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

[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.

[CrumblingCookie]

@Mauritio said:

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

I want it to be active in high concentrations already in the lumen of the proximal small intestine for on-site support of nystatine megadosing and the azole (+ maybe NAC). If I were to not have that target I'd indeed simply buy and use plenty of the OTC capsules.

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

+1. Great findings.
IMO much more promising, functional and better ROI than e.g. urolithin A or all those Mephistophelean crooked dopamine modulators far, far far downstream.
Melatonin is the other protagonist of mitochondrial health I'm currently swayed by.

Had been taking 160mg of it each night for a few weeks now. The daytime grogginess btw disappeared with a combo of large-dose niacin, riboflavin, biotin and P5P. Took 3grams melatonin last night. Same effect of relaxed sleepiness from about 1 hour in but much smoother skin today. However, at such doses it appears to be the most powerful inducer of the gastrointestinal MMC I've come across and that's way too much for me in my state of being. Probably great for the on-the-brink-of-constipation folks, though. Oh boy, I do hope to become better.

Back to the fungal topic:
I'm suspecting there's something profoundly wrong with the quality of pharmacy nystatine 500,000 IU tablets. They may be consistently underdosed or super-degraded garbage. Perhaps that's why they stopped working rather than from causes within the individual.
It's a bit of a mental barrier to start assuming such but every now and then throughout the years I have come across anecdotes of other pharmaceuticals where brand or origin is of crucial difference for therapeutic response.
Raw nystatine is super sensitive and quickly degrades upon exposure to light or humidity.

[Mauritio]

@CrumblingCookie said:

I want it to be active in high concentrations already in the lumen of the proximal small intestine for on-site support of nystatine megadosing and the azole (+ maybe NAC). If I were to not have that target I'd indeed simply buy and use plenty of the OTC capsules.

Where are you sourcing hesperitin?

@CrumblingCookie said:

Had been taking 160mg of it each night for a few weeks now. The daytime grogginess btw disappeared with a combo of large-dose niacin, riboflavin, biotin and P5P. Took 3grams melatonin last night. Same effect of relaxed sleepiness from about 1 hour in but much smoother skin today. However, at such doses it appears to be the most powerful inducer of the gastrointestinal MMC I've come across and that's way too much for me in my state of being. Probably great for the on-the-brink-of-constipation folks, though. Oh boy, I do hope to become better.

3g ?? That's wild. Did you buy it in bulk or what ? Lol
But melatonin seems to behave differently in different dosages. Although I thought high doses increase prolactin significantly. Do you notice any high prolactin symptoms ? Maybe super high doses behave differently.