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Lot of smart people here,thought I would put this up for discussion,just in case there is a possibility that this mechanism is involved somehow in IBD.

This is an old study,but now have to wonder if we are eating/supplementing
too many antioxidants. Something defective in iNOS pathway too much arginase,or SOD, not enough nitrate in diet. If I supplement with arginine,makes the UC worse,but that's now,what if I supplemented when first got UC.

I am still hot on the trail at just about all of the IBD drugs including biologics since 1942 control/kill MAP, except possibly pred. I ran across this study below. But right now not concerned with MAP in general,but something a little

different.

I mention many times over fortification of food, and importation of lots of fruits and veggies since say,late 1800's.

What if we are creating some form of immune deficiency with excess, antioxidants from an overly good diet,where the immune killing power is blunted,and in our case we can't clear bacteria efficiently in our guts.

Remember the DSS mice get better after the DSS is withdrawn,even after a massive chemical attack on the colon.

This might fit in well with the mucus breach theory, where once we have a breach,we cannot ward off

the massive bacteria invasion of the mucosa,because our killing power is prevented by excessive antioxidants,and other vitamins that suppress killing power.

Also I might add, when I supplemented with SOD, I got much much worse, perhaps now I know why. Was quenching peroxides, and impairing my killing power.

Perhaps the research docs concentrate on inflammation,and cytokine pathways too much and are not looking enough into immune clearance of bacterial invasion of the mucosa,and immune killing power in general.

As a side note, the incidence rate for crohns, peaks say around 25 years old,
then declines rapidly, I have to suspect that your antioxidant status at this age
is at a high level. They have just discovered that grey hair, and especially
people who get actual white hair,is a loss of SOD/perhaps also catalase,so your hair is being bleached by peroxides. Might be an interesting connection.
Less SOD,better killing of certain types of bacteria.
Of course older people also have less immune response in general,and higher
levels of inflammation.


Old Mike

SOD/arginine/iNOS MAP killing
http://www.jleukbio.org/content/49/...59c5e3da6ce3654fa8274ec8&keytype2=tf_ipsecsha


good paper on ROS and colitis/mice,tregs, cached version

"This argument is completely opposing the traditional concept that ROS is involved in the induction and progression of IBD [3]. According to the traditional concept, anti-oxidant intervention should be effective in the treatment of IBD, and large array of antioxidant compounds have been shown to be protective against IBD in experimental animals. Nonetheless, objective clinical data supporting anti-oxidant intervention of human IBD are still scarce [24]."



http://webcache.googleusercontent.c...ournal.pone.0095332+&cd=1&hl=en&ct=clnk&gl=us



another good one human

http://onlinelibrary.wiley.com/doi/10.1002/ibd.20607/pdf




antioxidant paradox-

The likely explanation is that free radicals aren’t as evil as advertised. (In fact, people need them to kill bacteria and eliminate new cancer cells.) And when people take large doses of antioxidants in the form of supplemental vitamins, the balance between free radical production and destruction might tip too much in one direction, causing an unnatural state where the immune system is less able to kill harmful invaders. Researchers call this the antioxidant paradox.



http://www.nytimes.com/2013/06/09/opinion/sunday/dont-take-your-vitamins.html?pagewanted=all&_r=0

paradox update
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575931/


periodontitis-this almost sounds like UC of the mouth

antioxidant status of people with peri is lower,which may sort of refute my case here,but

wonder if there is an alternative explanation, I don't have one but there might be one.

seems again a biofilm that is not easy to clear

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813562/




This one might be a must read:


well here is a different take;hard to kill p.gin

crap this could even explain some of the stuff going on with UC

http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020076




inos and mucus thickness

http://www.ncbi.nlm.nih.gov/pubmed/23977158




never saw this one,seems to support the mucus breach theory

http://www.ncbi.nlm.nih.gov/pubmed/24938744




mice diet and dss

http://www.ncbi.nlm.nih.gov/pubmed/24489720




france low food fortification sunlight study,lowers crohns incidence but not uc

http://www.ncbi.nlm.nih.gov/pubmed/24247650

this might show that oxidation is good where it blocks NF-KB
http://medicalxpress.com/news/2013-11-inflammatory-skin-mice-blocked-solution.html

here is the one on gray/white hair
http://medicalxpress.com/news/2013-05-gray-hair-vitiligo-reversed-root.html
 
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Interesting theory
If you find anything that explains why it can occur in kids extremely young as well .
DS was only 7 at dx but showed signs since birth.
 
Sorry to here this mlp, been trying to figure IBD out for the past 34 years, not yet.
I have two young grandchildren, I am sacred to death and driven to solve it.
You don't happen to live near any dairy farms, or rivers that drain farm land, do you.
I try and go out of the box on theories every once in awhile, just in case.
Then again starting to run out of good theories.
Old Mike
 
Well Old Mike to help your research,
my family and I do live on a dairy farm.
My one child has it but my other doesn't.
My DD, DS and myself are allergic to dairy (ironic I know).
My girl has never had our milk but we do have well water.
We are a big community here but IBD is almost unheard of.
 
Farmwife: Sorry to here about your daughter.
Growing up on a farm is associated to be protective for IBD,unstearlized water in China
also associated with protection.
Why just your daughter might have it don't know.
But even identical twins have different microbiomes,depending on different environmental
exposures. One can have IBD and the other not,while there can be a large genetic factor,since there is not 100% concordance in identical twins where one has IBD there is also a large environmental factor, the microbiome is also an environmental factor in addition to what we think of as an environmental factors. Such as diet,antibiotic use.
There are many theories of IBD,which is right, or perhaps none,or multiple causes.
People can go into remission at least for UC, from some off the wall treatments,such
as protease inhibitors,or histamine H1 blockers and mast cell stabilizers.
Myself and my son who lost his colon,dont have allergies.
My daughter and my brother have allergies, and no IBD neither one smoked.
I usually hang out in the healingwell UC forum, here is my Zyrtec thread.

http://www.healingwell.com/community/default.aspx?f=38&m=3206142

I have a zillion threads over there on various research subjects on IBD if your interested.
I know that is a different forum,but perhaps with what I call the internet brain, we can
solve this mess. I am always looking for, overlooked/forgotten treatments.
Old Mike
 
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One of the possible reasons crohn's disease diagnosis is most prevalent during teenage years is because the small intestine, especially the ileum, is covered with peyer's patches. Those peyer's patches are most active during teenage years. Bacteria such as AIEC are able to invade those through M Cells.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049390/


Those same M Cells and peyer's patches being inflamed are the first clinical signs in the intestine of crohn's disease.

http://www.ncbi.nlm.nih.gov/pubmed/17057202
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396064/
 
No question about it Kiny.
But my point might be that in most people, ones without IBD, was the immune system able to kill off the AIEC invasion. If not, why not.
Are all the exogenous antioxidants protecting bacteria from a rapid and deadly to them,immune response. Of course this also begs the age old question,why us and not everyone else,who eats a modern diet.
We are also seeing an large increase in incidence of pediatric crohn's,what
is really going on.

Old Mike
 
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I'm not sure. Lots of healthy people walk around with AIEC without disease. The difference between healthy and CD people is that in healthy people none of the bacteria are found in tissue. In crohn's disease, they're found in tissue, in macrohpages and neutrophils, they entered through M Cells or through tissue. In crohn's disease they're also of a more invasive type usually and there's usually many many more. What caused them to prevail, not sure.
 
See the internet brain is now sending me down a slightly different search path.
Now searching exogenous antioxidants stool.
Here is the first one I ran across.
Conclusion:
"So, antioxidant exacerbated B. hominis intensity but it decreased the pathological changes."

I say dual result, oxidative bursts quenched,therefore more b hominis,bursts quenched less pathological changes,but due to poor immune response,creating less collateral damage.

http://www.pubfacts.com/detail/1914...-antioxidants-on-Blastocystis-hominis-in-vivo.

bilirubin give some good info on what is going on in the gut.

http://webcache.googleusercontent.c...ournal.ppat.1003507+&cd=3&hl=en&ct=clnk&gl=us

pathways good paper
http://cdn.intechopen.com/pdfs-wm/29973.pdf

peroxide search the paper for exogenous
you will find that the body tries to counter act exogenous antioxidants

"When exposed to an excess of exogenous antioxidants, the cells are even prepared to suppress the intrinsic enzymatic antioxidative defence in order to preserve redox homeostasis [16]. From the evolutionary point of view, the refractory system had to be developed or otherwise signalling pathways involved in the regulation of crucial biological processes would have been diet sensitive (e.g., excessive consumption of fruits and vegetables would result in proreductive conditions and the obstruction of redox signalling pathways)."

So is all the juicing,fruit and veggie diets,supplements,antioxidant food additives,overwhelming this system,even fruit preserves,where in the old
days you would not have access to fresh fruits,depending where you live.
I might even say juicing, drinking orange juice,is an unnatural way of eating.
Getting huge concentrations of antioxidants at once.
How about all the BHT and food grade antioxidants in commercial foods,can the body deal with all of those.

You might also have read that endogenous antioxidant systems are depleted in IBD, is that because the body knows what it is doing and is trying to not quench oxidative bursts, and or it is lowering the system to counter act all the extra exogenous antioxidants/both reasons.

http://www.hindawi.com/journals/omcl/2012/596019/

here is one of my radical induction theory threads, keep in mind that back
then was trying to quench oxidation.
http://www.healingwell.com/community/default.aspx?f=38&m=2537173

h pylori\
http://www.ncbi.nlm.nih.gov/pubmed/20097867

Will add more stuff as I find it.
Does any of this mean anything, with IBD, who knows.
Old Mike
 
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oxidants are signalling molecules that can tell a cell when to enter apoptosis. If we consume to many unnatural levels of antioxidants, it may encourage a cell not to destroy itself. Apoptosis is one protective mechanism against developing cancer, a cell will destroy itself if it cannot repair itself when damaged.

Normal dietary sources of antioxidants probably wouldn't do harm, but supplements like vitamin e, melatonin, alpha lipoic acid, could do harm over along period of time.
 

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