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J. Pers. Med. 2023, 13, 1448. https://doi.org/10.3390/jpm13101448 www.mdpi.com/journal/jpm
Article
Ratings of the Effectiveness of 13 Therapeutic Diets for Autism
Spectrum Disorder: Results of a National Survey
Julie S. Mahews
1
and James B. Adams
2,
*
1
College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; julie@nourishinghope.com
2
School of Engineering of Maer, Transport and Energy, Arizona State University, Tempe, AZ 85287, USA;
jim.adams@asu.edu
* Correspondence: jim.adams@asu.edu; Tel.: +1-480-965-3316
Abstract: This study presents the results of the effectiveness of 13 therapeutic diets for autism spec-
trum disorder from 818 participants of a national survey, including benefits, adverse effects, and
symptom improvements. The average Overall Benefit of diets was 2.36 (0 = no benefit, 4 = great
benefit), which was substantially higher than for nutraceuticals (1.59/4.0) and psychiatric/seizure
medications (1.39/4.0), p < 0.001. The average Overall Adverse Effects of diets was significantly lower
than psychiatric/seizure medications (0.10 vs. 0.93, p < 0.001) and similar to nutraceuticals (0.16).
Autism severity decreased slightly over time in participants who used diet vs. increasing slightly in
those that did not (p < 0.001). Healthy and Feingold diets were the two top-rated diets by Overall
Benefit; the ketogenic diet was the highest for nine symptoms (though had fewer respondents); and
the gluten-free/casein-free diet was among the top for overall symptom improvements. Different
diets were reported to affect different symptoms, suggesting that an individual’s symptoms could
be used to guide which diet(s) may be the most effective. The results suggest that therapeutic diets
can be safe and effective interventions for improving some ASD-related symptoms with few adverse
effects. We recommend therapeutic diets that include healthy foods and exclude problematic foods.
Therapeutic diets are inexpensive treatments that we recommend for consideration by most people
with ASD.
Keywords: autism; autism spectrum disorder; diet; therapeutic diets; personalized nutrition;
gluten-free casein-free diet; ketogenic diet; Feingold diet; healthy diet; survey
1. Introduction
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder involv-
ing deficits in communication, behavior, and social interaction that affects 1 in 44 children,
and 4.2 times as many boys than girls [1]. ASD often involves many co-occurring symp-
toms, including intellectual disability, seizures, sleep disorders, gastrointestinal disor-
ders, feeding disorders, and mood disorders The lifetime cost of caring for a child with
ASD in the United States is $1.4–2.4 million (for those without and with an intellectual
disability, respectively) [2]. Current treatment options include behavioral therapy [3], spe-
cial education and other therapies [4], psychiatric/seizure medications [5], nutraceuticals
[6], gastrointestinal treatments [7], and therapeutic diets [6,8].
Of the various treatment options, therapeutic diets have received relatively lile re-
search despite being widely used by autism families [9]. Several survey studies have re-
ported benefits from therapeutic diets in some ASD symptoms, including behavior, com-
munication, and health, as well as gastrointestinal issues, aention, communication, and
socialization [10,11]. Clinical experience also demonstrates that dietary intervention can
improve some core ASD symptoms. Case reports describe the benefits of therapeutic diets
for children with ASD, including improvements in eye contact, communication, constipa-
tion, and vomiting from a gluten-free casein-free (GFCF) diet [12], as well as
Citation: Mahews, J.S.; Adams, J.B.
Ratings of the Effectiveness of 13
Therapeutic Diets for Autism
Spectrum Disorder: Results of a
National Survey. J. Pers. Med. 2023,
13, 1448. hps://doi.org/10.3390/
j
pm13101448
Academic Editor: Rajendra D
Badgaiyan
Received: 6 September 2023
Revised: 22 September 2023
Accepted: 26 September 2023
Published: 29 September 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Swierland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Aribution (CC BY) license
(hps://creativecommons.org/license
s/by/4.0/).
J. Pers. Med. 2023, 13, 1448 2 of 34
improvements in cognition, autism symptoms, and even a reduction in seizures from a
gluten-free casein-free ketogenic diet [13].
One of the major reasons for implementing therapeutic diets is that children with
ASD often exhibit self-limited diets, and may eat only a small number of foods, which
increases the risk of macronutrient and micronutrient deficiencies [14]. A meta-analysis
showed that children with autism spectrum disorder consume a diet lower in calcium,
vitamin D, thiamine, riboflavin, vitamin B12, selenium, phosphorus, and omega-3 than
typically developing control children, and calcium and vitamin D were under the recom-
mended daily intake [15]. Additionally, an observational study found children with ASD
were significantly lower than neurotypical controls in levels of calcium, magnesium, car-
otenes, vitamin B5, vitamin E, biotin, and lithium, with 7–31% of children below the ref-
erence ranges for these nutrients [16].
Another major reason to consider therapeutic diets is that a meta-analysis of eight
studies reported that children with ASD have many differences in their gut bacteria com-
pared to typical children [17], and many studies have reported elevated levels of intestinal
yeast in children with ASD compared to controls [18]. Both bacteria [19] and yeast [20] are
largely influenced by diet, and research shows the effects of food and therapeutic diets on
the microbiota in mental health disorders [21] including autism [22]. Some therapeutic
diets are designed to alter the gut microbiome, and it is suggested by researchers that they
can be used to influence the microbiome and be customized based on personal underlying
factors and needs [23].
ASD involves many more comorbidities and underlying factors for which dietary
intervention may be helpful, such as mitochondrial dysfunction [24], gastrointestinal is-
sues, immune system dysregulation, seizures, and sleep disturbances, as well as psycho-
logical conditions including anxiety, depression and behavior problems [3]. Further ab-
normalities include oxidative stress [25] disordered methylation, sulfation, and transsul-
furation [26], and disordered oxalate metabolism [27].
Most research on therapeutic diets in ASD has focused on gluten-free casein-free
(GFCF) diets, which are suggested because gluten and casein (from milk products) are
common allergens [28]; several studies have reported decreased levels of lactase (needed
to digest lactose in milk) in children with ASD [29–32], and there is a hypothesis that un-
digested casein may have an opioid-like effect in the brain [33]. The research on the effec-
tiveness of GFCF diets is mixed, but a meta-analysis of eight randomized controlled trials
of the GFCF diet found that it significantly improved stereotypical behavior of autism (5
studies) and cognitive function (3 studies) [34].
The ketogenic diet has also been found to be beneficial and improve ASD symptoms
[35]. Ketogenic diets are low carbohydrate, high fat, and adequate protein diets that are
widely used for seizure control for epilepsy [36], and about 30% of people with ASD even-
tually develop seizures, and about 80% have subclinical seizures [37]. A study on the ke-
togenic diet versus the GFCF diet in ASD found both diets were beneficial and provided
symptom improvements, although they had benefits in different symptoms [38]. The
Paleo diet and Specific Carbohydrate Diet (SCD) are additional diets that eliminate par-
ticular carbohydrates including grains and starches. The Paleo diet also avoids all leg-
umes, dairy, and most added sugars, while SCD avoids disaccharides and polysaccha-
rides including sucrose and lactose. Part of the reason for the use of these diets is that
children and adults with ASD often have low levels of disaccharidase enzymes, contrib-
uting to dysbiosis and digestive distress [32]. Research on SCD shows it is beneficial for
children with ASD by reducing autism symptoms [39].
Many other diets are commonly used for individuals with ASD, but there is less re-
search on them. Most diets focus on removal of specific foods and compounds that nega-
tively affect biochemistry and symptoms. The Feingold diet reduces artificial food addi-
tives and salicylates and is recommended because these substances are difficult to detoxify
in certain children, contributing to hyperactivity and negative behaviors [40]. A corn-free
diet, soy-free diet, or other food-avoidance diet (based on IgG or IgE food testing) removes
J. Pers. Med. 2023, 13, 1448 3 of 34
the problematic proteins from the diet that can cause inflammation and intestinal perme-
ability [41]. A low sugar diet is a diet low in added sugar and overall sugar intake and is
beneficial as there is no nutritional need for sugar and it can contribute to overweight,
digestive symptoms, poor growth, dental caries, and increase the risk of developing type
2 diabetes and cardiometabolic conditions [42], and also increase the risk of intestinal
yeast infections, which are common in children with ASD [18,43]. A food-avoidance diet
(based on observation) removes any foods that have been known to cause a reaction. A
low oxalate diet has been proposed because impaired oxalate metabolism is an underlying
factor in some individuals with ASD [27]. Many review papers examine the use of thera-
peutic diets for ASD, and most discuss the use of a targeted or personalized nutrition ap-
proach to dietary intervention, and include the following diets: the GFCF diet [44–48],
ketogenic diet [45–48], Specific Carbohydrate Diet [45,47,48], low sugar diet [44,45], Low
FODMAPs diet [45], elimination diet [48], low oxalate diet [48], Feingold diet [45,46], and
the Mediterranean diet [47].
Other effective diet strategies that have been reported include focusing on a healthy
diet by adding nutritious foods and removing unhealthy foods such as sugar and food
additives [46]. A randomized controlled study of a comprehensive diet and nutrition ap-
proach, which included a gluten-free, casein-free, and soy-free diet, focusing on healthy
foods along with nutrient supplementation for individuals with ASD, resulted in im-
proved non-verbal IQ, developmental age, and many symptoms and comorbidities of au-
tism spectrum disorder, such as language, sociability, anxiety, ritual behaviors, gastroin-
testinal distress, and more [49].
Many of the diets discussed above have had lile research on them, and there is al-
most no research to compare the efficacy of one diet vs. another. Survey research on ther-
apeutic diets for ASD provides initial evidence on the benefit and effects of many diet
strategies [9–11]. However, some studies are rather small with 37 respondents and report
on the improvement from therapeutic diets as a whole (not individual diets) [10], and
other surveys are limited to results on only one or a few diets [9,11]. One huge survey
study included data from over 27,000 families [50] on many treatments, including several
diets, and reported 45–71% of individuals improved on various diets with rare adverse
effects (2–7%), but did not specify which symptoms improved.
This paper reports on the results of a national survey of the effectiveness of 13 thera-
peutic diets for ASD and their associated symptom changes. This study is part of a larger
survey that included nutraceuticals [51], psychiatric/seizure medications [52], and thera-
pies, and involves 818 participants that reported on the effect of one or more therapeutic
diets. It includes information on the Overall Benefits and Overall Adverse Effects, as well
as specific symptoms affected.
The study was designed to obtain an understanding of the benefits and adverse ef-
fects of therapeutic diets for individuals with autism spectrum disorder, as rated by care-
givers of children and adults with ASD (and some individuals with ASD). The research
questions were, will therapeutic diets offer Overall Benefit and symptom improvements
for individuals with ASD, and will different diets help different symptoms?
2. Materials and Methods
This observational study was a cross-sectional study design that reported on the re-
sults of an online survey entitled, “National Survey on Treatment Effectiveness for Au-
tism”. The survey gathered data on the effectiveness of therapeutic diets, nutraceuticals,
medications, and therapies for ASD. This paper is focused on the results for therapeutic
diets.
It utilized two rating scales, one for benefits and one for adverse effects. The survey
also captured data on what percentage of participants reported changes in various bene-
ficial and adverse symptoms related to each diet.
The study design, survey, and ads for the study were approved by the Institutional
Review Board (IRB) of Arizona State University. The details of the creation, data
J. Pers. Med. 2023, 13, 1448 4 of 34
collection, and distribution of this survey can be found in a previously published study
using this survey [52].
The inclusion criteria were participants in the study, parents and caregivers of chil-
dren and adults with autism, autism spectrum disorder, Asperger’s syndrome, high-func-
tioning autism, pervasive developmental disorder not otherwise specified, as well as in-
dividuals with autism spectrum disorder. Since participation was anonymous, diagnosis
was not verified. Exclusion criteria were non-English speakers.
The survey had seven sections: medical history, psychiatric and seizure medication,
general medication, nutraceuticals, diets, therapies, and education. This study focuses on
the participants who reported the use of therapeutic diets, along with the demographics
and the medical history of those participants.
The diet portion of the survey began with a question of which diets the individual
with ASD had previously tried or was currently using, including a casein-free diet, corn-
free diet, Feingold Diet (defined as no artificial colors, flavors, or preservatives), food-
avoidance diet (based on IgG or IgE food testing), food-avoidance diet (based on observa-
tion), GAPS (Gut and Psychology Syndrome) Diet, gluten-free and casein-free (GFCF)
diet, gluten-free diet, healthy diet (defined as high intake of vegetables, fruit, protein; low
intake of junk food), ketogenic diet, low oxalate diet, low sugar diet, medium chain tri-
glyceride diet, modified Atkins diet, Paleo diet, rotation diet, soy-free diet, Specific Carbo-
hydrate Diet (SCD), other diet (with a write-in field), and none. Results are only reported
here for diets with 20 or more responses.
The survey asked respondents about the Overall Benefit and Overall Adverse Effects
of each diet used. There was an interval scale for rating the benefits and adverse effects of
the diets. The rating scale for perceived Overall Benefit was a scale of 0–4 (0 = no benefit,
1 = slight benefit, 2 = moderate benefit, 3 = good benefit, and 4 = great benefit). The per-
ceived Overall Adverse Effects (AE) rating scale was 0–3 (0 = no adverse effects, 1 = mild
adverse effects, 2 = moderate adverse effects, and 3 = severe adverse effects). The Overall
Benefit and Adverse Effects ratings of each diet were calculated as the mean of the scores
of the participants. Net benefit was calculated as Overall Benefit minus Overall Adverse
Effects.
The study also collected data on which symptoms changed with each diet; the list of
symptom improvements and adverse effects can be found in Table 1. For each diet, the
participant selected which symptom(s) were affected by the diet.
Table 1. List of Improved Symptoms and Adverse Effects.
Improved Symptoms Adverse Effects
General benefit (no one particular symptom)
Aggression/agitation
Anxiety
Aention
Cognition (ability to think)
Constipation
Depression
Diarrhea
Eczema/skin problem
Health (fewer illnesses and/or less severe illnesses)
Hyperactivity
Irritability
Language/communication
Lethargy (easily tired)
OCD
Reflux/vomiting
General worsening (no one specific symptom)
Aggression/agitation
Anxiety
Bedweing/bladder control
Behavior problems
Decreased cognition (difficulty thinking/remembering)
Depression
Dizziness/unsteadiness
Dry mouth
Fatigue/drowsiness
Gastrointestinal problems
Headache/migraine
Irritability
Liver/kidney problem
Loss of appetite
Nausea
J. Pers. Med. 2023, 13, 1448 5 of 34
Seizures
Self-injury
Sensory sensitivity
Sleep (falling asleep)
Sleep (staying asleep)
Social interaction and understanding
Stimming/perseveration/desire for sameness
Tics/abnormal movements
Other (with a write-in option)
Rash
Seizures
Self-injurious
Sleep problems
Stimming/perseveration/desire for sameness
Tics/abnormal movements
Weight gain
Weight loss
Other (with a write-in option)
The symptom improvements for each diet were reported as the percentage of people
who had improvement in that symptom with the diet. The adverse effects were reported
as the percentage of people who had that adverse effect with the diet. The top symptom
improvements were reported for each diet. Additionally, the diets that were highest rated
for specific symptom improvements were also reported.
Comparisons on the average Overall Benefit and Overall Adverse Effects of thera-
peutic diets vs. nutraceuticals and therapeutic diets vs. psychiatric/seizure medications
were run. The Mann–Whitney U test was used since the data was not normally distrib-
uted.
The survey also asked how strictly the participant followed the diet, as well as how
much advice they received. Statistics on correlation coefficients were run between how
strictly participants followed the diet and the benefits they received from the diet, between
how much dietary advice they received and how strictly they followed the diet, and how
much dietary advice they received and the benefits they received from the diet. Because
the data was not normally distributed, the Spearman’s rank correlation coefficient or
Spearman’s rho (rs) statistical test was used.
The survey gathered data on the severity of autism at 3 years of age and at the current
time the survey was filled out. A value of 1–5 was given with no autistic symptoms = 1,
nearly normal with only very mild symptoms = 2, mild autism = 3, moderate autism = 4,
and severe autism = 5. The severity at age 3 was subtracted from current severity to calcu-
late the change in severity. A negative number indicated a reduction in severity. The mean
of change in severity was calculated for the diet users and non-diet group. Additionally,
the Mann–Whitney U test was used (since data was not normally distributed) to compare
any change in autism severity between participants that used dietary intervention (n =
486) versus those that did not (n = 332).
The final diet question in the survey asked “Overall, what benefit do you think diet
had on your child?” This overarching question included a seven-point rating scale: the
first three were much beer (3), somewhat beer (2), or slightly beer (1); the middle re-
sponse was no effect (0); and the last three were mildly worse (−1), somewhat worse (−2),
or much worse (−3). The mean score was reported.
Survey data was analyzed through IBM SPSS Statistics software, version 28.0.1.1.
Comparisons between groups were performed with the Mann–Whitney U test and corre-
lations were performed with the Spearman’s rank correlation coefficient, as data were not
normally distributed. A p-value of less than 0.05 was considered statistically significant.
3. Results
3.1. Demographics
Of the 818 participants who filled out the survey, a vast majority were primary care-
givers (87%) and just over 9% were individuals with ASD. More than 50% of people with
ASD were 12 years old or under, 19% were 13–18 years old and 25% were over 18 years
old. Males made up 75% of the group and 25% were female. Demographic data are listed
in Table 2.
J. Pers. Med. 2023, 13, 1448 6 of 34
Table 2. Demographics and Medical History.
N %
Number of participants 818
Partipants that used dietary intervention 486
Partipants that did not used dietary intervention 332
Age of individual with ASD
Under 3 years 21 2.6%
3–5 years 131 16%
6–9 years 181 22%
10–12 years 124 15%
13–15 years 98 12%
16–18 years 60 7.3%
19–21 years 46 5.6%
22–30 years 80 9.8%
31–40 years 30 3.7%
41–50 years 23 2.8%
51–60 years 15 1.8%
Over 60 years 8 1.0%
Gender
Male 610 75%
Female 203 25%
Other 3 0.4%
Survey filled out by
Primary caregiver 711 87%
High functioning individual with autism, no guardian 58 7.1%
Completed by individual with autism, has guardian 17 2.1%
Other 32 3.9%
Diagnosis
Autism 349 43%
Autism Spectrum Disorder (this is less severe than a diagnosis of Autism) 199 24%
Pervasive Developmental Disorder—Not Otherwise Specified (PDDNOS) 47 5.7%
High-Functioning Autism 97 12%
Asperger’s Syndrome 119 15%
Other 7 0.9%
Developmental history
Normal development, followed by major regression 169 21%
Normal development, followed by a plateau in development that lasted for several months or longer 186 23%
Normal development, followed by a major regression and a plateau lasting several months or longer 101 12%
Abnormal development from early infancy, with no major regression or plateau in development 266 33%
Other 91 11%
Severity at age 3
No autistic symptoms 31 3.8%
Nearly normal, with only very mild symptoms 146 18%
Mild autism 180 22%
Moderate autism 300 37%
Severe autism 152 19%
Severity currently
No autistic symptoms 4 0.5%
Nearly normal, with only very mild symptoms 123 15%
J. Pers. Med. 2023, 13, 1448 7 of 34
Mild autism 254 31%
Moderate autism 309 38%
Severe autism 122 15%
Rounds of oral antibiotics from 0–36 months of age
Mean/Average 7
1st Quartile 1
Median 3
3rd Quartile 6
0 rounds 101 14%
1 round 135 19%
2 rounds 92 11%
3 rounds 111 16%
4 rounds 41 5.8%
5 rounds 48 6.8%
6 rounds 41 5.8%
7 rounds 15 2.1%
8 rounds 13 1.8%
9 rounds 6 0.8%
10–14 rounds 36 5.0%
15–19 rounds 13 1.8%
20–24 rounds 10 1.4%
25–29 rounds 4 0.5%
30+ rounds 45 6.1%
3.2. Medical History
Of the participants, 43% had a diagnosis of autism and 24% had autism spectrum
disorder, defined in the survey as less severe than an autism diagnosis (other diagnoses
can be found in Table 2). The developmental history included 33% who had abnormal
development from birth, with the majority (56%) having normal development followed
by some form of regression and/or plateau. Those with moderate to severe autism at 3
years of age consisted of 56% of participants and decreased to 53% at the current time of
the survey being conducted. There were a substantial number of antibiotics given in the
first three years of life with a median of 3 rounds, 1st quartile of 1 round, and 3rd quartile
of 6 rounds, where rounds were defined as “10 days = 1 round”. In total, 14% of individ-
uals had no antibiotics from age 0–36 months, approximately 70% had 1–9 rounds, 9% had
10–29 rounds, and 6% had over 30 rounds of antibiotics by the age of 3 years old (although
it is possible some of these participants confused rounds with days). Table 2 includes more
details of medical history data.
3.3. Diets in General
Table 3 lists the Overall Benefit score for each diet, which ranged from 2.0–2.7, with
an average of 2.36 across all diets. Table 3 also lists the Overall Adverse Effects (AE) scores
ranging from 0–0.4 and averaged 0.1. Net benefit scores (Overall Benefit minus AE) ranged
from 1.9–2.7, and these 13 diet scores were averaged for a net benefit score of 2.26. Overall
Benefit and Overall Adverse Effect are also graphed in Figure 1.
A separate question was asked about the overall benefit of diet in general with a
worse to beer rating of −3 to +3, which resulted in a mean of 1.7 ± 1.3. This score was
lower because the upper range only went to +3 vs. +4 and included negative scores for
those who reported diet made symptoms worse. Since all other individual diet scores used
the other benefit rating scale of 0–4, this particular score of 1.7 was not used outside of this
single datapoint.
J. Pers. Med. 2023, 13, 1448 8 of 34
Table 3. Overall Benefit, Overall Adverse Effect, Sorted by Highest Net Benefit.
Diet Overall Benefit
Overall Adverse
Effect Net Benefit
Healthy Diet 2.7 0 2.7
Feingold Diet 2.6 0 2.6
Food Avoidance, IgG/IgE 2.6 0 2.6
Low Sugar Diet 2.5 0.1 2.4
GFCF Diet 2.4 0.1 2.3
Food Avoidance, observation 2.5 0.3 2.2
Corn-free Diet 2.2 0 2.2
Specific Carbohydrate Diet 2.4 0.2 2.2
Casein-Free Diet 2.2 0.1 2.1
Soy-Free Diet 2.1 0 2.1
Paleo Diet 2.1 0 2.1
Ketogenic Diet 2.4 0.4 2.0
Gluten-free Diet 2.0 0.1 1.9
Average of All Diets 2.36 0.10 2.26
Figure 1. Overall Benefit and Adverse Effect of Therapeutic Diets, Sorted from Highest to Lowest
Overall Benefit.
3.4. Benefits and Adverse Effects of the Different Therapeutic Diets
The diet with the highest net benefit was a Healthy diet with an Overall Benefit score
of 2.7, followed by the Feingold diet and food avoidance diet based on IgG and IgE testing
with Overall Benefit scores of 2.6. The ketogenic diet had a net benefit of 2.0 (with an
J. Pers. Med. 2023, 13, 1448 9 of 34
Overall Benefit of 2.4 but a higher-than-average Adverse Effect score of 0.4). All of the
therapeutic diet ratings are listed in Table 3.
3.5. Frequency of Therapeutic Diet Usage
The number of individuals that used each diet is listed in Table 4. Some participants
used more than one diet. The average number of diets used per participant was 2.6 diets.
Three of the four most popular diets were gluten-free and/or casein-free related,
where the most commonly diet used was the GFCF diet with 221 people; next was a
healthy diet with 179 people; third was a casein-free diet with 134 responses; fourth was
gluten-free with 114 participants; and the final diet above 100 users was the Low Sugar
diet with 104 participants. The ketogenic diet and Paleo diet were used by only 21 re-
spondents, so caution is needed in interpreting these results due to the small sample size.
Since only diets with over 20 respondents were reported on, some diets such as the GAPS
diet, low oxalate diet, and others were not included in the results.
Table 4. Therapeutic Diet Frequency.
Diet # Respondents That Used Diet
GFCF Diet 221
Healthy Diet 179
Casein-Free Diet 134
Gluten-Free Diet 114
Low Sugar Diet 104
Food Avoidance, observation 82
Feingold Diet 74
Soy-Free Diet 62
Food Avoidance, IgG/IgE 54
Corn-Free Diet 46
Specific Carbohydrate Diet 37
Ketogenic Diet 21
Paleo Diet 21
3.6. Symptom Improvements from Diets
3.6.1. Average Symptom Improvements from All Diets
Figure 2 shows the percentage of respondents that reported symptoms improve-
ments due to diet, averaged across all diets. The top symptom improvements from all
diets were calculated by taking the unweighted average of all diets for each symptom.
General benefit received the highest percentage score (44%) but was excluded from Figure
2 to focus on specific individual symptoms, which ranged from 21% to 3%. The top symp-
tom improvements (with average percentage of users who improved) were aention
(21%), cognition (18%), irritability (18%), health (17%), hyperactivity (17%), aggression/ag-
itation (16%), anxiety (16%), constipation (15%), diarrhea (15%), and language/communi-
cation (13%).
Since these are averages of all participants, less common symptoms in ASD, such as
tics or seizures, tended to have a lower % that improved, since only a fraction of the par-
ticipants have the symptom. However, some diets are chosen due to a specific symptom;
for example, the ketogenic diet is used for seizures, so, presumably, more of the people
using the ketogenic diet probably experience seizures.
J. Pers. Med. 2023, 13, 1448 10 of 34
Figure 2. Percentage of Respondents that Reported Symptom Improvements Due to Diet, Averaged
Across All Diets. General Benefits were reported by 44% of participants, but are not displayed in the
graph in order to beer display the other results.
3.6.2. Symptom Improvements of the Different Therapeutic Diets
All symptom improvements are reported as the percentage of individuals who re-
ported improvement with that symptom with a specific therapeutic diet. The top diets per
symptom improvement were ranked by percentage of people who had improvement in
that symptom in Figure 3, and the top five diets for each symptom are listed in Table 5.
For the top five diets in Table 5, when the percentage was the same, they are ranked sec-
ondarily by which diet had a higher Overall Benefit rating. The diets that appeared in the
top five were, most often, the ketogenic diet, GFCF diet, Feingold diet, food avoidance
diet based on observation, and a Low Sugar diet.
The ketogenic diet was the top-rated diet for nine symptoms: aention (43%), cogni-
tion (37%), anxiety (33%), language/communication (29%), social interaction and under-
standing (29%), constipation (24%), seizures (19%), lethargy (19%), and depression (14%).
The Feingold diet was the top-rated diet for six symptoms: hyperactivity (45%), irri-
tability (38%), aggression (34%), sensory sensitivity (22%), falling sleep (19%), and staying
asleep (15%).
The GFCF diet was in the top two diets for cognition (29%), language/communication
(25%), diarrhea (22%), social interaction and understanding (22%), sensory sensitivity
(19%), and stimming/perseveration/desire for sameness 19%.
The top-rated diet for improving health was a Healthy diet (along with food avoid-
ance based on observation) at 24%.
The corn-free diet was the best diet for diarrhea with 26% of individuals improving
and second for constipation at 22%.
The Low Sugar diet was in the top two diets for hyperactivity (43%) and aggression
(23%) and in third place for irritability (23%).
The Paleo diet was the top-rated diet for tics, self-injury and OCD at 10% for each.
The SCD was in the top three diets for anxiety (19%), social interaction (14%), and
stimming (14%).
J. Pers. Med. 2023, 13, 1448 11 of 34
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J. Pers. Med. 2023, 13, 1448 13 of 34
Figure 3. Diets Ranked by Symptom Improvement.
Tab l e 5. Summary of Top 5 Diets for Each Symptom (% of dietary users that reported that the diet
improved that symptom).
Symptom Improvement Top Diets
Aggression
1. Feingold (34%)
2. Low Sugar (23%)
3. Food Avoidance, observation (21%)
4. Ketogenic (19%)
J. Pers. Med. 2023, 13, 1448 14 of 34
5. GFCF (17%)
Anxiety
1. Ketogenic (33%)
2. Feingold (28%)
3. Specific Carbohydrate Diet (19%)
4. Low Sugar (18%)
5. Food Avoidance, observation (16%)
Aention
1. Ketogenic Diet (43%)
2. Feingold (37%)
3. GFCF (31%)
4. Low Sugar (25%)
5. Specific Carbohydrate Diet (24%)
Cognition
1. Ketogenic (38%)
2. GFCF (29%)
3. Feingold (28%)
4. Specific Carbohydrate Diet (22%)
5. Low Sugar (18%)
Constipation
1. Ketogenic (24%)
2. Corn-free (22%)
3. GFCF (19%)
4. Paleo (19%)
5. Healthy (17%)
Depression
1. Ketogenic (14%)
2. Food Avoidance, observation (11%)
3. Paleo (10%)
4. Healthy (8%)
5. Low Sugar (6%)
Diarrhea
1. Corn-free (26%)
2. GFCF (22%)
3. Food Avoidance, observation (21%)
4. Specific Carbohydrate Diet (19%)
5. Gluten-free (18%)
Eczema/skin problems
1. Food Avoidance, IgG/IgE (22%)
2. Food Avoidance, observation (22%)
3. GFCF (20%)
4. Ketogenic (14%)
5. Casein-free (13%)
Health
1. Healthy (24%)
2. Food Avoidance, observation (24%)
3. Low Sugar (20%)
4. GFCF (20%)
5. Feingold (19%)
Hyperactivity
1. Feingold (45%)
2. Low Sugar (43%)
3. GFCF (22%)
4. Food Avoidance, observation (18%)
5. Ketogenic (14%)
Irritability
1. Feingold (38%)
2. Ketogenic (29%)
3. Low Sugar (23%)
4. Food Avoidance, observation (23%)
5. GFCF (20%)
Language/Communication
1. Ketogenic (29%)
2. GFCF (25%)
3. Gluten-free (15%)
4. Feingold (14%)
5. Specific Carbohydrate Diet (14%)
J. Pers. Med. 2023, 13, 1448 15 of 34
Lethargy
1. Ketogenic (19%)
2. Food Avoidance, observation (10%)
3. Paleo (10%)
4. Healthy (5%)
5. Low Sugar (5%)
OCD
1. Paleo (10%)
2. Ketogenic (10%)
3. Feingold (7%)
4. Food Avoidance, IgG/IgE (6%)
5. Low Sugar (6%)
Reflux/Vomiting
1. Food Avoidance, observation (16%)
2. Food Avoidance, IgG/IgE (13%)
3. Paleo (10%)
4. Ketogenic (10%)
5. GFCF (9%)
Seizures
1. Ketogenic (19%)
2. Paleo (5%)
3. Specific Carbohydrate Diet (3%)
4. GFCF (2%)
5. Soy-free (2%)
Self-injury
1. Paleo (10%)
2. Ketogenic (10%)
3. Feingold (8%)
4. GFCF (7%)
5. Low Sugar (5%)
Sensory sensitivity
1. Feingold (22%)
2. GFCF (19%)
3. Food Avoidance, observation (17%)
4. Paleo (14%)
5. Food Avoidance, IgG/IgE (13%)
Sleep (falling)
1. Feingold (19%)
2. Ketogenic (19%)
3. Low Sugar (11%)
4. GFCF (11%)
5. Food Avoidance, observation (11%)
Sleep (staying)
1. Feingold (15%)
2. Ketogenic (14%)
3. Food Avoidance, observation (11%)
4. Low Sugar (10%)
5. GFCF (10%)
Social Interaction and Understanding
1. Ketogenic (29%)
2. GFCF (22%)
3. Specific Carbohydrate Diet (14%)
4. Feingold (12%)
5. Food Avoidance, observation (11%)
Stimming/Perseveration/Desire for
Sameness
1. GFCF (19%)
2. Ketogenic (19%)
3. Specific Carbohydrate Diet (14%)
4. Food Avoidance, observation (13%)
5. Feingold (11%)
Tics
1. Paleo (10%)
2. GFCF (6%)
3. Food Avoidance, IgG/IgE (4%)
4. Casein-free (4%)
5. Feingold (3%)
J. Pers. Med. 2023, 13, 1448 16 of 34
Table 6 shows the symptoms that improved 10% or more for each diet. Different diets
were reported as beneficial for different symptoms.
Table 6. Top Symptom Improvements for Each Diet with at Least 10% of Respondents Improving.
Therapeutic Diets Top Symptom Improvement (% of Participants with
Improvement)
Healthy Diet
General benefit 67%
Health 24%
Constipation 17%
Aention 12%
Cognition 12%
Irritability 12%
Anxiety 11%
Hyperactivity 11%
Diarrhea 10%
Sleep (falling) 10%
Feingold Diet
Hyperactivity 45%
General benefit 41%
Irritability 38%
Aention 37%
Aggression/Agitation 34%
Anxiety 28%
Cognition 28%
Sensory sensitivity 22%
Health 19%
Sleep (falling) 19%
Sleep (staying) 15%
Constipation 14%
Language/Communication 14%
Social Interaction and Understanding 12%
Eczema/Skin problem 11%
Stimming/Perseveration/Desire for Sameness 11%
Food Avoidance Diet, Based on
IgG/IgE Testing
General benefit 43%
Eczema/Skin problem 22%
Health 15%
Reflux/vomiting 13%
Sensory sensitivity 13%
Anxiety 11%
Aention 11%
Cognition 11%
Constipation 11%
Hyperactivity 11%
Irritability 11%
Low Sugar Diet
Hyperactivity 43%
General benefit 39%
Aention 25%
Aggression/Agitation 23%
Irritability 23%
Health 20%
Anxiety 18%
Cognition 18%
J. Pers. Med. 2023, 13, 1448 17 of 34
Sensory sensitivity 11%
Sleep (falling) 11%
Language/Communication 10%
Sleep (staying) 10%
GFCF Diet
General benefit 39%
Aention 31%
Cognition 29%
Language/Communication 25%
Diarrhea 22%
Hyperactivity 22%
Social Interaction and Understanding 22%
Eczema/Skin problem 20%
Health 20%
Irritability 20%
Constipation 19%
Sensory sensitivity 19%
Stimming/Perseveration/Desire for Sameness 19%
Aggression/Agitation 17%
Anxiety 15%
Sleep (falling) 11%
Sleep (staying) 10%
Food Avoidance Diet, Based on
Observation
General benefit 32%
Health 24%
Irritability 23%
Aention 22%
Eczema/Skin problem 22%
Aggression/Agitation 21%
Diarrhea 21%
Cognition 18%
Hyperactivity 18%
Constipation 17%
Sensory sensitivity 17%
Anxiety 16%
Reflux/vomiting 16%
Stimming/Perseveration/Desire for Sameness 13%
Language/Communication 12%
Depression 11%
Sleep (falling) 11%
Sleep (staying) 11%
Social Interaction and Understanding 11%
Lethargy (easily tired) 10%
Corn-Free Diet
General benefit 44%
Diarrhea 26%
Constipation 22%
Aggression/Agitation 17%
Anxiety 11%
Cognition 11%
Eczema/Skin problem 11%
Hyperactivity 11%
Specific Carbohydrate Diet General benefit 57%
Aention 24%
J. Pers. Med. 2023, 13, 1448 18 of 34
Cognition 22%
Anxiety 19%
Diarrhea 19%
Health 16%
Irritability 16%
Language/Communication 14%
Social Interaction and Understanding 14%
Stimming/Perseveration/Desire for Sameness 14%
Aggression/Agitation 11%
Hyperactivity 11%
Sensory sensitivity 11%
Casein-Free Diet
General benefit 28%
Cognition 17%
Aention 16%
Constipation 16%
Aggression/Agitation 14%
Diarrhea 14%
Eczema/Skin problem 13%
Health 13%
Language/Communication 13%
Hyperactivity 11%
Anxiety 10%
Irritability 10%
Social Interaction and Understanding 10%
Soy-Free Diet
General benefit 45%
Diarrhea 16%
Health 11%
Aggression/Agitation 10%
Irritability 10%
Paleo Diet
General benefit 57%
Aention 19%
Constipation 19%
Irritability 19%
Anxiety 14%
Cognition 14%
Diarrhea 14%
Health 14%
Sensory sensitivity 14%
Aggression/Agitation 10%
Depression 10%
Eczema/Skin problem 10%
Hyperactivity 10%
Language/Communication 10%
Lethargy 10%
OCD 10%
Reflux/vomiting 10%
Self-injury 10%
Sleep (falling) 10%
Sleep (staying) 10%
Social Interaction and Understanding 10%
Stimming/Perseveration/Desire for Sameness 10%
J. Pers. Med. 2023, 13, 1448 19 of 34
Tics/abnormal movements 10%
Ketogenic Diet
Aention 43%
General benefit 38%
Cognition 38%
Anxiety 33%
Irritability 29%
Language/Communication 29%
Social Interaction and Understanding 29%
Constipation 24%
Lethargy 19%
Sleep (falling) 19%
Seizures 19%
Aggression/Agitation 19%
Health 19%
Stimming/Perseveration/Desire for Sameness 19%
Depression 14%
Diarrhea 14%
Eczema/Skin problem 14%
Hyperactivity 14%
Sleep (staying) 14%
OCD 10%
Reflux/vomiting 10%
Sensory sensitivity 10%
Self-injury 10%
Gluten-Free Diet
General benefit 36%
Aention 18%
Cognition 18%
Diarrhea 18%
Irritability 16%
Constipation 15%
Language/Communication 15%
Aggression/Agitation 12%
Health 12%
Anxiety 11%
Eczema/Skin problem 11%
Social Interaction and Understanding 11%
Stimming/Perseveration/Desire for Sameness 11%
Hyperactivity 10%
3.7. Comparison of Diets with Nutraceuticals and Medications
The Overall Benefit scores averaging over all the therapeutic diets were compared
with the average ratings for nutraceuticals [51] and psychiatric/seizure medications [52]
reported previously. The average Overall Benefit of diets was 2.36, substantially higher
than for nutraceuticals (1.59, p < 0.001), or psychiatric/seizure medications (1.39, p < 0.001).
The average Overall Adverse Effects of diets was 0.10, similar to that for nutraceuticals
(0.16), and much lower than that for psychiatric/seizure medications (0.93, p < 0.001).
3.8. Correlations between Strictly Following Diet, Advice Received, and Overall Benefit of Diet
Positive correlations were found between how strictly diets were followed and the
Overall Benefit users received from the diet. The following seven diets had correlations
between how strictly they were followed and the Overall Benefit rating of the diet: SCD
J. Pers. Med. 2023, 13, 1448 20 of 34
(rs = 0.45, p = 0.008), Food avoidance based on observation (0.40, p < 0.001), GFCF (rs = 0.30,
p < 0.001), gluten-free (rs = 0.32, p < 0.001), casein-free (rs = 0.26, p = 0.004), low sugar (rs = 0.25,
p = 0.015) and a Healthy diet (rs = 0.17, p = 0.003). These correlations indicated low to mod-
erate positive correlations that were statistically significant, and all correlations suggest
that more strictly following these diets resulted in slightly beer outcomes.
There were also positive correlations between the amount of advice they received
and how strictly the diets were followed for Paleo, gluten-free, food avoidance based on
observation, casein-free, food avoidance based on IgG/IgE, GFCF, Healthy, and Low
Sugar diets. Correlations were low to moderate ranging from rs = 0.21–0.49 (p < 0.05).
There were low to moderate positive correlations between the amount of advice re-
ceived and Overall Benefit from diet for food avoidance based on observation, gluten-free
Healthy, and GFCF diets with rs ranging 0.14–0.42 (p < 0.05).
In summary, more advice was associated with stricter following of the diets, and
stricter following of the diets was associated with slightly beer outcomes.
3.9. Change in Autism Severity between Participants Who Used Diet vs. Those Who Did Not
Of the 818 participants in this study, 486 used therapeutic diet(s) and 332 did not use
therapeutic diets. The change in autism severity between each participant at 3 years of age
and at the current time of the survey was calculated for the diet group and non-diet group.
Severity of autism at 3 years of age in the non-diet group was 3.33 vs. 3.50 at the current
time of the survey, and severity of autism at 3 years of age in the diet group was 3.59 vs.
3.54 at the current time of the survey. The mean of change in autism severity for those that
used diet was −0.05 (indicating a decrease in severity), and those that did not use diet was
0.18 (increase in severity). The Mann–Whitney U test showed that there was a significant
improvement in autism severity in the diet group compared to those that did not use diet
(p < 0.001).
4. Discussion
This paper highlighted the results of a survey of 18 therapeutic diets used by indi-
viduals with ASD. It reported the responses of the perceived benefits and adverse effects
of the 13 diets that had over 20 responses. On average, the diets had a moderate to good
benefit (2.36/4.0) with very small adverse effects (0.10/3.0).
Participants tried an average of 2.6 diets. However, the survey did not ask whether
the individuals had used the diets simultaneously or not, so the study was not able to
determine if some of the reported therapeutic diet results were due to diets used in com-
bination.
Top symptom improvements reported in this study, averaging over all therapeutic
diets, included aention, irritability, cognition, health, hyperactivity, aggression/agita-
tion, anxiety, diarrhea, constipation, and language. The results were consistent with a
meta-analysis of the GFCF diet for ASD, which reported significant improvements in ste-
reotypical autism behaviors and cognition [34]. Additionally, a meta-analysis on thera-
peutics diets for ASD, including the GFCF, gluten-free, and ketogenic diets, found im-
provements in the core symptoms of autism, as well as finding them safe and effective
[53]. However, most of the diets have not been formally evaluated.
The symptom improvement of “general benefit” is the highest improvement in al-
most all cases. This symptom improvement is very broad and unspecific and is probably
more prone to the placebo effect. As such, it is difficult to interpret this response, although
the higher percentage suggests that some general benefit did occur. Improvement with
rare symptoms is underestimated, as not everyone doing the diet will have these symp-
toms. For example, around 12% of children with ASD experience seizures, reaching 26%
by adolescence [54]; therefore, the effect on seizures is likely underreported for most diets,
except for those that are specifically used for seizures such as the ketogenic diet.
J. Pers. Med. 2023, 13, 1448 21 of 34
4.1. Diet Surveys
This study found similar results to other survey research, which found the top areas
of improvement from dietary intervention in ASD were behavior, communication, and
health [10]. Three of the top nine symptom improvements were in these areas. This study
also found consistent findings with another survey by Hopf et al. [9], with both studies
observing that the GFCF diet was the most commonly used diet. The Hopf survey also
found the low sugar, gluten-free, and Feingold diet were commonly used and had good
results as did this study. However, this study had differences because it was solely focused
on dietary interventions and gathered data on many more therapeutic diets. Rimland and
Edelson conducted a survey of over 27,000 participants in 2009 on medications, nutraceu-
ticals, and diets, and also found positive benefits from diet with low incidence of adverse
effects, but did not specify the symptoms affected [50]. The results included the following
diets and percentage of individuals who reported changes (“got beer”/“got worse”) with
the diet: candida diet (58%/3%), Feingold diet (58%/2%), GFCF diet (69%/3%), low oxalate
diet (50%/7%), removed chocolate (52%/2%), removed eggs (45%/2%), removed milk
products/dairy (55%/2%), removed sugar (52%/2%), removed wheat (55%/2%), rotation
diet (55%/2%), and Specific Carbohydrate Diet (71%/7%).
4.2. Therapeutic Diets
4.2.1. Healthy Diet
Healthy diet was defined as a diet high in the intake of vegetables, fruit, and protein
and low in junk food. A Healthy diet was shown to be very beneficial with the highest net
benefit (2.7) of all diets in the study, with no adverse effects reported. A Healthy diet was
rated highest for improving health. A Healthy diet was also beneficial for improving con-
stipation and symptoms of behavior and brain function such as aention, cognition, irri-
tability, anxiety, and hyperactivity. Other research support these findings. Children with
ASD were found to have a higher percentage of insufficient and unbalanced intake of
healthy foods compared to typically developing children, with significantly less intake of
fruit and less variety, and this was associated with lower working memory [55]. In chil-
dren with ASD, a healthy diet consisting of higher consumption of vegetables, fruit, leg-
umes, nuts and seeds and lower sugar was associated with a more beneficial gut microbi-
ome and beer GI symptom scores, while a diet with a lower intake of healthy foods was
associated with a less beneficial microbiome and worse GI symptoms [56].
This poor dietary intake appears to be in part due to picky eating in children with
ASD. Atypical eating behaviors were significantly greater in children with autism com-
pared with typically developing children. Atypical eating behaviors were present in 70%
of children with autism and 14.2 times more likely than in typical children [57]. Restricted
food variety and food texture hypersensitivity were two of the top atypical eating pat-
terns. In another study, food refusal was significantly higher in children with ASD with
oral sensory sensitivity [58]. In a third study of children with ASD, 67% had atypical eating
behaviors, 90% had one or more food intolerance as measured by IgG antibodies (to eggs,
milk, and wheat), and 80% had GI symptoms [59].
While no randomized controlled trials have been performed on a Healthy diet alone
for ASD, a randomized controlled trial that included a Healthy diet as part of a gluten-
free, casein-free, and soy-free (GFCFSF) diet, along with substantial micronutrient sup-
plementation, reported good results overall, and the healthy GFCFSF diet was rated the
third most effective of the six treatments in the study [49].
4.2.2. Feingold Diet
In this survey, the Feingold Diet was defined as a diet with no artificial colors, flavors,
or preservatives. The Feingold diet is also low in naturally occurring salicylates, a food
compound similar to aspirin which some people are sensitive to [60,61], found in foods
such as almonds, apples, berries, grapes, orange, peaches, cucumbers, pickles, and mint.
J. Pers. Med. 2023, 13, 1448 22 of 34
The Feingold diet was the second highest rated diet in the study, with a net benefit
score of 2.6 and no adverse effects. This study is consistent with the findings of the Hopf
et al. survey, where the Feingold Diet was rated by parents higher than the GFCF diet and
the Low Sugar diet [9]. The Feingold diet was rated first in six areas, particularly those
related to behavior and energy regulation, including hyperactivity, irritability, aggression,
sensory sensitivity, falling sleep, and staying asleep, as well as in the top three for aen-
tion, cognition, and anxiety.
In a published journal article by Dr. Ben Feingold, the creator of the diet, he stated
that roughly 50% of children with hyperactivity and learning disabilities improve with
the Feingold diet [40]. In his experience as a pediatric allergist, he found improvements
happened in this order: hyperactivity, aention, aggression, impulsivity, writing, speech,
clumsiness, cognition, and perception with the diet. This is consistent with this study,
where parents reported that 45% showed improvement in hyperactivity, 34–38% showed
improvements in irritability, aention, and aggression/agitation, 28% showed improve-
ments in anxiety and cognition, and 19% or more showed improvements in sensory sen-
sitivity and the ability to fall asleep.
A large randomized controlled trial also showed that artificial additives of preserva-
tives and artificial colors in levels typically consumed in the diet caused significant hyper-
activity in 3-year-olds and 8/9-year-olds, typically developing children, compared to pla-
cebo [62].
Salicylates are phenolic compounds, and phenols are catalyzed through sulfation by
the phenol sulfotransferase (PST) enzyme requiring adequate sulfate [63]. Children with
ASD are very low in sulfate and lack the ability to sulfate [16,63], so it is likely that this is
a mechanism of action that makes this diet particularly beneficial.
A potential limitation in this study is the Feingold diet definition was not thorough,
as it did not mention salicylates are removed in this diet. So, it is difficult to determine if
participants were responding to a diet with no artificial additives or a diet that also re-
duced salicylates.
4.2.3. Gluten and Casein Free Diets
This study separately evaluated a casein-free diet, a gluten-free diet, and a combina-
tion of a gluten-free and casein-free diet. The combined gluten-free/casein-free (GFCF)
diet showed slightly higher net benefit (2.3) compared to either the casein-free diet (2.1)
or gluten-free diet (1.9) alone. When looking at all symptom improvements, the GFCF diet
substantially outranked the gluten-free diet and the casein-free diet individually in all
symptoms. This may be because similar mechanisms of action are at play with gluten and
casein. For example, research has shown high opioid compounds [33], IgG levels [28], and
inflammatory markers [64] to both gluten and casein in ASD. If individuals react to both
food proteins, it is likely they benefit most from removing both.
Some of the top symptom improvements for the GFCF diet in this survey were aen-
tion, cognition, language/communication, diarrhea, hyperactivity, and social interaction.
The top diet for stimming/perseveration/desire for sameness was the GFCF diet. Random-
ized controlled trials show consistent results. While identifying high opioids from gluten
and/or casein in children with ASD, researchers found significant improvements with a
GFCF diet compared to controls in aention, cognition, non-verbal communication, lan-
guage, aloofness, routines and rituals, learning, peer-relations, anxiety, empathy, physical
contact, eye contact, sociability, sensory/motor function, and judgement of danger [65].
Children with ASD on a GFCF diet for 12 months had statistically significant improve-
ments over baseline in communication, social interaction, inaentiveness, and hyperac-
tivity [66]. In research that found high levels of IgG antibodies to gluten and casein in a
vast majority of children with ASD, 81% of individuals improved in 3 months on a gluten-
free/casein-free diet in most of the behaviors studied [28].
Results of a gluten-free only diet in children with ASD showed significant improve-
ments in gastrointestinal symptoms and behavior compared to baseline [67], and was
J. Pers. Med. 2023, 13, 1448 23 of 34
consistent with results from this survey. However, another study on the gluten-free diet
did not find improvement in GI or ASD symptoms [68]. High-zonulin levels, which are an
indication of intestinal permeability, are found in ASD, which can be caused by exposure
to gluten as well as other stressors, and high zonulin was associated with a higher severity
of autism [69], and may explain why some individuals find the gluten-free diet helpful.
Also, consistent with this study, the gluten-free diet was found to improve social interac-
tions in a meta-analysis of therapeutic diets for ASD; however, the meta-analysis did not
find improvements in cognition and language/communication, as this study did [53]. A
casein-free only diet for children with autism for 8 weeks resulted in significant improve-
ment in behavior [70]. So, while a combined gluten-free/casein-free diet showed the best
results, both individual gluten-free and casein-free diets showed improvement alone as
well. The underlying factors that affect an individual likely influence whether a gluten-
free and/or casein-free diet is best.
A common concern about a casein-free diet for ASD is possible calcium deficiency.
Children with ASD on a GFCF diet have been found to consume significantly lower
amounts of calcium than those on a regular diet [71]. However, children with ASD on a
regular diet also have lower calcium levels in the body. In a study of children with ASD,
where 84% were on a regular diet, the children with ASD had significantly lower levels of
Red Blood Cell (RBC) calcium (14% lower) compared to neurotypical children, and 31%
were below the reference range [16]. A follow-up randomized controlled trial study of a
multivitamin/mineral formula with a modest amount of calcium resulted in a 43% in-
crease in RBC calcium levels (bring it above the neurotypical control group level) [72].
Therefore, these results suggest that focusing on a healthy casein-free diet (and consider-
ing a multivitamin/mineral formula with calcium when needed) may be the best way to
obtain the benefits of a casein-free diet and meet nutritional needs.
4.2.4. Low Sugar Diet
The Low Sugar diet was the fourth highest rated diet with a net benefit rating of 2.4.
One reason a Low Sugar diet may be beneficial is because it provides beer balance of
blood sugar [73]. High sugar can also cause and contribute to inflammation [74], and a
mouse study shows sugar may be particularly detrimental (to glucose metabolism and
cardiometabolic risk) when mitochondrial dysfunction is present [75], which is common
in children with autism [24]. A Low Sugar diet was the second-best diet for reducing hy-
peractivity (43%, a percentage very similar to the Feingold diet) and for reducing aggres-
sion/agitation. Additional behavioral and emotional symptoms that improved on a Low
Sugar diet included aention, irritability, anxiety, and cognition. This is consistent with a
study on children with ASD where researchers observed an association between a higher
consumption of sugar sweetened beverages and emotional problems scores [76].
A Low Sugar diet may also be beneficial because of the negative effect sugar can have
on gastrointestinal health, and especially the effect on overgrowth of certain bacteria and
yeast [19,20]. In a cohort study of men and women (without autism), individuals that con-
sumed greater than one sugar sweetened beverage per day were at significantly higher
risk of inflammatory bowel disease (IBD) and Crohn’s disease than those that did not con-
sume them [77]. While these inflammatory bowel diseases are more severe than what is
typically seen in ASD, gastrointestinal symptoms are common in 49% of individuals with
ASD [78]. Therefore, avoiding foods that may contribute to gastrointestinal disorders,
such as sugar, seem warranted, especially given all the other benefits reported. However,
improvements in diarrhea and/or constipation were only found in only 8–9% of individ-
uals on a Low Sugar diet, so improving other aspects of the diet may be more important
for gastrointestinal support.
J. Pers. Med. 2023, 13, 1448 24 of 34
4.2.5. Soy-Free, Corn-Free and Food Avoidance Diets
Soy-Free Diet
A soy-free diet had an Overall Benefit rating of 2.1 with no adverse effects. This diet
is often implemented with a gluten-free and casein-free diet with beneficial results [49].
This is because soy can produce opioid compounds like gluten and casein [79], and soy
can be inflammatory to some individuals with ASD. A study of children with ASD evalu-
ated cytokine production to dietary proteins, and while cytokine production for soy was
not significant, 7 out of 75 children with ASD and GI symptoms had elevated IFN-γ levels
to soy [80]. In a study of children with autism spectrum disorder, a gluten-free, casein-
free, and soy-free (GFCFSF) or casein-free and soy-free diet was implemented depending
on food reactivity testing [81]. That study found that children with ASD and GI symptoms
had significantly higher IL-12 (pro-inflammatory cytokine) and significantly lower IL-10
(anti-inflammatory cytokine) than those without GI symptoms, and they produced signif-
icantly less IL-10 in the unrestricted diet than the elimination diet.
While this present study only showed 2% of individuals having improvements in
seizures from a soy-free diet, this is possibly due to a smaller number of people having
this symptom to start. Individuals with ASD who were fed soy formula as infants were
2.6 times more likely to have febrile seizures compared to those that were not fed soy
formula, 2.1 times more likely to have epilepsy, and 4 times more likely to have simple
partial seizures [82]. While this study was on the development of seizures from the con-
sumption of soy formula as infants, it may be judicious to avoid soy in cases of seizures
when there are other non-dairy and non-soy substitutes available.
One concern about soy and corn products is that over 95% of soy and corn in the US
is genetically modified to be more resistant to pesticides, so that higher amounts of pesti-
cides are used on those products, resulting in higher exposure to the child [83].
Corn-Free Diet
There are no known studies to date on a corn-free diet for ASD. The corn-free diet
was ranked in the middle for benefit with a score of 2.2 and no adverse effects. However,
it scored very high for diarrhea (26% improved) and constipation (22% improved). For the
symptoms of diarrhea and constipation, the corn-free diet was the top diet for diarrhea
and second for constipation. One concern with corn products is that they can be contami-
nated with aflatoxins due to fungi growth during storage [84], as well as the concern about
pesticides mentioned above.
Food Avoidance, Based on IgG/IgE Testing
A food avoidance diet based on IgG/IgE testing had the second highest net benefit
score (2.6) along with the Feingold diet, and scored the second highest for improvements
in eczema/skin problems and reflux/vomiting. Behavior and other symptoms improved
including hyperactivity, irritability, aention, cognition, anxiety, sensory sensitivity, and
health. Of the studies conducted on elevated IgG levels to foods in ASD, the most common
improvements found were related to behavior.
In a study of children with ASD, 90% had at least one IgG food sensitivity [59]. Eggs
were the top sensitivity (84% testing reactive), along with milk and wheat, and IgG anti-
bodies were correlated with stereotyped autism behaviors. IgG antibodies to gliadin were
reported in 87% of children with autism and 90% to casein [28]. In another study, anti-𝛼-
gliadin (AGA) and anti-deamidated 𝛼-gliadin IgG levels were significantly higher in chil-
dren with ASD on a regular diet, and AGA-IgG was lower on the GFCF diet. Casein IgG
was also significantly higher in children with ASD [85]. Researchers have used IgG testing
for gluten, casein, and soy to determine which food elimination diet to implement, and
found improvement in inflammatory markers when the diet was used [81]. In a previously
mentioned study, researchers found high-IgG levels for casein, as well as other
J. Pers. Med. 2023, 13, 1448 25 of 34
immunoglobulin levels for casein and proteins in dairy in children with autism at base-
line, and found behavioral improvement with a casein-free diet [70].
Food Avoidance Diet, Based on Observation
A food avoidance diet based on observation was ranked in the middle of the group
with a 2.2 net benefit rating and ranked first for reflux/vomiting. This makes sense since
most individuals with ASD and/or their caregivers may notice reflux or vomiting soon
after consuming a food that is problematic. An acute symptom such as this would be no-
ticed and reported on this survey. However, there are no studies on food avoidance based
on observation in ASD as this is a subjective measurement.
4.2.6. Grain-Free and Carbohydrate Limiting Diets
Ketogenic Diet
The ketogenic diet is the second most researched diet in autism spectrum disorder
after the GFCF diet. This is likely due to the clinical success in using of the ketogenic diet
for pediatric seizures [86] and the increased incidence of epilepsy in ASD. Specifically, one
study reported that the average prevalence of epilepsy in children with ASD between 2
and 17 years old was 12%, with the rate rising to 26% in adolescents 13 years of age and
older [54]. It is also a diet used in mitochondrial disease to improve mitochondrial func-
tion [87]; therefore, with mitochondrial dysfunction occurring as a co-morbid condition in
ASD, it is believed to be beneficial for these individuals.
The ketogenic diet had a good Overall Benefit score of 2.4, but a higher Overall Ad-
verse Effects score (0.4) than most diets, resulting in a lower Net Benefit score than most
diets. However, it is ranked the highest in nine symptoms, particularly those involving
cognitive and brain function including aention, cognition, anxiety, language/communi-
cation, social interaction and understanding, seizures, and depression, as well as lethargy
(related to mitochondrial function), and constipation.
Research shows consistent results with the findings of this survey. In a randomized
controlled trial of children with ASD, the Modified Atkins Diet (a form of ketogenic diet)
resulted in statistically significant improvements in Childhood Autism Rating Scale
(CARS) and Autism Treatment Evaluation Checklist (ATEC) scores, with the biggest im-
provements in cognition, speech, and social interaction [38]. These results were consistent
with the top three improvements found in this study. In another study, a modified keto-
genic diet with medium chain triglycerides (MCT) over 3 months provided a statistically
significant improvement in autism symptoms, and the subcategory of social affect com-
pared to baseline [35]. In a non-randomized controlled trial of children with ASD, after 3
months on a ketogenic diet containing MCT, which was also gluten-free, researchers
found statistically significant increases in ketones and acetylcarnitine (markers of im-
proved mitochondrial function) [88].
It should be noted that the ketogenic diet is an extreme diet and should be performed
under the supervision of an experienced nutritionist and/or physician.
Specific Carbohydrate Diet
The Specific Carbohydrate Diet had a net benefit of 2.2 (starting with an Overall Ben-
efit of 2.4 minus 0.2 Overall Adverse Effects). SCD was ranked second in general benefit
with 57% of people using the diet reporting general improvements. In total, 24% reported
improvements in aention, 22% in cognition, 19% in anxiety and diarrhea, along with im-
provements in health, irritability, language/communication, social interaction, stimming,
aggression, hyperactivity, and sensory sensitivity.
The Specific Carbohydrate Diet was first used and published by Drs. Sidney Haas
and Merrill Haas in 1955 for pediatric celiac disease. In this case, the report showed that
out of 191 children, 177 children had diarrhea, and 73 were able to control it within one
month with SCD and all 177 by 14 months [89]. The diet focuses on the consumption of
J. Pers. Med. 2023, 13, 1448 26 of 34
monosaccharides, and the avoidance of disaccharides and polysaccharides [89]. Disaccha-
rides and polysaccharides require carbohydrate digesting enzymes, and researchers have
found reduced levels of one or more carbohydrate digestive enzymes in 58% of children
with ASD that had gastrointestinal symptoms [31]. A reduction in disaccharidase activity
has been found to contribute to dysbiosis and gastrointestinal symptoms such as diarrhea
in ASD [32]. This survey found the diet was beneficial for diarrhea in 19% of participants
that used it. As it is unknown what percentage had diarrhea to begin with, this number
likely underrepresents those that had the symptom that improved.
In a case report of a 4 year old boy with ASD with gastrointestinal problems, after he
was placed on the Specific Carbohydrate Diet his gastrointestinal symptoms improved,
along with his behavior and nutrient levels [90]. A non-randomized controlled trial of
children with ASD on a SCD/GAPS diet plus omega 3s, ascorbyl-palmitate, probiotics,
vitamin D3, and vitamin C for three months found improvements in autism symptoms
[39] similar to this study. In the diet treatment group, ATEC (Autism Treatment Evaluation
Checklist) scores decreased by 23% from baseline with the most significant improvements
in health/behavior, socializing, irritability, and hyperactivity, as well as Parent Global Im-
pressions—Revised 2 improved significantly in 43% of the diet group vs. 14% of the con-
trol group.
Paleo
While the Paleo diet was not a top ranked diet for Overall Benefit, it was the number
one rated diet in three areas: OCD, self-injury and tics. Since these are less common symp-
toms, the effect of this diet on those symptoms may be underestimated. For example, 22%
of individuals with autism have a tic disorder [91], and 10% of those on a Paleo diet had
improvement in tics. This suggests that the Paleo diet may be very beneficial for tics. It is
also possible that, because of the relatively small number of respondents to the Paleo diet,
the results are not representative of the broader ASD population.
There is no published research known to date for the Paleo diet for ASD, but this
study suggests the diet is worthy of further research given the similarities (although some
differences) with other beneficial grain-free diets such as SCD, and its benefit for mental
health and neurological symptoms.
4.3. Personalized Nutrition for a Heterogeneous Condition
This study found that many diets may be helpful in autism spectrum disorder, and
different diets appear to be beer for addressing different underlying factors and affecting
different symptoms. Researchers believe that because ASD is a heterogeneous condition;
therefore, a personalized approach to therapeutic interventions is needed to provide the
most effective treatments [3,92], including personalized nutrition and diet strategies
[44,45]. The best diet for the individual may depend on a variety of factors.
Additionally, when diets are used in combination, it is possible greater benefits may
result. For example, people benefit from a GFCF diet more than a GF or CF diet alone, on
average. Furthermore, in the case report, a gluten-free/casein-free and ketogenic diet used
together was very beneficial, where the gluten-free/casein-free diet provided benefit ini-
tially, and then a ketogenic diet was added later [13]. Many other diet combinations are
possible, such as combining a Healthy diet, Low Sugar diet, and any of the other exclusion
diets.
Most therapeutic diets are based around the exclusion of certain foods, often based
on underlying factors that may contribute to reactions to the foods or food compounds.
This study also highlighted the importance of focusing on what to include in the diet,
particularly healthy nutrient-rich foods. Therefore, a personalized nutrition plan should
both exclude problematic foods and include healthy ones.
J. Pers. Med. 2023, 13, 1448 27 of 34
4.4. Performance of Diets vs. Nutraceuticals and Medications
Because this survey gathered information on diets, nutraceuticals, and medication
with the same rating scales, these treatments were able to be compared directly to one
another. Diet rated significantly higher than both nutraceutical and medications with very
low adverse effects. The data also suggests that dietary interventions are widely used for
individuals with ASD. Therefore, this study suggests that much more research is war-
ranted on therapeutic diets, including studies on how to determine which diet(s) are most
effective for an individual.
Diet is also an intervention that all families have access to regardless of location and
with only modest resources. Even on a moderate budget, families can choose the healthi-
est food options they have available and can often avoid gluten- and dairy-based foods
without a large expense by focusing on whole foods and avoiding expensive processed
foods. Feeding their child is an empowering act parents are already responsible for on a
daily basis, so parents should be encouraged by their physicians and nutritionists to ex-
plore dietary intervention. Since most physicians actually receive very lile nutrition ed-
ucation in medical school [93], it is recommended that families find a physician who has
that training and/or work with a nutritionist experienced with therapeutic diets for autism
spectrum disorder.
4.5. Correlations of Strict Adherence to Diet and Dietary Benefit
There were statistically significant low-to-moderate positive correlations found be-
tween those who strictly followed a therapeutic diet and the Overall Benefit score of the
diet. This suggests that the more strictly someone follows the diet, the beer results and
symptom improvement they will receive. This is significant, as this supports other re-
search [94] and highlights a possible way to get beer results with therapeutic diets. It also
may suggest that the more benefit a family sees, the more strictly they follow the diet, and
we suspect both are true.
There were also low-to-moderate positive correlations between the amount of advice
individuals received and how strictly they followed the diets, as well as correlations be-
tween the amount of advice received and Overall Benefit from diet. In the survey, the level
of advice received had four levels: no advice; limited information; some advice from a
reliable source including a nutritionist, physician, book, website; and ongoing personal
support from a qualified nutritionist. This suggests that the more advice an individual
receives the more strictly they do the diet, and the more strictly the follow the diet the
beer benefits they receive. While all these correlations were not found in each of the diets,
they were all present in the food avoidance based on observation, gluten-free, and Healthy
diet, and all variables were not needed to have benefited from the diet. Since geing more
advice and following the diet more strictly led each to beer benefits, families that want
to do a specific diet should be encouraged to seek out advice and follow the diet as strictly
as possible.
Given that not everyone followed the diet strictly, it is possible that these Overall
Benefit ratings are underestimated, and that the true benefit of the diet is higher when
someone follows it strictly. Additionally, because the highest level of following the diet
was considered an infraction less than once a week, this still provides a lot of potential for
infractions. If there had been another level, such as infraction once per month, it is possible
the correlation could have been stronger.
4.6. Change in Autism Severity with Therapeutic Diets
This study found there was a significant improvement in autism severity between
age 3 years old and the current time of the survey compared to those that did not use
dietary intervention. This data indicates that therapeutic diets can improve autism sever-
ity over time. Individuals with autism in this survey included a wide range of ages from
under 3 years old to over 60 years old. Since most of these individuals were much older
J. Pers. Med. 2023, 13, 1448 28 of 34
than 3 years old, this study shows that diet may be able to provide long term and lasting
improvements.
4.7. Diet Therapy Is Cost Effective
Implementing a therapeutic diet is relatively low-cost compared to many therapies,
such as behavior therapy, which can require several hours/day, several days/week, for
years with annual costs in the tens of thousands of dollars. In contrast, diet therapies can
be implemented with minimal cost, especially if preparing foods from raw ingredients
instead of relying on processed foods. However, they require extra learning by the food
preparer. Since most families do not have nutrition training, it is strongly recommended
that families work with nutritionists who are familiar with these diets and how to best
implement them. This is especially important to improve diet compliance for children
who are picky eaters. Enhanced understanding of the diets is likely to result in beer ad-
herence and beer effectiveness.
A nutritionist may also be able to help choose the best diet or combination of diets
and aid with personalizing the dietary intervention. Finding a diet that an individual will
accept and follow can be particularly challenging for people with ASD. Understanding
the texture and food preferences of an individual are important, and working alongside a
nutritionist can help create a diet that is more likely to be accepted. This can improve
compliance with dietary intervention, which in turn may improve results.
4.8. ANRC Autism Treatment Rater App
The ANRC Autism Treatment Rater app is a mobile app that displays some of the
data from this survey (the ratings for each diet), as well as data on many medications,
nutritional supplements, and therapies. In the app, caregivers and individuals with ASD
can directly compare these treatments and additional therapies to determine the best in-
terventions based on symptoms. It is available on iPhones and can be found by searching
the app store for “ANRC Autism Treatment Rater”.
4.9. Strengths and Limitations
Strengths of this study include the large sample size and the large number of diets
surveyed. Another strength is that this study asked about specific symptom improve-
ments with each diet; therefore, data could be gathered on whether different diets improve
different symptoms. It also included a separate rating for overall adverse effects and ad-
verse symptoms so that both benefits and adverse effects could be measured inde-
pendently.
Survey studies have inherent limitations due to errors in recalling the effectiveness
of the diet or the symptoms that were improved. There is also possible response bias,
where those that had benefited were more likely to complete the survey. There is also a
substantial placebo effect, but the comparisons between treatments should be relatively
immune to the placebo effect, assuming a similar placebo effect for all treatments. Addi-
tionally, each person may implement the same diet somewhat differently or with limited
compliance, which may cause some inaccuracy in the data. Because the age of participants
ranges from young children to older adults, the applicability may vary for specific popu-
lations.
5. Conclusions
The results of this study suggest that therapeutic diets are generally safe and often
effective for individuals with ASD. Therapeutic diets had significantly higher Overall Ben-
efit than medications and nutraceuticals from the same survey, and very low adverse ef-
fects, significantly lower than medications. Additionally, individuals that used therapeu-
tic diets had significant improvement in autism severity compared with those that did not
use diet.
J. Pers. Med. 2023, 13, 1448 29 of 34
This survey highlights the value of therapeutic diets to address and improve the
symptoms of autism spectrum disorder, as well as other common co-morbid symptoms.
Dietary interventions were reported to be most effective in improving (in descending or-
der): aention, cognition, health, hyperactivity, irritability, aggression/agitation, anxiety,
constipation, diarrhea, language/communication, eczema/skin problems, stimming/per-
severation/desire for sameness, sensory sensitivity, and social interaction and understand-
ing. The highest rated diet based on Overall Benefit was a Healthy diet, and the diets that
most often appeared in the top five for symptom improvements were the ketogenic diet,
GFCF diet, Feingold diet, food avoidance diet based on observation, and a low sugar diet.
Symptom improvement varied depending on the diet, likely due to different mechanisms
of action.
Implementing a therapeutic diet is inexpensive compared to many other treatments.
Hiring an expert nutritionist for one or a few sessions is inexpensive compared to, for
example, years of behavioral therapy or special education, and implementing a therapeu-
tic diet may result in beer response to those therapies.
The user-friendly mobile app, ANRC Autism Treatment Rater, provides data from
this study on the ratings of each therapeutic diet.
Because of the heterogeneous nature of autism spectrum disorder, a personalized
nutrition approach seems to be effective, and symptoms may be used to personalize the
most effective diet for the individual. Because healthy diets provided good benefit, and
poor diets and nutrient deficiencies are common in ASD, a therapeutic diet should both
avoid problematic foods and include nutrient-dense foods.
Author Contributions: Conceptualization, J.B.A. and J.S.M.; methodology, J.B.A.; validation, J.B.A.;
formal analysis, J.B.A. and J.S.M.; investigation, J.B.A.; resources, J.B.A.; data curation, J.B.A.; writ-
ing—original draft preparation, J.S.M.; writing—review and editing, J.S.M. and J.B.A.; visualization,
J.S.M.; supervision, J.B.A.; project administration, J.B.A.; funding acquisition, J.B.A. All authors have
read and agreed to the published version of the manuscript.
Funding: This research was funded by the Autism Research Institute and the Zoowalk for Autism
Research.
Institutional Review Board Statement: The study was conducted in accordance with the Declara-
tion of Helsinki and approved by the Institutional Review Board (or Ethics Commiee) of Arizona
State University (protocol code STUDY00003766 approved 26 January 2016).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study.
Data Availability Statement: The data from this study are available on request from the correspond-
ing authors.
Acknowledgments: We thank the following organizations for helping promote the Survey: Age of
Autism, ASU Autism/Asperger’s Research Program, Autism Academy for Education and Develop-
ment, Autism Canada, Autism Conferences of America, Autism File, Autism Free Brain, Autism Nu-
trition Research Center, Autism Research Institute, Autism Society of Alabama, Autism Society of
Bayou, Autism Society of Central Ohio, Autism Society of Central Texas, Autism Society of Dayton,
Autism Society of El Paso, Autism Society of Emerald Coast, Autism Society of Greater Akron, Au-
tism Society of Greater Harrisburg, Autism Society of Greater New Orleans, Autism Society of
Greater Phoenix, Autism Society of Hawaii, Autism Society of Indiana, Autism Society of Inland
Empire, Autism Society of Iowa, Autism Society—Kern Autism Network, Autism Society of Massa-
chuses, Autism Society of Michigan, Autism Society of Minnesota, Autism Society of Northern Vir-
ginia, Autism Society of Northwestern Pennsylvania, Autism Society of Oregon, Autism Society of
Pisburgh, Autism Society of Pennsylvania, Autism Society of San Diego, Autism Society of South-
ern Arizona, Autism Society of Southeastern Wisconsin, Autism Society of Treasure Valley, Autism
Society of Western New York, Autism Society of Westmoreland, Autism Society of West Virginia,
Autism Society of Wisconsin, Autism Speaks, Autism Spectrum Therapies, Autism Tennessee, Au-
tism Treatment Network, East Valley Autism Network, Generation Rescue, GOALS for Autism, Inc.,
Guthrie Mainstream Services, Hope Group, Independent Living Experience, National Autism Asso-
ciation, North Bridge College Success Program, Organization for Autism Research, Southwest
J. Pers. Med. 2023, 13, 1448 30 of 34
Autism Research and Resource Center (SARRC), SEEDs for Autism, S.E.E.K Arizona, STARS, Talk-
ing About Curing Autism (TACA), Unlocking Autism, US Autism and Asperger’s Association
(USAAA). We thank Devon Coleman for her work on designing and conducting the survey. We
thank Anisha Bhargava for assisting with data retrieval. We thank Steve Edelson for his detailed
review of the Survey. We thank Christina Shepard, Christy Alexon, Teresa Hart, and Robin DeWeese
for their support and review on various aspects of the manuscript. We especially thank the >1000
participants who participated in the Survey, and those who provided initial feedback on the early
versions of the Survey.
Conflicts of Interest: J.B.A. is President of the non-profit Autism Nutrition Research Center, but he
serves as a volunteer and does not receive any salary from them. He has received research grants
from ANRC. J.S.M. consults with autism families and practitioners about dietary interventions
through her organizations, Nourishing Hope and the BioIndividual Nutrition Institute. The funders
had no role in the design of the study; in the collection, analyses, or interpretation of data; in the
writing of the manuscript, or in the decision to publish the results.
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