Bile can serve as a reservoir for funghi, making them harder to treat
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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.
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@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)
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@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. -
@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. -
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.
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@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. -
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. -
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?
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. -
@Mauritio Yes I have it in bulk so I just grabbed my next best spoon and filled that up. It's indeed harmless. From within the EU you can get it from Lithuania via rawpowders(dot)eu.
Afaik the rise in PRL isn't chronic but only acute and like what a good night's light hygiene should do anyway. Nothing to take before any sexual or other endeavours. When I had first tested 10, 20, 30mg doses (during daytime) I felt and measured the drop in body temperature for the following hours.Hesperitin comes from the lands of pandas. Thinking that a 500mg dose should achieve a proven to be biofilm-busting 0.5-1mg/mL concentration in the duodenum and jejunum.
Nystatin is a blend of more than one molecule. Its activity is currently standardized to 5710 IU/mg in accordance with modern production techniques.
Taking two doses of 11 million IU within hours in one evening and followng up with 5 million IU four times throughout the next day has ascertained a serious chronic fungal burden.
Felt as if I wouldn't be able to bear it. Brutally strong headaches. Stiff neck. Super-high intracranial hypertension. Barely made it through two nights of not even being able to rest my head on my neck but only kind of sideways because of the intense pressure. Thought it could be a good idea to take NAC to relieve the liver of whatever but I assume it was NAC's biofilm-busting property which made things even worse. Lots of vomiting. Sort of an aseptic meningitis experience. Brutal, brutal, brutal.
Currently continueing, somewhat stable, with 2.5 million IU four times daily before daring to raise it or to add any extras. -
I've been reconsidering past supplements and their effects in the face of fungus and biofilm.
work in progress• All the B vitamins and also vitamin E quite strongly feed Candida glabrata (Caveat crucial differences to C. albicans).
• Magnesium feeds it too and the ambivalence is enhanced by its much stronger osmotic effect when mucosal absorption is impaired.
• Calcium significantly stabilizes biofilms, explaining possible initial symptom relief at the cost of long-term worsening. Perhaps even more effective against systemic effects of C. albicans than glabrata as it could temporarily "clog-up" the candidalysin etc toxins of C. albicans within the biofilm.
• Zinc and iron supplemenation feed it and greatly strengthen its biofilms. On the other hand zinc can significantly raise mucosal immune responses so it's quite double-edged; good for prolonging and intensifying any suffering even though most people need more zinc for many bodily functions.
• Copper, in contrast, is a disruptor and also raises defence mechanisms. It's quite a burden on the system but at least doesn't help out the fungus.
• Butyric acid and lactic acid act as topical biofilm disruptors and can therefore aggravate local symptoms. Nice to have endogenously as naturally prophylactic countermeasures.
• Alpha lipoic acid, interestingly, causes fungal membrane permeabilization at its subinhitory concentrations achievable by oral or iv. administration. I.e. it weakens fungal cells and makes them more sensitive to penetration by azoles and other antifungals or destruction by host immunity.
On the other hand, orally administered ALA exerts significant chelation of the metals and minerals like zinc and iron in the GI lumen and topically. Such sequestration significantly disrupts fungal biofilms and has the potential to aggravate local symptoms especially in the duodenum, jejunum and, if mucosal absorption is impaired by biofilms, further beyond.
Talk of ALA in the context of fungi is dominated by its half-time and redistribution issues (Cutler protocol) of toxic metals like cadmium and mercury and it is being argued by quite a few folks that these heavy metals were at the base and enablers of any chronic fungal infection. But from the aforementioned, ALA obviously has possible (over)straining impact also in the absence of pathological levels of Cd or Hg.
• EGCG binds iron, therefore a powerful biofilm disruptor especially topically; potential to aggravate local symptoms. EGCG weakens growth and resilience of Candida by inhibiting their endogenous folate synthesis.
• The major importance of (divalent) metals/minerals in biofilm composition and stability brings up the potential of oral EDTA administration as a more powerful chelation tool against intestinal fungal pools. EDTA's meagre oral absorption is of very good benefit and of relative merit over ALA's worrisome systemic heavy metal redistribution in this context.
• Enzymes: I've again been considering beta-glucanases against fungal biofilms and cell walls. Chitinases/(Hemi)-cellulases are of secondary importance. IMO the two only proper oral enzyme products against Candida are the Biofase by D & G Industries and the Ther-Biotic Interfase Plus by SFI Health / Klaire Labs. They are pricey and for some reason I keep skimping on them. I don't see great use of nattokinase or serrapeptase or fibrin targeting against fungal biofilms. However, I'm reconsidering bromelain in the face of strong past aggravating reactions to this compound. By what I can find the direct antibiofilm activity of bromelain is not so clear but most of its promises are shown against candidal adhesins. I.e. the extracellularly placed proteins used by Candida to attach themselves to surfaces and tissues.
In the face of bromelain's excellent systemic uptake and distribution I'm thinking that it may help weaken the apical attachment of fungus from the host's side at the base of their biofilms (rather than attacking the exterior layers). Bromelain appears to cover pretty much the same targets as papain: Maybe one is slightly more effective than the other but I see no need to take both. It will always somewhat irritate the mucosa, of course. Perhaps of extra benefit over papain is the dilution and degradation of mucus viscosity to increase its transmucosal cleavage of adhesins.
IME the disruptors are an everlasting pain without concurrent antifungals.
And the antifungals are (besides mostly underdosed) greatly insufficient if not combined with proper biofilm disruptors.
Current tools to use: Nystatin, an azole, hesperitin, NAC, bromelain. No or minimal supplemental minerals. Must look into EDTA (otherwise EGCG or ALA on an empty stomach).Addendum 1:
There's tetrasodium EDTA/edetate which is alkaline and disodium edetate which is slightly acidic.
The disodium form would seem to be more sensible to pass through the stomach. It's freely and cheaply available.
In contrast, for i.v. use it's always calcium disodium EDTA as it is supposed to release its pre-loaded calcium ion upon facing the greater binding affinity of a heavy metal ion. Quite necessary for i.v. use to lower acute cardiovascular risk and bone loss but it makes no sense for oral use against biofilm as one would explicitely want to sequester also calcium.
There was one poster one reddit 8years ago reporting on using disodium EDTA and feeling initial symptoms already from a mere 50mg before eventually creeping it up to 300mg once per day. Better to start humbly then.
Addendum 2:
Definitely encapsulate any oral disodium EDTA. It's not very acidic but obviously readily grabs calcium. If you know how freshly mineralized teeth feel: Having drunk Na2-EDTA dissolved in a glass of water, even after an immediate extra rinse, feels like the opposite of that.
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