What is it about grapefruit specifically that messes with pretty much every prescription in existence?
In:
It consumes an enzime in our bodies that deals with processing most medicines.
You eat the grapefruit, loose those enzimes. They quickly regrow, usually around the time you’ve had a second or third dose of your meds, while the previous ones are still unprocessed in you. Now your body goes and processes the drugs all at once, causing an OD.
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Pretty sure it either suppresses or induces cytochrome p450 which is involved in a lotttt of medication metabolism. So depending which, it would either decrease or increase blood levels of the medication which would obviously be problematic. Same mechanism by which a lot of medications mess with other ones.
Grapefruit inhibits a liver/ intestinal enzyme called CYP3A4 which is responsible for a large amount of drug metabolism. This can lead to either the drug not getting where it needs to go, or a build-up of the drug which can be dangerous
So other citrus doesn’t have this character? I wonder why.
Your body gets rid of medications in two main ways (there are others but these are the main two): pee them out or process them in your liver so the medications are inactivated and then pee or poop the inactivated medications out. There are a collection of enzymes in your liver (enzymes are kind of like fuel that powers the inactivation process) that modify medications so that they are inactivated. These enzymes can be turned up by some substances and can be turned down by others. Grapefruit is one of the substances that turns the enzymes down. So your body can’t clear medications as quickly -> you grt higher levels of medications in your body -> toxicity can occur.
Source: final year med student
When you ingest a medication it has to be broken down. Your liver has enzymes to do that, called cytochrome P450 (CYP450). There’s different types CYP450, but the most common one that break down a lot of medications (but not “every prescription in existence” though) is called CYP3A4. Grapefruit, in very large quantities, inhibits CYP3A4 from doing its job. Medications that need CYP3A4 to be metabolized and broken down will now stay in your system, build up and potentially increase the risk of toxicity/adverse effects.
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I’m seeing a lot of partially correct answers, so I wanted to point out that there are multiple different mechanisms in which grapefruit can interfere with drug metabolism. All of them are caused by certain chemical compounds found in the citrus (called furanocoumarins). The three main ways they can do this are:
1. Inhibit metabolizing enzymes from breaking down the active form of the drug to the inactive form. This can lead to increased concentration of the drug in your body which can be toxic and lead to overdose (lots of drugs are affected this way, such as antidepressants and cholesterol medications)
2. Inhibit metabolizing enzymes from activating a prodrug to the active form of the drug. This can lead to decreased concentration of the functional drug in your body, reducing the drugs effectiveness. (Certain blood thinners are affected this way)
3. Blocks intestinal transport proteins from absorbing the drug from your digestive tract into your blood stream. This causes the drug to pass through your body without being absorbed, reducing the drug’s effectiveness (Allegra is affected in this way)
For mechanisms 1 and 2, if only small amounts of grapefruit is consumed, only the intestinal metabolic enzymes are affected, meaning that only drugs taken orally would be impacted. If lots of grapefruit is consumed, liver enzymes are also affected, which means that drugs taken via any administration method are impacted.
Intro: Most oral medications need to enter the bloodstream at a reliable concentration to work, something not too high for your body (causes toxicity) and not too low (causes loss of efficacy). There’s a lot biochemical players involved in shuffling drugs towards the bloodstream, a handful of which vary a ton between different individuals and lifestyles.
Answer: One compound in grapefruit juice IRREVERSIBLY inhibits a primary drug metabolizing enzyme within your intestines, CYP3A4. The enzyme normally breaks down drugs before they can enter the bloodstream, at a regular/predictable pace that can be accounted for during drug development. But if the enzyme suddenly gets knocked out, affected drugs cross into the bloodstream unchecked and cause some degree of overdosing. At least, until your body can produce a fresh batch of enzymes to overwrite that glass of grapefruit juice.
PS: It doesn’t even end here. Oral drugs also recirculate through your body. More and more of it should get broken down by enzymes and excreted from your body with each pass. The drug cross from the intestines into the bloodstream, from the bloodstream into the liver, and from the liver back into the GI tract — where it might encounter the impaired enzyme yet again. If someone keeps chugging grapefruit juice, the drug hangs around longer than intended and accumulates with each scheduled drug dose.
Related: Some other drugs (like Allegra) can only enter the bloodstream through a transporter channel in the intestines. Grapefruit juice also seems to inhibit this transporter, which can lead to drug underdosing and loss of efficacy.
LPT: Drugs can have potent interactions not only with other drugs, but also with different botanical foods and supplements — grapefruit juice happens to be super well documented, along with St. John’s Wort. Always check with your pharmacist to see what’s right for you.
[https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix](https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix)
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