<<Disclaimer: Verify this information before applying it to your situation.>> Comment from Don Kasarda, Albany, CA. Laura Johnson-Kelly complained that no medical professional had replied to her question about guidelines on what is necessary for a challenge. I suspect the reason for a lack of response from the medical professionals has to do with the complexity of the issue. It would take many hours of literature review and writing to put together even a minimally adequate response. In the absence of comment from the medical professionals, however, I will offer some comments from a non-medical professional (me). Back in the mid 1970's, I thought it might be interesting to test celiac patients with bread from a wheat in which geneticists had removed a large block of alpha-gliadin genes (the protein product of which is known as A-gliadin) in the hopes that it might be a non-toxic wheat. At that time, we only knew for sure that gliadins as a whole were toxic and that the A-gliadin fraction was toxic (the only fraction that had been adequately tested). With the collaboration of a highly experienced and expert group at the National Institutes of Health (NCI), which had patients available for participation, we tested the nulli-6A bread (as I named it) by feeding it, and bread from a normal wheat as a control, to 6 well-characterized adult celiac patients. Characterization included biopsy. We fed either 1 loaf per week or 2 loaves per week (corresponding approximately to 4 grams and 8 grams of gluten, respectively, per day). Later we fed them the normal bread. This was almost entirely done with the patients hospitalized, so they were under complete control. The least responsive patient had only very minor symptoms after two weeks on the nulli-6A bread (4 loaves total), but showed mild to moderate villous atrophy when biopsied (biopsy had been normal at start). None of the patients showed severe symptoms on the nulli-6A bread, but all 4 who were biopsied showed at least some deterioration of the mucosa on biopsy. As a control, the normal bread was then fed to 4 of the same patients for 1 week (1 loaf) and all experienced diarrhea by the end of the week. Only 1 patient was biopsied at this point and showed mucosal damage. At that time, standard antibody screening had not been developed, so studies of antibody development upon challenge were not done. I should indicate that, unfortunately, when a paper on this work was submitted to the journal Gastroenterology, the referees and editor rejected the paper and so it has never been published. Personally, even after all these years, I don't think there was any adequate reason for rejection of the paper, which contained some very valuable information about gluten challenge with controlled amounts of bread only, as opposed to just putting the patient on a normal diet. Any defects in the presentation of the work in the manuscript could easily have been remedied, but rejection is not unusual in the world of scientific publishing. Some highly arbitrary decisions are made by very few people. Some junk gets published and some good work does not. We concluded that the nulli-6A bread was likely to be of lower toxicity than normal bread, but still definitely toxic. With our knowledge now that all gliadins are toxic, this would be expected. In another study that I know of, 0.5 gram of gluten per day (a relatively small amount) was fed to 4 adult patients for about 6 weeks. Two patients showed villous atrophy at the end of the period and the other two showed signs of infiltration by intraepithelial lymphocytes, which is considered to the be the very first sign of mucosal change in gluten challenge. In a paper published in 1988 by Ansaldi et al., they reported that of 13 children placed on a normal gluten-containing diet (Italy), 9 had symptoms at the end of one month and 12 showed a flat mucosal biopsy at that time. Finally, however, there are some reasonably well documented cases where properly diagnosed patients (usually children) have gone back to a normal diet for years before relapsing, as indicated by regular biopsies. Being aware of much of the literature involving challenges, I think it is extremely difficult to specify the amount of gluten and the time required for proper challenge because of the enormous variability among patients. Perhaps, however, the information I have given will be of some help to patients contemplating a gluten challenge. I am surprised by the number of people who write to the list about instant reactions to gluten. My long-time impression of many studies involving challenge has been that most celiac patients do not respond with immediate distress within hours of first eating wheat. Perhaps this is incorrect. Perhaps there has been a strong self-selection factor involved in that people who have severe reactions are not likely to volunteer for or agree to gluten challenge studies. There may also be a self selection factor for BBS communications in that the people who have the greatest problems and odd symptoms may tend to communicate to the list to a greater extent than those who have few problems.