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Title: Homocysteine, related B-vitamins, osteoporosis risk and a common polymorphism in MTHFR : investigations in healthy postmenopausal women and coeliac disease patients
Author: Whittle, Claire Ruth
ISNI:       0000 0004 2721 9133
Awarding Body: University of Ulster
Current Institution: Ulster University
Date of Award: 2009
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Lower bone mineral density (BMD) and increased fracture risk have recently been linked with elevated homocysteine and/or the metabolically related B-vitamins. The most important genetic determinant of homocysteine is the 677C~ T polymorphism (IT genotype) in methylenetetrahydrofolate reductase (MTHFR) which has been associated with lower BMD. The B-vitamins, folate and riboflavin can modulate the expected phenotype of elevated homocysteine, with riboflavin intervention resulting in a marked lowering of homocysteine levels specifically in those with the TT genotype. The overall aim of this thesis is to investigate the association between the IT genotype, homocysteine, the related B-vitamins and bone health in healthy women and an 'at-risk' patient group. In an observational study of well-nourished postmenopausal women this research showed no evidence of lower BMD in individuals pre-screened for the TT genotype (n = 77) when compared to age-matched heterozygous CT (n = 90) and wild-type CC (n = 84) genotypes. Furthermore, there was no evidence of a gene-nutrient interaction in relation to riboflavin status and BMD among participants with the IT genotype. This project presents the first intervention study to show that riboflavin can lower homocysteine in women pre-screened for the TT genotype, and also that a combination of folic acid and riboflavin is more effective than riboflavin alone. Coeliac disease (CD) is a condition which frequently presents with lower BMD and nutrient malabsorption, particularly folate. A case-control study from this thesis showed that compromised folate status and/or elevated homocysteine may contribute to lower BMD in female CD patients, particularly in untreated patients who have not commenced treatment with a gluten-free diet. In a pilot follow-up study with CD patients there was also a suggestion that lower folate status was associated with a greater rate of bone loss, however this effect appeared to be small compared with the role of vitamin D status. Thus individuals with more compromised B-vitamin status and/or elevated homocysteine, due to inadequate dietary intake or malabsorption may be more at risk of osteoporosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available