Complementary and Alternative Therapies for Autism Spectrum Disorder

Table 1

Dietary intervention in ASD.

Author	Year	Type and duration of study	Sample size	Type of intervention	Comparators	Outcome measure	Findings	Comments
Knivsberg et al. [13]	2002	Randomized, 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 Children	Significant improvement in all domains for the diet group compared to the control group	Parent 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]	2006	Randomized, double blind, repeated measures, crossover; Duration: 12 weeks	n = 15 (M 12; F 3); Age: 2–16 years	GFCF	Matched diet but with gluten and casein	CARS; 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 groups	Small 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]	2010	Randomized, 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 domains	Parent 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]	2011	Randomized, 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]	2003	Prospective, 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 weeks	None	CARS	Improvement	Low 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]	2010	Randomized, 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)	Hyperactivity	Significant improvement in hyperactivity in the elemental diet for patients with milk allergy and ASD without food allergy	Blinding not reported; Baseline data not complete; Preliminary report; Not standardized outcome measure; Sample size seems adequate but no power analysis
Chan et al. [19]	2012	Randomized, double blind, parallel group; Duration: 1 month	= 24 (M 20; F 4); Age: 7–17 years	Chan diet = 12	Normal diet = 12	ATEC, Five-Point Test, Tower of California, go/no go task, D2 Test of Concentration, CCTT	Significant improvement in ATEC in the experimental group	Blinding 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]	2013	Randomized, 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	CARS	Significant improvement in CARS after introduction of camel milk	Short study duration; Statistical analysis not optimal; Few baseline characteristics of patients; Number of patients not balanced between groups
Bashir and Al-Ayadhi [21]	2014	Randomized, 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	CARS	Significant improvement in CARS in the raw camel milk group	Short 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.