Ankylosing spondylitis

In previous editions of the Townsend Letter, I proposed an approach to the phytotherapy of autoimmune disease in general (1) and elaborated on this approach for multiple sclerosis. (2) In this article the further application of this treatment model to the herbal therapy for ankylosing spondylitis, Crohn's disease and ulcerative colitis are described.

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Ankylosing Spondylitis--Good Evidence to Implicate Molecular Mimicry

There is good evidence to implicate molecular mimicry in the cause of ankylosing spondylitis (AS). This has direct implications for its treatment.

Ankylosing spondylitis is often grouped with reactive arthritis. Both diseases occur predominantly in individuals who are positive for the HLA-B27 tissue marker. For cases of reactive arthritis and Reiter's syndrome, a clear association with an infecting organism such as Salmonella, Shigella, Chlamydia, Yersinia or Campylobacter is observed. Reactive arthritis can follow urogenital or intestinal infection with these bacteria.

In the case of AS there is no clear proof of infection, and considerable controversy still surrounds the concept of an infectious etiology. AS almost always follows a chronic course, whereas only 10% of patients with reactive arthritis have evidence of active disease 20 years after the onset. However, evidence is growing that AS is triggered by the asymptomatic presence of pathogenic bacteria, particularly in the intestine. The bacteria may not occur in sufficient numbers to cause a frank infection, but this fact may also help to sustain their persistence in the body, a persistence which can lead to a chronic course of disease.

The following evidence exists for a bacterial trigger for AS:

* Considerable evidence exists that bacteria such as Klebsiella, Enterobacter, Salmonella, Shigella and Yersinia immunologically cross-react with HLA-B27.3 (It is doubtful whether severe disease occurs in the small number of AS patients who are HLA-B27 negative.) (3)

* More than 50% of AS patients with peripheral arthritis have inflammatory gut lesions. 4 The degree of gastrointestinal inflammation was significantly correlated with the degree of joint inflammation in 45 patients with AS. (5) The chronic gut lesions resemble inflammatory bowel disease. (4) It was demonstrated that the intestinal secretory immune system was significantly overstimulated in active AS, and this was reflected by raised serum levels of IgA. (6) When the gastrointestinal anti-inflammatory drug sulfasalazine was given, there was normalization of immune activity in those patients who responded clinically. Another study found that chronic lesions of the gut were frequently found in patients with AS. (7)

* Of the above micro-organisms, Dr Alan Ebringer found that only Klebsiella could be consistently isolated from fecal cultures obtained from British patients with AS. (3) In a study of 63 AS patients by Ebringer's group, an increased recovery of Klebsiella could be obtained during the clinically active phases of the disease. (8) A second study showed that a positive culture of Klebsiella in patients with inactive disease was subsequently followed by a relapse. (9) The same research team found that the presence of Klebsiella was strongly associated with episodes of anterior uveitis in AS patients. (10) Some scientists in other countries have confirmed this association with Klebsiella, but several other research groups have not. It is possible that other organisms might be associated with AS in other countries (see below).

* Another group of scientists found that a substantial portion of patients with AS have antibodies which react to both HLA-B27 and Klebsiella pneumoniae nitrogenase. (11) Amino acid sequence similarities (ie molecular mimicry) had previously been demonstrated between the Klebsiella nitrogenase and HLA-B27. However molecular mimicry between the two proteins was not confirmed by a research team from Finland. (12)

* Since 1980, the British group led by Ebringer has concentrated on finding antibodies to Klebsiella in the bloodstream of patients with active AS. This association has been confirmed in several controlled studies using several different techniques to measure anti-Klebsiella antibodies. (3) However, in a New Zealand study, antibodies to Yersinia were also associated with AS in 4 out of 15 cases. (13) Twenty-nine control subjects had no serum antibodies to Yersinia.

* In what has been described as "the missing link" in the cause of the HLA-B27-associated arthropathies, B27-restricted CD8+ cells, which showed specificity for both autoantigens and arthritogenic bacteria such as Yersinia, have been isolated from the synovial fluids of patients with reactive arthritis and AS. (14)

* Nonsecretors of ABO blood group antigens are more susceptible to infection. The fact that nonsecretors of ABO are 2.6 times more likely to have AS supports an infectious etiology for AS. (15)

* The site of the bacterial trigger for AS is not necessarily always the bowel. An association between AS and chronic bacterial prostatitis has long been observed. The incidence of chronic prostatitis in male AS patients was 83%, compared to 33% in patients with rheumatoid arthritis. (16) This association was confirmed in a later study. (17) The fact that the prostate may harbor a bacteria which contributes to AS could explain the higher incidence of this disorder in males.

Consideration of the above and other similar findings led Dr. John Vaughan to conclude in a recent review: "The probability that AS is due to a peculiar immunologic relationship between the patient and his enteric organisms, and that this is determined by his HLA-B27 molecules, seems great." (18)

The information on possible sources of immune dysregulation in AS is less clear. However, enhanced gastrointestinal permeability, the so-called leaky gut, could be such a source. Normally, small amounts of lipopolysaccharides (endotoxin) enter portal venous blood and are eliminated by phagocytic cells in the liver. (19) Increased mucosal permeability may result in the increased exposure of the body to such pro-inflammatory bacterial fragments.

Studies have demonstrated an increased intestinal permeability in AS. (20-22) These findings also support the notion that asymptomatic gut inflammation, possibly due to pathogenic bacteria, is a factor in the pathogenesis of AS.

Other factors which have been associated with AS and may reflect on immune dysregulation include trauma (23) and delayed hypersensitivity. (24) Reactive arthritis and Reiter's syndrome have been reported after hepatitis B vaccination (25,26) and this could also be a factor in some cases of AS. Eliminating cow's milk products from the diet caused symptomatic improvement in AS in one study. (27)

Treatment Approach

From the above, a key part of the treatment approach to AS is to reduce the presence of Klebsiella or other potentially pathogenic organisms. This will not only reduce the stimulus for immune cross-reactivity, but will also decrease gastrointestinal inflammation and the resultant increased permeability.

Klebsiella in the bowel uses resistant starch processed to oligosaccharides by friendly bacteria as a major source of nutrition. So a low starch diet should decrease its numbers. Ebringer recommends that patients with AS should avoid bread, pasta, cereals of all sorts, rice, potatoes and sugary foods. They can eat unrestricted amounts of vegetables (excluding starchy root vegetables such as potatoes and yams), fruit, eggs, cheese, fish and meat. (28) Legumes such as soy beans and uncooked bananas contain a significant proportion of indigestible starch which may act as a food source for Klebsiella. They should also be avoided.

Ebringer claims that the majority of 200 patients on this diet had their disease process halted. However a significant result may take 6 months or more. (28)

Herbal treatment for AS should be selected from the following:

* Immune-enhancing herbs such as Echinacea, Andrographis and Astragalus to eliminate pathogenic organisms.

* Gastrointestinal antiseptics such as Berberis (barberry), Hydrastis (golden seal), Allium sativum (garlic) and propolis to eliminate pathogenic organisms from the bowel.

* Gastrointestinal healing and anti-inflammatory agents such as Calendula, Filipendula (meadowsweet), Matricaria (chamomile) and propolis to reduce inflammation and heal the gut wall.

* Echinacea and Silybum (milk thistle) to reduce the systemic impact of a leaky gut wall by improving hepatic phagocytosis (Kupffer cells).

* Suitable treatment for the prostate if chronic prostatitis is present, using herbs such as saw palmetto.

* Anti-inflammatory herbs such as Salix (willow bark), Glycyrrhiza (licorice) and Bupleurum to help control symptoms and break the vicious cycle sustaining the tissue destruction. A key anti-inflammatory herb is Boswellia, which can help to alleviate both the gut (see later) and the joint inflammation.

Crohn's Disease

Evidence exists to support the hypothesis of a microbial trigger for Crohn's disease (CD). Although the association of bacteria, viruses and bowel flora with CD 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 CD, 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 CD has been proposed by French scientists. (29)

Viruses

A group led by Dr Andrew Wakefield at the Royal Free Hospital in London completed a study of CD tissue specimens. Based on this study they proposed that the primary lesion in CD was a vasculitis caused by multifocal intestinal infarction. (30) They further proposed that this injury was consistent with a cell-mediated response to a persistent viral infection of mesenteric microvascular endothelium. Of the viruses known to infect vascular endothelium, the measles virus was of particular interest for two reasons: it localizes to the intestine and it can persist for many years. They began to search for the measles virus. Intestinal tissue from 10 patients with CD were all found to contain measles virus RNA. (31) Moreover, measles virus RNA was found within vascular endothelial cells associated with inflammatory foci in 9 out of the 10 CD patients. Other tests also supported the presence of measles virus. (31)

A Swedish epidemiological study subsequently found that children born during the three-month period following a measles epidemic were significantly more likely to develop CD in later life. (32) However no association with measles was observed for UC. (32)

Wakefield is of the opinion that measles vaccination may be responsible for the rise of CD cases in children. This rise is seven-fold in Scotland over the last 20 years, whereas cases of measles infections there have dropped dramatically. However, vaccination may not be the only explanation for this rise. Moreover, fewer cases of measles infection might not necessarily reflect that general exposure to the virus is less. Generally there is controversy over the association of CD with measles vaccination and several studies which could not find any association have been subsequently published.

Mycobacteria

Research attention has been given to the possible association of mycobacteria with CD. 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 CD. (33) This report initiated both interest and controversy about a mycobacterial etiology for CD. One problem is that, on culture, mycobacteria isolated from CD 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 CD patients. (34) M. avium has also been identified in the intestinal tissue of patients with CD. (35)

Many other groups of investigators have isolated mycobacteria from CD 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 CD patients, 4.3% of patients with UC and 12.5% of control patients. (40) Other researchers found raised antibodies specific to M. paratuberculosis in 84% of patients with CD. (41) Such findings led a scientist working in the field to conclude that the evidence for a mycobacterial association with CD 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 CD 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 CD may lack a cell wall. (42)

However, in accordance with the proposed model, mycobacteria are possibly acting as a source of immune crossreactivity 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

Other bacteria have been implicated in CD, but results are often conflicting. For example, one study found that 93% of patients with CD had antibodies against Chlamydia, compared to 26% in the control group. (43) However, another study failed to find evidence of Chlamydia infection in CD 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 CD. Antibodies to Klebsiella were also higher in a population of CD 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 CD. (46)

Bowel Flora

There is little doubt that the fecal stream plays an important part in the progression of CD. (47-49) Bowel flora are likely to be a strong source of immune dysregulation in CD. Monocytes from CD patients showed enhanced stimulation by bacterial cell wall products such as lipopolysaccharide. (50) Bacterial wall fragments in the bowel wall of CD patients caused enhanced immune responsiveness of monocytes. (51) When 36 tissues from 16 patients with CD 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 CD 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 CD patients. (53)

Pathogenic forms of E. coli adhere to the gut mucosa. E. coli isolated from patients with UC and CD showed a significantly greater index of adhesion when compared to normal controls. (54)

Bowel Permeability

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 CD. (55) In fact, so characteristic is this enhanced permeability that it is considered a good marker of active inflammation occurring in CD patients in remission. (56) Circulating levels of lipopolysaccharide are increased in patients with active CD. (57) There is a general leakiness of the intestinal mucosa in CD which is not dependent on the presence of inflammatory lesions. (55) It has been postulated that increased permeability may be a primary expression of CD and an important pathological factor. (55)

In support of the concept that increased permeability is a pathogenic factor, CD 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 UC.

Diet

Food is a potential source of many immune-provoking antigens, and food is probably therefore a potent source of immune dysregulation in CD. It is a well-accepted observation that many patients with CD 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 CD. (62)

The concept of using an exclusion diet to treat CD 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 CD, 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) Corticosteroid 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 CD. (64)

Patients with CD but not UC 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 CD 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

Diet

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 CD. (66-68)

Bowel Flora Regime

A correction of bowel flora in CD 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 CD than UC, possibly because of the favorable effect of fasting on CD.

Herbs for CD

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. (69) 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 CD, 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.

Ulcerative Colitis

In contrast to Crohn's disease, studies have consistently associated ulcerative colitis (UC) with cytomegalovirus (CMV). (70) A clear association between onset of UC 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 UC. (70) The simultaneous presence of DNA from several herpes viruses, including CMV, was much greater in UC patients compared to those with CD or normal controls. (73)

E. coli with specific surface hairs or pili that promote adhesion are found in significant amounts in patients with UC compared to controls. (54) (This phenomenon was also observed for CD 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 UC can degrade mucins and produce toxins.

Serological tests of patients with IBD found a connection between antibodies against Chlamydia (93% for CD and 45% for UC) compared to controls (26%). (74) A patient with AIDS developed UC after an episode of amebic dysentery. (75)

UC 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 UC 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 UC. (77)

Hypothesis

Cytomegalovirus (an enveloped virus) or similar viruses provide the source of the primary antigen in UC, possibly by molecular mimicry. Adhesive E. coli and other bacterial factors in bowel flora and elsewhere promote immune dysregulation.

Diet and UC

Studies have shown that elimination diets can help reduce symptoms of UC78 and clinical trials of fish oil supplementation have shown positive results. (79)

The association between a low-sulfur diet and a clinical benefit in UC 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 UC. (80) The authors suggested that increased production of sulfide in UC suggests that the action of mercaptides (sulfur compounds) may be involved in the genesis of UC.

Herbal Therapy

The suggested herbal therapeutic approach for UC is similar to that for CD, 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 CD and UC 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):

* St John's wort: 3 tablets per day, each tablet containing Hypericum perforatum (St John's wort) extract standardized to contain hypericin 990 mcg and hyperforin 9 mg, equivalent to 1.8 g of herb flowering top.

* Boswellia: 3 tablets per day, each tablet containing: Boswellia serrata extract standardized to contain boswellic acids 180 mg, equivalent to 1.2 g of Boswellia gum resin; Apium graveolens (celery) extract equivalent to 1 g of fruit; Zingiber officinale (ginger) extract equivalent to 300 mg of rhizome; and Curcuma longa (turmeric) extract standardized to contain curcuminoids 70.4 mg, equivalent to 2 g of rhizome.

* Echinacea: 2 tablets per day, each tablet containing: Echinacea angustifolia extract standardized to contain 2.0 mg of alkylamides, equivalent to 600 mg of root; Echinacea purpurea extract standardized to 2.1 mg of alkylamides, equivalent to 675 mg of root.

* Slippery elm powder: 2 teaspoons per day.

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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by Kerry Bone, FNIMH, FNHAA

P.O. Box 713 * Warwick QLD 4370, Australia

+61 7 4661 0700 * Fax +61 7 46610788 * www.mediherb.com

FNIMH = Fellow, National Institute of Medical Herbalists (UK)

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