Autism in Oman: Nutritional Deficiencies in Vitamin B12 and Folate Associated with Gender-Specific Abnormalities in Serum Thiol Levels

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
11:00 AM
N. Hodgson1, R. Deth2, M. I. Waly3 and Y. Alfarsi3, (1)Pharmaceutical Sciences, Northeastern University, Boston, MA, (2)Northeastern University, Boston, MA, United States, (3)Sultan Qaboos University, Muscat, Oman
Background:  Environmental factors (xenobiotics) appear to be largely responsible for increasing autism rates in the U.S., but nutritional factors may play a larger role in less developed countries such as Oman. The synthesis of glutathione (GSH) by sulfur metabolism plays a central role in the detoxification of many xenobiotics, and several studies have reported significantly lower plasma levels of GSH, in association with oxidative stress in autistic subjects. The folate and vitamin B12-dependent enzyme methionine synthase is a key redox switch, whose activity determines the balance between methylation activity and GSH synthesis through the re-routing of sulfur metabolites.

Objectives:  To evaluate the nutritional status of autistic children in Oman, particularly with regard to folate and vitamin B12, and to correlate nutrient levels with metabolites in redox and methylation pathways.

Methods:  We studied 20 male and 20 female autistic children in Oman, and examined dietary intake and serum levels of folate and vitamin B12. We then measured serum levels of sulfur metabolites, including cysteine, cysteine, cystathionine, reduced and oxidized GSH, homocysteine, homocysteine, methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM).

Results:  We found evidence of malnutrition and lower folate and vitamin B12 intake in both male and female autistic subjects vs. controls. Lower intake was reflected as a significant decrease in serum B12 and folate levels. Notably, control levels of folate and vitamin B12 were low in comparison to values for the U.S. In combined autistic subjects, serum levels of cysteine, homocysteine and SAH were increased, and GSH was decreased vs. controls. A comparison of male vs. female subjects revealed several significant differences. Serum levels of homocysteine and SAH were increased in male autistic subjects vs. male controls, while cysteine and GSH were decreased. However, the serum level of cysteine was increased in female autistic patients vs. female controls. Serum levels of cysteine and GSH were increased in autistic females vs. autistic males, while oxidized GSH (GSSG), homocysteine, and SAH were decreased. There were no differences in any of the sulfur metabolites between control males and females.

Conclusions:  We found differences in thiol metabolism and oxidative stress in Omani autistic children, similar to the findings of other studies. However, the presence of low B12 and folate levels indicates that the oxidative stress was largely due to a nutritional deficiency, which is not the case for autism in the U.S. Thus, a common metabolic abnormality (oxidative stress) is associated with autism of different origins. Further, our data shows gender specific differences in thiol metabolite levels among autistic subjects, with males showing a greater deficit in GSH and a higher level of oxidative stress. These differences could be essential to understanding the gender bias of autism diagnosis rates.

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