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Animal studies are often assumed to provide the necessary evidence to illustrate the safety of products prior to human consumption. However, though these tests may provide a starting point, animal studies often give unreliable results. In different cases, animal trials agree with human studies at a random rate (Van Norman, 2019). For instance, in a study where 76 animal trials were examined, only 37% were able to be imitated in people. In addition, in a review of 221 animal studies, only 50% correlated with human experiments. The U.S. National Toxicology Program also deduced that it was not possible to emulate toxicities in rats and mice with humans other than with carcinogens. Lastly, as stated by Gurley, even in in-vitro studies, the conditions rarely translate the same to human studies, therefore clinical trials are the preferred measure for toxicity evaluations (Gurley, 2016). Furthermore, as pointed out in the discussion by Kami Hector and the journal article by Ferdowsian & Beck, there are animal rights implications compounded with the reality that animal studies are often more invasive, deprivative of social needs, and reductive of natural behaviors when compared to clinical trials, which makes repeating these tests in people challenging (Ferdowsian & Beck, 2011; Hector, 2023). In the end, the dosages in animal studies are not a reliable predictor for human toxicity.
In the end, animal studies are limited in their ability to present clear evidence of safety or toxicity for products. For instance, in a two-year study where rats received 0-1000mg of GTE (green tea extract) there was a significant increase in liver necrosis for rats who ingested 1000mg/kg of GTE (Gafner & Blumenthal, 2014). On the other hand, mice who took 300 mg/kg had a reduced occurrence of primary liver neoplasms possibly from the chemopreventive effect of GTE. As represented by this rat study with GTE, there is no clear correlation of not only toxicity of GTE in rats but also humans because of the lack of information on how the dosages translate to human subjects. Essentially, how much GTE would an average person have to take to have the same effect as the mice who consumed 1000mg/kg? Would the amount be reasonable or outrageous for a person to consume in one sitting? Would it ultimately be beyond the recommended dosage for that brand of green tea? As demonstrated by Keira Kroin’s discussion, if this rat study was replicated in people, a 150-pound person would have to eat 68 grams of green tea extract (Kroin, 2023). This is beyond the reasonable amount a regular person would consume, so it is not surprising there would be an adverse reaction. In consequence, it is possible that reported toxicity from green tea was the result of someone ingesting more green tea than suggested. Lastly, what was the diet of the rats, and what would be the human equivalent for similar results? Is that diet reasonable and likely for a person to follow consistently for two years? This highlights a major issue with animal studies, their circumstances and requirements are not easily replicated in human trials.
Furthermore, authentication of herbal products is imperative for the safety of the consumer. Moreover, it is a crucial component for assessing the reliability of animal or clinical trials. As the trend in taking herbal products rises, the amount of people looking to take economic advantage of the herbal market is increasing. For example, in Pakistan tea combined with textile dyes and sawdust was uncovered in August 2022 (Momtaz et al., 2023). Additionally, in Pakistan 4000L of adulterated honey mixed with wax and chemicals was discovered in October 2022. Moreover, the FDA found 10% of imported honey was blended with unidentified sweeteners. Consequently, herbal authentication is necessary to confirm credibility by eliminating data interference in studies and approving safety of the product (Gafner & Blumenthal, 2014). There are various methods to check the authenticity of herbs such as morphology, chromatography or mass spectrometry, immunological assays, and DNA-barcoding (Delgado-Tejedor, et al., 2021). However, in the previous animal study, there was no mention of the authentication method, preparation procedure, or where the GTE came from (Gafner & Blumenthal, 2014).
Lastly, green tea is an age-old beverage that has been concluded by the second edition of the American Herbal Products Association’s Botanical Safety Handbook as a class 1 safety ingredient (Gafner & Blumenthal, 2014). This indicates that green tea has been ingested for hundreds of years and has a history of being safe when taken properly. The number of incidents compared to the amount of people who take green tea results in an insignificant occurrence of adverse effects. However, when consumed with medications such as nadolol, green tea can inhibit its uptake through the intestinal mucosa thus reducing the drug’s antihypertensive effects (Gurley, 2016). Green tea’s catechins, especially EGCG, can block uptake transporters and lead to the inability of certain medications to be absorbed. As discussed by Julie Newkirk, hydroalcoholic GTE in weight loss products are commonly reviewed for safety because of the effects of EGCG, which increases if employed while fasting (Newkirk, 2023). In conjunction, according to Navarro et al., most reports of hepatotoxicity caused by green tea occurred when taken with other components such as pharmaceutical drugs (Navarro et al., 2014).
Moreover, reports of adverse effects do not mean that the toxicity was caused by green tea. If there is no consideration for the ingested amount of green tea, frequency of consumption, and other herbal supplements the patient may be taking, then there is no clear answer that the green tea was the culprit. Furthermore, there are many other aspects to consider when accounting for possible adverse effects from herbal supplements. For example, what was the origin, brand, and condition of the green tea? These factors affect the quality of the herb, which alters the way the herb will affect the body. Unfortunately, this information is often not recorded in case reports (Gafner & Blumenthal, 2014). Though authentication methods such as microscopy and DNA-barcoding can verify that the herb is indeed the herb in question, it may not be able to examine the quality condition of the herb (Han et al., 2016; Osman et al., 2019). This is why human clinical trials are necessary because it considers factors that need to be controlled to truly analyze the effects of green tea on people.
Ultimately, one benefit of animal studies is that it researches concerns that may not be ethical to test in people. However, because of the differences in biology along with clinical conditions, animal testing may not provide an accurate picture of how an herb may react in a person (Gurley, 2016). As a result, in the case of adulteration, an animal may not be the best predictor of toxicity because of dosage differences. Therefore, methods such as DNA-barcoding and analysis of herb origin give a better idea of the authenticity of an herb, which can then be administered in clinical trials (Han et al., 2016).
References
Delgado-Tejedor, A., Leekitcharoenphon, P., Aarestrup, F. M., & Otani, S. (2021). Evaluating the usefulness of next-generation sequencing for herb authentication. Food chemistry. Molecular sciences, 3, 100044. https://doi.org/10.1016/j.fochms.2021.100044
Ferdowsian, H. R., & Beck, N. (2011). Ethical and Scientific Considerations Regarding Animal Testing and Research. PLoS ONE, 6(9). https://doi.org/10.1371/journal.pone.0024059
Gafner, S., & Blumenthal, M (2014). Perspectives on potential hepatotoxicity of various herbs including green tea extract. Herbalgram. 104, 52-59
Gurley, B. J. (2016, June 21). Herbal Dietary Supplements: The Good, The Bad, and The Ugly. Safety in Botanical Medicine. Retrieved February 15, 2023, from https://learn.muih.edu/courses/11719/pages/week-6-lecture?module_item_id=448323
Han, J., Pang, X., Liao, B., Yao, H., Song, J., & Chen, S. (2016). An authenticity survey of
herbal medicines from markets in China using DNA barcoding. Scientific reports, 6.
Hector, K. (2023). Week 6 Discussion: Overcoming Bias Reporting to Create a Useful Narratives For Assessing Safety. Safety in Botanical Medicine. Retrieved February 18, 2023, from https://learn.muih.edu/courses/11719/discussion_topics/157669
Kroin, K. (2023). Week 6 Discussion: Overcoming Bias Reporting to Create a Useful Narratives For Assessing Safety. Safety in Botanical Medicine. Retrieved February 18, 2023, from https://learn.muih.edu/courses/11719/discussion_topics/157669
Momtaz, M., Bubli, S. Y., & Khan, M. S. (2023). Mechanisms and Health Aspects of Food
Adulteration: A Comprehensive Review. Foods, 12(1), 199.
Navarro, V. J., Barnhart, H., Bonkovsky, H. L., Davern, T., Fontana, R. J., Grant, L., Reddy, K. R., Seeff, L. B., Serrano, J., Sherker, A. H., Stolz, A., Talwalkar, J., Vega, M., & Vuppalanchi, R. (2014). Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology (Baltimore, Md.), 60(4), 1399–1408. https://doi.org/10.1002/hep.27317
Newkirk, J. (2023). Week 6 Discussion: Overcoming Bias Reporting to Create a Useful Narratives For Assessing Safety. Safety in Botanical Medicine. Retrieved February 18, 2023, from https://learn.muih.edu/courses/11719/discussion_topics/157669
Osman, A. G., Raman, V., Haider, S., Ali, Z., Chittiboyina, A. G., & Khan, I. A. (2019).
Overview of Analytical Tools for the Identification of Adulterants in Commonly Traded
Herbs and Spices. Journal of AOAC International, 102(2), 376–385.
Van Norman, G. A. (2019). Limitations of animal studies for predicting toxicity in clinical trials. JACC: Basic to Translational Science, 4(7), 845–854. https://doi.org/10.1016/j.jacbts.2019.10.008
