The Grapefruit Rule

[The Kap'n]

Drugs that are incompatible with Grapefruit are also incompatible with Kava.​

Grapefruit juice:

Both grapefruit juice and the fruit itself can interact with more than 50 drugs—such as cholesterol-lowering statins, high blood pressure medications, and allergy drugs—raising the risk of side effects and other problems. Here’s how to know if you can safely enjoy grapefruit with your medication.

Grapefruit and medication could cause problems in two ways. First, grapefruit can block a key drug-metabolizing enzyme in your body, which in turn could lead to an increase in the blood levels of certain drugs. If that happens, it increases the risk of experiencing a side effect from that drug. On the flipside, it can also block absorption of certain drugs in your intestines. In that case, you could have less of the drug in your bloodstream than what you need, so the drug might not be effective for its intended purpose.

Surprisingly, it doesn’t take much of the fruit for a grapefruit and medication interaction to happen: As little as 1 cup of juice or two grapefruit wedges can be enough to cause problems, according to the Food and Drug Administration.
https://www.consumerreports.org/health/grapefruit-and-medications-can-be-a-dangerous-mix/

While kava has yet to be shown to block the absorption of certain drugs, the part we're interested in is how it interacts with the "key drug metabolizing enzyme in your body". They're speaking of the P450 group of enzymes.

Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. Genetic variability (polymorphism) in these enzymes may influence a patient's response to commonly prescribed drug classes, including beta blockers and antidepressants. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes.
https://www.aafp.org/afp/2007/0801/p391.html

Kava has the same action. It suppresses activity at the same locations.

In the present work the inhibition of P450 enzymes by kava extract and individual kavalactones in human liver microsomes (HLMs) was investigated. Whole kava extract (normalized to 100 microM total kavalactones) caused concentration-dependent decreases in P450 activities, with significant inhibition of the activities of CYP1A2 (56% inhibition), 2C9 (92%), 2C19 (86%), 2D6 (73%), 3A4 (78%), and 4A9/11 (65%) following preincubation for 15 min with HLMs and NADPH; CYP2A6, 2C8, and 2E1 activities were unaffected.
https://www.ncbi.nlm.nih.gov/pubmed/12386118

As you can see in the quote above, the 2D6 was inhibited 73% and the 3A4 inhibition at 78%. Very significant and similar (62%) to the profile of inhibition seen with grapefruit.

If you have any questions about your medication, see what your doctor says about taking it with grapefruit juice. If it's "go", then kava is unlikely to cause any issue with the metabolism of that drug.

TL/DR: Avoid kava if your medicine says "do not take with grapefruit or grapefruit juice". The drugs don't break down in your system like they should and could lead to problems when kava is combined.

 

[Zac Imiola (Herbalist)]

what do you guys think about coffee/ caffeine and kava then?
Personally I don't drink more caffeine after I have my kava. Since I've noticed it doesn't go away then for a too long and causes insomnia.

 

[recentreturn]

View attachment 9583 View attachment 9584
Drugs that are incompatible with Grapefruit are also incompatible with Kava.​

Grapefruit juice:


While kava has yet to be shown to block the absorption of certain drugs, the part we're interested in is how it interacts with the "key drug metabolizing enzyme in your body". They're speaking of the P450 group of enzymes.



Kava has the same action. It suppresses activity at the same locations.



As you can see in the quote above, the 2D6 was inhibited 73% and the 3A4 inhibition at 78%. Very significant and similar (62%) to the profile of inhibition seen with grapefruit.

If you have any questions about your medication, see what your doctor says about taking it with grapefruit juice. If it's "go", then kava is unlikely to cause any issue with the metabolism of that drug.

TL/DR: Avoid kava if your medicine says "do not take with grapefruit or grapefruit juice". The drugs don't break down in your system like they should and could lead to problems when kava is combined.

Does this mean that kava and grapefruit should not be combined?

 

[kastom_lif]

Does this mean that kava and grapefruit should not be combined?

Citrus supposedly breaks down kavain selectively. It can kill a nice fun buzzy session. In Vanuatu, they'll eat every other kind of fruit for wasemaot but NEVER citrus, even though their delicious aranis and pamplemus are legendary.

 

[The Kap'n]

Does this mean that kava and grapefruit should not be combined?

I cannot find very much information on combining inhibitors. It would seem to me, that the combination of two would simply net the inhibition at the site where the inhibition is stronger. Example: Kava inhibits CYP3A4 to around 79% whereas grapefruit inhibits around 62%. In this scenario you would see the inhibition at 79% since kava has a stronger affinity for that pathway. I think your question speaks to whether they're additive, and I believe they aren't, but it will take someone with more understanding than I to fully explain that.

 

[sɥɐʞɐs]

Citrus supposedly breaks down kavain selectively. It can kill a nice fun buzzy session. In Vanuatu, they'll eat every other kind of fruit for wasemaot but NEVER citrus, even though their delicious aranis and pamplemus are legendary.

I don’t mean to shit on your point, cuz this might be a general rule...I’m not sure. But, one night in PV a local guy walked me to a nakamal with a couple of his buddies and he was handing out slices of an Orange as chaser. That night was one the most ‘doped up’ (in a good way, but very inebriated) I’ve ever felt from kava. I’m not saying the citrus did or didn’t have any effect in the experience, just saying I ate citrus as a chaser with NiVans and still had one of the standout Kava experiences of my life. In my opinion, it was all due to the kava itself (which they claimed was from Tanna but I can’t verify that), and it likely would have felt the same without the Orange...but who knows, maybe it did break down the kavain a bit...what I do know, is that this kava was so powerful it didn’t matter at all.


[I’m saying all this separate from the grapefruit conversation, although I have also combined kava and grapefruit juice in the past as well.]

 

[kastom_lif]

That sounds fantastic. Tanna Kava with Aniwa Oranges is probably some kind of magic combination that makes it OK

 

[Zac Imiola (Herbalist)]

I do find it literally will break down the kava some times when I mix them but I don't know.
Maybe the double bonds are safe from it and they mean the sober euphoria rather than the double bonded krunk effect?

 

[Kojo Douglas]

I still really want to know how grapefruit got its name.

 

[Zac Imiola (Herbalist)]

Haha right

 

[Groggy]

what do you guys think about coffee/ caffeine and kava then?
Personally I don't drink more caffeine after I have my kava. Since I've noticed it doesn't go away then for a too long and causes insomnia.

I drink caffeine in the mornings and kava in the afternoons/early evening. (when I have it) I drink kava most often on weekends nowadays.

 

[Zac Imiola (Herbalist)]

Do you drink kava every day? I think that plays a role.
If you take regular breaks you may be less susceptible to the liver effects

 

[Groggy]

Do you drink kava every day? I think that plays a role.
If you take regular breaks you may be less susceptible to the liver effects

The first year maybe 1 1/2 years I did, I slowly started cutting back both because of the price tag but also because it made me lazy. I drink kava 2-3 days a week and often take a week off.

 

[Zac Imiola (Herbalist)]

I think that's what I should do lol because I overindulge. Although I do love it it doesn't always love me ... aka insomnia

 

[Groggy]

I think that's what I should do lol because I overindulge. Although I do love it it doesn't always love me ... aka insomnia

Same problem with me, because of my already addictive tendencies it's really easy to overindulge on too many shells. I only buy enough for a few days at a time. Plus I enjoy other herbs that enhance the overall experience

 

[Zac Imiola (Herbalist)]

Yeah I should do that lmao

 

[Groggy]

I still really want to know how grapefruit got its name.

So did I after you mentioned it but then found this more interesting info supporting what kapm has sad

https://en.wikipedia.org/wiki/Grapefruit
Drug interactions[edit]
Main article: Grapefruit–drug interactions
Grapefruit and grapefruit juice have been found to interact with numerous drugs and in many cases, to result in adverse direct and/or side effects (if dosage is not carefully adjusted.)[24]

This happens in two very different ways. In the first, the effect is from bergamottin, a natural furanocoumarin in both grapefruit flesh and peel that inhibits the CYP3A4enzyme, (among others from the P450 enzyme family responsible for metabolizing 90% of drugs). The action of the CYP3A4 enzyme itself is to metabolize many medications.[25][26] If the drug's breakdown for removal is lessened, then the level of the drug in the blood may become too high or stay too long, leading to adverse effects.[26] On the other hand, some drugs must be broken down to become active, and inhibiting CYP3A4 may lead to reduced drug effects.

The other effect is that grapefruit can block the absorption of drugs in the intestine.[26] If the drug is not absorbed, then not enough of it is in the blood to have a therapeutic effect.[26] Each affected drug has either a specific increase of effect or decrease.

One whole grapefruit, or a glass of 200 mL (6.8 US fl oz) of grapefruit juice may cause drug overdose toxicity.[27] Typically, drugs that are incompatible with grapefruit are so labeled on the container or package insert.[26] People taking drugs should ask their health care provider or pharmacist questions about grapefruit and drug interactions.[26]

Good thing I hate grapefruit..

 

[The Kap'n]

So did I after you mentioned it but then found this more interesting info supporting what kapm has sad

https://en.wikipedia.org/wiki/Grapefruit
Drug interactions[edit]
Main article: Grapefruit–drug interactions
Grapefruit and grapefruit juice have been found to interact with numerous drugs and in many cases, to result in adverse direct and/or side effects (if dosage is not carefully adjusted.)[24]

This happens in two very different ways. In the first, the effect is from bergamottin, a natural furanocoumarin in both grapefruit flesh and peel that inhibits the CYP3A4enzyme, (among others from the P450 enzyme family responsible for metabolizing 90% of drugs). The action of the CYP3A4 enzyme itself is to metabolize many medications.[25][26] If the drug's breakdown for removal is lessened, then the level of the drug in the blood may become too high or stay too long, leading to adverse effects.[26] On the other hand, some drugs must be broken down to become active, and inhibiting CYP3A4 may lead to reduced drug effects.

The other effect is that grapefruit can block the absorption of drugs in the intestine.[26] If the drug is not absorbed, then not enough of it is in the blood to have a therapeutic effect.[26] Each affected drug has either a specific increase of effect or decrease.

One whole grapefruit, or a glass of 200 mL (6.8 US fl oz) of grapefruit juice may cause drug overdose toxicity.[27] Typically, drugs that are incompatible with grapefruit are so labeled on the container or package insert.[26] People taking drugs should ask their health care provider or pharmacist questions about grapefruit and drug interactions.[26]

Good thing I hate grapefruit..

If you hate the bitterness of grapefruit, I suggest giving a Pomelo a shot. They can get to the size of a basketball (The skin is about 2 inches thick) and they have all the properties of Grapefruit without the bitterness.

 

[Intrepidus_dux]

[QUOTE Good thing I hate grapefruit..[/QUOTE]
Same! I'm wondering who would be very upset about not being able to consume it. No one I know! I have never said to myself, "today is a great day to eat some grapefruit!" I think it's not actually a fruit and just a trick to see how many humans will force themselves to eat it.

 

[recentreturn]

Same! I'm wondering who would be very upset about not being able to consume it. No one I know! I have never said to myself, "today is a great day to eat some grapefruit!" I think it's not actually a fruit and just a trick to see how many humans will force themselves to eat it.

I like grapefruit! Its like a less boring orange; and its less bitter than kava (though bitter enough that I won't touch the grapefruit juice in my fridge after drinking kava even when I want juice).