Vitamin D Supplementation is Beneficial for Children with Autism Spectrum Disorder: A Meta-analysis

Song, Liyao; Luo, Xiaomei; Jiang, Qing; Chen, Zhi; Zhou, Lifang; Wang, Dan; Ai, Chen

doi:10.9758/cpn.2020.18.2.203

Cited by 28 publications

(20 citation statements)

References 72 publications

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“…Interestingly, meta-analysis has shown that vitamin D3 800IU to 2,000IU supplementation improves core ASD symptoms as measured by the Social Responsiveness Scale or CARS in three studies in children with ASD who were not vitamin D deficient [104] and PQQ has been shown to improve social behavior in the bilateral whisker trimming for 10 days after birth in a mouse model which is characterized by its abnormal social behavior [105]. Thus, although no studies have been conducted in ASD or CFD to determine whether these supplements may improve function in children with ASD who have FRAAs or CFD, such supplements may have some utility in these children.…”

Section: Treatments That Support Folate Transport Into the Brainmentioning

confidence: 99%

Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

Rossignol¹,

Frye

2021

JPM

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The cerebral folate receptor alpha (FRα) transports 5-methyltetrahydrofolate (5-MTHF) into the brain; low 5-MTHF in the brain causes cerebral folate deficiency (CFD). CFD has been associated with autism spectrum disorders (ASD) and is treated with d,l-leucovorin (folinic acid). One cause of CFD is an autoantibody that interferes with the function of the FRα. FRα autoantibodies (FRAAs) have been reported in ASD. A systematic review was performed to identify studies reporting FRAAs in association with ASD, or the use of d,l-leucovorin in the treatment of ASD. A meta-analysis examined the prevalence of FRAAs in ASD. The pooled prevalence of ASD in individuals with CFD was 44%, while the pooled prevalence of CFD in ASD was 38% (with a significant variation across studies due to heterogeneity). The etiology of CFD in ASD was attributed to FRAAs in 83% of the cases (with consistency across studies) and mitochondrial dysfunction in 43%. A significant inverse correlation was found between higher FRAA serum titers and lower 5-MTHF CSF concentrations in two studies. The prevalence of FRAA in ASD was 71% without significant variation across studies. Children with ASD were 19.03-fold more likely to be positive for a FRAA compared to typically developing children without an ASD sibling. For individuals with ASD and CFD, meta-analysis also found improvements with d,l-leucovorin in overall ASD symptoms (67%), irritability (58%), ataxia (88%), pyramidal signs (76%), movement disorders (47%), and epilepsy (75%). Twenty-one studies (including four placebo-controlled and three prospective, controlled) treated individuals with ASD using d,l-leucovorin. d,l-Leucovorin was found to significantly improve communication with medium-to-large effect sizes and have a positive effect on core ASD symptoms and associated behaviors (attention and stereotypy) in individual studies with large effect sizes. Significant adverse effects across studies were generally mild but the most common were aggression (9.5%), excitement or agitation (11.7%), headache (4.9%), insomnia (8.5%), and increased tantrums (6.2%). Taken together, d,l-leucovorin is associated with improvements in core and associated symptoms of ASD and appears safe and generally well-tolerated, with the strongest evidence coming from the blinded, placebo-controlled studies. Further studies would be helpful to confirm and expand on these findings.

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Section: Treatments That Support Folate Transport Into the Brainmentioning

confidence: 99%

Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

Rossignol¹,

Frye

2021

JPM

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“…For example, Mazahery et al 12 showed that supplementation with vitamin D was superior over placebo in reducing irritability and hyperactivity 12 , while Kerley et al 13 did not find an effect of vitamin D on the severity of ASD symptoms 13 . Recently, Song et al 14 examined the efficacy of vitamin D supplementation in children with ASD through a meta-analysis 14 . However, it did not specially focus on symptoms of ASD such as social interaction, communication, and repetitive restrictive behaviors or interests (RRB) or symptoms or behaviors associated with ASD, including hyperactivity, irritability, and sensory issues.…”

Section: Introductionmentioning

confidence: 99%

The effect of vitamin D supplementation in treatment of children with autism spectrum disorder: a systematic review and meta-analysis of randomized controlled trials

Zhang

et al. 2020

Nutritional Neuroscience

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Objective: The effect of vitamin D supplementation on the risk of Autism Spectrum Disorder (ASD) is conflicting. The aim of this study was to estimate the efficacy of vitamin D supplementation on ASD in children. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) in which vitamin D supplementation was used as a therapy in children with ASD. The PubMed, PsychINFO, Cochrane CENTRAL library, Web of Science, and Cinahl databases were searched from inception to March 20, 2019, for all publications on vitamin D and ASD with no restrictions. Studies involving individuals aged <18 years diagnosed with ASD and with all functional outcomes assessed by measurement scales for ASD were included. Mean differences were pooled, and a meta-analysis was performed using a random-effects model due to differences between the individual RCTs. Results: There were five RCTs with 349 children with ASD in the review, of which three RCTs were included in the meta-analysis. Vitamin D supplementation indicated a small but significant improvement in hyperactivity scores (pooled MD: −3.20; 95% CI: [−6.06, −0.34]) with low heterogeneity (I 2 = 10%, p = 0.33), but there were no other statistically significant differences in ASD symptoms between groups as measured by validated scales. Conclusion: Vitamin D supplementation appears to be beneficial for hyperactivity but not for core symptoms or other co-existing behaviors and conditions of ASD. Future RCTs with large sample sizes examining the effect of vitamin D supplementation on ASD among individuals with low serum vitamin D levels at baseline are needed.

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“…The results of this study found significant benefits for many nutraceuticals with minimal adverse effects and are consistent with the findings of a number of clinical trials studying nutraceuticals in ASD. For example, double-blind, placebo-controlled studies, and/or meta-analyses have reported improvements in children with ASD using L-carnitine [ 32 , 33 ], Coenzyme Q10 (ubiquinone) [ 34 ], digestive enzymes [ 35 , 36 ], high dose folinic acid (1–2 mg/kg/day) [ 24 , 25 , 26 ], MB12 injections [ 37 ], melatonin [ 9 , 38 , 39 , 40 , 41 , 42 ], a multivitamin/mineral supplement designed specifically for ASD [ 26 , 27 ], NAC [ 29 , 43 , 44 , 45 ], omega 3 fatty acids [ 46 , 47 ], vitamin C [ 48 ], vitamin D3 [ 49 , 50 ], and possibly B6/Mg [ 51 , 52 ]. Open-label studies in ASD have also reported benefits for B vitamins [ 53 , 54 ], biotin [ 55 ], folic acid [ 56 ], an herbal formula [ 57 ], glutathione [ 58 ], iron [ 59 ], vitamin A [ 60 ] and zinc [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Ratings of the Effectiveness of Nutraceuticals for Autism Spectrum Disorders: Results of a National Survey

Adams

Bhargava

Coleman

et al. 2021

JPM

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Autism spectrum disorder (ASD) often involves a wide range of co-occurring medical conditions (“comorbidities”) and biochemical abnormalities such as oxidative stress and mitochondrial dysfunction. Nutritional supplements (“Nutraceuticals”) are often used to treat both core ASD symptoms and comorbidities, but some have not yet been formally evaluated in ASD. The potential biological mechanisms of nutraceuticals include correction of micronutrient deficiencies due to a poor diet and support for metabolic processes such as redox regulation, mitochondrial dysfunction and melatonin production. This paper reports on the results of the National Survey on Treatment Effectiveness for Autism, focusing on nutraceuticals. The Survey involved 1286 participants from across the United States. Participants rated the overall perceived benefits and adverse effects of each nutraceutical, and also indicated the specific symptoms changed and adverse effects. From these ratings the top-rated nutraceuticals for each of 24 symptoms are listed. Compared to psychiatric and seizure medications rated through the same Survey, on average nutraceuticals had significantly higher ratings of Overall Benefit (1.59 vs. 1.39, p = 0.01) and significantly lower ratings of Overall Adverse Effects (0.1 vs. 0.9, p < 0.001). Folinic acid and vitamin B12 were two of the top-rated treatments. This study suggests that nutraceuticals may have clinical benefits and favorable adverse effect profiles.

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Vitamin D Supplementation is Beneficial for Children with Autism Spectrum Disorder: A Meta-analysis

Cited by 28 publications

References 72 publications

Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

The effect of vitamin D supplementation in treatment of children with autism spectrum disorder: a systematic review and meta-analysis of randomized controlled trials

Ratings of the Effectiveness of Nutraceuticals for Autism Spectrum Disorders: Results of a National Survey

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