Thursday, April 26, 2018

Green tea catechins and liver damage

A report* about possible toxicity for the liver of green tea catechins at high doses has raised concerns among Friends of Pairteas, so I looked into the matter this week.

In the US green tea catechins are available over the counter as supplements. Drugs considered dietary supplements are not regulated in the US in any significant way for either safety, effectiveness, or dosage limits. 

Epigallocatechin gallate (EGCG), the major catechin in green tea. Image from Wikipedia.

A major problem in determining whether green tea extracts have any effect, either beneficial or adverse: people differ tremendously in how much catechin a person absorbs from a given dose of supplement (or brewed green tea, for that matter). One person may have up to 6 times more catechins in their blood than the next person with a given dosage!**

The reason for this huge difference may lie, at least in part, in genetic differences in a person's capacity to transport drugs and the products of their metabolism for excretion in the liver and kidney. When certain drugs fail to be cleared from cells due to transport problems they can damage mitochondria, and ultimately lead to cell death. This phenomenon may explain why catechins, which are metabolized and excreted by the liver, may cause liver damage.

The question is then: how much catechin is needed to cause damage? and how severe is that damage? and one more question: do catechins interact with other drugs/suplements?

We don't know the answers to any of these questions. 

The European white paper stems from a spate of case reports and animal studies that have suggested that liver damage with catechin supplements may occur. In the case of animals, huge doses were delivered over multiple years, so these studies should not be extrapolated to humans. 

With respect to humans, one study of case reports that really scared me concerned a supplement called Slimquick®, where a person had to have a liver transplant.*** 

But case reports are problematic because you can't exclude the possibility that other issues, such as disease, the use of other medications or supplements, or even the purity of the catechin supplements, aren't the real cause of problems. 

These are the reasons why Isomura and colleagues decided to review human randomized control trials of catechins.**** In these trials, catechin supplementation was compared directly with placebo or no treatment, so that one could decide with some degree of certainty that the catechins were responsible for any adverse effects. 

Of the 34 usable trials reviewed by Isomura and colleagues, liver-related adverse effects were found in only four. There were 8 adverse events among the people received catechins and one event in a person receiving a placebo.

Of these four trials with adverse effects, only one involved healthy volunteers. Of the others, one involved women with breast cancer, one men with prostate cancer, and the third post-menopausal women who may have taken other medications. In other words, we cannot say whether any of the condition in these three trials may have contributed to the adverse events. 

Furthermore, adverse events in these trials consisted of elevation of liver enzymes, but no active disease. That said, elevation of liver enzymes are indeed an indication of active liver damage. The liver happens to have a rather large, though not infinite, capacity to experience damage without long-term consequences. 

Bottom line: we really don't know at this point whether catechin supplements cause liver damage, to whom, and at what dose. But the amounts in your favorite cup of green tea come nowhere close to the amounts in supplements. 

My advice: enjoy your green tea as a drink in a cup for its taste and avoid "magical" supplements that promise life-changing effects. Liver disease would indeed be life-changing!

Incidentally, Cornell University hosts a National Institutes of Health database where you can look at the toxic effects of different drugs and supplements on the liver:
https://livertox-nlm-nih-gov.proxy.library.cornell.edu

Longing tea steeping in a gaiwan. Image from Wikipedia.

* EFSA ANS Panel (EFSA Panel on Food Additives and Nutrient Sources added to Food), Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, Frutos MJ, Galtier P, Gott D, Gundert‐Remy U, Lambré C, Leblanc J‐C, Lillegaard IT, Moldeus P, Mortensen A, Oskarsson A, Stankovic I, Waalkens‐Berendsen I, Woutersen RA, Andrade RJ, Fortes C, Mosesso P, Restani P, Arcella D, Pizzo F, Smeraldi C and Wright M, 2018. Scientific Opinion on the safety of green tea catechins. EFSA Journal 2018;16(4):523. 9, 89 pp. https://doi.org/10.2903/j.efsa.2018.5239

** Scholl C, Lepper A, Lehr T, et al. Population nutrikinetics of green tea extract. Atkin SL, ed. PLoS ONE. 2018;13(2):e0193074. doi:10.1371/journal.pone.0193074.

*** Zheng, E.X., Rossi, S., Fontana, R.J. et al. Risk of Liver Injury Associated with Green Tea Extract in SLIMQUICK® Weight Loss Products: Results from the DILIN Prospective StudyDrug Saf (2016) 39: 749. https://doi-org.proxy.library.cornell.edu/10.1007/s40264-016-0428-7

**** Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. European Journal of Clinical Nutrition. 2016;70(11):1221-1229. doi:10.1038/ejcn.2016.78.



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