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The following was written by Donald D. Kasarda who is a research chemist in the Crop Improvement and Utilization Research Unit of the United States Department of Agriculture. If you have any questions or comments regarding the piece, you can address them to Don at: kasarda@pw.usda.gov. The connection with wheat (and rye and barley) wasnt recognized until the 1950s - (a)nd it wasnt until the 1960s that intestinal biopsies began to become commonly used in the diagnosis of celiac disease. With regard to the harmfulness of barley malt, the situation is complicated. I will give you my best shot with the qualification that the ideal experiments have not been done and a definitive statement is not possible at this time. Because barley malt is made from barley grain that has been germinated it is reasonably certain to be less toxic than barley itself. The hordein proteins and starch in the endosperm of barley grains, like the equivalent gluten proteins and starch in wheat, are there for storage purposes. In a sense, they provide food for the new plant upon germination. In order to use the hordein proteins, the grain releases and generates enzymes upon germination that break down the storage proteins into their constituent amino acids. The problem is that the process is not complete during a short germination, so some peptides (short pieces of the proteins) remain intact in malted barley. There is experimental evidence for this. The resulting mix of peptides is highly complex. We know from work described in the scientific literature that relatively small polypeptide chains can still retain activity in celiac disease and we know something about a few sequences that seem to be harmful. But we probably dont know all the sequences that are harmful and we havent put our fingers on the common theme that gives rise to the activity in celiac disease. So the question arises as to whether or not the remaining sequences in malted barley are harmful. The possibilities that come to my mind are: There are sufficient remaining harmful peptides (with sizes including approximately 12 or more amino acid residues) to give a significant activity in celiac disease to barley malt (remember though that barley malt is usually a minor component of most foods in which it is used and processing might decrease the amount of harmful peptides in a malt product); There are traces of these peptides, but they are sufficiently minimal so as to cause no discernible harm; or The key harmful amino acid sequences are completely destroyed by the enzymes during germination (I can speculate that there might be an important enzyme, very active, in germination that clips a key bond in active sequences, thus reducing the concentration of those active sequences to almost nil while still allowing non-harmful peptides to exist; no evidence exists for this speculation, but it could be used as a working hypothesis for experimentation). There is no completely solid evidence for or against there being a threshold of gluten consumption below which no harm, or at least no lasting harm, occurs and above which definite harm occurs (but see my previous post to the list on starch/malt question). This is a difficult area to study where zero consumption is being approached and the arguments that come up are at least similar to those that have arisen in regard to the question of whether or not there is a minimal level of radiation exposure below which no harm is caused, but above which there is harm that increases with dosage. Accordingly, celiac patients must choose arbitrarily the path they feel comfortable with. Here are some references that deal with the question of peptide toxicity. It is not a simple situation: Shewry, P. R., Tatham, A. S., Kasarda, D. D. Cereal proteins and coeliac disease. In Coeliac Disease, Ed. M. N. Marsh. Blackwell Scientific, London 1992;pp. 305-348. Kasarda, D. D. Toxic cereal grains in coeliac disease. In: Gastrointestinal Immunology and Gluten Sensitive Disease: Proc. 6th International Symp. On Coeliac Disease, C. Feighery and C. OFarrelly, eds., Oak Tree Press, Dublin 1994;pp. 203-220. Wieser, H., Belitz, H.-D., Idar, D., Ashkenazi, A. Coeliac activity of the gliadin peptides CT-1 and CT-2. Zeitschrift fur Lebensmittel-Untersuchung und-Forschung 1986;182:115-117. De Ritis, G., Auricchio, S., Jones, H. W., Lew, E. J.-L., Bernardin, J. E., Kasarda, D. D. In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease Gastroenterology 1988;94:41-49. Fluge, 0, K. Sletten, G. Fluge, Aksnes, L., S. Elsayed. In vitro toxicity of purified gluten peptides tested by organ culture. Journal of Pediatric Gastroenterology and Nutrition 1994;18:186-192. Sturgess, R., Day, P., Ellis, H. J., Lundin, K. A., Gjertsen, H. A, Kontakou, M., Ciclitira, P. J. Wheat peptide challenge in coeliac disease. Lancet 1994;343:758-761. Marsh, M. N., Morgan, S., Ensari, A., Wardle, T., Lobley, R., Mills, C., Auricchio, S. In vivo activity of peptides 31-43, 44-55, 56-68 of a-gliadin in gluten sensitive enteropathy (GSE). Supplement to Gastroenterology 1995;108:A871.

The following was written by Donald D. Kasarda who is a research chemist in the Crop Improvement and Utilization Research Unit of the United States Department of Agriculture. If you have any questions or comments regarding the piece, you can address them to Don at: kasarda@pw.usda.gov. Most sprouted wheat still has gluten or gluten peptides remaining. Although the sprouting begins enzymatic action that starts to break down the gluten (a storage protein for the plant) into peptides and even amino acids. Generally this is not a complete process for sprouts used in foods so some active peptides (active in celiac disease) remain.

Celiac.com - 07/24/2001 Study: Holmes, Prior, Lane, et. al. Malignancy in Coeliac Disease - Effect of a Gluten-Free Diet Gut 1989; 30: 333-338 Comments Regarding the Study to the List (January 8, 1997): I would like to suggest that you check out some of the information on malignancy and celiac disease, especially lymphoma. One of the studies established three categories: One for those who adhere to the diet strictly; one for those who follow the diet, but not very strictly; and one for those who do not follow the diet. The first group, after 5 years, shows a significant reduction in risk. In fact, it is quite close to the risk experienced by members of the general population. The second group does experience some reduction in risk, but it remains closer to the rate of malignancy in untreated celiac disease. The third group has a very high risk of malignancy. Response by Donald D. Kasarda (January 9, 1997 - Donald D. Kasarda is a research chemist in the Crop Improvement and Utilization Research Unit of the United States Department of Agriculture): I point out that the people in the first group, which supposedly was adhering to a strict gluten-free diet, were likely to have been including foods made with wheat starch in their diet because that was, and is, common in England where the study was carried out. I have asked several celiac researchers in England if I am correct in this assumption. They agreed that I am. Therefore these people in the strictly gluten-free group were likely to be eating a small amount of gluten each day. The amount is unknown because we dont know the amount of gluten in the starch (this varies according to the manufacturer and possibly according to lot) nor which subjects ingested how much starch. The apparent small increase in cancer risk for the first group was not statistically significant for those who had been on the diet more than 5 years. In the group with a normal diet, the relative risk of lymphoma was increased 78 fold, but it should be pointed out that the incidence of lymphoma of the gastrointestinal tract in the normal population is rather low. For the 210 patients in the study, the cancer morbidity was expected to be 0.21. For the 46 patients in the normal diet group, 7 cases of lymphoma were observed. For the 108 patients on the strict gluten-free diet, 3 cases of lymphoma were observed. The statistical significance of the numbers is weak because of the relatively small numbers of patients involved. These are extremely valuable and well-done studies. No criticism is intended. To arrange a study with larger numbers will be extremely difficult although a group in Leiden (The Netherlands) is trying to arrange such a study. I have no quarrel with those who wish to play it safe, but I dont think we can say for sure that small amounts of gluten in the range of a milligram to a few milligrams per day are harmful on the basis of any scientific study of which I am aware. They may be, or they may not be. I offer these comments only with the intent of providing as much information to celiac patients as possible so that they can make informed decisions. If anything I have said is incorrect, I hope someone will point out my errors on the net. Don Kasarda, Albany, CA FYI: According to the calculations made with Don Kasarda in Nov 1995, 0.1 grams = 100 milligrams is about one-50th of a slice. Therefore, 10 milligrams is about one-500th of a slice of bread.

The following was written by Donald D. Kasarda who is a research chemist in the Crop Improvement and Utilization Research Unit of the United States Department of Agriculture. If you have any questions or comments regarding the piece, please address them to Don at: kasarda@pw.usda.gov The work from Prof. Auricchios laboratory (Troncone et al.) in Naples is certainly of interest and I shall look forward to seeing the details, but I will just point out for the sake of balance that studies with patients who ingest, or have instilled into their intestines, the substance to be tested represent the gold standard and in vitro testing (that is, in glass, or in the test-tube), while valuable, does not carry as much weight. The results from the Finnish group and from Dr. Feigherys group (not yet published), Dublin, Ireland, are very impressive. The results based on in vitro testing would have to be truly exceptional to undermine the excellent work that has been done on the safety of oats. So, we shall have to wait and see, but I doubt there is reason to be overly concerned just yet.

The following was written by Donald D. Kasarda who is a research chemist in the Crop Improvement and Utilization Research Unit of the United States Department of Agriculture. If you have any questions or comments regarding the piece, please address them to Don at: kasarda@pw.usda.gov I have not seen the NEJM article from the Finnish group although I had heard second hand about a meeting presentation of the work. I have no reason to doubt the results. I am co-author of a paper from an independent study carried out by the laboratory of Dr. Conleth Feighery, Trinity College, Dublin, Ireland, and this study (paper submitted) also supports the lack of toxicity for a PURE oats sample. I will remind people that it is EASY for oats to be contaminated with wheat both in the field and in processing. I have no reason to think that oats must be limited to small amounts, but, of course, it isnt good to focus ones diet too much on a single food, so moderation of the normal sort is probably good. There are bound to be some people who are sensitive to oats, possibly through an allergic reaction to one component or another (just as there are people allergic to rice), but this sensitivity, on the basis of current results, seems unlikely to be celiac disease in its strict sense. The term gluten in celiac disease is not used in a proper sense (in that sense it is present only in wheat), but rather as a shorthand term for peptides derived from prolamins (proteins) that include the harmful amino acid sequences found in wheat. These peptides set off (in an unknown way) a series of reactions that ultimately may lead to flattening of the mucosa, malabsorption, and possibly other effects as well. Wheat, rye, and barley have prolamins that contain the toxic sequence(s). The finding that oats is (are?) not toxic indicates that the key sequences are NOT found in the avenins, the prolamins of oats. Comparison of the amino acid sequences of avenins and gliadins yields clues to possibly important differences and I am pursuing the significance of these differences. I am currently trying to find sources of pure, uncontaminated oats, and will post them here as soon as they are available. -Scott The oats used in the Irish study (see Doctor #2 below) came from a company called Peter Kölln in Germany. The oats from this company were tested and found to be safe. Their address is: Peter Kölln Postfach 609 D-25306 Elmshorn Germany