15 ms·

From its name to its drug interactions, there’s a lot going on with grapefruit

393 points by gilad 6y ago

BelleOfTheBall 6y ago
I had no idea that grapefruits had so much risk associated with them if you're taking medication. Most of the ones listed in the article are actually hugely popular, I wonder how many people took some innocent stuff like Tylenol and then drank some grapefruit juice and felt weird, without realizing what happened.
- 1_player 6y ago
  https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions#Incomplete_list_of_affected_drugs https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_intera... They interact with so many drugs, if you take any medication for chronic illnesses, chances are you should not eat any grapefruit for the rest of your life. Also whether a drug is affected by it or not is not clear, so the common advice is just to avoid the fruit whatever the drug you're taking. It's one of my favourite fruits, and not being able to eat it once in a while hurts. Though I'm not sure how _dangerous_ it really is. Does it affect the half-life of a drug by 5%, or by 100%?
  - dmurray 6y ago
    TFA says it increases the bioavailability of felodipine, the drug where the effect was first noticed, by about a factor of 5. For most prescription drugs for chronic illness, you probably do not want to find out what happens when you move to 5x the effective dose.
    - jychang 6y ago
      Depends on the dose and drug. 5x the dose of adderall is probably pretty fun.
      - mardifoufs 6y ago
        Adderall/Vyvanse/Amphetamines don't interact well at all with vitamin C, of which grapefruits are full of. So sadly enough, you don't get any 5x intake boost with the enjoyable meds. Would have been way too much fun ;)
        3np 6y ago
        Isn't the vit C thing just because of acidity? Combining with a teaspoon of NaHCO3 would cancel that out, no?
        sudoaza 6y ago
        But apparently the effect lasts up to 12 hours, vitamin c should be gone from the stomach by then. Grapefruit has been anecdotally recommended for MDMA (an amphetamine).
        mdmthrowaway 6y ago
        The reason it's recommended for MDMA is because it inhibits the CYP3A4 enzyme which metabolizes MDMA (3,4-Methylenedioxymethamphetamine) to MDA (3,4-Methylenedioxyamphetamine). MDA is more neurotoxic than MDMA which is why it's advised to reduce the amount your body intakes.
        cik2e 6y ago
        The majority of adderall breaks down through the urea cycle due to urine acidity. Enzymes don’t play as significant a role as they do for other drugs. That’s why baking soda is the best potentiator for amphetamines, as it neutralizes urine acidity.
        3np 6y ago
        For anyone considering actually doing this, beware that it needn't take much baking soda to be harmful. People have died from overdosing. Maybe someone with journal access can dig out dosage ranges from any of these many sources: https://scholar.google.com/scholar?q=related:4ssWhTcQeYEJ:scholar.google.com/&scioq=Homespun+Remedy,+Homespun+Toxicity:+Baking+Soda+Ingestion+for+Dyspepsia&hl=en&as_sdt=0,5 https://scholar.google.com/scholar?q=related:4ssWhTcQeYEJ:sc...
    - seamyb88 6y ago
      Even for "some innocent stuff like Tylenol", as the original comment puts it, you do not want to be taking 5x the dose. This is a very harmful drug in (not very) large quantities. I know of somebody whose boyfriend ended things with her, she took a load of tylenol to end her life, but the doctors managed to resuscitate her. When she came to, she said to her mother "I'm so glad I didn't kill myself over that bastard". A week later she died from liver failure.
      - nullc 6y ago
        Tylenol is most of the most deadly (in terms of effective dose vs harmful dose) of anything commonly used.
      - TheOtherHobbes 6y ago
        That's a standard thing with Tylenol/Paracetamol. You can recover from the initial overdose, but then the metabolites build up in your liver over the next few days and trash it beyond any hope of repair. At that point it's either a transplant or death. The scary thing is that it's incredibly easy to overdose by accident. For some people the lethal dose is less than twice the recommended dose, and if you're in a lot of pain - e.g. from a dental abscess - you can easily overdo it.
    - mark-r 6y ago
      I'm on a blood pressure drug. My pharmacy ran out of the dose I needed and substituted a 2x size, with instructions to cut the pill in half. I ended up forgetting about the substitution and took the 2x dose daily for a couple of months. Didn't find out until I went to renew the prescription and was told I was trying to refill it too early. Suddenly the recent dizzy spells I had were easily explained.
  - hinkley 6y ago
    I think I knew about interactions with benzos, but didn’t know about Tylenol, Aleve, caffeine (!?) or protease inhibitors.
  - deleted 6y ago
    [deleted]
- mikestew 6y ago
  innocent stuff like Tylenol On a pedantic note, acetaminophen should not be considered innocent, but rather considered to be something very easy to get too much of because it’s in friggin’ everything. Cough syrup, Tylenol, many opioids that your doctor might prescribe. Read those labels, because if you take some Tylenol for those aches and pains and wash it down with some cough syrup for that cold, your liver might want to have a word with you.
  - mark-r 6y ago
    Acetaminophen is added to opiates to make sure there are bad side effects if you take too much.
    - et2o 6y ago
      That's not why. Acetaminophen is highly hepatoxic but it's only very delayed. It's added because they have a synergistic effect on pain relief.
      - unethical_ban 6y ago
        I'm not suggesting the parent comment is correct, but I think they are implying that medicines are "spiked" with a chemical in order to deter recreational use, lest someone injure themselves.
  - et2o 6y ago
    Agree! Acetaminophen is very dangerous in overdose. I've seen lots of 20 year olds who get liver transplants after they OD (intentionally) on Tylenol. If they had taken Motrin instead they'd have been fine.
  - TT3351 6y ago
    I have a close family member who works in pharma who regularly tells me there is no way the FDA would approve Tylenol over the counter if it was invented today.
pattusk 6y ago
I remember many years ago when I first moved to Asia, people looked at me wide-eyed whenever I took medicine with orange juice or a can of soda. I dismissed it as some urban legend on the level of the fan-death [1] until a doctor explained to me the adverse interactions of citrus fruits on all sorts of medicine. I have been taking my medicine diligently with water ever since, but it still amazes me how incredibly different the distribution of such common and potentially life-saving medical knowledge can be across countries and cultures. [1] https://en.wikipedia.org/wiki/Fan_death https://en.wikipedia.org/wiki/Fan_death
- strogonoff 6y ago
  Being a little pedantic, the drug interactions part of the article applies to bitter citrus specifically: not just grapefruit (despite the title!), but not all citrus either. Typically “orange” is used to refer to sweet oranges, not sour oranges. As to soda, I struggle to imagine a soda that has any amount of juice worth taking into account…
  - simonh 6y ago
    Sodas often contain significant amounts of ciric or phosphoric acid.
    - deleted 6y ago
      [deleted]
    - thw0rted 6y ago
      Per the article, the drug-interaction problem comes from furanocoumarins depleting your cytochrome P450. There's nothing in there to suggest that refined acid (as opposed to unprocessed juice) would include furanocoumarins.
      - mlyle 6y ago
        Indeed, "citric" acid produced today comes from mold cultures that A) don't produce significant quantities of FCs, and B) even remove FCs from their environment by adsorption.
dmurray 6y ago
My grandfather used to eat grapefruit every day, but had to give it up when he was prescribed Warfarin (a blood thinner). Ironically it seems that it would have been just fine for him to continue so long as he stuck to religiously eating grapefruit every day. He would have needed a substantially lower dose of the drug, but Warfarin is one where you adjust the dose a lot for each patient anyway: the manufacturer recommends starting with 6mg and ending up anywhere from 0.5 to 10mg depending on the patient's response [0]. He was also hospitalised several times, both for his heart problems and stomach cancer. I wonder if hospitals keep grapefruit on hand for patients like this, or if they ban it altogether. [0] https://www.nps.org.au/australian-prescriber/articles/how-to-manage-warfarin-therapy https://www.nps.org.au/australian-prescriber/articles/how-to...
- jalk 6y ago
  > the manufacturer recommends starting with 6mg and ending up anywhere from 0.5 to 10mg depending on the patient's response I tried to explain binary search to my gp when she was trying to find my dose of thyroxin. Unfortunately, according to her, a too high does carries a lot of unpleasant side effects - so linear search it was.
  - vikramkr 6y ago
    Yeah, binary search where you don't know what the upper bound is with a narrow therapeutic index drug is not necessarily the best option
  - buddhiajuke 6y ago
    We pretty much did binary search to find my lithium levels. The lethal concentration of lithium is very close to the therapeutic range, but we couldn’t afford to spend long on low doses (since you have to take blood tests to assess effective dosages.)
    - krageon 6y ago
      If you keep a good diary you can limit the blood tests to 1-2 times per year and assess therapeutic effect using self-reporting.
ricksunny 6y ago
The drug-discovery venture I lead goes into some detail on grapefruit, hesperidin, and naringin in context of drug interactions at the end of this article in Medium’s An Idea publication (just scroll to the graphic from the FDA): https://medium.com/an-idea/enter-flavonoids-f42662810c11 https://medium.com/an-idea/enter-flavonoids-f42662810c11 Conventionally was thought that the main culprit was bergamotin; but subsequent research showed that naringin (citrus in general but grapefruit especially) and hesperidin (citrus in general - orange, lime, lemon) have their own important interactions with drug-metabolizing enzymes.
- ricksunny 6y ago
  [Here is a link straight to the academic paper on naringin / hesperidin on the human OATP1A2 human medicine-processing enzyme (so you can skip having to find the link in the above Medium article): https://pubmed.ncbi.nlm.nih.gov/17301733/ https://pubmed.ncbi.nlm.nih.gov/17301733/ ] Flavonoids are a unique class of plant-derived compounds; They can bind a lot of things - in some cases that's bad according to some med chemists, and some cases its good according to other med chemists . . .
np_tedious 6y ago
What an interesting article. I am now very curious to try the mother fruits pomelo and citron. Based on the description here, grapefruits potentiate drugs by reducing the effects of a digestive system enzyme that would otherwise destroy much of the drug. Does this mean that it only has impact when drugs are taken orally?
- cik 6y ago
  Pomelos are great, assuming you get one that has some sweetness to it. This can very much depend on your geography, as pomelos where I am are significantly more sour than they were in North America. Citrons are just gross.
  - pvaldes 6y ago
    Pomelo is sweet and acid, grapefruit is acid and not so sweet. On the other hand, Citron is one of the best for to make candied citrus.
- 317070 6y ago
  Pomelo has been my discovery of 2020 (pre-covid). They are the ideal fruit to eat while watching a movie in the evening. They are a lot of work as you need to peel through all three layers. Yet, you don't get dirty, and every now and again you get to eat a bit and it tastes like more. Oranges and mandarins tend to get you dirty, and would still cause me to overeat.
  - hinkley 6y ago
    Mandarins are a crapshoot. Sometimes you come away clean, especially if you are willing to bite the peel to start the peeling process. Whether the wedges remain intact or not is the wildcard.
    - pvaldes 6y ago
      That depends on the type of mandarin You can have clementines, satsumas, tangors and tangerines (plus a few strange complex hybrids). Some have adherent skins that can be messy to peel, the skins in other are extra easy to remove. Clementines are more sweet, tangors are more acidic so are still much appreciated. It depends on the group and cultivar
jariel 6y ago
That 1 glass of grapefruit 10x the potency of Tylenol is shocking, but even more so, how we don't seem to have a reasonable system of 'public awareness' for these things. We 'make discoveries' and then just hope it wades through the network of doctors, pharmacists. Much like with COVID 'communications' it's kind of a disaster. There's nowhere for me to simply find out 'the latest official information' for my province/country in a reasonable and coherent way - a lot of web sites flush with tons of secondary, bureaucratic information, whereas there should be a 'single web page' with the current 'highly relevant information' and another 'single page' to visit with precautions and up-to-date instructions if you're symptomatic. Details on the side. Like the ostensible annual visit to the doctor, I wonder if each healthcare system should put out it's annual list of 'key information' in something easily digestible, written for those with Grade 10 reading ability because that's the lowest common denominator and frankly the intellectual level we're all at when not focusing. So thanks (I guess?) HN! No more grapefruit juice when I'm sick or having a headache with the ... Tylenol. Hey zeus. Hw is that not on the label ...
- gdrift 6y ago
  For the most up to date COVID information there's this from WHO: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public https://www.who.int/emergencies/diseases/novel-coronavirus-2... > These materials are regularly updated based on new scientific findings as the epidemic evolves. Last updated 5 October 2020.
forinti 6y ago
I already have to deal with citrus names in different languages: pomelo in Spanish, toranja in Portuguese , grapefruit in English . This article added a bit to the confusion: pomelo comes from grapefruit?
- simtel20 6y ago
  From prior reading I've done, grapefruit was cultivated by crossing pomelo with smaller, more bitter citrus. Here, the wikipedia says it was with a sweet orange [1] 1. https://en.wikipedia.org/wiki/Grapefruit https://en.wikipedia.org/wiki/Grapefruit
  - pauloya 6y ago
    The article actually explains this quite well.
- dzudndlf 6y ago
  Although “pomelo” in Spanish translates (typically) to “grapefruit”, “pomelo” in English refers to another fruit, that is like a grapefruit. Turns out English is surprisingly rich when it comes to describing citrus. The citrus family hybridizes very easily, so every planted seed will give you a “new species” with a unique cultivar. English appears to have assigned more unique names to citrus than the other two languages I know (Italian and Spanish)
  - mcv 6y ago
    Citrus names across languages are a mess. For example, citron is the English name for one of the base fruits, which after several hibridisation steps with other fruits results in the lemon. Dutch name for lemon? Citroen. In French it's citron. The French word for the English citron is cédrat. Sukade in Dutch. The Dutch for pomelo is pompelmoes, while the pomelo is a hybrid between the pompelmoes and the grapefruit, and is called shaddock in English according to the Dutch Wikipedia.
    - jdmichal 6y ago
mpettitt 6y ago
It's definitely on the label of my daily medication (in the UK), but it was interesting to see how the interaction seems to be fairly specific to grapefruit. Do either of the ancestor species have a similar effect? I do wonder if there are other dietary/medication interactions that we simply haven't spotted, but which could allow for lower doses of medication (potentially with fewer side effects, if the effect was on one active component) or simply avoid some side effects altogether.
- thw0rted 6y ago
  From the article: > This interaction, by the way, seems to affect all of the bitter citruses—the ones that inherited the telltale tang from the pomelo. Sour orange. Lime, too. But it’s unlikely that anyone would drink enough sour orange or lime juice to have this effect, given how sour it is. Grapefruit, on the other hand, is far more palatable in large doses.
  - hinkley 6y ago
    I wonder what the concentrations are in bottled lime juice, which is easier to consume than fresh lime.
thw0rted 6y ago
I've seen similar warnings about grapefruit before, but the article is the first time I've seen the specific mechanism discussed in this kind of depth. It's also the first time I've seen mention that all "bitter citrus" includes the problematic compounds, including lime and "sour orange" (is that the same as blood orange?). At least for me, it would be better if the headlines would cover this as the broader "bitter citrus", instead of grapefruit specifically. I can't stand grapefruit, so I never paid much attention to the warnings, but I love lime and blood orange, which means further investigation is warranted. TFA says it's "unlikely" anyone would consume enough lime to have an effect, but how much is "enough"?
- pvaldes 6y ago
  > "sour orange" (is that the same as blood orange?). Not. Sour orange is Citrus x aurantium whereas blood oranges are a type of cultivars of the common orange Citrus x sinensis sharing a red mutation. Both are hybrids but have different ancestors. Sour is inedible in fresh and must be processed, whereas the blood group are small but deliciously acid.
  - smcameron 6y ago
    Sour orange pie is a thing though (tastes much like key lime pie).
  - bserge 6y ago
    Citrus aurantium are used as a source of synephrine, a stimulant similar to ephedrine, which also interacts with various medication. According to OPs article, grapefruit works in a different way. This article also mentions grapefruit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655712/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655712/
- jrs235 6y ago
  FWIW, I don't think "sour orange" referred to blood orange. I believe it refers to Bitter Orange/Seville Orange: https://en.m.wikipedia.org/wiki/Bitter_orange https://en.m.wikipedia.org/wiki/Bitter_orange I think blood oranges are sweet.
sohkamyung 6y ago
For those interested in a infographic on the chemistry of grapefruit, see [1] [1] https://www.compoundchem.com/2014/03/07/why-does-grapefruit-interact-with-drugs-the-chemistry-of-a-grapefruit/ https://www.compoundchem.com/2014/03/07/why-does-grapefruit-...
mafumeira 6y ago
To learn more about how much grapefruit really impacts your detoxification checkout www.nutrahacker.com
mafumeira 6y ago
For a genetic investigation into how grapefruit impacts your detoxification processing checkout https://www.nutrahacker.com https://www.nutrahacker.com
headShrinker 6y ago
> “But Zoloft, Viagra, Adderall, and others do not. “Currently, there is not enough clinical evidence to require Zoloft, Viagra, or Adderall to have a grapefruit juice interaction listed on the drug label,” wrote an FDA representative in an email.” There is some pretty good research on the effects of grapefruit with viagra bioavailability. https://pubmed.ncbi.nlm.nih.gov/11823754/ https://pubmed.ncbi.nlm.nih.gov/11823754/ > “Grapefruit juice changed the area under the sildenafil plasma concentration-time curve from time zero to infinity [AUC(0-infinity) from 620 [1.53] ng/ml x h to 761 [1.58] ng/ml x h (geometric mean with geometric standard deviation), corresponding to a 23% increase (90% confidence interval, 13%-33%).”
- hinkley 6y ago
  I wonder if anyone is asking the “longer than four hours” crowd about food intake...
- Nvuti 6y ago
  Nvuti - https://nvuti.games https://nvuti.games
mcv 6y ago
Instead of labeling drugs "do not take with grapefruit", how about using a different dosage for when you take it with grapefruit? Having more of the drug survive the stomach could be a good thing. Or is that too unpredictable? More unpredictable than the effect of medication already is, I mean.
- xattt 6y ago
  People would eat variable amounts of grapefruit and might not eat it every day. Medications also have the potential to become toxic and have other effects other than the therapeutic effect. Can you imagine trying to explain this concept to an elderly family member? A blanket statement is easier to comprehend for the general population. People DO take insulin where the med is adjusted based on the blood sugar, but this is often accompanied with diabetic education component that takes weeks to complete.
  - hinkley 6y ago
    I have wondered though why no time release formulations increase longevity by including a small amount of the active ingredient of grapefruit. Likely due to the other interactions besides metabolism, like cardiac function.
    - xattt 6y ago
      Some antibiotics DO have adjuvants that prolong excretion. Examples are probenecid that was added to penicillin formulations to ensure there was enough supply. Imipenem (another antibiotic) is given with cilastin to reduce clearing of the drug by the kidney. Patients get into trouble when their renal clearance is already poor from long-standing kidney disease, so the potential is there for the drug to build to a level where it exhibits effects beyond its therapeutic intent (ie toxicity).
  - Talanes 6y ago
    The diabetes case is also most commonly accomplished with constant rapid testing. I don't think anybody loves grapefruit enough to bleed for it.
timbit42 6y ago
CBD causes the same problems with drugs as grapefruit.
- GotAnyMegadeth 6y ago
  Do people eat that?
  - ddingus 6y ago
    I see CBD edibles, oils, candies, etc... here in Oregon.
  - phjesusthatguy3 6y ago
    People ingest it, yes. my father-in-law preferred the effects of CBD over his hallucination medication, but couldn't take it because it interacted badly with his blood-pressure medication. He got some sort of mesh (sorry can't remember what) implanted which eliminated the use of his BP meds, and now he can replace his hallucination meds with CBD. He's in his late 70s, and lived hard (enjoyed every minute of it, but still).
- sertsa 6y ago
  Would definitely like to hear more about this. Citations?
MisterTea 6y ago
So uh, does this have any effect on THC uptake from cannabis edibles? Asking for a friend...
- shawnz 6y ago
  Yes, THC is also metabolized by the CYP3A4 enzyme that grapefruit inhibits
  - thelazydogsback 6y ago
    So, to be clear, you are saying that in this case the grapefruit would increase or decease the effect of the THC? In other words, to increase the effect of the cannabis, is it metabolites that we want to maximze, or the amount of unmetabolized free THC?
    - shawnz 6y ago
      Yes, grapefruit would increase the effect, and you want to maximize the unmetabolized THC. (although the first metabolite 11-OH-THC is also active, the next metabolite THC-COOH isnt)
- deleted 6y ago
  [deleted]
- hombre_fatal 6y ago
  I once took too much acid and the hour I spent in the peak was too strong and took a lot out of me. By the time it passed, I felt ravenous hunger for the massive grapefruit I had in the fridge. About halfway through eating through it's succulent splendor, I had to set the fruit aside and lay down because I felt like I was peaking again.
  - ak39 6y ago
    Forgive me, I pictured your experience and it made me laugh. :-D
  - 6y ago
throwgrapefruit 6y ago
https://www.scirp.org/journal/PaperInformation.aspx?PaperID=63660 https://www.scirp.org/journal/PaperInformation.aspx?PaperID=... I believe there are low FC varieties in development, and already extant. TBH if you're taking statins, you should really reconsider - those things are terrible for you like the underlying symptoms you're trying to treat. Maybe just not eat like a hog?
dr_dshiv 6y ago
In college, I used to always order cocktails with grapefruit juice in the hope that I'd get more drunk for my money. Was I only benefiting from the placebo effect? Does grapefruit affect alcohol metabolism?
- ros86 6y ago
  I don't think so, as alcohol is not degraded via P450 enzymes..
mkj 6y ago
This paper has some interesting reading on where the various citrus varieties evolved from Genomics of the origin and evolution of Citrus https://www.nature.com/articles/nature25447/ https://www.nature.com/articles/nature25447/ (Open Access)
chiefalchemist 6y ago
Does grapefruit's affect have anything to do with gut bacteria? That is, (good) bacteria plays a key role in digestion. Does this factor in anywhere?
surround 6y ago
I’m wondering, why not take advantage of this and add the grapefruit furanocoumarins to drugs to make smaller doses more effective?
- ricksunny 6y ago
  It would be worth big pharma looking further into. I fear however they'll identify that blood serum levels of an ingested drug are variable enough as it is due to the uniqueness of humans, that actively modulating humans ability to process exogenous chemicals is a recipe for disaster. Maybe they'll even get it close to right for Drug A, but what about Drug B that any given patient is concomitantly taking?
- chorsestudios 6y ago
  People often take multiple prescription medications, doing this might complicate things. The cytochrome P450 enzymes help metabolize a very wide range of compounds.
- cowboysauce 6y ago
  Because it would increase the number of medications that interact with each other. E.g. you're taking medications A and B, but now A and B come with the potentiating compounds in the pills. So taking both of them could be dangerous. You to go to the hospital and they need to give you C, but it would be dangerous because of the potentiator. It would also make medication management more difficult as people have to remember if they're taking the potentiated drug or not.
austincheney 6y ago
What the article does not mention is the connection of bitter taste to one of the two separate chemicals causing the drug interaction. It is a flavonoid called Naringenin. https://en.wikipedia.org/wiki/Naringenin https://en.wikipedia.org/wiki/Naringenin On its own the chemical is tasteless but in grapefruit in connection with other chemicals common to a variety of fruits, the derived glycoside Naringin, becomes the principle compound providing the bitterness. The chemical is present in many fruits including fruits that typically considered bitter, but it makes grapefruit noticeably more bitter due to its higher concentration there. Perhaps humans are sensitive to the flavor due to the potentially toxic nature. Strangely enough Naringenin is considered a toxin due to its interaction with human biochemistry but is not directly toxic. It allows increased sensitivity to other toxins. Though, to be fair, some drugs and nutrients are formulated in the GI tract due to microbial activity whose drug interaction and absorption can be directly modified by presence of this chemical. https://en.wikipedia.org/wiki/Naringin#Toxicity https://en.wikipedia.org/wiki/Naringin#Toxicity The link above indicates Naringin is a chemical isolate apart from 6',7'-Dihydroxybergamottin, the primary interacting furanocoumarin, and both independently suppress the P450 enzyme CYP3A4. https://en.wikipedia.org/wiki/6%27,7%27-Dihydroxybergamottin https://en.wikipedia.org/wiki/6%27,7%27-Dihydroxybergamottin
- dundarious 6y ago
  The article does mention other bitter fruits (descendants of pomelo) do share the “grapefruit effect”, but that you are less likely to consume large quantities of lemon juice, for example, compared with grapefruit juice. The extra information you provide is really interesting.
drewg123 6y ago
The article says that grapefruit wipes out cytochrome P450s for up to 12 hours. Lets say I'm taking a medication which is impacted by this. If I were to take my meds and then have a grapefruit 12 hours later, would it impact the dosage of the medication?
- WhompingWindows 6y ago
  Probably not. If the grapefruit is coming into your system 12 hours after the drug, the drug's already been processed by the P450 system. I think the odd coincidence here is that grapefruit is a "breakfast food" and thus people take it with their morning meds.
BFatts 6y ago
The first thing that struck me was "what about drugs that have little-to-no bioavailability after being ingested?" Would it make it possible to give drugs that are rejected for other reasons?
graeme 6y ago
Would grapefruit affect supplements as well?
MrYellowP 6y ago
Oh wow, my time to shine! Grapefruit juice combined with Vitamin D drops caused me a lasting headache, which, in hindsight, was like a sinus infection without the sinus infection part, but including the typically incredibly stiff neck. Lasting here means a whole month. One month of continuous headache. Not headaches. One gigantic headache. Mostly 7/10, two times 9/10, at which points we called the ambulance because I couldn't take it anymore. Don't ever mix grapefruit juice with anything.
- justusthane 6y ago
  That’s fascinating. Do you mean that you mixed vitamin D with grapefruit juice once and got a headache that lasted a month? Or were you continuing to drink grapefruit juice and take D during that month? How much vitamin D were you taking? How much time was there between taking vitamin D and drinking grapefruit juice?
  - MrYellowP 6y ago
    I had a grapefruit-juice phase (those only lasted days) and drank pretty much nothing else. I took the vitamin D for reasons I forgot. There was no time in between taking it and drinking the juice. It was what I drank most of the day. One can take a few of these drops (liquid, in case that's unclear) every day, but that makes my stomach gas up massively for some reason. One can take them once a week, too, but then he had to take the whole weekly dosage at once. Apparently it doesn't matter. I don't remember how much it was, but I'm talking about one or two dozen water droplets here. I'm sorry, I don't know how to express this any better. The headache started maybe two hours later.
    - justusthane 6y ago
      If I'm understanding you correctly, there was a period of a few days where you were both drinking grapefruit juice and taking vitamin D, and your headache lasted for a month afterwards?
      - 6y ago
dfalzone 6y ago
I wonder if this is at all related to the common pairing of citrus fruits with psychedelic drugs. A lot of people recommend eating an orange or drinking orange juice when you take LSD, and a lot of people recommend using lemons to enhance psilocybin mushroom trips. Maybe grapefruit would pair even better with these drugs.
- cyberbanjo 6y ago
  Grapefruit juice also has drug interactions with opiates and (I think) anti depressants, amongst other things.
- cowboysauce 6y ago
  The lemon-tek method of consuming psilocybin mushrooms isn’t related to this. Acidic conditions speed up the conversion of psilocybin into psilocin. This normally happens in your stomach, the lemon-tek method just does externally. This causes the overall experience to be shorter, but more intense. Psilocin also doesn’t appear to be metabolized by the enzymes that grapefruit inhibits.
  - SirLuxuryYacht 6y ago
    source?
    - cowboysauce 6y ago
      The wikipedia article for Psilocybin has all of the above. >Psilocybin [...] is a prodrug that is converted into [...] psilocin [...] This chemical reaction takes place under strongly acidic conditions And for metabolism >Psilocin is broken down by the enzyme monoamine oxidase [...] Some psilocin is not broken down by enzymes and instead forms a glucuronide [...] Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine
- TT3351 6y ago
  Certainly reminds me of the Kool Aid in "Electric Kool Aid Acid Test"
refresher 6y ago
Any relation between furanocoumarins and coumarins? The latter is in cinnamon which I’ve read lately can be quite hazardous depending on the ingested amount.
- ncmncm 6y ago
  It's hard to eat enough cinnamon to affect most people, but some are extra-sensitive to it. Apparently there is a lot less in the stuff labeled cinnamon and sold to Americans, which is actually not cinnamon at all, but cassia, a whole other species. The difference was understood in Europe in ancient times, so there is no excuse. Sometimes you can find the real stuff in the US labeled "Ceylon cinnamon". It's a darker red than cassia, which is unapologetically brown. Real cinnamon tastes more like red cinnamon candy than cassia does. Americans are always mystified as to why cinnamon candy doesn't taste anything like the cinnamon they put in their pies.
ncmncm 6y ago
The article doesn't say it, but there are some drugs that need processing, by the cytochrome P450 or the CYP3A4 pathway that grapefruit knocks out, in order to become active. Those drugs will lose their effect. Also, the same process may be part of the pathway that removes the precursor chemicals from the bloodstream, so those build up, potentially to toxic levels; you get the overdose without even the dose. Once, in Switzerland, I found a Lindt chocolate bar with dried grapefruit in it. I have never been able to find another. I wonder now if there are regulations about grapefruit ingredients in some countries. But I really love grapefruit. Haribo makes yellow and pink grapefruit gummi candy that is getting hard to find. I would really like to know if they have fouranocoumarins in them, but don't know of any way to find out.
- Lambdanaut 6y ago
  A web search turns up quite a few results for those lindt chocolate bars with grapefruit.
- copperx 6y ago
  To find that out you could buy a gas chromatography machine, but I'm not sure if they sell home appliance versions of the equipment.
SubiculumCode 6y ago
Seems like individual differences in bioavailability of drugs is a big problem in drug effectiveness. It seems that a procedure in which the amount getting to the bloodstream is measured, then adjusted (either by dosage increase, or bu supplementation with grapefruti) would be effective.
exabrial 6y ago
Why do I keep getting forwarded to a Norton Antivirus page?
dwighttk 6y ago
> The United States produces more grapefruit than any other country, from Florida and now California as well (and elsewhere, though in smaller quantities). Just a fwiw: Texas produces more Grapefruit than Florida or California. At least the past two seasons. https://www.nass.usda.gov/Statistics_by_State/Florida/Publications/Citrus/Citrus_Forecast/2019-20/cit0720.pdf https://www.nass.usda.gov/Statistics_by_State/Florida/Public...
GloriousKoji 6y ago
If grapefruit causes the bio availability of a drug 10x stronger, it makes sense to be to prescribe 1/10* the amount of a drug with a shot of grapefruit juice. Seems like a good way to make drugs more economical. * I'm assuming the active ingredient in drug is in the 10mg+ range. The way to get the accuracy needed from 1mg to 100ug sounds nontrivial to me.
- Taek 6y ago
  For most drugs the economics aren't about the cost of producing the chemicals but all of the R&D behind the companies. Whether it's 10mg or 1000mg I don't think it's typically a material part of the cost.
  - heavenlyblue 6y ago
    Why would a patient or doctor care about that?
    - pvaldes 6y ago
      Pills have more things than the active compound. Taking less may reduce any hypothetical secondary collateral effects from those substances, so it could be useful to explore it at least. On the other hand, taking just a tenth part of a pill would be not easy to measure. Specially if you need to take the pills often. Sometimes you would take 1/10, other 3/10 or 1/20. That could be a recipe for problems.
      - heavenlyblue 6y ago
        Ok, I agree with the first paragraph (it’s a point I did not think about). The second point is a weak one as you must be quite special to consciously decide on changing the prescribed dose of the pill without buying scales to measure the dose (although I agree these costs quite a lot).
chordalkeyboard 6y ago
Did anyone else get hostile redirects when they went to this site? I did.
TT3351 6y ago
In times of rationing, it was apparently not uncommon for grapefruit eaters to substitute added salt for the usual sugar to take some of the bitterness off.

393 points by gilad 6y ago

I had no idea that grapefruits had so much risk associated with them if you're taking medication. Most of the ones listed in the article are actually hugely popular, I wonder how many people took some innocent stuff like Tylenol and then drank some grapefruit juice and felt weird, without realizing what happened.

1_player 6y ago
https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions#Incomplete_list_of_affected_drugs https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_intera... They interact with so many drugs, if you take any medication for chronic illnesses, chances are you should not eat any grapefruit for the rest of your life. Also whether a drug is affected by it or not is not clear, so the common advice is just to avoid the fruit whatever the drug you're taking. It's one of my favourite fruits, and not being able to eat it once in a while hurts. Though I'm not sure how _dangerous_ it really is. Does it affect the half-life of a drug by 5%, or by 100%?
- dmurray 6y ago
  TFA says it increases the bioavailability of felodipine, the drug where the effect was first noticed, by about a factor of 5. For most prescription drugs for chronic illness, you probably do not want to find out what happens when you move to 5x the effective dose.
  - jychang 6y ago
    Depends on the dose and drug. 5x the dose of adderall is probably pretty fun.
    - mardifoufs 6y ago
      Adderall/Vyvanse/Amphetamines don't interact well at all with vitamin C, of which grapefruits are full of. So sadly enough, you don't get any 5x intake boost with the enjoyable meds. Would have been way too much fun ;)
      - 3np 6y ago
        Isn't the vit C thing just because of acidity? Combining with a teaspoon of NaHCO3 would cancel that out, no?
      - sudoaza 6y ago
        But apparently the effect lasts up to 12 hours, vitamin c should be gone from the stomach by then. Grapefruit has been anecdotally recommended for MDMA (an amphetamine).
        mdmthrowaway 6y ago
        The reason it's recommended for MDMA is because it inhibits the CYP3A4 enzyme which metabolizes MDMA (3,4-Methylenedioxymethamphetamine) to MDA (3,4-Methylenedioxyamphetamine). MDA is more neurotoxic than MDMA which is why it's advised to reduce the amount your body intakes.
      - cik2e 6y ago
        The majority of adderall breaks down through the urea cycle due to urine acidity. Enzymes don’t play as significant a role as they do for other drugs. That’s why baking soda is the best potentiator for amphetamines, as it neutralizes urine acidity.
        3np 6y ago
        For anyone considering actually doing this, beware that it needn't take much baking soda to be harmful. People have died from overdosing. Maybe someone with journal access can dig out dosage ranges from any of these many sources: https://scholar.google.com/scholar?q=related:4ssWhTcQeYEJ:scholar.google.com/&scioq=Homespun+Remedy,+Homespun+Toxicity:+Baking+Soda+Ingestion+for+Dyspepsia&hl=en&as_sdt=0,5 https://scholar.google.com/scholar?q=related:4ssWhTcQeYEJ:sc...
  - seamyb88 6y ago
    Even for "some innocent stuff like Tylenol", as the original comment puts it, you do not want to be taking 5x the dose. This is a very harmful drug in (not very) large quantities. I know of somebody whose boyfriend ended things with her, she took a load of tylenol to end her life, but the doctors managed to resuscitate her. When she came to, she said to her mother "I'm so glad I didn't kill myself over that bastard". A week later she died from liver failure.
    - nullc 6y ago
      Tylenol is most of the most deadly (in terms of effective dose vs harmful dose) of anything commonly used.
    - TheOtherHobbes 6y ago
      That's a standard thing with Tylenol/Paracetamol. You can recover from the initial overdose, but then the metabolites build up in your liver over the next few days and trash it beyond any hope of repair. At that point it's either a transplant or death. The scary thing is that it's incredibly easy to overdose by accident. For some people the lethal dose is less than twice the recommended dose, and if you're in a lot of pain - e.g. from a dental abscess - you can easily overdo it.
  - mark-r 6y ago
    I'm on a blood pressure drug. My pharmacy ran out of the dose I needed and substituted a 2x size, with instructions to cut the pill in half. I ended up forgetting about the substitution and took the 2x dose daily for a couple of months. Didn't find out until I went to renew the prescription and was told I was trying to refill it too early. Suddenly the recent dizzy spells I had were easily explained.
- hinkley 6y ago
  I think I knew about interactions with benzos, but didn’t know about Tylenol, Aleve, caffeine (!?) or protease inhibitors.
- deleted 6y ago
  [deleted]
mikestew 6y ago
innocent stuff like Tylenol On a pedantic note, acetaminophen should not be considered innocent, but rather considered to be something very easy to get too much of because it’s in friggin’ everything. Cough syrup, Tylenol, many opioids that your doctor might prescribe. Read those labels, because if you take some Tylenol for those aches and pains and wash it down with some cough syrup for that cold, your liver might want to have a word with you.
- mark-r 6y ago
  Acetaminophen is added to opiates to make sure there are bad side effects if you take too much.
  - et2o 6y ago
    That's not why. Acetaminophen is highly hepatoxic but it's only very delayed. It's added because they have a synergistic effect on pain relief.
    - unethical_ban 6y ago
      I'm not suggesting the parent comment is correct, but I think they are implying that medicines are "spiked" with a chemical in order to deter recreational use, lest someone injure themselves.
- et2o 6y ago
  Agree! Acetaminophen is very dangerous in overdose. I've seen lots of 20 year olds who get liver transplants after they OD (intentionally) on Tylenol. If they had taken Motrin instead they'd have been fine.
- TT3351 6y ago
  I have a close family member who works in pharma who regularly tells me there is no way the FDA would approve Tylenol over the counter if it was invented today.

pattusk 6y ago

I remember many years ago when I first moved to Asia, people looked at me wide-eyed whenever I took medicine with orange juice or a can of soda. I dismissed it as some urban legend on the level of the fan-death [1] until a doctor explained to me the adverse interactions of citrus fruits on all sorts of medicine. I have been taking my medicine diligently with water ever since, but it still amazes me how incredibly different the distribution of such common and potentially life-saving medical knowledge can be across countries and cultures. [1] https://en.wikipedia.org/wiki/Fan_death https://en.wikipedia.org/wiki/Fan_death

strogonoff 6y ago
Being a little pedantic, the drug interactions part of the article applies to bitter citrus specifically: not just grapefruit (despite the title!), but not all citrus either. Typically “orange” is used to refer to sweet oranges, not sour oranges. As to soda, I struggle to imagine a soda that has any amount of juice worth taking into account…
- simonh 6y ago
  Sodas often contain significant amounts of ciric or phosphoric acid.
  - deleted 6y ago
    [deleted]
  - thw0rted 6y ago
    Per the article, the drug-interaction problem comes from furanocoumarins depleting your cytochrome P450. There's nothing in there to suggest that refined acid (as opposed to unprocessed juice) would include furanocoumarins.
    - mlyle 6y ago
      Indeed, "citric" acid produced today comes from mold cultures that A) don't produce significant quantities of FCs, and B) even remove FCs from their environment by adsorption.

dmurray 6y ago

My grandfather used to eat grapefruit every day, but had to give it up when he was prescribed Warfarin (a blood thinner). Ironically it seems that it would have been just fine for him to continue so long as he stuck to religiously eating grapefruit every day. He would have needed a substantially lower dose of the drug, but Warfarin is one where you adjust the dose a lot for each patient anyway: the manufacturer recommends starting with 6mg and ending up anywhere from 0.5 to 10mg depending on the patient's response [0]. He was also hospitalised several times, both for his heart problems and stomach cancer. I wonder if hospitals keep grapefruit on hand for patients like this, or if they ban it altogether. [0] https://www.nps.org.au/australian-prescriber/articles/how-to-manage-warfarin-therapy https://www.nps.org.au/australian-prescriber/articles/how-to...

jalk 6y ago
> the manufacturer recommends starting with 6mg and ending up anywhere from 0.5 to 10mg depending on the patient's response I tried to explain binary search to my gp when she was trying to find my dose of thyroxin. Unfortunately, according to her, a too high does carries a lot of unpleasant side effects - so linear search it was.
- vikramkr 6y ago
  Yeah, binary search where you don't know what the upper bound is with a narrow therapeutic index drug is not necessarily the best option
- buddhiajuke 6y ago
  We pretty much did binary search to find my lithium levels. The lethal concentration of lithium is very close to the therapeutic range, but we couldn’t afford to spend long on low doses (since you have to take blood tests to assess effective dosages.)
  - krageon 6y ago
    If you keep a good diary you can limit the blood tests to 1-2 times per year and assess therapeutic effect using self-reporting.

ricksunny 6y ago

The drug-discovery venture I lead goes into some detail on grapefruit, hesperidin, and naringin in context of drug interactions at the end of this article in Medium’s An Idea publication (just scroll to the graphic from the FDA): https://medium.com/an-idea/enter-flavonoids-f42662810c11 https://medium.com/an-idea/enter-flavonoids-f42662810c11 Conventionally was thought that the main culprit was bergamotin; but subsequent research showed that naringin (citrus in general but grapefruit especially) and hesperidin (citrus in general - orange, lime, lemon) have their own important interactions with drug-metabolizing enzymes.

ricksunny 6y ago
[Here is a link straight to the academic paper on naringin / hesperidin on the human OATP1A2 human medicine-processing enzyme (so you can skip having to find the link in the above Medium article): https://pubmed.ncbi.nlm.nih.gov/17301733/ https://pubmed.ncbi.nlm.nih.gov/17301733/ ] Flavonoids are a unique class of plant-derived compounds; They can bind a lot of things - in some cases that's bad according to some med chemists, and some cases its good according to other med chemists . . .

np_tedious 6y ago

What an interesting article. I am now very curious to try the mother fruits pomelo and citron. Based on the description here, grapefruits potentiate drugs by reducing the effects of a digestive system enzyme that would otherwise destroy much of the drug. Does this mean that it only has impact when drugs are taken orally?

cik 6y ago
Pomelos are great, assuming you get one that has some sweetness to it. This can very much depend on your geography, as pomelos where I am are significantly more sour than they were in North America. Citrons are just gross.
- pvaldes 6y ago
  Pomelo is sweet and acid, grapefruit is acid and not so sweet. On the other hand, Citron is one of the best for to make candied citrus.
317070 6y ago
Pomelo has been my discovery of 2020 (pre-covid). They are the ideal fruit to eat while watching a movie in the evening. They are a lot of work as you need to peel through all three layers. Yet, you don't get dirty, and every now and again you get to eat a bit and it tastes like more. Oranges and mandarins tend to get you dirty, and would still cause me to overeat.
- hinkley 6y ago
  Mandarins are a crapshoot. Sometimes you come away clean, especially if you are willing to bite the peel to start the peeling process. Whether the wedges remain intact or not is the wildcard.
  - pvaldes 6y ago
    That depends on the type of mandarin You can have clementines, satsumas, tangors and tangerines (plus a few strange complex hybrids). Some have adherent skins that can be messy to peel, the skins in other are extra easy to remove. Clementines are more sweet, tangors are more acidic so are still much appreciated. It depends on the group and cultivar

jariel 6y ago

That 1 glass of grapefruit 10x the potency of Tylenol is shocking, but even more so, how we don't seem to have a reasonable system of 'public awareness' for these things. We 'make discoveries' and then just hope it wades through the network of doctors, pharmacists. Much like with COVID 'communications' it's kind of a disaster. There's nowhere for me to simply find out 'the latest official information' for my province/country in a reasonable and coherent way - a lot of web sites flush with tons of secondary, bureaucratic information, whereas there should be a 'single web page' with the current 'highly relevant information' and another 'single page' to visit with precautions and up-to-date instructions if you're symptomatic. Details on the side. Like the ostensible annual visit to the doctor, I wonder if each healthcare system should put out it's annual list of 'key information' in something easily digestible, written for those with Grade 10 reading ability because that's the lowest common denominator and frankly the intellectual level we're all at when not focusing. So thanks (I guess?) HN! No more grapefruit juice when I'm sick or having a headache with the ... Tylenol. Hey zeus. Hw is that not on the label ...

gdrift 6y ago
For the most up to date COVID information there's this from WHO: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public https://www.who.int/emergencies/diseases/novel-coronavirus-2... > These materials are regularly updated based on new scientific findings as the epidemic evolves. Last updated 5 October 2020.

forinti 6y ago

I already have to deal with citrus names in different languages: pomelo in Spanish, toranja in Portuguese , grapefruit in English . This article added a bit to the confusion: pomelo comes from grapefruit?

simtel20 6y ago
From prior reading I've done, grapefruit was cultivated by crossing pomelo with smaller, more bitter citrus. Here, the wikipedia says it was with a sweet orange [1] 1. https://en.wikipedia.org/wiki/Grapefruit https://en.wikipedia.org/wiki/Grapefruit
- pauloya 6y ago
  The article actually explains this quite well.
dzudndlf 6y ago
Although “pomelo” in Spanish translates (typically) to “grapefruit”, “pomelo” in English refers to another fruit, that is like a grapefruit. Turns out English is surprisingly rich when it comes to describing citrus. The citrus family hybridizes very easily, so every planted seed will give you a “new species” with a unique cultivar. English appears to have assigned more unique names to citrus than the other two languages I know (Italian and Spanish)
- mcv 6y ago
  Citrus names across languages are a mess. For example, citron is the English name for one of the base fruits, which after several hibridisation steps with other fruits results in the lemon. Dutch name for lemon? Citroen. In French it's citron. The French word for the English citron is cédrat. Sukade in Dutch. The Dutch for pomelo is pompelmoes, while the pomelo is a hybrid between the pompelmoes and the grapefruit, and is called shaddock in English according to the Dutch Wikipedia.
  - jdmichal 6y ago

mpettitt 6y ago

It's definitely on the label of my daily medication (in the UK), but it was interesting to see how the interaction seems to be fairly specific to grapefruit. Do either of the ancestor species have a similar effect? I do wonder if there are other dietary/medication interactions that we simply haven't spotted, but which could allow for lower doses of medication (potentially with fewer side effects, if the effect was on one active component) or simply avoid some side effects altogether.

thw0rted 6y ago
From the article: > This interaction, by the way, seems to affect all of the bitter citruses—the ones that inherited the telltale tang from the pomelo. Sour orange. Lime, too. But it’s unlikely that anyone would drink enough sour orange or lime juice to have this effect, given how sour it is. Grapefruit, on the other hand, is far more palatable in large doses.
- hinkley 6y ago
  I wonder what the concentrations are in bottled lime juice, which is easier to consume than fresh lime.

thw0rted 6y ago

I've seen similar warnings about grapefruit before, but the article is the first time I've seen the specific mechanism discussed in this kind of depth. It's also the first time I've seen mention that all "bitter citrus" includes the problematic compounds, including lime and "sour orange" (is that the same as blood orange?). At least for me, it would be better if the headlines would cover this as the broader "bitter citrus", instead of grapefruit specifically. I can't stand grapefruit, so I never paid much attention to the warnings, but I love lime and blood orange, which means further investigation is warranted. TFA says it's "unlikely" anyone would consume enough lime to have an effect, but how much is "enough"?

pvaldes 6y ago
> "sour orange" (is that the same as blood orange?). Not. Sour orange is Citrus x aurantium whereas blood oranges are a type of cultivars of the common orange Citrus x sinensis sharing a red mutation. Both are hybrids but have different ancestors. Sour is inedible in fresh and must be processed, whereas the blood group are small but deliciously acid.
- smcameron 6y ago
  Sour orange pie is a thing though (tastes much like key lime pie).
- bserge 6y ago
  Citrus aurantium are used as a source of synephrine, a stimulant similar to ephedrine, which also interacts with various medication. According to OPs article, grapefruit works in a different way. This article also mentions grapefruit: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655712/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655712/
jrs235 6y ago
FWIW, I don't think "sour orange" referred to blood orange. I believe it refers to Bitter Orange/Seville Orange: https://en.m.wikipedia.org/wiki/Bitter_orange https://en.m.wikipedia.org/wiki/Bitter_orange I think blood oranges are sweet.

sohkamyung 6y ago

For those interested in a infographic on the chemistry of grapefruit, see [1] [1] https://www.compoundchem.com/2014/03/07/why-does-grapefruit-interact-with-drugs-the-chemistry-of-a-grapefruit/ https://www.compoundchem.com/2014/03/07/why-does-grapefruit-...

mafumeira 6y ago

To learn more about how much grapefruit really impacts your detoxification checkout www.nutrahacker.com

mafumeira 6y ago

For a genetic investigation into how grapefruit impacts your detoxification processing checkout https://www.nutrahacker.com https://www.nutrahacker.com

headShrinker 6y ago

> “But Zoloft, Viagra, Adderall, and others do not. “Currently, there is not enough clinical evidence to require Zoloft, Viagra, or Adderall to have a grapefruit juice interaction listed on the drug label,” wrote an FDA representative in an email.” There is some pretty good research on the effects of grapefruit with viagra bioavailability. https://pubmed.ncbi.nlm.nih.gov/11823754/ https://pubmed.ncbi.nlm.nih.gov/11823754/ > “Grapefruit juice changed the area under the sildenafil plasma concentration-time curve from time zero to infinity [AUC(0-infinity) from 620 [1.53] ng/ml x h to 761 [1.58] ng/ml x h (geometric mean with geometric standard deviation), corresponding to a 23% increase (90% confidence interval, 13%-33%).”

hinkley 6y ago
I wonder if anyone is asking the “longer than four hours” crowd about food intake...
Nvuti 6y ago
Nvuti - https://nvuti.games https://nvuti.games

mcv 6y ago

Instead of labeling drugs "do not take with grapefruit", how about using a different dosage for when you take it with grapefruit? Having more of the drug survive the stomach could be a good thing. Or is that too unpredictable? More unpredictable than the effect of medication already is, I mean.

xattt 6y ago
People would eat variable amounts of grapefruit and might not eat it every day. Medications also have the potential to become toxic and have other effects other than the therapeutic effect. Can you imagine trying to explain this concept to an elderly family member? A blanket statement is easier to comprehend for the general population. People DO take insulin where the med is adjusted based on the blood sugar, but this is often accompanied with diabetic education component that takes weeks to complete.
- hinkley 6y ago
  I have wondered though why no time release formulations increase longevity by including a small amount of the active ingredient of grapefruit. Likely due to the other interactions besides metabolism, like cardiac function.
  - xattt 6y ago
    Some antibiotics DO have adjuvants that prolong excretion. Examples are probenecid that was added to penicillin formulations to ensure there was enough supply. Imipenem (another antibiotic) is given with cilastin to reduce clearing of the drug by the kidney. Patients get into trouble when their renal clearance is already poor from long-standing kidney disease, so the potential is there for the drug to build to a level where it exhibits effects beyond its therapeutic intent (ie toxicity).
- Talanes 6y ago
  The diabetes case is also most commonly accomplished with constant rapid testing. I don't think anybody loves grapefruit enough to bleed for it.

timbit42 6y ago

CBD causes the same problems with drugs as grapefruit.

GotAnyMegadeth 6y ago
Do people eat that?
- ddingus 6y ago
  I see CBD edibles, oils, candies, etc... here in Oregon.
- phjesusthatguy3 6y ago
  People ingest it, yes. my father-in-law preferred the effects of CBD over his hallucination medication, but couldn't take it because it interacted badly with his blood-pressure medication. He got some sort of mesh (sorry can't remember what) implanted which eliminated the use of his BP meds, and now he can replace his hallucination meds with CBD. He's in his late 70s, and lived hard (enjoyed every minute of it, but still).
sertsa 6y ago
Would definitely like to hear more about this. Citations?

MisterTea 6y ago

So uh, does this have any effect on THC uptake from cannabis edibles? Asking for a friend...

shawnz 6y ago
Yes, THC is also metabolized by the CYP3A4 enzyme that grapefruit inhibits
- thelazydogsback 6y ago
  So, to be clear, you are saying that in this case the grapefruit would increase or decease the effect of the THC? In other words, to increase the effect of the cannabis, is it metabolites that we want to maximze, or the amount of unmetabolized free THC?
  - shawnz 6y ago
    Yes, grapefruit would increase the effect, and you want to maximize the unmetabolized THC. (although the first metabolite 11-OH-THC is also active, the next metabolite THC-COOH isnt)
deleted 6y ago
[deleted]
hombre_fatal 6y ago
I once took too much acid and the hour I spent in the peak was too strong and took a lot out of me. By the time it passed, I felt ravenous hunger for the massive grapefruit I had in the fridge. About halfway through eating through it's succulent splendor, I had to set the fruit aside and lay down because I felt like I was peaking again.
- ak39 6y ago
  Forgive me, I pictured your experience and it made me laugh. :-D
- 6y ago

throwgrapefruit 6y ago

https://www.scirp.org/journal/PaperInformation.aspx?PaperID=63660 https://www.scirp.org/journal/PaperInformation.aspx?PaperID=... I believe there are low FC varieties in development, and already extant. TBH if you're taking statins, you should really reconsider - those things are terrible for you like the underlying symptoms you're trying to treat. Maybe just not eat like a hog?

dr_dshiv 6y ago

In college, I used to always order cocktails with grapefruit juice in the hope that I'd get more drunk for my money. Was I only benefiting from the placebo effect? Does grapefruit affect alcohol metabolism?

ros86 6y ago
I don't think so, as alcohol is not degraded via P450 enzymes..

mkj 6y ago

This paper has some interesting reading on where the various citrus varieties evolved from Genomics of the origin and evolution of Citrus https://www.nature.com/articles/nature25447/ https://www.nature.com/articles/nature25447/ (Open Access)

chiefalchemist 6y ago

Does grapefruit's affect have anything to do with gut bacteria? That is, (good) bacteria plays a key role in digestion. Does this factor in anywhere?

surround 6y ago

I’m wondering, why not take advantage of this and add the grapefruit furanocoumarins to drugs to make smaller doses more effective?

ricksunny 6y ago
It would be worth big pharma looking further into. I fear however they'll identify that blood serum levels of an ingested drug are variable enough as it is due to the uniqueness of humans, that actively modulating humans ability to process exogenous chemicals is a recipe for disaster. Maybe they'll even get it close to right for Drug A, but what about Drug B that any given patient is concomitantly taking?
chorsestudios 6y ago
People often take multiple prescription medications, doing this might complicate things. The cytochrome P450 enzymes help metabolize a very wide range of compounds.
cowboysauce 6y ago
Because it would increase the number of medications that interact with each other. E.g. you're taking medications A and B, but now A and B come with the potentiating compounds in the pills. So taking both of them could be dangerous. You to go to the hospital and they need to give you C, but it would be dangerous because of the potentiator. It would also make medication management more difficult as people have to remember if they're taking the potentiated drug or not.

austincheney 6y ago

What the article does not mention is the connection of bitter taste to one of the two separate chemicals causing the drug interaction. It is a flavonoid called Naringenin. https://en.wikipedia.org/wiki/Naringenin https://en.wikipedia.org/wiki/Naringenin On its own the chemical is tasteless but in grapefruit in connection with other chemicals common to a variety of fruits, the derived glycoside Naringin, becomes the principle compound providing the bitterness. The chemical is present in many fruits including fruits that typically considered bitter, but it makes grapefruit noticeably more bitter due to its higher concentration there. Perhaps humans are sensitive to the flavor due to the potentially toxic nature. Strangely enough Naringenin is considered a toxin due to its interaction with human biochemistry but is not directly toxic. It allows increased sensitivity to other toxins. Though, to be fair, some drugs and nutrients are formulated in the GI tract due to microbial activity whose drug interaction and absorption can be directly modified by presence of this chemical. https://en.wikipedia.org/wiki/Naringin#Toxicity https://en.wikipedia.org/wiki/Naringin#Toxicity The link above indicates Naringin is a chemical isolate apart from 6',7'-Dihydroxybergamottin, the primary interacting furanocoumarin, and both independently suppress the P450 enzyme CYP3A4. https://en.wikipedia.org/wiki/6%27,7%27-Dihydroxybergamottin https://en.wikipedia.org/wiki/6%27,7%27-Dihydroxybergamottin

dundarious 6y ago
The article does mention other bitter fruits (descendants of pomelo) do share the “grapefruit effect”, but that you are less likely to consume large quantities of lemon juice, for example, compared with grapefruit juice. The extra information you provide is really interesting.

drewg123 6y ago

The article says that grapefruit wipes out cytochrome P450s for up to 12 hours. Lets say I'm taking a medication which is impacted by this. If I were to take my meds and then have a grapefruit 12 hours later, would it impact the dosage of the medication?

WhompingWindows 6y ago
Probably not. If the grapefruit is coming into your system 12 hours after the drug, the drug's already been processed by the P450 system. I think the odd coincidence here is that grapefruit is a "breakfast food" and thus people take it with their morning meds.

BFatts 6y ago

The first thing that struck me was "what about drugs that have little-to-no bioavailability after being ingested?" Would it make it possible to give drugs that are rejected for other reasons?

graeme 6y ago

Would grapefruit affect supplements as well?

MrYellowP 6y ago

Oh wow, my time to shine! Grapefruit juice combined with Vitamin D drops caused me a lasting headache, which, in hindsight, was like a sinus infection without the sinus infection part, but including the typically incredibly stiff neck. Lasting here means a whole month. One month of continuous headache. Not headaches. One gigantic headache. Mostly 7/10, two times 9/10, at which points we called the ambulance because I couldn't take it anymore. Don't ever mix grapefruit juice with anything.

justusthane 6y ago
That’s fascinating. Do you mean that you mixed vitamin D with grapefruit juice once and got a headache that lasted a month? Or were you continuing to drink grapefruit juice and take D during that month? How much vitamin D were you taking? How much time was there between taking vitamin D and drinking grapefruit juice?
- MrYellowP 6y ago
  I had a grapefruit-juice phase (those only lasted days) and drank pretty much nothing else. I took the vitamin D for reasons I forgot. There was no time in between taking it and drinking the juice. It was what I drank most of the day. One can take a few of these drops (liquid, in case that's unclear) every day, but that makes my stomach gas up massively for some reason. One can take them once a week, too, but then he had to take the whole weekly dosage at once. Apparently it doesn't matter. I don't remember how much it was, but I'm talking about one or two dozen water droplets here. I'm sorry, I don't know how to express this any better. The headache started maybe two hours later.
  - justusthane 6y ago
    If I'm understanding you correctly, there was a period of a few days where you were both drinking grapefruit juice and taking vitamin D, and your headache lasted for a month afterwards?
    - 6y ago

dfalzone 6y ago

I wonder if this is at all related to the common pairing of citrus fruits with psychedelic drugs. A lot of people recommend eating an orange or drinking orange juice when you take LSD, and a lot of people recommend using lemons to enhance psilocybin mushroom trips. Maybe grapefruit would pair even better with these drugs.

cyberbanjo 6y ago
Grapefruit juice also has drug interactions with opiates and (I think) anti depressants, amongst other things.
cowboysauce 6y ago
The lemon-tek method of consuming psilocybin mushrooms isn’t related to this. Acidic conditions speed up the conversion of psilocybin into psilocin. This normally happens in your stomach, the lemon-tek method just does externally. This causes the overall experience to be shorter, but more intense. Psilocin also doesn’t appear to be metabolized by the enzymes that grapefruit inhibits.
- SirLuxuryYacht 6y ago
  source?
  - cowboysauce 6y ago
    The wikipedia article for Psilocybin has all of the above. >Psilocybin [...] is a prodrug that is converted into [...] psilocin [...] This chemical reaction takes place under strongly acidic conditions And for metabolism >Psilocin is broken down by the enzyme monoamine oxidase [...] Some psilocin is not broken down by enzymes and instead forms a glucuronide [...] Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine
TT3351 6y ago
Certainly reminds me of the Kool Aid in "Electric Kool Aid Acid Test"

refresher 6y ago

Any relation between furanocoumarins and coumarins? The latter is in cinnamon which I’ve read lately can be quite hazardous depending on the ingested amount.

ncmncm 6y ago
It's hard to eat enough cinnamon to affect most people, but some are extra-sensitive to it. Apparently there is a lot less in the stuff labeled cinnamon and sold to Americans, which is actually not cinnamon at all, but cassia, a whole other species. The difference was understood in Europe in ancient times, so there is no excuse. Sometimes you can find the real stuff in the US labeled "Ceylon cinnamon". It's a darker red than cassia, which is unapologetically brown. Real cinnamon tastes more like red cinnamon candy than cassia does. Americans are always mystified as to why cinnamon candy doesn't taste anything like the cinnamon they put in their pies.

ncmncm 6y ago

The article doesn't say it, but there are some drugs that need processing, by the cytochrome P450 or the CYP3A4 pathway that grapefruit knocks out, in order to become active. Those drugs will lose their effect. Also, the same process may be part of the pathway that removes the precursor chemicals from the bloodstream, so those build up, potentially to toxic levels; you get the overdose without even the dose. Once, in Switzerland, I found a Lindt chocolate bar with dried grapefruit in it. I have never been able to find another. I wonder now if there are regulations about grapefruit ingredients in some countries. But I really love grapefruit. Haribo makes yellow and pink grapefruit gummi candy that is getting hard to find. I would really like to know if they have fouranocoumarins in them, but don't know of any way to find out.

Lambdanaut 6y ago
A web search turns up quite a few results for those lindt chocolate bars with grapefruit.
copperx 6y ago
To find that out you could buy a gas chromatography machine, but I'm not sure if they sell home appliance versions of the equipment.

SubiculumCode 6y ago

Seems like individual differences in bioavailability of drugs is a big problem in drug effectiveness. It seems that a procedure in which the amount getting to the bloodstream is measured, then adjusted (either by dosage increase, or bu supplementation with grapefruti) would be effective.

exabrial 6y ago

Why do I keep getting forwarded to a Norton Antivirus page?

dwighttk 6y ago

> The United States produces more grapefruit than any other country, from Florida and now California as well (and elsewhere, though in smaller quantities). Just a fwiw: Texas produces more Grapefruit than Florida or California. At least the past two seasons. https://www.nass.usda.gov/Statistics_by_State/Florida/Publications/Citrus/Citrus_Forecast/2019-20/cit0720.pdf https://www.nass.usda.gov/Statistics_by_State/Florida/Public...

GloriousKoji 6y ago

If grapefruit causes the bio availability of a drug 10x stronger, it makes sense to be to prescribe 1/10* the amount of a drug with a shot of grapefruit juice. Seems like a good way to make drugs more economical. * I'm assuming the active ingredient in drug is in the 10mg+ range. The way to get the accuracy needed from 1mg to 100ug sounds nontrivial to me.

Taek 6y ago
For most drugs the economics aren't about the cost of producing the chemicals but all of the R&D behind the companies. Whether it's 10mg or 1000mg I don't think it's typically a material part of the cost.
- heavenlyblue 6y ago
  Why would a patient or doctor care about that?
  - pvaldes 6y ago
    Pills have more things than the active compound. Taking less may reduce any hypothetical secondary collateral effects from those substances, so it could be useful to explore it at least. On the other hand, taking just a tenth part of a pill would be not easy to measure. Specially if you need to take the pills often. Sometimes you would take 1/10, other 3/10 or 1/20. That could be a recipe for problems.
    - heavenlyblue 6y ago
      Ok, I agree with the first paragraph (it’s a point I did not think about). The second point is a weak one as you must be quite special to consciously decide on changing the prescribed dose of the pill without buying scales to measure the dose (although I agree these costs quite a lot).

chordalkeyboard 6y ago

Did anyone else get hostile redirects when they went to this site? I did.

TT3351 6y ago

In times of rationing, it was apparently not uncommon for grapefruit eaters to substitute added salt for the usual sugar to take some of the bitterness off.