Sunday, July 26, 2009

NOD2 Gene Mutation and Crohn's

There seems to be general consensus that Crohn's disease has some genetic component to it, so I figured it was worth learning more about it. As I discovered, studies have found that the NOD2 gene protein is somehow directly involved in a large percentage of Crohn's cases (25%). The NOD2 gene is expressed in the immune system leukocyte cells and plays a role in the body's immune response by recognizing some of the molecules (muramyl dipeptide - MDP) that are part of bacterial cell walls. In essence, they are a sensor for bacteria. And as we know, there are trillions of bacteria in the gut, so there are plenty of bacterial cell walls for them to respond to. The gene also has a connection with the NF-kB protein which regulates the immune system. Here is an excerpt from one of the articles I linked to:
Today, it is known that Nod2 expresses a protein that recognizes a building block of bacterial cell walls, called muramyl dipeptide (MDP), effectively making it a bacterial sensor. Nod2 is expressed primarily by bone-marrow-derived macrophages. In addition, the protein NOD2 appears to play a role in the activation of NF-{kappa}B, a major regulator of the production of pro-inflammatory cyto{kappa}ines such as tumour necrosis factor-{alpha} (TNF{alpha}) and interleukin IL-1ß. The relation is relevant because patients with Crohn's disease overproduce NF-{kappa}B and cytokines, and anti-inflammatory drugs represent the mainstays of treatment. Nevertheless, how Nod2contributes to the pathology of Crohn's disease has been an open question — one that the modelling of the disease in mice is beginning to answer.
So if everyone has the NOD2 gene, why do only Crohn's patients have problems with it? The problem arises due to mutations in the gene. The premise is that normal responses to bacterial infection should not create an overabundance of pro-inflammatory cytokines and hence should not create the inflammation associated with Crohn's disease. The mutated NOD2 genes cause the problems. But keep in mind, those genes are just responding to the environment - they don't cause it. Having a mutation in the NOD2 gene, then, doesn't necessarily cause the disease but instead makes people susceptible to it. Here's an excerpt:
The results of these studies help to explain the association between Nod2 mutations and Crohn's disease. In finding Nod2 to be an important immune mediator in the intestine, the studies also fuel the notion that bacterial infection is an important pathogenetic factor. Indeed, as Kobayashi and colleagues suggest, Nod2 mutations may not play a directly causative role but, rather, may create an environment in the gut that renders it susceptible to Crohn's disease. Further research is required to confirm this and to elucidate the link between Nod2 mutations and {alpha}-defensin, one that has already been established in humans.6 It is hoped that the results of this research will open future therapeutic avenues.
Obvious take-aways for future research (from the perspective of managing or preventing the disease) then are to look into how to undo or prevent mutations in the NOD2 gene. The stem cell treatment previously discussed is presumably (if I'm understanding it correctly) one way to undo these mutations (i.e. by creating all immune cells from scratch using stem cells). I'm curious to learn more about alternatives like nutrigenomics, though, for example that could help prevent mutations. But more on that in another post.

Saturday, July 25, 2009

Entocort and Budesonide

I came across a good video describing how EntocortEC works. Entocort is a corticosteroid formulated to localize its effect on the ileum and ascending colon through a delayed release mechanism. Most Crohn's disease patients have the majority of inflammation in that area, hence it is meant to be a targeted drug. Because of the targeted delivery mechanism, it is mostly metabolized before it has a chance to reach the rest of the body, limiting the side-effects that many other cortiosteroid drugs (like prednisone, etc.) can cause.

The specific drug used in Entocort is budesonide. I was quite surprised to find that it is also used to treat rhinitis (nasal inflammation).

Stem Cell Treatment for Crohn's

In skimming through some of the forums on, I saw someone mention a treatment option involving stem cells. A quick Google search revealed this article. Researchers in Barcelona, Italy, and the US have treated a handful of patients with promising results - with 80% achieving remission after being followed for 6 years after their treatment. The basic idea is to "reset" your immune system by 1) destroying all of your leukocyte cells (i.e. immune-system cells) via chemotherapy so that you can then 2) replace them all via a stem cell transplant. The premise is that the leukocyte cells you currently have are not working properly - i.e. they are incorrectly attacking microflora in your gut causing inflammation - and hence you need to get rid of all of them and re-build all your immune cells from scratch.

From the article it sounds like they only try this on patients that don't respond to medication or surgery, so it's kind of a last resort. And from the sound of it, it really should be. Sounds extreme.

Monday, July 20, 2009

Dr. Whitaker on Natural Remedies

Just read through Dr. Whitaker's website and his page on digestive health. He has a page on treating diarrhea using natural remedies. Here is the abbreviated list of what he recommends:
  • Drink plenty of water
  • Add soluble fiber (the kind in fruits and legumes)
  • Replenish the beneficial bactera (probiotics)
  • Take digestive enzymes
  • Eliminate foods you may have allergies to (perhaps via the Specific Carbohydrate Diet)
  • Take the herb Una de gato (cat's claw)
One of the products offered on his website is PearlBiotics. It is a specially formulated probiotic supplement (in tablet form) that has a special coating (made in Japan) that allows the bacteria to survive the stomach so that they make it alive to the intestines.

Sunday, July 19, 2009


I'm reading up on probiotics. Here are a collection of good articles on the topic with some interesting findings. There are numerous health benefits associated with probiotics (outlined in all of the articles below). But then again, the name itself means that the agent produces some benefit in the host, so by definition it must have health benefits.

Background and findings
  • Wikipedia article "Probiotic" - includes a history of how probiotics were discovered and research and a list of strains
  • NIH - "An Introduction to Probiotics" - covers much of the same stuff
  • Life Extension Magazine - "Optimizing Digestive Health" - this is a fantastic article and highlights the benefits of BACILLUS COAGULANS. Although many people take probiotics supplements, much of the effort can often be wasted because those probiotics are not able to survive and colonize in your gut. Part of the reason is that natural food sources with live cultures (e.g. yogurt) are often on the shelf too long. With supplements, many bacteria are not able to make it through the manufacturing process. Dead bacteria, no matter how many make it to the intestines, don't really help. The goal is to have colonization in the gut. Bacillus coagulans is a probiotic bacteria that is able to survive through the harsh conditions of the stomach to make it to your intenstines. It then quickly multiples via spores to colonize the intestines. An additional benefit of the bacteria is that it produces lactic acid which aids in digestion and helps to kill off other pathogens. For those three reasons, it is a superior probiotic to other alternatives.
Natural Food Sources:
From reading all this, it seems that the tablet form of Bacillus coagulans is worth a try, as is continued inclusion of natural forms of probiotics in the diet (yogurt, kimchi, etc.).

The Specific Carbohydrate Diet

I read through the Specific Carbohydrate Diet website (Breaking the Vicious Cycle). The basic premise of the diet is that proper GI function is dependent on having an appropriate balance of bacteria and microflora. When that balance is damaged, a vicious cycle is started that leads to the failure of the GI tract, GI diseases, and other related diseases stemming from malnutrition and the increase in toxins.

The GI tract has over 400 different kinds of bacteria (5 to 7 lbs of it in fact). Much of that bacteria should be "good" bacteria - organisms that aid in the digestion of foods and creation of vitamins. There are also "bad" bacteria present. These bacteria compete for limited space in your digestive system. These bacteria come into play, in particular, when you eat food that your body can't digest on its own. Whatever bacteria is present will break down and digest the bacteria. Good bacteria does good things while digesting this material. Bad bacteria produce bad things - like gas, toxins, etc.

This is where the "vicious cycle" begins. The good bacteria are lost (likely due to a poor diet or antibiotic drugs that are taken for other illnesses). In the absence of good bacteria, the bad bacteria proliferate. These bad bacteria contribute to inflammation in the GI tract. That inflammation further decreases the digestive tracts ability to absorb nutrients into the body. The lack of nutrition weakens the immune system, decreasing the body's ability to deal with the bad bacteria. The inflammation and change in pH also contribute to the loss of good bacteria.

And then the result of all of this is disease first in the GI tract - Crohn's disease, IBD, collitis - and then disease throughout the body - arthritis, excema, psoriasis, etc. Here's an explanation from the website on the vicious cycle and how it works:
When the balance in the gut is disturbed, an overgrowth of intestinal flora can result. Microbes migrate to the small intestine and stomach, inhibiting digestion and competing for nutrients. The gut then becomes overloaded with the byproducts of their digestion. This bacterial overgrowth can be triggered by overuse of antacids, reduced stomach acidity due to aging, weakening of the immune system through malnutrition or poor diet, and alteration of the microbial environment through antibiotic therapy.

The components of our diet, particularly carbohydrates, play an enormous role in influencing the type and number of our intestinal flora. When carbohydrates are not fully digested and absorbed, they remain in our gut, and become nutrition for the microbes we host. The microbes themselves must digest these unused carbohydrates, and they do this through the process of fermentation. The waste products of fermentation are gases, such as methane, carbon dioxide & hydrogen, and both lactic & acetic acids, as well as toxins. All serve to irritate and damage the gut. There is evidence that increased acidity in the gut due to malabsorption and fermentation of carbohydrates, may lead common harmless intestinal bacteria to mutate into more harmful ones. Further, lactic acid produced during the fermentation process has been implicated in the abnormal brain function and behaviour sometimes associated with intestinal disorders. The overgrowth of bacteria into the small intestine triggers a worsening cycle of gas and acid production, which further inhibits absorption and leads to yet more harmful byproducts of fermentation. The enzymes on the surface of the small intestines are destroyed by the now present bacteria, and this further disrupts the digestion and absorption of carbohydrates, leading to further bacterial overgrowth. As both the microbial flora and their byproducts damage the mucosal layer of the small intestine, it is provoked to produce excessive protective mucus, which further inhibits digestion and absorption.

Damage to the mucosal layer involves injury to the microvilli of our absorptive cells. These microvilli act as the last barrier between the nutrition we take in and our bloodstream. As our absorption is inhibited, folic acid and vitamin B12 deficiency can lead to impaired development of microvilli, while an abnormally thick layer of mucus prevents contact between microvilli enzymes and the carbohydrates we ingest. The small intestine responds to this spiraling irritation by producing more goblet (mucus-making) cells, creating yet more mucus. Finally, as the goblet cells become exhausted, the intestinal surface is laid bare, and is further damaged, and possibly ulcerated. As more carbohydrates are left in the gut, they cause water and nutrients to be pulled from the body into the colon, resulting in chronic diarrhea. Absorption is further hindered as diarrhea increases the rate with which food travels through the gut.

The Specific Carbohydrate Diet is intended to restore the proper balance in your system by 1) starving the bad bacteria, 2) introducing good bacteria, and 3) feeding the good bacteria so that it proliferates.

Here's an excerpt from the website with an explanation from them:
The allowed carbohydrates are monosaccharides and have a single molecule structure that allow them to be easily absorbed by the intestine wall. Complex carbohydrates which are disaccharides (double molecules) and polysaccharides (chain molecules) are not allowed. Complex carbohydrates that are not easily digested feed harmful bacteria in our intestines causing them to overgrow producing by products and inflaming the intestine wall. The diet works by starving out these bacteria and restoring the balance of bacteria in our gut.

The Specific Carbohydrate Diet™ is biologically correct because it is species appropriate. The allowed foods are mainly those that early man ate before agriculture began. The diet we evolved to eat over millions of years was predominantly one of meat, fish, eggs, vegetables, nuts, low-sugar fruits. Our modern diet including starches, grains, pasta, legumes, and breads has only been consumed for a mere 10,000 years. In the last hundred years the increase in complex sugars and chemical additives in the diet has led to a huge increase in health problems ranging from severe bowel disorders to obesity and brain function disorders. We have not adapted to eat this modern diet as there has not been enough time for natural selection to operate. It therefore makes sense to eat the diet we evolved with.
It certainly seems to make sense.

Testimonial Website About Specific Carbohydrate Diet

After coming up with the name for this blog, I came across a website by the same name - A young person shares his experience using the Specific Carbohydrate Diet to manage his illness. It sounded like he started with pretty bad symptoms that resulted in significant malnutrition and weight loss (e.g. he was down to 100 lbs). Through the diet he went on, he was able to eliminate all his symptoms and gain weight (up to 150+ lbs). Sounds very promising and I'm going to look into this diet more.

Life Extension Foundation Research on IBD

I just read through this excellent article from Life Extension Foundation on inflammatory bowel disease, including Crohn's disease and ulcerative colitis. Citing the latest research, they provide background on each to the diseases, complications associated with each, treatment options, and then outline recommendations on how to manage them.

They summarize their recommendations at the end of the post:

Life Extension Foundation Recommendations

First-line therapy for inflammatory bowel disease involves lifestyle changes and supplementation with valuable nutrients. A strong multivitamin is recommended to provide the basic nutrition needed. It is important to reinoculate the intestine with beneficial bacteria. Also, patients should be aware that many people with inflammatory bowel disease are anemic to some degree and should carefully monitor their iron levels. If iron levels are low, supplementation with iron is recommended. A standard dose is 15 mg/day of elemental iron. Inflammatory bowel disease is also strongly associated with elevated homocysteine levels. Blood testing is recommended to make sure homocysteine levels remain in safe ranges. For more information, see the chapter Homocysteine.

People who have Crohn's disease may respond to the 4-R Program:

  1. Remove all suspicious and proinflammatory foods, including processed foods and refined sugar. Also, foods high in saturated fat and trans fat should be removed. Instead, focus on intake of healthier fats, such as olive oil.
  2. Replace any missing nutrients with a high-potency multivitamin (and other nutrients as needed).
  3. Reinoculate the intestine with beneficial bacteria by taking L acidophilus and L bulgaricus with fructose oligosaccharides.
  4. Repair the inner wall of the damaged intestine with supplements that have been shown to support the integrity of the intestinal wall itself, including glutamine, zinc, vitamin C, and fructose oligosaccharides.

Specific supplements that have been shown to help reduce the symptoms associated with inflammatory bowel disease include:

  • Glutamine—1000 to 3000 milligrams (mg)/day
  • Probiotics—300 mg, three times daily, of Life Flora, or 900 mg, three times daily, of Primal Defense. Both products contain beneficial bacteria. It's suggested to start with a single dose and gradually add more.
  • Zinc—30 mg/day
  • Vitamin C—1000 to 3000 mg/day
  • Vitamin E—400 International Units (IU)/day with at least 200 mg of gamma-tocopherol
  • Vitamin K—10 mg/day
  • Vitamin B complex—A complete B-complex vitamin that includes high potencies of all the essential B vitamins including B1, B3, B6, and B12
  • Selenium—200 micrograms (mcg)/day
  • Arginine—1800 to 5400 mg/day
  • Butyrate enemas—Two enemas a day are suggested for patients who have ulcerative colitis or Crohn’s disease that affects their lower colon.
  • EPA/DHA—At least 1400 mg/day of EPA and 1000 mg/day of DHA
  • Gamma Linolenic acid (GLA)—900 to 1800 mg/day
  • Ginger extract—250 mg/day
  • Soluble fiber—5 to 15 grams (g)/day during remission periods
  • DHEA—Start with 15 to 75 mg (in 3 to 6 weeks have blood tested to make sure optimal blood levels are maintained)
  • Folic acid—800 micrograms (mcg)/day (in addition to the folic acid that is in the B-complex vitamin)

Because of the association between inflammatory bowel disease and osteoporosis, people with inflammatory bowel disease are encouraged to carefully monitor their bone density. For more information on supplements that can help prevent osteoporosis, see the chapter Osteoporosis.

Also, based on the association between colitis and colon cancer, patients are encouraged to closely monitor their colon health through regular screening. For more information on colon cancer screening and prevention, see the chapter Colon Cancer. Supplementation with folic acid and vitamin B12 (800 mcg of folic acid and 300 mcg of vitamin B12) has been shown to reduce the risk of colon cancer.

I thought the 4-R program was particularly useful. They expand on that in the body of the article:
The 4-R Program for Crohn’s Disease

The following steps are recommended to help patients with Crohn's disease first reduce their symptoms and then begin long-term repair of the damage caused by their disease:

  • Remove. Remove all suspicious foods from the patient's diet that precipitate inflammation. The following are the most likely to be troublesome: dairy, eggs, nuts, fruit, tomatoes, corn, wheat (or gluten), and red meat. All refined carbohydrates should be removed. All fats except for essential fatty acids should be eliminated, because hard or trans fats are detrimental to people with Crohn's disease (Heckers H et al 1988; Lorenz-Meyer H et al 1996). Products such as Vivonex®, UltraMaintain®, or UltraClear® can be used at the outset. UltraClear® is preferable because it contains sufficient fiber to maintain regular bowel evacuation. Removal of gastrointestinal parasites, undesirable bacteria, or fungal elements is important.
  • Replace. The diets of most patients who have inflammatory bowel disease are nutritionally imbalanced. Replacement of vital nutrients consists of a good multivitamin, together with minerals that are lacking. The vitamins that most patients with inflammatory bowel disease lack are the B-complex vitamins such as folic acid and vitamin B6, and particularly vitamin B12 (Rogler G et al 2004). Iron and calcium deficiencies are frequently found in patients with Crohn's disease (Capurso G et al 2002; Lomer MC et al 2004; Siffledeen JS et al 2003), as well as deficiencies in zinc, protein, vitamin D, and folic acid (Rath HC et al 1998; Siffledeen JS et al 2003). Patients with Crohn’s disease are usually under increased oxidative stress and have lower levels of antioxidant vitamins. Supplementation with vitamins C and E reduces oxidative stress (Aghdassi E et al 2003). Long-term use of corticosteroids warrants the inclusion of supplemental calcium and vitamin D to prevent corticosteroid-induced osteoporosis.
  • Reinoculate. A normal healthy intestine contains 5 to 7 pounds of friendly bacteria, the good bacteria that are responsible for manufacturing some vitamins and cell food in the intestine. In a diseased intestine, these bacteria are not present in adequate amounts or are absent, having been replaced by pathogenic organisms or yeast overgrowth. Reinoculation consists of taking mixtures of the friendly bacteria Lactobacillus acidophilus andLactobacillus bulgaricus along with fructose oligosaccharides to promote continued repopulation with these beneficial bacteria (Fedorak RN et al 2004). Inhibition of pathogens by lactobacilli follows the lowering of pH through liberation of acids, resulting in an antimicrobial action. Stool samples provide information regarding these overgrowth factors, pH, and the balance of fatty acids.
  • Repair. Frequently the lining of the small intestine becomes permeable, allowing antigens and other incompletely digested products to pass through the bowel wall. Repair of the protective layer consists of adding nutrients such as pantothenic acid (vitamin B5), zinc (Cario E et al 2000; Kapp A et al 1991; Weimann BI et al 1999), fructose oligosaccharides, and vitamin C to build up the integrity of the intestinal wall itself.
Great article. I'll likelly be summarizing other aspects of this article in future posts.

First Post

My goal with this blog is to collect the latest research and to share my personal experience on how to beat Crohn's Disease. It's mostly for my own use to keep track of interesting articles and treatment options, but it may be useful for others so I'll make it publicly available. I think at the very least it will ensure that I continue to make managing and treating this disease an integral part of my life. Good luck!