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

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.

The Core Strategy

My approach to dealing with autoimmune disease in general and Crohn’s specifically is very eclectic. There is no cure but there certainly are safe, effective and affordable strategies that will let most people live normal lives.

There is finally science that explains what is going on with these diseases. The core problem is in the functioning of the gut lining or leaky-gut where the gut lining is actually leaking undigested proteins into the bloodstream, kicking off an inflammatory response. The two key factors that create leaky-gut are the direct action of prolamines/gluten/lectins in grains & legumes, as well as the omega 6 fats in seed/grain oils — along with dysbiosis in the gut, where complex carbohydrates & fructans are poorly digested, ferment, and feed the growth of pathogenic bacteria.

So now we have a mess that needs to be unraveled. Here is the basic strategy:

• Stop eating the foods that cause leaky-gut
• Stop eating the foods that feed pathogenic bacteria
• Supplement to kill pathogenic bacteria and replenish good bacteria
• Supplement to reduce inflammation and heal leaky-gut

And here are the tactics:

• Diet – The most important component – 75% – is diet.  Eliminate all processed sugar, grains, legumes, and dairy. Although grains are the enemy, it’s also important to reduce high omega 6 fats and fructose. So what do you eat? Meats (hopefully grass-fed/pastured animals and wild caught seafood), Vegetables, Fruits and Nuts (and Tubers after some healing). Great diets for this include: SCD or Specific Carbohydrate Diet, GAPS or Gut and Psychology Syndrome Diet, and Paleo. Both SCD and GAPS are specifically designed for autoimmune disease and offer an intro phase and process for healing. Paleo doesn’t offer a process, but I’m partial to their evlolutionary biology approach to the world.  Here is a PDF that outlines a solid approach. It combines the best of SCD/GAP with its low FODMAP strategy, all within a Paleo foundation.
• LDN – For many, diet is enough, but for most diet needs to be combined with LDN and key supplements.The only drug that makes sense to me is LDN or Low Dose Naltrexone. LDN is safe, effective and affordable. Naltrexone has been around for over 30 years and is FDA approved, but LDN for Crohn’s would need to be prescribed “off-label” or purchased directly from an online pharmacy. LDN works by tricking your body into producing 3 times the amount of endorphins it normally would. Endorphins perform a critical function that is profoundly important for the proper functioning of the immune system. The result is reduced inflammation, and demonstrated healing of the gut lining. LDN works best when combined with a gluten, soy, casein restricted diet because these foods actually compete for the opioid receptors that LDN works on.
• Supplements– Athough you can go crazy with supplements, there are a core that have been shown to be effective. Few of them do much without the foundation of the right diet, but when combined, they can be very helpful:

–D3 Make sure your blood levels are between 60 – 80. For most, this might require supplementing with 5,000 or 10,000 iu’s per day. There are clinical trials going on right now at Penn State for vitamin D and Crohn’s. Here is a great resource for vitamin D.

–B12 Shots are critical for anyone with a damaged ileum. They are great for dealing with fatigue.

–Boswellia & Curcumin are both great, natural anti inflammatories with small clinical trials that show that they are as effective as mesalamine without any of the side effects. Take boswellia in 5Loxin form and take curcumin in BCM-95 form.

–Probiotics – There are some great probiotics that can help crowd out pathogenic bacteria and re-populate the gut with beneficial bacteria. One of the best ways is to ferment your own yogurt or vegetables. Or you can buy probiotics. The 3 strains that have some clinical trials to back them are S. Boulardii, VSL#3 and Mutaflor. S. Boulardii is affordable, available and works great for diarrhea, candida and c. diff. I’m partial to Mutaflor, but it is expensive, and unavailable in the US.

–Leaky-Gut Healers – There are a number of interesting supplements that either aid digestion or directly help with the healing of the gut lining: GAPS bone broth or gelatin,  Betaine hcl with pepsin has multiple benefits with GERD, CRP/homocysteine, and killing pathogenic bacteria. L. Glutamine,  Zinc Carnosine, Colostrum/Proline Rich Polypeptides (PRP) and Coconut Oil.

There are other strategies, but this is a great start. Follow the links, do some research. Share this with your doctor. And get started. You can get your life back. Let me know how it goes!

Alan