Paul Shattock & Dawn Savery
Autism Research Unit, University of Sunderland, UK
Article taken from 1997 Conference Proceedings "Living & Learning With Autism: Perspectives from the Individual, the Family and the Professional"
In the absence of any orthodox, biomedical intervention which has substantial, totally proven, benefits to people with autism, it is natural for parents and carers to explore all possibilities. Some of the ideas and the consequent therapies appear somewhat bizarre and have attracted a degree of denigration from professionals charged with the responsibility of responding to the problems of autism. European professionals, in particular, feel that they cannot be seen to advocate unproven therapies for which they do not have an adequate explanation. Parents and carers, on the other hand, have no such qualms and place themselves at the forefront of experimentation of this type. Additionally, professionals are bound by certain ethical requirements which constrain them from experimentation with such interventions. Parents are, on the whole, in a desperate situation and will try anything which offers to help their children. Many were seduced by the unsubstantiated promises of "Holding Therapy" or "Psychotherapy" and who can blame them? Others have used therapies which, at first sight, seem even more peculiar and inexplicable but, nevertheless, deserve a fair evaluation . Some of these ideas have been around for many years yet remain "unproven". It is the purpose of this presentation to investigate these methods, to explain their theoretical background and to examine the claims made on their behalf.
It has been suggested that the presence of yeast infections in the gut and, perhaps, other parts of the body, could result in autism. Crook (1984) has done much to publicise these ideas and has been ridiculed for them. Human intestines are packed with bacteria which break down certain foodstuffs in such a way that digestion is aided. Under certain circumstances, yeasts, which are fungi, can become established and will utilise foodstuffs to their advantage. The suggestion is that waste products from the yeast will be absorbed from the gut and create havoc within the body inhibiting development of the CNS and interrupting neurotransmission.
A factor which promotes the overgrowth of the gut by yeasts is the use of antibiotics. It is indisputable that when antibiotics are taken to kill pathological, disease causing bacteria, they will also kill those bacteria which are normal inhabitants of the gut. The result is that fungi, which are unaffected by the antibiotics, will be able to multiply ("While the cat's away the mice will play") and effectively take over. It has been commonly observed that children with autism often have a history of earache, ear infections or general hearing problems . In fact some authors (Gordon 1993) are convinced that autism is the result of ear infections and subsequent hearing impairments. Certainly, many children with autism have had grommets (known as tubes in the US) inserted in their ears prior to a diagnosis of autism. In any case, such children will be treated with antibiotics at a comparatively early age and the process could be triggered off by this means. Both the yeast and ear infections are explicable in other ways but the coincidental appearance of autism at around 2 years of age with ear infections and subsequent use of antibiotics cannot be ignored .
Shaw (1995) has isolated a number of metabolites (such as arabinose, tartaric acid and 3-keto-glutaric acid) from the urine of people with autism. Since these substances are, as far as we know, more or less (but not totally) restricted to fungal sources. It is argued that these are evidence of fungal infection. It is suggested that some of these chemicals are sufficiently similar to normal metabolites of human cells, and specifically those involved in Krebs Cycle that this basic metabolic process is disrupted and autism is the ultimate consequence. A variety of methods have been developed to counteract or eliminate the effects of yeasts. Avoid the use of antibiotics and the prescription of antifungal medications. Nystatin and Diflucan have, amongst others, been employed for this purpose and successes are claimed. There remains an absence of published results from clinical trials so such claims are difficult to assess. Avoidance of foods which encourage yeast growth. Refined sugars which are very easily fermentable by yeasts should be avoided; foods which contain yeast ("Marmite" for example) should be eliminated. Replacement with beneficial organisms normally found in the gut. Acidophilus capsules are readily available at "health food stores" or could be naturally augmented by eating yoghurts. It is recommended that they be taken for a month or so to restore the natural gut flora.
Gluten and Casein Free Diets
The fact that the idea to implement these diets has occurred to so many parents independently is, in itself, remarkable. Many parents have felt that bread (or other wheat containing products) or milk and dairy produce are harmful to their children and stimulate behaviours such as hyperactivity . In other children, an allergic response such as a rash, eczema or diarrhoea seems to follow ingestion of dairy produce. For whatever reason, many parents have "discovered" that ingestion of gluten (protein from wheat and other cereal crops) and/or casein (protein from milk) containing products seems to be detrimental to their particular children. The theoretical basis for this has been presented on a number of occasions together with evidence for the presence of potentially bioactive substances in the urine (e.g. Reichelt 1981, Shattock 1991). It is not necessary to rehearse the details at this point but a brief introduction may be appropriate.
The symptoms of autism and the effects of chronic morphine dosages are strikingly similar. Morphine produces an impressive array of effects on the human (and animal) body by mimicking the effects of naturally occurring substances known such as beta-endorphin or the enkephalins. These substances are, chemically speaking, peptides. That is, they are made up of comparatively short chains of amino-acids. Proteins consist of long chains of these acids but during digestion the enzymes in the alimentary canal break these proteins down into peptides and ultimately into basic amino-acids in which form they are absorbed into the body. Certain sequences of the amino acids found in gluten which is found principally in wheat but in modified form in barley, rye and oats, have the same opioid activity as the endorphins referred to earlier. Similarly, peptides with opioid activity are a well known product of incomplete breakdown of casein from milk from humans, cows or other mammalian sources. These products are known as gluteomorphins and casomorphins respectively.
It is proposed that, for some reason, the person with autism lacks the ability to break down these proteins completely and the peptides are able to enter the blood stream from the intestines and thence enter the brain and produce drastic effects on transmission and development. If this is the case, it is totally logical to remove those foods which present difficulties from the diet and numerous parents throughout the world have experimented in this way. The Norwegians have produced the only trial which is anything like satisfactory (Knivsberg 1990) [see associated details].
We are currently engaged in monitoring the urine of a small sample of children with autism who are currently on a gluten and casein free diet and, although full data are not yet available, it would appear that the urinary compounds which we have tentatively identified as being indicative of gluten or casein sensitivities, take a considerable amount of time (several months at least) to begin to disappear from the urine. This is in agreement with unpublished data from Reichelt and co-workers who state that there is often a considerable delay before improvements are noted after removal of the offending products from the diet.
The Use of Enzymes
If it is believed that a particular enzyme system is not functioning correctly, there are a number of logical steps which could be taken. A number of parents, sometimes encouraged by unorthodox practitioners or purveyors of remedies, have made use of enzymes with known proteolytic activity. Such products are available for a variety of purposes (meat tenderisers for example) and are not routinely marketed with autism in mind. It is unclear whether or not the parents utilising these remedies are aware of the "opioid excess theory" and it is equally unclear whether or not there are any beneficial results from their use.
Proteolytic enzymes will, as the name suggests, break down proteins so considerable care is necessary in their use. They could easily act upon the lining of the mouth, for example, if sprinkled upon foodstuffs before ingestion. In is understood that the majority of parents utilising this form of intervention make use of enzymes derived from Papaya plants. This mixture is marketed as "Papain". The structure of potentially opioid peptides from gluten and casein are known; and it would, on theoretical grounds at least, seem more appropriate to utilise the enzymes known as "Bromelain" that are obtained from the pineapple plant. Parents who utilise this approach do not consider it to be an alternative to a gluten or casein free diet but tend to use it as a back up for those occasions when such products have been accidentally ingested. It is worth recording that the use of betaine (Trimethylglycine, TMG) and Pepsin (again a proteolytic enzyme) is a traditional remedy for hyperactivity according to certain literature available in health food stores. However, until the offending peptide materials have been accurately identified, the use of enzyme mixtures must still be considered as speculative. It is hoped that more specific enzymes with appropriate activities will follow the identification of these compounds.
Waring (1993), encouraged and supported by O'Reilly (1993) and other parents, has published data which convincingly demonstrates deficiencies in the sulphur-transferase capabilities of people with autism . They have demonstrated also that this inadequacy is the consequence not of an absence of the responsible enzyme (sulphur transferase) but of the sulphate ions which are needed if proper sulphation is to be accomplished.
If this sulphation process is not functioning satisfactorily there are many possible consequences which may be of relevance in the autistic syndrome. These have been described elsewhere (Waring 1993). It is worth recording that similar deficiencies have been reported in people with migraine, rheumatoid arthritis, jaundice and other allergic conditions all of which are frequently reported as being common in the families of people with autism . Clearly, if there is a deficit of available sulphate in the body attempts can be made to replace it. Unfortunately, sulphate ions are not absorbed from the gut so this route is not a possibility. The main source of free sulphate in the body is the amino acid "cysteine" which is obtained from the breakdown of appropriate protein material and it is this stage which may be faulty in people with autism [see associated details]. Some parents have attempted to combat this by feeding their children with abnormally large doses of cysteine in tablet or powder form but, as far as I am aware, the only result is a high concentration of urinary cysteine. Other parents have introduced other sulphur containing amino-acids to the diet and claim these to be beneficial. Unfortunately the claims are difficult if not impossible to assess since those parents experimenting with this intervention are likely to be experimenting simultaneously with many others. Interestingly, the sulphur containing amino-acid "Taurine" which may be given to patients for this purpose, is reported as having an anti-opioid effect (Braverman 1987).
Since free sulphate is not absorbed orally, parents have been experimenting with alternative routes. One route which is increasing in popularity, is the trans-dermal route. Magnesium Sulphate (Epsom Salts) are placed in the bath water in the hope that the sulphate will enter the body, if not via the back door, via an alternative route. Many parents have claimed benefits from this therapy and some high functioning adults have tried it for themselves. The majority claim positive changes in behaviour but some of the high functioning people have reported increased irritability (and so stopped using this therapy). Any perceived benefits may, of course, be totally unrelated to the sulphate element of the salts. It could be that the Magnesium (which is often supplied as a supplement to people with autism,) is the significant component. The question arises as to whether sulphate ions could enter the body in this way but, if so, it could provide an intellectually satisfying explanation for the long history of the use of spas in the treatment of rheumatic conditions.
Sulphur-transferase activity is important for many biological reactions in the body; some of which may be of relevance in the aetiology of autism. For example, the system is involved in the breakdown of bilirubin and biliverdin, the breakdown products of haemoglobin which are seen where bruising has occurred. It may be pushing speculation a long way but it is possible that the dark rings so often seen around the eyes of people with autism may be evidence of a lack of activity within this system. This system is also required for the breakdown and removal of phenolic compounds, indeed the tests used for estimation of its activity relies upon the conversion of paracetamol to its sulphate. An inadequately functioning system will also result in abnormal metabolism of some neurotransmitters. In particular, serotonin, (5-HT) metabolism will be affected and the appearance of unusual metabolites (such as the hallucinogen bufotenin) could be predicted. Such an observation has been reported (Himwich 1972) but its significance is uncertain.
Other Interfering Foodstuffs
As indicated above, an adequately functional sulphur-transferase system is a prerequisite for the removal of phenolic compounds from the body. Since the availability of available sulphate ions is finite, the same will apply to the ability of the body to deal with such compounds. Thus when certain foodstuffs with high phenolic content are eaten they will utilise the available sulphur-transferase resources of the body and thus exacerbate the problems referred to above.
Many parents have observed that foods such as apples, oranges (and other citrus fruits), chocolate (possibly on account of the phenol flavouring vanillin) and certain other foods will induce severe deterioration in the behaviour of their children with autism. Interestingly, two parents (who must remain anonymous) have contacted me independently and stated that when this situation arises, they have observed that "Cranberry Juice" will markedly reduce or even eliminate these effects. Whether this due to the sulphur content of the juice or some other mechanism or whether the effects are imaginary remains to be determined. Some parents have found that there ate other foodstuffs which can cause problems; in particular they have removed all traces of pigment form the diet of the child (Johnson 1995). Since all of these dietary exclusions tend to be in addition to gluten and casein removal, it is difficult to ascertain precisely which elements of the exclusion are of relevance to any reported improvements.
There has been considerable discussion in the media for many years about the involvement of synthetic pigments, in particular tartrazine in worsening the symptoms of autism. Considerable anecdotal evidence exists for their role in increasing hyperactivity (where autism is not involved). Parental reports suggest that removal of synthetic pigments from the diet have, in the vast majority of cases, made no difference whatsoever.
In some parts of the world it is becoming routine practice to perform basic metabolic tests when a diagnosis of autism is made. In the UK we tend to rely solely on clinical and behavioural observations (with perhaps an EEG being performed). In cases of dyslexia it is reported that there is frequently an abnormally high level of Linoleic Acid (LA) and an abnormally low level of Gamma Linolenic Acid (GLA) which is made in the body from LA. The GLA is required for many purposes in the body such as the manufacture of the prostaglandins but it also has a role in maintaining the integrity of the gut wall. Thus where there is insufficient GLA the permeability of the gut wall increases and partially digested foodstuffs could, as described earlier, pass more easily into the blood stream (Oaten 1993). Given the similarities which exist between autism and some of the symptoms which can often accompany dyslexia, the relevance of these hypotheses is worth considering in the context of autism spectral disorders. It is interesting to note that Zinc is involved in this process of conversion of LA to GLA and this metal is sometimes reported as being low in people with autism (although the literature would suggest otherwise). If low levels of GLA are suspected (or found) it is a simple process to incorporate it into the diet in the form of Evening Primrose Oil or Star Flower Oil .
Some of the earliest attempts to identify metabolic correlates of autism involved estimations of the metal content of serum (and hair). Although the results were difficult to interpret due to large biological variations, certain trends can still be seen. As described above, there are often low levels of zinc and perhaps magnesium and in some people, particularly those with a tendency towards self injurious behaviour, low levels of calcium have been found. The levels of copper have been reported as being high. It may be that these variations are of no relevance whatsoever but, on the other hand, they could be of prime importance. Some practitioners feel that any abnormalities must be corrected before any other therapy can be attempted. They feel that it is pointless whilst the cause of the problems still remain. Although the recommendations are similar the theoretical justifications may not be the same. Please note that the following are my own interpretations of verbal explanations presented to me rather than a distillation of formally published papers. The enzymes responsible for breakdown of peptides have been irreversibly bound to toxic heavy metals which have entered the body. Correction of the electrolytic balance in terms of metals will permit enzymatic activity to restart. Practitioners tend to use low doses of molybdenum salts to assist this process. (Crowell 1995)
Since the enzymes require vitamins and trace elements to function, these should be included in the diet. Thus dietary supplements containing vitamins (of the B group) together with appropriate minerals (Zinc and Magnesium in particular) would be appropriate (Oaten 1993).
Discussion and Conclusion
It is readily conceded that the vast majority of the proposals included here have not been subjected to the rigours of full scientific scrutiny. Rather they are based upon the observations of parents and supportive professionals, and are in desperate need of confirmation or rebuttal. The mechanisms involved are all plausible but that does not make them factual or even relevant to the condition of autism. Nevertheless a comparatively cohesive picture which incorporates many of these aspects can be painted. It is dangerous to suppose that any one mechanism is applicable to all people with autism and it is certainly possible that with different individuals, different aspects come into play and may be of relevance. There are many other aspects (such as the specific roles of vitamins B6 and B12, variations in the pH of the stomach, and the possibilities presented by Enzyme Potentiated Desensitisation) which have not been mentioned but are clearly of relevance.
The metabolic aspects of autism have been largely ignored (particularly in the UK) for a variety of reasons. In part, this is due to the perceived difficulty in correlating any abnormalities with the symptoms of autism. Psychologists and educationalists who have to deal with the problems which autism presents cannot be expected to be familiar with the metabolism of the human body and how this can affect cognitive / mental development. The lack of interest from the Pharmaceutical industry is understandable in that their priorities are determined by the need to produce marketable commodities in the form of drugs. The priorities of parents are different; and so they will continue to attempt to force the pace in these studies. Until then they will continue to utilise any method which carries the promise of helping their children in any way. Even when the explanations may seem far fetched and are not fully understood they are worth exploring.
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