5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women

Fohr, Iris; Prinz‐Langenohl, Reinhild; Brönstrup, Anja; Bohlmann, Anja M; Nau, Heinz; Berthold, Heiner K.; Pietrzik, Klaus

doi:10.1093/ajcn/75.2.275

Cited by 99 publications

(58 citation statements)

References 31 publications

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“…This study, which comprised equal numbers of subjects with each MTHFR C677T genotype (n ¼ 42 of each), supports previous observations made in cohorts where only a small number of TT homozygotes were studied (Malinow et al, 1997;Nelen et al, 1998). Fohr et al (2002) have recently reported that subjects with the MTHFR TT genotype have a greater response to synthetic folates than other genotypes, but did not include a dietary intervention in their study. The gene frequency of C677T variant MTHFR in South Wales is 0.32, giving genotype frequencies of 12% TT, 40% CT and 48% CC (in keeping with other Caucasian populations; Clark et al, 1998).…”

Section: Discussionsupporting

confidence: 86%

A comparison of the effect of advice to eat either ‘5-a-day’ fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine

et al. 2003

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Objective: To assess and compare the effects of natural folate (100 mg) with those of folic acid from fortified sources (100 mg=day) on plasma folate and homocysteine. Design: Randomized controlled trial (parallel groups). Setting: Men and women living in South Wales, UK. Subjects: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). Interventions: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet -usual diet plus 100 mg=day folic acid from fortified foods; (2) natural folate diet -usual diet plus 100 mg=day folate from natural sources; (3) control -usual diet. Results: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P < 0.001) achieving an extra 98 mg=day (95% CI 88 -108). The natural folate group increased reported intake of natural source folates compared with the other two groups (P < 0.001), but achieved a mean increase of only 50 mg=day (95% CI 34 -66). Plasma folate increased (P < 0.01) by a similar amount in both intervention groups compared to controls (fortified group 2.97, 95% CI 0.8 -5.1; natural group 2.76, 95% CI 0.6 -4.9. Plasma homocysteine, vitamins B 6 and B 12 were not significantly changed. Conclusions: Subjects achieved increases in folate intake using fortified foods more easily than by folate-rich foods, however both sources increased plasma folate by a similar amount. These levels of intake were insufficient to reduce homocysteine concentrations in MTHFR CC homozygotes, but may be more effective in other genotypes. Sponsorship: This study was supported by the UK Ministry of Agriculture, Fisheries and Foods (latterly UK, Food Standards Agency, Project Reference N05002). The Kellogg Company of Great Britain provided funding for reimbursement of subjects for the cost of fortified foods.

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Section: Discussionsupporting

confidence: 86%

A comparison of the effect of advice to eat either ‘5-a-day’ fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine

et al. 2003

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“…Uma das mais estudadas é a mutação 677C → T no gene da enzima 5,10-metilenotetrahidrofolato redutase (MTHFR), que catalisa a conversão de 5,10-metilenotetrahidrofolato em 5-metiltetrahidrofolato, o co-substrato para metilação da homocisteína a metionina pela enzima metionina sintase. Vários estudos mostram que os portadores do genótipo T/T, quando comparados com portadores dos genótipos C/T ou C/C, apresentam menores níveis de folato plasmático e maiores níveis de homocisteína, especialmente em associação com baixos níveis de folato no plasma (Refsum et al, 2006), e apresentam melhores respostas à suplementação ou à ingestão dietética elevada de folato (Fohr et al, 2002;Silaste et al, 2001). Na gestação, o genótipo materno T/T, principalmente quando associado a um estado inadequado de folato e níveis elevados de homocisteína, aumenta o risco de defeitos do tubo neural nos fetos (Van der Linden et al, 2006).…”

Section: Uso De Indicadores Bioquímicos Na Avaliação Do Estado De Folunclassified

Epidemiologia nutricional

Kac¹,

Sichieri²,

Gigante³

2007

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“…As MTHFR is involved in the formation of 5-CH 3 -H 4 folate, this polymorphism could influence the outcome of the study. The proportion of the population homozygous at the T677 MTHFR allele is around 12% (Frosst et al, 1995;Malinow et al, 1997;Fohr et al, 2002). A poor folate status in these individuals leads to higher homocysteine concentrations compared to subjects who are not homozygous for this mutation (Jacques et al, 1996), and they show enhanced response to folic acid supplementation (Malinow et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans

et al. 2005

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Objective: The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is (partly) denatured in ultra-high-temperature (UHT)-treated milk. The effect of FBP on folate bioavailability is still unclear. Design, subjects and setting: Healthy, free-living subjects (n ¼ 69) aged 18-49 y participated in a 4-week double-blind, placebo-controlled dietary intervention study. Intervention: In addition to a fully controlled diet, the subjects consumed each day 500 ml of pasteurised or UHT milk, either fortified or not with 200 mg folic acid. Results: Consumption of fortified milk increased folate concentrations in serum and in red blood cells (RBC) by 6.6-7.0 nmol/l (Po0.001) and 32-36 nmol/l (Po0.01), respectively. Similarly, plasma homocysteine concentrations were lowered 0.88-0.89 mmol/l (P ¼ 0.001) in subjects who consumed fortified milk. The bioavailability of folic acid from pasteurised milk relative to that of folic acid from UHT milk was 74-94% (NS), depending on the parameter used. Conclusions: Milk fortified to supply an additional 200 mg of folic acid/s substantially increased folate status, and decreased plasma total homocysteine concentrations in young, healthy subjects. Milk is therefore a suitable matrix for fortification to enhance the folate status in humans. No significant effect of endogenous FBP was found on the bioavailability of folic acid from milk.

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5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women

Abstract: The response to tHcy-lowering therapy is influenced by MTHFR genotype. Women with the TT genotype seem to benefit the most from supplementation with either FA or MTHF. In women with the CT or CC genotype, FA is more effective than MTHF in lowering plasma tHcy.

Cited by 99 publications

References 31 publications

A comparison of the effect of advice to eat either ‘5-a-day’ fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine

A comparison of the effect of advice to eat either ‘5-a-day’ fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine

Epidemiologia nutricional

Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans

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