Thiamin deficiency and brain disorders

Abstract

Thiamin plays a key role in the maintenance of brain function. Thiamin diphosphate is cofactor for several enzymes involved in glucose metabolism whereas thiamin triphosphate has distinct properties at the neuronal membrane. Thiamin metabolism in the brain is compartmented between neurons and neighbouring glial cells. Thiamin deficiency is commonly encountered in severe malnutrition associated with chronic alcoholism, HIV-AIDS and gastrointestinal disease where it frequently results in Wernicke's encephalopathy (the Wernicke-Korsakoff syndrome). Wernicke's encephalopathy is severely underdiagnosed according to clinical criteria in both alcoholic and HIV-AIDS patients. Magnetic resonance imaging reveals bilateral ventricular enlargement, mammillary body atrophy and cerebellar degeneration indicative of selective neuronal loss that is characteristic of Wernicke's encephalopathy. Several mechanisms have been proposed to explain this selective loss of neurons including a cerebral energy deficit resulting from reductions in activity of thiamin diphosphate-dependent enzymes, oxidative stress and N-methyl-D-aspartate receptor-mediated excitotoxicity. Both microglia and perivascular endothelial cells are sources of NO and oxidative stress in thiamin deficiency. Decreased activities of thiamin diphosphate-dependent enzymes (in particular alpha-ketoglutarate dehydrogenase) have also been reported in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases independent of patient malnutrition. In these cases, decreased activities result from direct toxic actions of oxidative stress and beta-amyloid produced as part of the neuronal cell death cascade in these disorders.

A review of polioencephalomalacia in ruminants: is the development of malacic lesions associated with excess sulfur intake independent of thiamine deficiency?

“…In contrast, free-base thiamine and TMP were reduced to a minor extent relative to TPP reduction [26]. Poor absorption of thiamine from the gastrointestinal tract and the loss of liver thiamine stores due to some hepatic disease may also contribute to TPP deficiency in the brain [88].…”

“…This has been studied experimentally in humans and amongst men with Wernicke-Korsakoff syndrome (WKS) [88]. The research conducted to evaluate the relationship between the effects of thiamine deficiency on thiamine dependent enzyme activities, and neuronal loss has been particularly focused on α-KGDH.…”

“…The research conducted to evaluate the relationship between the effects of thiamine deficiency on thiamine dependent enzyme activities, and neuronal loss has been particularly focused on α-KGDH. It has been established that suppressed α-KGDH due to thiamine deficiency results in neuronal death [88,89], which is not surprising as α-KGDH is a rate limiting enzyme in the TCA cycle. These metabolic consequences decreased pyruvate oxidation and increased levels of alanine and lactate in the brain [90].…”

“…The α-KGDH enzyme is acting as a "sink" to its cofactor TPP. When this protein is reduced, the affinity of TPP for its apoenzyme would be diminished; unbound TPP will thereby be easily converted or hydrolyzed to TMP by TPPase [88,91].…”

Benfotiamine, thiamine monophosphate chloride and thiamine pyrophosphate chloride, as sources of vitamin B1 added for nutritional purposes to food supplements - Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food (ANS)

“…Thiamine diphosphate is an essential cofactor for enzymes involved in brain glucose metabolism such as transketolase, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (αKGDH). Thiamine pyrophosphate is then further phosphorylated to thiamine triphosphate or is dephosphorylated to thiamine monophosphate (Butterworth, 2003). The distribution and storage of thiamine in organs and tissues, its catabolism and its excretion with the urine and bile has been the subject of several reviews (Gubler, 1991;McCormick, 1988;Tettamanti, 1985).…”