Fixing Leaky Gut Helps ME/CFS, and Sometimes Achieves Full Remission

Hip

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Fixing Leaky Gut Helps ME/CFS, and Sometimes Achieves Full Remission

In a ME/CFS patient, Michael Maes found that treatment with anti-inflammatories, antioxidants and a leaky gut diet decreased the the leakage of the LPS endotoxin from Gram negative Enterobacteria in the gut, and this was accompanied by a complete remission of ME/CFS symptoms. See this 2007 study by Maes:

Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome.


And in this later 2008 paper, Michael Maes studied 41 ME/CFS patients who he put on "natural anti-inflammatory and anti-oxidative substances, such as glutamine, N-acetyl cysteine and zinc, in conjunction with a leaky gut diet" for a period of 10 to 14 months. Up to 24 patients showed a significant clinical improvement or remission after this protocol, along with attenuation of their IgA and IgM responses to LPS.

Maes also published this 2009 review of the evidence for increased LPS translocation through a leaky gut.



What Is Leaky Gut

Leaky gut involves a dysfunction of the tight junctions that bind together the epithelial cells in the inner lining of the gut. Some researchers suggest leaky gut can lead to LPS endotoxin leaking from the intestine into the liver and general circulation where this LPS may trigger inflammatory changes in the liver and other organs. Ref: 1



Some Factors That Cause Leaky Gut:
  • Micro-organisms in the gut increase intestinal permeability. Ref: 1
  • Lipopolysaccharide (LPS) endotoxin from Gram-negative bacteria increases intestinal permeability. Ref: 1 2.
  • Clostridium perfringens epsilon toxin increases small intestinal permeability in mice and rats. Ref: 1.
  • Clostridium difficile toxin A increases intestinal permeability. Ref: 1
  • Enteropathogenic Escherichia coli bacteria disrupt the tight junction barrier function and structure. Ref: 1
  • Many bacteria "alter tight junction state, presumably to enhance their own growth requirements. Vibrio cholerae secretes a variety of toxins and one of these, zonula occludens toxin, was recognised as increasing paracellular permeability". Ref: 1
  • Cytomegalovirus can cause increased intestinal permeability. Ref: 1
  • Mycotoxin ochratoxin A, that can contaminate cereals and animal feed, alters intestinal barrier function, and increases intestinal permiability. Ref: 1 2
  • Mycotoxins especially trichothecenes and patulin ingested via food contamination affect the intestinal barrier integrity and can result in an increased translocation intestinal contents into the body. Ref: 1 Note that Dr Joseph Brewer's study found ochratoxin A in 83% of ME/CFS patients, and trichothecenes in 44% of of ME/CFS patients.
  • Blastocystis hominis a protozoan parasite can cause increased intestinal permeability. Ref: 1
  • TNF-alpha an inflammatory cytokine causes an increase in intestinal permeability, likely by increasing ERK1/2. Ref: 1 Note that Saccharomyces boulardii inhibits ERK1/2, so may help counter the effects of TNF-alpha.
  • IL-1beta causes an increase in intestinal epithelial tight junction permeability. Ref: 1
  • Nonsteroidal antiinflammatory drug (NSAIDs) increase intestinal permeability. Ref: 1
  • NSAIDs compromise intestinal permeability in IBS patients to a greater extent than in healthy subjects. Ref: 1.
  • Capsaicin from chili peppers increases leaky gut. Ref: 1
  • Solanaceae spices (paprika, cayenne pepper) increase gut permeability. Ref: 1
  • Lectins from beans and vegetables can increase leaky gut. The most problematic lectins are found in grains (wheat, rye, barley, oats), legumes (beans, soybeans, peanuts) and nightshades (potatoes, tomatoes, peppers, aubergine). Interestingly, sucrose sugar helps neutralize the toxic effect of legume lectins on gut permeability. Ref: 1 And N-acetyl-glucosamine (NAG) may help neutralize lectins from potatoes, tomatoes, rice, barely and rye, as these foods contain chitin-binding lectins, which bind to glucosamine. Refs: 1 2
  • Chloramines (NH2Cl) in tap drinking water compromise tight junctions and so increase gut permeability. Ref: 1. Around 1 in 5 homes have chloramines in their tap water. Details on how to remove chloramines from your drinking water given here (10 mg of vitamin C neutralizes chloramines in 1 liter of water).
  • Gliadin (one of the components of gluten) increases gut permeability. Ref: 1 2
  • Nonalcoholic fatty liver disease (NAFLD) is associated with increased gut permeability, and this related to the increased prevalence of SIBO in NAFLD patients. Ref: 1
  • Traumatic brain injury (TBI) can increase intestinal permeability. Ref: 1
  • Low stomach acid (hypochlorhydria) is said to increase leaky gut (though I cannot find any scientific references for this). In this case gastric acid boosting supplements like betaine HCl (or just 1 or 2 tablespoons of vinegar) taken after each meal may help.
  • Vitamin C in 500 mg doses surprisingly increases leaky gut. Ref: 1
  • Compression of the vagus nerve can cause leaky gut, POTS, MCAS, anxiety, in the opinion of Dr Ross Hauser. See this video at 2:24.



Supplements and Drugs That Fix A Leaky Gut:
  • Glutamine "is presently the best known compound for reducing intestinal permeability". Ref: 1 Glutamine preserves gut mucosa integrity in an experimental mouse model. Ref: 1. This article says for repairing leaky gut, glutamine needs to be taken on a empty stomach, and at a dose of 5 to 10 grams of L-glutamine powder daily. L-glutamine powder can be bought here.
  • Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells. Ref: 1
  • Zinc carnosine supplement helps prevent leaky gut occurring. Ref: 1
  • Colostrum is a powerful means to repair laky gut. In a study on indomethacin-induced gut hyperpermeability, bovine colostrum was able to counter the leaky gut produced by indomethacin (which is an NSAID drug). Ref: 1
  • Triphala herbal formula (especially the Emblica officinalis component, aka "Indian gooseberry") protects against methotrexate-induced intestinal permeability in rat intestine. Ref: 1
  • Curcumin may help decrease intestinal permeability, and may work well with glutamine. Ref: 1
  • Probiotic bacteria might be beneficial in protecting intestinal epithelial cells from the deleterious effects of pathogenic bacteria. Ref: 1
  • Bifidobacterium longum CCM 7952 (but not CCDM 372) improves improved intestinal barrier function and reduces intestinal permeability. Ref: 1
  • Lactic acid bacteria probiotics significantly decreased small bowel permeability in IBS-D patients (decreasing the lactulose-mannitol permeability ratio from 0.038 down to 0.023). Ref: 1
  • Slippery elm bark (Ulmus fulva) may help reduce intestinal permeability. Ref: 1
  • Berberine attenuates disruption of tight junctions in the intestinal epithelium in a mice model of endotoxinemia. This may possibly have been mediated through down-regulation of NF-kB and myosin light chain kinase pathway. Ref: 1
  • Low-dose sulfasalazine (500 mg once or twice a day) prevents tight junction disruption induced by TNF-alpha. Ref: 1. Note that the drug sulfasalazine is a potent inhibitor of NF-κB activation, and TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-κB activation, so this explains how sulfasalazine can reduce leaky gut. Ref: 1 However, sulfasalazine may inhibit the antiviral Th1 response, which is undesirable in ME/CFS. Ref: 1
  • Chlorogenic acid (found in green coffee bean supplements) decreases intestinal permeability. Ref: 1
  • Lubiprostone (Amitiza), an IBS-C drug, improves intestinal permeability (lowering the lactulose-mannitol ratio down to 0.017, compared to 0.028 in controls). Ref: 1
  • EGCG, genistein, quercetin and myricetin promote and protect the intestinal tight junction barrier. Ref: 1
  • Collagen and gelatin are reputed to help heal leaky gut (found in bone broth). Gelatin can be easily obtained in the supermarket as jelly cubes (jello cubes) for making gelatin desserts.
  • Black pepper (piperine) and nutmeg may reduce intestinal permeability, possibly by causing cell swelling. Ref: 1



If you have diarrhea-predominant irritable bowel syndrome (IBS-D), there is a good chance you have leaky gut, as this is common in IBS-D:

This study found that approximately 39% of IBS-D patients had increased intestinal permeability as measured by the lactulose/mannitol test. This study found that colon permeability of IBS-D patients was significantly increased, and interestingly, this degree of colonic permeability correlated with stool frequency (the number of times a day a patient passes stools). This study found that IBS-D patients had increased proximal small intestinal permeability, and this permeability was higher in IBS-D patients with eczema, asthma, or hay-fever.

This study found raised levels of serine protease in the colons of IBS-D patients, and discovered that this serine protease causes epithelial barrier dysfunction and increased intestinal permeability; and this study determined that this serine protease came from pancreatic digestive enzyme secretions.
 
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Hip

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A leaky gut regimen that I derived benefits from is:

Leaky Gut Protocol
Saccharomyces boulardii (Jarrow) x 2 capsules
Grape seed extract 200 mg
Zinc carnosine 75 mg
Vitamin E 400 IU
N-acetyl-glucosamine 500 mg
Triphala 1500 mg
Glutamine powder 1 heaped tsp (6 grams)
Slippery elm bark 1000 mg
Zinc 20 mg

I took all these twice daily.

When I do this protocol again, I will add colostrum to my regimen. Sports scientist Neil Wootten says in this article that he finds the swiftest approach to curing intestinal hyperpermeability is the use of colostrum. A good dose of colostrum powder is one or two heaped teaspoons a day (= 5 to 10 grams). Athletes actually use doses as high as 60 grams daily. You can buy colostrum much more cheaply as a bulk powder — see the bulk powder supplement websites listed below.

Note that Triphala is a mix of three herbs:
Amla/Indian gooseberry (Emblica officinalis), Haritaki (Terminalia chebula), and Bibhitaki (Terminalia bellirica). It would seem that Amla is the most effective for leaky gut. Ref: 1.

It is also a good idea to remove chloramines from your tap drinking water. Chloramine is a disinfectant put in tap water (in about one-fifth of the country) in addition to chlorine. Chloramine compromises tight junction function and may lead to leaky gut. Ref: here. Details on how to remove chloramines from drinking water are given here.


Tip for Obtaining Supplements More Cheaply:
You can often buy supplements perhaps 10 times cheaper (90% off) if you search online for bulk powder sellers. Bulk powder sellers offer vitamins, herbs, and many other supplements in bags, pouches, or large tubs (in weights typically ranging from 100 grams to 1 kilogram). Some bulk powder suppliers include:

US purebulk.com, www.bulksupplements.com, www.nutraplanet.com
UK www.myprotein.com, www.bulkpowders.co.uk
AU www.bulkpowders.com.au

EBay is also often a good place to search for bulk powers.

From the above supplement list, I have been able to buy: grape seed extract, glutamine, slippery elm bark, zinc, and triphala herb as bulk powers.

Buying all these at often around 90% discount I find is well worth it.

If you are Google searching for bulk powder sellers for a particular supplement, just put the phrase: powder OR bulk in your Google search, and this will usually find what you are looking for.
 
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Hip

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Is there a way to know if you have leaky gut?
Yes, there is a simple test for leaky gut called the lactulose/mannitol test, which can detect if you have a leaky gut (intestinal permeability). Note however that this checks only the small intestine for leakiness, but does not test the colon for leakiness.

The polyethylene glycol (PEG) test for leaky gut checks your intestines as a whole for leakiness (the small intestine and the colon).
 
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Yes, there is a simple test for leaky gut called the lactulose/mannitol test.
Thank you very much for this thread. Do you have any advice on how one would go about finding a health provider to administer the lactulose/mannitol test and interpret the results? If I knew of a local doctor that could do this I would take the test tomorrow.
 

Enid

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This is a great help - thank you so much Hip. Simply put one can really work on fairly easily. (I registered high on a KdeM neurotoxic metabolite test a little while and assume it refers).
 

Hip

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Thank you very much for this thread. Do you have any advice on how one would go about finding a health provider to administer the lactulose/mannitol test and interpret the results? If I knew of a local doctor that could do this I would take the test tomorrow.
Genova Diagnostics do a Intestinal Permeability Test:

http://www.gdx.net/product/10122

This is a home test, involving drinking these two lactulose & mannitol sugars, and sending in a urine sample for analysis.
 

globalpilot

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YOu can also do it through directlabs.com if you can't get a doc to do it.

That was a very interesting study. It is noteworthy that the 13 year old had IgG3 class deficiency. maybe this is what caused her issues.
 
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Thanks Hip, good info, having had (viral) onset developing chronic IBS/gastritis, I am also biased towards the gut theory, if you can get your gut back to stellar functioning it could take care of the rest.
 

anniekim

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Thanks Hip for sharing this, very interesting. I used to not be convinced about the whole leaky gut and M.e connection, but now am realising that I seem to be wrong. I just watched Dr Peterson's recent talks on video that he did in Sweden. He too mentions that many people with M.e have leaky gut and treating it can bring about clinical improvement.

Are there are any thoughts what could be contributing to the leaky gut in people with M.E? Are we susceptible to the causes listed above due to a dysfunctional immune system?

When you say you derived benefits from your leaky gut regime supplements, may I ask what kind of benefits and for how long were you on this protocol? Are you still on the protocol? Also did you have the test to check for leaky gut? Did you follow any specific leaky gut diet as well? Sorry for all the questions! Thank you in advance
 

heapsreal

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Has anyone used rifaximin/xifaximin to rid intestinal bacteria. I hear KDM uses this for gut treatment??

Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, meaning that very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. It is used in the treatment of traveler's diarrhea and hepatic encephalopathy, for which it received orphan drug status from the U.S. Food and Drug Administration in 1998.





Contents
[hide] 1 Uses
2 Availability
3 References
4 External links


[edit] Uses

Rifaximin is licensed by the U.S. Food and Drug Administration to treat traveler's diarrhea caused by E. coli.[1] Clinical trials have shown that rifaximin is highly effective at preventing and treating traveler's diarrhea among travelers to Mexico, with few side effects and low risk of developing antibiotic resistance.[2] [3] It is not effective against Campylobacter jejuni, and there is no evidence of efficacy against Shigella or Salmonella species.

It may be efficacious in relieving chronic functional symptoms of bloating and flatulence that are common in irritable bowel syndrome.[4] There was recently a pilot-study done on the efficacy of rifaximin as a means of treatment for rosacea, according to the study, induced by the co-presence of small intestinal bacterial overgrowth.[5]

In the United States, rifaximin has orphan drug status for the treatment of hepatic encephalopathy.[6] Although high-quality evidence is still lacking, rifaximin appears to be as effective as or more effective than other available treatments for hepatic encephalopathy (such as lactulose), is better tolerated, and may work faster.[7] The drawbacks to rifaximin are increased cost and lack of robust clinical trials for HE without combination lactulose therapy.

A recent study suggests that treatment with rifaximin relieves symptoms for some sufferers of irritable bowel syndrome. [8]

[edit] Availability

Rifaximin is currently sold in the U.S. under the brand name Xifaxan by Salix Pharmaceuticals. It is also sold in Europe under the names Spiraxin, Zaxine, Normix, Rifacol and Colidur, and in India under the name Rixmin, Rcifax, Rifagut and Torfix.

India's Lupin and US firm Salix Pharmaceuticals have joined forces to develop and commercialise an extended-release version of rifaximin using Lupin's proprietary bioadhesive technology


cheers!!!
 

anniekim

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There was a post on here from two years ago, http://forums.phoenixrising.me/show...d-Xiflaxan-A-Dr.-Peterson-Patient-Improves/pa saying a patient of Peterson's found they ony made significant improvement when they treated their leaky gut with not only xifaxin but IVIG (immunoglobulins). They said this was because 'the Xifaxan wipes out the toxic overload of bacteria in the gut, and the IVIG greatly slows down their regrowth by making up for the deficit in the GI immune tract'. I have no chance of getting IVIG therapy here in the UK.... I think though I may pay out for the intestinal permability test...
 

heapsreal

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There was a post on here from two years ago, http://forums.phoenixrising.me/show...d-Xiflaxan-A-Dr.-Peterson-Patient-Improves/pa saying a patient of Peterson's found they ony made significant improvement when they treated their leaky gut with not only xifaxin but IVIG (immunoglobulins). They said this was because 'the Xifaxan wipes out the toxic overload of bacteria in the gut, and the IVIG greatly slows down their regrowth by making up for the deficit in the GI immune tract'. I have no chance of getting IVIG therapy here in the UK.... I think though I may pay out for the intestinal permability test...
Interesting, thanks
 

globalpilot

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candida antibodies

I'm so glad this topic has been posted. I've made arrangements to ship my blood to REDLABS for the intestinal bacteria test. The price is very fair which makes up for the high shipping.

I had forgot but a while ago I also did antibody testing for 3 candida species: albicans, krusei and tropicalis. The latter 2 IgG antibodies were high, IgM was near the high end.

Immunosciences did this but they no longer offer this test. Has anyone else had this testing done ?

Also I wish REDLABS would test IgG as that is the one that was high for the candida, not IgA or IgM.
 

Tristen

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I tested positive for Leaky Gut with what's now Genova. I've also tested positive for EV's and Dysbiosis via blood work, and H2S via urine test. I did the 2 month Xifaxin/VSL3 Tx. Did my month of Xifaxin, then got the VSL3 and found that I couldn't tolerate it. Tried a milder Probiotic, still couldn't tolerate it. So, I wasn't able to complete the second half of the Tx and because of this I'm unable to accurately judge if it was helpful. I didn't notice any changes with the month of Xifaxin alone. But I am convinced that GI Trans-location is a huge issue for me.

I do believe that correcting GI issues would bring about significant improvements. The Natural stuff I've been on for Leaky Gut is Glutamine, NAG, Aloe Vera juice, Digestive enzymes, and Zinc. Plan to start that again. The main thing is to avoid substances that aggravate the condition (ABX, NSAIDS, Food allergies, etc). The GI infections need to go, and the flora rebalanced to a friendly and supportive environment.
 

globalpilot

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Did the dysbiosis test identify the pathogens ? Or was this a stool test.
Too bad the rifaximin didn't help. It didn't help me either and I def have something in the upper area.
 

Hip

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Thanks Hip for sharing this, very interesting. I used to not be convinced about the whole leaky gut and M.e connection, but now am realising that I seem to be wrong. I just watched Dr Peterson's recent talks on video that he did in Sweden. He too mentions that many people with M.e have leaky gut and treating it can bring about clinical improvement.

Are there are any thoughts what could be contributing to the leaky gut in people with M.E? Are we susceptible to the causes listed above due to a dysfunctional immune system?

When you say you derived benefits from your leaky gut regime supplements, may I ask what kind of benefits and for how long were you on this protocol? Are you still on the protocol? Also did you have the test to check for leaky gut? Did you follow any specific leaky gut diet as well? Sorry for all the questions! Thank you in advance
I had severe IBS-D before getting ME/CFS, so my gut is a weak area, and I generally feel better across all CFS symptoms if I can stabilize the gut (ie, prevent diarrhea).

Having tried loads of things to treat my IBS-D, the leaky gut protocol I posted above worked the best: within 3 or 4 days of starting it, my digestion was much improved, and I generally felt better.

I am still taking the supplements, but now only once a day. I suspect that if I stop, my gut health may dwindle away slowly.

I unfortunately have not taken the leaky gut test, but I will do so in future.


In terms of what causes leaky gut: if you look at the list of causal factors above, you see that some causes are avoidable (NSAIDs like aspirin, chili peppers, paprika, cayenne pepper), but other causes are not so easy to avoid.

These unavoidable causes of leaky gut come from the micro-organisms in your gut:

LPS toxin made by certain bacteria in your gut, cytomegalovirus, which is a common virus, toxins from Clostridium perfringens and Clostridium difficile bacteria, enteropathogenic E. coli bacteria, and the common gut parasite Blastocystis hominis all increase gut leakiness.

So you can imagine, if an individual had several of the above simultaneously in their gut, the combined effect is going to more strongly promote gut leakiness.


It may well be that the leaking of LPS toxin from the gut into the bloodstream causes the most problems for CFS patients. LPS (lipopolysaccharide) not only helps cause leaky gut, but LPS is the pretty much the most pro-inflammatory substance known to man. Even tiny amounts of LPS can set off a whole cascade of inflammation. So if LPS is entering into the body at large, you can imagine that inflammation is going to be ramped up everywhere.

LPS also pushes the immune response away from the desired antiviral TH1 mode, and into the TH2 mode which is not good for CFS.

So LPS leakage form the gut is one way that leaky gut may be exacerbating CFS.