Editing Polyphenol (section)

=== Toxicity and adverse effects ===
[[Adverse effect]]s of polyphenol intake range from mild (e.g., [[gastrointestinal tract]] symptoms)<ref name=lpi/> to severe (e.g., [[hemolytic anemia]] or [[hepatotoxicity]]).<ref name="davies">{{Cite book |url=https://www.worldcat.org/oclc/820665797 |title=Flavonoid pharmacokinetics: methods of analysis, pre-clinical and clinical pharmacokinetics, safety, and toxicology |date=2013 |isbn=978-1-118-35440-7 |veditors=Davies NM, Yanez JA|publisher=Wiley |location=Hoboken, New Jersey |chapter=Flavonoids and drug interactions |oclc=820665797|last1=Davies |first1=Neal M. |last2=Yáñez |first2=Jaime A. }}</ref> In 1988, hemolytic anemia following polyphenol consumption was documented, resulting in the withdrawal of a catechin-containing drug.<ref>{{cite journal |vauthors=Jaeger A, Wälti M, Neftel K |date=1988 |title=Side effects of flavonoids in medical practice |journal=Progress in Clinical and Biological Research |volume=280 |pages=379–394 |pmid=2971975}}</ref> Polyphenols, particularly in beverages that contain them in high concentrations (tea, coffee, etc), inhibit the [[Small_intestine#Absorption|absorption]] of [[heme|non-haem iron]] when consumed together in a single meal.<ref name=lpi/><ref name="SACN">{{cite book |title=SACN Iron and Health Report |date=2010 |publisher=The Stationery Office |isbn=9780117069923 |pages=65, 68, 70, 73, 74 |url=https://assets.publishing.service.gov.uk/media/5a7df3dd40f0b62305b7fd53/SACN_Iron_and_Health_Report.pdf |access-date=3 September 2024}}</ref><ref name="WHO">{{cite web |title=Iron Deficiency Anaemia Assessment, Prevention, and Control A guide for programme managers |url=https://cdn.who.int/media/docs/default-source/2021-dha-docs/ida_assessment_prevention_control.pdf?sfvrsn=fb8c459c_1&download=true |publisher=World Health Organization |access-date=3 September 2024 |date=2001}}</ref><ref name="CDC">{{cite journal |title=Recommendations to Prevent and Control Iron Deficiency in the United States |journal=[[Morbidity and Mortality Weekly Report|MMWR]] |date=3 April 1998 |volume=47 |issue=RR-3 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm |access-date=3 September 2024 |publisher=Centers for Disease Control and Prevention}}</ref> Research is limited on the effect of this inhibition on [[Iron tests|iron status]].<ref name="SACN quote">{{cite book |title=SACN Iron and Health Report |date=2010 |publisher=The Stationery Office |isbn=9780117069923 |pages=74 |url=https://assets.publishing.service.gov.uk/media/5a7df3dd40f0b62305b7fd53/SACN_Iron_and_Health_Report.pdf |quote=Numerous cross-sectional studies have examined the association between total dietary iron intake and dietary modulators of iron absorption on biochemical markers of iron status ... These studies suffer from a number of limitations... Findings from cross-sectional studies assessing the effects of total iron intake, ascorbic acid, calcium and polyphenols, have been inconsistent...}}</ref>

Metabolism of polyphenols can result in flavonoid-drug interactions, such as in [[grapefruit–drug interactions]], which involves inhibition of the liver [[enzyme]], [[CYP3A4]], likely by grapefruit [[furanocoumarin]]s, a class of polyphenol.<ref name=lpi/><ref name="davies" /> The European Food Safety Authority established upper limits for some polyphenol-containing supplements and additives, such as [[green tea extract]] or [[curcumin]].<ref>{{cite journal|vauthors=Younes M, Aggett P, Aguilar F, Crebelli R, Dusemund B, Filipič M, Frutos MJ, Galtier P, Gott D, Gundert-Remy U, Lambré C, Leblanc JC, 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, Wright M |date=April 2018 |title=Scientific opinion on the safety of green tea catechins |journal=EFSA Journal |volume=16 |issue=4 |pages=e05239 |doi=10.2903/j.efsa.2018.5239 |pmc=7009618 |pmid=32625874}}</ref><ref>{{Cite journal |author=EFSA Panel on Food Additives and Nutrient Sources Added to Food |date=1 September 2010 |title=Scientific opinion on the re-evaluation of curcumin (E 100) as a food additive |url=https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2010.1679 |journal=EFSA Journal |volume=8 |issue=9 |doi=10.2903/j.efsa.2010.1679|url-access=subscription }}</ref> For most polyphenols found in the diet, an adverse effect beyond nutrient-drug interactions is unlikely.<ref name=lpi/>