I probably shouldn't post this

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
It's really should go in my pharma genetic thread but I'm working on it.
I will state this quite a few times but if you are on drugs, prescription for anything do not fuck around with this!
If you fuck around you will find out I promise you.
So I am sure all of y'all heard about grapefruit juice in medicine. If you read the insert in a lot of your medication it will say do not take with grapefruit. I'm doing this off memory here but grapefruit juice inhibits the CYP 3A gene which is responsible for about 50% of medication metabolism. What that means is it doesn't break down the medicine as fast so it stays in your system longer and depending on the med you may not get the therapeutic dose needed and or you'll be exposed to the effects of the drugs longer than necessary or healthy. But it also depends does the drug need to metabolize into something else before it takes effect or is it utilized directly.
anyway if something slows down there must be something that speeds it up....
And for the specific gene St John's Wort is one of those things that speed it up. I am poor metabolizer of the CYP3A Gene so I decided to experiment and take saw palmetto and a dose of Zyklon B that would have no effect on me. Obviously Zyklon B is code.
Let me stop here for a moment if you are any drugs rx or not do not fuck around with this.
Anyway holy shit you normal metabolizers are lucky as hell,
 
Last edited:
Joined
Jan 4, 2025
Messages
293
Reaction score
128
Points
43
It's really should go in my pharma genetic thread but I'm working on it.
I will state this quite a few times but if you are on drugs, prescription for anything do not fuck around with this!
If you fuck around you will find out I promise you.
So I am sure all of y'all heard about grapefruit juice in medicine. If you read the insert in a lot of your medication it will say do not take with grapefruit. I'm doing this off memory here but grapefruit juice inhibits the CYP 3A gene which is responsible for about 50% of medication metabolism. What that means is it doesn't break down the medicine as fast so it stays in your system longer and depending on the med you may not get the therapeutic dose needed and or you'll be exposed to the effects of the drugs longer than necessary or healthy. But it also depends does the drug need to metabolize into something else before it takes effect or is it utilized directly.
anyway if something slows down there must be something that speeds it up....
And for the specific gene saw palmetto is one of those things that speed it up. I am poor metabolizer of the CYP3A Gene so I decided to experiment and take saw palmetto and a dose of Zyklon B that would have no effect on me. Obviously Zyklon B is code.
Let me stop here for a moment if you are any drugs rx or not do not fuck around with this.
Anyway holy shit you normal metabolizers are lucky as hell,
Lol Zyclon b. I was like, wait, wasn't that what the NAZIS used to gas the Jews??

Sent from my SM-A156U using Tapatalk
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
Lol Zyclon b. I was like, wait, wasn't that what the NAZIS used to gas the Jews??

Sent from my SM-A156U using Tapatalk
Yeah I was just trying to think of a form of cyanide probably should have picked a different version. The subtle point I was trying to gett across with that was somebody's going to hurt themselves if they fuck around

Nice to see somebody learn more about history than they taught in school.
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
i take grapefruit juice w orals to get more out of less. works well w Var.
What I cannot find the data for is how much Furanocoumarin would be needed for an x percent decrease in metabolizing the drug. Too much it would be useless, not enough well it will still do its thing on normal people. Also if you're a poor metabolizer and you use grapefruit juice can you block or how long can you block the effects since most drugs have to be metabolized into a useful drug first before your body metabolizes the drug itself
 
Joined
Nov 18, 2024
Messages
12
Reaction score
4
Points
3
What I cannot find the data for is how much Furanocoumarin would be needed for an x percent decrease in metabolizing the drug. Too much it would be useless, not enough well it will still do its thing on normal people. Also if you're a poor metabolizer and you use grapefruit juice can you block or how long can you block the effects since most drugs have to be metabolized into a useful drug first before your body metabolizes the drug itself
interesting you look at furanocoumarin. Ive observed some of the research looking at naringin and ho it decreases the activity of 17 beta HSD in gut which can metabolize var before reaching circulation. This is all theoretical but using this research we could posit that naringin would make oral var more bioavailable.
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
Correction inducer is St John's Wort, I have no idea why saw palmetto was in my brain I will correct shortly.

Fixed
 
Last edited:
Joined
Jan 4, 2025
Messages
293
Reaction score
128
Points
43
i take grapefruit juice w orals to get more out of less. works well w Var.
I've seen this over and over again on both prescriptions drug warning labels and OCT drugs. Not to consume grapefruit juice. That it could increase the effects of the drug.

Sent from my SM-A156U using Tapatalk
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
For a few hundred I would recommend everyone get a Pharmacogenomics (also known as pharmacogenetic) test. It is very fascinating.
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
I've seen this over and over again on both prescriptions drug warning labels and OCT drugs. Not to consume grapefruit juice. That it could increase the effects of the drug.

Sent from my SM-A156U using Tapatalk
There are stronger inhibitors.

Here is a list of Cyp 3xx gene Inhibitors and inducers ranked by strength.
 

Attachments

  • Screenshot_20250129_081026_Firefox.jpg
    Screenshot_20250129_081026_Firefox.jpg
    121 KB · Views: 9

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
could you cite resources. looks interesting.
For the test itself I had a phaser test. Which it appears it's only done through veterans affairs. It's really for cancer and transplant patients to be given the most optimal drugs.
Now I was helping another member research testing, there are lots of places that do it Even at home mailing tests. But I have no experience with any other testing facility and how thorough they are. I know the test through the VA seems limited to me I think I posted the results. there's maybe 15 to 20 they test only in certain categories. I will reach out to the member to see if they chose a testing facility. Hell I wouldn't be surprised if quest diagnostics does it. Or if you have an appointment with a specialty or primary care soon you could ask them tell him whatever drugs you're taking don't seem to work and you've tried to punch a different drugs and they don't seem to work is there some genetic test you could do they might point you in something local.
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
I should probably be clear that there are other genes that also metabolize some of the same drugs some more than others so it's just not this specific gene. No but one day get around to finishing my article or I'll just piecemeal it together.
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
I actually found a really good write up on one of the genes i believe it's this one in particular on another board from years ago but it's concerning inhibiting which I'm sure is more of an interest to y'all. I'm more interested in inducing since I'm a natural inhibitor. But it's a really good read far more elegant than my talk-to-text ass. I will copy and paste it and make sure I give credit to the author before I go to bed tonight.
 
Joined
Jan 4, 2025
Messages
293
Reaction score
128
Points
43
I'm only familiar with topical also but I'm sure a quick Google search would tell us.
Yeah, they do come in pills. I've seen them several places. Not sure what they are used for though.

Sent from my SM-A156U using Tapatalk
 

Thrawn

Elite
Joined
Nov 18, 2021
Messages
3,263
Reaction score
3,345
Points
193
Ok this is from
Needtogetaas
June 5th 2010
Evolutionary. Org
It covers 2 genes cyp3a4 and cyp1a2
I guess I will cover the others.
This is for inhibiting Not inducing!
If you don't know what you are DON'T TRY.

'We have all gotten medication from the pharmacy at one time or another. How many of us read the warning? Even more so how many of us read the little pamphlet that on drug interactions they give you with the medication. You know the little folded up peace of paper with thousands of tiny words.

Well Of course I am write lolol.. Every time i read one there is something that sticks out to me. Almost all of them always say " do not consume with grapefruit juice do to harmful interactions" or something along these lines. Some medications it interacts so much that they find it important to put this directly on the bottle.

So of course this got me thinking why? How does Grapefruit juice effect medication?

So I did some research and I found out as always.

A enzymes in the liver called CYP3A4 and CYP1A2 are responsible for the rake down of many things "including medications. They even does the job of braking down mythelation and or other oral steroids as well. A sabstance in grapefruit juice known as "Naringin" HAs been medically proven to brake down both the CYP3A4 and CYP1A2 enzymes in the liver.

CYP3A4
YP3A4 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the [ame="[URL]http://en.wikipedia.org/wiki/Endoplasmic_reticulum[/URL]"]endoplasmic reticulum[/ame] and its expression is induced by [ame="[URL]http://en.wikipedia.org/wiki/Glucocorticoid[/URL]"]glucocorticoids[/ame] and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs which are used today, including acetaminophen, codeine, cyclosporin A, diazepam and erythromycin. The enzyme also metabolizes some steroids and carcinogens.[3]

Ingestion of naringin and related flavonoids can also affect the intestinal absorption of certain drugs, leading to increase circulating drug levels.

The discovery that grapefruit juice can increase the oral availability of some medications was an accidental discovery made when grapefruit juice was used to mask the taste of ethanol in a study involving the calcium channel blocker felodipine. Since then, more different drugs have shown to enhance oral availability when consumed with grapefruit juice. Most of the drugs affected by grapefruit juice have highly variable oral bioavailability. In addition, most of these drugs are chiefly metabolized in the body by CYP3A4, an enzyme present in the liver and intestine.
The major effect of grapefruit juice appears to reduce “first-pass” metabolism by reducing CYP3A4 activity.

As little as 250 mL of grapefruit juice can change the metabolism of some drugs.3 This drug–food interaction occurs because of a common pathway involving a specific isoform of cytochrome P450 — CYP3A4 — present in both the liver and the intestinal wall. Studies suggest that grapefruit juice exerts its effect primarily at the level of the intestine but to some degree within the liver

After ingestion, a substrate contained in the grapefruit binds to the intestinal isoenzyme, impairing first-pass metabolism directly and causing a sustained decrease in CYP3A4 protein expression. Within 4 hours of ingestion, a reduction in the effective CYP3A4 concentration occurs, with effects lasting up to 24 hours. The net result is inhibition of drug metabolism in the intestine and increased oral bioavailability. Because of the prolonged response, separating the intake of the drug and the juice does not prevent interference.

Individuals express CYP3A4 in different proportions, those with the highest intestinal concentration being most susceptible to grapefruit juice/–naringin drug interactions. An effect is seen with the whole fruit as well as its juice,and naringin extracts so caution should be exercised with ALL. There is no similar reaction with orange juice, although there is some suspicion that "sour oranges" such as the Seville variety, may have some effect. A recent study, however, that tested the known interference of grapefruit juice with cyclosporine showed no similar effect with Seville oranges.

There is some interest in the potential therapeutic benefit of adding grapefruit juice to a drug regimen to increase oral bioavailability. The limitation is the individual variation in patient response. However, if the chemical that causes grapefruit's CYP3A4 inhibition is elucidated, there may be an opportunity to modulate that pathway in a controlled fashion.

What to do: Much of the data obtained on grapefruit juice–drug interactions involved measuring serum drug concentrations in small numbers of healthy volunteers. Because of the limited data and only occasional case reports, it is difficult to quantify the clinical significance for individual patients. One may assume that the interaction occurs primarily with oral medicines, and only with those that share the CYP3A4 metabolism pathway, with the consequence being increased oral bioavailability, higher serum drug concentrations and associated adverse effects.


One of the things I found most interesting is when you look for a list of drugs effected by grapefruit juice every known list has "dbol" on this list of drugs effected by grapefruit juice. This means that dbol is Highly effected by the CYP3A4 pathway! and i suspect that many other oral drugs also do go by route of CYP3A4 pathway.

Also a drug known as Cyprotraine a anti androgen/dht, is metabolized by the [ame="[URL]http://en.wikipedia.org/wiki/CYP3A4[/URL]"]CYP3A4[/ame] enzyme, forming the active metabolite 15β-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity. Cyproterone acetate increases production of CYP3A4.


Dutasteride and SERMs are also metabolized by the CYP3A4 enzyme.


And lastly here is another list of drugs effected my the p450 enzyme system .


Statins (Cholesterol Lowering Drugs):
-Baycol (Cerivastatin)
-Mevacor (Lovastatin)
-Lipitor (Atorvastatin)
-Zocor (Simvastatin)

Antihistamines:
-Ebastine
-Seldane (Terfenadine, taken off the U.S. market)

Calcium Channel Blockers (Blood Pressure Drugs):
-Nimotop (Nimodipine)
-Nitrendipine
-Plendil (Felodipine)
-Pranidipine
-Sular (Nisoldipine)

Psychiatric Medications:
-Buspar (Buspirone)
-Halcion (Triazolam)
-Tegretol (Carbamazepine)
-Valium (Diazepam)
-Versed (Midazolam)

Intestinal Medications:
-Propulsid (Cisapride, taken off the U.S. market)

Immune Suppressants:
-Neoral (Cyclosporine)
-Prograf (Tacrolimus)

Pain Medications:
-Methadone

Impotence Drug:
-Viagra (Sildenafil)

Miscellaneous

-Losartan (Angiotensin II receptor blocker - ARB) - Grapefruit juice inhibits the body's ability to absorb the drug.
-Digoxin (for treating congestive heart failure) - Grapefruit juice inhibits the body's ability to absorb the drug.


Simple put many oral steroids are greatly enhanced by grapefruit juice or the extract naringin."
 

New Threads

Top