Crohn's disease is an autoimmune disease that is characterized by chronic inflammation of the gastrointestinal (GI) tract that can occur anywhere from the mouth to the anus. It affects nearly 500,000 people in the United States and is typically first diagnosed in patients between the ages of 15-30 years old. Crohn's disease can cause a number of symptoms including persistent diarrhea, abdominal cramping, bloating, loss of appetite, weight loss, rectal bleeding, and may even affect other systems outside of the digestive tract such as the joints, eyes, skin, and liver.
Conventional medicine and most physicians approach the treatment of Crohn's disease in one of two ways. They use a number of different medications to suppress the inflammation that is occurring or they perform surgeries to remove the part of the digestive tract that is inflamed and/or infected. While these methods certainly have their place and have provided much needed relief for many patients suffering from Crohn's disease they do not address the cause of the inflammation in the first place. What I hope to do in the remainder of this article is two things:
1) Explain how the inflammatory process develops and progresses in Crohn's disease to help you gain a better understanding of what is occurring in the GI tract.
2) Give you some approaches to treating Crohn's disease that are aimed at slowing or stopping the inflammatory process in the first place.
Let's get started by examining the inflammatory process in Crohn's disease. Below is only a simplified version of this process as the entire process is very complex and not completely defined by scientist yet. None the less, it should give you a basic picture of what is happening in Crohn's disease.
Inflammatory Process - How it Develops and Progresses
Your gut is made of a mucosal lining that contains hundreds of thousands of epithelial cells on the inside wall of your intestines which helps absorb beneficial nutrients and minerals into your body while at the same time keeping harmful substances (toxins, allergens, harmful bacteria, etc.) out of your body. Crohn's disease develops due to defects in the barrier function of this mucosal lining and an out of control immune response to antigens attacking this lining.
The gut is constantly being bombarded by various antigens which are foreign substances that produce an immune response by your body. In healthy people this immune response goes off without any problems and the antigens are destroyed or eradicated. But in a person with Crohn's disease the immune system remains chronically activated leading to chronic inflammation of the mucosal lining which can lead to more tissue injury and/or destruction of this lining. This process is affected by a number of different things including genetic, environmental, and immunological mechanisms.
The initiation of the inflammatory process starts with an antigen crossing through a compromised portion of the epithelial layer. These antigens can be harmful bacteria or from dietary sources. Once the antigen enters through the mucosal barrier it teams up with an antigen-presenting cell (APC) which are immune cells that include macrophages and dendritic cells. The APC is then activated and will promote another immune cell called a T-cell to either turn into a Th1 cell or a Th2 cell. Th1 cells are found in abundance in the mucosal lining of Crohn's disease compared with a smaller proportion of Th2 cells. Due to high Th1 cell counts this also suppresses another T-cell known as the Th3 cell which produces a substance called IL-10 that acts to suppress the inflammatory process in Crohn's disease. Th2 cells also produce this same IL-10 cytokine. A cytokine is just a substance secreted by your immune cells to carry out a specific job. On the other hand activated Th1 cells produce a number of pro-inflammatory cytokines such as interferon-Ƴ and IL-2 to name a few. These in turn promote a self sustaining cycle of activation of more macrophages. Remember macrophages act as antigen presenting cells (APC) as mentioned above. These macrophages also produce more pro-inflammatory cytokines namely IL-12, IL-1, IL-6, and tumor necrosis factor (TNF). The IL-12 produced by these macrophages then works to turn more T-cells into more Th1 cells further compounding the inflammatory process. It is also important to note that the TNF produced by macrophages is of primary importance in Crohn's disease as it targets endothelial cells in the mucosal lining to recruit more immune cells to join in on the inflammatory process. What you end up with if you're a Crohn's patient is literally one big inflammatory party going on in the inside walls of your intestines. As if that wasn't enough tumor necrosis factor (TNF) is also responsible in part for activating a transcription factor called NFkB inside various cells which we will talk about next. If this all sounds very confusing then don't get discouraged because it will make more sense when treatment options are discussed later on. Now on to the role of NFkB in Crohn's disease.
In addition to the above process, there is another key driving force behind the inflammatory process seen in Crohn's disease. It involves the transcription factor NFkB which is responsible for regulating cellular inflammatory responses and macrophage cell death. NFkB is found inside various cells throughout the body including macrophages and epithelial cells. In order for NFkB to carry out it's job it first needs to be activated. This is done by a number of different ways. One way is by the cytokines IL-1 and TNF which are produced by macrophages as mentioned in the above paragraph. Another way is by a substance called lipopolysaccharide (LPS) which is a component found in the cell walls of a select group of specific bacteria. Remember that harmful bacteria can be one of the antigens that starts the inflammatory process off in the first place. LPS is especially a problem in patients who have a known genetic mutation linked directly to Crohn's disease. The defective gene is known as the NOD2/CARD15 gene on chromosome 16 and is present in 17% to 27% of patients with Crohn's disease. Although a complete understanding of exactly how LPS works to activate NFkB is not fully known the fact remains that it does so leading to the progression of the inflammatory response. Once NFkB is activated it carries out two jobs. First, it prevents programmed cell death of the macrophages which is detrimental to the inflammatory process. Remember the more macrophages the more inflammatory substances produced. Second, the activated form of NFkB causes the cell to produce additional pro-inflammatory substances including various cytokines, chemokines, and interleukins (IL's) which compound and continue the inflammatory process.
As you can see the inflammatory process if very complex and the above is only a glimpse of the key components behind it all. The important thing to take away from all of this is that there are two main culprits driving the inflammatory process in Crohn's disease. One is the major imbalance between Th1, Th2, and Th3 cells whereby Th1 cells are predominantly present and also the ones responsible for causing all the problems. The second half of the equation is the activation of NFkB which sets off a number of events that further promote inflammation. Now onto some treatment strategies but before doing so please take a moment to watch this very useful and informative video on Crohn's disease by Dr. Lucy Rojo.
Various Non-pharmacological and Non-surgical Treatment Options in Crohn's disease
While medications and surgery have their place in the treatment of Crohn's disease they are ALWAYS accompanied by some type of risk and/or side effect(s). To be fair these approaches have undoubtedly helped many patients suffering from the ill effects of Crohn's disease and should not be overlooked. But they aim to control the disease by suppressing the inflammatory process from a reactive perspective on the back end of the disease or by permanently removing the affected area of the intestinal tract causing the problems. What I aim to do here is give you some insight into approaching things from the front end of the disease in hopes of reducing or eliminating the inflammation that occurs in Crohn's disease in the first place. With this being said, it is extremely important that you work with your physician to come up with a game plan that is right for your own individual situation.
Benefits of Probiotics
Your gut has trillions of bacteria in it some of which are good bacteria and some of which are harmful bacteria. Probiotics are nonpathogenic bacteria that benefit the host. In other words, probiotics are "good" bacteria that help your gut stay healthy.
Clinical trials have shown a benefit in using probiotics in the treatment of Crohn's disease. Probiotics exert their beneficial effects by the following ways :
- Block effects of harmful bacteria in the gut by producing antibacterial substances to fight off the bad bacteria. Probiotics also compete with harmful bacteria and their toxins (antigens) for binding sites to epithelial cells as they adhere to the mucosal lining and inhibit the bad bacteria from doing the same.
- Inhibit pro-inflammatory cytokine production (TNF, IL-2, and interferon-Ƴ) and increase anti-inflammatory cytokine production (IL-10).
- Repair epithelial barrier function after injury as well as preventing harmful bacteria from passing through the epithelial barrier and thus preventing the ensuing antigen cell presentation.
- Prevention of epithelial cell death which serves to strengthen the mucosal lining.
- Inhibit NFkB induced pro-inflammatory cytokine and chemokine production in epithelial cells.
A number of different probiotics have been used in the treatment of inflammatory bowel disease which include Lactobacilli (GG, acidophilus, and salivarius), Bifidobacterium bifidum, Streptococcus thermophilus, Saccharomyces boulardii, and E. Coli strain Nissle 1917 . If you're interested in more information regarding probiotics I would recommend you investigate the works of two of the leading experts in this field - Dr. S.K. Dash or Dr. Richard Fedorak.
Role of Diet and Food in Crohn's Disease
Modern medicine and even professional organizations supporting advancements in the treatment of Crohn's disease have largely ignored the link between diet and disease. There is some very clear and beneficial effects of certain foods in combating Crohn's disease that for whatever reason is going unspoken. On the contrary there's also evidence showing certain foods as being very detrimental in the fight against Crohn's disease. Let's take a look at what exactly this entails.
You've already been introduced to the topic of how the activation of NFkB triggers the inflammatory process. Well come to find out NFkB activation is in part due to the effect of free radicals which have been widely known to cause several chronic illnesses. So one of the keys to reducing NFkB activation and the inflammation that follows is to consume foods high in anti-oxidants which reduce free radical activation of NFkB. These foods would include a diet containing vegetables, fruits, green tea polyphenols, resveratrol (found in red wine and purple fruit), foods high in vitamin C and E (more fruits and veggies), circumin (found in an Indian spice called turmeric), and glutathione (found in lipoic acid and Coenzyme Q10 supplements).
A diet high in refined sugar, low in fiber, and that had a low consumption of raw fruits and vegetables was shown in one study to favor the development of Crohn's disease. Another study showed that patients with Crohn's disease have a higher dietary intake of sucrose (sugar), refined carbohydrates and omega-6 fatty acids (found in high quantities in meat and dairy products), and a reduced intake of fruits and vegetables. Dietary habits were looked at in children suffering from Crohn's disease and the evidence showed that those who consumed higher amounts of vegetables, fruits, fish, fiber, and omega-3 fatty acids in their diet had a lower risk of Crohn's disease.
Another topic worth mentioning is the prevalence of celiac disease in patients diagnosed with Crohn's disease. Studies have shown that those suffering from Crohn's disease may also have a high rate of celiac disease as well. Celiac disease is an autoimmune disease in which the lining of the small intestine is damaged from eating gluten and other proteins found in wheat, barley, rye, and possibly oats. It causes many of the same symptoms as Crohn's disease such as diarrhea, abdominal pain, decreased appetite, etc. This may be worth asking your doctor about so that they can perform some diagnostic tests to see if you have celiac disease. If it turns out that you do then a gluten-free diet should be started to alleviate this.
It is quite clear that diet does have a significant role in Crohn's disease which has been a topic previously ignored and even currently kept quiet by mainstream medicine. This certainly may not be intentional but the fact remains that you should take this information seriously and do your best to convert over to a plant-based diet full of fresh fruits and vegetables. It may be wise to avoid nuts though as they tend to irritate or worsen damaged/infected portions of the intestinal mucosal lining. You should also dramatically reduce your intake of refined sugars and carbohydrates as well as increase your fiber intake. To learn more about how to make these dietary changes part of your everyday habits please visit my website.
The Role of Vitamin D in Crohn's Disease
In recent times the benefits of Vitamin D has made headlines around the country in showing a reduction of several chronic illnesses and Crohn's disease is of no exception. The evidence supporting vitamin D in Crohn's disease should serve to encourage ALL patients to address this issue with their doctor.
Vitamin D exerts it's effect by a number of different ways and you may want to refer back to how the inflammatory process develops and progresses to gain a better understanding regarding the following points. First off, vitamin D antagonizes TH1 pro-inflammatory responses by interfering with antigen-presentation and TH1 activation, up-regulating TH2 cytokines, and down-regulating NFkB in macrophages. Secondly, vitamin D also acts directly on two specific genes that are important in fighting off foreign invaders (antigens) in the intestinal tract. These genes are the NOD2/CARD15 gene that we talked about earlier and also the beta defensin 2 gene. In patients with Crohn's disease these genes have been found to be deficient or defective and are highly linked to low vitamin D levels.
Several studies have shown a link between vitamin D (25-OH vitamin D levels) and Crohn's disease. One such study showed that vitamin D levels were significantly lower among patients with Crohn's disease and in addition vitamin D levels were even lower in those with severe disease activity and less sun exposure. Another study indicated that vitamin D deficiency was highly prevalent in children and young adults suffering from Crohn's disease. Additional proof in another study done on adults with Crohn's disease in Japan showed that nearly 30% were severely deficient in vitamin D and had a 25-OHD level of less than 10 ng/ml. A healthy 25-OHD level is considered to be above 50 ng/ml.
Vitamin D can naturally be obtained from sunlight during peak hours of the day usually between 10am-3pm. You only need about 20 minutes of exposure three to four times a week to make enough vitamin D in your skin from sunlight exposure. Sunscreens block this effect so it is important to get natural exposure for the time suggested. Of course if you are out in the sun longer than this then it is recommended you put on sunscreen to avoid the damaging effects of longer exposure times to the sun.
If a plan to get enough sunlight exposure is not easily achievable for you or is not getting your vitamin D levels up to a healthy level then you can supplement with vitamin D. There are two types of vitamin D supplements which include vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D3 (cholecalciferol) is the naturally occurring form in your body and is preferred. In patients with vitamin D deficiency a typical dose of vitamin D3 is 2,000 to 5,000 units per day. However, you should have your vitamin D level checked first and discuss what dose is optimal for you with your doctor before starting on a supplement of vitamin D.
Helminthic Therapy in Crohn's Disease
In the past decade there has been another very promising and yet often unspoken option for treatment of Crohn's disease. This treatment is called helminthic therapy and involves the use of parasites, otherwise known as helminths (aka. hookworms or whipworms), to combat the overactive immune response in patients suffering from Crohn's disease. Now before you literally "freak out" about this concept please bear with me and keep reading so that you understand the why's and how's of this new treatment option.
The hygiene hypothesis states that human populations may have adapted to parasites to such a degree that the lower exposure to infectious agents in modern developed societies results in immune imbalances, with autoimmune and allergic conditions being the outcome. It has been shown that poor sanitation actually protects against inflammatory bowel disease. With this being said, what researchers have found is that by inoculating Crohn's patients with a small dose of helminths they are able to balance out the body's immune system and reduce the signs and symptoms of Crohn's disease. How exactly does this happen you ask?
Helminths have been shown to inhibit the production of IL-12, interferon-Ƴ, and TNF while promoting the production of IL-10, transforming growth factor beta, and regulatory T-cell production. These beneficial actions are most likely due to helminths ability to down regulate Th1 cells and up regulate Th2 cells. Again please refer back to the explanation of the inflammatory process at the beginning of this article to gain a better understanding of all this.
So why isn't this treatment option readily available for those who suffer from inflammatory bowel disease? The answer to this is a few reasons. First, it is not FDA approved in the U.S. because it is so new and there hasn't been large enough studies or simply enough clinical studies done to warrant approval. However, in the preliminary trials that have been conducted there has been very good success with little to no risk involved. In fact, in one study over 79% of patients responded to whipworm therapy after 6 months with over 72% of patients going into remission with no side effects or complications attributable to therapy. Now find me a drug that can produce those results.
Another reason why you may not have heard of helminthic therapy is because your doctor probably hasn't even heard of it. If you are lucky enough to have a doctor who is aware of this and has reviewed the science then you are very fortunate. In my research I've found that many Crohn's patients who have presented this information to their doctor were met with a lot of resistance at first even though once they questioned their physician further they found out that he/she had not looked at any of the scientific literature available on helminthic therapy. Again, this is probably not intentional on your physician's part it's just that this is a new line of treatment and word hasn't gotten around regarding its benefits yet. In order to avoid any confusion or confrontation with your doctor it would be a good idea and look great on your part if you printed out the scientific studies on helminthic therapy to take to share with your doctor before seeing him/her. Many physicians really appreciate it when their patients are taking an active role in their own healthcare.
Another reason is that helminthic therapy is not currently available for purchase from a U.S. supplier. But you can still obtain it and find more information on it by going to the following sources:
Another useful source of information can be found at www.helminthictherapy.com.
Other Supplements and Additional Concerns in Crohn's disease
Omega-3 fatty acids have been studied in the treatment of Crohn's disease because of their anti-inflammatory effect. There have been mixed results on whether or not supplementing with omega-3's produces favorable results. Typically very large doses (more than is recommended for the general population) had to be used to produce any positive effects in Crohn's disease. In addition, it seems that the omega-3 supplement had to have special enteric-coating to resist stomach acid which allows for delayed absorption in the intestines before beneficial effects were seen. When this was the case as in one study relapse rates were only 32% compared to 73% for those taking a placebo pill. I would recommend discussing omega-3 supplementation with your physician before doing so due to these mixed results.
Many patients with Crohn's disease have been shown to be low in folate and vitamin B12 especially those who have had disease involvement or surgical resection of the ileum. It is important to address this with your doctor. Blood tests can easily be ordered to find out if you have low levels and there are over-the-counter supplements that can be started if needed. However, if you do need to supplement make sure you do so using the natural versions of these two products (folate and methylcobalamin) and not the synthetic versions. Synthetic folic acid has been shown to cause free radical formation and increase the risk of cancer[25,26]. The best way to get more folic acid is to obtain it naturally through the foods you eat (dark leafy greens, beans, broccoli, etc.). Methylcobalamin is the active form of B12 in your body while cyanocobalamin is not and has to be broken down into methylcobalamin and adenosylcobalamin leaving a small amount of cyanide behind.
Iron deficiency tends to also be an issue in patient's suffering from Crohn's disease. This may be due to lower dietary intake, reduced absorption of iron, or blood loss from increased bleeding. A few different blood tests can be performed by your doctor to determine if you are iron deficient. If you are found to be iron deficient it is important to work with your doctor to come up with a game plan on how to resolve this. You may be able to simply increase your intake of foods that are high in iron (dark leafy greens, prunes, raisins, beans, lentils, etc.) or you may have to take an iron supplement to get your iron level back up to normal.
Summary and Final Thoughts
In conclusion, Crohn's disease can be a tremendous challenge and burden on those who are afflicted with it as well as their families and friends. But in many cases it can be well controlled and even put into long term remission if the right steps are taken especially early on in the disease. By supplementing with probiotics, ensuring adequate vitamin D levels, adhering to a plant-based, nutrient rich diet, and addressing any nutrient deficiencies occurring due to Crohn's disease you can take back control of your health and your life.
If implementing all of these approaches still finds you suffering from complications of Crohn's disease then it's certainly worth the time and effort to look into helminthic therapy. All of these approaches offer numerous benefits with little or no adverse effects. It's important that you work with your physician along the way to ensure appropriate medical care. You may also find it more appealing to work with a naturopathic doctor who approaches treating diseases from a proactive approach on the front end instead of a reactive approach on the back end. It may still be the case for you that medications and surgery are inevitable but a future without these high risk approaches is certainly more attractive then implementing the low risk and yet proven methods talked about in this article. If you are already in the later stages of this debilitating disease then the approaches laid out in this article clearly can't hurt and can only serve to benefit you as you move forward.
I wish you the best of luck in your quest to conquer Crohn's disease and just remember that an open mind and a willingness to educate yourself about your medical condition will prove much more powerful than you think.
Now it'd be great to hear from you and get your feedback.
Did you find this article helpful?
Do you suffer from Crohn's or know someone suffering from Crohn's?
What have you tried to treat it with? What has worked? What hasn't worked?
Do you have any words of advice or support for your fellow Crohn's sufferers?
Thanks for taking the time to read this article and may you have a blessed and wonderful day!
Dustin Rudolph Pharm.D.
1 Hanauer SB. Inflammatory Bowel Disease: Epidemiology, Pathogenesis, and Therapeutic Opportunities. Inflamm Bowel Dis. 2006;12(1):S3-S9.
2 Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417-429.
3 Satsangi J, Morecroft J, Shah NB, et al. Genetics of inflammatory bowel disease: scientific and clinical implications. Best Pract Res Clin Gastroenterol. 2003;17:3-18.
4 Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucinerich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411:599-603.
5 Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001;411:603- 606.
6 Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflamm Bowel Dis. 2008 Nov;14(11):1585-96.
7 Dash SK. Inflammatory Bowel Disease. The Consumer's Guide to Probiotics. 2005;3:33-39.
8 Seaman D. What Is NFkB? It Could Kill You. Available: http://www.dynamicchiropractic.com/mpacms/dc/article.php?id=9441. Dynamic Chiropractic. 2003 Oct;21(21).
9 Thornton JR, Emmett PM, Heaton KW. Diet and Crohn's disease: characteristics of the pre-illness diet. Br Med J. 1979 September 29;2(6193): 762-764.
10 Mahmud N, Weir DG. The urban diet and Crohn's disease: is there a relationship? Eur J Gastroenterol Hepatol. 2001 Feb;13(2):93-5.
11 Amre DK, D'Souza S, Morgan K, et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn's disease in children. Am J Gastroenterol. 2007 Sep;102(9):2016-25.
12 Tursi A, Giorgetti GM, Brandimarte G, Elisei W. High prevalence of celiac disease among patients affected by Crohn's disease. Inflamm Bowel Dis. 2005 Jul;11(7):662-6.
13 Food and Nutrients in Disease Management, edited by Ingrid Kohlstadt. Boca Raton, FL: CRC Press, 2009. Pp. 217-40.
14 Wang TT, Dabbas B, Laperriere D, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn's disease. J Biol Chem. 2010 Jan 22;285(4):2227-31.
15 Joseph AJ, George B, Pulimood AB, et al. 25 (OH) vitamin D level in Crohn's disease: association with sun exposure & disease activity. Indian J Med Res. 2009 Aug;130(2):133-7.
16 Pappa HM, Gordon CM, Saslowsky TM, et al. Vitamin D status in children and young adults with inflammatory bowel disease. Pediatrics. 2006 Nov;118(5):1950-61.
17 Tajika M, Matsuura A, Nakamura T, et al. Risk factors for vitamin D deficiency in patients with Crohn's disease. J Gastroenterol. 2004 Jun;39(6):527-33.
18 Cannell JJ. Am I Vitamin D Deficient? Available: http://www.vitamindcouncil.org/health/deficiency/am-i-vitamin-d-deficient.shtml. Accessed Sept 20th, 2010.
19 Fumagalli M, Pozzoli U, Cagliani R, et al. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J Exp Med. 2009 Jun 8;206(6):1395-408.
20 Elliott DE, Summers RW, Weinstock JV. Helminths and the modulation of mucosal inflammation. Curr Opin Gastroenterol. 2005 Jan;21(1):51-8.
21 Elliott DE, Urban JF JR, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn's disease? FASEB J. 2000 Sep;14(12):1848-55.
22 Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005 Jan;54(1):87-90.
23 Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med. 1996 Jun 13;334(24):1557-60.
24 Yakut M, Ustun Y, Kabacam G, Soykan I. Serum vitamin B12 and folate status in patients with inflammatory bowel diseases. European Journal of Internal Medicine. Aug 2010; 21(4):320-323.
25 Figueiredo JC et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5.
26 Ebbing M et al. Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12. JAMA. 2009;302(19):2119-2126.