Thiamine And Autism

[Drareg]

Positive results from this study with thiamine for autism.

http://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20130102.11.pdf

 

[Grapelander]

Thanks - this is a great PDF on autism and use of Thiamine and Benfotiamine.

Prostaglandins (PGs)
The normal laminar pattern of cyclooxygenase-2 (COX-2) in the human cortex is altered in patients with Rett syndrome, a type of ASD. PTGS2, gene encoded for COX-2, polymorphism is associated with Korean trios with ASD. The expression of COX-2 and PGE2 selectively increased in vulnerable regions of TD encephalopathy animal models.
Benfotiamine inhibits the COX-2 expression and its product PGE2 in murine macrophages.

Reactive oxygen Species (ROS)
Lipid peroxidation elevated in people with autism. Plasma malonyldialdehyde (MDA) is significantly high in patients with autism. The F2-isoprostane 8-iso-prostaglandin F2α is enhanced in children with autism. The erythrocyte superoxide dismutase (SOD) activity decreases in children with autism. Lipid peroxidation product is accumulated in the remaining thalamic neurons in TH animal models.
Thiamine inhibits lipid peroxidation and free radical oxidation of oleic acid in rat liver microsomes.

Nitric oxide synthetase (NOS)
Increased erythrocyte nitric oxide (NO) levels and plasma glutathione peroxidase (GSH-Px) were detected in people with autism. GSH plasma levels were decreased in children with autism. GSH pathway gene variants are associated with ASD.
Benfotiamine inhibits iNOS expression in endotoxin-induced uveitis in rats.
Thiamine improved the reduced GSH level in acutely alcoholized rats.

NADPH
The NOX activity in the lymphocytic mitochondria of children with autism was significantly reduced compared with controls. Lower levels of plasma ATP and red blood cell NADH were reported in children with autism than in controls.
Vitamin and minerals supplements led to significantly improvement in ATP and NADH as well as on the hyperactivity, tantrum, and receptive language subscores in the autism group compared with placebo group. Gene variants of the NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5), an enzyme complex in the mitochondrial electron transport chain, are associated with autism.
Thiamine is an essential coenzyme for transketolase, which is a part of the pentose phosphate pathway that helps maintain cellular NADPH levels. In a study of hepatocytes with glyoxal toxicity, thiamin was cytoprotective and restored NADPH levels, glyoxal detoxification and mitochondrial membrane potential. NADPH cytochrome c-reductase levels increased in thiamine-deficient (TD) animals.
Benfotiamine treatment significantly down-regulated Nox4 expression under both normo- and hyper-glycemic conditions.
Animals fed a high-thiamine diet had approximately 57% of the NADPH-cytochrome c reductase activity of those fed a TD diet.

Pyruvate dehydrogenase (PDH)
A low pyruvate dehydrogenase (PDH) activity was reported in children with autism. Genetic defects in in pyruvate dehydrogenase complex (PDHC) are known to cause lactic acidosis, neurological deficits, and premature death. Patients with genetic defects in PDHC show reduced activity of PDHC and PDH (E1)α subunit and decreased affinity of PDHC for thiamine pyrophosphate (TPP).
Thiamine treatment is very effective in some PDHC-deficient patients.
Thiamine regulates the expression of enzymes that require thiamine as a cofactor and thiamine deficiency has been shown to reduce the mRNA levels of transketolaseand PDH.
Thiamine diphosphate (TDP) is an essential coenzyme for mitochondrial PDH, α-ketoglutarate dehydrogenases complexes, and cytosolic transketolase.
In thiamine deficiency, the levels of thiamine-dependent and nonthiamine-dependent enzymes (succinate and malate dehydrogenase) in the tricarboxylic cycle are reduced in the mouse brain.