Bile can serve as a reservoir for funghi, making them harder to treat
-
@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. @bearwithmeThe 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?
-
@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. ”
-
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
-
@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 mallesseziaberberine seems interesting, is it peaty ? it isnt right, because it is like metformin and metformin isnt peaty
-
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.
-
