Tinidazole, Cancer, and Grapefruit Seed Extract

paper from NIH National Library of Medicine said...

Abstract
The nitroimidazoles used in the treatment of anaerobic infection are well-tolerated by patients. With the possible exception of neurotoxic effects associated with high dosage, signs and symptoms of toxicity are transient and disappear soon after withdrawal of treatment. Teratogenicity tests in animals have given negative results in the case of metronidazole, ornidazole and tinidazole, and in the case of metronidazole no evidence of any adverse effect on the outcome of pregnancy was seen in women treated for trichomoniasis at various times during gestation, including the first trimester. The observed low general toxicity of nitroimidazoles is consistent with the non-occurrence of nitroreduction, as is the absence of chromosomal aberration in the circulating lymphocytes of patients receiving prolonged metronidazole therapy for Crohn's disease. Carcinogenicity tests involving the prolonged exposure of rats, mice and hamsters to a range of doses of metronidazole have given mixed results. In response to high doses, mice exhibited an increased risk of developing lung tumours, and female rats developed more liver tumours than controls. However, these effects may have been non-specific consequences of prolonged high dosage. No excesses of tumours were seen in response to lower doses and two tests in hamsters gave negative results. A follow-up of 771 women treated, 10 or more years previously, with metronidazole revealed no excess cancer risk. Thus the available information suggests that metronidazole, tinidazole and other 5-nitroimidazoles effective against anaerobic microorganisms are very safe both in the short-term and in the long-term.

Garzie said...
JMF - just a FYI - that article seems to be comparing 2 different things -

1, grapefruit - as in the citrus fruit itself
2, grape seed extract - an extract from the seeds inside grapes ( grapes as in wine - not citrus )

furanocoumarins are the compound in grapefruit that interferes with liver metabolism and causes drug interactions

info here https://pmc.ncbi.nlm.nih.gov/articles/pmc3589309/

i dont know if there are any / much in Grapefruit seed extract - its defo in the juice, pulp etc

Post Edited (JMF84) : 12/12/2024 4:47:55 PM (GMT-5)

Garzie said...
for what its worth i think the cysts phenomenon may be overstated - or at least somewhat confused with biofilms and persisters

borrelia do have a tendency to curl up and become dormant when stressed - eg by common antibiotics, or other stressors, like low nutrient availability etc

this state is variously termed "round body forms", "cysts" "L-forms" etc

however true cysts have impermeable outer membranes which i do not think occurs in borrelia

more - as far as i am aware - the round body forms are merely in a low metabolic state - exchanging very little with the outside world / their surroundings - and having switched off most of the genes on which common antibiotics act - are rendered up to 1000 x more tolerant of them than their free swimming brethren.

in other words they are equivalent to persister cells

persister cells are also highly associated with biofilm formation -
what seems to be happening here - is that as a survival strategy - after an initial fast growing phase - as pressure on a new colony of borrelia mounts from immune attack, nutrient depletion etc - a large proportion of them aggregate into biofilms, where they are more protected and most then switch to a similar low metabolic state - with the same 1000X abx tolerance increase

the additional factor here being that biofilms are not separate isolated round bodies - but are aggregates of a composite of borrelia and glue like extra cellular matrix made of proteins, dna, amyloid, adhesins, membrane proteins etc all excreted by the bacteria to form this resilient mass.

this composite biofilm structure is - contrary to common belief - highly permeable to antibiotics ( this has been demonstrated conclusively since the 1970's see Prof Bill Costerton, the father of biofilm research - so its a bit odd that the myth has persisted so long).

so that is not the mechanism which affords the bacteria protection from attack. What it does do is form a quite effective physical barrier to cells from the immune system accessing and killing the bacteria.

this is of vital importance as - again, something under appreciated in the lyme world - no matter how many antibiotics we take -it is ultimately the hosts immune system that has to clean up the remaining bacteria - of which there will always be some to re-start the infection - so this starts to underline just how critical to survival of the bacteria the biofilm phenomenon actually is. ie it is central to why lyme is hard to cure - rather than a peripheral quirk of its nature.

in chronic infections - what is most likely happening is the vast majority of borrelia inside the host are living in biofilm colonies inside tissues. these are growing only slowly - but at a rate that is equivalent to slightly greater than the rate at which the immune systems cells can gradually nibble away at the edges of the colonies - hence the stuck chronic condition.

hence i think there is a lot of co-location and overlap of properties of cysts/round bodies, biofilm and persisters.
as a result the drugs that tend to work on persisters also work on round bodies and vise versa

in summary biofilms are persisters - but biofilms also have the ESM/ Glue component - so can be attacked by things that dissolve or weaken the glue via numerous mechanisms


i thought it an interesting and under appreciated topic worth writing a few words on


i hope its of some help

Garzie said...
Tinidazole is pretty broad in action i think - so could well be

i think it was originally intended as an anti-amoebic or anti-protozoan drug - and was used for Amoebic dysentery, Giardia and Trichomonas vaginalis ( all protozoan infections )

but was later found to be effective for a bunch of stubborn bacterial infections too - they found it was particularly effective for some slow growing anaerobic bacteria - like Helicobacter pylori which forms biofilms and tends to be quite tolerant of a lot of common antibiotics. it's also used for diverticulitis - pockets of gut wall infected with gut bacteria, and for controlling flares of IBD - again indicating its v broad action as there are hundreds of different bugs in the gut. its very broad action seems to be specific to anaerobic bacteria ( borrelia are anaerobic - but it could well be that when other bacteria switch to their persister or biofilm forms - their aerobic genes used for faster growth are turned off - and anaerobic ones turned on - as we often see different abx specificity for fast growing cultures vs stationary phase cultures ( stationary phase cultures represent persister cells)

in general 90% of antibiotics we have today were developed to tackle the fast growing bacteria of acute infections - not the slow growing ones of chronic tick born infections like lyme, bartonella etc

we basically borrow those antibiotics - even though they are not purpose designed for what we have - and are therefore only moderately effective - as they are pretty much all we have in the toolbox.

tinidazole seems to act via a different mechanism than most - and that's why it has some effects on the slow growing bacteria that others do not ( slow growing bacteria are more or less synonymous with persister cells and biofilm formation)

other drugs that act on slow growing bacteria, biofilms and persister cells that may be of interest to you are:

- nitroxoline - is approved for chronic urinary tract bacterial infections in Europe where its been used for 50+ years with a good safety record. chronic UTI's have recently been confirmed to be biofilm forming infections - Nitroxoline was also shown to cause a decrease in the biofilm density of P. aeruginosa infections, which would allow access to the infection by the immune system in vivo.[ ref Nitroxoline Wikipedia page]
so it seems particularly good against biofilm forming infections ( BTW this could also be what tinidazole is doing ) - Zhang et al at Johns Hopkins found nitroxoline to be particularly good at killing bart persisters (one of the top 3 drugs i think in a screen of 3000+ FDA approved drugs against stationary phase bart cultures).

- nitazoxanide (alinia) - another drug originally designed as an antiprotozoal - but we have studies showing it has particularly good activity against borrelia and esp borrelia persisters - especially in multi drug combos - it also has a better safety profile vs tinidazole -

personally i think the evidence points to biofilms and the persister cells that reside in high proportions inside them to be the major impediment to effective treatment with most antibiotics today, rather than cysts.
the reasoning is pretty simple - persister cells are known to tolerate 1000x or more of the concentrations of antibiotics that kill all of the non-persister cells in a sample.

unfortunately, its just not possible to achieve those 1000x concentrations in a human patient
the closest we can get is combining 2-4 different drugs with persister cell activity - at levels we can tolerate.

this is effetely what most of the best know LLMD's are doing with their tough cases - eg
Dr J and his persister protocol
Dr H and his double and quadruple dapsone with high dose methylene blue and rifampicin etc

over time this does get a lot of people across the line

i hope its of some help

Post Edited (JMF84) : 12/16/2024 4:49:07 PM (GMT-5)