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

2012 Boston Patient & Family IBD Symposium – Important Education and Missed Opportunity

This Sunday I attended the CCFA 2012 Boston Patient & Family IBD Symposium at Babson College. It was a full house for a very professionally run education program about IBD. Although I was not able to go to every session, I did get a pretty good flavor. And while I did learn a few things, I couldn’t help but be struck by the huge missed opportunity. Here is a summary of what I heard:

• There is some real awareness that most autoimmune diseases are somehow connected by genetic and environmental factors.
• There is a recognition that microbiota/bacterial imbalance plays a significant role.
• Smoking makes Crohn’s worse.
• Those on Anti-TNF therapy have a 2.18 x increased risk of Non-Melanoma Skin Cancer, 6mp a 4.27 x and combined a 6.75 x increased risk.
• Vitamin D deficiency is recognized as an important issue – but there was little discussion of how, why or what to do about it. But don’t go out in the sun if you are on immune suppression therapy!
• Prednisone/Steroid therapy works to stop flares, but is to be avoided due to side effects.
• 5-ASAs/Mesalamine has little or no benefit for Crohn’s disease.
• Omega 3 fats can play a role in therapy.
• NSAIDs make IBD worse (but no understanding of why)
• One bright spot was the presentation by Dr. Matt Hand Director of Pediatric Integrative Medicine at NH’s Hospital for Children in Manchester. Dr. Hand gave a nice overview of Alternative therapies and he discussed the promising research in key anti inflammatory supplements like fish oil, boswellia and curcumin. And while he was certainly open to new ideas (quite refreshing), I don’t think he grasped the fundamental concepts that we’ve been discussing (particulary Fasanos work). A missed opportunity I hope to follow up with him on.

Unfortunately there was absolutely no mention or recognition of the role of intestinal barrier function and increased intestinal permeability in IBD. And there was a clear message sent that diet had nothing to do with the problem, or solution. Of course, there was no mention of LDN.

The basic approach was to tell folks to make sure they stayed on their medications. And there was alot of discussion about moving quickly to biologic drugs. There was quite a bit of discussion about risk/reward for these drugs, but the choices defined were “false-choices”. They positioned the choice as between going untreated and having a poor quality of life, risking emergency surgery and eventual disability due to the disease progressing, against the slightly elevated chances for getting some type of cancer years down the road. The increased cost of the drugs was meantioned.

On the whole I was very dissappointed and frustrated. I just don’t get why all the research that is being published now that explains what is really going on is being ignored. And what is worse, people going to these sessions are getting bad information. But it was important for me to go. There is no way I can make a difference in their educational programming if I don’t know what they are covering.

There is alot of work needed to be done.

Does it work?

The short answer is – Yes!

Although it’s an experiment of 1 and admittedly not at all scientific, I thought it would make sense to report on the recent results from my daughters blood work. It turns out that the strategy we are following – borrowed heavily from the Core Strategy I outline in this blog –  is working.  While no plan is perfect, its nice to know that this one is safe and effective.  We set a goal about 18 months ago…to find a way to provide some diet flexibility beyond the strict SCD program that we had successfully implemented in the past. It does appear that the addition of LDN and key supplements has made some diet flexibility possible. I’m sure we’ll have to make adjustments over time, but we’re pretty pleased with the results!

Here is the plan:

• Wheat/Gluten grain and mostly dairy free diet – potato & rice are well tolerated. (I’m sure there is some cheating going on, but not that much.)
• LDN – 4.5mg capsules each night
• Monthly B12 injections
• Daily supplements: Vitamin D3 10,000 iu, Boswellia/5Loxin 150mg, Curcumin/BCM95 500mg, Krill Oil 1,000mg & Bacillus Coagulans (DuraFlora – 2 capsules)

Here are the blood results:

• Vitamin D level – 25(OH)D = 79 (I think we are in “theraputic level” territory)
• C-reactive protein (CRP) = .56 (is a protein found in the blood, the levels of which rise in response to inflammation) anything under 1 is considered a low level of inflammation.
• The erythrocyte sedimentation rate (ESR), = 18 also called a sedimentation rate (SED) , is a common blood test  that is a non-specific measure of inflammation.  For women, anything under 20 is considered in the normal range.

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