Chinese green tea and acute hepatitis: a rare yet recurring theme

Sebastian Thomas Lugg; Darryl Braganza Menezes; Simon Gompertz

doi:10.1136/bcr-2014-208534

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Chinese green tea and acute hepatitis: a rare yet recurring theme

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Re:A case of misdiagnosis: chronic fluoride intoxication?
Declan T Waugh
Published on: 7 August 2018
A case of misdiagnosis: chronic fluoride intoxication?
Declan T Waugh
Published on: 7 August 2018
Claims of effects of green tea without analysis for tea contamination
Uli Jung
Published on: 7 August 2018
Misleading sentence in Summary
Shawn Weldon
Published on: 7 August 2018
Green tea toxicity?
Jeffrey B. Blumberg
Published on: 7 August 2018

Published on: 7 August 2018
Re:A case of misdiagnosis: chronic fluoride intoxication?
- Declan T Waugh, Environmental Scientist and Risk Management Consultant
Dear Editor,
I wish to draw attention to the following misdescription in my orginal letter (dated 28th Nov 2015). I had incorrectly stated that Amoxicillin was a fluoroquinolone. I had assumed that since Hong et al (2005) found a significant association between the use of this antibiotice and dental fluorosis that it must be a fluoroquinolone antibiotic. I was unaware that the letter had been published in the B...
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Dear Editor,
I wish to draw attention to the following misdescription in my orginal letter (dated 28th Nov 2015). I had incorrectly stated that Amoxicillin was a fluoroquinolone. I had assumed that since Hong et al (2005) found a significant association between the use of this antibiotice and dental fluorosis that it must be a fluoroquinolone antibiotic. I was unaware that the letter had been published in the BMJ until yesterday and feel that to safeguard the integrity of scientific debate and promote constructive dialogue among the scientific community it is important to correct this for the record. I have corrected my letter and in doing do have explained how amolicillin enhances fluoride toxicity.
Yours sincerely
Declan Waugh
A case of misdiagnosis: chronic fluoride intoxication? Lugg et al (2015) reported a case study of a 16 year old girl who presented with signs of chronic joint pain, dizziness and non-specific abdominal pains after consuming 3 cups per day of imported herbal green tea (as tea bags) for a period of 3 months [1]. There are a number of interesting points not addressed in the case study which physicians may not be aware of that are of clinical significance. Firstly, the description of the ailments which the subject presented with strongly suggest chronic fluoride intoxication. Hallanger et al (2007) reported that the clinical features associated with fluoride intoxication resulting from habitual tea consumption can include joint pain and gastrointestinal complaints and that fluoride toxicity is often overlooked by clinicians [2]. Despite the publication of a large number of reports addressing fluoride intoxication from habitual tea drinking [3] many health care professionals remain unaware of the risk of fluoride intoxication from tea and lack an understanding of the pathophysiology of fluoride toxicosis. The United States National Academy, National Research Council (2006) reported that excessive intake of fluoride will manifest itself in a musculoskeletal disease with associated symptoms including chronic joint pain and arthritic symptoms [4]. However, perhaps one the most detailed explanations of the pathophysiology of fluoride toxicosis is provided by Professor Alexander V. Akleyev [5]. In addition to musculoskeletal disorders, Akleyev reported that stage 2 fluorosis, the following symptoms are observed: subatrophic and atrophic rhinitis, pharyngitis, laryngitis, chronic conjunctivitis, retinal degeneration with visual impairment, hearing loss, increasing impairment of bronchial patency, and pulmonary insufficiency; mycrodial dystrophy with reduced contractility, chronic gastritis mainly with the reduction of secretory and acid forming function of the stomach, and chronic hepatitis with persistent liver failure; distinct astheno-vegetative syndrome, toxic polyneuritis and decrease in glucocorticoid function of adrenal cortex; and microhematuria and proteinura [4]. Kessabi et al (1986) also reported that acute hepatitis and degeneration in the liver develop following chronic fluoride intake [6]. Other studies have also found that fluoride toxicosis can induce hepatotoxicity and oxidative stress in humans [7-8] and animals [9]. In the case study described by Lugg and associates [1], the fluoride concentration in the tea samples ingested by the patient are unknown, as they were not tested. Chan et al (2013) reported high fluoride levels in tea infusions in the United Kingdom including green tea leaves which were found to contained up to 6.67mg/L when made with deionized water [10]. The European Food Safety Authority (EFSA) have reported that drinking just 2 cups of tea per day (with a fluoride content of 5mg/l), combined with an average consumption of fluoridated drinking water and use of fluoridated tap water in the preparation of food, but excluding all other sources (including solid foods, toothpaste and dental products), would provide a daily dietary intake of 6 mg per day [11]. The EFSA have established daily recommended intake levels (AI) and Tolerable Upper Intake Levels (ULs) for fluoride. For an adult female the AI is 2.9mg per day while the UL is 7mg per day [11-12]. Birmingham is the largest city in the England with artificially fluoridated water. Thus, the patient having consumed 3 cups of tea per day, is likely to have exceeded the recommended UL for fluoride, thereby increasing the risk of chronic fluoride intoxication. Secondly, Lugg and associates noted that the condition of the subject worsened following prescribing of amoxicillin [1]. While amoxicillin is not a fluoroquinolone, which like ciprofloxacin can significantly contribute to daily fluoride intake [13], amoxicillin has nevertheless been found to enhance the toxicity of fluoride [14]. The mechanism by which this appears to occur is by the ability of amoxicillin to increase cell permeability [15-16], thereby enhancing the absorption and activity of fluoride. This would perhaps explain why Hong et al (2005) reported that amoxicillin significantly increased the risk of fluorosis in children when compared with those who never used amoxicillin during the first year of life [17]. Thus, it is likely that administration of amoxicillin resulted in further contributing to chronic fluoride intoxication of the subject and a worsening of her condition. Thirdly, on cessation of the herbal tea and treatment with intravenous fluids and N-acetylcysteine, her condition resolved [1]. N-acetylcysteine is known to protect against fluoride-induced oxidative damage [18]. Overall, the evidence indicates the symptoms reported may be due fluoride toxicosis caused by high fluoride intake from tea, combined with other fluoride sources such as fluoridated drinking water and potentiated by the use of certain medications. There is a need for healthcare workers to be aware of the pathophysiology of fluoride toxicosis as well as dietary fluoride sources, particularly among habitual tea drinkers in communities with artificially fluoridated drinking water. Urinary or blood fluoride levels should be routinely monitored in patients with musculoskeletal and gastrointestinal disorders. Fasting serum fluoride concentrations ranging from 2.5 - 8.0 ?M/L can result in chronic fluoride intoxication and stage I and stage II skeletal fluorosis [19].
[1] Lugg ST, Menezes DB, Gompertz S. Chinese green tea and acute hepatitis: a rare yet recurring theme. BMJ Case Rep 2015, doi:10.1136/ bcr -2014-208534 [2] Hallanger-Johnson JE, Kearns AE, Doran PM, Khoo TK., Wermers RA. Fluoride-related bone disease associated with habitual tea consumption. Mayo Clinic Proceedings 2007;82(6):719-24. [3] Yi J, Cao J. Tea and fluorosis. Journal of Fluorine Chemistry, 2008, 129: 76-81. [4] National Research Council, Review of Fluoride in Drinking Water, U.S. National Research Council 2006. [5] Neurological Disorders of Non-Radiation Nature, Fluorosis, In Chronic Radiation Syndrome, Alexander V. Akleyev, Spriner-Verlag Berlin Heidelberg 2014. ISBN 978-3-642-45116-4 [6] Kessabi M, Hamliri A. Experimental fluorosis in sheep: Alleviating effects of aluminum. Vet. Hum. Toxicol., 1986, 28: 300-304. [7] Michael M, Barot VV, Chinoy NJ. Investigations of Soft Tissue Functions In Fluorotic Individuals of North Gujarat. Fluoride 1996, Vol.29 No.2 63-71. [8] Medvedeva VN. Characteristics of the course of chronic hepatitis in workers coming in contact with flourine compounds. Gigiena Truda; Professional'nye Zabolevaniia, Jan 1985. pg 24-6 [9] AL-Harbia MS, Hamzaa RZ, Dwarya AA. Ameliorative effect of selenium and curcumin on sodium fluoride induced hepatotoxicity and oxidative stress in male mice. J Chem Pharma Res, 2014, 6(4):984-998. [10] Chan L, Mehra A, Saikat S, Lynch P. Human exposure assessment of fluoride from tea (Camellia sinensis L.) Food Res Internat. 2013; 51: 564- 570. [11] European Food Safety Authority, Scientific Opinion on Dietary Reference Values for fluoride, EFSA Panel on Dietetic Products, Nutrition, and Allergies: EFSA Journal. 2013;11(8):3332. [12] European Food Safety Authority, Scientific Opinion of the Panel on Dietetic Products, Nutrition, and Allergies (NDA) on the tolerable upper intake level of fluoride. The EFSA Journal. 2005, 192, 1-65. [13] Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK. Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth. Acta Paediatr. 1995, 84:555-560. [14]Sahlberg C, Pavlic A, Ess A, Lukinmaa PL, Salmela E, Alaluusua S. Combined effect of amoxicillin and sodium fluoride on the structure of developing mouse enamel in vitro. Arch Oral Biol. 2013 Sep;58(9):1155-64. doi:10.1016/j.archoralbio.2013.03.007. Epub 2013 Apr 17. [15]Novo DJ, Perlmutter NG, Hunt RH, Shapiro HM. Multiparameter Flow Cytometric Analysis of Antibiotic Effects on Membrane Potential, Membrane Permeability, and Bacterial Counts of Staphylococcus aureus and Micrococcus luteus. Antimicrobial Agents and Chemotherapy. 2000;44(4):827- 834. [16] Khargharia S, Chakraborty AK., Bhattacharyya A, Manda T K. Disposition Kinetic of Amoxicillin in Healthy and Nephropathic Goats with Immunological and Residual Level in Blood and Tissues. J Drug Metab Toxicol S5:003. doi:10.4172/2157-7609.S5-003 [17] Hong L, Levy SM, Warren JJ, Dawson DV, Bergus GR, Wefel JS. Association of Amoxicillin Use During Early Childhood With Developmental Tooth Enamel Defects, Arch Pediatr Adolesc Med. 2005;159:943-948, 995-996. [18] Paw?owska-G?ral K, Kurzeja E, Stec M. N-acetylcysteine protects against fluoride-induced oxidative damage in primary rat hepatocytes. Toxicology in Vitro, December 2013, Volume 27, Issue 8, Pages 2279-2282. doi:10.1016/j.tiv.2013.09.019 [19] Xiang QY, Chen LS, Chen XD., Wang CS, et al. Serum Fluoride And Skeletal Fluorosis In Two Villages In Jiangsu Province, China. 178 Fluoride 2005;38(3):178-184
Conflict of Interest:
None declared
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Conflict of Interest:
None declared.
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Published on: 7 August 2018
A case of misdiagnosis: chronic fluoride intoxication?
- Declan T Waugh, Environmental Scientist and Risk Management Consultant
[Apologies for late edits to letter submitted yesterday, please note there are 3 new references addressing hepatotoxicity of fluoroquinolones that were not in orginal letter].
Lugg et al (2015) reported a case study of a 16 year old girl born who presented with signs of chronic joint pain, dizziness and non-specific abdominal pains after consuming 3 cups per day of imported herbal green tea (as tea bags) for a p...
Show More

[Apologies for late edits to letter submitted yesterday, please note there are 3 new references addressing hepatotoxicity of fluoroquinolones that were not in orginal letter].
Lugg et al (2015) reported a case study of a 16 year old girl born who presented with signs of chronic joint pain, dizziness and non-specific abdominal pains after consuming 3 cups per day of imported herbal green tea (as tea bags) for a period of 3 months [1]. There are a number of interesting points not addressed in the case study which physicians may not be aware of that are of clinical significance.
Firstly, the description of the ailments which the subject presented with strongly suggest chronic fluoride intoxication. Hallanger et al (2007) reported that the clinical features associated with fluoride intoxication resulting from habitual tea consumption can include joint pain and gastrointestinal complaints and that fluoride toxicity is often overlooked by clinicians [2]. Despite the publication of a large number of reports addressing fluoride intoxication from habitual tea drinking [3] many health care professionals remain unaware of the risk of fluoride intoxication from tea and lack an understanding of the pathophysiology of fluoride toxicosis. The United States National Academy, National Research Council (2006) reported that excessive intake of fluoride will manifest itself in a musculoskeletal disease with associated symptoms including chronic joint pain and arthritic symptoms [4]. However, perhaps one the most detailed explanations of the pathophysiology of fluoride toxicosis is provided by Professor Alexander V. Akleyev [5]. In addition to musculoskeletal disorders, Akleyev reported that stage 2 fluorosis, the following symptoms are observed: subatrophic and atrophic rhinitis, pharyngitis, laryngitis, chronic conjunctivitis, retinal degeneration with visual impairment, hearing loss, increasing impairment of bronchial patency, and pulmonary insufficiency; mycrodial dystrophy with reduced contractility, chronic gastritis mainly with the reduction of secretory and acid forming function of the stomach, and chronic hepatitis with persistent liver failure; distinct astheno-vegetative syndrome, toxic polyneuritis and decrease in glucocorticoid function of adrenal cortex; and microhematuria and proteinura [4]. Kessabi et al (1986) also reported that acute hepatitis and degeneration in the liver develop following chronic fluoride intake [6]. Other studies have also found that fluoride toxicosis can induce hepatotoxicity and oxidative stress in humans [7-8] and animals [9].
In the case study described by Lugg and associates [1], the fluoride concentration in the tea samples ingested by the patient are unknown, as they were not tested. Chan et al (2013) reported high fluoride levels in tea infusions in the United Kingdom including green tea leaves which were found to contained up to 6.67mg/L when made with deionized water [10]. The European Food Safety Authority (EFSA) have reported that drinking just 2 cups of tea per day (with a fluoride content of 5mg/l), combined with an average consumption of fluoridated drinking water and use of fluoridated tap water in the preparation of food, but excluding all other sources (including solid foods, toothpaste and dental products), would provide a daily dietary intake of 6 mg per day [11]. The EFSA have established daily recommended intake levels (AI) and Tolerable Upper Intake Levels (ULs) for fluoride. For an adult female the AI is 2.9mg per day while the UL is 7mg per day [11-12]. Birmingham is the largest city in the England with artificially fluoridated water. Thus, the patient having consumed 3 cups of tea per day, is likely to have exceeded the recommended UL for fluoride, thereby increasing the risk of chronic fluoride intoxication.
Secondly, Lugg and associates noted that the condition of the subject worsened following prescribing of amoxicillin [1]. Amoxicillin is a fluoroquinolone. The name fluoroquinolone comes from the presence of fluorine which is found in all fluoroquinolones. Hong et al (2005) reported that amoxicillin was associated with dental fluorosis in children [13]. Thus, it is likely that administration of amoxicillin resulted in further contributing to chronic fluoride intoxication of the subject and a worsening of her condition. Other fluoroquinolones such as ciprofloxacin have been found to significantly increase plasma fluoride levels in individuals [14]. Fluoroquinolones have also been found to be associated with severe hepatotoxicity [15-18]. It is likely that the toxicity of fluoroquinolones would be more immediate in persons with elevated background plasma fluoride levels.
Thirdly, on cessation of the herbal tea and treatment with intravenous fluids and N-acetylcysteine, her condition resolved [1]. N- acetylcysteine is known to protect against fluoride-induced oxidative damage [19].
Overall the evidence indicates the symptoms reported may be due fluoride toxicosis caused by high fluoride intake from tea, combined with other fluoride sources such as fluoridated drinking water and medications. There is a need for healthcare workers to be aware of the pathophysiology of fluoride toxicosis as well as dietary fluoride sources, particularly among habitual tea drinkers in communities with artificially fluoridated drinking water. Urinary or blood fluoride levels should be routinely monitored in patients with muscleoskeletal and gastrointestinal disorders. Fasting serum fluoride concentrations ranging from 2.5 - 8.0 ?M/L can result in chronic fluoride intoxication and stage I and stage II skeletal fluorosis [20].
[1] Lugg ST, Menezes DB, Gompertz S. Chinese green tea and acute hepatitis: a rare yet recurring theme. BMJ Case Rep 2015, doi:10.1136/ bcr -2014-208534.
[2] Hallanger-Johnson JE, Kearns AE, Doran PM, Khoo TK., Wermers RA. Fluoride-related bone disease associated with habitual tea consumption. Mayo Clinic Proceedings 2007;82(6):719-24.
[3] Yi J, Cao J. Tea and fluorosis. Journal of Fluorine Chemistry, 2008, 129: 76-81.
[4] National Research Council, Review of Fluoride in Drinking Water, U.S. National Research Council 2006.
[5] Neurological Disorders of Non-Radiation Nature, Fluorosis, In Chronic Radiation Syndrome, Alexander V. Akleyev, Spriner-Verlag Berlin Heidelberg 2014. ISBN 978-3-642-45116-4.
[6] Kessabi M, Hamliri A. Experimental fluorosis in sheep: Alleviating effects of aluminum. Vet. Hum. Toxicol., 1986, 28: 300-304.
[7] Michael M, Barot VV, Chinoy NJ. Investigations of Soft Tissue Functions In Fluorotic Individuals of North Gujarat. Fluoride 1996, Vol.29 No.2 63-71.
[8] Medvedeva VN. Characteristics of the course of chronic hepatitis in workers coming in contact with flourine compounds. Gigiena Truda; Professional'nye Zabolevaniia, Jan 1985. pg 24-6.
[9] AL-Harbia MS, Hamzaa RZ, Dwarya AA. Ameliorative effect of selenium and curcumin on sodium fluoride induced hepatotoxicity and oxidative stress in male mice. J Chem Pharma Res, 2014, 6(4):984-998.
[10] Chan L, Mehra A, Saikat S, Lynch P. Human exposure assessment of fluoride from tea (Camellia sinensis L.) Food Res Internat. 2013; 51: 564-570.
[11] European Food Safety Authority, Scientific Opinion on Dietary Reference Values for fluoride, EFSA Panel on Dietetic Products, Nutrition, and Allergies: EFSA Journal. 2013;11(8):3332.
[12] European Food Safety Authority, Scientific Opinion of the Panel on Dietetic Products, Nutrition, and Allergies (NDA) on the tolerable upper intake level of fluoride. The EFSA Journal. 2005, 192, 1-65.
[13] Hong L, Levy SM, Warren JJ, Dawson DV, Bergus GR, Wefel JS. Association of Amoxicillin Use During Early Childhood With Developmental Tooth Enamel Defects, Arch Pediatr Adolesc Med. 2005;159:943-948, 995-996.
[14] Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK. Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth. Acta Paediatr. 1995, 84:555-560.
[15] Hautekeete ML. Hepatotoxicity of antibiotics. Acta Gastroenterol Belg. 1995 May-Aug;58(3-4):290-6. [16] Vial T, Biour M, Descotes J, Trepo C. Antibiotic-associated hepatitis: update from 1990. Ann Pharmacother. 1997 Feb;31(2):204-20.
[17] Thiim M, Friedman LS. Hepatotoxicity of antibiotics and antifungals. Clin Liver Dis. 2003 May;7(2):381-99, vi-vii.
[18] Robles M, Andrade RJ. Hepatotoxicity by antibiotics: update in 2008. Rev Esp Quimioter. 2008 Dec;21(4):224-33. Article in Spanish.
[19] Paw?owska-G?ral K, Kurzeja E, Stec M. N-acetylcysteine protects against fluoride-induced oxidative damage in primary rat hepatocytes. Toxicology in Vitro, December 2013, Volume 27, Issue 8, Pages 2279-2282. doi:10.1016/j.tiv.2013.09.019.
[20] Xiang QY, Chen LS, Chen XD., Wang CS, et al. Serum Fluoride And Skeletal Fluorosis In Two Villages In Jiangsu Province, China. 178 Fluoride 2005;38(3):178-184
Conflict of Interest:
None declared
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Conflict of Interest:
None declared.
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Published on: 7 August 2018
Claims of effects of green tea without analysis for tea contamination
- Uli Jung, Postdoc Fellow
I have read with surprise the case report which makes rather wide sweeping claims about green tea being of health concern. After a quick literature review there have been rare cases after prolonged ingestion of green tea extract - but none ever analyzed the extract for components besides green tea. It is not a secret that there are problems with food safety in china, especially pesticide use, so making claims about the p...
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I have read with surprise the case report which makes rather wide sweeping claims about green tea being of health concern. After a quick literature review there have been rare cases after prolonged ingestion of green tea extract - but none ever analyzed the extract for components besides green tea. It is not a secret that there are problems with food safety in china, especially pesticide use, so making claims about the plant instead of doing at least a rough test for chemicals in the extract (or in that case the tea) seem in my opinion very much warranted prior to claims with such impact.
Conflict of Interest:
None
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Conflict of Interest:
None declared.
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Published on: 7 August 2018
Misleading sentence in Summary
- Shawn Weldon, Co-founder
In the summary of this article is the following:
"Only following specific questioning did she reveal that she had, in the preceding 3 months, regularly consumed internet ordered Chinese green tea, which contained Camellia sinensis."
My issue with this sentence is the word "contained". Chinese green tea, or any other true tea, must come from Camellia sinensis.
The word "contained" gives the imp...
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In the summary of this article is the following:
"Only following specific questioning did she reveal that she had, in the preceding 3 months, regularly consumed internet ordered Chinese green tea, which contained Camellia sinensis."
My issue with this sentence is the word "contained". Chinese green tea, or any other true tea, must come from Camellia sinensis.
The word "contained" gives the impression that this was added to the green tea.
Any "tea" from any other plant is considered an herbal tea.
I feel the article is well justified because the dangers of adulteration are very serious. I also agree with the dangers of supplements and liver toxicity from high levels of EGCG ingestion.
My concern is that green tea, oolong tea and black tea are all very healthy drinks and many bloggers will create misinformed conclusions from the summary which may derogate from the benefits of tea.
This misleading statement in the summary of this article has already been misinterpreted and published on "Grub Street" (http://www.grubstreet.com/2015/09/green-tea-hepatitis.html). A reader pointed out their mistake in the comments section and they have since retracted and corrected their error.
The real issue here is not the tea. It is the contaminants either sprayed on, or added to, the tea.
I think the sentence should be revised to prevent any further confusion.
Should this comment be posted on this or any other website, I ask that my email not be displayed.
Thank you for your time,
Shawn Weldon
Conflict of Interest:
I run a green tea information website promoting the benefits of green tea consumption. I focus primarily on Japanese green tea. I don't believe there are any competing interests.
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Conflict of Interest:
None declared.
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Published on: 7 August 2018
Green tea toxicity?
- Jeffrey B. Blumberg, Professor
- Other Contributors:
  none
Lugg et al. present a case of acute hepatitis in a 16-year old girl and, using the CIOMS/RUCAM scale, conclude the probable cause as a 3-month exposure to a Chinese green tea ordered via the internet. Other case reports have associated an idiosyncratic hepatoxicity with green tea though other factors, including adulterants, can contribute to its causality (Blumberg et al.). Regrettably, like many of these reports, this on...
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Lugg et al. present a case of acute hepatitis in a 16-year old girl and, using the CIOMS/RUCAM scale, conclude the probable cause as a 3-month exposure to a Chinese green tea ordered via the internet. Other case reports have associated an idiosyncratic hepatoxicity with green tea though other factors, including adulterants, can contribute to its causality (Blumberg et al.). Regrettably, like many of these reports, this one also fails to test the product and inappropriately presumes the product label is correct. Green tea adulterated with plant extracts and/or drugs is not green tea but an illegal product! A relatively simple analytical test would have revealed adulteration of this product and helped to remove it from the marketplace and prevent others from suffering a fate like this patient. Unsurprisingly, the story of this report carried widely by the media appear to have used only its title and summary to warn readers about the harm of drinking green tea, despite a strong likelihood that this product was not simply green tea. Thus, many people may now choose to forego what Lugg et al. note is "a very safe and healthy drink".
Jeffrey B. Blumberg Tufts University
Reference
Blumberg, JB, Bolling BW, Xiao H, Chen C-YO. Review and perspective on the composition and safety of green tea extracts. Eur J Nutr Food Safety 2015;5:1-31
Conflict of Interest:
None declared
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