Cure Ulcerative Colitis in 6 weeks

[GorillaHead]

I am starting to think Uc is a sugar issue

 

[Ismail]

NOW brand. It would be my go to. Extraordinary results.

Amazing! Thank you

 

[Ismail]

The capsules or? How much, mixed in how much what? Water?

That was going to be my next question to @ecstatichamster

 

[ecstatichamster]

That was going to be my next question to @ecstatichamster

the study used liquid E from NOW. Just put it into an enema thingie and squirt it up there, hold for 15 minutes.

https://www.nowfoods.com/products/supplements/vitamin-e-liquid

 

[ecstatichamster]

Rectal administration of d-alpha tocopherol for active ulcerative colitis: A preliminary report

AIM: To investigate the anti-oxidant and anti-neutrophil recruitment effects of rectal d-alpha (d-α) tocopherol administration on mild and moderately active ulcerative colitis (UC).METHODS: Fifteen patients with mild and moderately active ulcerative ...

www.ncbi.nlm.nih.gov

 

[Elie]

Rectal administration of d-alpha tocopherol for active ulcerative colitis: A preliminary report

AIM: To investigate the anti-oxidant and anti-neutrophil recruitment effects of rectal d-alpha (d-α) tocopherol administration on mild and moderately active ulcerative colitis (UC).METHODS: Fifteen patients with mild and moderately active ulcerative ...

www.ncbi.nlm.nih.gov

8000 IU of alpha tocopherol - that's a huge amount!
Interesting...

 

[cs3000]

IBD is constantly labeled as an autoimmune disease but it is not an autoimmune disease but a chronic inflammation due to the immune system attacking itself.
Dr. Jay Pravda claims to have found the cure for Ulcerative Colitis.

This is fuccking brilliant thanks , makes perfect sense
Just read through his 2022 paper great stuff.

i've had ileal ulcerative colitis for over a year , i almost had the pieces by looking at aspirin ulcers but didnt get the click - but this is the full insight

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453768/

-- (too much hydrogen peroxide H2O2 or not enough being neutralized = excess h2o2 inside & outside gut cells = neutrophils recruit to the site = damage of healthy gut tissue = recurrent inflammation and ulcers . colonic / intestinal h2o2 is the target --

Probably best to just read the paper but notes i took:

h2o2 = permeable from cells (colonic or lower small intestine)
h2o2 = chemotaxic with neutrophils (or in other words , amazingly neutrophils follow hydrogen peroxides trail Chemotaxis - Wikipedia)

So UC at its core is about the ratio of your individual level of H2O2 vs the ability to neutralize it.
acutely h2o2 can rise several fold it's dynamic , and overwhelm cells antioxidant capacity
without enough neutralizing of h2o2 , h2o2 is building inside and outside gut cells -
typically there's not enough h2o2 flooding to leave the cells , but in cases where excess is being produced (i.e in people with ulcerative colitis) this causes hydrogen peroxide to start leaking out of cells.
Usually only neutrophils produce h2o2 outside of cells. which attracts more neutrophils to places where its supposed to be beneficial to attack.
So neutrophils can't tell the difference they just follow where the excess h2o2 is and start damaging healthy cells where the h2o2 is . boom inflammation & ulceration

(this is also the cause for aspirin induced stomach ulcers btw, and probably covid induced lung damage, and i wonder if this guy has discovered the core mechanism for many "autoimmune" diseases)

treating it like an autoimmune problem is a lacking approach because its missing the fundamental issue - the immune system is normal & doing its job.
just the excessive h2o2 or lacking protection is pulling the neutrophils to the wrong place. which is why you get cases of continual reoccurance , if you wreck the immune system it didnt solve the core problem.


main cause of excess h2o2:
mitochondria electron leak from DNA damage by oxidative stressors toxins, and not enough oxidative stress protection

mitochondrial DNA damage -> disrupts electron flow in the electron transport chain -> the electrons leak -> combine with oxygen > hydrogen peroxide

So the level of h2o2 rises , which being local to mitochondria damages & mutates the mitochondria further,
and a loop of extra h2o2 builds up. and as its permeable to cells it leaves the cell , damages the gut tissue via attracting neutrophils , and h2o2 disintegrates the tight junction proteins holding the epithelial cells together (so leaky gut / more bacteria invades the lining)

In UC, core approach is to
1. neutralize the h2o2 outside the cells and inside the cells. and
2. protect mitochondria from further leaks & repair it (mitochondria can repair its own DNA given the right conditions Mitochondrial DNA repair in aging and disease)


main ways body deals with h2o2:
. GPx enzyme (and catalase but less so by the looks of it) (Glutathione)
. albumin (studies in UC patients have shown that mucosal healing is positively associated with high (> 4.4 mg/dL) serum albumin[73].)
. red blood cells scavenge h2o2

experiments show lower gene expression of Gluthathione peroxidase (GPx) in ulcerative colitis

" GPx2, a gastrointestinal-specific form of GPx [36], which is closely associated with H2O2 metabolism, and whose gene expression is downregulated in several experimental models of UC "

& mice lacking GPx develop colitis

----------
things mentioned to get / find alternatives to:
* RD-LA orally is the #1 if you can find it , 300mg x2 daily = 85% remission in <8 weeks along with the enema:
. mesalamine 3g [lowers inflammation specific to colonic mucosa]
. budespride 5mg [corticosteroid that inhibits neutrophil infiltration to colon]
. cromolyn sodium 100mg [mast cell stabilizer that prevents release of histamine in the gut]
. sodium butyrate 1.7g
* things that increase cellular glutathione, in the colon / intestine (reduces h2o2 to water, helps repair mitochondrial dna -> lower h2o2 production)
(RD-LA increases cellular gluthatione but is not commercially available)

* intracellular antioxidants
that deal with h2o2 , along with extracellular ones.
NAC 800mg , is sulfur based but shown benefit and increases intracellular glutathione N-Acetylcysteine (NAC): Impacts on Human Health and theres a human study https://www.researchgate.net/public...olitis_A_Randomized_controlled_clinical_trial which showed it kept remission rates at 93% vs 81% in placebo when tapering off corticosteroids

* Vit C is needed to prevent endothelial cell death when glutathione is depleted ,
but 10x more glutathione is needed to protect against hydrogen peroxide Vitamin C is an essential antioxidant that enhances survival of oxidatively stressed human vascular endothelial cells in the presence of a vast molar excess of glutathione - PubMed

* things that help mitochondrial DNA mtDNA repair
* Vitamin B5 (COA -> acetyl CoA -> same as below for efficient gut energy)
B5 doses are absorbed in high amounts. in a video ray peat said b5 is the only vitamin where you can give a cup full to monkeys and it doesn't show toxicity. but may reduce cholesterol somewhat at high doses. has stress regulation properties. 250mg - 500mg may help reverse intestinal paralysis (constipation)
* Butyrate (colonocytes -> mitochondria -> beta oxidation -> acetyl-CoA -> krebs cycle NAD+ to NADH -> electron transport chain -> oxidative phosphorylation for gut energy efficient ATP production)
(or soluable fiber alternatively to raise it? though that might have harms) (butyrate enema increases colonic GSH)
impaired butyrate oxidation also showed in ileal (lower small intestine) colitis - associated with h2o2 induced inhibition of mitochondrial thiolase. and has same neutrophil infiltration

[ he mentions later increasing electron transport chain activity is a problem with this because of the electron leak- but if you dont give it the fuel with b5 / butyrate for the acetyl CoA, cells use glutamine instead.
using up glutamine in this way leaves little around for GSH synthesis. tho glutamine supplementation has mixed results in studies


*inhibit gut mast cells / reduce histamine in gut
(specifically H4 antagonists work Histamine drives severity of innate inflammation via histamine 4 receptor in murine experimental colitis - Mucosal Immunology h4 antagonists = less mucosal neutrophil infiltration , less mast cells

H4R is expressed in the gut mucosa by mucosal immune cells.
Elevated mucosal histamine as well as N-methylhistamine metabolite excretion correlate well with patient disease activity.13, 20, 21, 22

More h4 in UC

*increase NADPH for GSH glutathione recycling
* reduce homocystine (inhibits GPx. take folate? maybe taurine?)
* stuff that increases nuclear factor E2 related factor 2? sulforaphane?

* (not antibiotics - even though theres 10x more h2o2 resistant bacteria in chronic UC - antibiotics generate more h2o2 due to electron transport chain alteration, ive seen mitochondrial dysfunction comes even with low doses of the tetracyclines)
* reduce serotonin in gut if too many bowel movements (excess is metabolised by mao and the reaction produces more h2o2)

* sufficient selenium at 60mcg daily (most ppl get this but intake may lower if the colitis lead to meat intake reduction)

* nicotine may only work in quitting smokers to get rid of withdrawal stress. but if it stimulates bowel movements in the constipation type thats helpful, NAD+ participates in at production. smoking may help by inhibiting electron transport chain so less electron leak , but more damage so creates a worse problem overall)

*he mentioned to avoid high levels of iron due to oxidative stress - but considering red blood cells take out h2o2 , if red blood counts are confirmed low maybe raising them with iron could give an overall benefit. along with folic acid / folate

Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health Polyphenols generate H2O2 , (which is why they raise antioxidant enzymes - they are signalling with a stress signal. where this protection increase could outweigh the h2o2 for a benefit in healthier people , the increased generation of h2o2 for UC maybe best to keep polyphenol intake low?) ascorbate may have a connection to degrading to h2o2 but overall lowering effect? idk yet



Videos https://www.youtube.com/@jaypravdaMD

[he mentioned RD-LA because it works both in the blood and inside cells as its both fat soluble and water soluble reducing agent -the annoying thing is its not commercially available. only r-lipoic acid which isnt the same thing as R-Dihydro , different form. tho lipoic is fat+water soluble it has to be reduced in the body to get to r-dihydro , so author says its no good because its oxidizing instead of reducing

but i wonder if it getting converted in the body would outweigh the initial negative effectColonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats in this one at 1g human dose each, lipoic acid reduced colonic h2o2 & NAC moreso. but combining them actually acted as a pro-oxidant and worsened h2o2. the damage was reduced taken individually but not fully. either way nac was more protective
]

 

[cs3000]

things mentioned to get / find alternatives to:
* RD-LA orally is the #1 if you can find it , 300mg x2 daily = 85% remission in <8 weeks along with the enema:
. mesalamine 3g [lowers inflammation specific to colonic mucosa]
. budespride 5mg [corticosteroid that inhibits neutrophil infiltration to colon]
. cromolyn sodium 100mg [mast cell stabilizer that prevents release of histamine in the gut]
. sodium butyrate 1.7g
* things that increase cellular glutathione, in the colon / intestine (reduces h2o2 to water, helps repair mitochondrial dna -> lower h2o2 production)
(RD-LA increases cellular gluthatione but is not commercially available)

* intracellular antioxidants

* things that help mitochondrial DNA mtDNA repair
* Vitamin B5
* Butyrate

*inhibit gut mast cells / reduce histamine in gut
(specifically H4 antagonists work
*increase NADPH for GSH glutathione recycling
* reduce homocystine (inhibits GPx. take folate? maybe taurine?)
* stuff that increases nuclear factor E2 related factor 2? sulforaphane?

So for a stack / replacements 1. NAC 400mg x2 daily might be able to replace the RD-LA (but would prefer something else if i can find it due to cysteine raising)

2. For the budespride - Bromelain should be a good replacement.
like the corticosteroid it will skew immunity at doses over ~50mg ( budespride might not effect T cells but the neutrophil migration blocking action probably means lower immunity - as a tradeoff to lowering the neutrophil damage),

Bromelain removes surface molecules of immune cells & changes immunity. specifically reduces neutrophil migration to sites of inflammation a lot,
so bromelain will give a similar effect as the drug used at 100mg+ Bromelain treatment decreases neutrophil migration to sites of inflammation - PubMed

In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity.

and is backed in ulcerative colitis orally by a case report about 2 women who gained benefit within a couple weeks of higher dose

https://www.deerland.com/wp-content/uploads/2015/04/60_Use-of-Bromelain-for-Mild-Ulcerative-Colitis.pdf

trying to find more accessible things that covers the full approach.
next on the list need something good at inhibiting mast cells / reducing histamine well in the gut, even better if it inhibits H4 receptors
(would loratadine work?)
Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway

Loratadine is #3 for the stack, ~25mg was the dose. if tolerated. replacement for the mast cell stabilizer cromolyn sodium
Mast cell stabilizing properties of antihistamines - PubMed loratadine has mast cell stabilizing properties

Weller and Maurer report that the H1 antagonist desloratadine possesses mast cell-stabilizing properties when challenged in an IgE-dependent or -independent fashion. Thus, desloratadine provides benefits that are independent of H1 receptor binding and based on mast cell stabilization.

(desloratadine is metabolised from loratadine) and typically low in side effects ,
and a bonus is it has a connection to improving survival with melanomas . which could potentially balance out the increased spread of melanoma from NAC (through cysteine increase). so balances well.
other target of getting rid of that metastasis effect of NAC would be finding a way to reduce the increase in plasma cysteine. reducing it reduces the metastatic effect without effecting the GSH raising effect

shRNA-induced inhibition of the main transport systems for Cys (ASC1) and cystine (xCT) shows that metastatic activity in NAC-treated mice decreases by approx. 50% if the cystine uptake is inhibited; whereas the inhibition of the Cys uptake does not significantly affect the effect of NAC

Vit B5 is accessible as a #4

 

[cs3000]

tried higher dose loratadine 20mg twice spread out and noticed negative effects both times (has a long half life also when u consider the metabolite).
think it crosses the BBB significantly at this dose in my experience. so will be sticking to 5mg-10mg in the future. not sure if acts as a decent mast cell stabilizer in this amount
low dose luteolin could be an alternative Mast Cells, T Cells, and Inhibition by Luteolin: Implications for the Pathogenesis and Treatment of Multiple Sclerosis but not aware on safety Luteolin ameliorates lipopolysaccharide-induced microcirculatory disturbance through inhibiting leukocyte adhesion in rat mesenteric venules
--

Sodium butyrate 1. is very hit or miss in studies and 2. is only sold by lesser known brands where im at

So a replacement for this as #5 is 6g - 10g of wheat bran fiber.
which gives +25% butyrate at 6 grams daily
works by increasing the amount of butyrate producing bacteria

Effect of Wheat Bran on Fecal Butyrate-Producing Bacteria and Wheat Bran Combined with Barley on Bacteroides Abundance in Japanese Healthy Adults
increased firmicutes % (butyrate producing bacteria) from 0.53 to 0.79 by week 4
6g for 4 weeks . butyrate 0.78 -> 0.96 , 12g oat + wheat fiber gave 0.78 -> 0.91

The Effects of Intact Cereal Grain Fibers, Including Wheat Bran on the Gut Microbiota Composition of Healthy Adults: A Systematic Review
Thirty-nine of the forty-two studies demonstrated an increase in microbiota diversity and/or abundance following intact cereal fiber consumption, with effects apparent from 24 h to 52 weeks. Increases in wheat fiber as low as 6–8 g were sufficient to generate significant effects

mice in vivo study:

" Of the diet treatments that we examined, the WB-enriched diet continuously produced the highest concentrations of total SCFAs, including butyrate"

"butyrate can stimulate the production of mucus–associated bacteria to enhance the intestinal barrier function in the host. "
Along with the ATP boost it helps restore barrier permeability & mucus


and a good tip is the finely powdered products are better than eating the whole bran
(powdered wheat bran fiber -> you get butyrate effects hitting by 1 week instead of over 3 weeks, and more butyrate)
(guess as its spread through the intestine more this way)

https://journals.sagepub.com/doi/full/10.1177/1934578X20917791
blue PWB = powdered
in this one butyrate went up 4x

and immunoglobulin A went up a lot too

Besides neutralizing pathogens in the intestinal lumen, SIgA can intercept microbes and toxins inside IECs (12). Of note, SIgA delivers these protective functions without activating the complement cascade (12, 17), thus impeding inflammatory damage to the epithelial barrier.

 

[cs3000]

& a great #6 for the h2o2 (or #1 as might be able to replace NAC without generating cysteine)

Milk thistle (standardized extract)

Silymarin extract of milk thistle , product standardized to high silymarin or silibinin %

oral consumption of silibinin was associated with a significant increase in both glutathione S-transferase (GST) and quinone reductase (QR) activities in liver, lung, stomach, skin and small bowel in a dose- and time-dependent manner

GST enzymes protect cells against h2o2 induced death

silymarin protects against h2o2 cell damage silymarin possesses substantial protective effect and free radical scavenging mechanism against exogenous H(2)O(2)-induced oxidative stress damages


in mice ~500mg -600mg human dose in cottonseed oil raised GST big time in the gut Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention - PubMed
and most of the effect was in the small bowel +110% increase so doubled GST,

In the case of GST activity, compared with vehicle-treated controls, treatment with 100 and 200 mg/kg doses of silibinin for 3, 7 and 15 days resulted in 8–110 and 10–140% increases ( P < 0.1–0.001, Student's t -test) in enzyme activity. The observed increase in GST activity was maximum in small bowel at both the doses employed in the study and accounted for the 110 and 140% increases

(effect rose day to day into 14 days, was still rising - so may have continued even more than 2x at 500mg
and the main increase of +110% or 140% was found in the small intestine. they didnt test lower but probably means a big increase in the colon too.

https://sciforum.net/manuscripts/8562/manuscript.pdf in rats ~1g human dose orally silymarin , completely or close to completely protected against h2o2 challenge. restored GSH etc

& human trial using 140mg silymarin 14% of remission cases rebounded with the silymarin , vs 54% return of UC in the placebo group

big cancer protective effect topically at 3mg 6mg and 12mg in mice A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model - PubMed



Swanson or Life extension have milk thistle standardized without silica / silicon dioxide / titanium dioxide in at least 1 of the products

good site for finding interactions between stuff https://supp.ai/a/hydrogen-peroxide/C0020281

 

[cs3000]

& a great #6 for the h2o2 (or #1 as might be able to replace NAC without generating cysteine)

Milk thistle (standardized extract)

Silymarin extract of milk thistle , product standardized to high silymarin or silibinin %

Silymarin Ameliorates Oxidative Stress and Enhances Antioxidant Defense System Capacity in Cadmium-Treated Mice

Cadmium is an environmental pollutant which induces oxidative stress while silymarin as an antioxidant is able to scavenge free radicals. The aim of the present study was to investigate the effect of silymarin on oxidative stress markers and antioxidant ...

www.ncbi.nlm.nih.gov

gastric cancer inhibition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775811/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775811/bin/or-42-05-1904-g06.jpg
pancreatic cancer inhibition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747396/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747396/bin/oncotarget-06-41146-g005.jpg
colon cancer inhibition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728169/

downside if low in iron, can drop iron over time. but some controversy whether its bad for hemochromatosis or not.
if low iron markers or low rbc , may be best to stick to doses closer to 100mg silymarin
https://link.springer.com/article/10.1007/s13181-010-0030-9

 

[Jonk]

@cs3000 super interesting stuff. About the wheat bran, do you think it needs to be cooked, or okay to add as is to smoothies?

 

[thetaflow]

@cs3000 super interesting stuff. About the wheat bran, do you think it needs to be cooked, or okay to add as is to smoothies?

Also maybe use oat bran instead?

 

[cs3000]

@cs3000 super interesting stuff. About the wheat bran, do you think it needs to be cooked, or okay to add as is to smoothies?

Also maybe use oat bran instead?

havent noticed negatives from eating it uncooked ,
wheat bran is more effective i think . e.g in the human study when they added 6g oat bran fiber to 6g wheat bran fiber the butyrate effect was the same vs just 6g wheat bran fiber


been taking 250mg-500mg silymarin . no negative effect on mood seems well tolerated so far. the higher folate / b5 doses idk about

Silymarin inhibits T cells potently at physiological concentrations ,
but the compounds have direct antiviral activity so it balances out

hepatitis C Multiple effects of silymarin on the hepatitis C virus lifecycle - Enlighten Publications Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin also blocked cell-to-cell spread of virus.

inhibits influenza

virus replication silymarin-mediated inhibition of influenza replication occurred through inhibition of late mRNA synthesis. However, whether or not silymarin could modulate other phases of the influenza life cycle was not investigated
Silymarin exhibited anti-influenza A/PR/8/34 virus activity of 98% with no cytotoxicity at the concentration of 100 μg/ml reducing the formation of a visible CPE
(but peak human blood concentration is ng at usual doses, not micrograms)

"Finally, in vivo oral administration of S0 and S3 not only increased the survival rate in mice infected with a lethal dose of IAV, but also decreased the viral titers in their lungs [23]. Interestingly, this finding is compatible with the accumulation of free silibinin in lung after oral administration that others and we have observed [15,24]. These results, together, point to a prominent role of silymarin as a potent IAV inhibitor."

* net benefit against viral infections in vivo Identification of 23-(S)-2-Amino-3-Phenylpropanoyl-Silybin as an Antiviral Agent for Influenza A Virus Infection In Vitro and In Vivo
s0 = silybin , s1-s5 are the derivatives
25mg/kg , 125mg-150mg silybin, gives +40% survival vs 0% controls in flu challenge. lower virus titer in lungs -
"The mice treated with the 25-mg/kg/day dose of S3 had at least a 100-fold decrease in virus titers in their lungs"

also the vitamin b5 raises glutathione peroxidase & reduced glutathione so dual effect with the increased gut energy Effects of dietary pantothenic acid on growth, antioxidant ability and innate immune response in juvenile black carp (might lower GST but the silymarin takes care of that) Curative role of pantothenic acid in brain damage of gamma irradiated rats


& butyrate reduces h2o2 damage in colon cells (& cancer cells , but other mechanisms exist so butyrate is anti-cancer in the colon Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1

Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells
Pre-incubation of the cells with physiological concentrations of butyrate (6.25 and 12.5 mM) reduced H2O2 (15 μM) induced damage by 33 and 51% in human colonocytes, 45 and 75% in HT29 and 30 and 80% in HT29 19A, respectively.
It should be stressed that butyrate and SCFA mixtures were used at concentrations and relative ratios thought to be physiological in the colon lumen (29

i think the effect scales with amount of bran fiber eaten. but too much fiber might lower cholesterol & bile acids (idk if that effect is in the small intestine or if its just lower down?)

 

[Elderflower j58]

@cs3000

havent noticed negatives from eating it uncooked ,
wheat bran is more effective i think . e.g in the human study when they added 6g oat bran fiber to 6g wheat bran fiber the butyrate effect was the same vs just 6g wheat bran fiber


been taking 250mg-500mg silymarin . no negative effect on mood seems well tolerated so far. the higher folate / b5 doses idk about

Silymarin inhibits T cells potently at physiological concentrations ,
but the compounds have direct antiviral activity so it balances out

hepatitis C Multiple effects of silymarin on the hepatitis C virus lifecycle - Enlighten Publications Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin also blocked cell-to-cell spread of virus.

inhibits influenza


"Finally, in vivo oral administration of S0 and S3 not only increased the survival rate in mice infected with a lethal dose of IAV, but also decreased the viral titers in their lungs [23]. Interestingly, this finding is compatible with the accumulation of free silibinin in lung after oral administration that others and we have observed [15,24]. These results, together, point to a prominent role of silymarin as a potent IAV inhibitor."

* net benefit against viral infections in vivo Identification of 23-(S)-2-Amino-3-Phenylpropanoyl-Silybin as an Antiviral Agent for Influenza A Virus Infection In Vitro and In Vivo
s0 = silybin , s1-s5 are the derivatives
25mg/kg , 125mg-150mg silybin, gives +40% survival vs 0% controls in flu challenge. lower virus titer in lungs -
"The mice treated with the 25-mg/kg/day dose of S3 had at least a 100-fold decrease in virus titers in their lungs"

View attachment 49439

also the vitamin b5 raises glutathione peroxidase & reduced glutathione so dual effect with the increased gut energy Effects of dietary pantothenic acid on growth, antioxidant ability and innate immune response in juvenile black carp (might lower GST but the silymarin takes care of that) Curative role of pantothenic acid in brain damage of gamma irradiated rats


& butyrate reduces h2o2 damage in colon cells (& cancer cells , but other mechanisms exist so butyrate is anti-cancer in the colon Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1

i think the effect scales with amount of bran fiber eaten. but too much fiber might lower cholesterol & bile acids (idk if that effect is in the small intestine or if its just lower down?)

Hi there I would love your thoughts on this very short video especially from the 7.7 minute time.

He speaks to any vinegar Neutralised by Potassium bicarbonate being A short change fatty acid Going directly into the mitochondria without the pathways that butyrate have to overcome .
He claims vinegar does a better job than actual butyrate.


View: https://youtu.be/ebBYWnVh1Eo

 

[cs3000]

@cs3000

Hi there I would love your thoughts on this very short video especially from the 7.7 minute time.

He speaks to any vinegar Neutralised by Potassium bicarbonate being A short change fatty acid Going directly into the mitochondria without the pathways that butyrate have to overcome .
He claims vinegar does a better job than actual butyrate.

hi. in the butyrate h2o2 study they used doses that can be found in the colon, and it protected cells decent against h2o2 damage,
so its significant at what can be restored by eating bran fiber especially powdered . (the direct oral butyrate studies going through the stomach are hit & miss so id rather have my gut produce it directly, only thing im weary of this way is if it lowers cholesterol & bile acids)

acetic acid (vinegar) is used to cause inflammation in animal models of colitis / ulcerative colitis
but taken orally theres a study showing benefit for UC https://pubs.acs.org/doi/abs/10.1021/acs.jafc.5b05415

normally its used to activate pain receptors & inflammation in animals Writhing Test - an overview | ScienceDirect Topics
its an irritant to the digestive tract & causes ulcers https://gut.bmj.com/content/gutjnl/38/6/832.full.pdf

so idk , guess the difference is it's neutralized enough when spread out added to drinking water? so main risk is not getting it neutralized enough?
id rather not **** around too much with oral ingestion & ulceration but if its safely neutralized maybe its a good option

i wouldnt recommend potassium bicarbonate for a neutralizing agent tho (its supposed to be a safer form but pretty sure its what started my small intestine ulcerative colitis in the first place - some studies before taking it made that form look safe enough, but didnt stop the harm of raw potassium intake for me & over months this caused the initial ulcer or worsened it significantly if it wasnt). like someone mentioned in the comments sodium bicarbonate is an alternative

wheat bran fiber boosts production of acetic acid too in the colon

 

[cs3000]

Something to know about high dose silymarin (+ in vitro effect on thyroid transport looks like it could balance out, but am testing my core temps to see)
https://ejhm.journals.ekb.eg/article_18236_8faa371ceb642445b4ca28df0d612846.pdf
they say its lower dose than usual conversion for some reason, 420mg, but seems like an error as usual conversion would be 1.5 - 2g human dose

by this study silymarin has contraceptive properties in females, & more sperm generation in males (when used short term)

it prevented pregnancy in 10/10 female rats, because of the big FSH increase 2x by 4 weeks 3x by 8 weeks. estradiol & LH increased also. (but FSH increase far outweighs the LH increase)
follicle stimulating hormone usually creates feedback inhibition so only 1 dominant follicle remains with the rest not getting enough FSH to grow well. then after an estrogen rise & Luteinizing surge hits the egg is released. but with this the FSH stays elevated.
in men FSH stimulates sperm production

[ https://www.scielo.cl/pdf/ijmorphol/v35n2/art54.pdf in this one, silymarin increased progesterone and reduced estrogen, and lowered the increased LH and raised the reduced FSH (so it normalized the skew), in PCOS polycystic ovary syndrome. ~1g - 2g human dose
human study Improving an Ovulation Rate in Women with Polycystic Ovary Syndrome by Using Silymarin | Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) showed lower dose of 750mg helpful but smaller effect]


hemoglobin & RBC did not lower. improved more in the silymarin groups

in males Testosterone increased in both controls & silymarin groups. silymarin higher testosterone at 4 weeks, higher LH, estradiol was around the same at 4 weeks but higher at 8 weeks. test declined by 8 weeks.
did lower white counts (inhibits t cell proliferation but has direct antiviral effect)
more sperm production at 4 weeks, but lower than controls by 8 weeks

so suitable timeframe for men using high dose silymarin for healing may be up to 4 weeks
and if a woman, (without PCOS) , the FSH impact on fertility while its raised by this is something to know


--
silymarin reduces ulcer formation , lowers stomach acidity and acid amount in response to something that increases it (would it decrease baseline levels though?) 600mg human dose

Silymarin, an antioxidant bioflavonoid, inhibits experimentally-induced peptic ulcers in rats by dual mechanisms

Antioxidants are reported to have antiulcer activity. We investigated silymarin, a bioflavonoid antioxidant, for antiulcer potential.Pylorus-ligated Shay rats (n=5) were used as the experimental gastric ulcer animal model. The rats, separated into three ...

www.ncbi.nlm.nih.gov

this one https://onlinelibrary.wiley.com/doi/abs/10.1111/j.2042-7158.1992.tb03239.x did not reduce gastric acidity or acid response
have noticed some moderate acid reflux lately, paused the milk thistle for a couple days and its still here so idk if its this

dose dependent healing effect up to 2g-2.5g human dose

Inhibition of Inducible Nitric-Oxide Synthase Expression by Silymarin in Lipopolysaccharide-Stimulated Macrophages lowers nitric oxide production in macrophages

https://journal.muq.ac.ir/article-1-2884-en.html ~600mg wound healing

 

[cs3000]

theory about copper , [this probably won't apply to most people as a smaller % of people with UC have copper insufficiency, most have normal levels going by most studies Micronutrient deficiency among patients with ulcerative colitis - The Egyptian Journal of Internal Medicine but some do show less copper Serum Concentrations of Trace Elements in Patients with Ulcerative Colitis
and no link was established between copper levels and UC severity, but gonna post this anyway
for the subset of ppl that might respond or in case the info leads somewhere]


i was taking 500mg vit C before for 2 months without much else and didnt notice any benefit for UC
https://www.mdpi.com/2072-6643/7/4/2574
vit C increases neutrophil chemotaxis 20% (transport to sources of h2o2) (so in UC where the h2o2 is skewed, may be best to avoid until its fixed, though that study is coming off suboptimal levels so that effect may just be restoring to normal)

vit C doesnt reduce copper, studied are mixed but in some they show reduced ceruloplasmin activity by 15% - 30% at 500mg+ (involved in copper & iron transport)

copper can increase neutrophil count, and overload can increase migration to epithelium,
but on the other side,

neutrophils get 'stiffer' in people with low copper and stick around in lungs for too long because they get stuck in smaller blood vessels
https://www.researchgate.net/public...ormability_of_Copper-Deficient_Neutrophilsthe

Using the in vivo rat model, we have shown that dietary copper deficiency causes an accumulation of neutrophils in the lung micro vasculature that is 3–4 times greater than that seen in control rats.
The current study was designed to determine whether a diet deficient in copper promotes neutrophil chemoattraction within the lung vasculature or if inadequate copper alters the mechanical properties of the neutrophil, thus restricting passage through the capillary bed

In addition to chemoattraction, neutrophil deformability is a key factor in determining whether neutrophils pass through the lung microvasculature or become lodged in the smallest vessels
copper-deficient neutrophils are less deformable (Fig. 2) and, therefore, are less likely to readily pass through the lung microcirculation

In vitro studies have shown that neutrophils from copper deficient rats pass more readily through endothelial cell monolayers (2, 3), migrate farther in response to IL-8 (3), adhere more to P-selectin (3), and express more CD11b (3) than copper-adequate controls

These results clearly correlate with the decreased deformability of the copper-deficient neutrophils seen in our study (Fig. 2) and suggest a proinflammatory activation of neutrophils in copper-deficient rats

The shape changes also suggest the occurrence of cytoskeletal remodeling, which is required for neutrophils to migrate to the borders of endothelial cells (17) and may account for the greater extravasation of copper-deficient neutrophils through endothelial cell monolayers

In summary, the current study addresses two possible mechanisms for the greater accumulation of neutrophils that occurs in the copper-deficient rat lung. The results
demonstrate that although the inflammatory response in copper-deficient rat lung is exaggerated (4), there is no increase in the production of the chemokine MIP-2 in the absence of an inflammatory stimulus (Fig. 1). The results also demonstrate that although the MIP-2 chemokine signaling is not enhanced, the copper-deficient neutrophils are stiffer (Fig. 2) and, therefore, less likely to deform and pass through the small caliber lung capillaries.

The data bolster our hypothesis that dietary copper deficiency causes proinflammatory changes in neutrophils (3). Further experimentation revealed that the reason for the loss of deformability is likely caused by greater polymerization of F-actin in the copper-deficient neutrophil (Fig. 4). Based on the results, we conclude that the excess accumulation of neutrophils in the copper deficient rat lung is the result of changes in the biomechanic-deformability properties of the neutrophil

https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1440-1711.2004.01231.x

During an acute inflammatory response, endothelial P-selectin (CD62P) can mediate the initial capture of neutrophils from the free flowing bloodstream.
adhesion of neutrophils to P-selectin in a flow chamber showed there were more adhered CuD [deficient] neutrophils than CuA ones
neutrophil migration under agarose showed that the CuD neutrophils moved farther than the CuA group in response to IL-8 but not fMLP
these results support the theory that dietary copper deficiency has proinflammatory effects on both neutrophils and the microvascular endothelium that promote neutrophil−endothelial interactions

In the current study, copper-deficient neutrophils migrated more readily through a monolayer of normal endothelial cells than did the copper-adequate neutrophils (Fig. 2). Similar increased neutrophil chemotaxis has been reported in vivo in the copper-deficient heifer

Nutritional supplementation with copper in the rat. I. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils - Inflammation Research The nutritional copper-supplementation: 1) significantly inhibited the adjuvant-arthritis development (33% ± 5, P<0.01); 3) significantly decreased the percentage of cell adhesion by an average of 41% ± 19 (P<0.01).¶Conclusions: The copper-supplemented diet has an anti-arthritic effect which may be also primed by the effect of copper on the expression of the neutrophil cell-adhesion molecules.

So could low copper be playing a big role in a subset of people with UC
by:
1. lowering deformability so the neutrophils dont flow through the blood vessels well
2. increasing endothelial capturing of the slow passing neutrophils (and damaging blood vessels)
3. increasing neutrophil migration through blood vessel walls as the copper deficient neutrophils pass endothelial cells easier
4. now you have a tonne of neutrophils in the lamina propria ready for war playing death metal music, heading towards the excessive h2o2 coming out of the colon / intestinal cells from defective mitochondria within them
5. the neutrophils get through the barrier to the surface as its degraded by the leaking h2o2, they enter into the crypt and start nuking everything with even more h2o2, which further damages the colonocytes / intestinal cells
6. blood leak from the vessels also gets through

so restoring copper could play decent a role in UC for the small subset of people who show low copper,
the copper forms in supplements don't work well. copper can be increased with small amounts 15g of beef or calf liver daily, gives ~2mg copper without pushing Vit A too much at ~3500iu (too far over 3000iu daily and the bone density increase reverses into bone loss, which may be offset by vitamin d intake). lamb liver also high in copper, chicken doesnt have much


but its not the solution alone. as the neutrophils will still leave the blood vessels because of the h2o2 trail. just would imagine in these cases there would be much less.
--

also reasonable doses of nicotine taken orally spread out could be used to help accelerate mitochondrial dna repair, if tolerated & free of additives like silica silicon dioxide Microdosing nicotine increases NAD levels and rejuvenates old mice

 

[cs3000]

2. For the budespride - Bromelain should be a good replacement.
like the corticosteroid it will skew immunity at doses over ~50mg ( budespride might not effect T cells but the neutrophil migration blocking action probably means lower immunity - as a tradeoff to lowering the neutrophil damage),

Bromelain removes surface molecules of immune cells & changes immunity. specifically reduces neutrophil migration to sites of inflammation a lot,
so bromelain will give a similar effect as the drug used at 100mg+ Bromelain treatment decreases neutrophil migration to sites of inflammation - PubMed

and is backed in ulcerative colitis orally by a case report about 2 women who gained benefit within a couple weeks of higher dose

https://www.deerland.com/wp-content/uploads/2015/04/60_Use-of-Bromelain-for-Mild-Ulcerative-Colitis.pdf

bonus
Diosmin and Bromelain Stimulate Glutathione and Total Thiols Production in Red Blood Cells

& protective against toxic metals https://www.researchgate.net/public...oxidative_injury_induced_by_aluminium_in_rats
(but i wonder about further potential iron & copper loss)

Bromelain from Ananas comosus stem attenuates oxidative toxicity and testicular dysfunction caused by aluminum in rats

Aluminum (Al) has been reported to induce testicular injury via oxidative stress. Ananas comosus stem extract is an inexpensive byproduct waste rich i…

www.sciencedirect.com

bromelain also cleaves surface molecules off some viruses like covid so they cant bind to cells, so may offset the changes in immune cells Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells

(body may build resistance to bromelain over time, so better to be cycled in this case)

 

[cs3000]

Found something very interesting i just stumbled on (graphic warning)
Successful Treatment of Pyoderma Gangrenosum with Potassium Iodide

Case report of a woman who had massive ulceration on legs and arms. cured with potassium iodide

Successful Treatment of Pyoderma Gangrenosum with Potassium Iodide​

A 35-year-old woman visited our hospital with multiple tender necrotic ulcers on her arms and legs. Laboratory examinations showed no abnormal findings except for a slight increase in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). A skin biopsy taken from the margin of a leg ulcer showed oedema and massive infiltration of neutrophilssurrounded by lymphocytes and histiocytes in the dermis, and necrotic epidermis with hyperplastic change. There was no evidence of vasculitis. Tissue cultures did not reveal any pathogenic microorganisms. She had neither systemic involvement nor accompanying complications such as arthritis, inflammatory bowel disease, haematological disorders or malignancy. A diagnosis of classical type idiopathic PG was made.
During the following 10 years, the ulcers constantly recurred on her extremities despite systemic treatments. This time, while continuing to take prednisolone 17.5 mg/day together with dapsone 50 mg/day and minocycline 200 mg/day as an adjuvant therapy, a well-demarcated new ulcer emerged and extended with marginal pustules following a minor injury on her left lower arm (Fig. 1a), and new lesions developed on both legs as well in 4 months. Instead of increasing the dose of steroid, we started oral KI at 900 mg/day. Surprisingly, the formation of new pustules almost stopped within a few days and improvement of the ulcers was observed accordingly (Fig. 1b and c). The dose of KI was increased to 1200 mg/day after 2 weeks, while the ulcers continued to regress.

by the photos the severe ulceration completely reversed to healthy tissue

Successful therapy of refractory erythema nodosum associated with Crohn’s disease using potassium iodide


article from the 1800s with case reports using potassium iodide for inflammatory problems

Iodide of Potassium in the Treatment of Cachexiæ and Other Diseased Conditions

Europe PMC is an archive of life sciences journal literature.

europepmc.org

. iodide gets converted into iodine by using up h2o2

https://www.york.ac.uk/org/seg/salters/ChemistryArchive/ResourceSheets/peroxide_iodide.PDF

Oxidation of I- [iodide] by the H2O2/peroxidase system leads to the formation of iodinium ions I+ which bond to thyroglobulin by electrophilic substitution. However, it is not clear whether I- is transformed directly to I+ or whether it passes through a molecular iodine intermediate

. Orally administered potassium iodide (15 mg/kg/day for 3 days) significantly inhibited the neutrophil chemotaxis in peripheral blood.
https://pubmed.ncbi.nlm.nih.gov/1972841/

polymorphonuclear leukocytes [neutrophils]. Three oxygen intermediates, superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH.) and chemiluminescence were included in assay studies. Dose response studies were performed with therapeutic doses of the drugs (10 microM--mM). We found that both potassium iodide and dapsone significantly suppressed the generation of oxygen intermediates, except for O2

https://pubmed.ncbi.nlm.nih.gov/7104217/

so this is another way to combat h2o2 overload induced inflammation / ulceration / blood vessel damage. [while fixing the cause of the h2o2 overproduction with other stuff by protecting & helping fix mitochondria ]
but:
1. would direct harm of raw potassium on ulcer in small intestine outweigh the other effects?
2. this megadose of iodide will shut down the thyroid. seems taking external T3 would get around this problem during the potassium iodide / for a week or 2 after?
3. does all of it get converted to iodine? the thyroid only takes a set amount then excretes the rest.
does the conversion saturate -> what is the lowest effective dose?
edit:

https://refp.cohlife.org/_iodine_p/_iodine_excess/Potassium%20iodide%20and%20the%20Wolff-Chaikoff%20effect-%20Relevance%20for%20the%20dermatologist.2000.r.pdf

Fortunately, with the dermatoses for which KI is currently indicated, it is likely that any therapeutic effect will be apparent within a few weeks. This is within the time frame that thyroid autoregulatory processes will ordinarily allow for escape from the WCE. If therapy with KI is continued for more than 1 month, however, a screening TSH would be prudent to ensure that iodide-induced hypothyroidism does not ensue. If iodide-induced hypothyroidism is detected, these changes are reversible by discontinuing the administration of KI. In a study of 7 patients with iodide-induced hypothyroidism, serum T4, T3, and TSH concentrations returned to normal within 1 month of iodide withdrawal.

^ so by this , taking it for the 2-4 weeks needed to see results would allow repair without enough time to see the thyroid adjusting effect reverse again, after the 'thyroid escape' occurs within 2-3 days of excess iodide
or put another way
thyroid inhibits iodide uptake initially, lowers thyroid hormone for 2-3 days, after this the 'thyroid escape' happens and the effect reverses, getting used to the extra iodide for a while and allowing normal thyroid function.
by the quote , if you stick with this for up to 1 month the thyroid function stays normal. but further than that, increased risk of hypothyroidism hits
though in some people who dont get the initial adjustment, the hypothyroid effect can be "permanent" Iodine-Induced hypothyroidism - PubMed.


4. aside from thyroid, is megadose safe for a few weeks? theres some cases of hypersensitivity


100mg KI contains ~76.4 mg iodide and ~23.6 mg potassium

900mg potassium iodide is ~700mg iodide 200mg potassium