In this, the first placebo-controlled trial of AV using the NLP formulation in IBS, there was no overall benefit found among patients taking the active treatment compared to patients taking a matching placebo. Although a slight benefit was seen in the diarrhoea predominant group whilst the treatment was being taken, this subgroup was not included as part of the protocol and therefore generates a hypothesis that warrants further study.
It is possible that the failure to find a benefit in the whole group was due to the study being underpowered from overoptimistic assumptions of the size of effect of the NLP AV preparation. A study size of 203 subjects per group would have been required for an 80% power to detect the differences observed in the whole group at the 5% level of significance based on an intention-to-treat analysis. However, our findings suggest that future studies should study diarrhoea predominant subjects, and based on the point estimates from the current study 46 subjects per group will be required.
The magnitude of the benefit we observed in the whole group, although not statistically significant, was equal to that observed for Alosetron, the IBS drug recently withdrawn for its side effects by Glaxo (41% versus 29% response rates for active and placebo respectively). Furthermore, AV using the NLP formulation was generally well tolerated, with distension as the only apparent side effect. Six patients did withdraw from the study with nausea and/or vomiting. However, a majority of these came from the placebo group and so was not considered to be a significant side effect.
This was a double-blind randomised placebo-controlled trial, thus reducing the potential for bias. All patients took the drug as requested and few patients were lost to follow-up. However, these results have to be considered in the light of the fact that the subjects included in this trial were all recruited from a pool of refractory patients in secondary and tertiary care, and as such the research protocol may have constituted an overly rigorous test of efficacy. By chance scores in the active group tended to be higher at baseline than in the placebo group and hence any apparent response in the group could be explained by regression to the mean, but the fact that the active group score returned to baseline after treatment had been discontinued argues against this. It is also possible that placebo responses were more marked in the active group because of their more severe symptoms at baseline. We have performed further analysis adjusting the response for the baseline score and this does little to change the message.
Aloe vera has long been recognised as having pain killing and healing properties. It is typically used for topical treatments of wounds, minor burns and skin irritations, but has also been used to treat constipation, ulcers, diabetes and cardiovascular risk factors. Despite a lack of evidence of its therapeutic effects, it is widely taken to control abdominal discomfort including IBS. Recently a trial was conducted investigating the efficacy of AV in patients with UC. The researchers found that after taking AV gel for 4 weeks the UC patients had greater reductions in their colitis and histological scores. No adverse events were recorded.
The mechanism of action of AV is unknown. AV juice is a complex mixture of more than 75 biologically active chemicals. It has proved difficult to isolate a single active ingredient and it is believed that there may be synergy between the different components. Mannose-6-phosphate, a polysaccharide, is one of these components, which for example is capable of activating fibroblast receptor and possibly promoting healing. The NLP formulation used in this study goes through a purification process to remove aloin, and enrich the polysaccharide content. Aloin is known to possess laxative effects and may be responsible for side effects when AV is ingested orally.
This study has demonstrated that AV is well tolerated among patients with IBS, and that whilst the patients were taking it there was some improvement in symptoms, specifically in the IBS score, pain score and proportion of days with pain in the past week, although this was only significant among patients with diarrhoea predominant or mixed symptoms. These patients had all failed previous therapeutic regimes and so were deemed as complex patients. The fact that there was some improvement is therefore encouraging.
We conclude that AV is safe to take and could possibly benefit patients with diarrhoea predominant or alternating diarrhoea and constipated IBS, although we were formally unable to demonstrate this. For these patients there was an improvement in pain (proportion with pain in the past week, pain score and proportion of days with pain in the past week) and bowel habit satisfaction score. These effects were not sustained off treatment. Further studies are warranted to assess the efficacy of taking AV for a longer period of time, with less complex patients and with a more convenient preparation. It remains to be determined whether the treatment would be effective in patients seen in primary care who were less complex and less likely to have failed other treatments.
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We would like to thank 'Natural Living Products' for funding the study.
Dr. Mike Mendall, Mayday University Hospital, 530 London Road, Thornton Heath, Croydon CR7 7YE, UK Tel.: + 44 020 8401 3680 Fax: + 44 020 8401 3606 Email: email@example.com
Int J Clin Pract. 2006;60(9):1080-1086. © 2006 Blackwell Publishing
Cite this: Randomised Double-Blind Placebo-Controlled Trial Of Aloe Vera For Irritable Bowel Syndrome - Medscape - Sep 01, 2006.