Table 5.
Recent research studies investigating the impact of dietary supplementation on ASD symptoms.
| Supplement | Intervention | Subject | Main Results | References |
|---|---|---|---|---|
| Mg+B6 | Mg: 50 mg for children aged 2–3 years, 100 mg for children aged 4–8 years, 200 mg for children aged 9–12 years. Vitamin B6: 25 mg for children aged 2–3 years, 50 mg for children aged 4–8 years and 100 mg for children aged 9–12 years. Duration of intervention: 3 months |
70 children with ASD | The improvement in the overall score of the treated group was statistically significant relative to the placebo group and the intervention group. The improvement in the cognition and emotion score was statistically significant. The improvement in the social, communication and sensory deficiency score was not statistically significant. | Khan et al. [119]. A randomized, double-blind, placebo controlled study |
| Fe | 3 mg/kg/day of liquid ferrous sulfate for 3 months | 20 children with ASD | An improvement in iron levels and a reduction in the overall severity score on the Sleep Clinical Global Impression Scale were observed. Actigraphy measurements did not reveal significant improvements in the primary outcome measure, i.e., sleep onset latency and wake time after sleep onset. | Reynolds et al. [120]. A randomized placebo-controlled trial |
| Fe | Infusion of ferrous carboxymaltose (FCM) at 15 mg/kg up to a maximum dose of 750 mg | 19 children with ASD (age: 4–11 years) | In most children (84.2%) exhibiting ASD, symptoms of restless legs, and serum ferritin levels below 30 μg/L experienced clinical amelioration and notably enhanced serum iron parameters following a sole intravenous ferric carboxymaltose (FCM) infusion. | DelRosso et al. [121]. Retrospective study |
| Se | Intervention group 1 received powdered selenium supplement at 1 × 20 g/day; intervention group 2 received a functional food product with a high content of selenium (bovine heart extract) at 50 g/day |
65 children with ASD (age: 2–6 years) | Supplementation did not induce significant differences in total glutathione peroxidase levels. | Triana et al. [122] Randomized controlled trial |
| Zn | A dietary nutraceutical formula containing Zn was administered for 12 weeks. The daily Zn dose was adjusted to the participants’ body weight in kg plus 15–20 mg. | 30 children with ASD (age: 3–8 years) | Zn supplementation markedly reduced CARS scores in children with ASD. Serum Zn and metallothionein levels increased significantly after Zn supplementation. |
Meguid et al. [123] |
| Vitamin A | Participants with low plasma retinol levels (<1.05 μmol/L) received a single oral dose of vitamin A at 200,000 IU and completed a 6-month follow-up study | 64 children (aged 1–8 years) with ASD | Vitamin A induced changes in the composition of gut microbiota and improved selected ASD-related biomarkers such as CD38 and RORA. In children with ASD, significant taxonomic associations with vitamin A were identified in the Bacteroidetes/Bacteroidales group. | Liu et al. [124] Single-blinded, non-randomized intervention pilot study |
| Vitamin A | 200,000 IU for 6 months | 33 ASD patients (mean age: 5.14 ± 1.33 years) | Vitamin A decreased serum levels of 5-hydroxytryptamine (5-HT). Differences in CARS scores were noted before and after the administration of vitamin A. Improvements were observed in social interactions, emotional responses, motor skills, adaptability, sensory sensitivity (including taste, smell, and touch), anxiety levels, and verbal and non-verbal communication. Moreover, the general impression and the overall score increased significantly after vitamin A supplementation. Furthermore, excluding restricted interests, all symptoms related to the neurodevelopmental deficits reported by parents improved substantially after vitamin A administration. | Guo et al. [125] |
| Vitamin B6 | 5 mg of vitamin B6/kg body weight per day for 2 weeks, followed by 10 mg of vitamin B6/kg body weight per day for 2 weeks. Total duration of treatment: 4 weeks | 17 children with ASD (mean age: 8.8 years) | Five clusters were identified. Cluster 1 consisted of all persons who responded to vitamin B6. Persons with ASD may be highly heterogeneous. | Obara et al. [126] Single-arm intervention |
| Vitamin B6 | No data | 236 children with ASD (age: 3–16 years) | Supplementation with vitamin B and magnesium induced significant changes in tryptophan levels. | Kałużna-Czaplińska, et al. [127]. |
| Vitamin B12 | 75 μg/kg every third day for 8 weeks | 57 children with ASD (age: 3–7 years) | Vitamin B12 improved the CGI-I score, but not ABC or SRS. The supplement increased plasma methionine levels, decreased SAH levels, and improved the SAM-to-SAH ratio. | Hendren et al. [128]. Randomized controlled trial |
| Vitamin cB12 replaced with mB12; hB12 | Four children with ASD | Anemia and metabolic acidosis showed improvement when cyanocobalamin (cB12) was replaced with methylcobalamin (mB12). Furthermore, homocysteine levels returned to normal after oral administration of 10 mg of hydroxocobalamin (hB12) in a single pediatric case. | Nashabat et al. [129]. | |
| Folic acid | 400 μg, twice daily for 3 months | 66 children with ASD (age: 4.5 ± 1.1 years) | Folic acid improved social engagement, cognitive language and preverbal abilities, receptive communication skills, emotional expression, and interactions and communication in children with ASD. In addition, positive changes in folic acid and homocysteine levels stabilized the glutathione-dependent redox balance. | Sun et al. [130]. Open-label trial |
| Folic acid | 600 μg twice daily for 3 months Additional supplements (omega-3 and omega-6 fatty acids, carnitine) were administered for 12 months | 67 children and adults with ASD (age: 3–58 years) | In a clinical assessment with blinding, folic acid improved non-verbal cognitive aptitude relative to the control (untreated) group. In a semi-blinded trial, the treated cohort demonstrated greater progress in ASD symptomatology and developmental progress than the control group. The concentrations of EPA, DHA, carnitine, vitamins A, B2, B5, B6, and B12, folic acid, and coenzyme Q10 increased markedly in the treated group and differed significantly from the control. | Adams et al. [52]. Single-blinded study |
| Vitamin D | 300 IU/kg/day (max. 5000 IU/day) for 3 months | 100 children with ASD (age: 6–9 years) | Vitamin D supplementation significantly alleviated the clinical symptoms of ASD measured on the CARS and ATEC scales. Supplementation did not induce significant changes in the serum levels of serotonin and IL-6 on the ABC-C scale. | Moradi et al. [131]. Randomized controlled trial |
| Vitamin D | 300 IU/kg/day (max. 6000 IU/day) for 15 weeks | A total of 43 children, including 22 children with ASD (age: 3–13 years) | Vitamin D supplementation induced a significant decrease in irritability and hyperactivity on ABC-C subscales. Supplementation decreased lethargy/social withdrawal, inappropriate speech, and stereotypic behavior. | Javadfar et al. [132]. Randomized, double-blind, placebo-controlled, parallel-group trial |
| Vitamin D3 | 2000 IU/day | 117 children with ASD (age: 2.5–8.0 years) | The rate of positive response (at least a 25% reduction in the ABC-hyperactivity score and the ABC-irritability score) was 68% and 63%, respectively. | Mazahery et al. [133]. 12-month randomized double-blind, placebo-controlled study |
| Vitamin D3 | Administered IM at 150,000 IU/month (a total of three injections) and orally at 400 IU per day for 3 months |
215 children with ASD (mean age: 4.76 ± 0.95 years (37 autistic children received vitamin D3) | Serum levels of 25(OH) D were negatively correlated with total ABC scores and language subscale scores. Vitamin D3 supplementation significantly decreased CARS and ABC symptom scores. The treatment effects were more pronounced in younger children with ASD (≤3 years). |
Feng et al. [134]. |
| Vitamin D3 | 2000 IU for 20 weeks | 42 children with ASD | The primary endpoint (stereotypical behavior subscale of the ABC) did not show any observable effect. The self-care score in the DD-CGAS improved in the D3 group (p = 0.02). There was a tendency toward reduced inappropriate speech in the placebo group compared to the D3 group (p = 0.08), although the difference was not significant. | Kerley et al. [135]. Parallel, randomized, double-blind, placebo-controlled trial involving two visits to a clinic |
| Omega -3–6-9 | 706 mg of omega-3 fatty acids (including 338 mg of EPA and 225 mg of DHA), 280 mg of omega-6 fatty acids (including 83 mg of GLA), and 306 mg of omega-9 fatty acids | 31 children aged 18–38 months | The magnitude of clinical benefit was moderate for anxious and depressed behaviors (p = 0.049) and internalizing behaviors (p = 0.05), and large for adaptive behaviors in interpersonal relationships (p = 0.01). The remaining behaviors and sleep were not affected. |
Boone et al. [136]. 90-day randomized (1:1), double-blinded, placebo-controlled trial |
| Omega-3 | 706 mg of omega-3 fatty acids (including 338 mg of EPA and 225 mg of DHA), 280 mg of omega-6 fatty acids (including 83 mg of GLA), and 306 mg of omega-9 fatty acids | 31 children (age: 18–38 months) | Greater reduction in ASD symptoms on the Brief Infant Toddler Social Emotional Assessment ASD scale. No other outcome measure reflected a similar magnitude or a significant effect. | Keim et al. [137]. 90-day randomized, fully blinded, placebo-controlled trial |
| Omega-3 | 1000 mg of omega-3 daily in the experimental group and 1000 mg of medium-chain triglycerides (placebo) daily in the control group for 8 weeks | 54 children, (age: 5–15 years) | Significant improvement in stereotyped behaviors (p = 0.02), social communication (p = 0.02), and the GARS score (p = 0.001). No significant change in scores on the social interaction subscale. | Doaei et al. [138]. A double-blind, randomized clinical trial |