Letter by Powers et al Regarding Article, “Riboflavin Lowers Homocysteine in Individuals Homozygous for the MTHFR 677C→T Polymorphism”
To the Editor:
We read with interest the paper by McNulty et al,1 in which it was shown that riboflavin supplements have a plasma homocysteine-lowering effect in people with marginal riboflavin status and moderately high plasma homocysteine (tHcy), apparently driven entirely by those people homozygous for the MTHFR C677T thermolabile variant. This finding makes an important contribution to the accumulating evidence of this gene–nutrient interaction.
Although it is reasonable to include riboflavin in considerations of the possible merits of food fortification with folate, it should be appreciated that the reported effect of riboflavin supplementation is confined to a selected group (people homozygous for the TT variant). Plasma tHcy levels in this group were almost twice those in a representative sample of men and women in the United Kingdom,2 in whom only the top 2.5% of women had values greater than 19μmol/L, in comparison with a mean value of 17.6μmol/L in the cohort presented by McNulty et al.
The sample of this study was not representative of the distribution of plasma tHcy and therefore cardiovascular risk in the United Kingdom and European populations.3 This compromises statistical inference and, in our opinion, the study should not be used as a basis for suggesting food policy.
Sources of Funding
Drs McDowell, Moat, and Powers received a research grant from the Food Standards Agency to study folate, riboflavin, and homocysteine lowering. Dr Powers has received funding from the Food Standards Agency to study riboflavin/genotype interactions.
McNulty H, Dowey, LC, Strain JJ, Dunne A, Ward M, Molloy AM, MccAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C→T polymorphism. Circulation. 2006; 113: 74–80.
Ruston D, Hoare J, Henderson L, Gregory J, Bates CJ, Prentice A, Birch M, Swan G, Farron M. The National Diet and Nutrition Survey: Adults Aged 19 to 64 Years. Volume 4: Nutritional Status. London, UK: HMSO; 2004.
Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Rouland FM, Tan KS, Higgins I, Garcon D, Andria G. Plasma homocysteine as a risk factor for cardiovascular disease. The European Concerted Action project. JAMA. 1997; 277: 1775–1781.