Evidence of a Role for One-Carbon Metabolism in Blood Pressure: Can B Vitamin Intervention Address the Genetic Risk of Hypertension Owing to a Common Folate Polymorphism?

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Hypertension in adulthood is recognized as the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease, whereas hypertension in pregnancy leads to serious adverse fetal and maternal outcomes. This article explores the under-recognized role of one-carbon metabolism in blood pressure (BP) and the potential for folate-related B vitamins to protect against hypertension. Genome-wide association studies and clinical studies provide evidence linking the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with BP and increased risk of hypertension and hypertension in pregnancy. A novel role for riboflavin (the MTHFR cofactor) has recently emerged, however, with evidence from randomized trials that supplemental riboflavin can lower BP specifically in adults with the variant MTHFR 677TT genotype. Further studies are required to elucidate the biological mechanisms linking one-carbon metabolism with BP and explore the effect of riboflavin in modulating the genetic risk of hypertension in early and later life. Curr Dev Nutr 2019;4:nzz102.

Original languageEnglish
Article numbernzz102
JournalCurrent developments in nutrition
Issue number1
Publication statusPublished - 16 Sep 2019

Bibliographical note

Funding Information:
Manuscript received May 7, 2019. Initial review completed July 23, 2019. Revision accepted August 30, 2019. Published online September 16, 2019. The research described in this review was supported in part by governmental funding from the Irish Department of Agriculture, Food and the Marine and the Health Research Board (under the Food Institutional Research Measure initiative) and from the Northern Ireland Department for Employment and Learning (under its Strengthening the All-Island Research Base initiative); and by DSM Nutritional Products. Author disclosures: CFH and KP, no conflicts of interest. HM, JJS, and MW hold an international patent on the use of riboflavin in the treatment of blood pressure. None of the entities providing support were involved in the writing of this article. Address correspondence to HM (e-mail: h.mcnulty@ulster.ac.uk). Abbreviations used: 5-methylTHF, 5-methyltetrahydrofolate; BP, blood pressure; CVD, cardiovascular disease; EGRac, erythrocyte glutathione reductase activation coefficient; eNOS, endothelial nitric oxide synthase; GWAS, genome-wide association study; MTHFR, methylenetetrahydrofolate reductase; NO, nitric oxide; PLP, pyridoxal 5’phosphate; PPO, pyridoxine-phosphate oxidase; RBC, red blood cell; THF, tetrahydrofolate.

Publisher Copyright:
Copyright © American Society for Nutrition 2019. All rights reserved.


  • Blood pressure
  • Folate
  • Gene–nutrient interaction
  • Hypertension
  • Hypertension in pregnancy
  • One-carbon metabolism
  • Personalized nutrition
  • Riboflavin
  • Single nucleotide polymorphism


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