What is it about grapefruit specifically that messes with pretty much every prescription in existence?
In:
When companies that develop medications calculate their dosages, one of the major things they have to take into account is bioavailability—how much of the drug actually ends up in your bloodstream after going through your digestive system.
The cytochrome P450 group of enzymes in your digestive system is a major factor in drug bioavailability. Grapefruits, for their part, contain a *lot* of furanocoumarins, which they use to protect themselves from fungus. When furanocoumarins meet cytochrome P450 enzymes, they *completely* wipe them out, and it can take your body upwards of *12 hours* to produce an entirely new batch.
So if you ingest a medication in that window of 12+ hours where those enzymes are nonfunctional, its bioavailability may end up being *many times* what the dosage was based off of. If, for example, the company developing the drug determined that it had *10% bioavailability* after digestion specifically due to cytochrome P450 enzymes, taking it with or in a huge window after eating grapefruit or drinking grapefruit juice will result instead in *100% bioavailability*—the equivalent of having taken a dose ***ten times larger***.
The Atlas Obscura article “[Grapefruit Is One of the Weirdest Fruits on the Planet](https://www.atlasobscura.com/articles/grapefruit-history-and-drug-interactions)” has more information on the process I’ve summarized here, as well as some fascinating details on the history of the fruit itself.
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)
ANYTHING YOU EAT GOES THROUGH YOUR LIVER. It is called the “first pass” metabolism. Imagine once everything is broken down in your stomach, each molecule becomes a *car.* Your liver has lots of *highways* that run through it to bring *cars* to be metabolized. These different highways all have different “street names” like CYP 2E1(for alcohol) and CYP2D6(opioids and antidepressants). So depending on the type of *car*, it would fit on a specific highway. Grapefruit breaks down into a *car* that fits onto the highway CYP3A4. CYP3A4 is a MAJOR highway in your liver. Cholesterol medicine, antibiotics, blood pressure medication, and more all travel on it. So if Grapefruit travels on the highway with all the other *cars*, then there becomes a traffic jam, and the *cars* can’t go through the highway and get metabolized. This can create more side effects of other medications because your liver is busy metabolizing the Grapefruit *cars*.
Medicines are designed to account for the fact that some of the medicine will get broken down by your liver, so they have more medicine in them than you actually need. Grapefruits have a chemical in them that makes your liver less good at breaking down the medicine, so you end up with more in your system than you’re supposed to.
Hi Everyone,
We’ve locked this post because comments are devolving into a combination of requests for medical advice and actual medical advice. We do not allow any form of medical advice on the subreddit, it can be incredibly dangerous to base prescription dosage decisions based on information from anonymous internet strangers.
The question itself passes the rule because a direct answer to this question cannot make someone not consult their doctor before pursuing a medical decision (not eating grapefruit at any time is not going to hurt you), but the comments have people weighing in with opinions that may.
I know no one likes a locked post, and we are sorry for that, if you have questions you can let us know in mod mail, and if you have any ideas for the sub feel free to use our suggestion box sub of r/IdeasForELI5
Also to pre-empt the “let stupid people die” argument we get every single time we remove a medical question, the answer is unequivocally “no”.
PS: if you see anyone in the comments giving medical advice that could result in problems please report it in case we missed any
Latest Answers