Can riboflavin offer a novel personalised strategy for maintaining healthy blood pressure in pregnancy in populations globally?

Hypertension affects 10%–15% of pregnancies worldwide and can lead to serious adverse fetal and maternal outcomes. In addition, women with hypertension in pregnancy are at greater risk of developing stroke and renal disease later in life, while hypertensive pregnancy complications can also affect the long-term health of the child. The identification of strategies to maintain healthy blood pressure in women before and during pregnancy should therefore be prioritised. Emerging research points to an important role for folate, one-carbon metabolism and the related B vitamin, riboflavin, in blood pressure. In particular, evidence from clinical and genome-wide association studies links the C677T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) with blood pressure and an increased risk of hypertension and hypertensive disorders of pregnancy. Riboflavin (in the form of flavin adenine dinucleotide) is required as a cofactor for MTHFR, and notably, randomised trials show that supplemental riboflavin can effectively lower blood pressure specifically in individuals with the variant MTHFR 677TT genotype, independently of antihypertensive medications. The evidence that better riboflavin status modifies the blood pressure phenotype in these genetically at-risk individuals has important public health implications, especially for populations worldwide with the highest frequencies of the variant TT genotype in MTHFR, including Guatemala (up to 66%), Mexico (32%) and Northern China (20%). This novel gene–nutrient interaction warrants particular attention in the context of blood pressure before and during pregnancy. Furthermore, the biological mechanisms require investigation, whereby one-carbon metabolism is linked with blood pressure and how riboflavin, a much-overlooked nutrient in health and research settings, can modulate the excess genetic risk of hypertension in affected individuals. Here, we review the generally unrecognised role of riboflavin as a novel personalised solution to prevent hypertension and hypertensive disorders of pregnancy in genetically at-risk women. This article should stimulate current thinking, with potentially important impacts for public health nutrition strategies to promote better pregnancy outcomes in women.