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

[Mauritio]

@sneedful said in Bile can serve as a reservoir for funghi, making them harder to treat:

EGCG at slightly alkaline pH is effective against candida. maybe some sort of liposomal egcg that makes it into the bile would work

EGCG is a small/medium sized molecule and only slightly water soluble. So there are better candidates than it. Maybe when it forms complexes with other molecules it makes it more water soluble .

[LucH]

@Mauritio said in Bile can serve as a reservoir for funghi, making them harder to treat:

Essential oils like thyme oil/thymol are fat soluble .
As per the posts above we need small, water soluble molecules .

What about dissolving the mix EO in alcohol before adding the "solution" in water, and last olive oil in the shake.?
Essential oils are miscible in alcohol. Then we mix EO and alcohol in water. Miscible too.

[Sunniva]

https://pubmed.ncbi.nlm.nih.gov/18451594/

Dimethyl sulfoxide (DMSO) inhibits the germination of Candida albicans and the arthrospores of Trichophyton mentagrophytes
Muhammad Akram Randhawa. Nihon Ishinkin Gakkai Zasshi. 2008.
Free article
Abstract
Dimethyl sulfoxide (DMSO) is commonly used as a solvent for antifungal drugs. Earlier the author has reported the inhibitory effect of DMSO on the growth of many strains of dermatophytes' colonies in dermasel agar and proposed that this could cause the variations between results of different studies for the evaluation of the activities of antifungal drugs. In studies regarding the determination of the effect of antifungal drugs on the germination of arthrospores of dermatophytes it was observed that relatively higher concentrations of DMSO were being used as a solvent for the antifungal drugs, the final concentration in the media being 5%. Therefore, the present study was aimed at determining the effect of different concentrations of DMSO (1.25 to 10%) on the growth of germ tubes of arthrospores of Trichophyton mentagrophytes and Candida albicans, in glucose peptone broth. With DMSO 10% there was a negligible growth of germ tubes of both the arthrospores and yeast; between 2.5 and 7.5% there was a rather linear dose-related inhibitory effect; whereas 1.25% had insignificant effect from controls. The present study shows that besides other factors, variations in the results of the susceptibility tests of antifungal drugs might occur due to the effect of DMSO on the growth of fungi and differences in the final concentration of DMSO in the medium.

[yerrag]

Have you considered turpentine? It has been used to fight candida albicans in the gut suçcessfully by Dr. Daniels

I once discovered by live blood analysis I have candida residing inside my red blood cells. It was causing hemolysis but was not detectable by standard lab testing. I took turpentine daily for 2 weeks and I believe the candida was gone but it also helped that I made sure I had acid-base balance by having good mitochondrial metabolism with also help using carbogen while I slept. I could not really verify but my urine had turned into a golden fluorescent color where it had been beer amber that showed tinges of blood.

[Mauritio]

@yerrag I took Haarlem oil daily for a while.
I believe it contains turpentine and sulfur. I got less and less of an effect as time went on so I stopped. But I recently reintroduced it and found that cycling it, seems to maintain its effects.

[dapose]

I think the idea of killing fungi in your body is absolutely ridiculous. Fungi digest dead material. They have no ability to digest living tissue. They exist like webs on dead or damaged tissue to slowly digest things that no bacteria can eat yet. If you have a fungal infection in you, it’s because you have dead or damaged tissue in you. Which is likely since our cells are turning over new cells constantly so we would constantly need things to remove the dead tissue. Hence the need for a high metabolism. Bile flow liver secretions, lymphatic drainage, pooping peeing, sweating. And I believe this is what people talk about needing a “good” microbiome. Lots of fungi! Lots of diversity or living bugs and fungi. Some parasites too. Your gut is a compost pile. And your metabolism is a motility motor. Right? Keeping your temperature high co2 high keeps your biochemistry just right for your internal garden.
Apples apple juice and tart cherries are a good way to increase bile production.
I like aloe Vera juice a couple shots a day for the emodin to get rid of extra crap. And cascara a couple times a week.
Pau D’arco and pu erh tea are great too.
There are some delicious moldy cheeses that have penicillin in them too that whenever I eat those a feel remarkable!
I hope to inspire people to look into what the point of fungus are. And not simply think, I have fungus in me! I need to kill it!
I mean Ray was never advising to kill candida. Didn’t he say fasting just makes candida way more embedded into the gut lining. And potentially lethal. He was saying keeping your small intestine clean and your motility moving etc. thyroid high.
‍🟫

[yerrag]

@Mauritio

Glad that it worked for you the 2nd time around. It could be about cycling, as that is something I forget to do at times. It it could be that you changed that made your interior more conducive to being fixed.

[yerrag]

@dapose You hit many right notes there. Usually there is an imbalance and that leads to a dominance that is seen as pathogenic. Perhaps we should see restoring balance as the goal. We never really kill or eliminate like genocides are natural, we only discourage dominance because uneven playing fields make it happen. Intentional or nor.

[CrumblingCookie]

@Mauritio said:

we need small and hydrophilic molecules for an anti-fungal effect

Im looking for anti-fungal candidates that fit the above category:

Encapsulated calciumhypochlorite granules ("Chloryte") may fit this bill for the upper GI and various deep tissues. It's rather rough and destructive and not a thing to do for more than two weeks at the very most, IMO.

@Mauritio said:

I took Haarlem oil daily for a while.
I believe it contains turpentine and sulfur. I got less and less of an effect as time went on so I stopped. But I recently reintroduced it and found that cycling it, seems to maintain its effects.

Turpentine (or more generally monoterpenes) reduce hepatic cholesterol synthesis, thereby reducing the cholesterol-saturation of bile which is then able to gradually dissolve cholesterol "plaque" or even proper stones along the bile ducts and in the gall bladder. That improves the biliary milieu along with better biliary flow. It's a very long-term process, however. It takes several months of taking monoterpenes ("Rawachol" capsules or tincture is an OTC product) 2-3 times daily. Tudca or Udca works well together with monoterpenes.

@Mauritio said:

I'm not sure how the treatment should look.
Increasing transit speed and frequently emptying the gallbladder by eating fiber, using specific supplements like FXR-agonists

Tudca and Udca also reduce the same enzyme of hepatic cholesterol synthesis, while additionally altering the bile acids composition towards being much more hydrophilic and less sticky, and also increasing the bile salt export pump for an in overall much greater bile flow (less stasis).
I'd rather use those daily instead of doing any more gall bladder flushes ever again (which only work in a very mechanical and macroscopic way).

[dapose]

@yerrag
Well said Ye!
I would say heavy hitters in the militaristic approach to a balanced system would be Castor Oil packs on the skin over the liver.
Higher dose Aloe Vera Juice.
Oregano oil + activated charcoal.
Russian Sauna. Or fever.
And Swedish Bitters one shot in warm chamomile tea.
The big guns!
Have you ever tried clove tea for your lungs!!?? Supposed to be great!!!

[Mauritio]

@Sunniva said in Bile can serve as a reservoir for funghi, making them harder to treat:

(DMSO) inhibits the germination of Candida albicans

That is so interesting . You just helped me to connect the dots.
Several times when I used Melanon topically on the area above my liver/gallbladder I experienced fungal die off. I attributed it to apigenin or naringenin, but it might as well be the DMSO.
Apigenin and naringenib are also anti-fungal. They're also small molecules, but not hydrophilic. But still Melanon should be a very effective anti fungal applied topically.
https://pubmed.ncbi.nlm.nih.gov/29346565/
https://pubmed.ncbi.nlm.nih.gov/33934490/

If the gallbladder is so hard to reach for anti-fungals maybe topical is the way to go.
Maybe using some anti-fungal IdeaLabs supplements over the gallbladder would be good, ideally one that uses DMSO as a solvent.

Alternatively dissolving MSM in DMSO should help. It is a small, hydrophobic molecule and it dissolves in MSM so it might be very potent if delivered directly to the gallbladder via topical application.

[CrumblingCookie]

@Mauritio
Very nasty! Thanks for pointing me back to this thread.
One thing I was immediately wondering about is whether the less-lipophilic fluconazole would then be more potent against bile fungi than the significantly more lipophilic itraconazole, even though fluco is quite completely being excreted renally and itra biliary.
But the answer lay in your linked study: Fluco was shown to be useless in bile. Utterly.
There no mentioning of itra in this context. Only a remark, that fungi increase their itraconazole-resistance in the presence of cholesterol. However, this mechanisms affects all azoles. Essentially, candida and other fungi can salvage exogenous cholesterol to make up for loss of ergosterol synthesis and are thus less affected by the inhibiting impact of azoles.

So how to tackle these biliarly persisters?
I doubt they will only serve as a reservoir without already being harmful where they are. In your linked studies it says, C. albicans hyphenates upon contact with bile acids. I therefore assume they do bad things already in the liver and gallbladder and potentially alter the function of these organs or of the bile composition. @bearwithme

The water-soluble flucytosine is available as 500mg tablets (ANCOTIL) on prescription for specific systemic fungal infections... certainly nothing anyone would easily obtain officially from a doctor because of a hunch of biliary fungal persistence!
I had never heard of it before.
Side effects are kind of the usual; don't get pregnant or impregnate anyone else within 6 months, blood cell discorders, skin detachment, fatal hepatic lesions, hypokalemia and heart troubles, the whole cluster of confusion, headaches, vertigo, neuropathies, hallucinations as well as respiratory impairments or arrest and reduced kidney functions.
What do you peeps reckon - is it wortwhile to try out?

@Mauritio said in Bile can serve as a reservoir for funghi, making them harder to treat:

Im looking for anti-fungal candidates that fit the above category:

MSM
Small molecule and highly water soluble , fits the bill.

Any info on how methylsulfonylmethane would be antifungal?

Oregano oil or winter savory oil mostly for the carvacrol and thymol are again strongly lipophilic.

Berberine is strongly synergistic with azoles and can overcome azole-resistance.
Propolis extract is antifungal as well and can overcome azole-resistance.
Boron.
Balsamic turpentine may be mostly anti-biofilm.
Especially boron may be mostly preventative at regular low doses but tbh I'm really disappointed with all of these on their own not being anywhere near to being effective on their own.

Maybe a topical antifungal like nystatin or amphotericin B for the GI lumen over quite a long term, plus a combination of systemic substances: boron, berberine, propolis extract, + pharmaceutical antifungal?

[CrumblingCookie]

@Mauritio said in Boron supplements:

@CrumblingCookie I agree with you on subclinical fungal infections.
They're very hard to get rid of. I posted a study about fungi hiding in the gallbladder when attacked. Let that sink in.

It's just as bad when we look into CNS persistence of fungal infections in chronic brain disorders, Alzheimers and dementia:
Tulane University & Tulane National primate research center, 2022

The potential contribution of pathogenic microbes to dementia-inducing disease is a subject of considerable importance. Alzheimer’s disease (AD) is a neurocognitive disease that slowly destroys brain function, leading to cognitive decline and behavioral and psychiatric disorders. The histopathology of AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide in the form of parenchymal plaques and abnormal aggregated tau protein in the form of neurofibrillary tangles.

Observational, epidemiological, experimental, and pathological studies have generated evidence for the complexity and possible polymicrobial causality in dementia-inducing diseases. The AD pathogen hypothesis states that pathogens and microbes act as triggers, interacting with genetic factors to initiate the accumulation of Aβ, hyperphosphorylated tau protein (p-tau), and inflammation in the brain. Evidence indicates that Borrelia sp., HSV-1, VZV (HHV-2), HHV-6/7, oral pathogens, Chlamydophila pneumoniae, and Candida albicans can infect the central nervous system (CNS), evade the immune system, and consequently prevail in the AD brain. Researchers have made significant progress in understanding the multifactorial and overlapping factors that are thought to take part in the etiopathogenesis of dementia; however , the cause of AD remains unclear .

“It has been suggested that Aβ functions as an antimicrobial peptide. Interestingly, C. albicans was found to be sensitive to synthetic Aβ and brain homogenates from AD patients that were capable of inhibiting fungal growth [178]. Additionally, it was demonstrated that Aβ protects against C. albicans in glial cells as well as invivo in nematodes [179]. ”

“Alonso and colleagues provided extensive evidence that disseminated mycoses are potential causative agents or risk factors for AD [173,180]. Different fungal genera detected in AD brain tissue include Malassezia, Fusarium, Candida, Cladosporium, Alternaria, and Botrytis [181]. An analysis of CSF revealed significant levels of Candida albicans and Candida glabrata in samples from AD patients. Approximately >89.6% of serum from AD patients tested positive for antibodies to Candida compared to 8.8% for controls [173].”

“The different species that were detected included Saccharomyces cerevisiae, Malassezia globosa, Malassezia restricta, and Penicillium. Furthermore, this group detected yeast and fungal proteins, including (1,3)-β-glucan, fungal polysaccharides, and mycoses, in the peripheral blood of AD patients, which suggests that a chronic fungal infection may increase the risk of dementia [173,180]. More strikingly, yeast-like cells and hyphal structures were observed in CNS tissue from AD patients using polyclonal antibodies against a variety of fungi [181].

Pisa et al. also provided strong evidence for fungal infection in AD patients [170]. Brain sections derived from AD patients showed that all were infected with fungi [170]. Fungal material was detected intra- and extracellularly in the neurons of tissues of AD patients, but no fungal material was observed in tissue from control individuals [170]. Moreover , fungal DNA and proteins were also found in brain regions including the frontal cortex, hippocampus, cerebellar hemisphere, and choroid plexus but not in control patient tissue. ”

[sunsunsun]

idk about in context of bile, but iron chelation in fungi via doxycycline makes fluconazole anti fungal against some candida rather than just fungistatic or no effect. aspirin is also an iron chelator.

there’s a study that suggests organ cancers often come with fungal infection of that organ too.

fwiw the warnings about ketoconazole being particularly liver toxic are apparently not actually proven. the symptomatic liver damage incidence rate in all the azoles is about the same.

overall for fungal issues i think the patient gets treatment with a normal pharmaceutical antifungal dose and length (could be months), and then keep the antifungals on hand to pulse dose as needed if symptoms return. and then use things like aspirin and doxycycine, include some niacinamide, sunbathing and nutrition etc to keep the stuff in check. total eradication of fungi seems impossible on a realistic sense

if bile is a reservoir for fungi maybe just eating high bile binding foods regularly can flush it out. rather than recirculating bile more

[sunsunsun]

@CrumblingCookie nystatin is pretty weak ime but i guess it depends on which fungi
ketoconazole cream works way better ime but idk what strains it is working agaisnt. i think mallessezia

berberine seems interesting, is it peaty ? it isnt right, because it is like metformin and metformin isnt peaty

[CrumblingCookie]

Thanks for sharing.
Indeed I currently find myself in a situation wherein I don't know for how long in total to continue fluconazole. Months? It costs about $60/week for me. And it's difficult to say which depressive mental effects are true sides and which are due to various degrees of die-off.
I wonder what role the continous re-infection from bile plays in commonly required treatment length. The notion of it being impossible to clear from tissues is what I find unsettling, too.
Have started to add in berberine today, 500mg thrice daily. Along with ample propolis extract twice daily.
Luckily I've failed to make it to the store in time and stumbled upon some garlic in my kitchen drawers and have read up on allicin again.
One half to a full garlic bulb per day is allegedly a good guideline for powerful effects (about 1mg allicin per kg BW from 3-5mg allicin per g fresh garlic). Ground it/crush it, let it rest for 10 minutes for the allicidase to do its work before diluting it in food or adding any acids like vinegar.

@sunsunsun said in Bile can serve as a reservoir for funghi, making them harder to treat:

iron chelation in fungi via doxycycline makes fluconazole anti fungal against some candida rather than just fungistatic or no effect

That study is in-vitro and super misleading however, because few antibitiocs, if any other at all, are as fungal-infection promoting as the tetracyclines because of their powerful, continuous inhibition of phagocytosis lasting for days even after stopping further intake. Tetracyclines are one of the main risk factors for fungal infections in literature. Ime they are very overhyped and terrible.

As for ketoconazole I'm wary of its unique VDR antagonism which essentially inhibits innate immunity and reduces xenoautophagy of intracellular endomyceles. That also essentially makes ketoconazole topical creams a powerful antiinflammatory for skin conditions, saving the extra prednisolone so enamored by dermatologists.

[sunsunsun]

@CrumblingCookie https://www.sciencedirect.com/science/article/abs/pii/S2213716517302229

[CrumblingCookie]

@sunsunsun Wax moths? They don't even have neutrophils and I won't deep-dive into finding out how their hemolymphs specifically compare to human or mammalian neutrophils.
I really do harbor strong apprehensions against the potential (mis)use of doxy on fungal infections.

What I would much rather do is oral terbinafin + fluconazole.
The terbinafin by itself is useless against many fungi species but by disturbing an earlier point (Erg1) in the sterol biosynthesis pathway it is synergistic with azoles (which act upon Erg11).
allegedly it strongly inhibits expression of the fungal efflux pumps responsible for azole resistance!
(! Berberine is the one which inhibits efflux pump expression. I had mixed it up).
This still won't tackle activitiy in the biliary tract, though.

I've done some more reading of publications on biliary / gallbladder candida / fungi.
Fungi can be causes of calculous (lithiasic) or also acalculous cholecystitis with or without mixed bacterial infections (Escherichia coli, Enterococcus, Klebsiella, Enterobacter, Clostridia).
Even in such rare and often fatal cases that happened to be documented, candidemia was rare despite frequent (almost always) fungal infection of other organs.

https://pubmed.ncbi.nlm.nih.gov/8862389/
https://pubmed.ncbi.nlm.nih.gov/28703118/
https://pmc.ncbi.nlm.nih.gov/articles/PMC8764969/
https://pmc.ncbi.nlm.nih.gov/articles/PMC12338181/
https://pubmed.ncbi.nlm.nih.gov/24474028/
https://pubmed.ncbi.nlm.nih.gov/8207288/

I don't have visible gallbladder wall thickening or distention or an obviously, universally accepted liver disease (except for hepatomegaly) but if I had I sure as hell would want to insist on flucytosine, or flucytosine + i.v amphotericin B along with any broad-spectrum antibiotics and before mutilating surgeries they'd offer.

Have looked more into berberine again, too. It's impossible to achieve its antimicrobial concentrations (at least 0.1mg/mL) systemically. Serum concentrations are about 0.5 - 16 ng/mL. I.e. 0.000005 mg/mL. Ridiculous!
The berberine in practical doses of 500-1500mg will thus be acting mainly within the GI lumen in support of oral Ampho-B. Berberine has low absorption but some will spill over to reach the liver for extensive first-pass metabolism, yet probably not into biliary ducts.

[Mauritio]

Great points, guys.

My current working hypothesis is rotating and combining several anti fungals daily + keeping bile flowing.

If i don't rotate the antifungals they seem to loose effect surprisingly quickly.
But what is obvious from many studies, is that combining certain anti fungals can drastically increase their effectiveness. Nystatin is synergistic with thymoquinone and also thymol IIRC.

The other important part is to keep bile flowing and excreting it. The lowtoxin crowd actually has a point there. Inducing a bile dump seems very therapeutic to me and followed by certain time of remission/ relieve.
So having adequate fiber intake seems important. Pectin is helpful, vitamin D and K as well.
I also ordered an herb that's used for cholestasis in TCM called Artemisia capillaris it has a lot of studies on liver health and general anti-inflammatory effects.

[Mauritio]

@sunsunsun said in Bile can serve as a reservoir for funghi, making them harder to treat:

idk about in context of bile, but iron chelation in fungi via doxycycline makes fluconazole anti fungal against some candida rather than just fungistatic or no effect. aspirin is also an iron chelator.

Makes sense. I've been using an iron cast pan for years and my ferritin came back very high.
Maybe that contributed to my susceptibility to (fungal) infections.

@sunsunsun said in Bile can serve as a reservoir for funghi, making them harder to treat:

total eradication of fungi seems impossible on a realistic sense

if bile is a reservoir for fungi maybe just eating high bile binding foods regularly can flush it out. rather than recirculating bile more

Yes agreed