Vitamin B6 serves as a cofactor in the catabolism of tryptophan. 7 PLP deficiency can influence type 2 diabetes through several mechanisms. PLP is an essential cofactor for numerous enzymes involved in the metabolic conversion of tryptophan to niacin, specifically through the tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide pathways. 17 Disruption of these pathways results in the production of metabolites that reduce insulin bioactivity, contributing to insulin resistance, a hallmark of type 2 diabetes. Furthermore, PLP may impact insulin resistance by modulating the expression of genes related to adipogenesis. 17 Additionally, disruption of these metabolic pathways results in elevated levels of kynurenine metabolites, which in turn inhibit insulin secretion and diminish glucose tolerance. 7
Research indicates that an increase in daily supplementation of vitamin B6 from 1.3 mg to 1.6 mg significantly decreases the incidence of patients reporting coronary heart disease and myocardial infarction. Furthermore, additional research suggests a relationship between higher vitamin B6 intake and a reduced risk of coronary heart disease. 8 This could be due to a decrease in homocysteine via a PLP-dependent enzyme that converts homocysteine to cysteine. 8 The level of PLP in plasma among post-menopausal women is inversely associated with the risk of a myocardial infarction. 9
Vitamin B6 has the potential to reduce the damage caused by oxygen radicals, decrease the production of lipid peroxides, play a role in reducing inflammatory processes, and protect against vascular endothelial injury induced by low-density lipoproteins. 25
Research indicates that an increased intake of vitamin B6 could be an effective strategy in reducing the risk of stroke. 25 Research involving 24 214 participants indicated that individuals in the highest quartile of vitamin B6 intake exhibited a markedly reduced risk of stroke compared to those in the lowest quartile. 25
Vitamin B6 and the Metabolism of Homocysteine Homocysteine participates in two essential biochemical pathways. It can be transformed into S-adenosylmethionine, which is vital for DNA expression through the transfer of methyl groups, or it can be used to synthesise glutathione, enhancing its antioxidant properties. Elevated levels of homocysteine are linked to various health conditions, including an increased risk of cardiovascular diseases, dementia, and overall increased mortality. 26 PLP plays an important role in the homocysteine metabolic pathway, 5, 7, 9, 22, 24, 25 serving as a cofactor for two enzymes involved in cystathionine synthesis: it facilitates the transformation of homocysteine into cystathionine and cystathionase, as well as the production of cysteine from cystathionine, 5, 9 via a trans-sulphuration pathway by the PLP-dependent enzyme cystathionine β-lyase. 5, 22 Additionally, homocysteine undergoes methylation to form methionine through the action of 5-methyltetrahydrofolate, a crucial component in the synthesis of purines and thymidylate. 5 This methylation process is dependent on cobalamin and folate, and involves PLP-dependent enzymes such as serine hydroxymethyltransferase( SHMT), which facilitates the conversion of tetrahydrofolate( THF) into 5,10-methylene tetrahydrofolate. 5 A deficiency in vitamin B6 leads to elevated homocysteine levels, which can have significant health consequences. 9
Vitamin B6, the Nervous System and Mental Health Vitamin B6 is involved in neurological development. 19 Research has found that a greater intake of foods that contain high amounts of vitamin B6 correlates with better mental health. 5, 27 Pyridoxal-5-phosphate( PLP) plays an important role in the
7, 11, 20
metabolism of neurotransmitters such as serotonin, 5, 20, 28 5, 20, 28
dopamine, glutamate, 20, 28 gamma-aminobutyric acid( GABA), 20, 28 noradrenaline, 28 and adrenaline. 5 Phosphorylated vitamin B6 is needed as a cofactor for neurotransmitter synthesis 7 and neurotransmission. 13 PLP serves as a cofactor for glutamate decarboxylase, the enzyme responsible for the synthesis of GABA 9 and for the conversion of glutamate to GABA in the brain. 29 Vitamin B6 acts as a cofactor in the kynurenine pathway in which it reduces the amount of quinolinic acid, which is an agonist to the excitatory N-methyl-Daspartate( NMDA) receptor. 28 PLP plays a role in brain function. 13 Vitamin B6 regulates the synthesis and metabolism of 5-hydroxy tryptamine( 5HT), serotonin receptors, and catecholamines. 4 Pyridoxine reduces corticosteroid release peripherally. 4 Vitamin B6 is involved in the biosynthesis of sphinoglipids, 11 metabolism and regulation of sphingosine phosphate. 9
Results from a 7-month randomised double-blind crossover study 30 indicate that pyridoxine 50 mg daily produced a statistically significant positive effect on emotional symptoms such as depression, irritability, and fatigue during the premenstrual phase in women diagnosed with premenstrual syndrome; symptoms were reduced by approximately 50 % during treatment months when compared to the placebo months. No reports of neurological symptoms or other adverse effects associated with pyridoxine were noted. 30 A comprehensive systematic review was performed on randomised placebocontrolled trials assessing the efficacy of vitamin B6 in treating premenstrual syndrome. 31 The findings indicated that vitamin B6 was significantly more effective than placebo in alleviating general premenstrual symptoms and in reducing depression linked to premenstrual syndrome. Furthermore, no evidence of neurological side effects was observed at doses ranging from 50 to 500 mg per day. 31
A double‐blind study investigated the effects of pyridoxine hydrochloride 100 mg or methylcobalamin 1,000 micrograms, compared to placebo, for
70 | vol31 | no2 | JATMS