My protocol

Dr Briggs said...
Thanks. :) And sorry it's too late for you. :(

Thank you. Yes, well... I'm utterly depressed at the moment by how everything has turned out, so I think this had better be my last post on HW for today :-/

Just wondering: do you have access to medical sites and all the research papers? Don't worry, I'm not going to ask you for log-in details... >_>. It's just that when I do research on the internet, pay-to-view content is the bane of my life: I either have to find older stuff which is free to view or rely on abstracts to give me the gist.

aguywithuc said...
I would love to get your opinion on Neutrophils. I followed an anti-TNF protocol and flared, I think it was that cherry juice craze or something similar.

In Japan they can stop a flare for about 2 years merely by filtering out Neutrophils an immune component. It is expensive and GI doctors here only know about and talk about medication. The Neutrophils are quickly replaced by the body within a few hours but the NEW ones are not programmed to attack the colon. This is a key element of the inflammation.

I haven't heard of this - are there any papers on it you could point me to? My concern with it would be that the reason our immune system ends up causing the damage isn't because our immune system has suddenly started attacking our colon (a very common myth) - it is that our immune system is responding to a stimulus, resulting from a leaky gut. In people who develop IBD, out immune system over-reacts, and there are some positive feedbacks that result in our immune cells continually ramping up that response. Based on your description, it seems like they are removing immune cells to blunt the response. I think that would be fine - if they then took that opportunity (the reduced inflammatory response) to focus on healing the gut, to fix the underlying problem. If you don't, the leaky gut will gradually push you back to the same state, with those immune cells hyperactively responding to bacteria leaking through your leaky gut.

Canada Mark said...
There's lots of cytokines involved (or show up in various research) because of their many roles - Cytokines generally speaking can be thought of as soluble molecules that bind to their respective cellular receptors. The difference found in most cases between Crohn's and Ulcerative Colitis is generally the adaptive vs. innate response respectively.

The commonality arises from the fact that TNFa is part of the TNF-TNF receptor family. TNFa can function either as a pro-inflammatory cytokine in some cases, yet in others it can actually trigger cell death (apoptosis). In our case with IBD, both TNFa and Histamine together stimulate the breakdown of tight junctions between epithelial cells - this is what causes the characteristic swelling of acute inflammation in our affected areas or throughout our colon in some people's cases like mine and NCOT's or Levi's with Crohn's-Colitis.

TNFa can do a lot of things as well - if TNFa is produced in large enough amounts it can signal to the bone marrow to increase the output of neutrophils (@AguywithUC) - which are found in very high levels in IBD and I believe (but am not 100% sure) but more so in Ulcerative Coltis than in Crohn's. Which also goes back to the difference between the two innate and adaptive immune responses between the two conditions:

TNFa is largely dependent on the NF-kB pathway, which I think we've all read about or heard the term from time to time on here. Opposite to the above, when at low concentrations TNFa acts locally (or in the immediate area) to increase the expression of adhesion molecules on leukocytes AND to stimulate other cells to produce pro inflammatory molecules. When at high concentration as mentioned above, it actually stimulates epithelial cells to synthesize nitric oxide - hence the increase seen in IBD.

Now - what I find of utmost curiosity is that one of the main agents that induce TNF secretion is LPS (Lipopolysaccharides) from gram negative bacteria. - But I'm a bacteria guy.. and don't by into the auto-immune thing.

Very interesting and well explained. I also don't buy the auto-immune explanation of IBD. The research seems to pretty convincingly illustrate that it is due to a hyper immune response to bacteria crossing through a "leaky gut" (paracellular and transcellular bacterial translocation, in the science jargon).

It isn't clear though how much that hyperactive immune response is innate to the individual (genetic) versus an acquired adaptation - and if the latter, if it is a temporary one that can subside over time if we heal our intestines, and limit bacteria from stimulating immune cells.

Canada Mark said...
Interestingly as well - this is why before we take a drug such as Remicde we are tested for tuberculosis, because when this pathway is blocked it can lead to the re-emergence of active tuberculosis.

So in a nutshell we take Remicade more so as a means to reduce damage to our epithelial cells or the "swelling" so to speak and restore the tight junctions. This is why we have colonoscopies - to verify that these tight junctions have been restored and if so we are deemed in clinical remission. Though far from a cure lol.. But hey, we can get our lives back for a bit at least or well, at least for a period of time when it works, which it does not in some cases.

Personally, I don't think the colonoscopy verifies that the tight junctions have been restored - all it is verifying is that there is no inflammation. The tight junctions could still be leaky, but the TNF alpha being produced by the immune cells is all being bound by the Remicade. Or am I misinterpreting something?

If it healed our tight junctions, then presumably inflammation should not rapidly come back once the Remicade is stopped - but it generally does.

I think that by binding to TNF alpha, it creates a better condition to allow us to heal our tight junctions - but that won't happen if we don't provide the resources necessary, and continue doing things that promote damage to them.

Canada Mark said...
These can be either interpreted as an immune "disfunction" where our body is attacking something "self"... or our bodies ARE actually attacking something... and herein lies the whole mystery of IBD.

See this study and let me know what you think:
Kovarik, JJ, et. Al, “Impaired anti-inflammatory efficacy of n-butyrate in patients with IBD”, Eur J Clin Invest. 2011 Mar;41(3):291-8

Patients with IBD all exhibited a heightened production of inflammatory cytokines in response to bacterial stimulation of immune cells. So - they were responding to bacteria - not attacking the body itself.

There is a lot of that kind of data, which to me should end the auto-immune theory.

Hi Dr. Briggs:

Good stuff. Couple questions. You said you tried SCD and didn't do so well on it, for me SCD works like a magic pill. If I ever get into a flare by cheating, then going back to SCD pretty much puts me back into remission in a few weeks, i.e. BM's return to almost normal, no mucus, blood, etc. However, it's hell to be on this diet, I'm always feeling tired, dehydrated, etc.

I have never been on any immunosuppressant drugs. My question is, can your protocol be modified for someone for whom SCD does work. Instead of using the TNFa inhibitors, since I'm already without inflammation on the diet, can I somehow proceed to step 2? The problem is I see that in step 2 you recommend lots of fibre and resistant starches and as soon as I take these I go back into a flair. So any recommendations for successful SCDers? I know SCD is not the answer because it's hell to be on the diet, but at least it keeps me drug free. I do want to perhaps try a FMT at some point but don't have access to a donor as of now. What do you think?

brucen36 said...
Hi Dr. Briggs:

Good stuff. Couple questions. You said you tried SCD and didn't do so well on it, for me SCD works like a magic pill. If I ever get into a flare by cheating, then going back to SCD pretty much puts me back into remission in a few weeks, i.e. BM's return to almost normal, no mucus, blood, etc. However, it's hell to be on this diet, I'm always feeling tired, dehydrated, etc.

I have never been on any immunosuppressant drugs. My question is, can your protocol be modified for someone for whom SCD does work. Instead of using the TNFa inhibitors, since I'm already without inflammation on the diet, can I somehow proceed to step 2? The problem is I see that in step 2 you recommend lots of fibre and resistant starches and as soon as I take these I go back into a flair. So any recommendations for successful SCDers? I know SCD is not the answer because it's hell to be on the diet, but at least it keeps me drug free. I do want to perhaps try a FMT at some point but don't have access to a donor as of now. What do you think?

Sorry for not responding sooner, I haven't checked this site in a while.

My contention with SCD is that it is not only "bad" bacteria who rely on complex carbs for food - all of them do (other than sulfate reducing bacteria, which we don't want in there). So it doesn't selectively starve off the "bad" bacteria as people are led to believe. It starves off them all. A low amount can survive, but at low enough levels that the amount leaking through the leaky gut is insufficient to sustain the immune cascade, so symptoms disappear. Then people think they are cured. But, since commensal bacteria play many important roles in the maintenance of our intestinal barrier, people on SCD likely all continue to have a leaky gut - so if they go off the diet, and eat something that feeds the low levels of remaining bacteria, they start to bloom, migrate through the leaky gut, and trigger the immune response - i.e. they flare again.

So, you need to heal the gut. That is my approach. The problem is that friendly bacteria play an important role in healing and maintaining the gut, but those same bacteria leak through a leaky gut triggering the immune response that also damages the gut. So, you need to temporarily suppress the immune response so you can start to heal the barrier, and rebuild the microbiota (ideally through fecal transplant).

Ultimately, my approach does not work with SCD, since my approach (just like Borody's approach) relies heavily on feeding a healthy microflora, as they play an important role in our health, especially gut health.

Now that I've had 4 people with increased neuropathy since trying this little experiment I've been meaning to drag up this thread and post this


www.dramyyasko.com/resources/autism-pathways-to-recovery/chapter-4/
All of Dr Amy's stuff would be helpful, but especially reading starting at :Controlling Excitotoxins Neurotransmitters: Balancing GABA & Glutamate
chronicdiseasetalk.wordpress.com/2013/03/13/glutamate-and-balance/comment-page-1/


Alot of us are suffering from anxiety or depression
www.intechopen.com/download/get/type/pdfs/id/17574

Eventually I'll start a thread in this, but dr Amy will have to do for now ;)

Briggs said...
See this study and let me know what you think:
Kovarik, JJ, et. Al, “Impaired anti-inflammatory efficacy of n-butyrate in patients with IBD”, Eur J Clin Invest. 2011 Mar;41(3):291-8

OM brought up this post again tonight. I’m sorry I didn’t see or read anything on it till now. I can’t access the full paper but that doesn’t matter - it does leave me with a question though at the end:

That’s quite the interesting study - TLR2 hyper-responsive versus TLR4. Aside from their conclusion, it suggests that we (those of us with IBD) are hyper-responsive to gram positive bacteria, parasites and fungal/yeast organisms. Ultimately TLR2 binds with extracellular ligands (TLR2/1 certain bacteria and parasites and TLR2/6 to Gram Positive Bacteria and fungi) and this leads to the release of NF-kB. Release of NF-kB in turn activates certain gene expressions. The various Toll Like Receptors activate different transcription factors (such as NF-kB etc) which leads to the variation of genes turned on to help protect us against invading pathogens.

Genes turn on for the production of various cytokines etc.

IL12 (a cytokine) produced monocytes (as in the study) or alternatively produced by macrophages and dendric cells as well act upon CD4 and CD8 T-cells. What IL-12 does is induce the TH1 phenotype and “activates”

TH1 response protects against intracellular pathogens.

SO the whole immune cascade response thing... that's the basic progression.

More interesting is that I think IL-6 and IL-18 are also up-regulated in IBD and again these are also associated with protection from intracellular pathogens, fungal and bacterial infections.

Most of the time it’s said these are all up-regulated due to “autoimmune” because they are associated with a variety of autoimmune conditions, but I still say it’s equally, if not more plausible they are up-regulated because the body is simply trying to protect itself…

IL10 being the anti-inflammatory side of things to keep aberrant inflammation in check.

That all being said: On to the question....

"Further analysis revealed that the impaired sensitivity of PBMC to the anti-inflammatory action of n-butyrate was independent from hyperreactivity of immunocompetent cells.”

This statement from the results section of your link seems to suggest that perhaps there is a defect “independent” of the hyper-responsiveness. Unless I am reading that wrong. So it would be interesting to read the whole study or get some clarification on this. Again, to me this suggests not only a hyper-responsiveness to gram positive bacteria and fungi/yeast (or an actual on-going infection) but also a possible primary defect that leads to decreased IL-10 production.

To be perfectly honest, to me, it further supports the defective or impaired barrier function vs autoimmune. Fix the barrier defect/mucus/leaky gut - whatever one wants to call it - fix the issue at root.

Post Edited (Canada Mark) : 7/19/2014 12:45:13 AM (GMT-6)

This  what is going on with butyric acid and UC.

If we have impaired oxidation of butyric acid,then if we eat too much fermentable starch or other material

that makes butyric acid in the colon,causes ulceration ,if the amount made exceeds our ability to utilize it. 

Why paleo and SCD work on some people,they have cut out the fermentables and make less butyric acid,

from all bacteria that can produce butyric acid.

I don't know why 90 plus percent of the papers refer to it as butyrate.

Butyrate is the ionized form, such as sodium butyrate, or named as an ester such as ethyl acetate.

It might be a good idea to determine why we cant oxidize butyric acid correctly,tnf perhaps.

Sure the docs are using sodium butyrate enemas,but the bugs are making butyric acid.

So taking sodium butyrate might be ok,it is not butyric acid,not 100% sure.

Old Mike

butyric acid causing ulcers in colon of mice

http://gut.bmj.com/content/52/1/79.full

sulfide perhaps the problem impairs oxidation

http://www.ncbi.nlm.nih.gov/pubmed/8287651

methionine,you would think we get enough from the diet,or something is wrong with our cycles

many of us have high homocysteine

http://en.wikipedia.org/wiki/Methionine

perhaps not hydrogen sulfide

http://www.ncbi.nlm.nih.gov/pubmed/11508674

gene expression

http://www.ncbi.nlm.nih.gov/pubmed/21987487

perhaps nothing really wrong except for inflammation

which might lead you back to lowering tnf,which leads me back to a mucus breach in the first place exposing the immune system to, too many bacteria

http://www.ncbi.nlm.nih.gov/pubmed/9823806

more on inflammation

http://www.ncbi.nlm.nih.gov/pubmed/18942762

no enzyme problem

http://www.ncbi.nlm.nih.gov/pubmed/8984028

primary metabolic disorder not found,then what the hell is going on

http://www.ncbi.nlm.nih.gov/pubmed/11447021

impaired

http://www.ncbi.nlm.nih.gov/pubmed/21707682

transport problem glucose oxidation

http://www.ncbi.nlm.nih.gov/pubmed/19774643

more

http://www.ncbi.nlm.nih.gov/pubmed/18054563

back to tnf

http://www.ncbi.nlm.nih.gov/pubmed/15905703

more

http://www.ncbi.nlm.nih.gov/pubmed/11191284

ammonia

http://www.ncbi.nlm.nih.gov/pubmed/12637251

uc an energy deficiency disease

http://www.ncbi.nlm.nih.gov/pubmed/6106826

increased butyrate usage a consequence of healing not RS

http://nutrition.highwire.org/content/134/3/493.full

butyrate enema as good as salt water

http://www.researchgate.net/publication/14308096_Treatment_of_left-sided_ulcerative_colitis_with_butyrate_enemas_a_controlled_trial

 

Post Edited (Old Mike) : 7/19/2014 5:37:54 PM (GMT-6)

For those of us who can't get Wellbutrin we might want to concentrate on the mechanism of action on tnf

lowering. Perhaps we can get somewhere by looking at this info,also notice it up regulates IL-10.

Putting this info in both current threads.  Just starting to look into this,up regulation of cAMP.

How else can we do it,easily if possible.

Would appreciate any help, especially from our biochemists.

Old Mike

http://arca.icict.fiocruz.br/bitstream/icict/2741/1/Brustolim_Ribeiro_Kast_etal.pdf

Abstract

In a wide range of human diseases of inflammatory nature like Crohn's disease, pathology is mediated in part by pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic antidepressant bupropion, in wide use worldwide to treat depression in humans for a decade now, <u>profoundly</u> lowers levels of TNF, interferon-gamma, and interleukin-1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model. Mice challenged with an otherwise lethal dose of LPS were protected by bupropion and levels of the anti-inflammatory cytokine interleukin-10 were increased. Previous data in rodents and humans indicate antidepressant effects of bupropion are mediated by its weak reuptake inhibition of norepinephrine and dopamine. Concordant with this, TNF suppression by bupropion in our mouse LPS model was largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not by a D2 antagonist. TNF synthesis is controlled by an inverse relationship with intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either beta-adrenoreceptors or D1 dopaminergic receptors result in increased cAMP but stimulation of D2 receptors lowers cAMP. We conclude that bupropion may suppress TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1 receptors, resulting in increased cAMP that inhibits TNF synthesis. Bupropion is well tolerated also in non-psychiatric populations and has less risk with long term use than current anti-inflammatory, immunosuppressive or TNF suppressive treatments such as prednisone, azathioprine, infliximab, or methotrexate. New anti-inflammatory treatments are needed. We believe a new chapter in antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's use for this in humans should be explored.

 

Started taking Bupropion 75mg twice a day 3 days ago. I feel like crap today, I feel dehydrated, upset stomach, slight nausea, head hurts some, just feel run down. Reading about this drug it appears these are the initial symptoms. Has anyone on here had these before and do they go away?

Briggs said...
In case anyone is interested, here is the very long paper I wrote summarizing the 150 or so research papers I read this summer while coming up with a plan to "cure" myself. Towards the end I lay out the protocol I developed. And since I have a massive ego, I named the protocol after myself.

I posted the paper on our server:
pubpages.unh.edu/~msbriggs/IBD-Briggs-beta6.pdf

I don't frequent the forums much anymore, but will check in occasionally in case anyone has any questions about it. Also note that there are parts of it I haven't finished yet - there is never enough time....

here ya go janez -

oops - sorry - first rule of trying to help = know the flip what you are doing !

we mere mortals may not have access ?????!!!!!

NiceCupOfTea said...

juststud said...
oops - sorry - first rule of trying to help = know the flip what you are doing !

we mere mortals may not have access ?????!!!!!

It used to be available, but isn't anymore. It must have been removed.

The only hope of seeing it now is for Briggs, or somebody else who saved it, to reupload it.

And here it is! Seems like word of it spread beyond HW.

thepowerofpoop.com/wp/wp-content/uploads/2015/07/IBD-Briggs-July-21-2015-1-1.pdf

well done my friend - I always knew there was more to you than just a pretty face !