Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype

Abstract

This study aimed at assessing the effect of folic acid supplementation quantitatively in each MTHFR C677T genotype and considered the efficiency of tailormade prevention of atherosclerosis. Study design was genotype-stratified, randomized, double-blind, placebocontrolled trials. The setting was a Japanese company in the chemical industry. Subjects were 203 healthy men after exclusion of those who took folic acid or drugs known to effect folic acid metabolism. Intervention was folic acid 1 mg/day p.o. for 3 months. The primary endpoint was plasma total homocysteine level (tHcy). In all three genotypes, there were significant tHcy decreases. The greatest decrease was in the TT homozygote [6.61 (3.47-9.76) lmol/l] compared with other genotypes [CC: 2.59 (1.81-3.36), CT: 2.64 (2.16-3.13)], and there was a significant trend between the mutated allele number and the decrease. The tHcy were significantly lowered in all the genotypes, but the amount of the decrease differed significantly in each genotype, which was observed at both 1 and 3 months. Using these timeseries data, the largest benefit obtained by the TT homozygote was appraised as 2.4 times compared with the CC homozygote. Taking into account the high allele frequency of this SNP, this quantitative assessment should be useful when considering tailor-made prevention of atherosclerosis with folic acid.

Serum Folate and Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism Adjusted for Folate Intake

“…These frequencies were similar to those reported in other Japanese subjects. 39 - 41 Although the present subjects consisted of visitors to an H. pylori clinic, the results may be extended to the general population in Japan.…”

Biomarkers of Nutrient Bioactivity and Efficacy

“…19 Although still controversial, 20 the effect of folate supplementation in lowering Hcy levels has been demonstrated. [21][22][23][24] In addition, it has been recently shown that riboflavin (vitamin B 2 ) supplementation has a similar effect, 25 This gene-diet interaction has become even more interesting as riboflavin was associated with lowering blood pressure in hypertensive individuals with a TT genotype. 26 This example shows the need for thoroughly evaluating gene-diet interactions in randomized controlled clinical trials.…”

A systems biology approach to nutritional immunology – Focus on innate immunity

“…Most genetic variations arise from single base pair changes referred to as single-nucleotide polymorphisms (SNPs), and can have substantial effects on an individual's health and susceptibility to disease. Using nutrigenetics, several genes have been identified with polymorphisms that alter the metabolism of nutrients such as folate and consequently susceptibility to nutrition-related chronic diseases including atherosclerosis and cardiovascular disease (Miyaki et al, 2005). Several vitamin D receptor (VDR) polymorphisms have been identified including VDR-Fok1, which is associated with reduced dietary calcium absorption, and VDR-Bsm1 and VDR-Apa1 associated with glucose intolerance and insulin resistance, respectively (Ames et al, 1999;Oh and Barrett-Connor, 2002;Smolders et al, 2009).…”