Maintaining optimal one-carbon metabolism (OCM) is essential for health and pregnancy. In this cross-sectional study, folate status was assessed based on 5-methyltetrahydrofolate (5-MTHF) levels, and the association between 5-MTHF and OCM-related metabolites was investigated in 227 female Japanese university students aged 18–25 years. The participants were divided into high and low 5-MTHF groups based on their folate status. Serum samples of the participants were collected while they were fasting, and 18 OCM-related metabolites were measured using stable-isotope dilution liquid chromatography–electrospray tandem mass spectrometry. The association between serum 5-MTHF and OCM-related metabolite concentrations was assessed using Spearman’s rank correlation coefficient. Serum 5-MTHF concentrations were negatively correlated with total homocysteine (tHcy) concentrations and positively correlated with S-adenosylmethionine (SAM) and total cysteine (tCys) concentrations. Serum 5-MTHF concentrations demonstrated a stronger negative correlation with tHcy/tCys than with tHcy alone. The negative correlation between betaine and tHcy concentrations was stronger in the low 5-MTHF group than in the high 5-MTHF group. The 5-MTHF status could be linked to Hcy flux into the transsulfuration pathway via SAM. Therefore, the tHcy/tCys ratio may be a more sensitive indicator of the 5-MTHF status than tHcy alone. Furthermore, a low 5-MTHF status can enhance Hcy metabolism via betaine.

Homocysteine is a methionine metabolism intermediate and its increased blood levels are associated with a higher risk of noncommunicable diseases. Reportedly, blood homocysteine levels increase with inadequate folate, vitamin B₆, and vitamin B₁₂ intake; however, its relationship with dietary factors other than these three vitamins remains unknown. Thus, we investigated the relationship of homocysteine with other nutrient intake. We performed a dietary survey on 227 young women using a food record with approximate amounts for 7 consecutive days in conjunction with digital imaging. We collected early morning fasting blood samples the day after the dietary survey was completed and analyzed the serum homocysteine levels. We observed that the serum homocysteine concentrations were significantly negatively associated with soluble, insoluble, and total fiber intake. In addition, participants with high fruit and mushroom intake displayed lower serum homocysteine concentrations, suggesting dietary fiber involvement from these foods. However, we observed no serum homocysteine concentration-related association with cereals and vegetables (well-documented dietary fiber sources) or with fruits and mushrooms. In conclusion, fiber quality-related differences could thus be caused by different sources, including antioxidant components such as fruit polyphenols and mushroom antioxidant and anti-inflammatory factors.

While homocysteine is produced as an intermediate metabolite during methionine metabolism, increased blood homocysteine levels are associated with various diseases. In a previous cross-sectional study, we reported a significant negative association between the serum concentrations of homocysteine in 227 young women and their dietary fiber intake. In the present study, we examined the relationship between dietary fiber intake from food sources and serum levels of homocysteine and its metabolites. Homocysteine and its metabolites 5-methyltetrahydrofolate (5MTHF), cystathionine, glycine, methionine, and S-adenosyl-methionine were measured using LC-MS/MS. The soluble, insoluble, and total fiber intake from fruits and mushrooms was significantly inversely correlated with the homocysteine concentrations. Furthermore, the soluble, insoluble, and total fiber intake from fruits was significantly positively associated with the serum 5MTHF concentrations, while the fiber intake from mushrooms was positively correlated with the cystathionine concentration and negatively correlated with the methionine and glycine concentrations. These results suggest that ingesting dietary fiber in the form of fruits and mushrooms maintains a low concentration of homocysteine by activating two different homocysteine-scavenging metabolic pathways.