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

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR; EC 1.7.99.5) supplies the folate needed for the metabolism of homocysteine. A reduction in MTHFR activity, as occurs in the homozygous state for the 677C-->T (so-called thermolabile) enzyme variant (TT genotype), is associated with an increase in plasma total homocysteine (tHcy). OBJECTIVE: In vitro studies suggest that the reduced activity of thermolabile MTHFR is due to the inappropriate loss of its riboflavin cofactor. We investigated the hypothesis that MTHFR activity in the TT genotype group is particularly sensitive to riboflavin status. DESIGN: We studied tHcy and relevant B-vitamin status by MTHFR genotype in a cross-sectional study of 286 healthy subjects aged 19-63 y (median: 27 y). The effect of riboflavin status was examined by dividing the sample into tertiles of erythrocyte glutathionine reductase activation coefficient, a functional index of riboflavin status. RESULTS: Lower red blood cell folate (P = 0.0001) and higher tHcy (P = 0.0082) concentrations were found in the TT group than in the heterozygous (CT) or wild-type (CC) groups. However, these expected relations in the total sample were driven by the TT group with the lowest riboflavin status, whose mean tHcy concentration (18.09 micromol/L) was almost twice that of the CC or CT group. By contrast, adequate riboflavin status rendered the TT group neutral with respect to tHcy metabolism. CONCLUSIONS: The high tHcy concentration typically associated with homozygosity for the 677C-->T variant of MTHFR occurs only with poor riboflavin status. This may have important implications for governments considering new fortification policies aimed at the prevention of diseases for which this genotype is associated with increased risk.

Parental Responsibility and the Duty to Consult - the public's view

This article considers the imposition, by the courts, of a parental duty to consult on matters of importance in a child’s life. The results of a survey of 2,300 respondents, who were asked to respond to a number of scenarios, are analysed and discussed. The survey provides some interesting reflections on the views of the general public as to who should be ‘in control’ over decision making for children.

The Tragedy of Darfur and the Limits of the Responsibility to Protect

The view that states which claim sovereign status must comply with the responsibility to protect their own citizens is gaining ground in international politics. When a state is unable or unwilling to meet this responsibility, the international community is justified in intervening militarily to end widespread human rights violations. This article argues that a diffuse responsibility to protect, as currently conceived, may have important negative consequences. By using the ongoing tragedy of Darfur as an example, the article argues that the responsibility to protect is reactive and focused on the short term, contributes to the outbreak of violence and perversely provides repressed groups with a further incentive to continue their armed struggle after war breaks out. The tragedy of Darfur shows that effective protection requires case-specific policies aimed at prevention, democratization and economic and political development.