Abstract

Current nutritional recommendations are focused on energy, fat, carbohydrate, protein and vitamins. Less attention has been paid to the nutritional demand of one-carbon units for nucleotide and methionine synthesis. Here, we investigated the impact of sodium formate supplementation as a nutritional intervention to increase the dietary intake of one-carbon units. A cohort of six female and six male mice received 125 mM of sodium formate in the drinking water for three months. A control group of another six female and six male mice was also followed up for the same period of time. Tail vein blood samples were collected once a month and profiled with a haematology analyser. At the end of the study, blood and tissues were collected for metabolomics analysis and immune cell profiling. Formate supplementation had no significant physiological effect on male mice, except for a small decrease in body weight. Formate supplementation had no significant effect on the immune cell counts during the intervention or at the end of the study in either gender. In female mice, however, the body weight and spleen wet weight were significantly increased by formate supplementation, while the blood plasma levels of amino acids were decreased. Formate supplementation also increased the frequency of bifidobacteria, a probiotic bacterium, in the stools of female mice. We conclude that formate supplementation induces physiological changes in a gender-specific manner.

Highlights

  • Folic acid, vitamin B9, is an essential cofactor in one-carbon metabolism, a network of biochemical reactions mediating the synthesis of methionine and nucleotides [1]

  • One-carbon units can be obtained from the amino acid serine, glycine and methionine; from methyl containing molecules such as choline, methanol, methylamine and creatine; and from the quintessential one-carbon precursor, formate [4,5]

  • We investigated the impact of dietary formate intake on mammalian physiology

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Summary

Introduction

Vitamin B9 , is an essential cofactor in one-carbon metabolism, a network of biochemical reactions mediating the synthesis of methionine and nucleotides [1]. The nutritional requirements for folic acid have been extensively addressed in the scientific literature [2], including the interaction between folic acid and vitamin B12. Methionine synthase requires vitamin B12 as a co-factor to transfer one-carbon units from the folate pool to the methyl pool [1]. New studies have highlighted the urgent need to investigate the nutritional requirements of the one-carbon units per se [4,5]. One-carbon units can be obtained from the amino acid serine, glycine and methionine; from methyl containing molecules such as choline, methanol, methylamine and creatine; and from the quintessential one-carbon precursor, formate [4,5].

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