Is regional heterogeneity due to differences in folate intake?
It has been suggested that the observed geographical differences relate to nutritional habits, widespread use of vitamin supplements, or fortification of breakfast cereals with folate in North America and Europe in contrast with more unfavourable intakes of folic acid in other regions.11 Differences in homocysteine concentrations by MTHFR C677T genotype have been shown to be greater at lower levels of folate intake and are reduced after folate supplementation.14 In our meta-analysis we found relatively modest differences in homocysteine concentrations by genotype in the United States, where fortification of foods with folate is mandatory, but larger differences in other regions. A recent meta-analysis that used mendelian randomisation to examine the association of homocysteine with stroke confirmed the lower mean difference between TT and CC MTHFR C677T genotypes in homocysteine concentration for North American but not European studies, but the numbers of participants studied were much
