Autism has been defined as a behavioral syndrome excluding biology as part of the definition or the prognosis. In truth, autism is a whole body, multi-system, metabolic disorder. One of the systems affected is the gastrointestinal system. 

Research shows that more than 80% of children on the autistic spectrum have GI symptoms, food allergies, and maldigestion or malabsorption issues. Many adults with autoimmune disorders have similar gut problems, some for the majority of their lives. It is obvious from talking to parents that GI problems are a major concern in children with autism. Antifungal use, both prescription and alternative remedies, is a common topic. Parents have tried anti-yeast diet and natural remedies, but they do not seem to solve the microbial problems these children have. Prescription drugs are more helpful. Many parents will pursue chelation for their children, but are unable to do so because of their inability to get the gut pathogens under control. Altered intestinal permeability, known as ‘leaky gut syndrome,’ is common in many autistic patients. Leaky gut means that there are larger than normal spaces present between the cells of the gut wall. When these large spaces exist in the small intestine, it allows undigested food and other toxins to enter the blood stream. When incompletely broken down foods enter the body, the immune system mounts an attack against these “foreign” substances which manifests as food allergies and sensitivities. The release of antibodies triggers inflammatory reactions when the foods are eaten again. The chronic inflammation lowers IgA levels. Sufficient levels of IgA are needed to protect the intestinal tract from certain bacteria and yeast. The decreasing IgA levels allow for even further microbe proliferation in the intestinal tract. Vitamin and mineral deficiencies are also found due to the leaky gut problem. 

In order to treat this gut problem, the diet must be cleaned up first.  In our clinical work we recommend an organic diet, not one that is genetically modified or engineered.  The “right” diet can be:

GFCF, soy and corn free
Specific Carbohydrate Diet (SCD)
GAPS diet
Low phenol
Low Salicylate
Low Oxalate
Reduced glutamate/aspartate diet
Ketogenic diet
Allergy/sensitivity elimination/rotation diet

One of the problems created by the vitamin deficiencies that occur within a leaky gut is vitamin B12 deficiency. B12 absorption is inhibited early in this process as microbes enter the small intestine because B12 is absorbed in the ileum, the last segment of the small intestine. Vitamin B12 is essential for the metabolism of fats and carbohydrates and the synthesis of proteins. Vitamin B12 is involved in the manufacture of the myelin sheath, the fatty layer that insulates the nerves in the brain. It is also essential for the formation of neurotransmitters and repair of damaged, flattened microvilli in the intestine. With sufficient B12 and folic acid in the bloodstream, the intestinal cells and microvilli can rejuvenate every 3 to 4 days. However, most children in the autistic spectrum have metabolic abnormalities in folate and B12 metabolism and cannot utilize these vitamins in the natural state. The latest studies have shown that 75% of patients on the autism spectrum and their mothers have cerebral folate antibodies which interfere with the metabolic pathways affecting neurotransmitter and glutathione production, among others. In the normal intestinal tract the small intestine and stomach are not inhabited by bacteria. When the bacterial balance in the colon is lost or when the gut is never colonized with ‘good’ bacteria, the microbes can migrate into the small intestine and stomach, hampering digestion. They compete for nutrients and their waste products overrun the intestinal tract. Yeast has the ability to produce toxins that actually allow them to bore into the intestinal wall. They also produce toxins such as organic acids which can damage the intestinal wall. Bacterial growth in the small intestine destroys enzymes on the intestinal cell surface, which prevents carbohydrate digestion and absorption. The final stage of carbohydrate digestion takes place at the microvilli. Enzymes embedded in the microvilli break down complex carbohydrates so they can be absorbed properly and enter the blood stream. When the microvilli are damaged, the last stage of digestion cannot take place. At this point only monosaccharides, or simple carbohydrates can be absorbed because of their single molecule structure. The complex carbohydrates can cause overgrowth of bacteria and yeast. In the small intestine, the body should absorb the nutrients needed from what is eaten. In the case of malabsorption, the undigested carbohydrates left in the small intestine cause the body to draw water into the intestinal tract. This pushes undigested carbohydrates into the colon where the microbes can feed on them. This allows further proliferation of the unwanted microbes and continued increase in malabsorption problems.autistic children have significantly lower intestinal carbohydrate digestive enzyme activity. 

Cleaning up the Diet

Avoiding genetically modified foods such as soy, corn, potatoes which can lead to unexpected allergic reactions and changes in the digestive tract.
Avoiding genetically engineered foods containing certain bacteria that is lethal to living cells.
Gluten – while celiac testing is often negative, it is known that gluten can set off distinct reaction in the intestines and the immune system even in people who don’t have celiac disease. Gluten sensitivity and gluten sensitive enteropathy have been associated with ataxia, migraine, dementia, seizures, visual and auditory disturbances, hypotonnia, depression, anxiety, fibromyalgia and chronic fatigue.
Bovine casomorphin, similar to opiates has been shown to affect the brain maturation, decrease cysteine, glutathione and methionine levels in neuronal cells.  Milk-free diet affects folate receptor autoimmunity in cerebral folate deficiency syndromes which occurs in 75% of autistic patients and their mothers.
Phenols affect sulphation which can lead to metabolic dysfunction (Waring, 1999). This may result from an enzyme deficiency or reduced enzyme activity.
Salicylates, found in foods with artificial dyes, food preservatives, flavorings, sweeteners, are a natural plant toxin found in most stone fruits, berries, citrus fruits, some vegetables, honey, yeast extracts and almonds.  Dr. Benjamin Feingold (1975) reported that foods and additives containing high salicylates can cause hyperactivity in children.  Salicylate sensitivity can result in headaches, lack of concentration, breathing problems, hyperactivity, electrolyte abnormalities, gastrointestinal problems.  Studies by the American Academy of Pediatrics (2008) support the idea that a wide variety of chemicals can results in neurobehavioral toxicity and some children will benefit from a preservative-free, food coloring-free diet.
The Feingold Diet prohibits foods containing naturally occurring and synthetic forms of salicylates, for example berries, stone fruits, citrus fruits, except for lemon, certain apples, almonds, cucumber, tomato, peppers, yellow, red, blue and other dyes.
Oxalate, a highly reactive molecule that is abundant in many plant foods.  When in human cells in high amount, oxalates can lead to oxidative damage, depletion of glutathione, ignition of the immune systems inflammatory cascade and the formation of crystals which seem to be associated with pain and prolonged injury (Owens).  When there is leaky gut, prolonged diarrhea or constipation, excess oxalate can be absorbed from the GI tract and become a risk to other cells in the body.  Oxalates are found in chocolate, soy bean, black bean, kidney bean, navy bean and pinto bean, sesame oil, blackberries, currants, dates, figs, oranges, raspberries, buckwheat, millet, rye, oregano, cinnamon, black pepper, almonds, cashews and other nuts.
Specific Carbohydrate Diet (SCD), pioneered by Gottschall, advocates the elimination of carbohydrates which require numerous digestive processes, resulting in an environment that supports overgrowth of intestinal yeast and bacteria.  SCD deprives the microbes in the intestine of the food they need to overgrow.  Pre-digested carbohydrates in the diet can maximally nourish the individual without over-stimulation of the intestinal microbial population.
GAPS (Gut and Psychology Syndrome) Diet prohibits all grains, gluten, casein and corn, phenol and salicylate containing foods.  It prohibits starchy vegetables and food produced from them, sugar, starchy beans, lactose and lactose containing foods such as milk, dried milk, yogurt and sour cream.

Toxins involve more that metals.  They can be pesticides, petrochemicals, i.e. PCB’s, Industry by-products (pthalalates), plastics (bisphenol-A), disinfection by-products (chloramines). Exposure to heavy metals may be from fluorescent lights, seafood, dental amalgams, paint, vinyls, jet and automobile fuel exhaust, contaminated water and foodsand controversially from vaccine adjuvants

Heavy metal detoxification is accomplished using a procedure known as chelation. Studies have shown that patients on the autistic spectrum are at least 50% more toxic than those who are neurotypical and cannot detoxify heavy metals. Other patients with autoimmune disorders including heart disease, chronic fatigue syndrome, fibromyalgia and rheumatoid arthritis mayexperience the same problems.The usual metals found are mercury, lead, arsenic, aluminum, cadmium, nickel, antimony, tin, tungsten and uranium! Chelation has been described in pediatric and adult medical literature as the treatment of choice to remove toxic metals from the body once removal from the source of exposure has been accomplished. Different chelating agents have the ability to bind to different types of toxins, all of which are present in the air we breathe, the water we drink, the soil and the dust we come in contact with every day. These toxins interfere with the manufacture of glutathione, the major antioxidant (detoxifier) in our body. They are also toxic to brain cells and neurons. 

Chelation is performed in our facility by our physician or staff in a comfortable setting. It is performed in a one to one encounter by slow IV push infusion with careful monitoring. The optimal protocol involves the administration of IV medications such as Calcium-EDTA  and oral administration of Chemet, also known as DMSA, and Cuprimine (D-Penicillamine generically). These medications will help break the bonds of the metals from the solid organ cells, primarily brain and bone. Infusion of IV Glutathione will assist in the body’s ridding itself of these substances without risk of the metals reaccumulating in the organs. Monthly lab work is done to ensure that the patient has no aberrations in bone marrow or liver function. Serial urine testing is done to quantify the excretion of the metals as an indicator of the effectiveness of the chelation as well as measuring the essential elements to be sure the body’s supply is not depleted. In over 2000 infusions, we have seen subtle to dramatic positive effects in hundreds of patients chelated in our practice.

Autistic spectrum disorders appear to have a biomedical basis which adversely affects the immune system. Greater than 95% of autistic children have significant environmental and food sensitivities and allergies. Food allergies and sensitivities occur in 5-8% of the general population, 36% of the autistic population (Lucarelli, 1995) and up to 50% of surveyed families report evidence of food allergy/sensitivity in the autistic child (Horvath, 2002).  These allergies can affect any part of the GI tract and manifest as pain, diarrhea, constipation, gastritis, skin rashes, hives, eczema, hyperactivity and self-injurious behavior.

It is important to test for these allergies by removing offending foods, confirming using IgE blood testing, rotation diets. Conventional allergy testing/immunotherapy usually involves blood or skin testing at the lowest possible level of reaction to environmental allergens, i.e. dust, molds, trees, grasses, weeds, etc.  Skin testing for food sensitivities is rarely done. Serial End Point Therapy is a treatment method done at our office that has been found to alleviate allergic symptoms by using dilute injections of the offending allergens. The allergic symptoms may be manifested in different organ systems such as respiratory, skin, nervous and gastrointestinal. Many children on the spectrum will manifest increasingly aberrant behaviors during times of the year when the pollen counts are at their highest. Serial End Point Testing is only done in a few centers in this country yet is widely accepted in European countries as the first line testing modality.

Serial end point testing consists of a series of skin tests to determine the precise dose of extract that will alleviate symptoms without producing side effects. A small amount of allergy extract is injected under the skin and a wheal (a welt or bubble) forms. The wheal is measured, timed for seven to ten minutes and measured again. The strongest dose that does not produce significant skin reaction is called the neutralizing dose. In addition, careful note is made of any symptoms that may be induced. Symptoms may be provoked, especially when testing with foods, which is helpful in the diagnosis and treatment of the condition. At the conclusion of the testing, an extract is made either as a nasal spray or injectable extract. The extract is preservative free and requires refrigeration. New extracts are prepared monthly for the individual patient.

Treatment with neutralization therapy usually produces rapid relief from symptoms. The dose is constant, and does not have to be built up and increased over a four to twelve month period as in conventional immunotherapy. Serial End Point/Neutralization Testing can alleviate sensitivity to foods and inhalants.

It is medically accepted that folate and methylation are vital in neurological development. Autism and PDD interfere with normal development of language and socialization. Multiple theories regarding causality have been generated, and typically these focus on genetic vulnerability and environmental risk factors.

Clinically available testing for the methylenetetrahydrofolate reductase (MTHFR) gene mutations (polymorphisms) has become available and has been incorporated into our evaluation process for developmentally delayed children. Dr Boris etal. presented data that demonstrates these polymorphisms as significantly associated with ASD. Disturbances in methylation can lead to problems with DNA , RNA, creatine, proteins, phospholipids and neurotransmitter production and function. Based on the observed MTHFR-related genetic variations in children with ASD, it is reasonable to treat with folinic acid and its cofactors in the methylation cycle, for example B vitamins, N-acetyl cysteine, and methyl B12 for these children. 

The administration of injectable or inhaled methyl cobalamin has resulted in many of these children becoming more aware of everything around them. They may start speaking, and/or acting like other children and progress dramatically in their Special Ed and therapeutic environments. Some advance so far that they attend mainstream classes and are not labeled as autistic any longer. Methyl cobalamin (methyl B12) is available in our office in a preservative free compounded injectable liquid. We provide ultra fine syringes and give parents individual instruction on administration of these injections to their children. Once the effectiveness of this treatment is established, we can modify the injections to contain folinic acid, N-acetyl cysteine and glutathione when necessary. The availability of these ‘vitamin shots’ in the office guarantees that parents will always be able to obtain what they need for their children. If an injection is unacceptable to the child or parent, a methyl cobalamin nasal spray can be made for use as an alternative to the injections.

Enzyme therapy is one of the fastest emerging successful alternatives for people on the autism spectrum as well as other neurological conditions. Reports of significant improvements in health, pain reduction, language, food tolerance, socializing and other benefits emerge daily. 

Drawing on long-standing scientific research and trials by a wide range of families, Autism Associates of New York, deals comprehensively with all the information on enzymes that parents or those new to enzymes need: how enzymes work, who may benefit, what to expect, practical tested advice on selecting and introducing the right kind of enzymes, and how this can be combined with other approaches and therapies.

Studies have shown that the FDA approved PPAR agonist, Actos, used to treat type 2 diabetes, is effective in treating many autoimmune disorders. These include rheumatoid arthritis, ulcerative colitis. Crohn’s Disease, Alzheimers Disease, Multiple Sclerosis and psoriasis. In patients with secondary Multiple Sclerosis daily treatment with Actos induced clinical improvement without adverse events. Peroxisome proliferator activated receptors (PPARs) have been found to reduce inflammation of brain glial cells. Glial cells are inflamed in children with autism. PPAR’s function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPAR’s are expressed in liver, muscle, kidney, heart, intestine and adipose tissue. PPARs have been suggested in the potential role of not only metabolic but also in inflammation control. PPAR activators have been shown to inhibit the activation of inflammatory response gene, NF-kB. Actos inhibits the NF-kB signaling pathway. It is for similar reasons that PPAR agonists have potential therapeutic applications in inflammation-related diseases such as inflammatory bowel disease and autistic spectrum disorders It is for similar reasons that PPAR agonists should be considered for use in children with ASD. In over 350 cases in our office, there have been significant subjective responses in over 75% of the children. These include improved speech and language, focusing and socialization skills. We are planning a double blind controlled study with the Department of Neurology at the University of Illinois to evaluate the clinical response of Actos in ASD patients.

The Specific Carbohydrate Diet (SCD) is intended to stop the cycle of malabsorption and intestinal overgrowth by removing the source of energy from the microbes. The SCD allows simple sugars that do not need to be broken down in order to be absorbed. By eliminating foods that cannot be properly digested, the energy for the undesirable gut organisms is eliminated. These organisms then die off, inflammation is decreased and the immune system can return to normal. Once the immune system is returned to adequate levels, it can begin to keep the intestinal microbes in proper balance leading to healthy digestion. The SCD allows simple carbohydrates, but prohibits complex carbohydrates. For the most seriously affected patients, all carbohydrates should be eliminated for a period of time to allow the intestinal tract to heal. For others, the beginning stage of the diet requires that all fruits and vegetables be peeled, seeded and cooked in order to make them easier to be digested. Raw fruits, vegetables, nuts and seeds are added later.

The next stage of the diet allows many more foods. To properly follow this diet, it is advisable to read “Breaking the Vicious Cycle” by Elaine Gottschall. The book details the progression of allowed foods as well as providing many delicious recipes.

Seizure disorders occur in 1-2% of the population as opposed to 35% - 80% of the autistic population.  There is no gender bias and can occur before age 5 and in adolescence.  Long term studies have shown that up to 38% of adults diagnosed with autism as children will have seizures.  This can result in lower intelligence, more maladaptive behaviors and a higher rate of psychotropic medications. (Frye).

Epilepsy in autism spectrum disorders can be caused by brain malformations which is why MRI studies are important, metabolic disorders affecting mitochondrial function, folate metabolism, and other enzyme deficiencies, and genetic disorders such as Fragile X, Rett Syndrome and Tuberous Sclerosis.  Excess glutamate production, over activity of NMDA receptor, glutamate receptor activity can affect the excitatory/inhibitory balance in the brain.  Glutamate activity peaks during the second year of life which is when most regression occurs.  As a result of excitotoxicity, excess peroxinitrite is produced which also damages the mitochondrial complexes.

Ketogenic diet, developed for treatment of pediatric epilepsy in 1920s, allows the body to burn fats rather than carbohydrates.  The liver converts the fats into fatty acids and ketones which pass into the brain and replace glucose as an energy source.  The state of ‘ketosis’ reduces the frequency of seizures.  Medium and short chain triglycerides (MCT’s) are more ketogenic than those made from long chain fats.

Immune dysfunction has been associated with children with autism. In clinical study, the participant’s overall aberrant behaviors decreased substantially soon after receiving their first dose of IVIG. IVIG has been proven to inhibit NF-kappaB activation induced by inflammatory cytokines such as TNF-alpha. Non-specific inflammatory markers; increased platelets and ESR (erythrocyte sedimentation rate), autoantibodies to myelin basic protein, thyroid antibodies, confirmed biopsies for colitis, low immunoglobulin levels, elevated anti-DNASE and anti-streptolysin O titers, all indicators of autoimmune disease, have been positively affected by IVIG. Decreases in hyperactivity, inappropriate speech, irritability, lethargy and stereotypy were proven. A NIH Consensus Statement asserted that the risks involved in the use of IVIG are minimal. After many years of experience, the safety of IVIG has been established. Thus, there is a reasonable rationale considering the risk/reward ratio to utilize IVIG therapy in children with autism.

Secretin is an enzyme that is found in the pancreas and brain. It has been used in the treatment of ASD patients with some children responding in normalization of bowel function, behavior, speech and language. Secretin can be administered intravenously or as a daily nasal spray. 

The initial administration is IV and given in two monthly doses to determine its effectiveness. Secretin therapy is continued for six months. Patients have responded favorably in 50-85% of the trials. It is available in our office.