Author Year Type and duration of study Sample size Type of intervention Comparators Dose Outcome measure Findings Comments Omega 3 Amminger et al. [22 ] 2007 Randomized, double blind, placebo controlled, parallel group Omega 3 Placebo 0.84 g/day EPA and 0.7 g/day DHA ABC No significant difference between the two groups No details about blinding Bent et al. [23 ] 2011 Randomized, double blind, placebo controlled, parallel group Omega 3 Placebo 0.7 g/day EPA and 0.46 g/day DHA ABC, PPVT-III, EVT, SRS, BASC, CGI-Improvement No statistically significant difference Only per-protocol analysis Bent et al. [24 ] 2014 Randomized, double blind, placebo controlled, parallel group Omega 3 Placebo 1.3 g/daily of omega 3 (1.1 g/day of EPA plus DHA) ABC, CGI, SRS No statistically significant difference Small sample size Meguid et al. [25 ] 2008 Open label Omega 3 None 240 mg/day DHA; 52 mg/day EPA; 68 mg/day Omega-6 fatty acids CARS Improvement in 20 children Statistical analysis incorrect (conducted only on children which showed a reduction in symptoms) Politi et al. [26 ] 2008 Open label Omega 3 None 0.93 g/day EPA plus DHA, 5 mg/day vitamin E Rossago behavioral checklist No significant change from baseline Small sample size Voigt et al. [27 ] 2014 Randomized, double blind, placebo controlled, parallel group Omega 3 Placebo 200 mg/day DHA CGI-Improvement scale, CDI, ABC, BASC No significant difference between active group and placebo Small sample size Vitamins Findling et al. [28 ] 1997 Randomized, double blind placebo controlled, crossover Vitamin B6-magnesium Placebo B6: 30 mg/kg/day (max = 1 g/day); Mg: 10 mg/kg/day (max = 350 mg/day) CARS, CGI, CPRS, OCS No difference between the two groups Small sample size Kuriyama et al. [29 ] 2002 Randomized double blinded placebo controlled parallel group Vitamin B6 Placebo B6: 200 mg/day IQ (WISC-III) and SQ (SM) No difference between active group and placebo Small sample size Tolbert et al. [30 ] 1993 Randomized double blind placebo controlled, asymmetric crossover with 10 week treatment blocks (B6/Mg 20 w-placebo 10 w; or B6/Mg 10 w-placebo 10 w-B6/Mg 10 w) Vitamin B6-magnesium Placebo B6: 200 mg/70 kg; Mg: 100 mg/70 kg RLRS No difference No information on placebo Bertoglio et al. [31 ]
2010 Randomized, double blind, placebo controlled, crossover Methyl B12 Placebo 64.5 mcg/kg every three days CGI-I, PIA-CV, CARS, PPVT-III, ABC, CBC, Stanford Binet Fifth Edition Routing Subsets, MCDI No significant difference between active treatment and placebo Small sample size Frye et al. [32 ] 2013 Open label trial Methyl B12 vitamin plus folinic acid None 75 Vineland Improvement in all Vineland subscales Only patients with abnormal redox metabolism were included Dolske et al. [33 ] 1993 Randomized double blinded placebo controlled, crossover with asymmetric design with 10 w block (randomly assigned to vitC-vitC-placebo or vitC-placebo-vitC) Vitamin C Placebo 8 g/70 kg/day RLRS Significant improvement in vitC treated Small sample size Adams et al. [34 ] 2011 Randomized double blinded placebo controlled trial Multivitaminic supplement Placebo Each supplement was titrated to be over the recommended daily allowance but under the tolerable upper limit PDD-BI, ATEC, SAS, parent-rated behaviors Improvement of parent-rated irritability in the active group No power calculation Danfors et al. [35 ] 2005 Randomized, double blind, placebo controlled, crossover Tetrahydrobiopterin (BH4) Placebo 3 mg/kg/day CARS (baseline, 3 and 6 month) Small changes in CARS total score Small sample size Frye et al. [36 ] 2013 Open label Tetrahydrobiopterin (BH4) None 20 mg/kg/day PLS, SRS, CARS, ASQ, Vineland Significant improvement in PLS, CARS, ASQ, and Vineland Open label Klaiman et al. [37 ] 2013 Randomized, double blind, placebo controlled, parallel group Tetrahydrobiopterin (BH4) Placebo 20 mg/kg/day CGI, PLS, ABC, SRS, Vineland No significant difference between the two groups Improvement only in post hoc analysis on secondary measures L-carnosine Chez et al. [38 ] 2002 Randomized double blinded placebo controlled L-Carnosine Placebo 800 mg/day CARS, GARS, CGI Significant improvement in the active group in GARS and in the Receptive One-Word Picture Vocabulary test Small sample size Flavonoids
Taliou et al. [39 ] 2013 Open label Flavonoid None Luteolin (100 mg/capsule), quercetin (70 mg/capsule), and the rutin (30 mg/capsule) Vineland, ABC, ATEC, CGI-improvement Improvement in Vineland and ABC scores Open label design Probiotics
Kałuzna- 40 ] 2012 Open label Probiotic None Lactobacillus acidophilus (strain Rosell-11, containing 5 × 109 CFU/g)Observer rated autism core symptoms Improvement Open label design Enzyme supplementation Munasinghe et al. [41 ] 2010 Randomized double blinded placebo controlled crossover Duration: 6 months Digestive enzyme supplement Placebo Peptizyde GBRS, ARS of gastrointestinal symptoms, and the Rescorla LDS No difference High drop-out rate Herbal remedies Hasanzadeh et al. [42 ] 2012 Randomized double blinded placebo controlled Ginkgo biloba Placebo 80 mg/day if weight <30 kg; otherwise 120 mg/day ABC No difference Small sample size Miyaoka et al. [43 ] 2012 Open label Yokusan None 5.0–7.5 g/day CGI-Severity, ABC Improvement in CGI and the irritability subscale of ABC Open label design Chan et al. [44 ] 2014 Open label Bornel and Borax nasal drops None 10 mL/day BRIEF, Tower of California, CCTT, CPRS, event-related EEG assessment Improvement Not placebo controlled
