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Gulf War Syndrome: some observations

Paul Shattock, Autism Research Unit
University of Sunderland, UK

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Our interest in “Gulf War Syndrome” (GWS) was fired, initially, by the coincidence of some of the symptoms we had seen in subjects presenting with GWS and which we had seen in autism and associated disorders. Our hypotheses on GWS are based upon our work with autism and the “Opioid Excess Theory” to which we subscribe. Our work will be explained in terms of autism and then extended to demonstrate that the same principles could be relevant in GWS.

The symptoms of autism are, we believe, the consequence of metabolic abnormalities (Shattock 1991). Normally, proteins are digested in the gut and broken down into amino-acids. During this process, and for a comparatively limited period of time, intermediate compounds, known as peptides, are formed. These peptides, typically of 2 - 8 amino-acids, are usually biologically inert but some are known to have marked biological activity. Thus, various casomorphins (from the milk based protein casein) and gliadinomorphins (from gluten from wheat and some other cereals) will be produced. The activity of these compounds is, as their names would imply, opioid in nature.

Under normal conditions, only a small percentage of these compounds would cross from the lumen of the gut into the blood stream and a small proportion of these would cross the Blood-Brain Barrier (BBB) and enter the Central Nervous System (CNS). Once in the CNS they would result in opioid activity. This could either be the result of the direct opioid activity of the molecule or the fact that the molecule would form a ligand for the enzymes which would normally break down the naturally occurring opioids, such as the endorphins and enkephalins, so that these would persist for much longer than normal. Whatever the source of the opioid activity, these compounds would affect (and usually inhibit) transmission in all of the main neurotransmission systems. Perception; cognition; emotions; mood and even motor activities would be affected by the presence of these compounds.

In particular, the executive control functions would be affected (inhibited) with the result that aggression and difficulties in controlling temper as well as speech would be consequent. Both of these abnormalities are clearly evident in the subjects with GWS with whom we have come into contact. The effects of GWS on bowel function would also seem to confirm that some form of enteropathological effects are present.

Since opioids are intimately involved in the immune system, elevated levels of these compounds would have profound effects on this system and predispose to infections of all sorts. the implementation of a severe active immunisation programme would, under these conditions, have very predictable and deeply unfortunate consequences. We suspect (and have some unpublished evidence to suggest that) some of the symptoms seen in some veterans in the Gulf War could result from lingering disease states caused by a grossly inflated requirement made upon a subject with a compromised immune system.

We have identified a key marker compound (trans-indolyl-3-acryloylglycine, IAG) which is a (the) major component in some 75-80% of people with autism. This compound has no opioid activity itself. We have determined the structure of this compound and feel that it most likely represents the detoxified version of a compound which could have severe but subtle consequences. One of the major actions of this compound would be to render all membranes very permeable. Thus, the gut wall and the BBB would become much more permeable.

This compound is a major component in some 20-25% of the normal, asymptomatic (as far as we know) population. However, it is either the largest or second largest component in each of the (15 so far) subjects reporting GWS we have examined. We do not know the source of the compound but believe that it could be the result of Organo Phosphorous compounds upon the normal metabolic processes. Alternatively it could be there as a normal metabolite in those individuals with a predisposition to these problems.

We see IAG as being indicative or, more likely, involved in the causation of increased permeability of membranes. The active compounds are peptides which are exogenously derived from gluten and casein.

For many years, following advice from a variety of sources or based upon their own observations, parents have been experimenting with diets devoid of gluten and casein in an attempt to ameliorate the symptoms of autism in their children. We are currently conducting a pilot study using such interventions and the preliminary results would appear to be very encouraging and supportive of the results published by Reichelt (1991). For this reason we have suggested to a number of individuals presenting with GWS that they experiment with a diet which is devoid of gluten and casein. The hypothesis is that by doing so, the symptoms would be ameliorated.

No formal study has been performed but it is our very clear impression that those individuals who have experimented in this way, entirely at their own expense, have shown impressive improvements in many diverse ways including speech and aggression control and bowel function.

There are many other interventions which these hypotheses would indicate as being helpful in dealing with the syndrome but, if nothing else, our studies convince us that removal of gluten and casein containing foods is worthy of consideration in cases of GWS.

Reichelt KL,  Knivsberg A-M, Lind G, Nodland M. (1991) “Probable Etiology and Possible Treatment of Childhood Autism” Brain Dysfunction  4. 308-319

Shattock P, Lowdon G. (1991) “Proteins, Peptides and Autism Part II: Implications for the Education and Care of People with Autism” Brain Dysfunction 4. 323-334.

Please note that any decision to try dietary intervention of this type is only recommended with
the support of both a General Practitioner and a state-registered dietitian / nutritionist.

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