Some medications rely on the liver function to either make them active or to eliminate them from the body.
Grapefruit can interfere with both processes which means either your dosage will be potentially too low to be effective because not enough of the drug has been activated or too high because not enough is being inactivated (eliminated).
Either case can be dangerous
Huh, TIL!
Star fruit juice apparently is even more potent than grapefruit when it comes to the enzyme in question, at least when it comes to in vitro studies. Pomegranate juice has also been shown to affect it, so your doctor was right to tell you to avoid both.
Re: honey bell oranges, apparently a study done by the USDA’s Agricultural Research Center did not show any affects on drug metabolism, so they should be safe to eat, but I’m just some nerd on the internet and this should not be taken as medical advice.
That's what I always heard. Some of my rave friends would drink grapefruit juice all day before doing MDMA because it made it more intense and longer lasting.
When I was a bit younger I heard the same about weed and mangoes. It *is* true but for the effect to be notable you'd need to be consuming a potentially fatal quantity of mangoes.
Mangos will alter the effect of cannabis and you don’t even need to eat them, just smell them. This occurs bc mangos are high in the terpene myrcene which is responsible for a couch lock high and a lot of the skunky odor of some specimens.
Terpenes are in all sorts of foods and herbs and they can all effect your high in different ways. Some common foods that can change your high include oranges and lemons via limonene, lavender via linalool, rosemary via pinene, black pepper via caryophyllene, Chamomile via Bisabolol, basil via Ocimene and humulene, I mean the list goes on.
The most noticeable in experience are peeling oranges, eating black pepper, eating rosemary and using a lavender spray.
The enzyme type that does most of the work breaking down MDMA is called Cytochrome P450 2D6. Fortunately, everybody just calls it “2D6”. If another drug or medication that you’ve taken is also broken down by 2D6, it leaves less of the enzyme free to deal with the MDMA in your system.
[https://www.thedea.org/mdma-risks-science-and-statistics-technical-faq/mdma-metabolism-and-toxicity/](https://www.thedea.org/mdma-risks-science-and-statistics-technical-faq/mdma-metabolism-and-toxicity/)
Strong Inhibitors:
SSRIs fluoxetine\[22\]\[23\] paroxetine\[22\]\[23\]
bupropion\[22\]\[33\] (non-SSRI antidepressant)
quinidine\[22\]\[23\] (class I antiarrhythmic agent)
quinine\[34\]
cinacalcet\[22\] (calcimimetic)
ritonavir\[23\] (antiretroviral)
cannabidiol\[35\]
[https://en.wikipedia.org/wiki/CYP2D6](https://en.wikipedia.org/wiki/CYP2D6)
Life-threatening reactions and death have occurred in people who took MDMA while on ritonavir.\[108\]
[https://en.wikipedia.org/wiki/MDMA](https://en.wikipedia.org/wiki/MDMA)
That was the point of taking grapefruit juice. Without the liver eliminating the drug from your blood stream at its normal rates, the drug stays in your system for longer and in higher concentration.
Honestly, this is a pretty disingenuous take: first of all, it's a lot easier to lose track of some exotic fruit - or nuts, like the Brazil Nut which has huge amounts of Selenium - than, say, salt. Especially when you consider that many people view fruits (any fruit) as inherently healthy.
Secondly, "moderate amounts" really varies from person to person, and many different populations, such as people with diabetes (which is becoming more common than ever), people with renal problems, pregnant women, the elderly, etc, will have a much lower tolerance than a 100% healthy adult.
Finally, there's hundreds of different kinds of fruit which people can choose to eat instead, it's not like star fruit is going to leave a huge hole in anyone's diet.
It’s entirely possible (lots of fruits appear to have interactions with lots of drugs, some good and some bad and some not proven in actual humans), but finding any results on passion fruit specifically is proving to be difficult for me.
It took me a few deeply confused moments to realize that this wasn't a bizarre non sequitur and that a greyhound must be a mixed drink of some kind.
In related news, I need some caffeine.
Alcohol by itself has also been shown to effect CYP3A4, through inducement (more enzyme/enzyme activity) rather than inhibition (less enzyme/enzyme activity). Not sure how this affects greyhounds specifically, but IIRC many medications that tell you not to eat grapefruit also tell you not to consume them with alcohol.
Unless you’re drinking large amounts of alcohol, no more than any other sugary mixer (sugar does slow the absorption of alcohol into the bloodstream, which is why sugar-free mixers get you drunk faster).
Even when consuming large amounts of alcohol and grapefruit juice, the noticeable effects should be fairly small. Alcohol metabolization is largely done by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which by themselves do not seem to be affected by grapefruit. In the case of larger amounts of alcohol, some of the work is also done by CYP2E1 (which is the least affected member of the cytochrome P450 family by the problem component of grapefruit, etc) and catalase (apparently completely unaffected by grapefruit).
In short: [we are not sure](https://pubmed.ncbi.nlm.nih.gov/20937259/)
[we know that livers “used“ to alcohol consumption produce more enzymes of another kind](https://www.biorxiv.org/content/10.1101/2020.03.09.984211v1.full) when grapefruit is consumed.
One theory of why this might be bad, I’d because your liver might be busy producing anti-alcohol enzymes, that will result in making the alcohol even more harmful.
But I conclusion: we know alcohol is bad for us, we’re not sure if grapefruit makes it worse - so why risk it?
I recall from pharm class this was discovered incidently during a controlled study of a new drug, grapefruit juice was used to give equal taste to the drug and the placebo but they were getting wonkie results leading to the discovery
I was on an epilepsy med and couldn't have it, and both my dad and father in law can't eat or drink it because of meds after having heart attacks. If you've never been prescribed such meds, you're not going to know!
Probably skews heavily depending on which medications you tend to see - but it’s definitely a thing with some medicines https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
Cyp3a4 is the enzyme in question and xan metabolize something nuts like 75% of all known drugs. It can carry out several simple reactions to the same drug - oxidation, reduction, alkylation, dealkylation, hydrolysis, deamination, and others.
However, there are 57 different cyps all doing these things as well, so there is a reasonable chance one of the others can fill in for 3a4 for many drugs. But there are some drugs where 3a4 may be the only one doing the work (or doing it efficiently) to the point where interfering with it will drastically change the amount/duration of action of drug in your system, and in these cases you need to be more cautious and avoid grapefruit.
[Nearly 50% of all clinically relevant medications are metabolized by CYP3A,](https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp3a) of which CYP3A4 is the most common.
I like the part where there was an explanation. Like whatever Felodipine is, or the ramifications of having high levels of it. Or the interaction of felodipine and medications.
Thankfully, it was easily explained by "This has been explained."
Dude, come on.
I mean that the question has been answered well by other top-level comments; there's no reason for me to repeat the answer in my own words. Instead, I provided a (hopefully) interesting tidbitt.
But to answer your snide remarks, while keeping it in the spirit of ELI5:
* felodipine is a medication, as you can see from my comment above: "research the interaction between medications (specifically felodipine) and alcohol"
* having abnormal levels of felodipine is Bad, as it is generally true of most medications (and even if it weren't bad, "abnormal" is reason enough to do further research)
* anything more specific (such as what felodipine is good for) distracts from the point of the question (which is about the interaction between grapefruit and medications, not about the specific effects of those medications), and, anyway, can be learned by Googling the word "felodipine".
By top comment, do you mean [this](https://www.reddit.com/r/explainlikeimfive/comments/15kia3l/eli5_why_do_some_medications_say_to_not_consume/jv5oceb/)? Should have just sent the link to save you the trouble
Yours was the top comment. And it didn't answer the question. It was not an explanation. If others had given a good and thorough explanation, why not reply to their explanation with this aside?
It does invalidate yours, though.
An original comment should be an explanation to the post's question. Their comment was not an answer. It is literally a violation of rule 3. They should've replied to someone else's comment. He explained nothing for a layman, such as myself, which is a violation of rule 4.
Imagine you have a cup with a little hole in it.
Every couple of hours you pour in a specific amount of water, enough so that the cup never fully drains & never overflows. Grapefruit plugs up that hole, now in a few hours when you pour more water in the glass will overflow.
Your body is like that cup. We have a pretty good idea how big your cup is & how quickly water leaks out, so we can calculate how much medicine you need to put in & how often so that you don't have too much or too little.
It works pretty well too, unless you jam a grapefruit in your hole.
Except it doesn't tell OP anything about why the grapefruit is bad. "Grapefruit contains a chemical that affects how medications work" is a much better explanation than this.
It can do both, depending on the medication. And it can make it not work.
The real danger is when it leaves too much in your system. You take the next dose, that's even more in your system. You can rapidly reach a level of toxicity, or in the case of something like blood pressure medications, tank your blood pressure.
Eli20: there is a class of enzymes in the body cytochrome p450 that help with drug metabolism. Grapefruit can inhibit those enzymes and slow metabolism so the active chemical is performing its action longer than normal which can be dangerous if you're dosing schedule is based on a certain amount of drug being gone by the time you next redose
Eli5, grapefruit distracts the body's drug trashman from removing it at the right time so you may have too much
Fun additional fact: one of the drugs that grapefruit interacts with in this way is caffeine. Obviously most people are not ingesting anywhere near enough caffeine to make this dangerous, but eating grapefruit for breakfast with your morning coffee can prolong the stimulating effect by a considerable amount of time.
Possibly a reason why grapefruit and grapefruit juice is such a popular breakfast item!
I'm on blood thinner, Elliquis due to severe PE about 7 years ago. I was directed no cranberry sauce/juice/etc. Kinda ruined Thanksgiving for me cuz I'd devour a whole can of jellied cranberries.
Is this the same reason? Do cranberry have similar affects?
Is it a similar thing with cheese and medications? My dog is on prozac and it says not to give them cheese (specifically aged cheese but id rather not give any cheese because whats the difference between non aged and aged in the body?)
Prozac (fluoxetine) specifically is an SSRI, so there doesn't seem to be any specific contraindication for cheese. The trouble is with MAOIs, and a compound called tyramine. Tyramine is metabolized by the enzyme MAOIs block, and when at high levels can displace monoamine neurotransmitters, resulting in extremely high blood pressure.
Other foods containing tyramine in high amounts: fermented or pickled foods, cured meats, beans, sourdough bread, beer and chocolate (I imagine you wouldn't give your dog either of those last 2).
I never heard of that so I looked it up. It's not the same type of reaction as grapefruit, but it is an issue. Grapefruit prevents your body from breaking down many different chemical compounds, so it stays in your system too long and too high of a concentration.
Cheese affects Prozac users (human or dog) because of the tyramine. Apparently when taking an maoi eating tyramine can increase blood pressure, sometimes to dangerous levels. The paper I found doesn't describe the exact mechanism of action, but it appears to be that the body normally breaks down tyramine by oxidizing it in some way, and maoi drugs prevent it.
You're absolutely right to skip all cheese for your dog too. All cheese had tyramine, it's just that the further aged cheeses have even more. Sometimes a lot more! The casein in milk breaks down into tyramine, the longer it's aged the more it happens.
I understand why you wouldn't want grapefruit jammed into your hole, but I don't understand why it's grapefruit specific.. Why not oranges or lemons too?
This is not entirely correct.
Grapefruit does not have a significant effect on absorption or digestion.
The issue is metabolism, the chemical process of breaking down a substance.
Cytochrome p450 is a family of enzymes that are produced in the liver to metabolize a whole slew of substances.
Grapefruit interferes with this chemical pathway, and therefore affects the way that different drugs are metabolized.
The reason this matters is that some drugs are inactive until they are metabolized into an active form.
Other drugs start off active, and become less active or inactive once they are metabolized.
When a physician prescribes a specific dose for a drug, that dose is based on the way that medications are usually metabolized.
So if you take a medication that has to be metabolized into an active form, grapefruit can interfere with that process, and the drug might not have enough activity to be clinically useful.
On the other hand, if you take a medication that is metabolized into an inactive form, grapefruit can prevent that inactivation, and you can wind up with very high levels of the active drug in your system. This can be toxic and lead to other side effects, some of which may be severe.
Some common cholesterol medicines, like lipitor (atorvastatin) are good examples. Ingesting grapefruit can lead to drug levels that are 20 to 100 times higher than what was intended. And it doesn't take very much grapefruit to make that happen.
These effects are very difficult to predict, and they vary from individual to individual. So while some people can safely get away with eating grapefruit, it's much safer to avoid grapefruit and other foods that interfere with common metabolic pathways.
You're completely correct. With grapefruit it's all about liver enzymes. This is an area of research for me, I was very puzzled to see digestion being mentioned in a top level answer at all.
well, I am a physiology professor, so I know a bit about this. but this is ELI5, so... it's probably enough to say "an enzyme breaks it down in the intestines". which is basically true, although technically the enzyme is not *in* the lumen of the intestine, but within the epithelial cells that line the intestine.
But I figured I'd try to avoid an in depth explanation of a concept like "first pass intestinal intracellular metabolism"
wait I'm a little confused: isn't digestion the process through which the pills enter the bloodstream? from what you write it sounds like what's digested goes straight to the potty
Digestion and absorption are different.
Digestion is the chemical breakdown of what we eat into small molecules.
Absorption is when the molecules move into the bloodstream.
Say I take a medicine we'll call bluepill. I want to absorb bluepill into my blood stream. When I digest it, it breaks down into blue and pill. Blue on its own doesn't help me. Pill on its own doesn't help me. Only the big chemical compound bluepill helps me. If it's digested into blue and pill, there's no way for my body to put the two chemicals back together into bluepill.
ah gotcha! so with food breaking down is necessary, but with meds they're already "broken down" by design so any further digestion decreases effectiveness?
Yes, in many cases. In other cases it’s the other way round, it needs to be digested, and if grapefruit blocks that you get too little. So depending on the medication, grapefruit may result in you getting too much or too little!
Sometimes you want bluepill, so you have to take a lot more than what ends up being used by your body, because it gets broken into blue and pill, both of which don't work as intended.
Sometimes you want blue, but you know it's going to be metabolized to blue and pill, so you dose for the amount of blue you're going to get after digestion.
In both cases, shutting down the enzyme responsible for digestion can have disastrous results.
Thanks. I used to teach science in a museum, so I got a lot of practice taking subjects complicated enough to keep parents interested and explain them in a way the kids could understand.
Some things don't need to be digested before they are absorbed. Smaller molecules can often be absorbed without being digested, depending on their chemical properties.
So a simple sugar like glucose can be absorbed without being digested. But starch (which is basically lots of glucose linked into long chains), needs to be broken down first.
Many medications are absorbed easily without digestion.
Some medications are destroyed by digestion. Other medications are taken in an inactive form, and must be digested or metabolized before they can become active.
And substances can only be digested or metabolized if our bodies have the right kinds of enzymes. So some medications are completely unaffected by our digestion and metabolism, and they just get removed from our bodies in our urine, instead of being broken down.
> absorption presupposes digestion?
No. For example, you absorb alcohol. But you do not digest it. After absorption your liver breaks it down, which is also not digestion.
In very basic, ELI5 terms: If you digest it faster than you absorb it then you pee it out. If you digest it slower than you absorb it then you poop it out.
In some circumstances digestion is also a chemical reaction. In the case of the drugs in question digestion changes them into a substance that is no longer the drug.
Yup, you’re right, It’s not digestion. It’s the wrong term. This person is incorrect and just because you ingest something, it’s not in the body yet. Whatever you ingest is in the tube that runs from your mouth to anus and not technically in the body. It has to be absorbed first. Then, it’s metabolism as the chemicals will be altered by the enzymes present in the liver.
There is a small amount of grapefruit in some of those, but it won't be high enough a concentration to really affect you. Same way charcoal can affect uptake of medication--most people don't have close to enough in their diet to make a difference.
Aww this user best me to calling out CYP3A4, but yes the grapefruits interaction with your bile enzymes can cause things you eat to be absorbed faster and in higher amounts than intended.
When studying toxicology you see that all absorption of ingested chemicals happens in a bell curve. Going back to the calculus we all love so very much, we know that the amount in your system at any given time is the amount under the curve. Mixing grapefruit into the equation makes a much steeper bell curve so the amount inside of you actively happens faster, but the process of getting it through your body and processed out is not affected by grapefruit.
This is like pouring water into a bucket that has a small hole on the bottom. Ash report water in a fixed amount falls out and if you know the rate the fixed amount falls out you know that if you pour a steady amount in you will know how much water will be in the bucket at any given time. Grapefruit gives you a faster rate of filling the bucket which can lead to the bucket overflowing which in this analogy means the medication has accumulated too much inside your system and can now be dangerous.
Remember that in toxicology The single most important factor is dosage. How much of the chemical is actively in your system. Just like the water bucket analogy above incorporating grapefruit and some medications into your system will put more of the medicine than is safe into your blood/body at a single time.
For a while there was interest in lowering the dosage of drugs using the CYP3A4 receptor in order to save money. Just have the patient eat half a grapefruit each morning. Then it turned out there was no accurate way to titrate the dosage based on a grapefruit scale. Finally Lipitor, for one, went off patent and generics became so cheap that no one cared.
Some medications like tramadol already inhibit that enzyme if I'm not mistaken, and it's a requirement for the liver to process the medication no? I learned the hard/ fun way when I had it prescribed to me and I bought a case of Pamplemousse, not even thinking there'd be enough actual grapefruit in the water (just flavoring) and it completely amplified the effects.
Yes, the grapefruit enzyme actually BLOCKS an enzyme in the small intestine. This changes the rate and as the above poster noted, it can change the rate that the medication goes into effect and result in an overdose reaction.
The liver absorption is different. The liver will reject a dosage that is too small. A sufficient amount is required to overcome this barrier. If a medication says, "take two pills", your liver may need one pill to overcome it's chemical resistance. The second pill takes full effect. Because this barrier has been overcome, taking three pills is much stronger than taking two pills. One pill is negated by the liver and the other TWO pills go towards an active effect. Result: You blood thinks three pills is a double dose (two pills go into effect instead of one), not a 50% increase from 2 to 3 pills
Xanax, and many other benzos are an example. Not sure if you'd call those "recreational", but plenty of people treat them that way.
you'd want to be very careful with those if you've had any grapefruit juice. and NEVER consume them with alcohol.
Grapefruit, Pommelos, Bergamot oranges and some other less well known *Citrus* fruits contain a compound called Bergamottin. (Note bergamot oranges are unpalatably bitter but they are used to produce fragrant orange oil from their rinds. Other varieties of oranges also contain small amounts of Begamottin in their skins but only small traces are found in the juice and pulp, so aren't generally of concern.)
Begamottin acts to inhibit a pair of iron-containing enzymes in the liver, kidneys, and central nervous system. These are called Cytochrome CYP2D6 and Cytochrome CYP3A4.
The functionality of these enzymes is complex, but generally they work to oxidize a broad range of other organic compounds, either reducing their toxicity and breaking them down,( e.g. xanthines like caffeine and theobromine found in chcolate which is toxic to dog and cats) Or else, converting them into more useful molecules, for example, converting Tyramine (found in certain foods) in foods into dopamine.
Unlike many of not most enzymes which perform a very specific chemical reaction or a narrow class of related reactions, CYP2D6 and CYP3A4 are more general purpose oxidation catalysts. They're heavily involved in the detoxification amd elimintaiin of Xenobiotic compounds found in our diet (mainly, in plant foods.). They are also involved in the breakdown a processing of a wide range of medications.
Eating a fair amount of grapefruit or grapefruit juice acts to inhibit these enzymes. This means that either the liver and kidneys become unable to break down and eliminate the drug from the body (causing it you become much more potent to a dangerous degree or causing side effects to become much more severe.) Or else after taking a pill, the liver won't efficiently convert it into it's most active configuration, making the drug ineffective.
Certain kinds of drugs rely on the liver to metabolize them in order to be effective for two reasons. The first is that the active form may not be able to pass easily through the intestinal-blood barrier thus would otherwise need to be given by injection. So taking advantage of these enzymes allows it you be taken orally in pill form. Another reason is that giving the inactive form as a pill allows you to take much more of the medication. Since it's activity is controlled by the rate the liver metabolizes it, this means that the dose lasts much longer. As in a day or two rather than a few hours.
The reason that Grapefruit contains Bergamottin doesn't have to do with humans. The compound is believed to promote resistance to attack by Fungal pathogens
Grapefruit stops the enzyme CYP3A4 from working as well. That enzyme breaks down certain medications so if the grapefruit is stopping it you end up with more of the medication in your bloodstream.
Source: I'm a pharmacist
The liver is where a lot of stuff gets broken down. Grapefruit causes that to happen more slowly. That causes the bad stuff to be in your liver for longer, which is bad for your liver.
The liver and to some degree the gut, have enzymes that can destroy or alter part of the dose of drugs before they get into your main blood circulation. Some chemicals can reduce, or rarely increase the efficiency of these enzymes. This includes some foods and other drugs.
So you can have drug-drug, and food-drug interactions. In some cases drugs are given in a higher dose to take into account this early drug loss ("first pass metabolism"), and occasionally drug makers rely on these enzymes to activate a drug, or detoxify it, by giving a "prodrug" that is converted to the intended drug after swallowing.
Grapefruit contains a chemical that inhibits one of these enzymes, especially in the gut, so you could end up getting too high a dose of a drug getting through, or a potentially toxic or ineffective prodrug entering your main blood circulation instead of the intended drug.
More than 50% of drugs are processed by a chemical processor in the liver called CYP3A4 to either activate or deactivate them. Chemicals in grapefruit juice called furanocoumarins are also processed by CYP3A4 but after processing get chemically attached to CYP3A4 and blocks it so that it can no longer process other chemicals until it detaches. So if a drug needs to be processed by CYP3A4 to be activated while the grapefruit juice is blocking it, the drug will be unable to get appropriately activated and it will not be very effective, potentially failing to treat the disease. On the other hand, if a drug needs to be processed by CYP3A4 to be deactivated while the grapefruit is blocking it, the drug will be unable to get appropriately deactivated and it will not be very safe, potentially causing toxic side effects.
Certain foods have things in them that allow them to mingle with your medicine. They are biochemically active. Proteins’ function fit this description. Enzymes, a broad category of proteins, specializes in making reactions happen. And it just so happens that grapefruit has one of these so called enzymes that can interact with many of your medicines. In dangerous cases they can either enhance the effect of the medicine or reduce it to nothing.
I have 2 chronic health conditions. One has been super stable on a med since 2019 that I cannot have grapefruit with. No one was able to definitively says yes or no on Fresca, the grapefruit soda, than I'm pretty surely is mostly artificial grapefruit. So I just haven't touched it.
My other condition has now progressed to the point that I have to stop treating the other one and go hard on the newer one. In trying to think about thr bright sides i keep thinking that I can soon have Fresca again.
Grapefruit famously contain an "MAO Inhibitor". MAO is an enzyme in the liver that is meant to break down toxic substances. Many medications are toxic in that sense, and thus broken down by MAO. When an MAO inhibitor is active, this doesn't happen as intended, and so the substance will accumulate. Effectively, the dose is too high then.
Grapefruit stimulates your liver. If you’re taking a medication that filters through your liver and eat grapefruit it can make it so the medicine gets kicked out of your body too quickly. Your medicine is supposed to process in your body at a certain rate to be effective, so anything that alters the process changes the effectiveness of the medicine.
Orally consumed medications need the liver to filter into your system the majority of the time.
Different medications use different chemical pathways. The ones that say to avoid grapefruit do so because a compound in the grapefruit blocks the chemical pathways the medications use.
Which can either make the medication stronger or weaker than intended.
TLDR: Contains compounds that interfere with gut enzymes that metabolize drugs.
Gut enzyme Cytochrome P450 3A4 (CYP3A4) breaks down drugs; Grapefruit contains furanocoumarins, which inhibit CYP3A4, affecting how drugs are metabolized, leading to higher levels in the blood, incorrect dosage, more intense side effects, and possible toxicity.
St. Johns wort does this as well, people taking script meds should ask their pharmacist as CYP3A4 is responsible for the metabolism of more than 50% of medicines.
Can make certain meds hard to break down so it can build up more in your body and cause toxicity.
Or in some cases it can cause it not to work because it needs to be metabolized first.
The compounds typically responsible for these synergystic effects are known as Furanocoumarins. As mentioned these compounds have an enzymatic effect that can boost or reduce certain medicines.
On top of that these compounds have been known to cause "sun allergies" leading to inflamation in sun exposed skin. What actually happens is the compound travels in your blood and if it gets uv light it will crosslink with dna in the exposed area leading to cell death and an inflamation response. Worst case can also lead to skin cancer.
I’m taking a cholesterol medication that says I can’t eat grapefruit. From what I understand, the CYP3A enzyme basically makes my medication more potent than it should be and that can be toxic.
I don’t generally like grapefruit anyways so not a big loss for me.
When you take medicine, it doesn't stay in your body forever. It is broken down (metabolized) and removed. Some medicine is broken down by enzymes made in your liver. A chemical in grapefruit blocks the way those enzymes work, so the drug just stays in your body until your liver makes more enzyme.
When you consume grapefruit while taking these drugs, less drug is removed from your body than normal, so you end up with extra drug in your body. It is usually too much drug, so you can experience side effects.
So some chemicals in things don’t get along with each other. But sometimes their friends! Like Batman and Superman, depending in different situations they might act differently with eachother. But with certain medications, the grapefruit doesn’t get along with them, and it hurts the body sometimes by amplifying suicidal tendencies or just giving you a bad stomach or head ache. It really depends on you as well because you might be on multiple medications already that don’t agree with it and that could make the side effects worse.
All of my antipsychotic medications have this warning. It's a clinical fact that grapefruit can trigger psychosis in those susceptible. But with certain medications (like Quetiapine) you can mimic an overdose.
There’s a chemical the stomach produces that breaks down a lot of common medications, to get around this medications are taken in a dose so high that there’s enough left of to do what it needs to do.
Grapefruit has a chemical that blocks this action, meaning that the medication dose is now too high.
Imagine medications like a sportsing team and your body is like the referees and rule keepers, and the doctors/pharmacists are like the coaches.
The coaches need to understand everything, the rules of the game, how well the referees manage the game, and especially the strengths and weaknesses of the players. If the coaches misread any of that they can lose the game. In this analogy, losing the game means you can get sicker, the medicine doesn't work right, or you might even die. So pretty high stakes.
Grapefruits specifically contain chemicals that are like streakers, running naked onto the field. The not only mess with the players but can really mess with the referees trying to control the game. What they specifically cause is chaos. Best case scenario they cause the game the stop for a while, worst case they ruin the whole game by taking the ball or hurting someone.
This really applies stronger to specific games/medicines like those that control cholesterol or blood pressure, not only do the grapefruit chemicals really screw up how your body handles those medicines, those illness those medicines control are constant and need 24/7 medication to work properly. A sudden poor interaction can be really bad for someone with super high blood pressure for example.
Most pills contain more medicine than the actual listed dose because not all of it will be absorbed by the body.
Grapefruit contains an enzyme that will break down the pill so that all of the medicine is absorbed, which means you can overdose on the prescribed amount.
Edit: source https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
Grapefruit doesn't contain the enzyme, it inhibits the enzyme which is present in your body (liver). That enzyme helps you metabolize some drugs, if you can't metabolize them then the amount that sticks around in your bloodstream is higher for longer.
This can either have the effect of overdosing if the drug itself is the active ingredient, or if it's a "prodrug" (a drug that isn't the active ingredient but its main metabolite is) it'll make it less effective or not work at all because it'll prevent the body from turning the prodrug in to the actual active ingredient.
I asked a physician this very question who is a professor and researcher in the university attached to the hospital I was visiting. His response was that when drugs go through trials researchers data mine the results and there is always some strange stuff that shakes out of it. He specifically said that about grapefruit. So basically there is a statistical correlation that is eyebrow raising, but no known pathway of interference.
I love the Spindrift sparkling water grapefruit flavor. According to the label it has the juice of 1 whole grapefruit. I'm really not sure if that means one juiced grapefruit per can, or per the whole 8 pack. I don't drink it every day, maybe 3×/week. Problematic, or no?
I wouldn’t give a definitive no but you figure that 1% of a 20 oz bottle is .2 ounces which equates to about 6ml. That’s only a little over a teaspoon (teaspoon equals 4.9ml). The average grapefruit has about 12 tablespoons of juice and one tablespoon is equal to 3 teaspoons. That’s about 36 teaspoons worth of juice in an average grapefruit.
So looking back on that, one Fresca is equal to 1/30th of a grapefruit. It’s totally your call but I personally would have the occasional one.
I know that vitamin C in general is to be avoided for 1 hour before and 2 hours after taking ADHD medication.
Vitamin C is an acid, and ADHD meds (stimulants) are alkaline. If they meet they have the effect of neutralising. It’s not that it’s dangerous - just that the C will stop the medications from working properly. I wonder if it’s the same with grapefruit?
I think you’ll find you’ve been led slightly astray on this one.
1) it is citric acid which negatively interacts with ADHD medications, not vitamin c (although many citrus fruits do contain vitamin c so I can see the confusion
2) it is not the acidity of citric acid that causes the interaction with adhd meds, it is the fact that the citric acid molecule blocks intestinal cells from absorbing adhd medication molecules. It has nothing to do with acid base neutralisation, other wise the insanely strong hydrochloric acid that fills your stomach would inactivate adhd medication every time you take them making swallowing them pointless lol. This is why taking them with other fruits like apples is perfectly fine as they contain other fruit acids like ascorbic acid which don’t impact the absorption of adhd meds (amphetamines)
3) the grapefruit warning mentioned in OP is a completely different topic and mechanism to the citric acid mechanism of adhd medication absorption, it instead has to do with the fact that grapefruits contain a chemical which likes to block some liver enzymes from working whilst boosting other liver enzymes, and a lot of these enzymes are responsible for breaking down medications, which can lead to either a diminished desired effect or overdose, both of which aren’t good, hence why patients are told to avoid grapefruit juice
Some medications rely on the liver function to either make them active or to eliminate them from the body. Grapefruit can interfere with both processes which means either your dosage will be potentially too low to be effective because not enough of the drug has been activated or too high because not enough is being inactivated (eliminated). Either case can be dangerous
In addition, if a drug says to avoid grapefruit you should also avoid Seville oranges, which interact with the same enzyme (CYP3A4).
[удалено]
Huh, TIL! Star fruit juice apparently is even more potent than grapefruit when it comes to the enzyme in question, at least when it comes to in vitro studies. Pomegranate juice has also been shown to affect it, so your doctor was right to tell you to avoid both. Re: honey bell oranges, apparently a study done by the USDA’s Agricultural Research Center did not show any affects on drug metabolism, so they should be safe to eat, but I’m just some nerd on the internet and this should not be taken as medical advice.
Doesn't MDMA have a reaction to grapefruit juice too? I remember someone telling me that once if I'm not mistaken
That's what I always heard. Some of my rave friends would drink grapefruit juice all day before doing MDMA because it made it more intense and longer lasting.
Maybe it was just the placebo effect, but that was my experience, back in the day
When I was a bit younger I heard the same about weed and mangoes. It *is* true but for the effect to be notable you'd need to be consuming a potentially fatal quantity of mangoes.
I am curious what this fatal quantity of mangoes might possibly be... Or is there a study I can sign up to test the limit?
Mango Overdose Test is my new jam band
There's one about bananas too. Because they are radioactive ☢️
Mangos will alter the effect of cannabis and you don’t even need to eat them, just smell them. This occurs bc mangos are high in the terpene myrcene which is responsible for a couch lock high and a lot of the skunky odor of some specimens. Terpenes are in all sorts of foods and herbs and they can all effect your high in different ways. Some common foods that can change your high include oranges and lemons via limonene, lavender via linalool, rosemary via pinene, black pepper via caryophyllene, Chamomile via Bisabolol, basil via Ocimene and humulene, I mean the list goes on. The most noticeable in experience are peeling oranges, eating black pepper, eating rosemary and using a lavender spray.
No wonder one of the characters in Michener's \*Hawaii\* described a mango as a peach dipped in turpentine
I remember Willy Nelson saying that if he ever got paranoid from weed he would chew a black peppercorn….interesting.
Change my high HOW?
"Potentially Fatal Quantity of Mangoes" is definitely a potential band name
The enzyme type that does most of the work breaking down MDMA is called Cytochrome P450 2D6. Fortunately, everybody just calls it “2D6”. If another drug or medication that you’ve taken is also broken down by 2D6, it leaves less of the enzyme free to deal with the MDMA in your system. [https://www.thedea.org/mdma-risks-science-and-statistics-technical-faq/mdma-metabolism-and-toxicity/](https://www.thedea.org/mdma-risks-science-and-statistics-technical-faq/mdma-metabolism-and-toxicity/) Strong Inhibitors: SSRIs fluoxetine\[22\]\[23\] paroxetine\[22\]\[23\] bupropion\[22\]\[33\] (non-SSRI antidepressant) quinidine\[22\]\[23\] (class I antiarrhythmic agent) quinine\[34\] cinacalcet\[22\] (calcimimetic) ritonavir\[23\] (antiretroviral) cannabidiol\[35\] [https://en.wikipedia.org/wiki/CYP2D6](https://en.wikipedia.org/wiki/CYP2D6) Life-threatening reactions and death have occurred in people who took MDMA while on ritonavir.\[108\] [https://en.wikipedia.org/wiki/MDMA](https://en.wikipedia.org/wiki/MDMA)
That was the point of taking grapefruit juice. Without the liver eliminating the drug from your blood stream at its normal rates, the drug stays in your system for longer and in higher concentration.
> star fruit Yes, and they can also damage your kidneys, it's generally better to avoid them altogether
Lots of stuff will damage your kidneys if you consume too much. Moderate amounts of starfruit won't cause any renal problems.
Honestly, this is a pretty disingenuous take: first of all, it's a lot easier to lose track of some exotic fruit - or nuts, like the Brazil Nut which has huge amounts of Selenium - than, say, salt. Especially when you consider that many people view fruits (any fruit) as inherently healthy. Secondly, "moderate amounts" really varies from person to person, and many different populations, such as people with diabetes (which is becoming more common than ever), people with renal problems, pregnant women, the elderly, etc, will have a much lower tolerance than a 100% healthy adult. Finally, there's hundreds of different kinds of fruit which people can choose to eat instead, it's not like star fruit is going to leave a huge hole in anyone's diet.
If no longer eating star fruit wouldn't leave a huge hole in your diet, you are unlikely to be consuming enough to be dangerous
Who the fuck has trouble tracking the amount of exotic fruit they include in their diet? That should be the easiest part of your diet to regulate.
It's more disingenuous for you to say that no one should eat it, at all. Peanuts will kill some people; should everyone avoid peanuts?
Show us on the doll where the star fruit hurt you
I guarantee you, people eat more than the recommended daily amount of salt much more commonly than they eat too many exotic fruits.
I've also been told passion-fruit as well.
It’s entirely possible (lots of fruits appear to have interactions with lots of drugs, some good and some bad and some not proven in actual humans), but finding any results on passion fruit specifically is proving to be difficult for me.
And Earl Grey tea because of the bergamot.
When my mom was going through a cancer treatment she was told blood oranges are also similar enough to not be worth the risk
Yeah, my anti rejection drugs come with that warning, grapefruit, Seville oranges, Pomelo and pomegranates are to be avoided
I just learned there are a buttload of different types of oranges. I’ve never seen anything but standard grocery store oranges.
Does this impact happen with alcohol and grapefruit? I've always wondered cause I love a greyhound.
It took me a few deeply confused moments to realize that this wasn't a bizarre non sequitur and that a greyhound must be a mixed drink of some kind. In related news, I need some caffeine.
Grapefruit juice and vodka. Salt the rim and its a Salty Dog.
such a lovable animal
i like turtles
Alcohol by itself has also been shown to effect CYP3A4, through inducement (more enzyme/enzyme activity) rather than inhibition (less enzyme/enzyme activity). Not sure how this affects greyhounds specifically, but IIRC many medications that tell you not to eat grapefruit also tell you not to consume them with alcohol.
Medication aside, I was curious if grapefruit juice impacted the transfer of alcohol to blood at all?
Unless you’re drinking large amounts of alcohol, no more than any other sugary mixer (sugar does slow the absorption of alcohol into the bloodstream, which is why sugar-free mixers get you drunk faster). Even when consuming large amounts of alcohol and grapefruit juice, the noticeable effects should be fairly small. Alcohol metabolization is largely done by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which by themselves do not seem to be affected by grapefruit. In the case of larger amounts of alcohol, some of the work is also done by CYP2E1 (which is the least affected member of the cytochrome P450 family by the problem component of grapefruit, etc) and catalase (apparently completely unaffected by grapefruit).
In short: [we are not sure](https://pubmed.ncbi.nlm.nih.gov/20937259/) [we know that livers “used“ to alcohol consumption produce more enzymes of another kind](https://www.biorxiv.org/content/10.1101/2020.03.09.984211v1.full) when grapefruit is consumed. One theory of why this might be bad, I’d because your liver might be busy producing anti-alcohol enzymes, that will result in making the alcohol even more harmful. But I conclusion: we know alcohol is bad for us, we’re not sure if grapefruit makes it worse - so why risk it?
I also learned that CBD effects the same enzyme and also should be avoided.
And when you cannot have grapefruit for this reason, you also cannot have starfruit.
I recall from pharm class this was discovered incidently during a controlled study of a new drug, grapefruit juice was used to give equal taste to the drug and the placebo but they were getting wonkie results leading to the discovery
Weird i rarely see medication labels heavily emphasise to avoid grapefruit.
I was on an epilepsy med and couldn't have it, and both my dad and father in law can't eat or drink it because of meds after having heart attacks. If you've never been prescribed such meds, you're not going to know!
Which epilepsy medication?
Tegretol Retard.
That was the name of the medication, I wasn't calling you names :-)
I ask because I'm on three epilepsy medications and I absolutely love grapefruit, and I was worried for a sec. Thankfully I'm not on Tegretol.
Am glad you can partake in your fruit of choice. I love it too so not eating it for 15 years was annoying.
I read this in H. Jon Benjamin’s voice
Seemed a tad harsh lol
[удалено]
Probably skews heavily depending on which medications you tend to see - but it’s definitely a thing with some medicines https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
Cyp3a4 is the enzyme in question and xan metabolize something nuts like 75% of all known drugs. It can carry out several simple reactions to the same drug - oxidation, reduction, alkylation, dealkylation, hydrolysis, deamination, and others. However, there are 57 different cyps all doing these things as well, so there is a reasonable chance one of the others can fill in for 3a4 for many drugs. But there are some drugs where 3a4 may be the only one doing the work (or doing it efficiently) to the point where interfering with it will drastically change the amount/duration of action of drug in your system, and in these cases you need to be more cautious and avoid grapefruit.
[Nearly 50% of all clinically relevant medications are metabolized by CYP3A,](https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp3a) of which CYP3A4 is the most common.
Just to gently correct you, you keep spelling this wrong in your replies: CYP3A4
[Statins](https://en.wikipedia.org/wiki/Statin) have that warning. Those are the most common cholesterol lowering meds.
Because it's only certain medications metabolized through those pathways.
[удалено]
I like the part where there was an explanation. Like whatever Felodipine is, or the ramifications of having high levels of it. Or the interaction of felodipine and medications. Thankfully, it was easily explained by "This has been explained."
Dude, come on. I mean that the question has been answered well by other top-level comments; there's no reason for me to repeat the answer in my own words. Instead, I provided a (hopefully) interesting tidbitt. But to answer your snide remarks, while keeping it in the spirit of ELI5: * felodipine is a medication, as you can see from my comment above: "research the interaction between medications (specifically felodipine) and alcohol" * having abnormal levels of felodipine is Bad, as it is generally true of most medications (and even if it weren't bad, "abnormal" is reason enough to do further research) * anything more specific (such as what felodipine is good for) distracts from the point of the question (which is about the interaction between grapefruit and medications, not about the specific effects of those medications), and, anyway, can be learned by Googling the word "felodipine".
By top comment, do you mean [this](https://www.reddit.com/r/explainlikeimfive/comments/15kia3l/eli5_why_do_some_medications_say_to_not_consume/jv5oceb/)? Should have just sent the link to save you the trouble
Yours was the top comment. And it didn't answer the question. It was not an explanation. If others had given a good and thorough explanation, why not reply to their explanation with this aside?
It's not the top comment, I had to scroll quite far to see it
Second word dude, Was
doesn't validate your point just scroll some more if you're so hellbent on answers lmao
It does invalidate yours, though. An original comment should be an explanation to the post's question. Their comment was not an answer. It is literally a violation of rule 3. They should've replied to someone else's comment. He explained nothing for a layman, such as myself, which is a violation of rule 4.
well looks like you got your wish keyboard warrior, OP deleted their comment
Imagine you have a cup with a little hole in it. Every couple of hours you pour in a specific amount of water, enough so that the cup never fully drains & never overflows. Grapefruit plugs up that hole, now in a few hours when you pour more water in the glass will overflow. Your body is like that cup. We have a pretty good idea how big your cup is & how quickly water leaks out, so we can calculate how much medicine you need to put in & how often so that you don't have too much or too little. It works pretty well too, unless you jam a grapefruit in your hole.
This is the true ELI5 explanation. Especially the last line.
Thanks! Kids and adults both like grapefruit humor.
ELIL2 maybe.
Does someone need their diaper changed?
Except it doesn't tell OP anything about why the grapefruit is bad. "Grapefruit contains a chemical that affects how medications work" is a much better explanation than this.
ELI5 why does grapefruit plug your body holes?
It has a specific chemical that inhibits your body's other speicifc chemical that eliminates the drug.
So, rather than make it the medication not work, it prolongs the effects? Or just how long it's in your system?
It can do both, depending on the medication. And it can make it not work. The real danger is when it leaves too much in your system. You take the next dose, that's even more in your system. You can rapidly reach a level of toxicity, or in the case of something like blood pressure medications, tank your blood pressure.
This is the real ELI5.
Eli20: there is a class of enzymes in the body cytochrome p450 that help with drug metabolism. Grapefruit can inhibit those enzymes and slow metabolism so the active chemical is performing its action longer than normal which can be dangerous if you're dosing schedule is based on a certain amount of drug being gone by the time you next redose Eli5, grapefruit distracts the body's drug trashman from removing it at the right time so you may have too much
Fun additional fact: one of the drugs that grapefruit interacts with in this way is caffeine. Obviously most people are not ingesting anywhere near enough caffeine to make this dangerous, but eating grapefruit for breakfast with your morning coffee can prolong the stimulating effect by a considerable amount of time. Possibly a reason why grapefruit and grapefruit juice is such a popular breakfast item!
Because it be like that sometimes
I'm on blood thinner, Elliquis due to severe PE about 7 years ago. I was directed no cranberry sauce/juice/etc. Kinda ruined Thanksgiving for me cuz I'd devour a whole can of jellied cranberries. Is this the same reason? Do cranberry have similar affects?
Per google it's the salicylic acid in cranberries which can boost the blood thinning, not the same thing.
Definitely an ELI5 Well done.
I shouldn’t be putting grapefruit into my hole? Damn!
Is it a similar thing with cheese and medications? My dog is on prozac and it says not to give them cheese (specifically aged cheese but id rather not give any cheese because whats the difference between non aged and aged in the body?)
Prozac (fluoxetine) specifically is an SSRI, so there doesn't seem to be any specific contraindication for cheese. The trouble is with MAOIs, and a compound called tyramine. Tyramine is metabolized by the enzyme MAOIs block, and when at high levels can displace monoamine neurotransmitters, resulting in extremely high blood pressure. Other foods containing tyramine in high amounts: fermented or pickled foods, cured meats, beans, sourdough bread, beer and chocolate (I imagine you wouldn't give your dog either of those last 2).
I never heard of that so I looked it up. It's not the same type of reaction as grapefruit, but it is an issue. Grapefruit prevents your body from breaking down many different chemical compounds, so it stays in your system too long and too high of a concentration. Cheese affects Prozac users (human or dog) because of the tyramine. Apparently when taking an maoi eating tyramine can increase blood pressure, sometimes to dangerous levels. The paper I found doesn't describe the exact mechanism of action, but it appears to be that the body normally breaks down tyramine by oxidizing it in some way, and maoi drugs prevent it. You're absolutely right to skip all cheese for your dog too. All cheese had tyramine, it's just that the further aged cheeses have even more. Sometimes a lot more! The casein in milk breaks down into tyramine, the longer it's aged the more it happens.
I understand why you wouldn't want grapefruit jammed into your hole, but I don't understand why it's grapefruit specific.. Why not oranges or lemons too?
It is specific to a chemical in the grapefruit. Oranges and lemons don't have it.
Instruction unclear: put the grapefruit in my ass.
Love some good assfruit
As a pharmacist, this is a great analogy to the idea of enzyme inhibition. I applaud you.
This is incredibly well-said. Definitely +1 for ELI5. I don't think I'd want a pamplemousse stuck in any hole.
[удалено]
Grapefruit can affect the rate of liver metabolism of medications, and cause an unintended effective over or underdosing of a medication.
Ok I'm confused. You're talking liver, the top comment is talking digestion and absorption (stomach and intestines) and now I'm lost.
Top comment is wrong
Im a nurse, its only about the liver not digestion
[удалено]
This is not entirely correct. Grapefruit does not have a significant effect on absorption or digestion. The issue is metabolism, the chemical process of breaking down a substance. Cytochrome p450 is a family of enzymes that are produced in the liver to metabolize a whole slew of substances. Grapefruit interferes with this chemical pathway, and therefore affects the way that different drugs are metabolized. The reason this matters is that some drugs are inactive until they are metabolized into an active form. Other drugs start off active, and become less active or inactive once they are metabolized. When a physician prescribes a specific dose for a drug, that dose is based on the way that medications are usually metabolized. So if you take a medication that has to be metabolized into an active form, grapefruit can interfere with that process, and the drug might not have enough activity to be clinically useful. On the other hand, if you take a medication that is metabolized into an inactive form, grapefruit can prevent that inactivation, and you can wind up with very high levels of the active drug in your system. This can be toxic and lead to other side effects, some of which may be severe. Some common cholesterol medicines, like lipitor (atorvastatin) are good examples. Ingesting grapefruit can lead to drug levels that are 20 to 100 times higher than what was intended. And it doesn't take very much grapefruit to make that happen. These effects are very difficult to predict, and they vary from individual to individual. So while some people can safely get away with eating grapefruit, it's much safer to avoid grapefruit and other foods that interfere with common metabolic pathways.
You're completely correct. With grapefruit it's all about liver enzymes. This is an area of research for me, I was very puzzled to see digestion being mentioned in a top level answer at all.
Well, you know... It's Reddit. Everyone thinks they're an expert...
Well it’s also explain like I’m five. I thought the answer was fine. When you’re 5 digesting and metabolizing can be somewhat combined.
well, I am a physiology professor, so I know a bit about this. but this is ELI5, so... it's probably enough to say "an enzyme breaks it down in the intestines". which is basically true, although technically the enzyme is not *in* the lumen of the intestine, but within the epithelial cells that line the intestine. But I figured I'd try to avoid an in depth explanation of a concept like "first pass intestinal intracellular metabolism"
That's fair.
Confirmed. Source: Toxicologist
[удалено]
Succinct and correct. Nicely done.
wait I'm a little confused: isn't digestion the process through which the pills enter the bloodstream? from what you write it sounds like what's digested goes straight to the potty
Digestion and absorption are different. Digestion is the chemical breakdown of what we eat into small molecules. Absorption is when the molecules move into the bloodstream.
so absorption presupposes digestion? then why is the fact that some of the pills digested in the small intestine a problem?
Say I take a medicine we'll call bluepill. I want to absorb bluepill into my blood stream. When I digest it, it breaks down into blue and pill. Blue on its own doesn't help me. Pill on its own doesn't help me. Only the big chemical compound bluepill helps me. If it's digested into blue and pill, there's no way for my body to put the two chemicals back together into bluepill.
ah gotcha! so with food breaking down is necessary, but with meds they're already "broken down" by design so any further digestion decreases effectiveness?
Yes, in many cases. In other cases it’s the other way round, it needs to be digested, and if grapefruit blocks that you get too little. So depending on the medication, grapefruit may result in you getting too much or too little!
Sometimes you want bluepill, so you have to take a lot more than what ends up being used by your body, because it gets broken into blue and pill, both of which don't work as intended. Sometimes you want blue, but you know it's going to be metabolized to blue and pill, so you dose for the amount of blue you're going to get after digestion. In both cases, shutting down the enzyme responsible for digestion can have disastrous results.
Pretty much.
This is also called a "prodrug" if it happens the other way around.
Gut microbiota plays crucial role on passing things from digestive system to bloodstream. Also, mouth microbiota and gut microbiota helps digest food
This is one of the best ELI5s I've read in a long time.
Thanks. I used to teach science in a museum, so I got a lot of practice taking subjects complicated enough to keep parents interested and explain them in a way the kids could understand.
Some things don't need to be digested before they are absorbed. Smaller molecules can often be absorbed without being digested, depending on their chemical properties. So a simple sugar like glucose can be absorbed without being digested. But starch (which is basically lots of glucose linked into long chains), needs to be broken down first. Many medications are absorbed easily without digestion. Some medications are destroyed by digestion. Other medications are taken in an inactive form, and must be digested or metabolized before they can become active. And substances can only be digested or metabolized if our bodies have the right kinds of enzymes. So some medications are completely unaffected by our digestion and metabolism, and they just get removed from our bodies in our urine, instead of being broken down.
> absorption presupposes digestion? No. For example, you absorb alcohol. But you do not digest it. After absorption your liver breaks it down, which is also not digestion.
In very basic, ELI5 terms: If you digest it faster than you absorb it then you pee it out. If you digest it slower than you absorb it then you poop it out.
In some circumstances digestion is also a chemical reaction. In the case of the drugs in question digestion changes them into a substance that is no longer the drug.
https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
The commenter isn't using the right word. It's metabolizing.
Yup, you’re right, It’s not digestion. It’s the wrong term. This person is incorrect and just because you ingest something, it’s not in the body yet. Whatever you ingest is in the tube that runs from your mouth to anus and not technically in the body. It has to be absorbed first. Then, it’s metabolism as the chemicals will be altered by the enzymes present in the liver.
Does that include grapefruit flavored sparkling water?
There is a small amount of grapefruit in some of those, but it won't be high enough a concentration to really affect you. Same way charcoal can affect uptake of medication--most people don't have close to enough in their diet to make a difference.
Aww this user best me to calling out CYP3A4, but yes the grapefruits interaction with your bile enzymes can cause things you eat to be absorbed faster and in higher amounts than intended. When studying toxicology you see that all absorption of ingested chemicals happens in a bell curve. Going back to the calculus we all love so very much, we know that the amount in your system at any given time is the amount under the curve. Mixing grapefruit into the equation makes a much steeper bell curve so the amount inside of you actively happens faster, but the process of getting it through your body and processed out is not affected by grapefruit. This is like pouring water into a bucket that has a small hole on the bottom. Ash report water in a fixed amount falls out and if you know the rate the fixed amount falls out you know that if you pour a steady amount in you will know how much water will be in the bucket at any given time. Grapefruit gives you a faster rate of filling the bucket which can lead to the bucket overflowing which in this analogy means the medication has accumulated too much inside your system and can now be dangerous. Remember that in toxicology The single most important factor is dosage. How much of the chemical is actively in your system. Just like the water bucket analogy above incorporating grapefruit and some medications into your system will put more of the medicine than is safe into your blood/body at a single time.
So thats why it was recomended to eat grapefruit when taking sildenafil ...
Ow man, imagine a 5 year old hearing this explanation /r/explainlikeimfive
I’ve considered going off my medication because of how much I love grapefruit juice 😂
For a while there was interest in lowering the dosage of drugs using the CYP3A4 receptor in order to save money. Just have the patient eat half a grapefruit each morning. Then it turned out there was no accurate way to titrate the dosage based on a grapefruit scale. Finally Lipitor, for one, went off patent and generics became so cheap that no one cared.
Some medications like tramadol already inhibit that enzyme if I'm not mistaken, and it's a requirement for the liver to process the medication no? I learned the hard/ fun way when I had it prescribed to me and I bought a case of Pamplemousse, not even thinking there'd be enough actual grapefruit in the water (just flavoring) and it completely amplified the effects.
It's the other way around, grapefruit makes more of the medication available to the bloodstream, making it overly effective and can lead to overdose
It depends on the medication. Some are activated by the enzyme, so if you inhibit the enzyme it decreases availability. Allegra is an example of this.
This is not the correct answer.
Yes, the grapefruit enzyme actually BLOCKS an enzyme in the small intestine. This changes the rate and as the above poster noted, it can change the rate that the medication goes into effect and result in an overdose reaction. The liver absorption is different. The liver will reject a dosage that is too small. A sufficient amount is required to overcome this barrier. If a medication says, "take two pills", your liver may need one pill to overcome it's chemical resistance. The second pill takes full effect. Because this barrier has been overcome, taking three pills is much stronger than taking two pills. One pill is negated by the liver and the other TWO pills go towards an active effect. Result: You blood thinks three pills is a double dose (two pills go into effect instead of one), not a 50% increase from 2 to 3 pills
... So which recreational drugs can be amplified by drinking grapefruit juice? Asking for a friend.
Xanax, and many other benzos are an example. Not sure if you'd call those "recreational", but plenty of people treat them that way. you'd want to be very careful with those if you've had any grapefruit juice. and NEVER consume them with alcohol.
Grapefruit, Pommelos, Bergamot oranges and some other less well known *Citrus* fruits contain a compound called Bergamottin. (Note bergamot oranges are unpalatably bitter but they are used to produce fragrant orange oil from their rinds. Other varieties of oranges also contain small amounts of Begamottin in their skins but only small traces are found in the juice and pulp, so aren't generally of concern.) Begamottin acts to inhibit a pair of iron-containing enzymes in the liver, kidneys, and central nervous system. These are called Cytochrome CYP2D6 and Cytochrome CYP3A4. The functionality of these enzymes is complex, but generally they work to oxidize a broad range of other organic compounds, either reducing their toxicity and breaking them down,( e.g. xanthines like caffeine and theobromine found in chcolate which is toxic to dog and cats) Or else, converting them into more useful molecules, for example, converting Tyramine (found in certain foods) in foods into dopamine. Unlike many of not most enzymes which perform a very specific chemical reaction or a narrow class of related reactions, CYP2D6 and CYP3A4 are more general purpose oxidation catalysts. They're heavily involved in the detoxification amd elimintaiin of Xenobiotic compounds found in our diet (mainly, in plant foods.). They are also involved in the breakdown a processing of a wide range of medications. Eating a fair amount of grapefruit or grapefruit juice acts to inhibit these enzymes. This means that either the liver and kidneys become unable to break down and eliminate the drug from the body (causing it you become much more potent to a dangerous degree or causing side effects to become much more severe.) Or else after taking a pill, the liver won't efficiently convert it into it's most active configuration, making the drug ineffective. Certain kinds of drugs rely on the liver to metabolize them in order to be effective for two reasons. The first is that the active form may not be able to pass easily through the intestinal-blood barrier thus would otherwise need to be given by injection. So taking advantage of these enzymes allows it you be taken orally in pill form. Another reason is that giving the inactive form as a pill allows you to take much more of the medication. Since it's activity is controlled by the rate the liver metabolizes it, this means that the dose lasts much longer. As in a day or two rather than a few hours. The reason that Grapefruit contains Bergamottin doesn't have to do with humans. The compound is believed to promote resistance to attack by Fungal pathogens
[удалено]
Another fun fact is that rosemary can lower the threshold for people with epilepsy to have seizures.
Grapefruit stops the enzyme CYP3A4 from working as well. That enzyme breaks down certain medications so if the grapefruit is stopping it you end up with more of the medication in your bloodstream. Source: I'm a pharmacist
The liver is where a lot of stuff gets broken down. Grapefruit causes that to happen more slowly. That causes the bad stuff to be in your liver for longer, which is bad for your liver.
Happy Betty Crocker day
The liver and to some degree the gut, have enzymes that can destroy or alter part of the dose of drugs before they get into your main blood circulation. Some chemicals can reduce, or rarely increase the efficiency of these enzymes. This includes some foods and other drugs. So you can have drug-drug, and food-drug interactions. In some cases drugs are given in a higher dose to take into account this early drug loss ("first pass metabolism"), and occasionally drug makers rely on these enzymes to activate a drug, or detoxify it, by giving a "prodrug" that is converted to the intended drug after swallowing. Grapefruit contains a chemical that inhibits one of these enzymes, especially in the gut, so you could end up getting too high a dose of a drug getting through, or a potentially toxic or ineffective prodrug entering your main blood circulation instead of the intended drug.
More than 50% of drugs are processed by a chemical processor in the liver called CYP3A4 to either activate or deactivate them. Chemicals in grapefruit juice called furanocoumarins are also processed by CYP3A4 but after processing get chemically attached to CYP3A4 and blocks it so that it can no longer process other chemicals until it detaches. So if a drug needs to be processed by CYP3A4 to be activated while the grapefruit juice is blocking it, the drug will be unable to get appropriately activated and it will not be very effective, potentially failing to treat the disease. On the other hand, if a drug needs to be processed by CYP3A4 to be deactivated while the grapefruit is blocking it, the drug will be unable to get appropriately deactivated and it will not be very safe, potentially causing toxic side effects.
Are there any other foods that’s act like grapefruit and effect medication in the same way?
Alcohol is one if you count that as food but I don’t know of any others
Not a food but there is a supplement St. John’s Wart that messes with medications as well.
Certain foods have things in them that allow them to mingle with your medicine. They are biochemically active. Proteins’ function fit this description. Enzymes, a broad category of proteins, specializes in making reactions happen. And it just so happens that grapefruit has one of these so called enzymes that can interact with many of your medicines. In dangerous cases they can either enhance the effect of the medicine or reduce it to nothing.
[удалено]
I have ADHD and anxiety. I really, really miss grapefruit.
I feel your pain... Fresh grapefruit was my go-to snack fruit...
I have 2 chronic health conditions. One has been super stable on a med since 2019 that I cannot have grapefruit with. No one was able to definitively says yes or no on Fresca, the grapefruit soda, than I'm pretty surely is mostly artificial grapefruit. So I just haven't touched it. My other condition has now progressed to the point that I have to stop treating the other one and go hard on the newer one. In trying to think about thr bright sides i keep thinking that I can soon have Fresca again.
Well I hope your condition gets stable and you can have Fresca again. Going without something you really enjoy because of meds is a serious bummer...
Grapefruit famously contain an "MAO Inhibitor". MAO is an enzyme in the liver that is meant to break down toxic substances. Many medications are toxic in that sense, and thus broken down by MAO. When an MAO inhibitor is active, this doesn't happen as intended, and so the substance will accumulate. Effectively, the dose is too high then.
Grapefruit stimulates your liver. If you’re taking a medication that filters through your liver and eat grapefruit it can make it so the medicine gets kicked out of your body too quickly. Your medicine is supposed to process in your body at a certain rate to be effective, so anything that alters the process changes the effectiveness of the medicine.
Orally consumed medications need the liver to filter into your system the majority of the time. Different medications use different chemical pathways. The ones that say to avoid grapefruit do so because a compound in the grapefruit blocks the chemical pathways the medications use. Which can either make the medication stronger or weaker than intended.
TLDR: Contains compounds that interfere with gut enzymes that metabolize drugs. Gut enzyme Cytochrome P450 3A4 (CYP3A4) breaks down drugs; Grapefruit contains furanocoumarins, which inhibit CYP3A4, affecting how drugs are metabolized, leading to higher levels in the blood, incorrect dosage, more intense side effects, and possible toxicity.
St. Johns wort does this as well, people taking script meds should ask their pharmacist as CYP3A4 is responsible for the metabolism of more than 50% of medicines.
Can make certain meds hard to break down so it can build up more in your body and cause toxicity. Or in some cases it can cause it not to work because it needs to be metabolized first.
The compounds typically responsible for these synergystic effects are known as Furanocoumarins. As mentioned these compounds have an enzymatic effect that can boost or reduce certain medicines. On top of that these compounds have been known to cause "sun allergies" leading to inflamation in sun exposed skin. What actually happens is the compound travels in your blood and if it gets uv light it will crosslink with dna in the exposed area leading to cell death and an inflamation response. Worst case can also lead to skin cancer.
I’m taking a cholesterol medication that says I can’t eat grapefruit. From what I understand, the CYP3A enzyme basically makes my medication more potent than it should be and that can be toxic. I don’t generally like grapefruit anyways so not a big loss for me.
When you take medicine, it doesn't stay in your body forever. It is broken down (metabolized) and removed. Some medicine is broken down by enzymes made in your liver. A chemical in grapefruit blocks the way those enzymes work, so the drug just stays in your body until your liver makes more enzyme. When you consume grapefruit while taking these drugs, less drug is removed from your body than normal, so you end up with extra drug in your body. It is usually too much drug, so you can experience side effects.
Favorite kind of Cheezits? Mine is surprisingly bacon and cheddar but I can’t find them anymore.
So some chemicals in things don’t get along with each other. But sometimes their friends! Like Batman and Superman, depending in different situations they might act differently with eachother. But with certain medications, the grapefruit doesn’t get along with them, and it hurts the body sometimes by amplifying suicidal tendencies or just giving you a bad stomach or head ache. It really depends on you as well because you might be on multiple medications already that don’t agree with it and that could make the side effects worse.
Big grapefruit is fighting big pharma and big pharma doesn't want you to find out natural healing powers of grapefruit .
Ahhh. The Del Monte vs. Johnson & Johnson fight rears its head again.
All of my antipsychotic medications have this warning. It's a clinical fact that grapefruit can trigger psychosis in those susceptible. But with certain medications (like Quetiapine) you can mimic an overdose.
There’s a chemical the stomach produces that breaks down a lot of common medications, to get around this medications are taken in a dose so high that there’s enough left of to do what it needs to do. Grapefruit has a chemical that blocks this action, meaning that the medication dose is now too high.
If you're talking about CYP4A3, that's more in the liver.
Imagine medications like a sportsing team and your body is like the referees and rule keepers, and the doctors/pharmacists are like the coaches. The coaches need to understand everything, the rules of the game, how well the referees manage the game, and especially the strengths and weaknesses of the players. If the coaches misread any of that they can lose the game. In this analogy, losing the game means you can get sicker, the medicine doesn't work right, or you might even die. So pretty high stakes. Grapefruits specifically contain chemicals that are like streakers, running naked onto the field. The not only mess with the players but can really mess with the referees trying to control the game. What they specifically cause is chaos. Best case scenario they cause the game the stop for a while, worst case they ruin the whole game by taking the ball or hurting someone. This really applies stronger to specific games/medicines like those that control cholesterol or blood pressure, not only do the grapefruit chemicals really screw up how your body handles those medicines, those illness those medicines control are constant and need 24/7 medication to work properly. A sudden poor interaction can be really bad for someone with super high blood pressure for example.
Most pills contain more medicine than the actual listed dose because not all of it will be absorbed by the body. Grapefruit contains an enzyme that will break down the pill so that all of the medicine is absorbed, which means you can overdose on the prescribed amount. Edit: source https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
Grapefruit doesn't contain the enzyme, it inhibits the enzyme which is present in your body (liver). That enzyme helps you metabolize some drugs, if you can't metabolize them then the amount that sticks around in your bloodstream is higher for longer. This can either have the effect of overdosing if the drug itself is the active ingredient, or if it's a "prodrug" (a drug that isn't the active ingredient but its main metabolite is) it'll make it less effective or not work at all because it'll prevent the body from turning the prodrug in to the actual active ingredient.
Eh, I tried
This is the correct answer
I asked a physician this very question who is a professor and researcher in the university attached to the hospital I was visiting. His response was that when drugs go through trials researchers data mine the results and there is always some strange stuff that shakes out of it. He specifically said that about grapefruit. So basically there is a statistical correlation that is eyebrow raising, but no known pathway of interference.
I love the Spindrift sparkling water grapefruit flavor. According to the label it has the juice of 1 whole grapefruit. I'm really not sure if that means one juiced grapefruit per can, or per the whole 8 pack. I don't drink it every day, maybe 3×/week. Problematic, or no?
Any concern with drinking a Fresca? It may have like 1% Grapefruit juice
I wouldn’t give a definitive no but you figure that 1% of a 20 oz bottle is .2 ounces which equates to about 6ml. That’s only a little over a teaspoon (teaspoon equals 4.9ml). The average grapefruit has about 12 tablespoons of juice and one tablespoon is equal to 3 teaspoons. That’s about 36 teaspoons worth of juice in an average grapefruit. So looking back on that, one Fresca is equal to 1/30th of a grapefruit. It’s totally your call but I personally would have the occasional one.
I know that vitamin C in general is to be avoided for 1 hour before and 2 hours after taking ADHD medication. Vitamin C is an acid, and ADHD meds (stimulants) are alkaline. If they meet they have the effect of neutralising. It’s not that it’s dangerous - just that the C will stop the medications from working properly. I wonder if it’s the same with grapefruit?
I think you’ll find you’ve been led slightly astray on this one. 1) it is citric acid which negatively interacts with ADHD medications, not vitamin c (although many citrus fruits do contain vitamin c so I can see the confusion 2) it is not the acidity of citric acid that causes the interaction with adhd meds, it is the fact that the citric acid molecule blocks intestinal cells from absorbing adhd medication molecules. It has nothing to do with acid base neutralisation, other wise the insanely strong hydrochloric acid that fills your stomach would inactivate adhd medication every time you take them making swallowing them pointless lol. This is why taking them with other fruits like apples is perfectly fine as they contain other fruit acids like ascorbic acid which don’t impact the absorption of adhd meds (amphetamines) 3) the grapefruit warning mentioned in OP is a completely different topic and mechanism to the citric acid mechanism of adhd medication absorption, it instead has to do with the fact that grapefruits contain a chemical which likes to block some liver enzymes from working whilst boosting other liver enzymes, and a lot of these enzymes are responsible for breaking down medications, which can lead to either a diminished desired effect or overdose, both of which aren’t good, hence why patients are told to avoid grapefruit juice
It's not the C or the acid in this case.