Bile can serve as a reservoir for funghi, making them harder to treat

[Mauritio]

@yerrag I am not doubting that it has these effects, I was just surprised that there isnt any studies on it (as opposed to gentian for example)

BTW I took it again today and the stimulating effects seem to be a lot less pronounced already.

[yerrag]

@Mauritio It's admirable that you have caught on to Ray's method of feel when using substances. I slowly become more sensitized such as when I make a connection between feeling skin allergies when I observe a pattern emerge that my skin allergy would coincide with pale stools signifying the lack of bile production. But it's notable that I only make that connection because skin allergy is not a common experience with me that when it happens it stands out for me to be able to make a cause and effect relationship to it. Yet, my pattern recognition ability fails me when I take dandelion root, as I dont feel any palpable effect from taking it. I would only get confirmation that it is working after 2 weeks of taking it when I see my stools look darker followed up by the loss of skin allergy. Still, knowing the skin is a secondary mechanism of detox helps me connect the dots in being able to identify loss of bile production with my liver and gallbladder.

I am not as sensitive as you and Ray when it comes to directly feel the effect of taking aubstances and I have to rely on observing outward effects after a given amount of time to allow for the delay for effects to be observed. I even have to shy away from outright using stacks as opposed to a gradual addition of substances, just to be able to identify which substance has an outsize effect, and which can be removed from the stack because it gives diminishing returns or even has unintended effects that confound rather than elucidate. Still, I rely on feel as much as I can.

Although I am more tech ( personal devices such as bp, spO2, and ECG) and test (blood test as the most common example) oriented, as feel isn't enough for me when I can't rely on it when it is absent.

As to you noting the absence of studies for various herbs in the apothecary of herbal medicine, there are many studies that have yet to be made given the richness that abounds in flora. But for those where studies have been made, many are not searchable despite the efforts of Google to make them aearchable, and many are even intentionally siloed and disappeared. Thus, we are able only to benefit from a small subset of herbs that mankind has discovered if we were to rely on the limited scope modern and commercial medical science and its curators limit us to.

[CrumblingCookie]

Hesperitin, as in the aglycone flavonol with CAS # 520-33-2, is said to be super-potent against fungal biofilms,
in contrast to the Hesperidin glycoside CAS # 520-26-3.
The latter is actually a precursor whose rutenoside group must first be hydrolyzed for it to become active hesperitin. Practically, this means for anyone suspecting/targeting fungal biofilm in the (distal) colon, hesperidin is a sound option. It's available as consumer-targeted dietary supplements extracted from citrus fruit.
But for anything more proximal, all along the small intestine, direct hesperitin is needed. No domestic OTC-products are available, but raw powders can be obtained with extra costs and efforts.

I'm not done with this fungal topic yet. I've looked into every side avenue of why fluconazole past a certain dosage thresold was so effective on me for the short time I had taken it.
And none of the alternative explanations via potassium efflux pumps (IRk specifically) or its cytochrome inhibition profile make any sense as to why it would alleviate diarrhea. It likely really is a C. glabrata-dominated fungal biofilm background to it all.

Taking the flucotysin by itself btw was really stupid of me. Since I reckon nobody who had been reading here had the experience of being a clinical fungal disease expert who could have told me before I will stress it from the lay level:
5-FC was/is idiotic to take by itself because resistance/tolerance to it arises essentially immediately.
So that's why it had no significant effect at all.
Among the echinocandins group of antifungals, rezafungin is the latest and most hydrophilic / hygroscopic and also provides a very long half-life in-vivo allowing for once-weekly i.v. administration schedules.

[sunsunsun]

@CrumblingCookie so did you stack stuff with fluconazole to lower its MIC and MFC?
are you gonna get brexafemme?

[CrumblingCookie]

@sunsunsun Yes, a bulb of garlic/d, oregano oil 4-5 drops/d, borax water, propolis extract. Maybe, maybe it will take even more than 300mg/d to show effects without such a stack.

It's also quite certain from studies that (flucon)azole is really pretty useless against C. glabrata biofilms as it simply doesn't penetrate nor dissolve it. Probably that's why some treatments call for weeks of really high dosage (800mg/d) followed by months or forever of a lower maintenance dosage. With the latter probably just keeping whatever's already established itself under check yet without further removing any of it.
If going with azoles, maybe superdosing hesperitin could be of intestinal and systemic complementary merit and maybe superdosing nystatin (20M IU/d) for the intestinal lumen could be, too.

The brexafemme in the patient studies doesn't even look as exceptional but more or less equally successful, empirically, as fluconazole when treatment groups aren't separated according to prior susceptibility testing.
It should be distinctly more promising wrt biofilms, however, because fungal biofilms can sustain themselves with almost no ergosterol (azoles) whereas the β-(1,3)-glucan (ibrexafungerp or echinacandins) is much more essential to their structure and survival.

At this point there is so little data on the brexafemme, though. I'd prefer an echinocandin. Mica- or rezafungin are reported to be efficacious against biofilms yet their mucocutaneous use, albeit highly promising, is still on the fringe side. Maybe the reza even therapeutically reaches the bile? Its distribution pattern and volume suggests it pretty much goes everywhere and its excretion is mostly fecal (not biliary but by passive diffusion) and still in its active drug form.

[Mauritio]

@CrumblingCookie Hesperedin/ Hesperitin are interesting substances. IIRC @cs3000 posted some good studies on them on the RPF.

And not only is it anti-fungal, but in accordance with the topic of this thread, it could help with fungal issues via alleviating cholestasis / helping with bile flow.

It is an FXR agonist:
"HP prevented bile acid toxicity in HepaRG cells, and this effect was blocked by FXR silencing. HP appears to activate FXR to prevent cholestatic liver injury."

And a Cholagogue:
"...HP promoted bile acid excretion into feces..."

https://pubmed.ncbi.nlm.nih.gov/32841642/

---

Also seems to be anti-estrogenic and activates 5HT1a

https://pubmed.ncbi.nlm.nih.gov/23238426/
https://pubmed.ncbi.nlm.nih.gov/22996046/

[CrumblingCookie]

Satish Rao MD seems to be one of the few who actually tackle SIFO, i.e. a non-invasive persistent fungal burden in the small intestine, without parroting health-scene mumbo-jumbo. In this short interview he briefly talks about the beginnings and reluctance of medical peers, but also how one can essentially pretty much forget about any sensible testing methods other than culturing of samples of duodenal juice obtained from gastroduodoscopy (caveat: Taking a duodenal juice sample instead of discarding the pumped-off fluids sounds simple enough and I've known about it for years, yet still pretty much not even any universitiy clinic does this! To my surprise, it's not only me being surrounded by stubborn idiots but he also mentions this situation in practice and how gastroenterologists just need to discuss these goals once in advance with their microbiology lab provider to set up such a then routine diagnostic)
Youtube Video

He also tackles SIBO by choosing the Abx according to the individual antibiograms of such sample cultures. Which makes a lot of sense. Another facepalm moment to not do so.

As for the SIFO, if the culture is unavailable he goes by clinical suspicion and states that a three weeks' regimen of fluconazole 100mg daily is well tolerated and of very little worry in comparison to the hoops and ordeals to otherwise (or subsequently) go through.

I must remark, however, that fluconazole is of very little efficacy and at best only fungistatic against C. glabrata in contrast to the better-suited posaconazole.
On a side note: C. glabrata or C. krusei don't produce D-arabinitol. Only C. albicans does. Testing for D-arabinitol in urine can therefore only show presence of C. albicans.

@mauritio Thanks! I had found cs3000's three RPF threads on it and they had great info. Nice to see that the Iranians have already run some human trials with 500-1000mg p.o. of it daily. It's four times as bioavailable as an equimolar amount of hesperidin (from colonic hydrolysis in healthy people). Lemons containing much more precursors for it than oranges.
Hesperitin's boosting of mitochondria and efficacy against senescence is mightily impressive. It's also synergistic with other flavonoids like the naringin which you had been all over about. Hesperitin is being sold for about USD150-250/kg.

[CrumblingCookie]

I was hoping for more impressive results when I stumbled upon a potential anti-fungal-biofilm effect of melatonin but the addition of MEL shows no truly reliable effect on any Candida species nor their biofilms.
Instead, posting this table here rather serves as an illustration of how insanely resistant biofilm-embedded Candida spp. are to antifungals:

From: The effect of melatonin on antifungal susceptibility in planktonic and biofilm forms of Candida strains isolated from clinical samples, Kilinçel et al., 2019

On the plus side, only 19 out of 350 clinical samples of Candida strains were at all biofilm-building in vitro, i.e. not every fungal strain one could have or get will be as devilish.

[Mauritio]

@CrumblingCookie said:

@mauritio Thanks! I had found cs3000's three RPF threads on it and they had great info. Nice to see that the Iranians have already run some human trials with 500-1000mg p.o. of it daily. It's four times as bioavailable as an equimolar amount of hesperidin (from colonic hydrolysis in healthy people). Lemons containing much more precursors for it than oranges.
Hesperitin's boosting of mitochondria and efficacy against senescence is mightily impressive. It's also synergistic with other flavonones like the naringin which you had been all over about. Hesperitin is being sold for about USD150/kg.

Nice. do you have any exerience with hesperedin ? (since hesperetin is so hard to get)

[CrumblingCookie]

@Mauritio I'm going to dot the i's and cross the t's in this case and source the hesperitin for 500mg of it twice daily with antifungals.
Haven't tried any hesperidin/bergamot extract before, of which I've only heard that it's effectively lowering triglyceride and total cholesterol levels in people whose digestion isn't whacked.

[Mauritio]

@CrumblingCookie
Why aren't you taking much higher doses of hepseredin and let your gut do the conversion ?

I think taking hesperidin / hesperitin might be one of the highest ROIs in the bioenergetic field.
Especially if you take into account the studies @cs3000 posted on the RPF and I've also added some here. It's wild how many benefits it has.

[alfredoolivas]

@Mauritio said:

I think taking hesperidin / hesperitin might be one of the highest ROIs in the bioenergetic field.

I have done 3l of orange juice for a few months which apparently has 1,800 mg Hesperidin.

I didn't notice any benefits from this. If this multi factoral experiment means anything.

[Mauritio]

@alfredoolivas I think I notice more from a hesperidin supplement than from an equivalent amount of orange juice.
I call this "the isolated compound paradox" . Happens frequently, not sure why.