invest New Drugs. 2010 Jun;28(3):216-24.

Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7. Life Sci. 2009 Feb 13;84(7-8):194-204. Epub 2008 Dec 3. Sen T, Moulik S, Dutta A, Choudhury PR, Banerji A, Das S, Roy M, Chatterjee A.

Tea polyphenols can restrict benzo[a]pyrene-induced lung carcinogenesis by altered expression of p53-associated genes and H-ras, c-myc and cyclin D1.   Manna S, Mukherjee S, Roy A, Das S, Panda CK. J Nutr Biochem. 2009 May;20(5):337-49.

Contribution of p53-mediated Bax transactivation in theaflavin-induced mammary epithelial carcinoma cell apoptosis. Lahiry L, Saha B, Chakraborty J, Bhattacharyya      S, Chattopadhyay S, Banerjee S, Choudhuri T, Mandal D, Bhattacharyya A, Sa G, Das T. Apoptosis. 2008 Jun;13(6):771-81.

Polymeric black tea polyphenols inhibit mouse skin chemical carcinogenesis by decreasing cell proliferation. Patel R, Krishnan R, Ramchandani A, Maru G.  Cell Prolif. 2008 Jun;41(3):532-53. Epub 2008 Apr 7. v

Potential O-acyl-substituted (-)-Epicatechin gallate prodrugs as inhibitors of DMBA/TPA-induced squamous cell carcinoma of skin in Swiss albino mice. Vyas S, Manon B, Vir Singh T, Dev Sharma P, Sharma M. Chem Biodivers. 2011 Apr;8(4):599-613. doi: 10.1002/cbdv.201000219.

Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethylhydrazine induced colorectal carcinoma in rats.Nirmala P, Ramanathan M.Eur J Pharmacol. 2011 Mar 1;654(1):75-9. Epub 2010 Dec 21.

Epigallocatechin-3-gallate (EGCG) downregulates EGF-induced MMP-9 in breastcancer cells: involvement of integrin receptor a5ß1 in the process.Sen T, Chatterjee A.Eur J Nutr. 2011 Sep;50(6):465-78.

Intrinsic apoptosis and NF-?B signaling are potential molecular targets for chemoprevention by black tea polyphenols in HepG2 cells in vitro and in a rat hepatocarcinogenesis model in vivo. Murugan RS, Priyadarsini RV, Ramalingam K, Hara Y, Karunagaran D, Nagini S. Food Chem Toxicol. 2010 Nov;48(11):3281-7.

Apoptotic effect of green tea polyphenol (EGCG) on cervical carcinoma cells.Asif Siddiqui F, Naim M, Islam N. Diagn Cytopathol. 2011 Jul;39(7):500-4. doi: 10.1002/dc.21434. Epub 2010 Jul 6.

Black tea polyphenol (theaflavin) downregulates MMP-2 in human melanoma cell line A375 by involving multiple regulatory molecules. Sil H, Sen T, Moulik S, Chatterjee A. Environ Pathol Toxicol Oncol. 2010;29(1):55-68.

Black tea polyphenols-mediated in vivo cellular responses during carcinogenesis. Kumar G, Pillare SP, Maru GB. Mini Rev Med Chem. 2010 Jun;10(6):492-505.

Inhibitory effects of tea polyphenols by targeting cyclooxygenase-2 throughregulation of nuclear factor kappa B, Akt and p53 in rat mammary tumors.Roy P, George J, Srivastava S, Tyagi S, Shukla Y.Invest New Drugs. 2011 Apr;29(2):225-31.

Tobacco, alcohol and tea drinking as risk factors for esophageal cancer: A case-control study from Mumbai, India. Ganesh B, Talole SD, Dikshit R. Cancer Epidemiol. 2009 Dec;33(6):431-4.
Gastric Ulcer:

Association Between p16, hMLH1 and E-cadherin Promoter Hypermethylation and Intake of Local Hot Salted Tea and Sun-dried Foods in Kashmiris with Gastric Tumors. Mir MR, Shabir N, Wani KA, Shaff S, Hussain I, Banday MA, Chikan NA, Bilal S, Aejaz S. Asian Pac J Cancer Prev. 2012;13(1):181-6.

Recent developments on polyphenol-protein interactions: effects on tea and coffee taste, antioxidant properties and the digestive system. Bandyopadhyay P, Ghosh AK, Ghosh C. Food Funct. 2012 Mar 30. [Epub ahead of print]

Role of the COX-independent pathways in the ulcer-healing action of epigallocatechin gallate. Adhikary B, Yadav SK, BandyopadhyaySK, Chattopadhyay S. Food Funct. 2011 Jun;2(6):338-47.

Comparative healing property of kombucha tea and black tea against indomethacin-induced gastric ulceration in mice: possible mechanism of action. Banerjee D, Hassarajani SA, Maity B, Narayan G, Bandyopadhyay SK, Chattopadhyay S. Food Funct. 2010 Dec;1(3):284-93.

Epigallocatechin gallate accelerates healing of indomethacin-induced stomachulcers in mice.Adhikary B, Yadav SK, Bandyopadhyay SK, Chattopadhyay S.Pharmacol Rep. 2011;63(2):527-36.

Black tea and theaflavins suppress various inflammatory modulators and i-NOS mediated nitric oxide synthesis during gastric ulcer healing.Adhikary B, Yadav SK, Chand S, Bandyopadhyay SK, Chattopadhyay S.Free Radic Res. 2011 Jul;45(7):767-78.
Aging, Neurodegeneration:

Intracellular uptake of  (-)epicatechin by human erythrocytes as a function of human age. Maurya PK, Prakash S. Phytother Res. 2011 Jun;25(6):944-6. doi: 10.1002/ptr.3343.

Protective effects of epigallocatechin gallate following 3-nitropropionic acid-induced brain damage: possible nitric oxide mechanisms. Kumar P, Kumar A. Psychopharmacology (Berl). 2009 Dec;207(2):257-70. Epub 2009 Sep 18.

Protective role of tea catechins on erythrocytes subjected to oxidative stress during human aging. Maurya PK, Rizvi SI. Nat Prod Res. 2009;23(12):1072-9.

Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate. Srividhya R, Jyothilakshmi V, Arulmathi K, Senthilkumaran V, Kalaiselvi P. nt J Dev Neurosci. 2008 Apr;26(2):217-23. Epub 2007 Dec 15.
Liver Disease:

Black Tea Prevents High Fat Diet-induced Non-alcoholic Steatohepatitis. Karmakar S, Das D, Maiti A, Majumdar S, Mukherjee P, Das AS, Mitra C. Phytother Res. 2011 Mar 31. doi: 10.1002/ptr.3466.

Hepatoprotective properties of kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis. Bhattacharya S, Gachhui R, Sil PC. Pathophysiology.2011 Jun; 18(3):221-34.

Inhibitory effect of tea polyphenols on hepatic preneoplastic foci in Wistar rats.Srivastava S, Singh M, Roy P, Prasad S, George J, Shukla Y.Invest New Drugs. 2008 Dec 5.

Black tea polyphenols modulate xenobiotic-metabolizing enzymes, oxidative stress and adduct formation in a rat hepatocarcinogenesis model. Murugan RS, Uchida K, Hara Y, Nagini S. Free Radic Res. 2008 Oct;42(10):873-84.

Black tea-induced amelioration of hepatic oxidative stress through antioxidative activity in EAC-bearing mice. Bhattacharyya A, Mandal D, Lahiry L, Bhattacharyya S, Chattopadhyay S, Ghosh UK, Sa G, Das T. J Environ Pathol Toxicol Oncol. 2007; 26(4):245-54.

Radio-modulatory effects of Green Tea Catechin EGCG on pBR322 plasmid DNA and murine splenocytes against gamma-radiation induced damage. Richi B, Kale RK, Bhantiku A. Mutat Res. 2012 Apr 12. [Epub ahead of print].

Protective effects of green and white tea against benzo(a)pyrene induced oxidative stress and DNA damage in murine model. Kumar M, Sharma VL, Sehgal A, Jain M. Nutr Cancer. 2012; 64(2):300-6. Epub 2012 Jan 13.

Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss albino mice. Sinha D, Roy M. J Environ Pathol Toxicol Oncol. 2011;30(4):311-22.

Synergistic antioxidant activity of green tea with some herbs. Jain DP, Pancholi SS, Patel R. J Adv Pharm Technol Res. 2011 Jul;2(3):177-83.

Black tea (Camellia sinensis) decoction shows immunomodulatory properties on an experimental animal model and in human peripheral mononuclear cells. Chattopadhyay  C, Chakrabarti N, Chatterjee M, Mukherjee S, Sarkar K, Chaudhuri AR. Pharmacognosy Res. 2012 Jan;4(1):15-21.

Green tea prevents hyperglycemia-induced retinal oxidative stress and inflammation in streptozotocin-induced diabetic rats. Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R. Ophthalmic Res. 2012; 47(2):103-8.
Reproductive Systems:

Effect of green tea (Camellia sinensis L.) extract on morphological and functional changes in adult male gonads of albino rats. Chandra AK, Choudhury SR, De N, Sarkar M. Indian J Exp Biol. 2011 Sep;49(9):689-97.

Protective Role of Black Tea Extract against Nonalcoholic Steatohepatitis-Induced Skeletal Dysfunction. Karmakar S, Majumdar S, Maiti A, Choudhury M, Ghosh A, Das AS, Mitra C. J Osteoporos. 2011;2011:426863.

Effect of green tea catechin, a local drug delivery system as an adjunct to scaling and root planing in chronic periodontitis patients: A clinicomicrobiological study. Kudva P, Tabasum ST, Shekhawat NK. J Indian Soc Periodontol. 2011 Jan;15(1):39-45.

Green tea extract for periodontal health. Venkateswara B, Sirisha K, Chava VK. J Indian Soc Periodontol. 2011 Jan;15(1):18-22.

Effect of different doses of un-fractionated green and black tea extracts on thyroid physiology. Chandra AK, De N, Choudhury SR. Hum Exp Toxicol. 2011 Aug;30(8):884-96. Epub 2010 Aug 27.

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