Early Nutritional Intervention in Patients With Autism Spectrum Disorders
Condition: Autism Spectrum Disorders; Stable Clinical Condition in the Last 3 Months
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Interventional

Summary: 
      Nutritional supplements like vitamin B6 and magnesium have demonstrated to have beneficial
      effects in patients with autism spectrum disorders (ASD). The underlying theory for these
      effects is that specific metabolic pathways in neuronal cells, e.g. the methionine cycle,
      will be more balanced. Most studies have been focused on the clinical outcome with this
      treatment. The present proposal will examine the effects on the different intermediates of
      the methionine cycle (methylation and transulfuration capacity), suggested to play an
      important role for the pathogenesis of ASD. The design is a prospective pilot study,
      including 40 patients, aged 2-6 yrs, with newly diagnosed ASD. All participants will receive
      the supplement (vitamin B6, magnesium; Kirkman formula) and placebo in a cross over design.
      Metabolites in blood and urine will be measured prior to and at the end of the treatments in
      the different groups. The results will then provide us with information, which will link
      clinical outcomes with biological markers. Furthermore, the study has also the potential to
      shed light on the pathogenesis of ASD.
    

Detailed description: 
      Autism spectrum disorders (ASDs) are neurodevelopment disorders characterized by impairments
      in social relatedness and communication, repetitive behaviors, abnormal movement patterns,
      and sensory dysfunction that affect children from birth or the early months of life, but only
      recognized by most parents between 12 and 24 months of age.

      Studies have shown that a diagnosis of autism can be reliably made between 2 and 3 years of
      age, although a diagnosis of the broader autistic spectrum is less reliable at this age than
      in older children While genetic factors are recognized as being important in the pathogenesis
      of ASDs, a metabolic and biochemical factors are considered to play an important role for the
      pathogenesis. Treatment is directed on the impairing core features of the disorder.

      Pyridoxine (vitamin B6) was first used with children diagnosed with "autism syndrome" when
      speech and language improvement was observed in some children as a result of large doses of
      B6. Magnesium was added to prevent the possibility of hyperactivity and peripheral
      neuropathy, which can occur if the vitamin B6 is taken by itself. An impairment of the
      methionine cycle and transsulfuration was previously reported in autistic children. Recent
      studies in autistic children have suggested a decreased capacity for methylation as
      contributing factor to the development and clinical manifestation of the disease .

      Homocysteine is removed either by its irreversible conversion to cysteine (transsulfuration)
      or by remethylation to methionine. There are two separate remethylation reactions, catalyzed
      by betaine. The reactions that remove homocysteine are very sensitive to B vitamin status as
      both the transsulfuration enzymes contain pyridoxal phosphate, while methionine synthase
      contains cobalamin and receives its methyl group from folic acid one-carbon pool.

      In addition, vitamin B6 is required for over 100 enzymatic reactions, including the
      production of major neurotransmitters (serotonin, dopamine, and others) and glutathione
      (needed for detoxification).

      A number of studies attempted to assess the effects of vitamin B6-Magnesium (Mg) on
      characteristics such as verbal communication, non-verbal communication, interpersonal skills,
      and physiological function, in individuals with autism. There are over 22 studies of vitamin
      B6 with Magnesium for ASD, including 11 double-blind, placebo-controlled studies, making it
      one of most studied treatments for autism. Many of these studies found some of the children
      with ASD benefited from high-dose supplementation of vitamin B6 with Magnesium in many areas
      of the spectrum including language, eye contact and behaviour . Twenty-one of these yielded
      positive results, and only minor adverse effects were reported , In the Cochrane Database
      Systematic Review only study yielded no significant performances between treatment and
      placebo group performances following the B6 intervention on measures of social interaction,
      communication, compulsivity, impulsivity or hyperactivity.

      However, none of the above studies evaluated the effect of the vitamin B6 on the methionine
      cycle.

      In summary, the proposed study will compare biochemical alterations in a key metabolic
      pathway, i.e. the methionine cycle, suggested by previous studies to play an important role
      in the pathogenesis of ASD, with clinical parameters, during treatment with nutritional
      supplement. Therefore, the results will provide clinicians with important information for
      improvement and optimization of the treatment of patients with ASD.
    

Intervention name(s): Pyridoxine hydrochloride; Tang orange powder
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 2.5 grams per day for subjects weighing upto 27 kilos and 5 g per day for greater than 27 kgs for 12 weeks; 2.5 grams per day for subjects weighing upto 27 kilos and 5 g per day for greater than 27 kgs for 12 weeks
Other intervention name(s): Vitamin B6; Super Nu -Thera Registered trade mark kirkman Laboratories
Intervention MeSH terms: Pyridoxine; Vitamin B 6
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Autism; Children; ASD; Vitamin B6; Magnesium