A meta-analysis of numerous studies from around the world showed that individuals with the MTHFR 677TT genotype have a significantly higher risk for coronary heart disease (14-21%, McNulty et al 2008), but only when their folate status and/or riboflavin status is low (Klerk et al 2002; McNulty et al 2002). This may be influenced by the fact that high plasma homocysteine concentrations are an independent risk factor for heart disease. The overall risk was significantly higher in individuals with the TT genotype in Europe, but not in North America. This difference could be due to the fact that fortification of flour, cereals and other foods with folic acid and riboflavin (vitamin B2) has been mandatory in the US for several years, but is currently not carried out in Europe. It has also been demonstrated that having optimal levels of riboflavin (vitamin B2) can compensate for the effect of the TT genotype on plasma homocysteine concentrations (McNulty et al 2002).