Framework Matters: Study Links for Safe & Effective Crohn’s Strategies

This post is really a reference guide that includes an outline and framework for thinking about Crohn’s strategies in a differnent way, along with links to a series of studies that go into depth about each area. This is a good place to start research, and a good resource to share with your doctor.

 
“Nothing in biology (nutrition or medicine) makes sense except in the light of evolution”. Dr. Loren Cordain

Intestinal Barrier Function & Leaky Gut:

These studies provide the framework for all the rest. Essentially all modern diseases of inflammation can be linked to a series of mismatches between our genes and environmental factors. The origin of this inflammation starts in the gut with a breakdown in intestinal barrier function.

• The Western diet and lifestyle and diseases of civilization: Cordain, Research Reports in Clinical Cardiology: 2011 March
• Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Fasano Nat Clin Pract Gastroenterol Hepatol. 2005 Sep
  Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer Alessio Fasano Physiol Rev 2011 Jan
• Leaky Gut and Autoimmune Diseases Fasano Clinic Rev Allerg Immunol 2011 Nov. 

  

Below is a simple chart that list the stressors/environmental factors that either increase intestinal permeability directly or damage the balance of the gut flora, all leading to inflammation.

Increasing Intestestinal Permeability

Gluten/Prolamines	Casein	HBC	Stress
Lectins & Saponins	Low Vitamin D	PPI	Sleep Deprivation
Omega 6 Fats	Antibiotics	Alcohol	Endurance Exercise
FODMAPs	NSAIDs	Capsaicin

 

Below is a simple chart that list the environmental factors that either decrease intestinal permeability directly or improve the balance of the gut flora, all leading to reduced inflammation and healing.

Improving Intestestinal Permeability

IBD Diet	Krill Oil	Probiotics & Fermented Food	Colostrum
Proline (Broth & Gelatin)	Curcumin — BCM95	Mutaflor, VSL#3, Lactobacillus paracasei	LDN
CLA (Bones & Butter)	Boswellia — 5Loxin	S. Boulardii,  B. Coagulans	Cannaboids (CBD)
D3 & K2	L. Glutamine & Arginine	Sleep, Meditation/Yoga, Acupuncture	IF & HIIT = Growth Hormone

Diet:

• SCD — Pilot Testing a Novel Treatment for Inflammatory Bowel Disease Clinical and Translational Science Research Retreat. 2011 May.
• Does gluten cause gastrointestinal symptoms in subjects without coeliac disease? J Gastroenterol Hepatol. 2011 Apr
• Dietary Lectins as Disease Causing Toxicants Pakistan Journal of Nutrition 2009
• Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol. 2010 Feb
• Dietary fructooligosaccharides increase intestinal permeability in rats. J Nutr. 2005
• Indigestible disaccharides open tight junctions. Dig Dis Sci. 2004 Jan
• GAPS – www.gaps.me, SCD – www.scdlifestyle.com Paleo – www.robbwolf.com

  

 Fat Balance:

• Linoleic Acid, a Dietary N-6 Polyunsaturated Fatty Acid, and the Aetiology of Ulcerative Colitis – A European Prospective Cohort Study. Gut 2009 July
• The Type of Dietary Fat Modulates Intestinal Tight Junction Integrity, Gut Permeability, and Hepatic Toll-Like Receptor Expression. Alcohol Clin Exp Res. 2011
• Conjugated linoleic acid modulates immune responses in patients with Mild to Moderately active Crohn’s disease. Clinical Nutrition 2012 March.
• Lipid based therapy for ulcerative colitis-modulation of intestinal mucus membrane phospholipids as a tool to influence inflammation. Int J Mol Sci. 2010 Oct
• Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr. 2009

   

Microbiota & Probiotics:

• Gut Microbiota and Pediatric Disease Dig Dis 2011
• Association between the use of antibiotics and new diagnoses of Crohn’s disease and ulcerative colitis. Am J Gastroenterol. 2011 Dec
• Association of Repeated Exposure to Antibiotics With the Development of Pediatric Crohn’s Disease–A Nationwide, Register-based Finnish Case-Control Study. Am J Epidemiol. 2012 Apr
• Influence of Saccharomyces boulardii (Florastor) on the intestinal permeability of patients with Crohn’s disease in remission. Scand J Gastroenterol. 2008
• Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid dendritic cells from patients with Crohn’s disease and ulcerative colitis. Am J Physiol Gastrointest Liver Physiol. 2011 Dec
• The probiotic Escherichia coli Nissle 1917 (Mutaflor) reduces pathogen invasion and modulates cytokine expression in Caco-2 cells infected with Crohn’s disease-associated E. coli LF82. Trop Med Int Health. 2011 May
• Probiotic Bacteria Produce Conjugated Linoleic Acid Locally in the Gut That Targets Macrophage PPAR γ to Suppress Colitis. PLoS One. 2012
• Lactocepin Secreted By Lactobacillus Exerts Anti-Inflammatory Effects By Selectively Degrading Proinflammatory Chemokines Cell Host & Microbe 2012 April
• Helminthic therapy: improving mucosal barrier function. Trends Parasitol. 2012 Mar 

Supplements:

• Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer.Therap Adv Gastroenterol. 2011 Jan 

Target Vitamin D Levels 25(OH)D – 10,000 iu/day
Dr. Jaquelyn McCandless	65 – 90
Robb Wolf	60 – 80
www.VitaminDCouncil.org	50 – 80
www.GrassRootsHealth.net	40 – 60
Vitamin D IBD Study	30 – 60

• Curcumin Ameliorates Hydrogen Peroxide-Induced Epithelial Barrier Disruption. Dig Dis Sci. 2012 March.
• Therapy of active Crohn disease with Boswellia. Z Gastroenterol. 2001 Jan
• Dietary supplementation of krill oil attenuates inflammation and oxidative stress in experimental ulcerative colitis. Scand J Gastroenterol. 2012 Jan
• Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial. Dig Dis Sci. 2011 Oct
• Combined Glutamine and Arginine Decrease Proinflammatory Cytokine Production by Biopsies from Crohn’s Patients J Nutrition 2008
• Zinc supplementation tightens “leaky gut” in Crohn’s. Inflamm Bowel Dis. 2001 May
• Intestinal immune system influenced by cocoa-enriched diet. J Nutr Biochem. 2008 Aug 

Drugs:

• Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial. Dig Dis Sci. Smith & Zagon 2011 Jul 

  

• Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn’s disease. Gastroenterology. 2012 May
• Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology. 2010 Aug
• Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability British Journal of Pharmacology 2011
• Linaclotide in the management of gastrointestinal tract disorders. Drugs Today (Barc). 2012 Mar
• 5-aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. Am J Gastroenterol. 2011 Apr
• Efficacy of 5-aminosalicylates in Crohn’s disease: systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr

Fasano’s Spectrum of Gluten-related disorders

In February 2012, Alessio Fasano published a new study – Spectrum of gluten-related disorders: consensus on new nomenclature and classification – in it he and his team lay out the broad range of gluten related disorders, including Celiac(CD)/Autoimmune and Wheat Allergy (WA)/Allergic, but not autoimmune.  He also discusses at some length what he calls Gluten Sensitivity (GS) “The symptoms in GS may resemble those associated with CD but with a prevalence of extraintestinal symptoms, such as behavioral changes (depression, foggy-mind, headache), abdominal pain/diarrhea,  eczema, bone or joint pain, muscle cramps, leg numbness, weight loss, anemia and chronic fatigue.”

Conclusions
“It is now becoming apparent that reactions to gluten are not limited to CD, rather we now appreciate the existence of a spectrum of gluten-related disorders. The high frequency and wide range of adverse reactions to gluten raise the question as to why this dietary protein is toxic for so many individuals in the world. One possible explanation is that the selection of wheat varieties with higher gluten content has been a continuous process during the last 10,000 years, with changes dictated more by technological rather than nutritional reasons.
Wheat varieties grown for thousands of years and mostly used for human nutrition up to the Middle Ages contain less quantities of the highly toxic 33-mer gluten peptide. Apparently the human organism is still largely vulnerable to the toxic effects of this protein complex, particularly due to a lack of adequate adaptation of the gastrointestinal and immunological responses.
Additionally, gluten is one of the most abundant and diffusely spread dietary components for most populations, particularly those of European origin.  All individuals, even those with a low degree of risk, are therefore susceptible to some form of gluten reaction during their life span. Therefore, it is not surprising that during the past 50 years we have witnessed an ‘epidemic’ of CD and the surging of new gluten-related disorders, including the most recently described GS.”

The point is that gluten is toxic…even if you don’t have Celiac Disease.  Fasano notes that Gluten Sensitivity may be at play in a wide variety of disorders including: eczema, Autism & Autism Spectrum Disorders, Neuropsychiatric disorders/Schizophrenia, IBS, Diabetes, MS and Dimentia to name a few.

Glutens Impact Goes Beyond Celiac – An interview with Dr. Fasano

Here is a blog post by Tender Foodie that includes a recent interview with Dr. Alessio Fasano and thought it was important enough to link to. I hope he doesn’t mind. What is critical here is that gluten has impacts on leaky-gut beyond celiac disease. If you have an autoimmune disease, grains are central to the problem.

How many forms of gluten reactions are there?
Dr. Fasano:  There are 3 forms.  Celiac Disease, and Gluten Sensitivity, and Gluten/Wheat Allergy – and there are four different types of wheat allergy that all behave differently.

What is behind all of these reactions?
Dr Fasano:  Gliadin.  Gliadin is one of the proteins found in gluten.  When someone has a reaction, it’s because gliadin cross talks with our cells, causes confusion, and as a result, causes the small intestine to leak.  Gliadin is a strange protein that our enzymes can’t break down from the amino acids (glutamine and proline) into elements small enough for us to digest.  Our enzymes can only break down the gliadin into peptides.  Peptides are too large to be absorbed properly through the small intestine.  Our intestinal walls or gates, then, have to separate in order to let the larger peptide through.  The immune system sees the peptide as an enemy and begins to attack.  The difference is that in a normal person, the intestinal walls close back up, the small intestine becomes normal again, and the peptides remain in the intestinal tract and are simply excreted before the immune system notices them.   In a person who reacts to  gluten, the walls stay open as long as you are consuming gluten.  How your body reacts (with a gluten sensitivity, wheat allergy or Celiac Disease) depends upon how long the gates stay open, the number of “enemies” let through and the number of soldiers that our immune system sends to defend our bodies.  For someone with Celiac Disease, the soldiers get confused and start shooting at the intestinal walls.

 That sounds like everyone is gluten intolerant in some way.  Is that true?  Everyone?
Dr Fasano: Yes.  No one can properly digest gluten.  We do not have the enzymes to break it down.  It all depends upon how well our intestinal walls close after we ingest it and how our immune system reacts to it.