Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements

McNulty, Helene; McKinley, M. C.; Wilson, Barbara J.; McPartlin, Joseph; Strain, JJ; Weir, Donald G.; Scott, John M.

doi:10.1093/ajcn/76.2.436

Cited by 140 publications

(93 citation statements)

References 29 publications

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“…This response was not observed in individuals with CC or CT genotypes (even when baseline riboflavin status was suboptimal) despite a significant improvement in riboflavin status post-intervention in both genotype groups. Such evidence confirmed the independent modulating role of riboflavin in determining homocysteine concentrations specifically in individuals with the TT genotype as first suggested by earlier observational studies (18,19) .…”

Section: Proceedings Of the Nutrition Societysupporting

confidence: 88%

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

et al. 2013

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Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme which requires riboflavin as its co-factor. A common polymorphism (677C→T) in the MTHFR gene results in reduced MTHFR activity in vivo which in turn leads to impaired folate metabolism and elevated homocysteine concentrations. Homozygosity for this polymorphism (TT genotype) is associated with an increased risk of a number of conditions including heart disease and stroke, but there is considerable variability in the extent of excess risk in various reports. The present review will explore the evidence which supports a role for this polymorphism as a risk factor for a number of adverse health outcomes, and the potential modulating roles for B-vitamins in alleviating disease risk. The evidence is convincing in the case which links this polymorphism with hypertension and hypertensive disorders of pregnancy, particularly preeclampsia. Furthermore, elevated blood pressure was found to be highly responsive to riboflavin intervention specifically in individuals with the MTHFR 677TT genotype. Future intervention studies targeted at these genetically predisposed individuals are required to further investigate this novel gene–nutrient interaction. This polymorphism has also been associated with an increased risk of neural tube defects (NTD) and other adverse pregnancy outcomes; however, the evidence in this area has been inconsistent. Preliminary evidence has suggested that there may be a much greater need for women with the MTHFR 677TT genotype to adhere to the specific recommendation of commencing folic acid prior to conception for the prevention of NTD, but this requires further investigation.

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Section: Proceedings Of the Nutrition Societysupporting

confidence: 88%

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

et al. 2013

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“…An earlier animal study showed a significant association between vitamin B 2 and MTHFR that the enzyme activity and the relative amounts of 5-methyl THF were reduced in the liver of riboflavin-deficient rats (Bates & Fuller, 1986). Hustad et al (2000), McNulty et al (2002), and Jacques et al (2002) demonstrated that plasma vitamin B 2 was an independent determinant of plasma homocysteine, and this inverse dose-response relation was essentially confined to subjects with the C/T or T/T genotype of the MTHFR C677T polymorphism where the requirement of FAD for maximal catalytic activity might be increased (Hustad et al, 2000;Ueland et al, 2001). Several investigators have suggested that vitamin B 6 deficiency may lead to hyperhomocysteinemia, which is an established risk factor for adverse pregnancy outcome (van den Berg et al, 1994;Leeda et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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Objective: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. Design: A cross-sectional study. Setting: Ewha Womans University Hospital, Seoul, Korea. Subjects: A total of 177 normal pregnant women, 24.671.1 weeks of gestation, in a 6-month period during [2001][2002]. Interventions: Serum vitamin B 2 , vitamin B 6 , and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B 12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (Po0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (Po0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). Conclusions: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B 2 , and vitamin B 12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.

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“…It has recently been suggested that riboflavin, the precursor for flavin adenine dinucleotide, might act by increasing MTHFR activity, and thereby lower plasma tHcy concentrations (Bates and Fuller, 1986;Ross and Hansen, 1992;McNulty et al, 2002). Examining the effects of folic acid, riboflavin, and the MTHFR genotype on human lymphocytes grown in culture media, Kimura et al (2004) observed that the tHcy concentration decreased as the riboflavin concentration increased.…”

Section: Introductionmentioning

confidence: 99%

Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects

et al. 2005

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Objective: To investigate the effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma plasma total homocysteine (tHcy) concentrations in young Japanese male subjects. Design: In a double blind, randomized controlled trial. Intervention: Subjects were randomly assigned to one of four groups and received a placebo (control group), 800 mg/day folic acid (FA group), 8.4 mg/day riboflavin (R group), or both (FAR group) for 2 weeks. Setting: Tokyo, Japan. Subjects: In total, 32 healthy male volunteers aged 20-29 years. Results: At the end of the 2 week supplementation period, the tHcy concentration decreased significantly in the FA group. Serum folate concentrations had increased between 2.7 and 2.0-fold in the FA and FAR groups, respectively, but the mean within-group changes in serum folate and plasma tHcy concentrations did not differ between these two groups. At the end of the study, alanine amino transferase was decreased in the R and FAR groups, while alanine amino transferase was increased in the FA group. Conclusion: Supplementation with folic acid, 800 mg/day, for 2 weeks, increased the serum and red blood cell folate concentrations and decreased the plasma tHcy concentrations in healthy young male subjects. Riboflavin supplementation may have blunted the effect of folic acid, which resulted in a diminished reduction of tHcy in our subjects.

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Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements

Cited by 140 publications

References 29 publications

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects

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