Table 1: Dietary intervention in ASD.

Author Year Type and duration of study Sample size Type of intervention ComparatorsOutcome measureFindings Comments

Knivsberg et al. [13]2002Randomized, placebo controlled, single blind, parallel group  
Duration: 12 months
n = 20 (gender not reported)  
Age: 59–127 months
Gluten- and casein-free diet (GFCF)  
n = 10
Normal diet  
= 10
DIPAB (a Danish assessment of autistic trait), Leiter International Performance Scale, ITPA, Reynells språktest, Movement Assessment Battery for ChildrenSignificant improvement in all domains for the diet group compared to the control groupParent not blinded to diet  
Small sample size  
Not standardized assessment of autistic traits  
No accounting for potential confounders (medication, other therapies)  
Few baseline characteristics for patients  
No assessment of dietary fidelity

Elder et al. [14]2006Randomized, double blind, repeated measures, crossover  
Duration: 12 weeks
n = 15 (M 12; F 3)  
Age: 2–16 years
GFCFMatched diet but with gluten and caseinCARS  
Urinary Peptide Levels, ECO Language Sampling Summary, behavioral observation by at home videos
(at week 6 and week 12)
No significant differences between the two groupsSmall sample size  
High heterogeneity in patients  
Short study duration  
Dietary fidelity not always adequate  
Missing data for some variables  
No accounting for potential confounders (medication, other therapies)

Whiteley et al.
[15]
2010Randomized, double blind, placebo controlled, partly crossover (at 12 months, not responders in the control group switch to diet)  
Duration: 24 months
n = 72 (gender not reported)  
Age: 4–11 years
GFCF (n = 38)  
Drop-out at 12 months n = 11, one patient removed additionally for protocol deviation  
Analysis at 12 months carried out on 26 children (M 21; F 5)  
Analysis at 24 months carried out on 18 children
Normal diet ( = 34)  
Drop-out at 12 months  
= 4, one patient removed additionally for protocol deviation  
Analysis at 12 months carried on 29 children (M 28; F 1)  
Analysis at 24 months carried out on 17 children
ADOS-G, VABS, ADHD-IV, and GARS (at baseline and 8–12–20–24 months) Significant improvement in the diet group at 12 and 24 months in ADOS-communication and repetitive domains, GARS social domainsParent not blinded to diet  
Sample size seems adequate but not power analysis provided  
Only per-protocol statistical analysis  
High attrition rate  
Study design and crossover not completely clear  
No accounting for potential confounders (medication, other therapies)  
No assessment of dietary fidelity  

Johnson et al. [16]2011Randomized, parallel groups  
Duration: 3 months
n = 22 (M 18; F 4)  
Age: 3–5 years  
Diagnosis of ASD only in 20 patients, PDD-NOS in 2 patients
GFCF  
= 8
Low sugar healthy diet  
= 14
Mullen Scales of Early Learning, CBC, direct observation of behavior (at baseline and after 3 months) No significant clinical difference between the two groups (improvement in CBC aggression and CBC ADHD in GFCF group)Blinding not reported (parent not blinded)  
Small sample size  
Low dietary adherence in GFCF group  
No accounting for potential confounders (medication, other therapies)

Evangeliou et al. [17]2003Prospective, open label  
Duration: 6 months
= 30 (M 16; F 14)  
Drop-out  
= 7  
Age: 4–10 years
Ketogenic diet according to John Radcliffe (30% medium-chain triglyceride oil, 30% fresh cream, 11% saturated fat, 19% carbohydrates, and 10% proteins) was administered for 6 months, with intervals of 4 weeks interrupted by two diet-free weeksNoneCARSImprovementLow dietary tolerance and subsequent high attrition rate  
Small sample size  
Open label trial  
Assessors not blinded  
Statistical analysis not optimal  
All patients were taking haloperidol

Karkelis et al. [18]2010Randomized, placebo controlled, parallel group  
Duration: 4 months
= 45 (gender not reported)  
Age: 2–8 years  
IgE positive for milk allergy n = 17
Elemental formula diet (containing free amino acids) with no milk product  
= 22 (positive for milk allergy = 9)
Normal diet = 23 (positive for milk allergy = 8)HyperactivitySignificant improvement in hyperactivity in the elemental diet for patients with milk allergy and ASD without food allergyBlinding not reported  
Baseline data not complete  
Preliminary report  
Not standardized outcome measure  
Sample size seems adequate but no power analysis

Chan et al. [19]2012Randomized, double blind, parallel group  
Duration: 1 month
= 24 (M 20; F 4)  
Age: 7–17 years
Chan diet = 12Normal diet = 12ATEC, Five-Point Test, Tower of California, go/no go task, D2 Test of Concentration, CCTTSignificant improvement in ATEC in the experimental groupBlinding not reported (parents appear not blinded, which could alter ATEC)  
Small sample size  
Short study duration  
Statistical analysis not optimal 

Al-Ayadhi and Elamin [20]2013Randomized, double blind, placebo controlled, parallel group  
Duration: 2 weeks
= 60 (gender not reported)  
Age: 2–12 years
Camel milk raw ( = 24) or boiled ( = 25)Cow milk as placebo  
= 11
CARSSignificant improvement in CARS after introduction of camel milkShort study duration  
Statistical analysis not optimal  
Few baseline characteristics of patients  
Number of patients not balanced between groups

Bashir and Al-Ayadhi [21] 2014Randomized, double blind, placebo controlled, parallel group  
Duration: 2 weeks
= 45 (M 40; F 5)  
Age: 2–12 years
Camel milk raw (n = 15) or boiled ( = 15)  
Additionally 6 patients dropped out (4 in the boiled group and 2 in the raw)
Cow milk as placebo  
n = 15  
Additionally 3 patients dropped out
CARSSignificant improvement in CARS in the raw camel milk groupShort study duration  
Only per-protocol analysis  
High drop-out rate

ADHD-IV, Attention-Deficit Hyperactivity Disorder-IV rating scale; ADOS, Autism Diagnostic Observation Schedule; ATEC, Autism Treatment Evaluation Checklist; ASD, autism spectrum disorder; CARS, Childhood Autism Rating Scale; CBC, Child Behavior Checklist; CCTT, Children’s Color Trails Test; ECO, Ecological Communication Orientation; GARS, Gilliam Autism Rating Scale; GFCF, gluten- and casein-free diet; ITPA, Illinois Test of Psycholinguistic Abilities; PDD-NOS, Pervasive Developmental Disorder Not Otherwise Specified; VABS, Vineland Adaptive Behavior Scale.