“…The high MARS levels enhance sensitivity to changes in homocysteine levels in these developing and proliferating cells. Although hyperhomocysteinemia is associated with many major diseases, it consistently requires a more severe homocysteine elevation (> 150 lM) to induce adult diseases such as neurodegenerative disorders (Kruman et al, 2000;Mattson & Shea, 2003), whereas birth defects are associated with even a very slight Hcy elevation (8-15 lM) (Mills et al, 1995;van der Put et al, 1998;Bakker et al, 2009;Peker et al, 2016). This notion is substantiated by the finding that folate supplementation failed to prevent cardiovascular diseases (Wierzbicki, 2007) or other adult disorders (Brattstrom et al, 1998) and promoted the growth of preneoplastic cells and subclinical cancers (Kim, 2003;Ulrich & Potter, 2007), but prevented birth defects.…”