Novel Approaches to Investigate One-Carbon Metabolism and Related B-Vitamins in Blood Pressure

Abstract

Hypertension, a major risk factor for heart disease and stroke, is the world’s leading cause of preventable, premature death. A common polymorphism (677C→T) in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with increased blood pressure, and there is accumulating evidence demonstrating that this phenotype can be modulated, specifically in individuals with the MTHFR 677TT genotype, by the B-vitamin riboflavin, an essential co-factor for MTHFR. The underlying mechanism that links this polymorphism, and the related gene-nutrient interaction, with hypertension is currently unknown. Previous research has shown that 5-methyltetrahydrofolate, the product of the reaction catalysed by MTHFR, appears to be a positive allosteric modulator of endothelial nitric oxide synthase (eNOS) and may thus increase the production of nitric oxide, a potent vasodilator. Blood pressure follows a circadian pattern, peaking shortly after wakening and falling during the night, a phenomenon known as ‘dipping’. Any deviation from this pattern, which can only be identified using ambulatory blood pressure monitoring (ABPM), has been associated with increased cardiovascular disease (CVD) risk. This review will consider the evidence linking this polymorphism and novel gene-nutrient interaction with hypertension and the potential mechanisms that might be involved. The role of ABPM in B-vitamin research and in nutrition research generally will also be reviewed.

Astronaut ophthalmic syndrome

“…This would be a simple, and again, low‐risk approach to correct endogenous antioxidant decrements and even to improve BBB function, which has been shown to occur in patients with hyperhomocysteinemia that is treated with B vitamin supplementation (96). Riboflavin supplementation has been shown to reduce blood pressure in hypertensive patients with the minor form of the MTHFR 677 polymorphism (TT), and may play a role in preventing endothelial dysfunction (97, 98). Attention to details, including the dose and form of vitamins, would need to be considered because folic acid can inhibit 5‐MTHF transport across the BBB and potentially exacerbate a cerebral folate deficiency (22, 99, 100); therefore, use of reduced folate (5‐MTHF or THF) should be considered.…”

A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels

“…Hypertension is one of the major risk factors for stroke and cardiovascular disease. Riboflavin is a potent B vitamin to reduce blood pressure significantly in individuals with this genetic polymorphism [29], and in combination with folic acid, a significant decrease of homocysteine was achieved [30]. This again underlines the interaction between the individual B vitamins.…”

The association of MTHFR (rs1801133) with hypertension in an indigenous south African population

“…The MTHFR gene encodes methylenetetrahydrofolate reductase, a key regulatory enzyme in folate and homocysteine (Hcy) metabolism, and in the production of nitric oxide, a potent vasodilator that is important in blood pressure regulation (Goyette et al, 1994;McMahon et al, 2016). The rs1801133 polymorphism (677 C > T) is found on exon 4 of the MTHFR gene.…”