Thiamine (Vitamin B1) Is Often Misunderstood to Be Consumed by Excessive Carbohydrate Intake

Objectives Thiamine acts as a coenzyme (prosthetic group) after converting to thiamine pyrophosphate in crucial metabolic enzymes of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. Theoretically, thiamine should not be consumed by an increase in the number of substrates for those enzymes. However, thiamine is often described to be consumed by excessive carbohydrate intake. Such a possible misunderstanding is assessed in the relevant literature. Methods The original paper (Elmadfa, et al. Int J Vitam Nutr Res 2001), which seems to mislead the reader into considering an increase in thiamine requirement for excessive carbohydrate intake, and the relevant papers were reviewed. Results The original paper demonstrated that increases in carbohydrate intake from 55% to 65% and 75% of total energy caused decreases in plasma and urine concentrations of thiamine, while erythrocyte transketolase activity remained unchanged. This seems to misleadingly support the idea that excessive carbohydrate intake increases the thiamine requirement for carbohydrate metabolism. It could be interpreted as the decreases of thiamine concentrations were observed only during an adaptation period. It was reported that diabetic patients had low plasma thiamine levels in association with increased renal clearance and fractional excretion of thiamine, without a decrease in erythrocyte transketolase activity (Thornalley, et al. Diabetologia 2007). As a similar case of possible misinterpretation, a case report (Watson, et al. Ir J Med Sci 1981) demonstrated that glucose loading precipitated thiamine deficiency in malnourished patients with latent thiamine deficiency. Conclusions From the relevant literature, it is inferred that excessive carbohydrate intake in people without hyperglycemia could lead to a small increase, if any, in urinary thiamine excretion, but not to an increase in thiamine requirement for glucose metabolism. Even in the academic field, it seems that thiamine is often misunderstood to be consumed by excessive carbohydrate intake. Funding Sources None.

Reduced Thiamine Availability and Hyperglycemia Impair Thiamine Transport in Renal Glomerular Cells through Modulation of Thiamine Transporter 2

Thiamine helps transketolase in removing toxic metabolites, counteracting high glucose-induced damage in microvascular cells, and progression of diabetic retinopathy/nephropathy in diabetic animals. Diabetic subjects show reduced thiamine levels. Hyperglycemia and reduced thiamine availability concur in impairing thiamine transport inside the blood-retinal barrier, with thiamine transporter-2 (THTR2) primarily involved. Here, we examined the behavior of thiamine transporter-1 (THTR1), THTR2, and their transcription factor Sp1 in response to high glucose and altered thiamine availability in renal cells involved in diabetic nephropathy. Human proximal tubule epithelial cells, podocytes, glomerular endothelial, and mesangial cells were exposed to high glucose and/or thiamine deficiency/oversupplementation. Localization and modulation of THTR1, THTR2, and Sp1; intracellular thiamine; transketolase activity; and permeability to thiamine were examined. Reduced thiamine availability and hyperglycemia impaired thiamine transport and THTR2/Sp1 expression. Intracellular thiamine, transketolase activity, and permeability were strongly dependent on thiamine concentrations and, partly, excess glucose. Glomerular endothelial cells were the most affected by the microenvironmental conditions. Our results confirmed the primary role of THTR2 in altered thiamine transport in cells involved in diabetic microvascular complications. Lack of thiamine concurs with hyperglycemia in impairing thiamine transport. Thiamine supplementation could represent a therapeutic option to prevent or slow the progression of these complications.

Thiamine transporter 2 is involved in high glucose-induced damage and altered thiamine availability in cell models of diabetic retinopathy

Thiamine prevents high glucose-induced damage in microvasculature, and progression of retinopathy and nephropathy in diabetic animals. Impaired thiamine availability causes renal damage in diabetic patients. Two single-nucleotide polymorphisms in SLC19A3 locus encoding for thiamine transporter 2 are associated with absent/minimal diabetic retinopathy and nephropathy despite long-term type 1 diabetes. We investigated the involvement of thiamine transporter 1 and thiamine transporter 2, and their transcription factor specificity protein 1, in high glucose-induced damage and altered thiamine availability in cells of the inner blood–retinal barrier. Human endothelial cells, pericytes and Müller cells were exposed to hyperglycaemic-like conditions and/or thiamine deficiency/over-supplementation in single/co-cultures. Expression and localization of thiamine transporter 1, thiamine transporter 2 and transcription factor specificity protein 1 were evaluated together with intracellular thiamine concentration, transketolase activity and permeability to thiamine. The effects of thiamine depletion on cell function (viability, apoptosis and migration) were also addressed. Thiamine transporter 2 and transcription factor specificity protein 1 expression were modulated by hyperglycaemic-like conditions. Transketolase activity, intracellular thiamine and permeability to thiamine were decreased in cells cultured in thiamine deficiency, and in pericytes in hyperglycaemic-like conditions. Thiamine depletion reduced cell viability and proliferation, while thiamine over-supplementation compensated for thiamine transporter 2 reduction by restoring thiamine uptake and transketolase activity. High glucose and reduced thiamine determine impairment in thiamine transport inside retinal cells and through the inner blood–retinal barrier. Thiamine transporter 2 modulation in our cell models suggests its major role in thiamine transport in retinal cells and its involvement in high glucose-induced damage and impaired thiamine availability.

Downregulation of Transketolase Activity Is Related to Inhibition of Hippocampal Progenitor Cell Proliferation Induced by Thiamine Deficiency

In animal experiments, hippocampal neurogenesis and the activity of thiamine-dependent transketolase decrease markedly under conditions of thiamine deficiency. To further investigate the effect of thiamine deficiency on the proliferation of hippocampal progenitor cells (HPCs) and the potential mechanisms involved in this effect, we cultured HPCs in vitro in the absence of thiamine and found that proliferation and transketolase activity were both significantly repressed. Furthermore, specific inhibition of transketolase activity by oxythiamine strongly inhibited HPC proliferation in a dose-dependent manner. However, thiamine deficiency itself inhibited the proliferation to a greater degree than did oxythiamine. Taken together, our results suggest that modulation of transketolase activity might be one of the mechanisms by which thiamine regulates the proliferation of hippocampal progenitor cells.