Nutrient Power

In 1939, Winston Churchill referred to Russia as “a riddle wrapped in a mystery inside an enigma.” Today these words could be used to describe autism. First reported by psychiatrist Leo Kanner113-114 in 1943, autism spectrum disorders have reached epidemic proportions, increasing from 3 in 10,000 births to about 1 in 100 in the USA.115 A typical schoolteacher in the period 1940 to 1980 encountered one or two cases in an entire career. Today most teachers learn of new autism cases in their districts each month. For several decades, the increasing numbers were attributed to better efficiency of diagnosis. However, this cannot explain the continuing sharp increases since 1990 when the syndrome of autism became well known throughout the medical field.

There is an undeniable heritable component to autism, with about 60-90% concordance in identical twins in contrast to less than 10% for fraternal twins.116 Since concordance is less than 100%, a very significant environmental component exists. I once studied an autistic adult with wild behavior and severe cognitive delays, and then I met his identical twin who was a personable, highly successful professional. They had identical physical appearance and blood/urine chemistry, but the difference in their level of functioning was staggering. The mother said both sons developed normally the first 18 months, after which one twin developed severe autism symptoms while the other continued to thrive. She had no explanation for the difference in her sons. Another case involved identical twin boys (age 3) who presented with very similar autism symptoms and biochemistry. After a few years of biochemical treatment, one twin achieved a full recovery and has been excelling in a mainstream classroom. His brother had a partial improvement but is still on the autism spectrum. Since their treatments and diets were identical for years, it seems likely one twin experienced more severe environmental insults, such as exposure to pesticides or toxic metals.

Many people ask, “How can there be an epidemic of a genetic disorder?” And, in fact, there cannot be a purely genetic epidemic. Heritable DNA mutations usually require centuries to develop. Spontaneous DNA abnormalities in human beings occur about once in every 500,000 cell divisions, and few are transferred to the next generation. As described in Chapter 4, fetal development during the first month of pregnancy is sensitive to environmental insults that can disrupt epigenetic processes that govern which genes are expressed and which are silenced. These epigenetic abnormalities usually persist throughout life, and, in certain cases, may be passed on to future generations. In any case, it is clear that the increased rates of autism are due to changes in the environment over the past 70 years. More than two-dozen theories have been suggested, including increased vaccinations, toxic metal exposures (also possible via vaccines), changes in the water supply, a compromised in utero environment, industrial food processing, and changes in family dynamics. There is little agreement among autism researchers and clinicians regarding the environmental triggers, but one thing has become very clear: the usual recipe for autism is a combination of an inherited predisposition and severe environmental insults prior to age three.

Approximately four out of every five children diagnosed with autism are male. Until 1960, most cases involved clear symptoms at birth. During the ensuing decades, regressive autism rates gradually increased and now represent about 80% of cases.117 The reason(s) for the increased prevalence of regressive autism is still being debated. In typical regression cases, children develop normally until age 16-24 months, when a fairly sudden decline in functioning occurs.

I have met hundreds of parents who reported their child had developed normally until they approached age two. In a typical case, the child was in good health, happy, and beginning to speak when an unexpected regression occurred over a few days or weeks. Most families reported loss of speech; a divergent gaze; odd, repetitive movements; disinterest in parents and siblings; gastrointestinal symptoms; and emotional meltdowns. A visit to the pediatrician usually was followed by evaluation at a child development center. Many families tearfully described their horror at receiving a diagnosis of autism and being told the condition was incurable and would result in a lifetime of severe handicap. This scenario is still common today, and many families are advised to institutionalize their child, despite the fact that many children are recovering—losing their autism classification and becoming indistinguishable from their same-age peers—with appropriate, individualized interventions.

The psychiatry profession has provided great benefits to society over the past century. However, mainstream psychiatry’s theories regarding autism were dead wrong for about 30 years, resulting in lack of scientific progress and failed therapeutic approaches. Leo Kanner’s first publication in 1943 described autism as a severe developmental disorder caused by poor parenting.113 He summarized 11 case histories and reported that all of the parents were uncaring and lacking in empathy. Kanner concluded that these children had been emotionally deprived during the early years, resulting in enduring deficits in socialization and communication. A popular early treatment involved isolating the children from their “incompetent” parents, and showering them with affection and encouragement in an institutional setting. This well-intentioned—but ineffective—approach persisted for decades. In 1967, famed autism expert Bruno Bettelheim of the University of Chicago published a book118 titled The Empty Fortress: Infantile Autism and the Birth of the Self that influenced autism therapists for several decades. Bettelheim claimed that autism was the result of a “refrigerator mother” who wished the child had never been born and a weak or absent father.

My first experience with autism involved a research colleague whose only child was diagnosed with autism in the 1960s. When we became close friends, he confided that he and his wife were being treated for clinical depression that began upon learning of their son’s autism, and the depression dramatically worsened after experts explained they were failures as parents and had caused their son’s disorder. During this time period, countless thousands of parents suffered great anguish when the finger of blame was pointed directly at them. The world now knows that the concept of a refrigerator mother and distant father was completely wrong and did great harm. In fact, the exact opposite is true. Most parents of children diagnosed with autism are remarkably loving and extremely dedicated to helping their child.

A misguided belief that still persists is that autism is incurable and affected children face a dismal future. Recent advances in biomedical and behavioral therapies have resulted in thousands of reports of recovery throughout the world. Most of these reports involved intervention prior to age four, but significant progress can be made at any age. I once received a phone call from a mother from Connecticut who said her 17-year-old daughter began speaking after two months of biochemical therapy! (Biochemical therapy, which uses chemicals natural to the body, is a subset of biomedical therapy.) Medical science is sometimes slow to adopt new effective therapies, and lack of compelling scientific evidence—the funding and publication of which is prey to political roadblocks—is often part of the problem. I look forward to the time when the medical and scientific communities acknowledge that autism is treatable, and parents of affected children are urged to seek aggressive (yet safe) treatment immediately after diagnosis.

There is an old saying that “Once you’ve met one autistic child, you’ve met one autistic child.” There is great variation in symptoms and traits from child to child. Some are hyperactive, and others are lethargic. Many are completely nonverbal, whereas others have significant speech. About 30% have abnormal EEG brain waves and a tendency for seizures. Some have explosive behavior, and others are quite calm. Despite these individual differences, there are classic symptoms and traits usually present in four key areas.73

Socialization: This includes very poor social skills, including lack of interest in others, resistance to cuddling and holding, and an apparent preference to retreat into their own world.

Language: This includes either absence of speech or a major speech delay, inability to start a conversation or keep one going, a tendency to repeat the sounds of others (echolalia), an unusual tone or rhythm of speech, and a very limited expressive vocabulary.

Behavior: This category includes repetitive movements, such as rocking, spinning or hand flapping; behavioral routines or rituals; little or no eye contact; an obsessive interest in certain objects, such as spinning toys, or using the parts of toys in an atypical way (e.g., perseverating on spinning the car wheels); an inability to make transitions; sensitivity to touch, light, and sounds; and impulsive actions, such as running into the street.

Cognition: This involves slowness in acquiring new knowledge or skills and weakness in applying knowledge to everyday life.

In addition, a high percentage of children diagnosed with autism have significant physical problems, including poor immune function, severe constipation, food allergies, intestinal yeast overgrowth, and heightened sensitivity to toxic metals. These fall under broader physiological issues that include oxidative stress, immune dysregulation, and detoxification impairment.

Autism spectrum disorders consist of three major types: (1) classical or Kanner’s autism, (2) pervasive developmental disorder—not otherwise specified (PDD-NOS), and (3) Asperger’s disorder (aka Asperger’s syndrome).73 There are great differences in severity among the three groups. Asperger’s syndrome is often referred to as high-functioning autism and typically involves normal or above-normal intelligence and competent speech. However, Asperger’s individuals exhibit very poor socialization, divergent gaze, atypical behaviors, and obsessive or ritualistic interests. Many are savants with extraordinary abilities in mathematics, memory, or music. Dustin Hoffman’s character in the movie Rain Man provides an excellent example of Asperger’s syndrome.

Classical or Kanner’s autism is the most severe disorder in the autism spectrum, and its sufferers usually exhibit most of the above symptoms and traits by age three. Without effective treatment, these individuals are likely to experience a lifetime of frustration and unhappiness as well as severe deficits in cognition, socialization, and speech. Fortunately, advanced biochemical therapies usually result in exciting partial progress, with many reports of complete recovery. There is a great need for controlled scientific studies to accurately measure effectiveness of these new therapies. Such studies are hampered by the very high placebo rate (about 40%) in autism, perhaps arising from an inability to control the environment of children who are highly sensitive to a multitude of factors (known and unknown). In many cases, placebo effects do not involve imaginary improvements but actual improvements that have nothing to do with the treatment. In addition, it is difficult to recruit families if their child might be in a control group that uses the placebo.

Children diagnosed with PDD-NOS have symptoms that are intermediate in severity between classical autism and Asperger’s syndrome. The distinction between classical autism and PDD-NOS is not always clear, and many children receive both diagnoses after evaluation by separate professionals. A large chemistry database study in 2001 reported very disordered blood and urine chemistries for all members of the autism spectrum, with no detectible difference between classical autism, PDD-NOS, and Asperger’s.119 This finding suggests that all members of the autism spectrum may have the same inherited predisposition but differ in the type, severity, or timing of environmental insults. For example, children who achieve a higher degree of brain development prior to the insults would be expected to be capable of higher functioning.

Although experts are able to detect subtle autism tendencies by studying early video tapes, the extreme deterioration that often occurs within a few days needs explanation. I have met hundreds of parents who reported very rapid regressions, including cases in which vaccinations, illnesses, or known toxic exposures were not involved. The global nature of the regressions can be striking, including loss of speech, odd repetitive movements, divergent gaze, sudden intolerance to certain foods, and extreme personality change. It seems clear that a major event has occurred within the brain—and perhaps throughout the entire body.

Wilson’s disease73 and schizophrenia are other medical conditions that involve a rapid deterioration in cognitive functioning after a period of relative normalcy. An important difference is that autism develops during a critical early phase of brain development. The median age of onset of Wilson’s disease is 17 years. In this disorder, the ability to remove copper from the liver and other organs is impaired, resulting in extreme deterioration in physical and mental functioning. Wilson’s disease, schizophrenia, and autism are similar in that all involve oxidative overload, with extreme depletions of protective proteins MT and GSH. In Wilson’s, gradual worsening of oxidative stress can progress until the MT and GSH antioxidant functions are overwhelmed, resulting in (a) sudden impairment of bile transport of copper from the liver and (b) dramatic worsening of symptoms.

The onset of schizophrenia usually occurs after age 16 during a period of severe emotional or physical stress that may increase oxidative overload and trigger the mental breakdown event. These similarities suggest that a study of the regressions in Wilson’s disease and schizophrenia could provide valuable clues to the origin of autism spectrum disorders.

The extreme suddenness of autistic regressions raises many intriguing questions, but the permanence of the autistic condition is even more mysterious. In the absence of early biochemical therapy, autism most often leads to a lifetime of disability. After age six, therapies that effectively overcome oxidative stress, toxic overloads, food sensitivities, yeast overload, metal metabolism imbalance, and weak immune function can provide significant improvements, but the essential autistic condition of cognitive and/or social and/or speech impairment usually remains at some level. I have witnessed hundreds of cases of autism recovery, but nearly all involved aggressive intervention prior to age four. This strongly suggests that (a) the central problem in autism is early brain development that has gone awry, and (b) a full recovery is extremely unlikely unless treatment begins before completion of this critical stage of brain maturation. Autism researchers and clinicians disagree on many points, but they unanimously agree that early intervention is essential. Medical institutions, government agencies, and insurance companies should rally to make this available to children immediately after diagnosis. Although early intervention is the most optimal route, there have been recoveries and major improvements—such as verbalization beginning in adulthood—that have occurred even when biomedical therapies were begun well after early childhood. Every individual with autism deserves our best dedicated efforts to improve their quality of life.

Many of the mysteries shrouding this illness have begun to be solved by autism researchers. Some of the more important findings involve differences in brain structure and organization. German researchers120 have found anatomical abnormalities of the amygdala-fusiform system, indicating poor connectivity between these brain areas. Researchers at Harvard121-122 and elsewhere have reported that primitive areas of autistic brains are immature, having failed to complete development of brain cells and synaptic connections. This knowledge suggests that therapies aimed at completion of brain development may be a high priority. Casanova123-124 has reported abnormalities in the cortex of autistic brains, especially narrowing of minicolumn arrays of cells. McGinnis and colleagues125 have reported threadlike accumulations of damaged fats in autistic brains, indicating oxidative damage. Courchesne126 found that many children with autism experience a rapid acceleration in brain size during the first year of life. Approximately 25% of autistics develop unusually large heads during early development. All of these findings suggest that early intervention is of critical importance since brain abnormalities that develop in the initial years may persist throughout life. The plasticity of brain cells and synapses is greatest in infancy and early childhood, and exciting progress is possible during this window of time.

We all start life with billions of short, dense, brain cells that are immature. Brain development involves four basic phases:

Researchers have reported an excessive number of short, undeveloped brain cells in the cerebellum, pineal gland, hippocampus, and amygdala of individuals with autism. This brain immaturity is primarily in areas with little or no protection from the blood-brain barrier, suggesting that chemical insults or excessive oxidative stress may have stunted brain development. In addition, these children exhibit a poverty of dendrites and synaptic connections. The number of brain cells in a typical human brain is roughly equal to the number of trees in the United States; the number of dendrites has been likened to the number of leaves on those trees. In autism there are a reduced number of developed brain cells and fewer branches on the cells. The net result is a lessened ability to develop synaptic connections needed for learning, speech, and socialization.

The brain area with the most pronounced immaturity in autism is the cerebellum, which is responsible for smooth, controlled movements. A majority of individuals with autism exhibit odd, repetitive movements, possibly due to an impaired cerebellum. Another affected brain area is the amygdala that enables a person to develop social skills. Deficits in socialization are a hallmark of autism, and an immature amygdala may be part of the problem. The hippocampus partners with Wernieke’s area and Broca’s area in the development of speech. Mutism and speech delay are common in autism, and a poorly functioning hippocampus may be responsible.

Fortunately, the ability to develop immature brain cells and new synapses continues throughout life. This capability enables many paralyzed stroke victims to recover and also offers hope for children with autism. The speed with which new brain cells and synapses are developed is extremely rapid until about age four when a gradual slowing occurs. This explains why a four-year-old visiting Paris may speak fluent French within six weeks, while a teenager may require a year or more, and a senior citizen might never achieve this capability. Clinicians working with autistic children are aware of the critical need for early intervention. In my experience, greater progress can be achieved in one month with a two-year-old, than in six months with an eight-year-old. Doctors and parents need to be aware that immediate action is essential once the diagnosis of autism has been made.

Brains of individuals with autism also appear to be afflicted with significant inflammation127 that may inhibit brain development and cause a myriad of symptoms, including irritability, speech delay, sleep disorders, cognitive delay, and increased head size. The sudden regression experienced by many children may be caused by events that result in brain inflammation.

In addition to the brain being structurally impacted, most children diagnosed with ASD experience physical problems128 that can bring considerable misery to the child and make parenting very difficult. Many are afflicted with severe GI tract problems, including malabsorption, food sensitivities, esophagitis, reflux, incomplete digestion of proteins, yeast overgrowth, constipation, parasite overloads, and an incompetent intestinal barrier. Other common problems include poor immune function, seizures, sleep disturbances, chemical sensitivities, poor appetite, sensitivity to touch and sound, and enuresis (involuntary urination). There are numerous reports of high anxiety, apparent pain, frustration, and emotional meltdowns. Caregivers and educators would do well to first look to underlying physiological conditions that cause pain and other symptoms before attributing challenging behaviors to purely behavioral roots.

Many parents report their child’s autism started immediately after a vaccination, and this is a hotly debated issue today. Most mainstream medical experts deny this relationship, but a genetic or acquired hypersensitivity to certain vaccines or an impaired ability to detoxify vaccine components remains a definite possibility. Another controversial and widespread belief is that autism is caused by exposure to mercury and other toxic metals. A 1999 FDA recommendation called for reducing or eliminating the mercury-containing preservative (Thimerosal) in childhood vaccinations. This has resulted in a major reduction of mercury exposures in the USA, although the elimination of mercury exposures to children is far from complete. Notwithstanding, autism rates have continued to escalate since the FDA’s action,115 suggesting that mercury is not the only suspect in autism causation. However, mercury is a highly poisonous substance, and the recommendation to remove Thimerosol from vaccines was a sensible public health measure.

The multiplicity of autism symptoms has hampered the ability to measure treatment effectiveness in clinical experiments. ASD children are highly sensitive to their environment, and there is continual waxing and waning of some symptoms due to changing conditions that may be imperceptible to the family. As a result, virtually every treatment approach will result in numerous reports of improvement. The result is that several ineffective therapies have gained popularity, and potentially effective therapies may have escaped notice. In autism research studies, the percent of improvement in control groups is usually greater than 40%, which presents a significant barrier to accurate evaluation of new therapies. Another research problem is that most ASD children have a history of aggressive therapy interventions that can alter the underlying condition. This has led some researchers to restrict their experiments to treatment naïve ASD children who have never been treated. Finally, what helps one child may not help another at a given time because of the order in which the interventions were done. For example, educational strategies work better after biochemical or other dietary therapies have already been initiated.

For several years, we tested for gluten and casein intolerance by measuring casomorphin and gluteomorphin levels in blood. These abnormal proteins result from incomplete breakdown of certain dairy and grain proteins in the digestive tract. There is considerable evidence that these deviant proteins can readily pass intestinal and brain barriers and cause a myriad of behavioral and cognitive problems. Children diagnosed with these food sensitivities were routinely placed on strict gluten-free/casein-free (GF/CF) diets. A study of 500 autism cases showed that 85% of families adopting the special diet reported major benefits. Hundreds of parents told me of very rapid and striking improvements in their children. A study of the 15% nonresponders revealed that about half had a family history of Crohn’s disease or other inflammatory bowel disorder. This experience has convinced me that all autism spectrum children deserve a trial of the GF/CF diet, with or without the benefit of special laboratory testing.

Children with autism exhibit distinctive chemical imbalances not present in the general population. By 1999, I had collected a database of 50,000 chemical assays of blood and urine for autistic children and was invited by the late Dr. Bernard Rimland of the Autism Research Institute to present the findings at a think tank in Cherry Hill, New Jersey. The assembled audience of autism researchers and clinicians was familiar with my findings:

However, the group expressed great surprise at data indicating that more than 90% of autistics were undermethylated. Subsequent research by S. Jill James,69 Richard Deth,70 and others has shown that undermethylation is a distinctive feature of autism. By 2009, a wealth of biochemical information had been collected by autism researchers throughout the world. Table 7-1 lists typical biochemical features of autism spectrum disorders.

Table 7-2 lists popular biomedical therapies aimed at normalizing body/brain chemistry in ASD patients. These treatment approaches have resulted in hundreds of reports of significant improvement, and each has developed a cadre of enthusiastic supporters. However, in every case, the treatment must be regarded as unproven until careful double-blind, placebo-controlled studies can prove efficacy. At present, none of these approaches has been adopted by mainstream medicine.

Table 7-1.
Biochemical Features of Autism (partial list)

• Low levels of glutathione

• Undermethylation

• Elevated mercury, lead, and other toxins

• Copper overload and insufficient ceruloplasmin

• Zinc deficiency

• Vitamin A deficiency

• Elevated urine pyrroles

• Depressed metallothionein protein levels

• Elevated carboxyethylpyrroles

• Low levels of magnesium

• Deficiency of selenium and cysteine

While evaluating extensive blood and urine chemistries for thousands of ASD patients, I learned that more than 99% exhibit evidence of excessive oxidative stress.119 Chemical biomarkers for this condition include pervasive zinc deficiency; elevated pyrroles; low Cu/Zn SOD;129 copper overload; low ceruloplasmin; undermethylation; low levels of glutathione, selenium, and MT proteins; and elevated levels of mercury, lead, and other toxic metals. Recent research studies have heightened interest in this area, and many experts now believe that oxidative stress is central to the etiology of autism.

Examination of the popular biochemical therapies shown in Table 7-2 reveals that nearly all provide an antioxidant effect. For example, the most commonly prescribed drug for autism patients is Risperdal, which has antioxidant properties. Therapies to overcome hypomethylation result in more robust levels of the natural antioxidants glutathione, MT proteins, and cysteine. The GF/CF diet results in reduced inflammation, which lowers antioxidant requirements.

Many respected researchers and clinicians believe that mercury poisoning is the central problem in autism and use chelating chemicals that strip this toxin out of the body. Chelation is a standard medical procedure used by mainstream medicine for cases of severe lead or mercury poisoning. We encountered several cases of toxic metal poisoning in depressed patients, and we were very impressed by the rapid and permanent recoveries following four or five days of in-hospital chelation therapy. However, I’ve learned that chelation of children with autism usually presents a very different picture. In the late 1990s, we surveyed hundreds of families with an ASD child who had utilized chelation. In most cases, they reported very exciting improvements in their child during early stages of the therapy. Most parents said the improvements began to fade away after two to three weeks, with their child returning to the pretreatment condition. Many doctors concluded they needed to remove more mercury, and the 5-10 day chelation procedure was repeated. I met several families who had repeated this process more than 20 times over more than a year with the same result: definite improvement that faded away after about 17 days. It was clear to me that most of the excess mercury should have been removed after the first few chelations, and I concluded that the primary benefit was the powerful antioxidant effect of the chelating agent(s) rather than mercury removal. My chemical studies of thousands of children with autism revealed most to have high-normal levels of mercury but not mercury poisoning. High-normal toxic metal levels can result from weak antioxidant capability, without unusual mercury exposures. We did encounter a few autistic children with severe mercury poisoning, and a few weeks of oral DMSA chelation were administered to correct this problem.

Table 7-2.
Popular Biomedical Therapies for Autism (partial list)126

• Methyl-B12 and other methylation therapies

• Supplementation with vitamins/minerals found in deficiency

• Transdermal glutathione

• Casein-free, gluten-free diets

• Chelation (removal of toxic metals)

• Metallothionein-Promotion therapy

• N-Acetylcysteine and alpha lipoic acid

• Therapies to combat yeast overgrowth

• Antibacterials and antifungals

• Decoppering protocols

• Amino acid supplements

• Digestive enzymes

• Hormonal treatments

• Secretin

• Hyperbaric therapy

Weakness in antioxidant protection makes individuals with autism especially sensitive to mercury, and the 1999 recommendation to remove mercury preservatives in childhood vaccinations was a sensible public health action. It must be noted that mercury can have a devastating effect on a developing brain. All families need to be vigilant in protecting their children from sources of toxic metals, including untested well water, contaminated toys, and lead-based paints. Even more important may be the need to avoid exposure to toxins during pregnancy. The bottom line is that elimination of excess oxidative stress is a requirement of an effective autism therapy program.

Roughly one-third of children diagnosed with an autism spectrum disorder have a history of either seizures or abnormal electroencephalograms (EEGs). A careful study of 503 ASD children that excluded subjects with a history of seizure tendencies found about 99% to have copper and zinc imbalances. Several studies of ASD populations that include subjects with seizure tendencies reveal that a substantial number of ASD children do not exhibit these imbalances. This suggests that the combination of ASD and seizures may represent a phenotype that is distinctly different from other ASD children.

When a child is diagnosed with ASD, most families begin an intensive study of the disorder and quickly learn that early intervention is essential. The problem is that there are a multitude of treatments, and it is impossible to do all of them. The first decision is whether to limit therapy to the recommendations of mainstream medicine. After involvement with thousands of ASD patients, I’ve learned that most families are initially told that autism is incurable, and the most common recommendations are applied behavior analysis (ABA), Risperdal, and/or institutionalization. Most families who utilized ABA reported that this system helped their child, although the benefits were painstakingly slow, expensive, and quite limited. Risperdal is an atypical antipsychotic medication developed for schizophrenia that many psychiatrists prescribe for autism spectrum children and adults. The high risks associated with Risperdal are described later in this chapter. I doubt if doctors would suggest institutionalization if they knew that recovery was possible using advanced biochemical therapies. It seems clear that ABA is an excellent recommendation for families who can afford it or whose children can obtain this via the school system, and it is especially effective when used together with biochemical treatments.

While psychotherapy and counseling have lost credibility in autism, ABA continues to be very popular and effective, and a number of different ABA protocols130 -134 are used extensively. In general, ABA involves a multitude of direct interactions with an affected child over a period of months or years. The protocols are aimed at elimination of inappropriate behaviors and development of positive behaviors to enable improvements in speech, socialization, and learning. In general, without assistance, ABA is very expensive and requires great patience. However, research studies have consistently shown benefits,135-136 and ABA is recommended by most mainstream autism experts today. In addition to ingraining positive behaviors and traits, it’s likely that ABA stimulates the development of new brain cells and synaptic connections that can result in a permanent improvement in functioning.

A good example of biomedical interventions working well together with educational/behavioral interventions exists in the area of gastrointestinal tract improvement. Many children exhibit disruptive behaviors because they are in pain from GI issues like constipation, esophageal inflammation, and reflux. A behavior plan simply won’t suffice. When the underlying GI issues are addressed, such as with therapeutic diet and anti-inflammatory agents, children have less pain and exhibit behaviors more suitable to learning in a classroom. However, due to remembering the pain caused by trying to have a bowel movement, ABA behavior strategies may need to be implemented to reteach appropriate toileting habits. Repairing the gut also can accomplish the following important goals:

Prevents undigested proteins from reaching the brain and causing aberrant behavior

Allows desired nutrients to reach the brain and nourish it for tasks like learning

Allows foods to be digested so that harmful overgrowths of detrimental flora (e.g., clostridia) do not proliferate, thereby releasing toxic byproducts that travel to the brain and cause detrimental behavioral effects

Precludes further inflammation of the gut, which hithertofore would have initiated a cascade of events whereby gut inflammation increased proinflammatory immune messengers that also traveled to the brain causing immune activation

There are a multitude of biomedical therapies to choose from, with new ones introduced each year. I have arbitrarily separated them into three general categories.

In many ways, children with autism are quite sick and can benefit greatly from treatments that overcome malabsorption, food sensitivities, yeast overgrowth, parasites, constipation, enuresis, poor immune function, and so on. These treatments can often provide a rapid reduction of symptoms that make life more manageable and comfortable for both the child and family. However, these treatments do not directly address the abnormalities in brain development that are central to learning, speech, and socialization.

It is increasingly clear that brain inflammation is a common feature of autism137 that can cause irritability, erratic behavior, and diminished brain function. Treatments that reduce brain inflammation may result in striking and rapid improvements in symptoms. These benefits accrue mainly from more efficient functioning of the brain in its present state of development. As described previously, many ASD children cannot completely break down casein and gluten proteins in their diets, resulting in casomorphin and gluteomorphin aggregates138 that can enter the brain and cause inflammation. Numerous families adopting a GF/CF diet report a rapid reduction in autism symptoms. Since brain development is a gradual process that occurs over several years, it is likely that the sudden improvements in behavior, bedwetting, speech, and socialization are due to lessening of brain inflammation.

In another example, hyperbaric therapy139 is known to reduce brain inflammation in patients suffering from head injuries or strokes. Hyperbaric therapy has become a popular autism treatment with many reports of impressive improvements. However, in many cases, these benefits are temporary and repeated hyperbaric sessions are required to maintain improvements.

Copper overload is a distinctive feature of autism associated with inflammation, and decoppering therapies have resulted in reports of lessened autism symptoms. These are all examples of therapies that improve symptoms but may not directly enhance brain maturation. A general rule is that any autism therapy that results in sudden improvement has reduced brain inflammation but that therapy may not be the best technique for development of new brain cells, dendrites, and synaptic connections needed for advances in cognition, speech, and socialization.

Recent studies indicate that severe oxidative stress is a distinctive feature of autism and may be the most important barrier to achieving proper brain function. The symptoms associated with excessive oxidative stress mirror the classic symptoms of autism spectrum disorders. If all we knew about a patient was the presence of severe oxidative stress, we would expect the following:

Depressed levels of glutathione, cysteine, and metallothionein protective proteins

Each of these problems is very familiar to autism clinicians, strongly suggesting that oxidative stress is a distinctive feature of autism. Moreover, most therapies reported to benefit individuals with autism (including Risperdal) have strong antioxidant properties.

Elevated oxidative stress in the womb could modify epigenetic imprinting of gene expression, alter brain development, and weaken development of lymphoid and thymic tissues needed for immune function. Continuing oxidative stress in early childhood could alter development of brain cell minicolumns needed for learning, memory, and other cognitive functions; could inhibit brain maturation; could impair connectivity of adjacent brain regions; could increase vulnerability to toxic metals; and could alter brain neurotransmitter levels. In addition, elevated oxidative stress is associated with neurodegenerative destruction of brain cells. It appears that autism may be slowly neurodegenerative, with gradual loss of brain cells and IQ, especially after puberty. For years, I was puzzled by mainstream medicine’s belief that mental retardation was common in autism, which is described in the DSM-IV-TR. After working with thousands of families, it appeared to me and my colleagues that young individuals with autism are very alert and bright, despite their odd behaviors and speech and socialization deficits. In contrast, most of our adult autism patients were heartbreaking cases involving severe mental retardation. Exceptions are Asperger’s adults who generally exhibit continuing high intelligence. These observations imply that classic autism involves a tendency for gradual degeneration of brain cells and a loss of IQ. Research studies by McGinnis and colleagues125 have indicated oxidative damage in brain tissues of children with autism. The good news is that inexpensive antioxidant therapy may overcome this tendency if continued throughout life. There are a number of antioxidant therapies including:

Supplementation of glutathione, selenium, alpha lipoic acid, zinc, and vitamins C and E

Risperdal is an atypical antipsychotic medication developed for schizophrenia that is often prescribed for autistic children by mainstream doctors. Published research by McCracken and others has demonstrated that this medication can effectively reduce irritability and emotional meltdowns in autistics.141 However, the safety of Risperdal has never been established for young children, and its impact on early brain development is unknown. Recent MRI studies have heightened these concerns due to strong evidence that atypical antipsychotic medications reduce brain cortex volumes.

The first warnings came from published reports of reduced cortical gray matter volumes and glial cell numbers in macaque monkeys after administration of atypical medications.142 -144 These results were especially significant since they were very similar to the findings from postmortem studies in schizophrenia.145 The most decisive and troubling study was published in 2011 by Beng-Chung Ho and colleagues from the University of Iowa’s Department of Psychiatry.88 The Iowa researchers studied 211 schizophrenics who underwent repeated high-resolution MRI scans over a period of 5-14 years. They found brain shrinkage similar to that observed in the monkey studies, and they also discovered that the brain volume loss was directly related to the dosage and duration of atypical medication treatment.

These results have caused great concern in the psychiatry community since atypicals have become the treatment of choice for schizophrenia patients. A February 2011 editorial146 in the prestigious Archives of General Psychiatry stated that the risk/reward ratio for use of atypicals may be far greater than previously believed and urged psychiatrists to “prescribe the minimal amount(s) needed” in management of schizophrenia patients. The editorial also recommended increased use of nonpharmacological approaches and pursuit of alternate medications.

These disturbing findings do not prove that Risperdal causes brain shrinkage in children with autism since similar experiments have never been performed for this population. However, the risk of Risperdal use in young children appears very real, especially for those who have not yet completed the brain development process. Risperdal’s benefits for autism patients are very real but are limited to behavioral improvements. It appears these benefits may come at an unacceptable price. The new findings of brain shrinkage after atypical medications make it very difficult to justify the use of Risperdal in autism.

While treatments to enhance health, eliminate toxins, reduce inflammation, and overcome oxidative stress are essential, the greatest potential for progress lies in treatments aimed directly at the autistic brain. These treatment initiatives may be divided into two general categories:

Therapies that promote formation of new dendrites, receptors, and synaptic connections.

Brain-directed therapies may be the best way to make decisive advances in cognition, speech, and socialization, but they have received relatively little attention.

In 2000, I discovered that elevated copper and depressed zinc occurred throughout the autism spectrum, suggesting low activity of MT proteins that regulate these metals. Pervasive deficiency of cerulloplasmin (copper-binding protein) in ASD indicated that this copper elevation could not be attributed to inflammation. MT proteins are intimately involved in all phases of early brain cell development, including pruning, growth, and growth inhibition. Suspicion that low MT activity was involved in brain immaturity was supported by the fact that MT levels are highest in brain areas known to be immature in autism (e.g., amygdala, hippocampus, pineal gland, and cerebellum). Testing of ASD patients and controls revealed low MT levels in the individuals with autism. Encouraged by this knowledge, I developed an MT-Promotion therapy147 using amino acids, minerals, and vitamins known to enhance genetic expression and regulation of MT proteins. In our patient population, this therapy resulted in clear improvements in efficacy, based on an open-label study.

Dr. Amy Holmes performed an independent study of MT-Promotion therapy and also reported excellent results. However, use of this therapy has been hindered by the proliferation of improper commercial lab tests that generated many erroneous reports of elevated MT in autism spectrum patients. A possible limitation of MT-Promotion therapy is that it doesn’t directly address the reduced number of dendrites and receptors in the brain cells of persons with autism. Development of new and effective therapies to stimulate brain maturation is a very high priority. A recent discovery is the role of semaphorin proteins in guiding axonal growth to form effective synapses and minicolumns. Other promising research areas that could lead to therapies for promoting brain plasticity include parvalbumin, GABAergic signaling, and Reelin (a protein that helps regulate processes of neuronal migration and positioning). Better understanding of these processes could lead to effective therapies for improving mental functioning in autism.

About 50 years ago, the world was shocked by an epidemic of physically deformed babies caused by Thalidomide, an anti-nausea pill used by many expectant mothers. Along with severe physical abnormalities, a surprisingly high number of these children developed classic autism. Researchers eventually discovered an interesting fact—autism was present only if the mother took Thalidomide between days 20-24 of gestation.148 Since the medication was taken by thousands of mothers at different stages of their pregnancy, this window of time clearly was a period of heightened autism susceptibility. The researchers theorized that the toxic chemical interfered with closing of the neural tube, a major event occurring at this stage of embryonic development.

Another major event during days 20-24 is the establishment of many epigenetic bookmarks that determine expression rates for a multitude of genes. These marks usually are permanent, persisting throughout the life of the child. Exposure to toxic chemicals during this period can cause permanent abnormalities in physical health and mental function. An unfortunate fact is that these predispositions for autism are imprinted before most mothers know they are pregnant. The most important protective measures against autism may be those taken prior to knowledge of conception.

A handful of natural biochemical factors are dominant in epigenetic processes, with methylation and acetylation having special prominence. It is interesting to note that more than 95% of autistic children are undermethylated, and this may be central to the autism condition. After meeting thousands of affected families, I have been struck by the high percentage of competent parents who make a scientific study of autism and dedicate their entire lives to helping their children. After evaluating more than 30,000 persons for methyl status, I am convinced that most parents of autistic children exhibit symptoms of undermethylation, including high accomplishment, obsessive-compulsive traits, attention to detail, and seasonal allergies. If both parents possess the same methylation imbalance, epigenetic abnormalities are far more likely.

There is mounting evidence149 that certain gene expression tendencies can be transmitted to future generations by the process we identified earlier as TEI. More than 100 transgenerational epigenetic conditions have been identified in early research, and many more are anticipated. Animal research has provided strong evidence of TEI, and there are early indications of TEI in humans. It is possible that TEI is a major factor in the autism epidemic. Toxic insults during days 20-24 of gestation could transfer autism predisposition to future generations, especially to nonaffected females less prone to developing autism. In this way, the population of parents at risk for giving birth to ASD children could greatly increase over time—without changes in DNA.

Many of the mysteries regarding autism have been resolved, and this devastating disorder is gradually coming into clear view. I believe an important first step is to recognize that autism is a gene programming (epigenetic) disorder. Evidence of autism’s epigenetic nature includes:

Persistence of autism after onset, indicating that a life-changing event has occurred

Violation of classic laws of genetics in autism, a condition with a strong heritable component

It appears the combination of undermethylation, oxidative overload, and epigenetics represents the Bermuda Triangle of autism. I believe an unfortunate convergence of these three factors is the cause of most cases of autism. In essence, autism appears to be a gene programming disorder that develops in undermethyated persons who experience environmental insults that produce overwhelming oxidative stress.

In the history of science, progress has often been hastened by the development of theories that attempt to explain the mechanisms of poorly understood phenomena. In this spirit, I present the Walsh Model of Autism that is largely based on the research advances and dedicated efforts of others.

1. Predisposition to autism results from in utero hypomethylation that that causes over-expression of several genes, weakened protection against oxidative stresses, and increased vulnerability to environmental insults.

2. Sometime between conception and age three, environmental insults reach a threshold in which oxidative stresses overwhelm oxidative protectors (a tipping point). This triggers an epigenetic event in which DNA and histone marks are altered, producing the syndrome with the diagnostic label of autism. Since the deviant marks are maintained during future cell divisions, the condition doesn’t go away and can result in a lifetime of disability.

3. Autism onset may occur in utero or after birth, depending on the timing and severity of the environmental insults.

4. The altered marks result in abnormal brain development, a tendency for serious brain inflammation and oxidative stress, and significant biochemical imbalances.

5. Many genes are adversely affected, producing a myriad of physical problems, such as weakened immunity, food sensitivities, seizure tendencies, heightened sensitivity to toxins, and poor behavioral control.

Since autism involves deviant gene marks that survive many cell divisions, the condition can persist throughout life. The severity of autism may depend on the relative progress in brain development prior to inundation by oxidative stress and the number and type of deviant gene marks. With these insights, I believe the following three approaches have the highest promise for achieving major improvements in cognition, speech, and behavior.

1. Antioxidant therapies: Many symptoms of autism are directly related to elevated oxidative stress. The following are examples of benefits that may be achieved by effective antioxidant therapy:

Reduction of brain inflammation may reduce irritability and enhance development of speech, cognition, and socialization.

Improved glutathione and metallothionein levels can enhance memory by increasing glutamate activity at NMDA receptors.

Reductions in the number of oxidative free radicals would enhance immune response, protein digestion, and eliminate the tendency for yeast overload.

The filtering action of intestinal and blood-brain barriers can be improved by eliminating oxidative overload.

Increased activity of metallothionein proteins could promote development of new brain cells and synaptic connections.

Elimination of oxidative overloads would protect against brain cell death (apoptosis) and cognitive impairments.

It cannot be stressed enough that continuous, strong antioxidant therapy should be employed as appropriate under medical oversight in order to prevent progressive and severe cognitive deterioration as the individual with autism ages; this can be accomplished with fairly routine and inexpensive supplementation.

2. Normalization of chromatin methyl/acetyl levels: Undermethylation is a distinctive feature of autism that results in altered kinetics of gene expression. Epigenetic therapies aimed at increasing methyl levels at CpG islands and histone tails have great promise. In many cases, this requires removal of acetyl groups and substitution with methyl at these locations. The dominant factors that control the methyl/acetyl competition are four families of enzymes: acetylases, deacetylases, methylases, and demethylases. Standard methylation protocols may be inappropriate due to the impact of specific nutrients on these enzymes. For example, folic acid supplements can reduce chromatin methylation due to folate’s powerful role in enzymatic demethylation of histones. Development of nutrient therapies to normalize methyl/acetyl levels at CpG islands and histone tails is a very fertile area for research.

3. Reversal of deviant gene marks: Cancer researchers are actively investigating epigenetic therapies aimed at reversing abnormal gene marks believed responsible for many types of cancer. If autism truly is an epigenetic disorder, this approach could eventually lead to effective autism prevention. For example, early infant genomic testing could determine if autism-predisposing marks are present, and it’s likely that future research will identify clinical methods for normalizing the marks with natural, biochemical therapy. This line of research may represent the ultimate solution for this devastating disorder, and it should be a high national priority.