Thiamine (Vitamin B1)-An Essential Health Regulator

Abstract

Thiamine (vitamin B1) is key in maintaining cellular health and energy metabolism. Thiamine is required for proper functioning of enzymes involved in glucose metabolism, which is critical for providing energy to cells. This energy is essential for various cellular processes, including DNA repair mechanisms. In addition, it is a prerequisite for the functioning of key enzymes in the biosynthesis of pentose sugars, which are essential in the synthesis of nucleic acids. Additionally, thiamine has antioxidant properties that help reduce oxidative stress in cells; thus, by relieving this stress, thiamine indirectly supports the maintenance of DNA integrity. Ensuring adequate thiamine intake through diet or supplements can support overall cellular health and potentially aid in DNA repair processes. This review aims to highlight the essential role of vitamin B1 in supporting metabolic health, especially given that deficiencies can develop in patients with disease-related malnutrition as well as in those with an inadequate diet.

Keywords: antioxidant; mitochondria/ROS; oxidative stress; thiamine.

Figure 1

Thiamine phosphorylated forms.

Figure 2

(A) The formal hydrogen transfer mechanism. (B) The radical adduct formation mechanism [45,48,49]. The FHT mechanism results in the neutralization of the aggressive radical by attaching hydrogen to it, thereby quenching it and forming a more stable radical derived from the antioxidant. In contrast, the RAF mechanism results in the formation of a radical adduct that is less reactive than the original radical.

Figure 3

The influence of vitamin B1 on the level of oxidative stress (according to [30,40,54]). Thiamine deficiency inhibits PDC activity and contributes to the accumulation of pyruvate and the deficiency of acetyl-CoA. The latter is used to convert oxaloacetate to citrate in the Krebs cycle. Pyruvate accumulation causes activation and stabilization of HIF-1, thereby increasing NF-κB and TNF-α levels and the inflammatory response. Thiamine deficiency also inhibits TKT activity, which, by blocking the supply of non-oxPPP metabolites to ox-PPP, decreases NADPH levels. This NADPH is used to maintain normal GSH and TRX levels, and its deficiency impairs the ability of cells to neutralize ROS and RNS. The decrease in αKGDH activity caused by B1 deficiency limits NADH production, leading to increased ROS and activates eNOS, which increases RNS. Inhibition of 2-HALC activity in the α-oxidation process during vitamin B1 deficiency contributes to the accumulation of phytanic acid, which stimulates eNOS activity, while increasing RNS levels use glutathione reserves. ROS—reactive oxygen species, RNS—reactive nitrogen species, eNOS—endothelial nitric oxide synthase, 2-HACL—2-hydroxyacyl-CoA Lyase, NAD+/NADH—nicotinamide adenine dinucleotide, NADP+/NADPH—nicotinamide adenine dinucleotide phosphate, αKGDH—α-ketoglutarate dehydrogenase, CoA—coenzyme A, acetyl-CoA-acetyl coenzyme A, PDC—pyruvate dehydrogenase, HIF-1—hypoxia-induced factor-1α, NF-κB—nuclear factor kappa-B, TNF-α—tumor necrosis factor-α, GPI—glucose-6-phosphate isomerase, oxPPP—oxidative branch of the pentose–phosphate pathway, Non-oxPPP—non-oxidative branch of the pentose–phosphate pathway, G6PD—glucose-6-phosphate dehydrogenase, 6PGD—6-phosphogluconate dehydrogenase, GR—glutathione reductase, GSH—glutathione, GSSG—glutathione disulfide, TRX—thioredoxin, TRX(ox)—oxidized thioredoxin, TRXR—thioredoxin reductase, TKT—transketolase; Red color—chemical compounds whose deficiency occurs with vitamin B1 deficiency.