Cessation of Nocturnal Enuresis after Intervention with Methylcobalamin in an 18-Year-Old Patient with Autism

Čorejová, Adela; Jánošíková, Daniela; Pospíšilová, Veronika; Rauová, Drahomíra; Kyselovič, Ján; Hrabovská, Anna

doi:10.1089/cap.2014.0023

Cited by 5 publications

(12 citation statements)

References 19 publications

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“…One study initially used cB12 injections and switched to mB12 injections due to worsening anemia from cB12 in 2 children and also used oral hB12 in one child [ 51 ]. The remaining 8 studies used mB12 [ 8 , 11 , 35 , 52 , 53 , 54 , 55 , 56 ]. Thus, of the 12 studies specifying the type of B12 used, 10 (83%) used mB12 by itself or in combination with cB12.…”

Section: Resultsmentioning

confidence: 99%

“…Six studies used subcutaneously (SC) injected mB12 [ 8 , 11 , 35 , 53 , 55 , 56 ] and 4 studies used intramuscularly injected B12 [ 32 , 46 , 47 , 51 ]. Five studies used oral B12 [ 44 , 48 , 49 , 50 , 54 ]. One study used both injected cB12 and oral hB12 [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

“…One study used a lower dose of 25–30 µg/kg/dose (up to 1500 µg), but the route of administration was not specified [ 52 ]. One study used oral mB12 at a dose of 500 µg per day [ 54 ] while 2 studies used oral cB12 in doses of 500–1600 µg per day along with a multivitamin/mineral supplement (MVI) [ 48 , 49 ]. Another study used a 50/50 mixture of mB12 and cB12 500 µg per day combined in an MVI [ 50 ].…”

Section: Resultsmentioning

confidence: 99%

“…Of the 17 treatments studies, 2 were DBPC studies using mB12 injections alone [ 35 , 55 ], 2 were DBPC studies using oral cB12 in a MVI preparation [ 48 , 49 ], 1 was a prospective, controlled study [ 50 ], 6 were prospective, uncontrolled studies [ 8 , 11 , 44 , 45 , 52 , 53 ], and 6 were retrospective case series/reports [ 32 , 46 , 47 , 51 , 54 , 56 ]. Two studies reported on the same cohort of patients [ 11 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

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The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Rossignol¹,

Frye

2021

JPM

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Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5–75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Rossignol¹,

Frye

2021

JPM

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“…Interestingly, the age-dependent decrease in methionine synthase, the target of mB12 in the methionine pathway, may be accelerated in the ASD brain (Muratore et al, 2013 ). Treatment with cobalamin has been shown to be therapeutic in ASD in both case (Pineles et al, 2010 ; Corejova et al, 2015 ) and double-blind placebo-controlled (Bertoglio et al, 2010 ; Hendren et al, 2016 ) studies.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials

et al. 2018

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Autism spectrum disorder (ASD) affects about 1 in 45 individuals in the United States, yet effective treatments are yet to be defined. There is growing evidence that ASD is associated with abnormalities in several metabolic pathways, including the inter-connected folate, methylation and glutathione pathways. Several treatments that can therapeutically target these pathways have been tested in preliminary clinical trials. The combination of methylcobalamin (mB12) with low-dose folinic acid (LDFA) and sapropterin, a synthetic form of tetrahydrobiopterin (BH4) have been studied in open-label trials while high-dose folinic acid has been studied in a double-blind placebo controlled trial. All of these treatments have the potential to positively affect folate, methylation and glutathione pathways. Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways. Furthermore, the recent study using high-dose folinic acid (HDFA) did not analyze the change in metabolism resulting from the treatment. Thus, we compared changes in methylation and glutathione metabolism and biomarkers of chronic oxidative stress as a result of these three treatments to individuals receiving placebo. In general, mB12/LDFA treatment had a significant effect on glutathione and cysteine metabolism with a medium effect size while BH4 had a significant effect on methylation and markers of chronic oxidative stress with a large effect size. HDFA treatment did not significantly influence biomarkers of methylation, glutathione or chronic oxidative stress. One caveat was that participants in the mB12/LDFA and BH4 studies had significantly worse markers of glutathione metabolism and chronic oxidative stress at baseline, respectively. Thus, the participants selected in these two clinical trials may have been those with the most severe metabolic abnormalities and most expected to respond to these treatments. Overall this study supports the notion that metabolic abnormalities in individuals with ASD may be amenable to targeted treatments and provide some insight into the mechanism of action of these treatments.

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Improvement of the Clinical and Psychological Profile of Patients with Autism after Methylcobalamin Syrup Administration

et al. 2022

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(1) Background: Autism, also known as autism-spectrum disorder, is a pervasive developmental disorder affecting social skills and psychological status in particular. The complex etiopathogenesis of autism limits efficient therapy, which leads to problems with the normal social integration of the individual and causes severe family distress. Injectable methylcobalamin was shown to improve the clinical status of patients via enhanced cell oxidative status and/or methylation capacity. Here we tested the efficiency of a syrup form of methylcobalamin in treating autism. (2) Methods: Methylcobalamin was administered daily at 500 µg dose to autistic children and young adults (n = 25) during a 200-day period. Clinical and psychological status was evaluated by parents and psychologists and plasma levels of reduced and oxidized glutathione, vitamin B12, homocysteine, and cysteine were determined before the treatment, and at day 100 and day 200 of the treatment. (3) Results: Good patient compliance was reported. Methylcobalamin treatment gradually improved the overall clinical and psychological status, with the highest impact in the social domain, followed by the cognitive, behavioral and communication characteristics. Changes in the clinical and psychological status were strongly associated with the changes in the level of reduced glutathione and reduced/oxidized glutathione ratio. (4) Conclusion: A high dose of methylcobalamin administered in syrup form ameliorates the clinical and psychological status of autistic individuals, probably due to the improved oxidative status.

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Cessation of Nocturnal Enuresis after Intervention with Methylcobalamin in an 18-Year-Old Patient with Autism

Cited by 5 publications

References 19 publications

The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials

Improvement of the Clinical and Psychological Profile of Patients with Autism after Methylcobalamin Syrup Administration

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