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Vitamin B 6-magnesium treatment for autism: the current status of the research

Magnesium Research. Volume 23, Numéro 2, 115-7, June 2010, Letter

DOI : 10.1684/mrh.2010.0209

Auteur(s) : Kimberly A Murza, Stacey L Pavelko, Melissa D Malani, Chad Nye , University of Central Florida, Center for Autism and Related Disabilities, Orlando, USA.


Auteur(s) : Kimberly A Murza, Stacey L Pavelko, Melissa D Malani, Chad Nye

University of Central Florida, Center for Autism and Related Disabilities, Orlando, USA

In 2005, a systematic review was published by the Cochrane Collaboration that reviewed the effects of vitamin B6-magnesium (vit B6-Mg) treatment for autism [1]. The focus of the review was to assess the impact of vit B6-Mg for improving the communication and behavioural responses of children and adults with autism. The review summarized and synthesized only studies that reported randomized controlled trial (RCT) research designs as the basis for determining the efficacy of the treatment. The primary conclusion drawn from this review was that there was insufficient evidence to warrant the advocacy of vit B6-Mg as a treatment to improve communication and behaviour of individuals with autism. However, with the continued interest in the use of the vitamin vit B6-Mg as a treatment protocol, the purpose of this paper is to provide a brief update to the Cochrane review using the same standards of study inclusion, information retrieval, data extraction, and analysis as presented by Nye and Brice [1].

Updated review

For the Cochrane review [1] a total of five databases were searched. All studies meeting their inclusion criteria were retrieved from three databases: MEDLINE, ERIC, and PsycINFO. For this update, a new search was conducted using those three databases along with the same key terms and included the years January 2005 through March 2010. A total of 154 titles/abstract citations were retrieved and evaluated for potential inclusion (MEDLINE = 128, ERIC = 4, PsycINFO = 22) of which 144 citations were excluded due to non-RCT design reports, the absence of outcomes associated with communication and behaviour, or participants were not diagnosed with autism spectrum disorder (ASD). Thus a total of, ten citations appeared to potentially meet inclusion criteria and a full-text of each study was obtained for further analysis.

A review of the full text of these studies resulted in the exclusion of seven studies. Two of the seven studies [2, 3] measured the level of vit B6 in the plasma of children with ASD and typically developing peers who were not taking supplements. A third, [4] compared the macro- and micro-nutrients consumed from three-day diet records of children with ASD and their typically developing peers. A fourth study [5] reported a vit B6-Mg treatment study in which participants were diagnosed with Attention Deficit Hyperactivity Disorders (ADHD) rather than autism spectrum disorder. The fifth study retrieved reviewed nutritional and environmental approaches to treating ASD and ADHD [6] while a sixth study reviewed alternative intervention approaches to autism [7]. A seventh study [8] reported on a survey of 19 parents of children with ASD to assess their satisfaction with the vit B6-Mg treatment for their child.

Of the three remaining studies, two were narrative summaries of alternative treatments of autism [9, 10]. Wallace [10] supported the lack of efficacy of vitamin vit B6-Mg treatments but did not provide any new research in the area. Rossignol [9] summarized several novel and emerging treatments in ASD including vit B6-Mg treatment. Each treatment was given a grade according to the research evidence, which supported its effectiveness. The specific review of vit B6-Mg treatment was given a grade of “C” because it was either supported by at least one nonrandomized controlled trial or at least two case studies. The review included a discussion of the Nye and Brice review [1] but supported evidence of effectiveness with the Mousain-Bosc et al. [5] study cited above. It should be noted, as discussed above, the participants in the Mousain-Bosc et al. [5] study were not diagnosed with ASD; therefore, any comparison across studies would be inappropriate.

Only one of the articles retrieved at the full-text stage reported an RCT design that investigated the effect of B6-Mg on the behaviour of persons with ASD [11]. A summary of this study follows.

Review of intervention studies

Adams and Holloway [11] investigated the levels of vitamin B6, vitamin C, and alpha lipoic acid in 25 children three to eight years of age and diagnosed with autism spectrum disorder (ASD). The purpose of this study was to determine whether a moderate dose of a multivitamin/mineral supplement was effective in reducing symptoms associated with ASD. Children included in the study demonstrated no changes in any treatment therapies for the two months preceding the intervention phase of the study, and none of the participants were currently taking a multivitamin or mineral supplement. A total of 25 children met the inclusion criteria for enrolment in the study. Participants were matched in pairs by sex and age and randomly assigned to the intervention or control group. Precisely how this was accomplished was unclear due to the odd number of participants qualifying for study inclusion. Five of the participants did not complete the study – three children in the control group and two in the intervention group leaving a final sample size of n = 9 in the control and n = 11 in the treatment group for which data were provided.

Participants in the intervention group initially received Spectrum Support II (SSII) vitamin supplement at 1/8 of the dose, which was increased linearly over 24 days to the maximum dose of SSII. The maximum dosage was held constant until day 34. From days 35-50, the participants in the treatment group were gradually transitioned to Spectrum Support III (SSIII), which continued until day 90 at the same level. Participants were given a daily intake of 3 mL/22.3 kg (5 pounds) bodyweight. Participants in the control group received a placebo designed to look identical to the actual supplement.

To assess the impact of the vit B6-Mg treatment for communication and behaviour, mothers of the children in both groups completed a global impressions survey to evaluate changes in their child‘s behaviour at the conclusion of the intervention. Mothers of children in the intervention group reported statistically significant improvements in sleep and gastrointestinal symptoms (p < 0.05). Measures of expressive and receptive language, general behaviour, eye contact, and sociability all yielded statistically non-significant (p > 0.05 differences between treatment and control participants.

The findings are consistent with the results reported by Nye and Brice [1]. However, methodological short-comings of the study make interpretation of the results problematic on several accounts:

  •  the method of group assignment of participants is unclear,
  •  the RCT design was compromised due to differential group dropout rates and a failure to utilize appropriate statistical procedures.


While Adams and Holloway [11] met the same inclusion criteria used by Nye and Brice [1], the measures of communication and behaviour change were accomplished by the indirect measurement of a parent survey. The methodological issues of the study limit the robustness of the results and their interpretation for other children diagnosed with ASD. Overall, these data can at best be seen as consistent with the Nye and Brice review/conclusions and at worst these data do not contribute any new findings to the existing literature.

Taken as a whole, the research reported since 2005 support the original conclusions of Nye and Brice [1], “Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced based on this review regarding the use of B6-Mg as a treatment for autism. There is simply not sufficient evidence to demonstrate treatment efficacy”.


1 Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database 2005; 4: CD003497.

2 Adams J, George F, Audhya T. Abnormally high plasma levels of vitamin B? in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med 2006; 12: 59-63.

3 Strambi M, Longini M, Hayak J, Berni S, Macucci F, Scalacci E, Vezzosi P. Magnesium profile in autism. Biol Trace Elem Res 2005; 109: 96-104.

4 Herndon A, DiGuiseppi C, Johnson S, Leiferman J, Reynolds A. Does nutritional intake differ between children with autism spectrum disorders and children with typical development? J Autism Dev Disord 2009; 39: 212-22.

5 Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. Magnes Res 2006; 19: 46-52.

6 Curtis L, Patel K. Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): A review. J Altern Complement Med 2008; 14: 79-85.

7 Hjiej H, Doyen C, Couprie C, Kaye K, Contejean Y. Approches substitutive et diététique du trouble autistique de l'enfant: intérêts ou limites? L'Encéphale 2008; 34: 496-503.

8 Green VA. Parental experience with treatments for autism. J Dev Physic Dis 2007; 19: 91-101.

9 Rossignol DA. Novel and emerging treatments for autism spectrum disorders: A systematic review. Ann Clin Psychiatry 2009; 21: 236-313.

10 Wallace L. What's the Scoop on Autism Spectrum Disorders and Nutrition? Exceptional Parent 2009; 39: 28-30.

11 Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorders. J Altern Complement Med 2004; 10: 1033-9.


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