Early Nutritional Intervention in Patients With Autism Spectrum Disorders

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.