Research needed to investigate the use of bael fruit in ulcerative colitis
A 34-YEAR-OLD male had been diagnosed with ulcerative colitis (UC) two years earlier. His other past medical history included beta thalassaemia trait (he had a microcytic anaemia, MCV [mean corpuscular volume] 65). He was a non-smoker.
Since diagnosis the patient had had four flare ups of UC, requiring oral prednisolone 45mg daily for several weeks, and a daily prednisolone enema as well as mesalazine enema 2g nocte. Despite maintenance therapy of high dose steroids and a 5-aminosalicylic acid (mesalazine 2.4g bd) he was still passing mucus and blood in his stool.
Initial colonoscopy on diagnosis in 2008 showed inflammation in the rectum only, and histology confirmed the diagnosis of UC. Repeat colonoscopy in 2010 showed pancolitis and mildly active disease with granular mucosa. These findings were consistent with UC, and this was confirmed on histology.
The patient went on to develop right knee pain and had raised intraocular pressure of 28 mmHg (picked up on a routine eye examination) secondary to steroids. He had TPMT (thiopurine methlytransferase) levels done in preparation for commencing azathioprine because his last flare up lasted nine months. Because he did not wish to take azathioprine, he looked into alternative ways in which to control his flare ups. He came across the use of bael fruit (Aegle marmelos Correa) in intestinal and digestive disorders associated with bloody diarrhoea.
The patient ate bael fruit (fresh when in season and dried when not) twice daily (30 minutes before breakfast and 30 minutes before his evening meal).
Since adding this fruit to his diet, the patient’s bloody diarrhoea has resolved and he has been off steroids. His mesalazine has been reduced to 1.2g bd. His intraocular pressure has returned to normal and his knee pain has settled. He believes that eating this fruit twice daily has allowed him come off steroids and to avoid the use of immunosuppressant drugs.
Bael fruit belongs to the same family as the orange. It has a thin hard woody shell that turns yellow when ripe. The pulp of the fruit is orange, with numerous hairy seeds embedded in it. The fruits, leaves, bark, roots and seeds of Aegle marmelos Correa are used in Ayurvedic medicine and various folk medicine. The fruit’s medicinal value is said to be high when it just begins to ripen so it is thought to be best eaten fresh at this time.
Bael fruit exhibits antidiabetic and antihyperlipidaemic properties.1 It has been shown to have high levels of phenolic compounds, which may give it high antioxidant2 and antiviral properties.3
Could high antioxidant or antiviral properties control UC symptoms? Further studies are needed to determine the effect of bael fruit in UC.
See case comment below.
Case report references
- Kamalakkannan N, Prince PS. The effect of Aegle marmelos fruit extract in streptozotocin diabetes: a histopathological study. Journal of Herbal Pharmocotherapy 2005;5(3):87–96.
- Abdullakasim P, Songchitsomboon S, Techagumpuch M et al. Antioxidant capacity, total phenolics and sugar content of selected Thai health beverages. International Journal of Food Sciences & Nutrition 2007;58(1):77–85.
- Badam L, Bedekar SS, Sonawane KB, Joshi SP. In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses B1-B6. Journal of Communicable Diseases. 2002;34(2):88–99.
Case comment: Anja St Clair-Jones lead pharmacist surgery and digestive diseases
I HAD not heard of bael fruit but soon found information on the internet. Some articles that review the use of Aegle marmelos in inflammatory bowel disease (IBD) are available1–3 but most of the information is about Ayurvedic medicines that contain the fruit along with other traditional Indian herbal ingredients. It appears that the research into these medicines has only just started — the articles are fairly recent and no in vivo research is available.
The beta thalassaemia trait indicates that the patient is of Asian origin. IBD is uncommon in Asians (probably due to the relatively low carbohydrate and fat in the Asian diet) but the incidence has been rising.
Caution in interpretation
The references attached to this case report are not really linked to the disease and are for either animal or in vitro studies. I agree that bael fruit might, potentially, have an effect in ulcerative colitis but this is based on theoretical conjecture and needs a lot more research. Any effect could just as much be attributed to the high tannin content of the unripe fruit and its astringent effect helping to control diarrhoea.
Mucosal healing — not just symptom control — is the aim of current treatment strategies but there is no mention of it in the report. Only endoscopy can establish this.
Currently the relationship of viral infection and UC is not clear. Antiviral agents are not routinely used. The role of antioxidants in the inflammation of the colon is not established and purely based on theoretical postulations.
Pharmacists should be aware that single case reports cannot be used as a basis for evidence-based practice — they are anecdotal and are low in the hierarchy of evidence.
Ulcerative colitis: a reminder
UC is characterised by the chronic inflammation of the mucosal layer of the rectum and a varying degree of the colon and is described by disease extent:
Symptoms include bloody diarrhoea and abdominal pain and disease activity is classified as mild, moderate or severe.
Tests reveal raised C reactive protein and raised faecal calprotectin (an emerging intestinal function test correlated to clinical disease activity), and endoscopic findings include inflammation and ulceration of the colonic mucosa.
UC is still mainly a disease of developed countries. In the UK, between 60,000 and 120,000 people (about one in 600) are affected and between 6,000 and 12,000 new cases are diagnosed each year. Diagnosis is most between the ages of 15 and 35 years. Men and women are equally affected.4
The causes of UC have not been established but genetic, environmental and immunological factors are thought to contribute. (In the case report, whether the thalassaemia trait might have any bearing on the genetic component of UC is an interesting consideration. There is not enough research on genetic influences in IBD.)
Aims of treatment
Treatment aims to control acute attacks, to maintain remission (complete resolution of symptoms and endoscopic mucosal healing) and to prevent hospital admissions, surgery and colon cancer. Most people with UC never develop colon cancer but two factors that increase the risk are the duration of the disease and how much of the colon is affected.
Initial treatment is usually based on mesalazine. Corticosteroids are used for flare ups. For patients with more than one relapse a year current strategies require a step up to immunomodulator therapy (eg, azathioprine or mercaptopurine) and ultimately to biologics.
The thiopurines (eg, azathioprine [unlicensed indication]) are widely used as step up maintenance therapy, and allow patients to use fewer steroids. However, a slow onset of action means a course of initial steroids (eg, prednisolone 40mg daily, reducing by 5mg weekly) is needed as a bridging therapy.
Thiopurine methyl-transferase (TPMT) metabolises azathioprine. Patients deficient in the enzyme TPMT are at increased risk of myelotoxicity and TPMT activity is now routinely measured before starting thiopurines. Myelosuppression occurs in around 3 per cent of patients throughout the treatment and regular blood monitoring is essential while a patient is on thiopurines.
About 20 per cent of patients experience adverse drug reactions such as fever, nausea and diarrhoea, arthralgia and rash at around week 2 or 3, which resolves on withdrawal. However if the therapy is tolerated beyond three weeks long-term benefit can be expected. There is a theoretical risk of increased viral and bacterial infections but the incidence does not seem to be different between those not on immunosuppression therapy and those receiving high dose steroids. Concerns about increased risk of cancer or lymphoma with the use of thiopurines have not been resolved. Some reports seem to suggest that the risk is no greater than that of the general population whereas others find a four-fold increase in risk for IBD patients treated with thiopurines.
Dietary and complementary interventions are still in their infancy and lack good clinical trials. Limited data and poor trial designs do not allow for safe conclusions of their usefulness in IBD. Prebiotics (non-digestible dietary carbohydrates producing short-chain fatty acids) are unproven. Probiotics lack the evidence in view of which strain, what dose, when to take and how long for. There is some evidence of benefit for VSL#3 in UC but further research is needed.
A Cochrane review was unable to make recommendations for the benefit of omega-3 fatty acids due to a lack of adequate information and poor trial designs.
Many herbal medicines are being investigated in the Asian-Pacific population but this requires care when extrapolating to a western population due to the genetic factors involved in IBD.
Guidelines on managing UC include:
- Guidelines for the management of IBD in adults (British Society of Gastroenterology) Available at www.bsg.org.uk
- European Crohn’s and Colitis Organisation Consensus guidelines for IBD. Available at www.ecco-ibd.eu.
Case comment references
- Gandhi TR, Darji VC, Solanki RP et al. Effect of Aegle marmelos Linn. (Rutaceae) fruits in inflammatory bowel disease. Indian Drugs 2009; 46(6):460–4.
- Darji VC, Bariya AH, Deshpande SS et al. Natural agents for inflammatory bowel disease. International Journal of Research in Ayurveda and Pharmacy 2011;2(1):84–9.
- Seidner D, Lashner BA, Brezzinski A et al. An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: A randomized, controlled trial Clinical Gastroenterology and 2005;3:358–69.
- Crohn’s and Colitis UK website (accessed on 20 January 2012).
Citation: The Pharmaceutical Journal URI: 11097769
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