The authors have no conflicts of interest to declare.
Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired communication and social interaction. Children with ASD are frequently diagnosed with gastrointestinal (GI) issues, including inflammatory bowel disease (IBD), gastroesophageal reflux, abdominal pain, diarrhea, and constipation, although the association between ASD and GI conditions is unclear. Underlying nutritional deficiencies are more common in children with ASD, and increase the risk of them developing medical conditions secondary to the behavioral diagnosis. This objective of this study was to examine the use of an elemental diet (ED) in the treatment of gastrointestinal disease in 5 children with ASD ages 2-21 years of age. In the study participants, the ED was well-tolerated with improvements in anthropometric measures, nutritional markers, and/or GI functioning reported after 12 weeks of intervention. Further research to advance the development of specific evidence-based guidelines in the management and treatment of gastrointestinal concerns in the ASD population is warranted.
ASD is a complex pervasive developmental disorder characterized by impairments in social interaction, with deficits in verbal and non-verbal communication and/or restricted, repetitive and stereotyped patterns of behavior and interests
Associated functional GI abnormalities in children with ASD include low activities of disaccharidase enzymes
An elemental diet (ED) is an easily-digestible, liquid diet typically used for patients who have compromised digestive systems
Based on the above manifestations and clinical experience in treating the above symptoms with ED, the purpose of this investigation was to evaluate the tolerability and efficacy of ED in the amelioration of GI symptoms in children ages 2-21 years, with documented GI dysfunction, including duodenitis, ileitis, and/or colitis, and an ASD diagnosis.
This study was approved by the appropriate Institutional Review Board in accordance with local regulations and informed consent/assent was obtained from the subjects and/or their legal guardians after the nature of the procedures had been explained.
Male and female children (n = 5) aged 9-14 years, diagnosed with Autism Spectrum Disorder (ASD) and meeting the inclusion criteria below, were recruited sequentially through an out-patient clinic. If the caregiver expressed interest in their child participating in the study, the consent form was reviewed with the family and informed consent and assent (if applicable) obtained. Inclusion criteria were as follows: 2-21 year-old males and females with ASD with a diagnosis of inflammatory bowel disease. The participant had to be under the care of a caregiver.
Willing to participate in the study by attending regularly scheduled appointments and completing the necessary measures, and be accessible to a research staff member via phone or in-office on a weekly basis throughout the study intervention period. Exclusion criteria were as follows: pregnant or nursing females up to 21 years of age; requirement of receiving any nutrition via enteral or parenteral routes; infectious colitis, metabolic disorders such as phenylketonuria, leukodystrophy, lysosomal disorder, Wilson’s disease, and other concurrent physical or mental disorders that preclude participation in assessment procedures. Concurrent medications, dietary restrictions, and/or therapies were not exclusions to participation. However, concurrent interventions could not change during the period of the trial, unless there was a clear medical indication to do so.
Enrolled participants received total elemental nutrition for 12 weeks under the guidance of a registered dietitian and a clinician. Anthropometric measurements were collected at baseline, 4, 8, and 12 weeks, and at two follow-up appointments conducted at 6 and 12 months. Biochemical markers and dietary analysis were monitored throughout the study, and caregivers participated in weekly phone or in-office visits to address any concerns raised by the clinician, dietitian and/or caregiver.
The study procedures performed during each phase are summarized in
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Biochemical Markers | X | X | X | X | ||
Anthropometrics | X | X | X | X | X | X |
Dietary Analysis | X | X | X | |||
Clinical Evaluation | X | X | X |
Caregivers were given standardized written instructions and measurement guidelines to record all food and beverage intake for two weekdays and one weekend day that they considered typical for their child (Three-Day Food Diary, Supplementary Figure S1). Homemade recipes, brand names of packaged products and restaurant information of foods consumed were required. Food records were analyzed using Food Processor SQL (version 10.3.0, 2008, ESHA, Salem, OR; Supplementary Figure S2). Supplement data was not included in the nutrient analysis for an accurate assessment of dietary nutriture. Ideal body weight (IBW) was calculated as the appropriate weight for height according to the CDC growth charts. Estimated energy requirement for each patient was derived from height, weight, and a moderate physical activity level using the formulas developed by the Institute of Medicine
A clinical evaluation was performed at baseline and at the completion of the study to assess the health and well-being of participants. Participants were also monitored throughout the study to assess actual elemental nutrition intake and tolerance, and to ensure that caloric intake was adequate, hydration status normal, and nutritional goals were achieved and maintained. Caregivers were given a standard weight scale and received training on proper use in order to track weight outside of the clinic. Greater than 5% weight loss in one month was considered abnormal, and would either result in the clinician either changing the dosing of the elemental formula or withdrawing the participant from the study. Gastrointestinal tolerance was also assessed weekly using the Gastrointestinal Symptoms Rating Scale (GSRS)
Total daily nutrition was provided by elemental formulas that were provided at no cost to study participants. Three options for elemental nutrition were offered to the participants and their caregivers: two flavored powdered elemental formulas, Ross Nutricia Neocate and Elecare, and the ready-to-drink elemental formula, Neocate EO28 Splash. The powered formulas were prepared to provide appropriate caloric density to meet estimated energy requirements for weight maintenance or weight gain if indicated. Neocate EO28 Splash required no additional preparation. Two participants favored the ready-to-drink formula, while the other three chose the powdered formula. Formula was prescribed by the clinician and caregivers received sufficient formula for the 3 months study intervention period. Verbal and written instructions on titration and maintenance dose administration was provided to the caregiver under the guidance of a registered dietitian. Each participant received the optimal amount of formula appropriate for their daily energy and nutrient needs. Feedings occurred at meal or snack time, or ad libitum.
A daily food (formula) diary was maintained by the caregiver to record: i) all feedings with the elemental formula consumed on a daily basis, including documentation of any missed feedings and reasons for feedings being missed; ii) any ingested foods and beverages that were not allowed in the dietary intervention; and iii) suspected adverse diet-related events including the nature, severity and duration of such events. The daily food diaries were discussed during the weekly study appointments. At the end of 12 weeks, the clinician and dietitian reviewed all the study data and subsequently recommended that either the participant continue with elemental nutrition (outside of the study) or they begin the process to reintroduce solid foods, done under the guidance of a registered dietitian for a period of 4 weeks. In all cases, whether ED was continued or discontinued, follow-up assessments at 6 and 12-months were scheduled although not all families provided additional data past the study intervention period.
Primary outcomes examined the efficacy of the elemental formula, as evidenced by the improvement in bowel symptoms and height/weight gain. Secondary outcomes included assessments of nutritional status and nutrient intake based on measurements of blood concentrations of total protein, albumin, pre-albumin, ferritin, C-reactive protein, RBC, MCV, MCHC, AST and alkaline phosphatase. Vitamin and minerals that were assessed included: sodium, potassium, chloride, magnesium, calcium, phosphorous, zinc, vitamin D, E, and K and folate. Nutrient intake was assessed by comparing submitted 3-Day food diaries with baseline data.
A 14-year old boy with Crohn’s disease presented with abdominal pain, frequent daily loose stools, and low muscle tone. BMI was <1st percentile. Following the 12-week intervention, the participant reported a reduction in abdominal pain and improvement in stool consistency and frequency. Although there was a small overall loss in body weight from 94.5 lbs to 89 lbs from baseline to 12 weeks, this subject reported a 34% weight gain at the 6-month follow-up appointment (
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14.82 | 14.92 | 14.99 | 15.07 | 15.30 | 15.92 |
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94.5 | 95.6 | 93.75 | 89 | 120.5 | 120 |
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6.81 | 6.3 | 4.85 | 1.92 | 37.83 | 25.46 |
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-1.49 | -1.53 | -1.66 | -2.07 | -0.31 | -0.66 |
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68.0 | 68.0 | 68.0 | 68.0 | 68.0 | 68.0 |
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68.8 | 64.8 | 64.8 | 62.9 | 57.5 | 46.4 |
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0.5 | 0.4 | 0.4 | 0.3 | 0.2 | -0.1 |
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14.4 | 14.5 | 14.3 | 13.5 | 18.3 | 18.2 |
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<1 | <1 | <1 | <1 | 23 | 16 |
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-3.33 | -3.24 | -3.57 | -4.39 | -0.73 | -0.98 |
Abbreviations: BMI, body mass index; in, inches; lbs, pounds; Yr, Year.
An 11-year old boy diagnosed with gastropathy and enteritis and a history of pica presented with chronic constipation cycling with diarrhea, consistent abdominal pain prior to defecating, and chronic eructation. Weight, height and BMI were considered to be in a healthy range at baseline. After the 12-week study intervention, caregivers and/or participants reported improvements in GI symptoms and reduction in pain. The participant showed a consistent increase in body weight from 85.2 lbs at baseline to 93 lbs at 12 weeks, representing an increase of 7.8 lbs (
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11.72 | 11.81 | 11.88 | 11.96 | 12.28 | 12.73 |
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85.2 | 89 | 90 | 93 | 88.25 | 92 |
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47.6 | 54.38 | 52.79 | 59.1 | 40.52 | 38.97 |
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-0.06 | 0.11 | 0.07 | 0.23 | -0.24 | -0.28 |
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59 | 59.5 | 59.5 | 61.5 | 61.5 | 61.5 |
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63.7 | 67.4 | 64.8 | 83.9 | 75.5 | 61.8 |
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0.3 | 0.5 | 0.4 | 1 | 0.7 | 0.3 |
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17.2 | 17.7 | 17.9 | 17.3 | 16.4 | 17.4 |
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43 | 50 | 53 | 42 | 22 | 35 |
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-0.18 | 0.01 | 0.07 | -0.21 | -0.77 | -0.39 |
Abbreviations: BMI, body mass index; in, inches; lbs, pounds; Yr, Year.
A 13-year old boy with a history of esophageal ulcers and lymphonodular hyperplasia of the terminal ileum presented with abdominal pain and diarrhea. Weight, height and BMI were considered to be in a healthy range at baseline. After the 12-week study intervention, the participant’s weight increased from 104 lbs at baseline to 115.4 lbs at 12 weeks representing an increase of ~11 lbs during the intervention period (
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13.26 | 13.45 | 13.53 | 13.60 | 13.87 | 14.37 |
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104 | 111.4 | 116 | 115.38 | 118 | 119 |
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50 | 59.87 | 65.91 | 63.31 | 62.17 | 53.59 |
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0 | 0.28 | 0.41 | 0.34 | 0.31 | 0.09 |
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65.5 | 67.5 | 68.5 | 69.5 | 69.5 | 69.5 |
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84.4 | 93.1 | 95.7 | 97.5 | 95.8 | 90.3 |
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1 | 1.5 | 1.7 | 2 | 1.7 | 1.3 |
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17 | 17.4 | 17.4 | 16.8 | 17.2 | 17.3 |
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23 | 27 | 26 | 16 | 19 | 17 |
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-0.74 | -0.62 | -0.64 | -0.99 | -0.86 | -0.95 |
Abbreviations: BMI, body mass index; in, inches; lbs, pounds; Yr, Year.
A 9-year old boy, significantly underweight and diagnosed with gastropathy, esophageal ulcers, and aphthous ulceration of the rectosigmoid presented with abdominal distention and diarrhea. The participant’s weight increased from 49.5 lbs at baseline to 52.8 lbs at the end of the 12-week intervention period representing an increase of ~3.5 lbs. Weight gain continued after transitioning back to solid food with a reported weight of 54.4 and 67 lbs at the 6- and 12-month follow-up appointments, respectively placing him at the 3.6th and 20th percentile, respectively (
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9.58 | 9.71 | 9.79 | 9.95 | 10.13 | 10.8 |
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49.5 | 50 | 52.4 | 52.8 | 54.4 | 67 |
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1.7 | 1.54 | 3.29 | 2.87 | 3.67 | 20.61 |
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-2.12 | -2.16 | -1.84 | -1.9 | -1.79 | -0.82 |
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50 | n/a | n/a | n/a | n/a | n/a |
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6.8 | |||||
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-1.5 | |||||
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13.9 | n/a | n/a | n/a | n/a | n/a |
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4 | |||||
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-1.8 |
Abbreviations: BMI, body mass index; in, inches; lbs, pounds; Yr, Year.
A 9-year old boy with a history of enuresis, GERD, and lymphonodular hyperplasia of the terminal ileum and colon presented with abdominal pain, diarrhea, and vomiting. Weight, height and BMI were considered to be in a healthy range at baseline. There was no significant weight change over the 12-week intervention period however the child grew 1.25 inches (
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9.92 | 10.04 | 10.11 | 10.19 | 10.46 | 10.98 |
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69 | 70.8 | 70.4 | 70.4 | 73.2 | 74 |
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46.41 | 50 | 46.81 | 44.83 | 46.81 | 36.69 |
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-0.09 | 0 | -0.08 | -0.13 | -0.08 | -0.34 |
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54.5 | 55 | 55.75 | 55.75 | 55.75 | 57.5 |
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50 | 55.2 | 64.1 | 61.4 | 54.4 | 65.2 |
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0 | 0.1 | 0.4 | 0.3 | 0.1 | 0.4 |
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16.3 | 16.5 | 15.9 | 15.9 | 16.6 | 15.7 |
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44 | 45 | 33 | 33 | 43 | 21 |
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-0.14 | -0.12 | -0.44 | -0.44 | -0.18 | -0.79 |
Abbreviations: BMI, body mass index; in, inches; lbs, pounds; Yr, Year.
This is the first report describing the use of an ED in the treatment of IBD in children with ASD. In general, the ED was well-tolerated with improvements in clinical lab measures, and/or GI functioning reported by all 5 subjects after 12 weeks of intervention.
Children with Crohn’s disease, IBD and eosinophilic esophagitis are at high risk of nutrient malabsorption and weight loss, and in many cases, an ED may improve malabsorption and weight gain
Most of the clinical lab measures were within normal limits at baseline. CRP, a marker of active inflammation, was high in one participant at baseline but resolved following 12 weeks of ED intervention, as previously reported
Assessing GI symptoms in children can be challenging
Based on the case reports in our pilot study, it appears that 12 weeks of an ED intervention was a suitable timeframe to observe quantitative changes in laboratory measures, GI symptoms and/or anthropometric measures in most participants. In the clinical setting, a longer period of intervention may be required to see sustained effects.
Pica was a concern in two participants, which is more likely due to the need for a ‘chewing’ sensation than nutrient deficit. One participant was reportedly to occasionally eat mulch and leaves from the playground at school during the beginning of the study intervention. This child was subsequently diagnosed with roundworms requiring a parasite treatment protocol that lasted several weeks. It is not known how long the participant had roundworms, i.e. was this an underlying problem (the child had been treated for parasites before) or if this was the result of the pica, but it is highly likely that this may have affected nutritional and GI parameters during the ED intervention period. The participant’s mother also reported that the child had periods of unusual hyperactivity, visual stimming, bedwetting, and daytime incontinence. It is well known that parasite infections can lead to a range of symptoms including those described above
While an ED has not been used specifically in the ASD population before, it has been well documented in the pediatric population, especially for the treatment of Crohn’s disease
However, the use of an ED is not risk free
There are a number of limitations of this study. Although this is a prospective study, there were only 5 participants and thus it is descriptive in nature. Due to the complexity of each participant’s presentation, it is not possible to confer any specific benefits of the ED to the study group as a whole. Furthermore, some data were missing or not available and/or participants did not complete certain assessments at the required study visits. Controlling dietary infractions for the duration of the 12-week trial was challenging for some parents, especially for older children that attended school. One parent reported weekly food infractions, while two reported pica. Both food infractions and pica could impact the efficacy of the ED intervention but this could not be easily measured. While the inclusion criteria for this study required confirmed gastrointestinal diagnoses, this was identified from the patient’s medical records and did not require confirmation from a gastroenterologist at the time of study initiation. In the absence of active inflammation, an ED may not be efficacious. The GSRS questionnaire that was used to capture GI symptoms is designed for adults and is difficult to complete in the pediatric populations, especially in children that are non-verbal and unable to communicate their specific GI concerns
In conclusion, the ED was well tolerated in the participants in this study, all of who generally showed improvements in anthropometrics, clinical lab measures, and/or GI symptoms. Prospective longitudinal studies are needed to evaluate the effects of an ED on anthropometric measures, sleep, GI symptoms, and behavior in children with ASD and GI conditions to definitively determine the optimal treatment approach when an ED is warranted.
This study was funded by The Jane Botsford Johnson Foundation. We are very grateful to all the families that participated in this research study. We would also like to thank the staff at The Johnson Center for implementation of this study protocol. This study was approved by the Austin Multi-Institutional Review Board (AMIRB).
This study was approved by the appropriate Institutional Review Board in accordance with local regulations.