Effectiveness of Nutritional Supplements for Reducing Symptoms in Autism-Spectrum Disorder: A Case Report

Abstract

Objective:

This report presents a case of a 9-year-old boy with autism that responded positively to nutritional supplements.

Methods:

The supplements were dimethylglycine and a combination of a large dose of vitamin B6 (pyridoxal HCl) and magnesium. The Autism Treatment Evaluation Checklist (ATEC) was used for outcome assessment and administered by 2 of his family members both before the nutritional supplements and 5 months into the supplements, thereby referred to as pretest and post-test, respectively. Two (2) assessors independently performed evaluations. The ATEC evaluates four areas: communication, sociability, sensory/cognitive awareness, and behavior. The lower the scores are, the less severe the symptoms are.

Results:

The ATEC evaluations by 2 independent assessors showed that the changes in total ATEC were from 63 at pretest to 33 at post-test, and from 64 at pretest to 30 at post-test, respectively. These changes represented reductions of 47.6% and 53.1%. A strong inter-rater reliability was demonstrated, with an intraclass correlation coefficient of 0.988. The school teachers also noticed improvements in various areas consistent with the ATEC evaluations.

Conclusions:

Although the reported findings cannot be generalized, this case report provides useful preliminary evidence to an accumulating body of literature supporting the theory and efficacies of nutritional supplements in autism-spectrum disorders.

Introduction

A utism-spectrum disorder (ASD) has become an epidemic. According to a recent study,¹ approximately 1 in 91 children is diagnosed with autism in America. Individuals with ASD exhibit impairments in communication, social interaction, as well as an occurrence of a restrictive and repetitive pattern of behavior. Often, they also manifest abnormalities in cognitive functioning, attention, learning, sleeping pattern and sensory processing, etc.^2,3

Therapeutic intervention of ASD varies according to individual circumstances. Interventions consist of applied behavior analysis, speech and language therapy, social skill training, and occupational therapy and physical therapy. These interventions are applied to address the core symptoms of ASD. Medication is commonly prescribed to manage repetitive and impulsive behaviors, hyperactivity and inattention, sleep dysfunction, and other associated morbidity.⁴

It is now widely accepted that vitamins, amino acids, minerals, and other nutritional supplements play important roles in reducing the risks of chronic diseases and promoting optimal health. This type of approach is currently classified as complementary and alternative medical therapy (CAM).⁵ The selection of treatment between CAM and conventional medicine related to ASD has posed significant controversies during the past 10–15 years.⁶ Recently, emerging evidence has demonstrated the effectiveness of biomedical interventions in alleviating symptoms in ASD.⁷ Biomedical interventions applied in children and adults with ASD cover an array of treatment regimens, including but not limited to nutritional supplements. The current report presents data about the effectiveness of nutritional supplements on symptoms in ASD.

Case Report

The case subject (YH) was a 9-year-old boy with a diagnosis of pervasive developmental disorder–not otherwise specified, which is one of the conditions on the autism spectrum. He was born at full term, weighing 7 pounds 13 ounces. Throughout the development of his childhood, the main concerns and challenges had been his language delay, inability in social interaction, low eye contact, and behavioral difficulties, such as inflexibility and noncompliances.

Biomedical Intervention

At the age of 9 years old, YH began taking nutritional supplements daily. The initial supplement was a large dose of vitamin B6 (pyridoxine HCl; 12.5 mg each capsule) and magnesium (citrate-glycinate-oxide; 60 mg each), and was given three capsules per day. He was not on any prescriptive medicine at the time. About 4 months later, he started DMG (dimethylglycine; 125 mg each) three capsules each morning while continuing on vitamin B6 and magnesium (B6-Mg). DMG is classified as a type of amino acid that is closely linked to vitamin B12. DMG is metabolized in the liver into sarcosine via an oxidative demethylation pathway and can therefore facilitate conversion of methionine from homocysteine.⁸

These particular types of supplements were chosen because both were reported to have benefited children on the autism spectrum, such as improved language, better eye contact, and decreased behavior problems.⁹ The supplementation of high-dose vitamin B6 and magnesium as a treatment for autism appears to be very safe.^7,10 DMG generally has a very safe record. A small percentage of children may exhibit hyperactivity, which can be moderated by vitamins known as folates.¹¹

Evaluation of Outcomes

Quantitative assessment by family members

The Autism Treatment Evaluation Checklist (ATEC) was chosen to measure the outcomes of the treatment. The ATEC, developed by Bernard Rimland and Stephen M. Edelson of the Autism Research Institute of America, is designed to help researchers, parents, and teachers evaluate the effectiveness of various treatments for children and adults with autism. ATEC is a simple one-page form that can be copied freely.¹² It consists of four categories: I. Speech/Language Communication (14 items); II. Sociability (20 items); III. Sensory/Cognitive Awareness (18 items); and IV. Health/Physical/Behavior (25 items). The ranges of score are 0–28 for Scale I, 0–40 for Scale II, 0–36 for Scale III and 0–75 for Scale IV, respectively. The total range is from 0 to 179. The lower the scores are, the less severe the condition is. A number of published studies have shown the ATEC to be sensitive to changes resulting from a treatment.^13,14 Reliability test conducted on 1358 subjects showed that the internal consistence reliability was strong (r = 0.942) for the total score.¹⁵

Evaluations were undertaken before the administration of the biomedical intervention and at 5-month postintervention, thereafter referred to as pretest and post-test. Both grandfather and grandmother, living with YH and his mother at the time, performed outcome assessment. Before the evaluation, they received instructions on the use of ATEC. Each of his grandparents independently conducted the evaluation at stages of pretest and post-test. They were not masked during the performance of evaluations, since they were aware of the intervention.

Table 1 compares the outcomes and the changes between pretest and post-test scores in four categories evaluated by YH's grandparents, respectively. Both subscores and total scores are presented in the table. The change in scores was calculated by subtracting the pretest scores from the post-test scores. Percentage of the change in scores was defined as the change in scores between the pretest and post-test divided by the pretest scores. Clearly, the assessment outcomes were consistent between the 2 independent evaluators, as confirmed by an intraclass correlation coefficient of 0.988 (p = 0.000).

Table 1.

Comparison of ATEC Scores by 2 Assessors Between Pretest and Post-Test

	Grandfather's assessment			Grandmother's assessment
ATEC ^a	Pretest scores	Post-test scores	Change in scores (%) ^b	Pretest scores	Post-test scores	Change in scores (%)
I. Speech/Language/Communication	10	6	−4 (40.0%)	11	5	−6 (54.6%)
II. Sociability	20	8	−12 (60.0%)	18	8	−10 (55.6%)
III. Sensory/Cognitive Awareness	12	9	−3 (25.0%)	13	8	−5 (38.5%)
IV. Health/Physical/Behavior	21	10	−11 (52.4%)	22	9	−13 (59.1%)
Total scores	63	33	−33 (47.6%)	64	30	−34 (53.1%)

Autism Treatment Evaluation Checklist; range of score is 0–28 for Scale I, 0–40 for Scale II, 0–36 for Scale III, and 0–75 for Scale IV, respectively. The total range is from 0 to 179. The lower the scores are, the less severe the condition.⁸

The change in scores was calculated by subtracting the pretest scores from the post-test scores. The percentage of change in scores was defined as the change in scores between the pretest and posttest divided by the pretest scores.

Inter-rater reliability was assessed, with a strong intraclass correlation coefficient of 0.988 (p = 0.000).

Qualitative assessment by YH's mother and school teachers

YH's mother has also noticed tremendous improvements in him. His major responses to the treatment included his increased ability in communicating with others, more verbal, and more eye contacts. These improvements were observed both at home and at school, and occurred after the B6-Mg and before the DMG supplement. Within a few weeks after he started DMG, he exhibited marked improvements in following directions. His mother and grandparents also noticed that he fell asleep much faster than he previously did. He became calm and rarely threw tantrums since then. Before the treatment, he easily and frequently lost his temper, often in an unpredictable way. He was also more attentive and less hyperactive following the treatment. Thus, he could easily sit through for longer periods of time while working on his homework. Furthermore, he became much more flexible with respect to his daily routine as well as in many other areas of life. As a result of these positive responses, his mother has experienced a dramatic improvement in the quality of their lives.

At school, YH has shown changes in several aspects. His teachers commented in his notebook that he frequently used good eye contact and was more verbal. His mother has seen more and more positive notes on the school worksheets he brought home, such as “Wow,” “Great work,” and “Way to go” etc., to mention a few. They were the same teachers whom YH had worked with during the previous 2 academic years, and knew nothing about the ongoing intervention administered at home. Similar comments and feedback were also made and received from his Sunday school teachers at church.

Another major improvement is in the area of after-school programs. Prior to the use of nutritional supplements, YH had attended and tried several regular after-school programs within the same region. The switch from one to another program each time was forcefully made by his mother, due partially to his noncompliant behaviors reported by the after-school program staff. After the administration of nutritional supplements, he has had successes at the current after-school program since he enrolled more than 1 year ago.

Discussion and Conclusions

This case report describes positive responses to nutritional intervention in a 9-year-old boy with ASD. YH's mother feels that he has been transformed in the aforementioned areas resulting from interventions. His improvements, such as sleeping better at night, and being more compliant and more flexible, cannot simply be attributed to his growth or maturity over the course of treatment. They are undoubtedly the outcomes of nutritional treatment. Although his improvements in sleeping and temper became more evident after the DMG supplement, such benefits likely resulted from the effects of both supplements since they were concurrently used. A synergistic interaction exists between various vitamins and minerals.¹¹ When they work together, they may have released the beneficial effect more quickly than only one treatment. Children with ASD commonly exhibit sleep disturbances. Taira et al.¹⁶ reported that, of the 87 children, 56 (64%) experienced sleep disorders, with difficulty in falling asleep being the most common complaint, followed by frequent awakening and early-morning awakening. Sleeping well is critically important to overall conditions, which apparently contributes to YH's compliance and staying calm during his daily life.

It is common for children on the autism spectrum to have self-restrictive diets to a few limited usually unhealthy foods. Studies have shown that children with ASD often have gastrointestinal symptoms and dysfunctions, such as defective digestion.^17,18 Impairments in digestion and absorption of already-limited nutrition taken in could have led to a deficient level of nutrition and measurements of low neurotransmitters in ASD. B6-Mg has been shown to benefit children and adults with autism.^19,20 However, the study findings have been controversial due to the small number of studies, methodological quality of the studies, and limitations of the assessment tools used.

More recently, Mousain-Bosc et al.²¹ examined changes in clinical symptoms in response to this supplementation and the relationship between changes in clinical symptoms and biologic parameters of 33 children with pervasive development disorders or autism. Seventy percent (70%) of the children demonstrated improvements in social interaction, communication, stereotyped restricted behavior, and abnormal functioning. No adverse effects were observed. Vitamin B6 is essential for more than 100 enzymatic reactions, including production of important neurotransmitters in the brain.²² Magnesium is an essential mineral that is necessary for the health of every cell in the body and the proper functioning of the brain.²³ It is used to prevent the occurrence of hyperactivity, bedwetting, and sensitivity to sound, which often happen if vitamin B6 alone is given.²⁴

There is currently very little evidence on the effectiveness of DMG in autism. Two (2) studies, one utilizing a randomized, placebo-controlled design and the other employing a double-blinded placebo-controlled crossover design, were conducted to evaluate the efficacy of DMG in children and adults with autism and pervasive developmental disorder.^8,25 The results revealed no statistically significant difference in behavior measures and clinical rating scales between DMG and placebo. Lack of significant difference may partially be attributed to a small sample size, low dosage of DMG, and/or a heterogeneous group of participants in the study. To enhance the beneficial effect, use of a single supplement may require a longer period of treatment as the intervention lasted for only 4 weeks in the randomized-controlled study,⁸ since multiple supplements can often be more effective due to the interactive effect.¹¹

It has been nearly 2 years since YH first started nutritional supplements. Improvements he exhibited have thus far been retained and no side-effect has been observed or noticed. This case further proves that nutritional intervention is a safe substance that the human body routinely depends upon to keep the brain and body functioning smoothly and safely.⁷ Before YH's mother tried nutritional intervention on YH at home, she was highly suspicious about its efficacy. However, on the other hand, they had lived in deep struggles and frustrations on a daily basis for years. His mother had a desperate hope for improvement, anticipating their lives to change for better. It was in that very situation that she decided to try the nutritional therapy. In retrospect, the benefit and reward have been remarkable.

The unique aspects of this case report are that evaluations of treatment were quantified by 2 independent assessors using the assessment tool that is easily accessible, and the study was conducted in a home setting where many incidents are taking place, thus making utility of the study more applicable and transferable. Case studies, such as this report, help increase and expand awareness of ASD. This study reported both the effect of single treatment and the synergistic effect of multiple treatments. Beneficial effect associated with the interaction may be useful in the directive of future investigations. Due to the nature of case reports, the findings cannot be generalized. This case report provides useful data for accumulating evidence supporting the efficacies and theory of nutritional supplements in ASD. Future research is needed to guide evidence-based clinical decision-making in treatment of autism.

Footnotes

Disclosure Statement

No competing financial interests exist.

References

Kogan

, Blumberg

, Schieve

et al. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics, 2009; 124:1395–1403.

Wing

. The autistic spectrum. Lancet, 1997; 350:1761–1766.

Yeargin-Allsopp

, Rice

, Karapurkar

et al. Prevalence of autism in a US metropolitan area. JAMA, 2003; 289:49–55.

Myers

, Johnson

. American Academy of Pediatrics Council on Children With Disabilities: Management of children with autism spectrum disorders. Pediatrics, 2007; 120:1162–1182.

Zollman

, Vickers

. What is complementary medicine? BMJ, 1999; 319:693–696.

Levy

, Hyman

. Novel treatments for autistic spectrum disorders. Ment Retard Dev Disabil, 2005; 11:131–142.

Adams

. Summary of biomedical treatments for autism, 2007. http://autism.asu.edu/Additional/Summarybiomed07.pdf. 2011 February 24.

Kern

, Miller

, Cauller

et al. Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder. J Child Neurol, 2001; 16:169–173.

Rimland

, Baker

. Brief report: Alternative approaches to the development of effective treatments for autism. J Autism Dev Disord, 1996; 26:237–241.

10.

Rimland

. The second great autism watershed. Autism Res Rev Int, 1994; 8:3.

11.

McCandless

. Children with Starving Brains: A Medical Treatment Guide for Autism Spectrum Disorder, 3rd. US: Bramble Books, 2007.

12.

Autism Research Institute. Autism Treatment Evaluation Checklist (ATEC) Report. http://www.autism.com/ind_atec_survey.asp. 2011 February 24.

13.

Klaveness

, Bigam

. The GFCF kids diet survey: Preliminary results, 2001. www.gfcfdiet.com/dietsurveysept2.htm. 2011 February 24.

14.

Lonsdale

, Shamberger

, Audhya

. Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: A pilot study. Neuro Endocrinol Lett, 2002; 23:303–308.

15.

Autism Research Institute. Autism Treatment Evaluation Checklist (ATEC) report, 2005. http://legacy.autism.com/ari/atec/atec_report.htm. 2011 February 24.

16.

Taira

, Takase

, Sasaki

. Sleep disorder in children with autism. Psychiatry Clin Neurosci, 1998; 52:182–183.

17.

Horvath

, Papadimitriou

, Rabsztyn

et al. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr, 1999; 135:559–563.

18.

Horvath

, Perman

. Autistic disorder and gastrointestinal disease. Curr Opin Pediatrics, 2002; 14:583–587.

19.

Nye

, Brice

. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev, 2005; 4:CD003497.

20.

Rossi

, Visconti

, Bergossi

, Balestra

. Effects of vitamin B6 and magnesium therapy in autism. Conference on the Neurobiology of Infantile Autism. Tokyo, Japan, November 10–11, 1990.

21.

Mousain-Bosc

, Roche

, Polge

et al. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnes Res, 2006; 19:53–62.

22.

Holman

. Pyridoxine–vitamin B-6. J Aust Coll Nutr Environ Med, 1995; 14:5–16.

23.

Strambi

, Longini

, Hayek

et al. Magnesium profile in autism. Biol Trace Elem Res, 2006; 109:97–104.

24.

Rimland

. Vitamin B6 (and magnesium) in the treatment of autism. Autism Res Rev Int, 1987; 1:3.

25.

Bolman

, Richmond

. A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. J Autism Dev Disord, 1999; 29:191–194.