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Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study.

Abstract

We have previously found BMD and fracture risk to be significantly associated with the MTHFR (C677T) polymorphism in healthy postmenopausal women in the first years after menopause. Since then, other cohort studies have suggested that sufficient intake of riboflavin and/or folate may have the potential to prevent development of low BMD in women with the TT genotype. This could to some extent explain why this polymorphism is associated with low BMD or fracture in some study populations and not in others. It would also indicate that fractures associated with the TT genotype could be preventable by vitamin B supplementation. We have, therefore, reviewed baseline food record data from our original study to determine if BMD and fracture associations with the MTHFR genotype depended on the intake of folate, riboflavin, or other members of the vitamin B complex, associated with homocysteine metabolism. We analyzed genotype, BMD, and dietary records from 1700 healthy postmenopausal women who participated in the DOPS study. For the assessment of fracture risk, we used longitudinal observations from 854 women in the control group who remained compliant with their initial allocation of no treatment. Riboflavin intake was significantly correlated with femoral neck (FN) BMD in women with the TT genotype (r = 0.24, P < 0.01). FN and lumbar spine (LS) BMD were only associated with the MTHFR genotype in the lowest quartile of riboflavin intake. At the FN, similar threshold effects were shown for folate, vitamin B12, and vitamin B6. Among these vitamin B complex members, stepwise regression analysis identified riboflavin as the only significant predictor of FN BMD in the TT genotype. In conclusion, we confirm reports that BMD in the MTHFR TT genotype is only significantly reduced in the lowest quartile of riboflavin, B12, B6, and folate intake, at least at the time of menopause. Vitamin B supplementation would only be expected to benefit BMD in about 2% of the population, i.e., those with the TT genotype and low vitamin B intake.

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  • Authors+Show Affiliations

    ,

    Department of Endocrinology, Odense University Hospital, DK-5000 Odense C, Denmark. B.abrahamsen@dadlnet.dk

    , , , , , ,

    Source

    Bone 36:3 2005 Mar pg 577-83

    MeSH

    Bone Density
    Cytosine
    Denmark
    Diet Records
    Female
    Folic Acid
    Genotype
    Humans
    Methylenetetrahydrofolate Reductase (NADPH2)
    Middle Aged
    Osteoporosis
    Osteoporosis, Postmenopausal
    Riboflavin
    Thymine

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15777680

    Citation

    Abrahamsen, Bo, et al. "Are Effects of MTHFR (C677T) Genotype On BMD Confined to Women With Low Folate and Riboflavin Intake? Analysis of Food Records From the Danish Osteoporosis Prevention Study." Bone, vol. 36, no. 3, 2005, pp. 577-83.
    Abrahamsen B, Madsen JS, Tofteng CL, et al. Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study. Bone. 2005;36(3):577-83.
    Abrahamsen, B., Madsen, J. S., Tofteng, C. L., Stilgren, L., Bladbjerg, E. M., Kristensen, S. R., ... Mosekilde, L. (2005). Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study. Bone, 36(3), pp. 577-83.
    Abrahamsen B, et al. Are Effects of MTHFR (C677T) Genotype On BMD Confined to Women With Low Folate and Riboflavin Intake? Analysis of Food Records From the Danish Osteoporosis Prevention Study. Bone. 2005;36(3):577-83. PubMed PMID: 15777680.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study. AU - Abrahamsen,Bo, AU - Madsen,Jonna Skov, AU - Tofteng,Charlotte Landbo, AU - Stilgren,Lis, AU - Bladbjerg,Else Marie, AU - Kristensen,Søren Risom, AU - Brixen,Kim, AU - Mosekilde,Leif, PY - 2004/11/09/received PY - 2004/12/19/revised PY - 2004/12/27/accepted PY - 2005/3/22/pubmed PY - 2005/7/9/medline PY - 2005/3/22/entrez SP - 577 EP - 83 JF - Bone JO - Bone VL - 36 IS - 3 N2 - We have previously found BMD and fracture risk to be significantly associated with the MTHFR (C677T) polymorphism in healthy postmenopausal women in the first years after menopause. Since then, other cohort studies have suggested that sufficient intake of riboflavin and/or folate may have the potential to prevent development of low BMD in women with the TT genotype. This could to some extent explain why this polymorphism is associated with low BMD or fracture in some study populations and not in others. It would also indicate that fractures associated with the TT genotype could be preventable by vitamin B supplementation. We have, therefore, reviewed baseline food record data from our original study to determine if BMD and fracture associations with the MTHFR genotype depended on the intake of folate, riboflavin, or other members of the vitamin B complex, associated with homocysteine metabolism. We analyzed genotype, BMD, and dietary records from 1700 healthy postmenopausal women who participated in the DOPS study. For the assessment of fracture risk, we used longitudinal observations from 854 women in the control group who remained compliant with their initial allocation of no treatment. Riboflavin intake was significantly correlated with femoral neck (FN) BMD in women with the TT genotype (r = 0.24, P < 0.01). FN and lumbar spine (LS) BMD were only associated with the MTHFR genotype in the lowest quartile of riboflavin intake. At the FN, similar threshold effects were shown for folate, vitamin B12, and vitamin B6. Among these vitamin B complex members, stepwise regression analysis identified riboflavin as the only significant predictor of FN BMD in the TT genotype. In conclusion, we confirm reports that BMD in the MTHFR TT genotype is only significantly reduced in the lowest quartile of riboflavin, B12, B6, and folate intake, at least at the time of menopause. Vitamin B supplementation would only be expected to benefit BMD in about 2% of the population, i.e., those with the TT genotype and low vitamin B intake. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/15777680/Are_effects_of_MTHFR__C677T__genotype_on_BMD_confined_to_women_with_low_folate_and_riboflavin_intake_Analysis_of_food_records_from_the_Danish_osteoporosis_prevention_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(04)00496-X DB - PRIME DP - Unbound Medicine ER -