page_title: Naringin
section_title: Toxicity
hierarchical_section_title: Naringin / Toxicity
caption_attribution_description: English: Naringenase hydrolysis of naringin to naringenin
context_page_description: Naringin is a flavanone-7-O-glycoside between the flavanone naringenin and the disaccharide neohesperidose.
  The flavonoid naringin occurs naturally in citrus fruits, especially in grapefruit, where naringin is responsible for the fruit's bitter taste.
  In commercial grapefruit juice production, the enzyme naringinase can be used to remove the bitterness created by naringin.
  In humans naringin is metabolized to the aglycone naringenin by naringinase present in the gut.
context_section_description: The typical concentration of naringin in grapefruit juice is around  400 mg/l.  The reported LD50 of naringin in rodents in 2000 mg/kg.
  Naringin inhibits some drug-metabolizing cytochrome P450 enzymes, including CYP3A4 and CYP1A2, which may result in drug-drug interactions. Ingestion of naringin and related flavonoids can also affect the intestinal absorption of certain drugs, leading to either an increase or decrease in circulating drug levels. To avoid interference with drug absorption and metabolism, the consumption of citrus (especially grapefruit) and other juices with medications is advised against.
  However, in vitro studies have also shown that naringin in grapefruit is not what causes the inhibitory effects associated with grapefruit juice. Naringin solution when compared to grapefruit solution produced much less inhibition of CYP3A4. Furthermore, bitter orange juice, which contains considerably less naringin content than grapefruit juice, was found to produce the same level of inhibition of CYP3A4 as grapefruit juice. This would suggest than an inhibitor other than naringin, such as furanocoumarin, which is also found in Seville oranges, may be at work. At the same time, naringenin is known to be a more potent inhibitor of CYP3A4/5 than naringin  and in vitro studies have been unable to effectively convert naringin into naringenin. This leaves open the possibility that in vivo, naringin converted into naringenin by naringinase is what causes the inhibitory effect on CY3PA4. Due to the contradictory results of the effect of naringin it is hard to tell whether it is naringin itself or other components of grapefruit juice that cause drug-drug interaction and lead to its toxicity.
caption: Hydrolysis of naringin by naringinase to give naringenin.
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