A clinically significant improvement in IBS symptomatology was observed in patients eliminating foods to which they were found to exhibit sensitivity, as identified by an ELISA test for the presence of IgG antibodies to these foods. The number needed to treat of 9 for the group as a whole and 2.5 for patients closely adhering to the diet are both considerably better than the value of 17 achieved after three months of treatment with tegaserod,32
a drug that has been recently licensed in the USA for use in IBS. IBS symptom severity and global rating scores were chosen as primary outcome measures in this study as they represented the most direct measure of clinical improvement in this condition based on patient self assessment. Rather than using the traditional method of classifying global improvement as any value exceeding adequate relief of symptoms, we used a much stricter definition requiring patients to report symptoms as being either “better” or “excellent” compared with pretreatment levels. Despite this, the diet still achieved a significant improvement. However, as might be expected, the placebo response using this end point was somewhat lower than that usually reported in IBS treatment trials which have used less demanding criteria. The observation that patients on the sham diet also improved, although to a lesser extent, emphasises the importance of conducting double blind randomised controlled trials of such non-drug interventions in order to avoid overestimating their potential.
Most patients with IBS have attempted at least some form of dietary modification, which in some cases can be very extreme. Conflicting results have been reported using exclusion diets4,5,33–36
and this approach also suffers from the limitation that it has to be empirical. Thus potentially offending foods can only be identified after their elimination and subsequent reintroduction. This time consuming process would be much reduced if the offending foods could be identified beforehand. Attempts to do this using IgE antibodies have been disappointing8–10
but the results of this study suggest that measuring IgG antibodies may be much more rewarding. The response to the IgG based diet in our trial did not correlate with atopic status, the prevalence of which was found to be no greater than that occurring in the general population.37
The observation that adherence to the diet is critical in determining a good outcome in the “true” diet group but not the “sham” group is indicative of the fact that the diet is an “active treatment” which if not adhered to, does not seem to have an effect. This notion is further supported by the observation that a significantly greater deterioration was observed in subjects in the true diet group compared with those in the sham group when they reintroduced eliminated foods at the end of the diet phase of the trial. Furthermore, the improvement of 98 in the symptom severity score in those fully adherent in the true diet group is well above the value of 50, which is regarded as being of clinical significance both in validation studies24
and clinical practice.26–28
It was interesting to note that patients exhibiting a greater number of sensitivities, as determined by the IgG test, experienced a greater symptom reduction if they adhered to the true but not the sham diet.
There is currently considerable interest in the concept that at least in some patients, IBS may have an inflammatory component.38–42
Most of the work in this area has centred on post dysenteric IBS, with gut pathogens being viewed as the initiators of this process which can be identified by subtle changes on histology.38
However, if, as indicated in this study, IgG antibodies to food are important in the pathogenesis of IBS in some patients, they too may be of relevance. Not all patients exhibiting histological features consistent with post dysenteric IBS give a history of a previous dysenteric illness. This is usually assumed to be due to the fact that this has been forgotten by the patient but our results may suggest an alternative mechanism for immune activation and inflammation without the need for prior infection.
It is now well recognised that up to 70% of patients with IBS have evidence of hypersensitivity of the rectum,43
which probably extends to involve most of the gut in many individuals.44
It is possible that this hypersensitivity renders patients more reactive to a low grade inflammatory process which would not necessarily cause symptoms in a normal individual. This would explain why excluding foods to which patients have IgG antibodies might be particularly beneficial in IBS despite the fact that these antibodies may also be present in the general population. Indeed, if this mechanism is particularly important in IBS, it might be anticipated that IgG food antibodies would be relatively common in this condition, as was the case in our study.
Many patients with IBS would prefer a dietary solution to their problem rather than having to take medication, and the economic benefits of this approach to health services are obvious. It is well known that patients expend large sums of money on a variety of unsubstantiated tests in a vain attempt to identify dietary intolerances. The results of this study suggest that assay of IgG antibodies to food may have a role in helping patients identify candidate foods for elimination and is an approach that is worthy of further biomedical and clinical research.