SULPHATION ISSUES Many children with autism spectrum disorders appear to be sensitive to compounds known as phenols that are present in certain foods. The foods that contain the greatest concentration of phenols are: • Apples • Oranges and other citrus fruits • Bananas This sensitivity to phenols appears to be linked to the Phenol sulfotransferase (PST) enzyme system, which plays an important role in Phase II liver detoxification. Normally, PST is involved in a process called sulfoconjugation, whereby the potentially harmful phenols are attached to sulfate ions and thereby eliminated from the body. Researchers have found that the action of PST is compromised in many children with autism.1 Rosemary Waring, a researcher in England, conducted a study in which it was found that the PST enzyme system was functioning at sub- optimal levels in more than half of the autistic children tested.2 This does not so much appear to be due to an actual deficiency in the PST enzyme itself, but rather to a deficiency of sulfur in the bloodstream.3 When there is a shortage of available sulfate in the body, there are not enough sulfate ions available to ensure the adequate functioning of the PST enzyme system. Consequently, phenolic compounds are not being adequately excreted and may build up in the brain and nervous system, which can in turn interfere with the action of neurotransmitters. This is why the consumption of phenol containing foods can have such adverse effects on areas like behavior, mood, and neurological function. In addition to its detrimental effects on neurotransmitter function, impaired sulfation may also play a role in some of the gastrointestinal problems seen in children with autism. This is because sulfation is normally necessary for the production of peptides, bile acids, CCK, Secretory IgA, and possibly secretin.4 Since all of these are involved in supporting the health and proper functioning of the digestive system, a sulfation deficit may be one explanation for the maldigestion and malabsorption that are common problems for children with autism. Addressing this sulfation deficit is essential not only as a means of correcting food sensitivity and gastrointestinal dysfunction, but also for ensuring that the liver’s Phase II detoxification pathways are functioning as optimally as possible. Signs And Symptoms A number of clues may be present to suggest the presence of a sulfation deficit and PST enzyme weakness in a child with ASD.5 These include the following: • Sensitivity to phenol containing foods, including behavioral, neurologicial, and gastrointestinal symptoms • Migraine headache, or history of migraines in a family member • Red face • Red ears • Dark circles under the eyes • Abdominal bloating • History of colic in infancy • Chronic runny nose or post-nasal drip • Eczema • Asthma • Excessive thirst • Perspiration during sleep (night sweats) • Unexplained high fevers with or without vomiting • Bad odor with perspiration Possible Causes As discussed above, compromised sulfation is usually the result of a deficiency of sulfate ions in the body, leading to a weakness in the Phenol sulfotransferase enzyme system. Diagnosis Many parents suspect the presence of sulfation problems based on a sensitivity to phenolic foods and the presence of one or more of the signs and symptoms listed above. A more accurate assessment of a child’s sulfation status may be made through the following laboratory tests: 1. Liver Detoxification Profile With PST Assessment This assessment for Phenol sulfotransferase is part of the general Liver Detoxification Profile and requires the use of acetaminophen (Tylenol) to measure the activity of PST via urine markers. 2. MHPG Glucuronide / MHPG Sulfate This urine test measures the ratio of two metabolites, MHPG Glucuronide and MGPH Sulfate, to provide an indication of sulfation status. Treatment Approach 1. Dietary Interventions An elimination diet that restricts the child’s intake of phenol-containing foods (see list of foods above) can be both diagnostic and therapeutic in Researchers have found that the action of PST is compromised in many children with autism.1 Rosemary Waring, a researcher in England, conducted a study in which it was found that the PST enzyme system was functioning at suboptimal levels in more than half of the autistic children tested.2 This does not so much appear to be due to an actual deficiency in the PST enzyme itself, but rather to a deficiency of sulfur in the bloodstream.3 When there is a shortage of available sulfate in the body, there are not enough sulfate ions available to ensure the adequate functioning of the PST enzyme system Eliminating these foods for a period of time while undergoing the therapies mentioned below is helpful, followed eventually by a careful and gradual reintroduction of the foods in question. With the proper therapy, some children will once again be able to consume dietary phenols, while other children do better with continued avoidance of these compounds in their diet. 2. Oral Supplementation Since PST weakness is usually due to a deficiency sulfate ions in the body, the most logical and clinically useful approach to correcting this enzyme insufficiency is to supplement with nutrients that provide the system with available sulfur. Many parents and physicians have attempted to correct this sulfur deficiency through oral supplementation with sulfur-containing nutrients. This can provide some improvement in symptoms but may not correct the problem completely because free sulfate is poorly absorbed from the gastrointestinal tract. Nonetheless, some positive clinical benefits have been reported from supplementation with the following sulfur containing compounds: • Methylsulfonylmethane (MSM) • The amino acid Cysteine (Lcysteine or N-acetyl cysteine) • The amino acid Taurine 3. Transdermal Supplementation Because of the apparent inadequacy of oral sulfur supplementation, the focus has recently shifted to the possibility of transdermal (through the skin) administration. In general, parents are reporting much more positive benefits from this transdermal administration than from oral supplementation, although the two may also complement one another. The two most common ways to boost sulfur levels transdermally are: • Epsom Salt Baths: This is an easy and inexpensive way to provide sulfur that can be absorbed through the skin. Epsom salts are actually magnesium sulfate, and appear to have their positive benefits through both the magnesium and the sulfate components. Parents have reported improvements in their child’s language, behavior, mood, cooperation, sleep patterns, and motor skills when administering these baths on a daily basis. A general dose is 1/2 cups of Epsom salts per bathtub full of water. One drawback appears to be the development of dry, irritated skin in some children, which may be offset by adding 1/2 cup of Baking Soda to the bath. - Magnesium Sulfate Cream: Recently, some laboratories and compounding pharmacists have developed magnesium sulfate cream to reproduce the effects of Epsom salt baths in a form that is easier to administer. While the use of this therapy is relatively new, both physicians and parents have found very positive results with using the transdermal form of magnesium sulfate. More information on dosage is available in the section of Chapter 5 on Supplements. REFERENCES - Sulfation Deficits 1 Alberti A, Pirrone P, Elia M, Waring RH, Romano C. “Sulphation deficit in ‘low-functioning’ autistic children: a pilot study.” Biol Psychiatry 1999 Aug 1;46(3):420-4. 2 Waring RH, et al. “Biochemical parameters in autistic children.” Dev Brain Dys 1997;10:4043. 3 Waring RH, Klovrza LV. “Sulphur metabolism in autism.” J Nutr Env Med 2000;10:25-32. 4 Shattock P, Whitely P. “Back to the future: an assessment of some of the unorthodox forms of biomedical intervention currently being applied to autism.” Paper presented at the Durham Conference, 1995. Available on the website of the University of Sunderland’s Autism Research Unit: (www.osiris.sunderland.ac.uk/autism ) 5 Baker, S.M., M.D. and Pangborn, Jon, Ph.D. Biomedical Assessment Options for Children with Autism and Related Problems. ©1999, Autism Research Institute, p. 22. Available from the Autism Research Institute website ( www.autism.com/ari /).