Kava vs Green Tea

Compare and contrast regarding liver toxicity.

Hi kava lovers. Today, we will explore the irony surrounding liver health warnings and the beverages we regularly consume. It is worth noting that some drinks and supplements that we frequently consume, in addition to alcohol, carry their own hepatic (liver) risks. In this essay, we will focus on one such compound: EGCG, which naturally occurs in green tea and is abundant in green tea extracts (GTE). My aim is not to issue a cautionary statement against green tea, but to draw a comparison between the liver issues associated with green tea and those we have witnessed with kava. Instances of injuries linked to green tea or green tea extracts are exceedingly rare and are not a cause for widespread concern. In the subsequent sections, we will delve into the research concerning idiosyncratic herb injuries, drawing a correlation between this and reports of liver injury associated with kava.

Let us now examine the various forms of herb-induced liver injury (HILI) and their respective features. We will begin with idiosyncratic injury, a rare condition that is not directly linked to dosage, and little is known about individuals at an increased risk. This type of injury is unpredictable, and there are no research models for the study of idiosyncratic HILI. Its development is poorly understood and cannot be prevented [1]. Intrinsic toxicity and injury, on the other hand, follow a classic dose-dependent curve and are predictable above specific thresholds. Essentially, the intrinsic toxicity of an herb or drug refers to the toxicity of the product itself, which is independent of the variables affecting the individual [2]. A notable example of intrinsic toxicity is acetaminophen, commonly known as Tylenol, APAP, or Panadol. At normal dosages in typical situations, it can be metabolized by the body without any harmful effects. However, at excessive dosages, APAP becomes toxic and leads to liver injury [3].

1. Idiosyncratic herb-induced liver injury

   1. Unpredictable.

   2. Does not depend on the dose.

   3. Long and variable latency periods

   4. Variable liver injury types.

   5. Low incidence in humans.

   6. Lack of experimental reproducibility.

1. Intrinsic Herb-Induced Liver Injury

   1. Predictable.

   2. Clear dependance on the dose.

   3. Short and consistent latency period.

   4. Distinct liver injury patterns.

   5. High incidence in humans.

   6. Can be reproduced in an experiment.

When an herb is believed to be responsible for causing liver injury, it is categorized into one of the two groups mentioned earlier. Within the idiosyncratic category, there are additional classifications, such as metabolic and immunologic types of injury. Metabolic idiosyncrasy is characterized by liver injury resulting from metabolic pathway interruption (CYP) [4]. On the other hand, the immunologic type of injury involves the immune system and inflammatory activities that are more closely related to allergy [5].

1. Metabolic Type

   1. Duration of exposure requires 1 week to several months

   2. Lack of hypersensitivity features

   3. Delayed response to reexposure in the time frame of weeks

1. Immunologic Type

   1. Duration of exposure: few weeks

   2. Hypersensitivity features

   3. Prompt response to reexposure with 1 or 2 doses.

Now, let us establish what exactly is meant by “liver damage” and how researchers can use this term. It turns out that there are several familiar classifications with one new one, adaptive change. No liver damage diagnosis can be made without a proper metabolic test that looks at AST/ALT/ALP/GGT and/or bilirubin levels. In addition, liver toxicity and adaptation cannot be claimed until the noted levels below are reached.

Liver Changes:

1. Adaptive: Sometimes misdiagnosed as liver injury or hepatotoxicity. Liver adaptation or tolerance in connection with herbal uses represents mild modification of liver integrity due to metabolic interactions between chemicals and the liver, as evidenced by small increases in liver tests. Going back a little bit to kava, GGT has been seen as an adaptive change in the presence of kava, and this is considered a normal function seen with adaptive changes in the liver [6].

   1. ALT values are less than 5 times the upper limit of normal

   2. ALP values are less than 2 times the upper limit of normal

   3. Develops at the recommended daily dosages

1. Idiosyncratic: Liver injury was ascribed to the interactions between the phytochemical in question and the patient’s individual factors.

   1. ALT is less than or equal to 5 times the upper limit of normal.

   2. ALP is less than or equal to 2 times the upper limit of normal.

   3. Develops at the recommended daily dosages.

1. Intrinsic: Toxicity related to the herb itself.

   1. ALT is greater than or equal to 5 times the upper limit of normal.

   2. ALP is greater than or equal to 2 times the upper limit of normal.

   3. Emerges quickly after acute herbal overdose [7]

Tea, a drink consumed by billions of people around the world, is prepared from the leaves of the plant Camellia sinensis. The most well-known types are black, oolong, and green tea, with black tea being the most consumed (80% of the market). In addition to caffeine and theobromine-type alkaloids, polyphenols are considered as the major active molecules in tea. These are known as catechins, and of the catechins found in tea, EGCG is the most abundant and possesses the highest antioxidant potential [8]. EGCG has been preliminarily shown to protect against various types of cancers to a small degree [9,11] and aids in weight loss [3]; however, the science on cancer prevention with ordinary tea is contested [12]. Research on EGCG from natural sources in the diet has been met with limited success, and some evidence of liver enzyme elevation has been observed [13]. Along with instances of liver test abnormalities, liver damage and necrosis have also occurred [14]. Since 1966, at least 216 case reports of green tea extract toxicity have been published. It was found that doses of EGCG as little as 5.9g over 5 days to a maximum of 240g over 120 days may be harmful [15].

Edit As of 12/28/2022: Australia’s Therapeutic Goods Administration (TGA) has now proposed adding green tea extract as an entry into the Poisons Standards. Warning labels will now include words such as “WARNING: Green tea extract (Camellia sinensis) may harm the liver in some people. If you experience yellowing of the skin / eyes, dark urine, discolored stool, nausea, vomiting, unusual tiredness, weakness, abdominal pain, and/or loss of appetite, stop using this product and consult your doctor.” [16]

Obviously, we know that green tea is not a ubiquitous liver poison and has never been, so what is really going on here? What these researchers tell us is that green tea extracts, in parallel to kava extracts, can cause extremely rare idiosyncratic liver reactions in some individuals. This shows us that idiosyncratic reactions are isolated, can have serious or benign outcomes, and can occur with an enormous array of herbs and drugs. Even with positive proof of this reaction from EGCG, we still see no warnings issued for its consumption. When you buy a bottle of green tea from a gas station, there is no liver warning on the side of the product. With kava, we do not even have that positive proof. Studies regarding kava’s possible hepatotoxicity have all come up empty-handed with only suggestions as to what could be occurring. I postulate that the idiosyncratic issues with green tea as a beverage are on the same level or more serious than those seen with kava as a beverage, and as such neither has a reason to concern the general population. In the same vein, the extracts of herbal products should be viewed with a degree of scrutiny. When it comes to quality, using it as nature made it gives us the best and safest option for consumption.

Quick Summary:

There are more well-documented cases of liver injury from green tea and green tea extracts than from kava. No liver warning exists for green tea, and no general understanding of risk is held by the consumer base related to any toxicity by green tea. Injuries caused by herbs can be categorized into two types: toxicity of the herb itself and toxicity of the herb when in the presence of people with certain issues that are not compatible, also known as idiosyncrasies. I theorize that kava as a beverage, having fewer incidences of idiosyncratic injury (most likely being immunologic also known as “allergy”), as well as no evidence supporting intrinsic toxicity, is as safe or safer than green tea for the liver, and we know that green tea is safe.

[1] Chalasani, Naga, and Einar Björnsson. 2010. “Risk Factors for Idiosyncratic Drug-Induced Liver Injury.” Gastroenterology 138 (7): 2246–59. https://doi.org/10.1053/j.gastro.2010.04.001

[2] Lin, Nai-Hui, Hsiu-Wu Yang, Yu-Jang Su, and Chen-Wang Chang. 2019. “Herb Induced Liver Injury after Using Herbal Medicine: A Systemic Review and Case-Control Study.” Medicine 98 (13): e14992. https://doi.org/10.1097/MD.0000000000014992

[3] Larson, Anne M. 2007. “Acetaminophen Hepatotoxicity.” Clinics in Liver Disease 11 (3): 525–48, vi. https://doi.org/10.1016/j.cld.2007.06.006

[4] Uetrecht, Jack, and Dean J. Naisbitt. 2013. “Idiosyncratic Adverse Drug Reactions: Current Concepts.” Pharmacological Reviews 65 (2): 779–808. https://doi.org/10.1124/pr.113.007450

[5] Mak, Alastair, and Jack Uetrecht. 2017. “Immune Mechanisms of Idiosyncratic Drug-Induced Liver Injury.” Translational Research: The Journal of Laboratory and Clinical Medicine 3 (1): 145–56. https://www.ncbi.nlm.nih.gov/pubmed/30873473

[6] Everhart, James E., and Elizabeth C. Wright. 2013. “Association of γ-Glutamyl Transferase (GGT) Activity with Treatment and Clinical Outcomes in Chronic Hepatitis C (HCV).” Hepatology 57 (5): 1725–33. https://doi.org/10.1002/hep.26203

[7] Teschke, R., and T. D. Xuan. 2019. “Suspected Herb Induced Liver Injury by Green Tea Extracts: Critical Review and Case Analysis Applying RUCAM for Causality Assessment.” Japanese Journal of Gastroenterology and Hepatology.

[8] Mazzanti, Gabriela, Antonella Di Sotto, and Annabella Vitalone. 2015. “Hepatotoxicity of Green Tea: An Update.” Archives of Toxicology 89 (8): 1175–91. https://doi.org/10.1007/s00204-015-1521-x

[9] Du, Guang-Jian, Zhiyu Zhang, Xiao-Dong Wen, Chunhao Yu, Tyler Calway, Chun-Su Yuan, and Chong-Zhi Wang. 2012. “Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer Chemopreventive Polyphenol in Green Tea.” Nutrients 4 (11): 1679–91. https://doi.org/10.3390/nu4111679

[10] Chen, I-Ju, Chia-Yu Liu, Jung-Peng Chiu, and Chung-Hua Hsu. 2016. “Therapeutic Effect of High-Dose Green Tea Extract on Weight Reduction: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.” Clinical Nutrition 35 (3): 592–99. https://doi.org/10.1016/j.clnu.2015.05.003

[11] Yuan, Jian-Min. 2013. “Cancer Prevention by Green Tea: Evidence from Epidemiologic Studies.” The American Journal of Clinical Nutrition 98 (6 Suppl): 1676S – 1681S. https://doi.org/10.3945/ajcn.113.058271

[12] Eisenstein, Michael. 2019. “Tea’s Value as a Cancer Therapy Is Steeped in Uncertainty.” Nature 566 (7742): S6–7. https://doi.org/10.1038/d41586-019-00397-2

[13] Yu, Zheming, Hamed Samavat, Allison M. Dostal, Renwei Wang, Carolyn J. Torkelson, Chung S. Yang, Lesley M. Butler, et al. 2017. “Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States.” Cancer Prevention Research 10 (10): 571–79. https://doi.org/10.1158/1940-6207.CAPR-17-0160

[14] Patel, Shreena S., Stacey Beer, Debra L. Kearney, Garrett Phillips, and Beth A. Carter. 2013. “Green Tea Extract: A Potential Cause of Acute Liver Failure.” World Journal of Gastroenterology: WJG 19 (31): 5174–77. https://doi.org/10.3748/wjg.v19.i31.5174

[15] Navarro, Victor J., Herbert L. Bonkovsky, Sun-Il Hwang, Maricruz Vega, Huiman Barnhart, and Jose Serrano. 2013. “Catechins in Dietary Supplements and Hepatotoxicity.” Digestive Diseases and Sciences 58 (9): 2682–90. https://doi.org/10.1007/s10620-013-2687-9

[16] Scattergood, Gary. 2022. “Melatonin, Green Tea Extract: Australian Regulator Considering Changes to Rules Governing Use in Supplements.” Nutraingredients-Asia.com. William Reed Ltd. October 12, 2022. https://www.nutraingredients-asia.com/Article/2022/10/12/melatonin-green-tea-extract-australian-regulator-considering-changes-to-rules-governing-use-in-supplements/.