Assessment of Antifungal Drug Therapy in Autism by Measurement of Suspected Microbial Metabolites in Urine with Gas Chromatography-Mass Spectrometry
WILLIAM SHAW, PHD
DIETARY INFLUENCES ON BEHAVIORAL PROBLEMS IN CHILDREN
James Greenblatt MD, Author of Finally Focused (www.finallyfocusedbook.com), Chief Medical Officer and Vice President of Medical Services at Walden Behavioral Care
It is well known that our food choices play a role in our long-term physical health. It is less recognized that nutrition can have profound effects on our mental health and our behavior. Overall, malnutrition in childhood can affect the brain throughout the lifespan, while specific food components can affect our short-term well-being. Sugar, wheat, and milk are among the most common dietary triggers for ADHD symptoms. Fluctuating blood sugar levels and partially-digested foods can also cause a wide range of symptoms from fatigue to hyperactivity. This article will discuss the dietary influences on behavioral problems in children, review how laboratory testing can be critical in identifying food sensitivities, and how to enhance digestion for maximum absorption of nutrients.
One of the most debated treatments for ADHD is the Feingold Diet, introduced in the early 1970’s by pediatrician and allergist Ben Feingold, MD. He initially suggested that children who are allergic to aspirin (which contains salicylates) may react to artificial food colors and naturally occurring salicylates. The Feingold Diet eliminates artificial food additives like flavorings, preservatives, sweeteners, and colors to reduce hyperactivity. The research over the years on the Feingold Diet has been mixed – some studies show no behavior change and some show increases in hyperactivity when children consume artificial ingredients. A landmark study conducted in the UK on three hundred 3-year-old and 8/9-year-old children in the general population found artificial colors or a sodium benzoate preservative (or both) in the diet resulted in increased hyperactivity (McCann et al., 2007). This study led the European Union to ask manufacturers to voluntarily remove several artificial food colors from foods and beverages or to add a warning label that the artificial food color “may have an adverse effect on activity and attention in children” (Arnold et al., 2012). Conversely, in the US, the FDA reviewed the study and determined that a causal relationship between consumption of color additives and hyperactivity in children could not be definitively established (Arnold et al., 2012).
Genetics often play a role in how a child’s ADHD symptoms are exacerbated. The children most likely to be affected by food additives have a genetic inability to metabolize the compounds. Genetic tests were conducted on the 300 UK children from the artificial food color study. Children with specific variations in the HNMT gene, which helps break down histamine in the body, had stronger behavioral reactions to artificial food colors than children without this variation (Stevenson et al., 2010). This means that in some children, food additives spur the release of histamine that in turn affect the brain.
The Barbados Nutrition Study was a longitudinal case-control study that began in the late 1960’s and investigated the physical, mental, and behavioral developmental effects of infant malnutrition. The 204 participants of this study experienced a single episode of moderate to severe malnutrition during their first year of life. Data was collected on these children through adulthood and compared to data from healthy children. By the end of puberty, all children completely caught up in their physical growth. However, cognitive and behavioral issues persisted into adulthood.
The consequences of malnutrition in infancy manifested in many ways. IQ scores of the children with a history of malnutrition at age 5-11 were significantly lower than those of the control children. 50% of the malnourished children had scores at or below 90 while only 17% of the control children had scores this low (Galler et al., 1983). According to teacher reports, attentional deficits, including shorter attention span, poorer memory, and more distractibility and restlessness, were found in 60% of the malnourished children compared to only 15% of the controls. They also had worse social skills, general health, sleepiness in the classroom, and emotional stability (Galler et al., 1983). When the children were reassessed on these measures at age 9-15, a history of early malnutrition was still associated with behavioral impairment at school, especially attention deficits (Galler & Ramsey, 1989).
Behavior problems reported by teachers when the participants were aged 5-11 significantly predicted conduct problems at age 11-17 (Galler et al., 2012). Age at 5-11, children malnourished as infants had lower performance on 8 out of 9 academic subject areas. 37 children (36 malnourished, 1 control) were below the expected grade for their age (Galler, Ramsey, & Solimano, 1984). Compared to control children, previously malnourished children at age 5-11 had significantly worse scores on parent-rated measures of good behavior (no antagonism between mother and child, obedience), social skills, mother-child relationship, frustration level, eating habits, sleeping habits, and school avoidance. Compared to their siblings, previously malnourished children had significantly worse scores on social skills, good behavior, helpfulness, mother-child interaction, eating habits, toilet training, and language (Galler, Ramsey, & Solimano, 1985). When the children were reassessed on these measures at age 9-15, the same results were seen, especially for aggression and distractibility (Galler & Ramsey, 1989). Problems with self-regulation, displayed as reduced executive functioning and aggression toward peers, persisted through adolescence (Galler et al., 2011).
Years later when the subjects were aged 37-43, attention problems were assessed using an adult ADHD scale and a computerized test of attention-related problems. There was a higher prevalence of attention deficits in the previously malnourished group relative to controls. 69% of the previously malnourished participants had at least one test score that fell within the clinical range for attention disorders (Galler et al., 2012). Previously malnourished participants also had worse educational attainment and income across the entire 40-year study (Galler et al., 2012).
Multiple connections have been made between sugar, hyperactivity, and the risk for ADHD. In group of almost 400 school-age children, researchers found that children with the greatest “sweet” dietary pattern had almost four times greater odds of having ADHD compared to those who ate sweets (ice cream, refined grains, sweet desserts, sugar, and soft drinks) less often (Azadbakht & Esmaillzadeh, 2012). In a similar study on 1,800 adolescents, having a “Western” dietary pattern (higher intakes of total fat, saturated fat, refined sugars, and sodium) more than doubled the odds of an ADHD diagnosis (Howard et al., 2011). Likewise, a study on 986 children, average age 9 years, found a high intake of sweetened desserts (ice cream, cake, soda) was significantly associated with worse inattention, hyperactivity-impulsivity, aggression, delinquency, and externalizing problems. In contrast, a high-protein diet was associated with better scores on these measures. A high level of sweetened dessert consumption was also associated with lower scores on tests of listening, thinking, reading, writing, spelling, and math (Park et al., 2012).
Certain foods may not only influence behavioral and physical symptoms, but may also modify brain activity. When children aged 6-15 with food-induced ADHD consumed provocative foods, they showed an increase in beta activity in frontotemporal regions during EEG topographic mapping of brain electrical activity (Uhlig et al., 1997). Beta waves are involved in normal waking consciousness and tend to have a stimulating effect; while too much beta can lead to anxiety.
A food sensitivity to a protein found in milk or a protein found in wheat is a prevalent but neglected cause of ADHD. Milk and milk products like cheese and butter contain a protein called casein. Casein is different from lactose which is a milk sugar. Grains like wheat, rye, and barley contain a protein called gluten. During digestion, casein becomes casomorphin and gluten becomes gliadorphin. For most people, these proteins are further broken down into basic amino acids. For some with ADHD, they have inactive dipeptidyl peptidase IV, a zinc-dependent enzyme that breaks down both casein and gluten, leaving these opioid peptides substances to build up.
Children with ADHD who have high levels of casomorphin or gliadorphin often have severe, uncontrolled symptoms. Both casomorphin and gliadorphin are morphine-like compounds which attach to opiate receptors in the brain. These substances can act like an addicting drug in susceptible children and cause fatigue, irritability, and brain fog. A child with high levels of casomorphin may have strong cravings for milk products (ice cream, yogurt) and may become irritable when he or she doesn’t eat these types of foods. The Gluten/Casein Peptide Test is a simple urine test that can measure levels of casomorphin and gliadorphin. If a child has high levels of casomorphin or gliadorphin, they should try to eliminate casein or gluten. Supplementation with DPP-IV enzymes can also be beneficial and often required for clinical improvement.
Malnutrition can negatively affect behavior and cognition, but certain nutrients can have detrimental effects on children as well. Louise Goldberg, pediatric dietitian, put it succinctly: “Food allergies and sensitivities can come at children with a one-two punch - first making them agitated, and next robbing them of nutrients that might rein in their behavior” (Peachman, 2013). We are biochemically unique and have different physiological and psychological responses to different foods. The right food for one child may the wrong food for another. For instance, peanut butter on whole wheat toast may be a nutritionally-balanced, energy-boosting snack for one child, while this snack would be harmful to a child who cannot tolerate neither nuts nor wheat. Medical testing can clarify which nutrients a child is sensitive to. Fortunately, eliminating offending substances can rapidly improve physical and behavioral symptoms.
References:
Arnold, et al. (2012). Artificial food colors and attention-deficit/hyperactivity symptoms: Conclusions to dye for. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics, 9(3), 599-609.
Azadbakht & Esmaillzadeh. (2012). Dietary patterns and attention deficit hyperactivity disorder among Iranian children. Nutrition, 28(3), 242-249.
Galler et al. (1983). The influence of early malnutrition on subsequent behavioral development I. Degree of impairment in intellectual performance. Journal Of The American Academy Of Child And Adolescent Psychiatry, 22(1), 8-15.
Galler et al. (1983). The influence of early malnutrition on subsequent behavioral development II. Classroom behavior. Journal Of The American Academy Of Child And Adolescent Psychiatry, 22(1), 16-22.
Galler & Ramsey. (1989). A follow-up study of the influence of early malnutrition on development: Behavior at home and at school. Journal Of The American Academy Of Child And Adolescent Psychiatry, 28(2), 254-261.
Galler, Ramsey, & Solimano. (1984). The influence of early malnutrition on subsequent behavioral development III learning disabilities as a sequel to malnutrition. Pediatric Research, 18(4), 309-313.
Galler, Ramsey, & Solimano. (1985). Influence of early malnutrition on subsequent behavioral development: V. child’s behavior at home. Journal Of The American Academy Of Child Psychiatry, 24(1), 58-64.
Galler et al. (2011). Early malnutrition predicts parent reports of externalizing behaviors at ages 9-17. Nutritional Neuroscience, 14(4), 138-144.
Galler et al. (2012). Infant malnutrition predicts conduct problems in adolescents. Nutritional Neuroscience, 15(4), 186-192.
Galler et al. (2012). Infant malnutrition is associated with persisting attention deficits in middle adulthood. The Journal Of Nutrition, (4), 788.
Galler et al. (2012). Socioeconomic outcomes in adults malnourished in the first year of life: a 40-year study. Pediatrics, (1), 1.
Howard et al. (2011). ADHD Is Associated with a "Western" Dietary Pattern in Adolescents. Journal of Attention Disorders, 15(5), 403-411.
Lacy. (2004). Hyperactivity/ADHD-- new solutions. AuthorHouse.
Langseth & Dowd. (1978). Glucose tolerance and hyperkinesis. Food And Cosmetics Toxicology, 16(2), 129-133.
McCann et al. (2007). Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: A randomised, double-blinded, placebo-controlled trial. The Lancet, 370(9598), 1560-1567.
Niederhofer. (2011). Association of Attention-Deficit/Hyperactivity Disorder and Celiac Disease: A Brief Report. Primary Care Companion For CNS Disorders, 13(3), pii: PCC.10br01104.
Park et al. (2012). Association between dietary behaviors and attention-deficit/hyperactivity disorder and learning disabilities in school-aged children. Psychiatry Research, 198, 468-476.
Stevenson et al. (2010). The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms. The American Journal of Psychiatry, 167(9), 1108-15.
Uhlig et al. (1997). Topographic mapping of brain electrical activity in children with food-induced attention deficit hyperkinetic disorder. European Journal of Pediatrics, 156(7), 557-61.
The Role of Oxidative Stress, Inflammation and Acetaminophen Exposure from Birth to Early Childhood in the Induction of Autism
By: William Parker, Chi Dang Hornik, Staci Bilbo, Zoie E. Holzknecht, Lauren Gentry, Rasika Rao, Shu S. Lin, Martha R. Herbert and Cynthia D. Nevison
Lithium Deficiency: Common in Mental Illness and Social Ills
William Shaw, PhD
Jim Adams found that in an evaluation of hair samples from children with autism that lithium values were significantly lower in young children of autism and their mothers. I have made similar observations on many children with autism tested through The Great Plains Laboratory. The lithium values of some children with autism are in the lowest one percentile. Ironically, the use of highly purified water to prevent ingestion of toxic chemicals may have deprived pregnant women of a trace amount of lithium found in tap water needed for normal brain development and this deficiency appears to be a significant autism risk factor. This switch to purified bottled water has taken place in the past 20 years during the same time as the surge in the autism epidemic.
The tenfold increase in bottled water consumption (image 1) coincides nearly exactly with an approximate ten-fold increase in autism incidence over the same time period. It is possible that this factor might in fact be equal in importance to mercury exposure as an autism risk factor.
In very small amounts lithium appears to be an essential element needed for good mental health. Areas of the country where lithium is present at high levels in the drinking water have less violence and crime. A study of 27 Texas counties found that the incidences of suicide, homicide and rape were significantly higher in counties whose drinking water supplies contained little or no lithium compared to counties with higher water lithium levels, even after correcting for population density.
Corresponding associations with the incidences of robbery, burglary and theft were also significant, as were associations with the incidences of arrests for possession of opium, cocaine and their derivatives. In addition, I have commonly found very low lithium values in hair samples of patients with schizophrenia. Furthermore, hair lithium has been shown to be a good indicator of lithium deficiency. Scalp hair lithium levels reflect the average intakes of bioavailable lithium over a period of several weeks to months and represent a noninvasive means of determining the dietary lithium intakes. Furthermore, lithium is needed to transport folate and vitamin B-12 into the brain. The common deficiencies of lithium may be one of the reasons children with autism require such high doses of certain forms of these vitamins.
A typical hair profile of a child with autism is shown in the adjoining diagram, demonstrating the extremely low lithium intakes common in autism. Blood tests done at conventional medical laboratories measure lithium but only are useful to measure the extremely high lithium levels associated with lithium drug therapy. Such tests are useless for the measurement of the very low lithium levels associated with nutritional lithium.
A provisional Recommended Daily Allowance (RDA) for a 70 kg adult of 1,000 mcg/day (about 1% of the dose of lithium commonly used as a pharmaceutical agent) has been suggested for a 70 kg adult, corresponding to 14.3 mcg per kg body weight. Note carefully that mcg stands for micrograms, not milligrams (mg)! Doses of lithium between 150-400 mcg per day (doses that are nutritional rather than pharmacological) resulted in improved mood in drug abusers, some of whom had a long history of drug abuse. The nutritional use of lithium is completely safe. No safety assessments or blood tests need to be done for nutritional supplementation of lithium in contrast to the use of lithium as a drug, which requires blood testing to prevent toxic overdose. If hair values are low or a person only drinks purified deionized or reverse-osmosis water, I think the person should take lithium supplements. New Beginnings Nutritionals has a convenient liquid that contains 50 mcg lithium per drop. I remember when the bottled water products were first launched and I was incredulous that people would pay for a product they could get for virtually nothing simply by turning on their faucets. Now I drink reverse-osmosis water, which is essentially free of trace elements (and toxic chemicals), and I take 500-mcg lithium daily by adding lithium drops to my orange juice.
Clinical References
Moore GJ, et al. Lithium-induced increase in human brain grey matter. Lancet. 2000 Oct 7; 356(9237): 1241-2. http://www.ncbi.nlm.nih.gov/pubmed/11072948
Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr. 2002 Feb;21(1):14-21.http://www.ncbi.nlm.nih.gov/pubmed/11838882
Schrauzer G.N., Shrestha K.P., Flores-Arce M.P. Lithium in scalp hair of adults, students and violent criminals. Effects of supplementation and evidence for interactions of lithium with Vitamin B and other trace elements. Biological Trace Element Research, 1992 Aug 34 (2): 161 – 76. http://www.ncbi.nlm.nih.gov/pubmed/1381936
J.B. Adams, C.E. Holloway, F. George, D. Quig. Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers. Biological Trace Element Research. 110: 193-209, 2006.http://www.ncbi.nlm.nih.gov/pubmed/16845157