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Crohn's DiseasePhytotherapy Review & Commentary
by Kerry Bone, FNIMH (Fellow, National Institute of Medical Herbalists)
Townsend Letter For Doctors & Patients - June 2004
Evidence exists to support the hypothesis of a microbial trigger for Crohn's disease. Although the association of bacteria, viruses and bowel flora with Crohn's Disease may confound a clear infectious cause, such a multiplicity of factors is consistent with the proposed model for the development of autoimmune disease. In the case of Crohns Disease, a virus could provide the primary lesion but bacteria are more likely to be involved. A combination of effects from bacteria, imbalanced bowel flora, diet and stress trigger a state of immune 'dysregulation' which results in active disease. A similar theory for the cause of Crohns Disease has been proposed by French scientists.29
Research attention has been given to the possible association of mycobacteria with Crohns Disease. The original account by Crohn described a disease that closely resembled intestinal tuberculosis. Johne's disease, which occurs in cattle and other ruminants, is very similar to Crohn's Disease and is caused by Mycobacterium paratuberculosis.
In 1984 Chiodini and co-workers reported the isolation of a strain resembling M. paratuberculosis from the intestinal tissue of three patients with Crohns Disease.33 This report initiated both interest and controversy about a mycobacterial etiology for Crohns Disease. One problem is that, on culture, mycobacteria isolated from Crohns Disease tissue initially appear as cell wall-deficient forms that are difficult to identify by conventional techniques.34 With the development of the enzyme PCR (polymerase chain reaction), which replicates DNA, DNA from M. paratuberculosis has been detected in cultures from Crohns Disease patients.34 M. avium has also been identified in the intestinal tissue of patients with Crohns Disease.35
Many other groups of investigators have isolated mycobacteria from Crohns Disease patients, 36,37 although not all patients and not all studies have yielded positive results.35-39 In a study reported by Sanderson and co-workers, M. paratuberculosis DNA was identified in gut wall tissues from 65% of Crohns Disease patients, 4.3% of patients with Ulcerative Colitis and 12.5% of control patients.40 Other researchers found raised antibodies specific to M. paratuberculosis in 84% of patients with Crohns Disease.41 Such findings led a scientist working in the field to conclude that the evidence for a mycobacterial association with Crohns Disease is "stronger now than it has been before."37
One problem which has led to skepticism about the above statement is that there is inconclusive evidence that Crohns Disease results from an actual mycobacterial infection. Only the presence of mycobacteria has been proven. PCR technology can detect very small amounts of bacterial DNA, as low as several hundred bacteria per g of tissue. From an immunological point of view, it is difficult to see how so few organisms alone could elicit such a strong inflammatory response, especially since the form of M. paratuberculosis implicated in Crohns Disease may lack a cell wall.42
However, in accordance with the proposed model, mycobacteria are possibly acting as a source of immune cross-reactivity or immune dysregulation, and the main inflammatory stimulus is elsewhere. Therefore the presence of mycobacteria is still a significant finding, despite their low numbers.
Other bacteria have been implicated in Crohns Disease, but results are often conflicting. For example, one study found that 93% of patients with Crohns Disease had antibodies against Chlamydia, compared to 26% in the control group.43 However, another study failed to find evidence of Chlamydia infection in Crohns Disease patients.44 This discrepancy could be due to the testing of different patient populations. That is, depending on environmental circumstances, Chlamydia may act as a pathogenic factor in Crohns Disease. Antibodies to Klebsiella were also higher in a population of Crohns Disease patients.45
Mollicute-like organisms (MLO) are cell wall-deficient intracellular bacterial pathogens. They cannot be cultured by microbiological techniques and can only be detected in cells with an electron microscope. MLO were found in the white blood cells of patients with Crohns Disease.46
There is little doubt that the fecal stream plays an important part in the progression of Crohns Disease. 47-49 Bowel flora are likely to be a strong source of immune dysregulation in Crohns Disease. Monocytes from Crohns Disease patients showed enhanced stimulation by bacterial cell wall products such as lipopolysaccharide.50 Bacterial wall fragments in the bowel wall of Crohns Disease patients caused enhanced immune responsiveness of monocytes.51
When 36 tissues from 16 patients with Crohns Disease were examined, no evidence of the presence of many pathogenic bacteria and viruses were found.52 However, E. coli and streptococcal antigens were found in 69% and 63% of the 16 cases studied, respectively. Both E. coli and streptococci are normal inhabitants of bowel flora. The above results suggest that some of the granulomas in Crohns Disease may result from the immunological processing of bowel flora antigens following their penetration through a compromised mucosa.52 Serum antibodies to bowel flora bacteria are increased in Crohns Disease patients.53
Pathogenic forms of E. coli adhere to the gut mucosa. E. coli isolated from patients with Ulcerative Colitis and Crohns Disease showed a significantly greater index of adhesion when compared to normal controls.54
A leaky gut would enable enteric antigens to penetrate the mucosa to an increased extent, and the capacity for removal or degradation of this antigenic load could then be exceeded. This would create a state of immune dysregulation. Several studies indicate permeability abnormalities for both the small and large intestine in Crohns Disease.55 In fact, so characteristic is this enhanced permeability that it is considered a good marker of active inflammation occurring in Crohns Disease patients in remission.56 Circulating levels of lipopolysaccharide are increased in patients with active Crohns Disease57. There is a general leakiness of the intestinal mucosa in Crohns Disease which is not dependent on the presence of inflammatory lesions.55 It has been postulated that increased permeability may be a primary expression of Crohns Disease and an important pathological factor.55
In support of the concept that increased permeability is a pathogenic factor, Crohn's Disease has been associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are responsible for increased gut permeability and small intestinal inflammation.58,59 A group of researchers from Jersey reported that of 60 new cases of colitis, 23 had developed while the patient was taking NSAIDs.60 None of these 23 patients had a known pre-existing IBD. Diclofenac (Voltaren) and mefenamic acid (Ponstan) were the most frequently observed associations. On endoscopic examination, some cases were indistinguishable from Ulcerative Colitis.
Food is a potential source of many immune-provoking antigens, and food is probably therefore a potent source of immune dysregulation in Crohns Disease. It is a well-accepted observation that many patients with Crohns Disease improve substantially when they are placed on an elemental diet, that is, a predigested liquid diet free of antigenic challenge consisting of amino acids, dextrin, vitamins, vegetable oil, minerals and so on.61 An elemental diet also decreases small intestinal permeability in Crohns Disease.62
The concept of using an exclusion diet to treat Crohns Disease was first proposed by a group at Cambridge, 63 and subsequent publications have originated from England. The Cambridge group found that during a controlled trial of 20 patients with Crohns Disease, 7 of 10 patients on an exclusion diet remained in remission for 6 months, compared to none of the 10 on a normal fiber-rich diet. 63 In an uncontrolled study, an exclusion diet allowed 51 of 77 patients to remain well on diet alone for periods up to 51 months, with an average annual relapse rate of less than 10%.63
These results were confirmed in a controlled trial on 78 patients.64 Cortico-steroid therapy was compared to an exclusion diet. Patients on the exclusion diet also received placebo. Results for diet treatment were favorable, median remission periods were 3.8 months in the corticosteroid group and 7.5 months in the group treated by diet. Intolerances discovered were predominantly to cereals, dairy products and yeast. The authors concluded that diet provides a further therapeutic strategy in active Crohns Disease.64
Patients with Crohns Disease but not Ulcerative Colitis were found to have significantly high levels of antibodies to baker's yeast in blood samples. These results were confirmed in a later study which also found that raised antibodies to yeast occurred in Crohns Disease patients regardless of whether they were yeast intolerant or not.65 The pathogenic importance of these findings has not been established.
Phytotherapy for Crohn's Disease
An individually determined exclusion diet, as outlined above, is an important part of therapy. However, if this is not practical, the case history may provide clues to food sensitivities. In particular, dairy or wheat avoidance should be considered. Supplementation with fish oil can be beneficial in Crohns Disease.66-68
Bowel Flora Regime
A correction of bowel flora in Crohns Disease may reduce the dysregulation caused by an abnormal flora, and could also create an unfavorable environment for intracellular pathogens such as mycobacteria and viruses. Phytotherapist Hein Zeylstra has developed a successful treatment regime for IBD. The regime is outlined in Table 1. This approach originated from the naturopathic approach to Johne's disease in cows described by Roger Newman-Turner, Sr. Although Hein Zeylstra provides no explanation as to why this approach may work, it is my interpretation that the regime has a favorable influence on bowel flora.
Basically, the routine is to periodically fast, taking fresh garlic (Allium sativum) and slippery elm (Ulmus rubra). Pathogenic bacteria in the bowel lumen would be weakened by fasting, since they rely on a ready source of nutrients. The garlic then reduces the population of all bacteria in the bowel lumen, and the slippery elm encourages only the growth of favorable bacteria. This last aspect of the therapy takes advantage of the ability of favorable organisms, such as bifidobacteria, to utilize the mucilage in the slippery elm as a food source, whereas pathogenic bacteria cannot.
Thus there is an increase in favorable bacteria. If the routine is repeated several times over a few months, a "normalization" of bowel flora will result. According to Zeylstra the regime works faster in Crohns Disease than Ulcerative Colitis, possibly because of the favorable effect of fasting on Crohns Disease.
The Bowel Flora Regime as developed by phytotherapist Hein Zeylstra.
This may need to be followed for several months.
|Day 1:||Fast - no food, but water and medicines are allowed.|
|Day 2 and 3:||Continue as for Day 1. Twice during the day take one to two cloves of crushed fresh garlic with a copious quantity of water. This has the effect of flushing the fresh garlic quickly into the small intestine. At different times take one to two teaspoons of slippery elm powder with copious water.|
|Day 4:||Gradually introduce allowed foods and continue with medicines and slippery elm.|
|Day 5 to 14:||Follow exclusion diet and take medicines and slippery elm.|
|Day 15:||Begin again as for Day 1, etc.|
Herbs for Crohns Disease
Immune enhancement with herbs such as Echinacea, Andrographis and Astragalus will help resolve the presence of any virus, mycobacteria and abnormal bowel flora. If any virus involved is enveloped, hypericin found in Hypericum would be active against the virus. Hypericum has also been shown to be active against mycobacteria in vitro.69
Other herbs with such in vitro activity against mycobacteria include Allium sativum and Cinnamomum zeylanicum. Berberine-containing herbs such as Berberis species and Hydrastis have a good broad-spectrum antimicrobial activity and are useful to help correct bowel flora. Matricaria is useful for the symptoms of spasm and together with Calendula will help to repair a leaky gut. Because of the leaky gut, phagocytic screening by the liver should be increased using Echinacea and Silybum.
Anti-inflammatory herbs which inhibit leukotriene production such as Boswellia are also strongly indicated. Cell-mediated immunity is a factor in the pathogenesis of Crohns Disease, so selective use of Tylophora 1:5 (for 10 days of each month) may be useful in the early stages of treatment. As with all autoimmune diseases, best results come with long-term treatment.
In contrast to Crohn's disease, studies have consistently associated ulcerative colitis (UC) with cytomegalovirus (CMV).70 A clear association between onset of Ulcerative Colitis and primary CMV infection was confirmed by virus studies in two patients.71,72 Higher frequency and amount of antibodies to CMV was found in patients with Ulcerative Colitis.70 The simultaneous presence of DNA from several herpes viruses, including CMV, was much greater in Ulcerative Colitis patients compared to those with Crohns Disease or normal controls.73
E. coli with specific surface hairs or pili that promote adhesion are found in significant amounts in patients with Ulcerative Colitis compared to controls.54 (This phenomenon was also observed for Crohns Disease but was less marked.) Pathogenic E. coli show mucosal adhesion, and this is a necessary condition for their pathogenicity. Several workers have shown that isolates of E. coli obtained from patients with Ulcerative Colitis can degrade mucins and produce toxins.
Serological tests of patients with IBD found a connection between antibodies against Chlamydia (93% for Crohns Disease and 45% for Ulcerative Colitis) compared to controls (26%). A patient with AIDS developed Ulcerative Colitis after an episode of amebic dysentery.75
Ulcerative Colitis patients receiving probiotic therapy with a live nonpathogenic strain of E. coli (enteric coated capsules), following a one-week course of an antibiotic, experienced a similar benefit to therapy with mesalazine in maintaining remission.76 The authors suggested that this finding confirms a link between Ulcerative Colitis and bowel flora. Implantation of normal colonic flora from a donor following reduction of endogenous bowel flora led to a favorable outcome in one patient with Ulcerative Colitis.77
Cytomegalovirus (an enveloped virus) or similar viruses provide the source of the primary antigen in Ulcerative Colitis, possibly by molecular mimicry. Adhesive E. coli and other bacterial factors in bowel flora and elsewhere promote immune dysregulation.
Diet and Ulcerative Colitis
Studies have shown that elimination diets can help reduce symptoms of Ulcerative Colitis 78 and clinical trials of fish oil supplementation have shown positive results.79The association between a low-sulfur diet and a clinical benefit in Ulcerative Colitis has already been described. One study found that the metabolic effects of sodium hydrogen sulfide on butyrate oxidation along the length of the colon closely mirror metabolic abnormalities observed in active Ulcerative Colitis.80 The authors suggested that increased production of sulfide in Ulcerative Colitis suggests that the action of mercaptides (sulfur compounds) may be involved in the genesis of Ulcerative Colitis.
Herbal Therapy & Ulcerative Colitis
The suggested herbal therapeutic approach for Ulcerative Colitis is similar to that for Crohns Disease, although there should be a greater emphasis on antiviral treatments, especially St John's Wort. Bowel flora modification by whatever means (for example by the regime described in Table 1 although the sulfur in garlic could be detrimental) is an essential part of the treatment. Boswellia is an important anti-inflammatory herb for both Crohns Disease and Ulcerative Colitis as outlined below.
A Key Role for Boswellia in Inflammatory Bowel Disease
Pharmacological studies have found that extracts from the gum resin of Boswellia serrata (Indian olibanum, a relative of frankincense) possess anti-inflammatory properties. In particular, the boswellic acids inhibit the enzyme 5-lipoxygenase which is responsible for the production of leukotrienes. Since the inflammatory process in inflammatory bowel disease (IBD) is associated with increased function of leukotrienes, the benefits of Boswellia in the treatment of both chronic colitis (ulcerative colitis) and Crohn's disease have been recently investigated.
Twenty patients with chronic colitis received Boswellia gum resin (900 mg per day for 6 weeks) and another 10 patients were given sulfasalazine (3 g per day for 6 weeks).1 Out of 20 patients treated with Boswellia, 14 went into remission (70% compared to 40% for sulfasalazine).
The safety and efficacy of a Boswellia extract was compared against mesalazine for the treatment of 102 patients with active Crohn's disease in an eight-week randomized, double-blind study.2 The primary clinical outcome measured was the change in Crohn's Disease Activity Index (CDAI). After therapy with Boswellia extract (3.6 g per day) the average CDAI was reduced by 90, compared to a reduction of 53 for the mesalazine group (4.5 g per day). The authors concluded that the Boswellia extract was as effective as mesalazine, which is the state-of-the-art treatment for this disorder. Considering the observed fewer side effects and better safety profile of Boswellia, they suggested that this novel herbal treatment appears to be superior to mesalazine in terms of a risk-benefit evaluation.
The chronic colitis study described above follows from a similar, earlier study of the efficacy of Boswellia for this disorder. Unfortunately, the design flaws in the earlier study (fewer patients in the control treatment group, study was open) are reflected in the current trial. In contrast, the study on Crohn's disease was well designed and conducted in Europe. It adds serious weight to the suggestion that Boswellia is a useful anti-inflammatory agent for IBD.
Ulcerative Colitis: A Brief Case History
A female patient aged 55 presented with ulcerative colitis (12 years of history). Her drug treatment was 6 tablets per day of Salazopyrin (sulfasalazine). She was also on prednisone due to an episode of severe bleeding (but was tapering off). Over the past 15 months her condition had become much worse.
Based on recent research she was placed on a low sulfur diet (no dairy, no cabbage family, no eggs, no onions or garlic, reduced red meat, no sulfur-based additives).
The following herbs were prescribed
(tablets were used because alcohol made her bowel worse):
The rationale for the treatment:
- St John's wort: antiviral, nervine tonic
- Slippery elm: demulcent and improves bowel flora
- Echinacea: balance immunity
- Boswellia, ginger, celery and turmeric: anti-inflammatory
Her progress was as follows:
- After 2 months - stopped prednisone and no blood, drug down to 4 per day
- Two months later - bowel a lot better, fewer motions, biopsy normal, drug down to 2 per day
- Two months later - bowel action up (but no blood or cramping), drug back to 3 per day
- Two months later - everything OK, drug down to 2 per day
- Six months later there were no symptoms and biopsy showed no sign of ulcerative colitis, drug at 2 per day
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1. Bone K. Automimmune disease: Townsend Letter 1999 Aug/Sep #193 94-98
2. Bone K. Phytotherapy for autoimmune disease: Townsend Letter 2004 #250
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