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

[Mauritio]

@CrumblingCookie thanks for sharing!
Very interesting. Let us know how your anti fungal cycle goes. I might try some stronger anti fungals ,too.

[Mauritio]

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

there is a study showing pancreatic cancer patients usually have a fungal infection of the pancreas

I found this study.
The microenvironment of a pancreatic tumor has a distinct micro biome including bacteria and fungi. Fungi are increased in mice and human samples with pancreatic cancer. Malassezia was the most prevalent species (interestingly most people with hair loss have a scalp infection of it)

They found that fungi caused cancer growth!
"...the fungal mycobiome promotes pancreatic oncogenesis (11)."

And more importantly, killing that fungus stopped cancer growth!
"Ablation of mycobiome with antifungal medications, such as amphotericin B or fluconazole, protected mice against oncogenic progression."

Has this been tried in humans ?
This should be another reason why Haiduts anti cancer protocol works, high dose B3 and Aspirin are anti fungal.

P.S. the authors also mention how bacteria influence tumor progression.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7607088/

"PDA tumors harbored a ~3000-fold increase in fungi compared to normal pancreas in both mice and humans."
https://pmc.ncbi.nlm.nih.gov/articles/PMC6858566/

Itraconazole inhibits proliferation of pancreatic cancer cells through activation of Bak-1
https://pubmed.ncbi.nlm.nih.gov/30260036/

Pancreatic cancer patient was already admitted to palliative hospital. Then received itraconazole, the tumor became operable, survived several years.

"After he received his nine-month course of itraconazole, the pancreatic cancer was readdressed and he was then deemed to be resectable and had a Whipple procedure. Over the next several years, he showed no evidence of pancreatic metastases or relapse."
https://pubmed.ncbi.nlm.nih.gov/25670260/

[sunsunsun]

@Mauritio high dose niacinamide is not nearly as effective in vivo for dogs against what im pretty sure is mallessezia compared to a normal dose of fluconazole. and ketoconazole seems about the same as fluconazole. no experience with itraconazole but will prob try it at some point, it is very expensive in north america or europe. just observations not really scientific. in humans iirc terbinfine might be pretty good for mallessezia but in dogs they excrete it too quickly apparently.

if a dog has itchy ear , one dose of fluconazole will knock it out for a couple weeks. no need to give everyday.

imo cancer patients could probably all try an antimicrobial protocol with an antibiotic, antifungal, and antiparasite drug. reaearchers keep looking for a side target of the above drugs but im guessing the actual antimicrobial part is probably anticarcinigenic

i also have seen evidence anti serotonin drugs are anti parasite. theres a study on cyproheptadine being an anti parasite drug, from https://www.cabidigitallibrary.org/doi/full/10.5555/19900860028?__cf_chl_tk=ThtQHEaB7fbCcC9qnD19tIV6PYSAm9plCdzDERWJ0R0-1775529914-1.0.1.1-pMIrmBv2QC7gUB4mLmBDUGspQSWjaQ7agFuosFIZ.fI

[Ecstatic_Hamster]

The late and great Travis believed that boron is antifungal and that's why borax often works against arthritis. I wonder if reasonable qualities of borax could help kill fungi in the body. Travis believed so

[maplesyrupbro]

@Ecstatic_Hamster Late Travis? Is he dead?

[yerrag]

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

The late and great Travis believed that boron is antifungal and that's why borax often works against arthritis. I wonder if reasonable qualities of borax could help kill fungi in the body. Travis believed so

Good idea. My knees are sore and there are many reasons to make if sore. But it is as context specific just as it is for high blood pressure.

I need to add borax to my daily supplements to see if this works.

[yerrag]

@ecstatic_hamster

How much borax is a daily dose you woukd recommend?

[CrumblingCookie]

@Mauritio said in Boron supplements:

What symptoms did you see improvement with ?

I had been taking:
Amphotericin B (per os), 100mg, four times daily
Nystatin 1 mn IU, three times daily
Borax 5g/L in drinking water for 7 days,
Itraconazole 200mg pd for 8 days, followed by
Fluconazole 200mg pd (400mg initially) for 12 days
Berberine 500mg, three times daily
Propolis extract, c. 1200mg, twice daily
1 bulb of squeezed fresh garlic pd
Simeticone 250mg once to twice daily to ease the garlic-induced flatulence,
Trans-resveratrol 500mg, twice daily
Bidifobacteria & lactobacilli blend, 1 bn, twice daily
Clostridium butyricum myairi, 600 mn three times daily

Effects of the added AmB, Nys, Itr / Flu were:
+ Halving of daily BMs (and no more liquid diarrhea), - but all associated issues remaining
+ Significant decrease of long-standing (years!) chronic pains in lymph nodes
+ Notable but unstable, fluctuating improvements of swollen sinuses (chronic sinusitis)
+ Improvements of elevated resting heart rate and blood pressure readings.

Notable improvement wrt fat maldigestion/malabsorption only set in three days after introducing the following:
Increasing Flu from 200mg to 300mg pd
Oregano essential oil, c. 4-5 drops in total pd (in food or oil)
Colloidal silica 2.8%, 15ml pd in a cup of water
Borax 0.5g/L in drinking water

The propolis extract seemed of little systemic use and was removed from the regimen.
Nystatin has slowly been removed as well after c. 2.5 weeks because of the overlapping with oral AmB.

Adverse effects of the Itr /Flu:
- Profound headaches (only in part relieved by psyllium with clinoptilolite)
- Enhanced depression, sadness, mental exhaustion. Especially initially, raising suspicions of cerebral fungal afflictions.
- Very dry skin and scalp. Very dry, dark-red, painful, peeling lips.
-> This is a known side effect of azoles. Especially fluconazole. MoA is unknown; something to do with renewal of skin cells. When this sides effect shows on the exterior skin I suspect GI cell renewal is affected, too.

I'm no fan of the oregano essential oil. However, it appears to be one of the most powerful adjuvants. Obviously very bad for already damaged lips and the bottle always dispenses more drops per serving than I intend (should really use an eyedropper for it).
Intuitively I'd say the oregano EO and garlic are the two most powerful adjuvants.
I'm really underwhelmed by internal use of borax. If Travis was right and there's indeed substantial antifungal effect from it for an extensive part of the population I must suspect either a predominantly prophylactic effect (rather than therapeutic) and/or a highly varying susceptibility of fungal strains to boron.
I suspect the borax to dry out skin, too, and possibly making riboflavin profoundly unavailable (Boron forms very hydrophilic (easily washed out) complexes with B2).

Currently:
Have stopped the 300mg Flu pd after 8 days and letting it fade out of the system over at least four days because it is said to negatively interact with the action of flucytosine.
Two days later: Strong joint pains, feeling very cold and insatiable which may all be immunological rebound effects by the Cyp27B1 inhibition (25-OH-D3 to 1,25-OH-D3) of Itr + Flu.
Three days later: Notable recession of the digestion improvements which had come with the 300mg pd. Return of chronic abdominal pains.

Flucytosine is essentially 5-Fluorouracile, the bread-and-butter chemotherapy cytotoxin. It converts to 5-FU in susceptible yeast cells, yet to an unknown and varying degree also in the microbiome which is the mainly assumed cause of its adverse systemic effects.
-> As far as I could find out, neither Lactobacilli nor Bifidobacteria nor Clostridioides convert 5-FC to 5-FU but E. coli and Enterococci and Citrobacter do! Quite impossible therefore to avoid such intestinal conversion.
5-FC has a very short half-time and must be taken 4 times daily at regular intervals and peak serum concentrations ought to be measured three days into treatment. Empirically, the majority of treated patients exhibit peak and through serum concentrations out of range; either too high (toxicity!) or too low (treatment failure).

Only today have I stumbled across differing treatment recommendations for oral AmB:
Some package slips say 100mg four times daily
yet in other countries the standard dosage is stated as 500mg four times daily. Both refer to exactly identical product compositions! What's up with this?
Maybe there's a profound lack of knowledge wrt dosage and 200-500mg AmB are more appropriate for (lower) GI effectivity in contrast to upper oropharyngeal treatment.
That could potentially render the coated 100mg AmB tablets escpecially daft and misleading because they are A. oropharyngally unavailable and B. the lowest bottom end and possibly insufficient dosage for targeting the lower GI system.
Given the lack of absorption and systemic side effects it'd therefore probably be wise to not slouch about with 100mg but to increase the oral AmB dosage to 200-500mg four times daily.

@mauritio
Had read your old thread on the RPF again on riboflavin activity against Candida. Unfortunately, there are crucial caveats to it: That only applies to C. albicans.
C. glabrata, however, thrives on it. Throwing B2 or B1 or B3 at C. glabrata acts as a strong growth stimulant. C. glabrata (and Aspergillus spp.), in stark contrast to C. albicans, even feeds on bismuth subsalicylate (Pepto Bismol) / subcitrate to grow its biomass!
Unfortunately the C. glabrata is a definitely cultured part of my pathogenic mycobiome and I couldn't get an antimycogram on it.

@Mauritio said:

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.

I'd say to maintain a multi-pronged approach at all times. Afaik if resistancies develop they can rise within a couple of days. Don't know if any ineffective compound may prove to be effective again at a later time? Do strongly suggest to take biofilm breakers only in intermittent intervals as they can be way too harsh long-term.

@yerrag said:

But this should explain to me why it has become common practice for doctors to administer antifungal drugs after successfully treating a patient with antibiotics. But they cannot explain why

Thanks for sharing. What most wondrous and advanced country do you live in where doctors routinely prescribe antifungals with or following upon ABx treatments? Never happened to me. Never. And I have had incredibly absurd amounts and varieties of ABx. No medical practitioner ever mentioned fungi in over 20 years.

[Mauritio]

@CrumblingCookie Thanks for your answer.
Will be interesting to see if you find long term benefits from this hardcore treatment.

Have you checked your iron and ferritin levels ?
Candida thrives on iron and makes it more virulent.

My bile flow issues could be caused by a fungal infection as well. Found a few studies on that.

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

Don't know if any ineffective compound may prove to be effective again at a later time?

I think only partly. And thats kind of creepy. Does the fungus remember for months lol . Probably something like a epigenetic adaption. Not sure.

[sunsunsun]

re: iron chelating effect of doxy assisting antifungal effect of fluconazole study, the user above has concerns with doxy use so aspirin is probably suitable

idk if mentioned but using taurine or tudca directly to thin out the bile (this is actually a thing described in the merck manual for the latter with UDCA) is probably a good idea. im guessing the more watery the bile is the less hospitable it is to fungus

[CrumblingCookie]

@Mauritio Serum iron has been at the top of ref. range since almost forever.
Serum ferritin used to be low between 30-60 but to my probable detriment I had received four i.v. iron treatments four years back due to persistent anemia and ever since ferritin has been above 120 (-240).
Only when I stumbled upon copper Morley's high-tier references did I see that serum ferritin is another essential lie and sort of like serum liver enzymes: In general it shouldn't be floating about freely in any significant amount.

@sunsunsun Such combos are def worth a thought!
All I can report is that TUDCA or taurine without antifungals had been making things significantly worse. Perhaps it did release fungi from a biliary reservoir and could turn out differently when combined with antifungals at the same time.
Similar to how some dietary sugar can be a good complement to antifungals as the thereby enhanced metabolism of yeasts raises their susceptibility to antifungals. Just like we need bacteria to not be in a dormant but replicative state to be harmed by ABx.
I may want to try TUDCA again in this context. Have also been thinking of pinning some i.m. thiamine or taking it orally for the same reasons. Yet only once I'm feeling sufficient confidence wrt the effectivity of the antifungal treatment!

[yerrag]

@CrumblingCookie

I live in Manila, Philippines. I apologize for giving the wrong impression that treating for fungus is common after a round of antibiotics. It depends on the attending physician, and the one that took care of my mom delayed my mom's discharge by giving her antifungals after the antibiotics treatment.

I felt it was odd because it seemed to worsen my mom's condition. I felt fungus is not well understood by doctors. It's hit or miss.

I think that practicing solely germ theory detracts from a better understanding of fungus, given that pleomorphism in terrain theory allows for the idea that bacteria can change into fungus.

[Mauritio]

@sunsunsun yeah I think so too and minimizing intake first. I stopped using my iron cast pan about 6 weeks ago. Had another blood test on Friday so we'll see if ferritin is still high.

Taurine always makes my cholestasis worse for some reason. It is constipating.
TUDCA I should give another try.

[CrumblingCookie]

@sunsunsun
The Japanese had found increased susceptibility to severe fungi infetion and mortality thereof in liver injuries. Additional transferrin negated the extra mortality from liver injury in rodent studies.
I.e., liver injuries lead to less transferrin (and UIBC (unbound iron binding capacity) and TIBC (total iron binding capacity) and it is that decrease of transferrin which enhances fungal infections.
https://pubmed.ncbi.nlm.nih.gov/2960898/
https://pubmed.ncbi.nlm.nih.gov/2975353/

Copper (and retinol) are therefore very essential in prevention of fungal infections.
Not sure about any treatment efficacy after infection has already occured, though. Surely more free iron will stimulate fungal growth - but does iron restriction assist when aiming for fungal eradication from tissues?

I have been trying to raise my ceruloplasmin (and thus functional transferrin) by regular copper intake since late last year.

Also, in this paper from 2000 a strong clinical distinction was suggested between acute disseminated candidiasis and chronic disseminated candididiasis: Again, in CDC, there's typically no candidemia and whereas ADC involves several organ system, CDC predominantly befalls the spleen and liver. Typical findings are hepatosplenomegaly, and focal hepatic lesions by ultrasound imaging and recurrent fevers although I reckon the presentation of the latter two will be subject to the mentioned individual immunological response and existence of an even more latent phenotype of CDC (as abundantly shown in other publications in this thread).
Interestingly, cultures and histophathology of liver biopsies again frequently failed to detect fungi proven to be present by clinical signs and PCR of liver biopsies (no positive fungi PCR in healthy control group).

In this 1992 publication intrabiliary Amphotericin B was successfully used in a child after (typical) failure of priorly administred systemic AmB to clear the biliary infection. Good for her. Yet only downstream of the hepatic tumor she had been hospitalized for.

[Mossy]

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

Copper (and retinol) are therefore very essential in prevention of fungal infections.

I have been trying to raise my ceruloplasmin (and thus functional transferrin) by regular copper intake since late last year.

Do you think consuming beef liver would be enough to help with this?

[LucH]

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

Do you think consuming beef liver would be enough to help with this?

In prevention, yes. Not when contaminated.
Copper (Cu):
in beef liver (3 oz.): 12 400 mcg
in chicken pan-fried (3 oz.): 455 mcg
in seeds the best options include sesame seeds, almonds, sunflower seeds, and cashews. A 1-ounce serving of these crunchy seeds can supply around 0.5 to 0.9 milligrams of copper.
In pumpkin seeds 1,34 mg per 100 g. 1 tbsp is 7.44 g and brings 99 mcg Cu. => I put 1 big tsp in my smoothie with pomegranate.

Ceruloplasmin is a protein your liver makes. It helps copper circulate throughout your body and plays an important role in making the iron that you get from food ready to move from your intestines to organs like your spleen. You need copper to help maintain energy and bone health.
So, no direct need for blood or liver needs but well for SOD enzyme. Copper is required for sod enzyme in infection control. Cu and Zn are required for superoxide dismutase enzymes. Interaction between HD take (+/ 1/10 Cu/Zn).
And Yes, retinol is also required in the immune process (interaction with A D K). I take 2x/wk. 5 000 UI (retinyl palmitate).

[Mauritio]

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

but does iron restriction assist when aiming for fungal eradication from tissues?

I suspect so. At least on the sense that lower iron will make fungi more susceptible to anti-fungal treatment.

"The SC5314-strain and oral isolates showed enhanced antifungal-resistance towards most antifungals tested, under high iron."
https://www.tandfonline.com/doi/full/10.1080/20002297.2022.2044110#abstract

[CrumblingCookie]

This study has an interesting hint: we need small and hydrophilic molecules for an anti-fungal effects that isn't reduced by bile.

"In contrast, small and hydrophilic molecules, such as cycloheximide, flucytosine, or sodium azide kept their antifungal properties. "

It's difficult to not despair in the face of things continueingly worsening since the stop of fluconazole 300mg pd in spite of having commenced flucytosin treatment (100mg/kg BW /day) already 5 days ago.
Flucytosine's mechanism of action is a slow, gradual, delayed intracellular conversion and poisoning in contrast to the rather immediate mechanism of action of fluconazole.
Whilst Flu especially accumulates in mucosal tissues, it principally seems true that FCy doesn't even start to work within a couple of days but requires about 2 weeks to get going:
Fluconazole vs. flucytosine in the treatment of esophageal candidiasis in AIDS patients: a double-blind, placebo-controlled study, 1995
On the other hand, the FCy (5-FC) has been making me feel weak and woozy in the head since day one. It's also been exerting a weak cardiovascular burden.

I've read in some paper that the fear of developing resistancy to FCy monotherapy is much exaggerated as there have been very few reported cases of it happening in-vivo.
The urgent recommendation of pairing FCy with i.v. AmB for at the very least 2 weeks of treatment induction must be, to a great extent, down to bridging the temporal gap until onset of FCy efficacy.

Serologically, my C. albicans antibodies are nil and serum CAGTA antigen is also nil (that's the Candida spp. hyphal protein).
Thus, unless there's a specific humoral defect, C. albicans has no involvement at all in my case. C. glabrata, however, generally doesn't do hyphae but is able to be sufficiently nasty and virulent in its yeast form.
Circulating serum 1,3-beta-D-Glucan levels (as a systemic marker for most fungal species) also aren't elevated but at half of the lab's threshold.
There are therefore really no lab markers at all to support any physician in joining speculations on a hepatic/biliary fungal infection. It's difficult to not despair.

Have stopped the borax drinking water.
Have started 500-1000mg of UDCA per day to enhance bile solubility and hydrophilicity.
Also trialled alpha-GPC for two days in this context. However, that turned super awful. Choline and in particular alpha-GPC is a superfood to fungi which they gobble up for its choline and phosphate.
Kind of disadvantageous when you know that the liver needs substantial amounts of choline for itself.
Have pinned 100mg Thiamin-HCl i.m.

@mossy I wouldn't know! I dislike and distrust liver so have gone for the isolated substances and followed them up with testing of serum (free) copper, ceruloplasmin and retinol. IIRC there was one guy writing on the old RPF that he had eaten lots of liver regularly and his lack of copper was surprisingly unaffected until he started supplements.

[sunsunsun]

any opinion on pH and yeasts?

[Mauritio]

@CrumblingCookie I hear you. It's frustrating.

Molybdenum might be good addition to help die off and metabolize acetaldehyde.

Ive recently noticed that eating radish seems to help me . I think it is downstream from improved liver and gallbladder health. Raddish can increase phase 2 detox in the liver and help with bile flow.
It's metabolites (sulforophane) also activate Nrf2.

I've also ordered TUDCA and some homeopathic remedies, to help with bile flow.