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 <i>Naringenin</i>.<p><a href="https://en.wikipedia.org/wiki/Naringenin" rel="nofollow">https://en.wikipedia.org/wiki/Naringenin</a><p>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.<p>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.<p><a href="https://en.wikipedia.org/wiki/Naringin#Toxicity" rel="nofollow">https://en.wikipedia.org/wiki/Naringin#Toxicity</a><p>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.<p><a href="https://en.wikipedia.org/wiki/6%27,7%27-Dihydroxybergamottin" rel="nofollow">https://en.wikipedia.org/wiki/6%27,7%27-Dihydroxybergamottin</a>
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.<p>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.<p>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.<p>[1] <a href="https://en.wikipedia.org/wiki/Fan_death" rel="nofollow">https://en.wikipedia.org/wiki/Fan_death</a>
Oh wow, my time to shine!<p>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.<p>Lasting here means a whole month. One month of continuous headache. Not headache<i>s</i>. One gigantic headache. Mostly 7/10, two times 9/10, at which points we called the ambulance because I couldn't take it anymore.<p>Don't ever mix grapefruit juice with anything.
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?).<p>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"?
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].<p>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.<p>[0] <a href="https://www.nps.org.au/australian-prescriber/articles/how-to-manage-warfarin-therapy" rel="nofollow">https://www.nps.org.au/australian-prescriber/articles/how-to...</a>
That 1 glass of grapefruit 10x the potency of <i>Tylenol</i> is shocking, but even more so, how we don't seem to have a reasonable system of 'public awareness' for these things.<p>We 'make discoveries' and then just hope it wades through the network of doctors, pharmacists.<p>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.<p>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.<p>So thanks (I guess?) HN! No more grapefruit juice when I'm sick or having a headache with the ... <i>Tylenol</i>. Hey zeus.<p>Hw is that not on the label ...
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.
> The United States produces more grapefruit than any other country, from Florida and now California as well (and elsewhere, though in smaller quantities).<p>Just a fwiw: Texas produces more Grapefruit than Florida or California. At least the past two seasons.<p><a href="https://www.nass.usda.gov/Statistics_by_State/Florida/Publications/Citrus/Citrus_Forecast/2019-20/cit0720.pdf" rel="nofollow">https://www.nass.usda.gov/Statistics_by_State/Florida/Public...</a>
> “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.”<p>There is some pretty good research on the effects of grapefruit with viagra bioavailability.<p><a href="https://pubmed.ncbi.nlm.nih.gov/11823754/" rel="nofollow">https://pubmed.ncbi.nlm.nih.gov/11823754/</a><p>> “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%).”
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?
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.<p>* 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.
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.<p>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.<p>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.
This paper has some interesting reading on where the various citrus varieties evolved from<p>Genomics of the origin and evolution of Citrus
<a href="https://www.nature.com/articles/nature25447/" rel="nofollow">https://www.nature.com/articles/nature25447/</a> (Open Access)
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):<p><a href="https://medium.com/an-idea/enter-flavonoids-f42662810c11" rel="nofollow">https://medium.com/an-idea/enter-flavonoids-f42662810c11</a><p>Conventionally was thought that the main culprit was bergamotin; but subsequent research showed that naringin (citrus in general but grapefruit <i>especially</i>) and hesperidin (citrus
in general - orange, lime, lemon) have their own important interactions with drug-metabolizing enzymes.
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.
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?<p>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.
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?
For those interested in a infographic on the chemistry of grapefruit, see [1]<p>[1] <a href="https://www.compoundchem.com/2014/03/07/why-does-grapefruit-interact-with-drugs-the-chemistry-of-a-grapefruit/" rel="nofollow">https://www.compoundchem.com/2014/03/07/why-does-grapefruit-...</a>
What an interesting article. I am now very curious to try the mother fruits pomelo and citron.<p>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?
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.
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.<p>Or is that too unpredictable? More unpredictable than the effect of medication already is, I mean.
The article says that grapefruit wipes out cytochrome P450s for up to 12 hours.<p>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?
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?
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?
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.
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.
<a href="https://www.scirp.org/journal/PaperInformation.aspx?PaperID=63660" rel="nofollow">https://www.scirp.org/journal/PaperInformation.aspx?PaperID=...</a><p>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?