ANTI AGING HEALTH
Autism
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This protocol provides a working knowledge of autism, its prevalence, suspected causes, effects on physiological systems, and nutritional treatment interventions. Although yet unproven, there are indications that genetics and environmental insults play a role in autism. Immunological considerations and damage to the gut that occurs with autism are equally as important.
The treatment of autism as a biological disorder is a complex problem requiring that each child be individually assessed. This protocol will primarily help families with a child diagnosed with autism to start addressing the damaged GI tract and by doing so to positively impact the neurological system and behaviors seen in autism. For the healing process to begin, defective biochemistry must be addressed first. This is a major goal of this protocol.
Important: The implementation of a new diet restricting toxins that are thought to impair neurological function (i.e., gluten and casein) can yield withdrawal symptoms at the onset due to the removal of substances that the body craves. The protocol below is best implemented with oversight by a licensed, practicing physician or a nutritionist versed in the biology and nutrition of autism.
Post-diagnosis, the following should be implemented under advisement of a nutritionist or neurodevelopmental pediatrician experienced in the management of autism:
For more information, contact:
Life Extension Mix Children’s Formula, Life Flora, taurine, glutamine, Se-Methylselenocysteine, Gamma E Tocopherol with Sesame Lignans, melatonin, Super Carnosine, zinc, Cran-Max (cranberry juice concentrate), Super EPA/DHA with Sesame Lignans, Mega GLA with Sesame Lignans (essential fatty acids), grapefruit seed extract, DMG, vitamin C, Complete B Complex, colostrum, Super Digestive Enzymes, magnesium, vitamin B6, are available by telephoning (800) 544-4440 or by ordering on-line. Some of the products are only available through a physician who understands the complexity of autism. A list of physicians is available from the Autism Research (www.autism.com/ari/).
Autism is a disorder characterized by impairment of reciprocal social interaction and communication with others. Children with autism have a tendency to display repetitive and stereotypical behaviors encompassing preoccupation with restricted patterns of interest; inflexibility to nonfunctional routines or rituals (perseverative behavior); repetitive motor mannerisms (e.g., hand/finger flapping or twisting or complex whole-body movements); and a persistent preoccupation with parts of objects. Autism is the most severe of the Autism Spectrum Disorders (ASD), a broad continuum of brain illnesses including Asperger's syndrome, Childhood Disintegrative Disorder, Rett's syndrome, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) . All of these disorders fall under the umbrella of Pervasive Developmental Disorders (PDD).
Present research indicates that autism is a complex gastrointestinal (GI), immunological, endocrinological, and neurological disorder arising from a combination of genetic factors and environmental insults. Most children with autism present with some combination of clinical and laboratory abnormalities1 such as:
This protocol will explore the suspected causes of autism and its epidemic status, changes to the body systems at the anatomical and cellular level, and pharmacological and nutritional interventions employed to treat and sometimes abate the signs and symptoms of the disorder thereby improving the quality of life of individuals on the autistic spectrum. While medical opinions as to the cause(s) and treatment(s) of autism abound, one fact will never waiver among professionals—early diagnosis and intervention is critical for the management of ASD to disrupt the behavioral and neurological patterns associated with autism before they become permanently ingrained. A younger nervous system is more adaptive to change than an older one with established patterns.
Studies published prior to 1985 showed prevalence rates of 4 to 5 cases per 10,000 children on the autism spectrum. More current epidemiology studies suggest every 62.6 people in 10,000 are affected by autism.2 Autism is one of the fastest growing mental disabilities, increasing at a rate of 10-17% annually.3 The increasing growth rates of autism in recent years are shown in Figures 2 and 3.
There is no evidence linking autism to any socioeconomic or immigrant status or to any ethnicity.4 The male-to-female ratio found in autism is 3:1.5 The cause(s) of a higher prevalence in males remains unidentified. The increase in autism within the last 20 years is controversial throughout the medical community. However, clinicians now have a broader understanding of autism as well as expanded and clarified diagnostic criteria. As a result, more disorders such as attention deficit hyperactivity disorder (ADHD) and Tourette's syndrome are beginning to fall under the umbrella of ASD (Autism Spectrum Disorders).6
Autism typically begins in early childhood and impairs thinking, feeling, language, and the ability to relate to others. As early as 18 months, signs such as lack of social smile or facial expression, eye contact, emotional expression, and appropriate gestures and a preference for being alone are characteristics identified by parents whose child was later diagnosed with autism.7 Babies may exhibit two common characteristics: arching their backs away from caregivers to avoid physical contact and failing to anticipate being picked up (i.e., becoming limp). As infants, they are often described as either under-reactive referring to an infant who is quiet and makes few demands on caregivers or over-reactive referring to an infant who cries (sometimes non-stop) and continuously rocks or bangs its head against something. There is usually impairment in one or more of the senses causing sensory integration dysfunction (SID). SID is an inability to take in, sort out, and connect information from the surroundings in an organized manner. If sensory input is not processed and organized accurately, the result is abnormal motor output and feedback. A disorganized central nervous system is characterized by developmental lags and behavioral, emotional, and learning disabilities.
Multiple genetic factors are speculated in the cause of autism.8 There is no single gene that causes autism, but studies have found that regions on chromosomes 2, 7, and 13 may contain one or more susceptibility genes.9
Autism as a heritable disorder has recurrence rates in siblings of affected individuals that are 2-8% higher than in the general population with occurrence rates of 60% for identical twins vs. near 0% for fraternal twins.10 There is 100% overlap in genes in identical twins, whereas fraternal twins show a 50% overlap—similar to non-twin siblings. If autism were not due to some genetic factor, the association of autism in identical twins would not be higher than that for fraternal twins.
Unless there is a known underlying genetic defect, such as in Rett 's syndrome or Fragile X syndrome (an X-linked inherited disorder characterized by mental retardation and large physical features), it is necessary to accept a developing fetus, a newborn infant, or a toddler as starting out with normal biochemistry, physiology, and neurology. This developing child is then hit with environmental insults after fertilization.11 Heavy metal toxicity; a specific environmental insult, is a consistent finding in many autistic children.
Metals such as lead, arsenic, and aluminum contaminate the environment. Evidence that mercury is a cause of autism is strong, yet unproven.12 Mercury is present in water, air, and food, especially seafood. It depletes glutathione and other antioxidants, thus destroying immune defenses (causing autoimmunity); impairing enzyme and receptor function; and robbing the cells in the body of energy by attacking the subcellular organelles called mitochondria that produce most of the energy. Mercury is loosely bound to tissues and possibly detectable in the urine for a few weeks to months after exposure. Then mercury becomes tightly bound to enzymes and other proteins and is distributed to the liver, kidney, brain, and other organs with little remaining in the blood, urine, or hair.13
The role of childhood vaccines is more controversial than metal toxicity in the pathology of autism. The increasing number of vaccines (containing mercury) given to young children might compromise their immune and neurological systems. Many parents report their children were normal until receiving MMR (measles, mumps, and rubella) vaccines. Eighty percent of autistic children studied developed symptoms within a week of vaccination.14 An association is found between measles, mumps, rubella vaccination, and onset of behavioral symptoms in children with regressive autism.15
Over 90% of MMR antibody-positive autistic sera were found to be positive for myelin basic protein (MBP) auto-antibodies. Myelin is a fatty substance formed around nerve fibers to facilitate nerve conduction. This suggests a strong association between autism, MMR, and autoimmunity in the central nervous system (CNS). An inappropriate antibody response to MMR (specifically the measles component) might be related to pathogenesis of autism.16 In susceptible newborn infants or toddlers, multiple exposures to mercury-containing and multiple-antigen vaccines during gestation is highly suspected (particularly the vaccine for rubella). Mercury leaching from dental amalgams that were placed during early pregnancy, or from other environmental toxins, may cause symptoms of autism.17-19 The GI tract, liver, pancreas, kidneys, immune system, and brain are major sites of mercury absorption.
Research in a subset of children with autism shows a form of chronic inflammatory bowel syndrome (IBS) due to vaccine-strain measles.20-26 Researchers detected27 and sequenced vaccine-strain measles virus from peripheral blood mononuclear (white) cells in patients with IBS and autism. In a few children, Many copies of a vaccine-strain measles genome were detected in the cerebral spinal fluid surrounding the brain.28-30
Thimerosal is a mercury-based preservative added to childhood vaccines to prevent microbial contamination of doses. Limited studies have addressed the suspicion that autism arises from the neurotoxic mercury, especially in immature brain.31 The number of vaccines given to children has risen over the past two decades. Most of those vaccines containing thimerosal, which is 50% mercury.32-34 The clinical signs of mercury toxicity are very similar to the symptoms of autism with onset of autism coinciding with immunization and exposure to thimerosal.35
Hypotheses for the increased incidence of autism, allergies, and other chronic illnesses suggest that excess dietary iron could be a factor. One hypothesis proposes that excessive dietary iron consumed by infants is the root cause of increased cases of autism, allergies, and other childhood diseases.36 About the same time that autism rates soared in California (from 1987 to 1998), the amount of iron consumed by infants also rose. Since the 1970s, infant formulas and cereals have been fortified with iron to eliminate iron deficiency anemia (IDA). Although IDA has since dropped from 20% to less than 3%, other childhood disorders have increased exponentially.37
A typical infant receives 20-50 mg/day of iron from iron-fortified formulas and cereals and juices that have been fortified with calcium and vitamin C to aid absorption of iron. 50% of children receive supplements containing iron.38 This is more iron per day than is needed for normal development. Young children require about 10 mg/day of iron. Children predisposed to metabolic disorders (e.g., hereditary hemochromatosis (see the Protocol on Hemochromatosis) in which iron deposits rise throughout the body, absorb four times more iron than normal children. Hereditary hemochromatosis is one of the most common genetic disorders in the U.S. It results when a child inherits a defective HFE gene from both parents (which regulates the amount of iron absorbed from food). Hereditary hemochromatosis is the most common form of iron-overload disease. No studies on long-term effects on children genetically predisposed to metabolic disorders were undertaken prior to food industry changes in food processing.39 Some children can become burdened with excess dietary iron and labeled with PDD (Pervasive Developmental Disorders) when they might have developed normally without the food industry's mass fortification of infant food.
Consisting of only 2.5% of bodyweight, the brain controls growth, body temperature, coordination, balance, sleep, learning, taste, speech, moral judgment, problem solving, hand-eye coordination, affection, aggression, creativity, and so much more. Billions of neurons relay information so the body can perform these functions. Brain activity requires a sequential flow of electrical impulses by nerve cells (neurons, the structural and functional units of the central nervous system which process information).
The brain has a protective mechanism called the blood-brain barrier which limits the types of substances that can travel from the blood into the brain. This barrier protects the brain from some, but not all toxins. When toxins penetrate the brain they can disrupt the brain's ability to function. Children are especially vulnerable to environmental toxins during neural development, which extends from the embryonic period through adolescence. Neurotoxicity can interfere with this developmental process resulting in clinical disorders such as schizophrenia, dyslexia, epilepsy, and autism.40
The digestive system is responsible for digestive juice secretion, breaking down of nutrients and absorbing them into the bloodstream for distribution to body cells, and elimination of undigested foods from the body. These processes are under the control of a separate (enteric) nervous system that innervates the gut wall and the endocrine system. The surface of the intestinal wall absorbs nutrients while acting as a barrier to keep other intestinal contents from entering the blood system. The physical integrity of the intestinal barrier can be assessed using a sugar permeability test.41 Excessive mannitol excretion in the urine after an oral load is indicative of damage to epithelial cells in the gut, indicating increased permeability of the gut by undigested proteins or toxins. Immunological reactions and pathologies can ensue.
Because the gut is the portal of entry for all ingested materials, a damaged gut, poor digestion and absorption, and an excessive immune response leads to dysfunction in other organs. Poorly digested food causes allergic responses and absorption of biologically and neurologically active peptides. Incomplete digestion also results in poor absorption of many nutrients and nutritional deficiencies.42 Nutrient deficiencies decrease cellular functions, reduce protein and enzyme production, disturb cell membrane function, and cause abnormal carbohydrate metabolism.43
The body protects itself from foreign invaders with the immune system. Much of our immunity is acquired. Immunity develops after substances are recognized by the body as foreign and provokes an immune response. These foreign invaders are known as antigens. In response to antigens, the body produces antibodies, a type of protein produced by specific white blood cells. Each antibody can bind only to a specific antigen helping to destroy the antigen. Depending on the nature of the antigen, antibodies can work in several ways: destroying antigens directly or facilitating the white blood cells destruction of the antigen.44
The following are antibodies involved in immune responses:
Allergies (or immune hypersensitivities) can develop incidental to the role of the immune system in warding off infection. Children with autism commonly have food allergies.
A classic IgE-mediated response is a food allergy. This type of allergic response occurs in only 2-5% of the population, usually in genetically-predisposed individuals. It occurs immediately or within a few hours following ingestion of food. IgE responses occur quickly and are usually associated with recently ingested food. Histamine is released from circulating blood cells (mast cells) which stimulates gastric secretions, constricts bronchial smooth muscle, and dilates blood vessels. Stomach cramping, diarrhea, skin rashes, hives, swelling, wheezing, and anaphylaxis can follow a massive histamine response.45,46
More common, established food allergies are IgG-mediated. IgG-mediated allergic responses occur in 70-80% of the population. This type of reaction is delayed. It can occur in hours or days after ingestion of food. In IgG-mediated allergic responses, the immune system creates an overabundance of IgG antibodies to a specific food. Instead of attaching to mast cells (as in IgE responses), the IgG antibody attaches to the food itself as it enters the bloodstream. Because IgG-mediated responses are delayed, they are often difficult to self-diagnose. One can suffer for years from a medical condition never suspecting that the underlying culprit is the diet. The most reliable method to detect IgG-mediated responses is laboratory testing.45,47
The neuropathology of autism is based on Bauman and Kemper's findings on the limbic system which controls emotional behavior and motivation.48 Abnormalities in the neurons revealed a decreased size and increased density compared to controls.49 The cerebellum (which controls learned, patterned movements show low number of Purkinje cells (the primary output cells of the cerebellum). The inferior olivary nucleus (in the cerebellum) did not show the expected neuronal loss secondary to a decrease in Purkinje cells, suggesting that these abnormal findings occurred prior to the olivary body and Purkinje cells making a connection, usually after 30 weeks of gestation.50 The mini-columnar organization in the brain (the lowest level of organization) is abnormal in autistic children, indicating the neuropathology of autism.51
Up to 20% of autistic children have a head circumference above the 97th percentile. Postmortum studies suggest an increased brain mass is characteristic of autistic children with head growth early in life.52 However, the corpus callosum (which communicates between the two hemispheres of the brain) is reduced in size and unlike the rest of the brain. The corpus callosum is important in lateralization (using both sides of the body together). Reduced corpus callosum size suggests a reason for the motor and language impairment seen in autistic children and lateralization difficulties such as increased left-hand dominance and mixed dominance (equal use of both hands).
Many children with autism experience a variety of gastrointestinal (GI) ailments, including diarrhea, constipation, bloating, and abdominal pain. Horvath, Perman & Wakefield43 reported these symptoms in 46-76% of children with autism compared to 10-30% in normal controls.53 Wakefield found that GI symptoms developed with the onset of autistic behaviors. Endoscopy revealed ileal-lymphoid-nodular hyperplasia and non-specific colitis in 12 children, 9 who had autism.54 The pathology was described as a “subtle new variant of inflammatory bowel disease with uncharacteristic features of either Crohn's disease or ulcerative colitis”.55
Anecdotal reports over 30 years pointing to a disturbed GI tract and food intolerance in autistic children led to the term “leaky gut syndrome.” Leaky gut refers to a highly inflamed intestinal lining that is more permeable by large proteins, bacteria, fungi, metals, and toxins than a normal intestine lining because of large “holes” between the cells of the intestinal lining caused by biological insults. The intestinal lining acts as a barrier to prevent the intestinal contents from entering the blood system. Excessive use of oral antibiotics in the early years and abnormal pH levels that create an overly acidic environment are two insults that can create a permeable intestinal lining. A compromised intestinal tract leads to allergic responses and absorption of biologically and neurologically active peptides. When the peptides cross into the bloodstream and then cross the blood-brain barrier into the cerebrospinal fluid, interfering with central nervous system function, symptoms of autism appear.56
Two proteins, gluten (from wheat, barley, oats, and rye) and casein (from all dairy products), are only partially digested in the small intestine by proteolytic enzymes.57 The incomplete digestion results in release of short chain peptides (gliadomorphins from partial gluten digestion and casomorphins from partial casein digestion) that are structurally similar to endorphins, producing long-lasting effects on the CNS.58 These peptides can “leak” into the bloodstream, cross the blood-brain barrier, and bind to opiate receptors in the brain. This process, termed the “opioid excess theory,” causes delayed and altered maturation; adverse and often self-injurious behavior or seizures; decreased motor skills; speech and language deficits; and even irregular sleeping patterns.59 Researchers60 found that opiate-like behaviors in autistic subjects mimicked those seen in opiate addicts and babies exposed in utero to narcotics. Because brain opiates modulate social-emotional processes which are dysfunctional in autistic children, the researchers suggested61 that blockade of opioid activity in the brain may be therapeutic for early childhood autism. Incomplete digestion of food peptides also results in poor absorption of many nutrients and chronic nutrient deficiencies.62
Opioids also affect the immune system. When the GI environment is compromised, there is an imbalance between the “good” bacteria (bifidobacterium or lactobacillus) needed for digestion and yeast (candidiasis) which normally lives in the gut in small, controlled quantities. Normally, yeast does not overgrow because it is controlled by the immune system. However, if the gut wall is compromised by an overgrowth of yeast or bacteria which causes holes in the mucosa and leaking of GI contents into the bloodstream, an immune response is triggered when the body recognizes these large products as foreign. If a child is born with an immune system defect and has had long-term antibiotic use due to early childhood infections, yeast can overgrow in the gut and cause an autoimmune response. Alternatively, the immune system may “remember” yeast from early in life and mistakenly accept its presence, refraining from directing antibodies against it.63
Inflammation of the mucosal lining causes GI disturbance. Additionally opioids are reported to lower phenol sulfotransferase needed to break down these proteins. Deficiencies in enzymes that maintain sulfation may contribute to increased permeability of the intestinal mucosa allowing the leakage of proteins.64
Stools are often abnormal in children with ASD (Autism Spectrum Disorders). Stool cultures can reveal numerous abnormalities resulting from altered metabolism and bacterial imbalances in both beneficial (symbiotic) and non-beneficial (dysbiotic) flora (Table 3) . Pathogenic organisms can attack the GI system and produce toxins which have systemic effects. Dysbiosis (non-beneficial flora) is an almost routine result of repeated antibiotic treatment.65 A comprehensive and digestive stool analysis (CDSA) is recommended in all children with ASD.
pH of the stomach can also play a role in leaky gut syndrome. The role of secretin, a hormone which stimulates the pancreas to release sodium bicarbonate to neutralize digestive acid, is impaired in autistic children.66 A reduced level of secretin allows the pH level of the intestinal tract to decrease, creating a more acidic environment, thus altering the intestinal mucosa. The integrity of the intestinal wall can be compromised leading to increased permeability and allowing leakage of toxins. In autistic individuals with hyposecretion of secretin, intravenous secretin infusions resulted in marked GI improvement and improvement in eye contact, alertness, and expressive language.43 It may be clinically beneficial to enhance GI performance with supplemental secretin. To alleviate leaky gut syndrome, implement a diet that removes all gluten and casein from the child (the gluten-free/casein free diet; see Nutritional Therapy).
Serotonin acts as a growth factor during embryogenesis. A crucial part of the cascade of events that leads to changes in brain structure is serotonin receptor activity. Therefore, disruption of the serotonergic system may contribute to CNS disorders associated with impaired brain development. Additionally, serotonin imbalances are seen in sensory integration problems, auditory processing problems, speech delay, repetitive behaviors, self-stimulation, and sleep disturbances—all characteristic of ASD. Serotonin also affects the rate of hormone release and tissue inflammation. Individuals with autism have increased levels of serotonin in their blood.67 They produce, absorb, or metabolize serotonin differently than those who are not autistic.
Endorphin levels in autistic subjects are higher than in normal individuals, resulting in decreased pain sensitivity and increased self-destructiveness in psychotic autistic children.68
Dopamine is a neurotransmitter in the brain that regulates movement, emotion, and motivation. Dopamine is associated with the pleasure or reward system of the brain, providing a reinforcement that motivates us to engage in an activity or to continue doing a certain activity. Dopamine is released by experiences such as food, sex, and drugs that are naturally rewarding. The theory of a connection between autism and altered dopamine pathways is often discussed because drugs such as narcotics directly release dopamine (important in neurobiological theories of addiction). Dopamine pathways are pathologically altered in addicted persons, such as the cravings for or the “addiction” to wheat and dairy products seen in autistic children.
An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, their serum melatonin levels differed from normal levels (in amplitude and rhythm). Marginal changes in diurnal rhythms of serum thyroid-stimulating hormone (TSH) and possibly prolactin were identified. The subjects with seizures have an abnormal pattern of melatonin release (correlated with EEG changes). Other subjects showed a parallel between thyroid function and impairment in verbal communication. There appears to be a tendency for neuroendocrinological abnormalities in autistics. Melatonin, and possibly TSH and prolactin, could serve as biochemical variables of the biological parameters of autism.69
Reports of an impaired serotonin synthesis in the brain justified use of drugs targeting the serotonin system. Selective serotonin reuptake inhibitors (SSRIs) such as fluvoxamine (Luvox®) and fluoxetine (Prozac®) have been shown to improve mood, ritualistic behaviors, obsessive compulsive disorders (OCDs), and social behaviors. Fluvoxamine causes less agitation than fluoxetine.70 Clomipramine, an antidepressant, demonstrated various degrees of effectiveness in young children and significant reduction of repetitive behaviors and aggression in adults. Side effects have limited use of this drug.
As discussed earlier, abnormal dopamine function may play a role in autism. Dopamine modulates attention and motivation. Haloperidol (Haldol), a dopamine antagonist, was shown clinically to improve coordination, self-care, and exploratory behavior in autism.71 Haloperidol also had high efficacy in improving social behavior, stereotypical behavior, and behavioral impairments associated with autism (aggressiveness and hyperactivity.72 Monitoring for the cardiac and hepatic side effects of haloperidol is required.73 Pimozide, a dopamine antagonist, has been shown to be effective in reducing motor and vocal tics in Tourette's disorder.
Desipramine, prescribed for depression, is a selective norepinephrine uptake inhibitor that is helpful in reducing hyperactivity. Clonidine, prescribed for hypertension, is effective in Tourette's symptoms and has fewer side effects than haloperidol. Improvements in hyperactivity and irritability occur in autistic children, but side effects of sedation and decreased blood pressure are reported.74
Naltrexone, an opiate antagonist, has positive effects on hyperactivity, verbalization, attention, socialization, and self-injurious behavior in several unduplicated studies.75
Risperidone is an antipsychotic agent that loweres the frequency and intensity of tantrums, outbursts, and aggression in autistic children. Side effects include weight gain and, most significantly, tardive dyskinesia, a very serious side effect (with involuntary jerky movements of the face, tongue, jaws, trunk, and limbs) that often persists long after the drug is discontinued.76
Children with autism typically have a poor nutritional state caused by their acceptance of a restricted range of foods, difficulties in digesting food, and poor absorption of nutrients. Intake of vitamins, minerals, and other essential nutrients is reduced and requires supplementation.
Supplementation with vitamin B6 and magnesium is a common intervention strategy to improve attention and language in autistic children.77 Vitamin B6 is essential for the metabolic pathways of neurotransmitters, including serotonin, dopamine, epinephrine, and norepinephrine, where it functions in enzymatic decarboxylation of modified amino acids such as tyrosine and phenylalanine which are precursors to these neurotransmitters. Magnesium is a mineral required for a variety of enzyme-catalyzed reactions.78 The combination of vitamin B6 and magnesium in clinical trials improves behavior in autistic children.79,80
EFAs are major components of cell membranes important in relaying signal information in and out of the cell, and essential for brain development.81 Children with bowel inflammation poorly absorb many important short-, intermediate-, and long-chain fats. Many children with autism have dysfunctional cellular organelles called peroxisomes which metabolize long-chain fatty acids. Thus most of these children have deficiencies and imbalances of fatty acids. Good polyunsaturated fatty acids allow membrane-bound proteins to function efficiently and can balance dysfunctional inflammatory pathways. The brain is primarily composed of fat, indicating how important good fats are to brain function.
Omega-3 and omega-6 fatty acids comprise two families of essential fatty acids. Nutritional science has validated the healthful benefits of omega-3 fatty acids for the human brain and body. EFAs are deficient in nearly 100% of ASD cases.82,83 Most processed foods and vegetable oils have high amounts of saturated and omega-6, but little omega-3 fatty acids. The long-chain forms of omega-3 fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), are found almost exclusively in deep, cold water fish. EPA is needed to create prostaglandins that support cardiovascular health and cell membranes. DHA is vital for a healthy brain, eyes, and reproductive system. The body works best when both types of fatty acids are combined in the right proportions. Because of the presence of omega-6 fatty acids in commercially processed foods, people in industrialized nations have a disproportionately high intake of omega-6 fatty acids. Alpha-linolenic acid (ALA), a third essential fatty acid, is derived from flax seed, avocados, and walnuts. ALA is converted into EPA and DHA by the body, but the process is slow and varies with age and gender. Fish and fish oils remain the best sources of DHA and EPA. Although there are few controlled trials testing EFAs in autism, physicians report autistic patients benefit from omega-3 supplementation.84
Omega-6 fatty acids are usually well supplied through dietary means; however, omega-3 fatty acids are typically lacking in the Western diet. Increasing intake of omega-3 is suggested. One way to add good dietary fats is to add omega-3 fatty acids. Gradually increase these oils and frequently rotate the type of oils in the diet. Cold-pressed whole oils such as sesame seed, almond, flaxseed, and walnut oils are best. Some oils with long-chain fats should be avoided because they are difficult for autistic children to metabolize, including the long-chain fatty acids from peanut oils.
Note: See Appendix for Cautions and Contraindications
Vitamin A is present in leafy green vegetables, yellow fruits and vegetables, liver from cod and other fish, liver, milk cheese, butter, and egg yolk. It occurs in animal tissues as retinol. Provitamins for the formation of vitamin A occur in abundance in vegetables. The yellow and red carotenoid pigments in vegetables are converted to vitamin A in the liver and stored.85 Vitamin A is required for formation of visual pigments and normal growth of most body cells.85 An excellent source of vitamin A is deep-sea fish. This source is in the form of retinol which is easily absorbed.85 Only the recommended daily allowance of vitamin A should be given. Vitamin A is fat soluble and can build up in body tissues and although infrequent, it can reach toxic levels. Vitamin A is required for proper immune system function. In a study of a group of 60 autistic children who were given cold liver oil for 3 months or longer,86 within days of receiving the cod liver oil, some cases had marked improvement in the core autism signs of reduced eye contact, lack of socialization, and disturbed sleep patterns.87
Vitamin C has been shown in well-designed studies to improve sensory motor scores.88 Vitamin C is present in high concentrations in the hypothalamus. Its presence in synaptic vesicles and release into extracellular space by neuronal activity has been demonstrated to characterize vitamin C as a neurotransmitter.89
Sulfur, in its most oxidized form of sulfate, is extremely low in virtually every autistic child. There are many enzyme systems that will not function without sulfation. Impaired sulfation is linked to poor metabolism of dietary phenols. Researchers90 advise that foods high in phenols such as bananas, onions, and coffee should be removed from the diet of individuals with ASD91. Epsom salts baths, which provide sulfate and aid in detoxification of metabolites, are suggested.92 When detoxification capacity is limited, the cysteine/cystine ratio, and methionine, taurine, and glycine levels are abnormal. The essential sulfur amino acids methionine and cysteine are low in autistic children under 4 years of age. Cysteine is important for the formation of glutathione and taurine. Glutathione is low in children with ASD. The pathway that incorporates cysteine into GSH is flawed and cysteine's abnormalities are due to impairments in the pathway: methionine > S-adenosylmethionine > S-adenosylhomocysteine > homocysteine > cystathionine > cysteine > taurine.93 One enzyme in methionine metabolism, methionine synthase, which makes methionine from homocysteine through methylation reactions catalyzed by folic acid (5-methyltetrahydrofolic acid) and methylcobalamin (vitamin B12), is shut down by miniscule amounts of mercury such as Thimerosal.94
Vitamin B12 cannot optimally be absorbed in the presence of a leaky gut. Malabsorption of vitamin B12 results in impaired nerve function by interfering with the formation of myelin, the lipoprotein found in the protective sheath surrounding nerve fibers that enables nerve conduction over great distances.95
Children with autism experience significant oxidative stress requiring additional antioxidants. Vitamin E is an antioxidant that provides protection by preventing oxidation of unsaturated fats. In the absence of vitamin E, unsaturated fats in cells decrease through peroxidation, causing abnormal structure and function of cellular organelles producing energy such as mitochondria, digestion such as lysosomes, and a functional cell membrane.85 A supplement containing mixed tocopherols and tocotrienols is preferred.
Zinc is required for the development and maintenance of the brain, adrenal glands, GI tract, and immune system. Synthesis of serotonin requires zinc-activated enzymes. Zinc is essential for antioxidant enzyme activity. It is required to make stomach acid and is a component of lactic dehydrogenase, an enzyme important for interconverting pyruvic acid and lactic acid, associated with ‘burning' muscles after exercise. Zinc is a component of peptidases that digest proteins.96 Zinc is critical for digestive processes damaged or dysfunctional in autistic children, yet it is deficient in 90% of ASD cases.97,98
Typically, selenium and glutathione are low in autistic children. Selenium is helpful in detoxification of heavy metals. It replaces toxic metals that are removed by detoxifying and chelating agents (discussed below). Selenium functions as an antioxidant, works cooperatively with vitamin E, and helps promote growth.
Glutathione taken orally helps replenish the GI tract mucosa. However, transdermal, subcutaneous, or intravenous routes may be necessary to restore levels of glutathione in the body. Glutamine is associated with improving gut associated lymphoid tissue (GALT) functions; stimulating mucosal growth and promoting intestinal health.99
Two thirds of autistic children have abnormal amino acid levels.100 Carnosine is an amino acid dipeptide that may enhance function in the frontal lobe area of the brain. Children given 800 mg of carnosine daily for 8 weeks showed significant improvement in neurological function.101 The frontal lobes of the brain control volitional behavior, emotion, epileptic activity, cognitive function, expressive speech, and abstract thinking. Carnosine administered to 1000 children successfully improvement (90%) receptive language, auditory processing, socialization, awareness of surroundings, fine motor planning, and expressive language.102
DMG (dimethylglycine) is a naturally occurring amino acid produced from choline catabolism. DMG positively impacts language processing. Although DMG can cause hyperactivity in autistic children, hyperactivity fades with addition of folic acid.63
Modifying a child's diet to improve GI system function is a common suggestion in autism treatment.103 Parental observations have reported a reduction of autistic behavior; increased social and communicative skills with a good diet, but reappearance of autistic traits after the diet has been abandoned.104 A gluten-free/casein-free (GFCF) diet removes casein (milk and dairy products) and gluten (wheat and other grain products) and is one therapy of choice for many parents to treat leaky gut syndrome. Implementation almost always leads to symptomatic improvement. 80% of autistic children on the diet improved following strict adherence to the GFCF protocol.105 Elimination of these proteins usually takes 3-4 weeks. A trial period of at least 6-12 months is recommended.106 Food intolerance testing (see below) can determine if a child has immune-mediated responses to these proteins. Food allergies in autism are IgG-mediated and take hours or days to develop, whereas classic allergies (e.g., those causing hives) are IgE-mediated and show an immediate sensitivity.
The simple carbohydrate diet (SCD) is a “hot topic” because it benefits so many on the autistic spectrum. The SCD limits carbohydrate intake and avoids complex starches such as soy, potatoes, and corn. Reducing carbohydrate intake may reduce inflammatory processes in the gut. The SCD starves bacteria, yeasts, and fungi in the intestines by only allowing foods easily absorbed by the intestines. Easily digested foods do not reach bacteria, yeasts, and fungi, so over time they will “starve.”
Sensitivities and allergies to food are common. Several food additives are notorious trouble-makers. These are avoided in the Feingold Diet. Food additives that are highest in problematic phenolic compounds are (1) synthetic food dyes such as Yellow No. 5 and Red No. 40; (2) artificial flavorings (also synthetic sweeteners such as Nutrasweet™ and Equal™); and (3) synthetic preservatives such as BHA, BHT, and TBHQ. These overload phenol sulfotransferase (PST) needed in neurotransmission. Individuals with attention deficit hyperactivity disorder (ADHD) and autism are low in PST. Dyes and preservatives are made from petroleum. Artificial flavoring can be made from petroleum and industrial waste products (e.g., artificial vanillin). In a sample of 1875 3-year-old children, artificial food coloring and benzoate preservatives adversely effected behavior.107 Foods containing “natural” salicylates (apples, grapes, and strawberries) can cause ill effects for some individuals. A chemical similar to acetylsalicylic acid (aspirin) is created in plants for protection purposes. Sensitivity to aspirin is well-known, but most healthcare providers are not aware that fruits can trigger similar sensitivities. The inability to effectively metabolize certain compounds; particularly phenolic amines that are toxic to the CNS, could exacerbate autistic behavior.108
The Feingold Diet suggests removing salicylates and artificial colorings, flavorings, and preservatives for at least 1 week. When the child is doing well, substances can be reintroduced and evaluated one at a time. Some people prefer to remove only synthetic additives and later consider removing salicylates. Even wholesome fruits can be threatening if a child's system is sensitive to them.
To make nutrients available to bodily processes needing them, digestive enzymes (such as salivary amylase) are required to break down carbohydrates, and trypsin and chymotrypsin are required to digest proteins. In many autistic children with poorly functioning or impaired GI tracts, enzymes are among the safest and most effective supplements to aid metabolism and break down foods not completely digested by an impaired system. This prevents formation of neurotoxic molecules and reduces undigested food that provides a breeding ground for pathogenic organisms such as Candida and Clostridia.
Probiotics replenish good bacteria normally in the gut to aid digestion and prevent overgrowth of harmful organisms that enter a leaky gut. Two probiotics used are bifidobacteria and lactobacillus. To remain on a gluten-free/casein-free diet while implementing probiotics, some bifidobacteria and lactobacillus probiotics are designed to be gluten-free/casein-free. Probiotic replacement should occur subsequent to laboratory testing to determine the extent of intestinal dysbiosis, the need for therapy, and the dosage required for therapy. Laboratory testing includes a complete digestive stool analysis with bacteriology and parasitology. Many laboratories perform these tests (see Summary for details).
Chelation therapy is the process of detoxifying the system of accumulated undesirable metals improve neurological function damaged by these metals. Improvement is seen in the autistic population using chelation therapy.109 Dimercaptosuccinic acid (DMSA) is approved by the U.S. Food and Drug Administration (FDA) for lead poisoning. DMSA is proven and safe for the autistic population. Because adverse effects can occur, chelation therapy must be undertaken by a qualified professional to assess the treatment. Chelation therapy is taxing on the patient because it depletes the body of offending toxins, but desirable minerals which need to be replaced by supplementation. Following chelation therapy, clinical signs such as dilated pupils; increased heart rate; excessive sweating; knee jerks; and hand flapping were improved.110 Laboratory results that indicate improvement include blood, urine, red blood cell, and immune markers (IgE, IgG).111
Note: The full benefits from mercury detoxification are not realized until GI disturbances and dysbiosis are corrected.112
Secretin, a pro-oxidant and a GI and CNS hormone, is secreted by cells of the upper intestinal tract in response to food intake. Secretin stimulates the pancreas to release bicarbonate to raise pH in the intestine for the digestive enzymes secreted by the pancreas. Secretin stimulates the liver to release bile and the stomach to release pepsin. GI disturbances occur in two thirds of autistic children. Using secretin treatment may benefit, yet it is widely criticized. In 1998 a “secretin craze” began when findings of an uncontrolled study in three subjects indicated secretin improved their socialization, communication, and GI symptoms.43 Several controlled clinical trials yielded mixed results.113 However, another study left open the possibility of a 10 % response rate to secretin.114 Research115 indicates that severely autistic children respond better to secretin therapy than mildly autistic children.
Colostrum is the yellow fluid produced by mammary glands just prior to giving birth. It is excreted in mother's milk for 3 days following birth only. It supplies immune and growth factors and a perfect combination of vitamins and minerals for newborns. Colostrum contains immunological properties providing bacteriostatic activity while preventing penetration of pathogenic microorganisms and absorption of potential allergens into the digestive and respiratory tract.116 Colostrum is well-tolerated and highly effective in the treatment of severe diarrhea, AIDS, and acute rotavirus.117,118
First, it is imperative to determine GI damage and leaky gut syndrome (poor stomach acid production, poor stimulation of small intestine secretions, and further disruption of digestion) with laboratory tests. Chronic infection of the gut lining causes swelling and impedes nutrient absorption. If the body is to heal itself, then therapy should focus on the GI tract. Foods need to be predigested as much as possible and cleared of toxins, antibiotics, and hormones. Stomach acid should be stimulated by oral acid-forming supplements or by medicinal agents. Oral enzymes should be given as a substitute for insufficient or absent stomach, pancreas, and upper bowel (duodenum) enzyme production. Good bacteria are necessary to displace anaerobes and fungi. Healing substances should be taken in adequate quantity. Implementation of alternative, elimination diets, and administration of probiotics to repair the leaky gut are of primary importance. Stabilizing the body systems with the proper nutrients can balance faulty systems; improving neurological manifestations of autism. Figure 4 shows the treatment options to be considered in autism management.
Comprehensive laboratory testing is first required to determine food allergies, heavy metals, and if the GI tract is compromised from leaky gut syndrome or other disorders. The following clinical tests should be considered:
Included in this test are digestive function (e.g., presence of undigested food); metabolic function (presence of short-chain fatty acids that reflect probiotic activity); microbiology (from bacterial culture); mycology (presence and types of yeast and other fungi); and parasitology.119 The following laboratories specialize in these tests:
Medical research has linked IgG-mediated food allergies to over 118 ill-health conditions. FoodScan is the first and most comprehensive IgG ELISA Food intolerance test that can be implemented in the home. A simple pin-prick to the end of the finger allows the necessary amount of blood required (50 microliters) to perform the test. The following laboratories specialize in these tests:
The following therapies are suggested subsequent to laboratory findings which indicate a compromised GI system:
Begin by making dietary changes one meal at a time. Eliminating these proteins from the diet should not be abrupt. Rather implement dietary changes according to a strict protocol, in various phases, to minimize a withdrawal reaction which will undoubtedly follow restriction of “toxins”. A 6- to 12-month trial of a GFCF diet might be necessary to observe benefits because these neurologically active peptides are retained and clearance is delayed.
Step 1. Remove all dairy products. Dairy products include milk, skim milk, butter, yogurt, lactose, powdered milk, goat's milk, cheese, casein, caseinate, and whey. Switch to milk substitutes such as rice milk or soy milk. Eggs and mayonnaise do not contain dairy even although they are sold in the dairy aisle.
Step 2. Remove all gluten products. Gluten products contain wheat, oats, rye, barley, spelt, kamut, triticale, and semolina. Many foods contain gluten, but this information is not stated on the label. Instead, it is hidden in label information as “modified food starch and natural or artificial flavorings”.63 It is important to read labels and become familiar with food ingredients.
Once converted to a GFCF diet, observe the child for signs of reactions to any products you are using. The range of things that cause children to react is endless, so watch your child as you make substitutions.
Note: Lisa Lewis has written an excellent book, Special Diets for Special Kids120, which is helpful for parents implementing dietary management.120 Another helpful book is Unraveling the Mystery of Autism and Pervasive Developmental Disorder: A Mother's Story of Research and Recovery.63
Stage One. Stage One is the initial period when substances are avoided to obtain a favorable response. Avoid the following:
Synthetic (artificial) colors: Food dyes may be listed as "food coloring, U.S. Certified Color, Color Added" or by their Food and Drug Administration number (FD&C Yellow No. 5). These dyes were formerly made from coal tar. They are now made from petroleum.121
Stage Two. After observance of a favorable response to Stage One of at least 4-6 weeks, proceed to Stage Two. During Stage Two, carefully re-introduce the salicylate items one at a time.
Synthetic (artificial) flavors. Artificial flavors may be listed in ingredients as "flavoring" or "artificial flavoring." Vanillin is the only synthetic flavoring clearly labeled by name. Many of thousands of flavoring chemicals are made from petroleum. Three synthetic antioxidant preservatives are BHA (butylated hydroxyanisole); BHT (butylated hydroxytoluene); and BHQ (tertiary butylhydroquinone). These preservatives are related to petroleum and in high doses impair blood clotting, and promote tumor development in the lungs, liver, bladder and thyroid.122-124
Salicylates. Salicylate is found in some fruits and vegetables (e.g., apples, apricots, all berries, cherries, chili powder, coffee, cucumbers and pickles, grapes and raisins) and over-the-counter medicines (e.g., aspirin). Medications containing aspirin should be avoided. See www.feingold.org for a complete list.
Important: Petroleum-based additives are never reintroduced.
Peptides are small polymers of amino acids that regulate or signal neurotransmitter systems regulating behavior. In Autism, certain peptides can be abnormally elevated in urine125 and indicate poor digestive function. Incompletely digested peptides with opioid activity could be cause autism.126
Abnormal peptides with opioid activity are found in urine of 22 of 25 autistics studied,125 while excessive endorphin-like substances, (exorphins), are found in the CSF of autistics.127 Dietary exorphins are produced from foods containing casein or gluten which breaks down into casomorphins, gluteomorphins, and gliadomorphins.
Raw foods provide enzymes that metabolize food for absorption. Digestive enzymes can aid absorption and promote a healthy digestive system. Digestive enzymes should be taken immediately before meals.
GI tract damage changes the gut environment, often causing an imbalance in normal bacterial flora. If the GI environment is imbalanced, overgrowth of yeast, parasites, and undesirable anaerobic bacteria occurs.128-130 Bad organisms negatively affect digestion and produce toxic substances such as alcohols and aldehydes.131,132 Many natural herbs and antibiotics are available to control these organisms. A simple method to help restore the normal gut flora is to overwhelm the “bad” bacteria with large doses of “good” bacteria. Strains of acidophilus, lactobacillus, and soil-based organisms which adhere to the gut wall can be given in daily doses over 100 billion organisms.133 The success of this therapy is evaluated by measuring urine for metabolites from yeast and other pathogens, or by stool analysis. Some acidophilus products are grown in a milk base which results in casein contamination. If these products are used, then simultaneous supplementation with digestive enzymes with dipeptidylpeptidase 4 (DPP4) activity is necessary. It is best to avoid any source of casein.
Saccharomyces boulardii (pure encapsulations), a "good" yeast, produces substances that eliminate "bad" yeast organisms. Use of S. boulardii may lead to a severe “die-off” reaction, making the child clinically worse for several days.134 Activated charcoal can help absorb toxic materials released from dying yeast and carry these toxins out with the feces.135 Digest RC contains Linden tree bark charcoal which is used internally for intestinal disorders136 and is useful in absorbing toxins.
Life Flora Mix contains important probiotic strains Bifidobacterium lactis, Lactobacillus acidophilus, Bifidobacterium longum, Lactobacillus paracasei subsp. paracasei, and Streptococcus thermophilus. These strains adhere to the GI mucosal membrane, tolerance stomach acid, colonize the intestinal tract, and control overgrowth of harmful bacteria, yeast, and viruses.137
An equally important step is to test for toxic heavy metals, specifically mercury and lead. Testing for mercury requires a urine challenge test with chelating agents utilizing either oral DMSA (2,3-dimercaptosuccinic acid) or intravenous dimercaptopropanesulfonate (DMPS). Systemic removal of mercury is important in helping autistic children. Mercury removal requires a carefully designed, physician-monitored program of chelation. A DAN (Defeat Autism Now!) physician or physician specializing in allergy and integrated medicine is recommended. A list of DAN physicians may be found at www.autism.com/ari.
Clinical trials with secretin are inconclusive. Secretin administered by oral, intravenous, intramuscular, or transdermal routes138 stimulates speech in some children and wild hyperactivity in others.43,139-142 Secretin is a pro-oxidant and a hormone acting on the GI and CNS. A secretin protocol is available from any DAN physician.
400 mg of carnosine benefited autistic children.143 Zinc may augment intracellular carnosine activation and vitamin E may enhance the antioxidant neuroprotective properties of carnosine. A high dose of carnosine may overstimulate the frontal lobe, causing increased irritability, hyperactivity, or insomnia commonly observed in hyperactive autistic children.144
When taurine levels are low, bile acids (which contain taurine) fall, causing poor digestion of fats and impaired liver function.145 Taurine deficiency exists in 62% of autistic children,146 is highly concentrated in brain, and is labeled the “brain amino acid” by the medical community. Taurine nourishes brain cells and membranes maintaining neurotransmitters that promote cognitive processes.147
Glutamine is an energy source for cells of the small intestine and helps form glucosamine for connective tissue. Glutamine is low in autistic children, particularly those who don't consume meat or poultry.148
A leaky gut causes an imbalance between good and bad bacteria in the GI and overgrowth of yeast. A history of antibiotic use for childhood illnesses often leads to leaky gut syndrome. Combating pathogens in the GI tract with excessive use of antibiotics will lead to resistant strains and a leaky gut. Normalizing the intestinal flora caused by an overuse of antibiotics is possible with a natural product such as cranberry extract or grapefruit seed extract. (Cranberry juice is therapeutic for urinary tract infections). Cranberry extract possesses antibacterial properties against pathogens such as Escherichia coli, Staphylococcus. aureus, and Pseudomonas aeruginosa. One capsule provides the same therapeutic efficacy as 16 eight-ounce glasses of cranberry juice. Grapefruit seed extract is anti-germicidal and a bioflavonoid from seed and pulp that inhibits growth of bacteria, fungi, parasites, and viruses.
Children with autism spectrum disorders have dysfunctional sleep patterns149 and often have insomnia.150 Many have gastroesophageal reflux which causes awakenings.151,152 Melatonin is effective in some children with abnormal melatonin circadian patterns.153,154
[Composition: See end of document for Figure 4.]
Figure 4 Autism Biomedical Treatment Options
Post-diagnosis, the following should be implemented under advisement of a nutritionist or neurodevelopmental pediatrician experienced in the management of autism.
Laboratory tests to include blood chemistry (including thyroid), complete blood count (CBC), urinalysis, serum iron levels, amino acid screening (urine), organic acids screening for inborn errors of metabolism (urine), PKU screening, chromosomal studies (Fragile X, Rett's syndrome, when indicated), and heavy metal testing (Additional assessments for signs of neurological damage including MRI, CAT scan, X-rays, and EEG (evaluation of epilepsy) may be required.)
Stool analysis to include bacteriology and parasitology assessments for a compromised GI tract and malabsorption, dysbiosis, intestinal hyperpermeability, and IgG/IgE food intolerance testing (blood).
Implementation of GFCF (gluten-free/casein-free) diet, SCD (simple carbohydrate diet), and/or the Feingold Diet or other elimination or additive-free diets should be considered.
A daily regimen of probiotics to include bifidobacteria and lactobacillus (based on bacteriological testing) to maintain optimal gut function is suggested.
DMSA must be used only under the advisement of a physician or nutritional specialist who will prescribe the proper usage and dosages for the following listed supplements. Epsom salts baths can supply some sulfur needed for liver detoxification.
This protocol was written and edited by Sharon Ruben, B.S., M.S. whose daughter recovered from autism through various early intervention modalities including the nutritional therapies included in this protocol. She is author of Awakening Ashley: Mozart Knocks Autism on Its Ear.
Sections were written and edited by Randall Lee Kohl, Ph.D., R.Ph., FCP, Senior Editor for LE Publications, Inc. Please direct your comments only to rkohl@lef.org. Direct questions to the Life Extension Health Advisory staff at (800) 544-4440.
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