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

Adams, James B.; Bhargava, Anisha; Coleman, Devon M.; Frye, Richard E.; Rossignol, Daniel A.

doi:10.3390/jpm11090878

Cited by 16 publications

(17 citation statements)

References 70 publications

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“…A moderate dose of folinic acid (below 5 mg/day orally) improved language/communication (20%). The overall adverse effect rating was minimal [81].…”

Section: Tablementioning

confidence: 96%

“…Supplementary Table S6 lists the five studies [37,72,74,80,81] performed by three different sets of investigators which have examined the use of d,l-leucovorin in children with idiopathic ASD without additional treatments in order to determine if d,l-leucovorin administered by itself is a useful treatment for ASD. Table 4 outlines the effect sizes of some of the key outcome measures used in these studies.…”

Section: Treatment With Dl-leucovorin In General Asd: Leucovorin Onlymentioning

confidence: 99%

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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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“…A moderate dose of folinic acid (below 5 mg/day orally) improved language/communication (20%). The overall adverse effect rating was minimal [81].…”

Section: Tablementioning

confidence: 96%

Section: Treatment With Dl-leucovorin In General Asd: Leucovorin Onlymentioning

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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“…26,28,32 Two studies did not specify the age group. 30,31 Only three studies used any imaging exam, namely, magnetic resonance spectroscopic imaging after the intervention with CBD in two studies and with CBDV in one study to search for brain changes. 26,28,32 The other studies used questionnaires, forms and subjective reports of family members or caregivers.…”

Section: Resultsmentioning

confidence: 99%

Cannabis and cannabinoid use in autism spectrum disorder: a systematic review

Silva¹,

Medeiros²,

Torro-Alves³

et al. 2021

Trends Psychiatry Psychother

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction, associated with the presence of restricted and repetitive patterns of behavior, interests, or activities. Cannabis has been used to alleviate symptoms associated with ASD. Method: We carried out a systematic review of studies that investigated the clinical effects of cannabis and cannabinoid use on ASD, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA checklist). The search was carried out in four databases: MEDLINE/PubMed, Scientific Electronic Library Online (SciELO), Scopus, and Web of Science. No limits were established for language during the selection process. Nine studies were selected and analyzed. Results: Some studies showed that cannabis products reduced the number and/or intensity of different symptoms, including hyperactivity, attacks of self-mutilation and anger, sleep problems, anxiety, restlessness, psychomotor agitation, irritability, aggressiveness perseverance, and depression. Moreover, they found an improvement in cognition, sensory sensitivity, attention, social interaction, and language. The most common adverse effects were sleep disorders, restlessness, nervousness and change in appetite. Conclusion:Cannabis and cannabinoids may have promising effects in the treatment of symptoms related to ASD, and can be used as a therapeutic alternative in the relief of those symptoms. However, randomized, blind, placebo-controlled clinical trials are necessary to clarify findings on the effects of cannabis and its cannabinoids in individuals with ASD. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO), code 164161.

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“…Two papers examine general treatments for children with ASD. In a large national survey of 1286 participants across the US, several nutraceuticals, including folate and cobalamin, were found to be rated by families to have greater benefits than a similar survey of psychiatric and seizure medications [19]. Another study demonstrates how examining genetic variations can help consider targeting common nutraceutical treatments on a personalized basis [8].…”

mentioning

confidence: 99%

“…Perhaps most apparent, these articles underline the primacy of mitochondria in ASD, including oxidative stress and redox regulation, which are themselves major functions of mitochondria. Although the connection between ASD and this important cellular organelle is hardly new, this collection of papers serves to demonstrate the ubiquitous nature of the connection, which ranges from mitochondrial aspects in the prenatal and environmental risk factors/exposures [2,3,8] to biomarkers/metabolites [5,8,[12][13][14][15][16], enzymology [12], and the positive response to therapy, at least in part targeting the mitochondria [8,11,12,15,16,18,19].…”

mentioning

confidence: 99%