Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24–87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 ± 0.55 vs 1.85 ± 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure.
Bibliographical noteFunding Information:
Plasma samples from participants who had previously participated in studies at the Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, and had been screened for the MTHFR 677TT genotype were accessed for the current study. In all cases, participants provided informed, written consent and agreed for samples to be used in subsequent studies. Samples were accessed from the GENOVIT study (ORECNI ref 08/NIR03/40) , the GENOVIT follow-up study (ORECNI ref 08/NIR03/40)  and the RIBOGENE study (ORECNI/12/0338). Ethical approval for the analysis reported in the current study was granted by Ulster University Research Ethics Committee (FCBMS-18-040). All three studies had identical inclusion (pre-screened for MTHFR C677T polymorphism) and exclusion (history of gastrointestinal, hepatic or renal disease, consumers of B vitamin supplements, use of medication known to interfere with B vitamin metabolism) criteria. Clinic BP was measured in accordance with guidelines from the National Institute of Care and Excellence (NICE) . In brief, after 10 min at rest, BP was measured in the reference arm, i.e. the arm with the highest BP, with the participant in the seated position. Mean BP was calculated as the average of two BP readings within 5 mmHg, with a maximum of six readings obtained. Anthropometry, health and lifestyle information and blood samples were collected according to appropriate standardised operating procedures as part of each study, described in detail elsewhere [9,10].This was supported by GRO-UR-Networks funding from Ulster University to cover travel for MR to the Center of Metabolomics, Baylor Scott & White Research Institute in Dallas for sample analysis. The PhD studentship for MR was funded by the Vice Chancellors Research Scholarship at Ulster University. DSM provided part support for the RIBOGENE study but were not involved in the design, implementation, analysis, or interpretation of the data.
This was supported by GRO-UR-Networks funding from Ulster University to cover travel for MR to the Center of Metabolomics, Baylor Scott & White Research Institute in Dallas for sample analysis. The PhD studentship for MR was funded by the Vice Chancellors Research Scholarship at Ulster University . DSM provided part support for the RIBOGENE study but were not involved in the design, implementation, analysis, or interpretation of the data.
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- One-Carbon Metabolism
- One-carbon metabolism