HAND2 and vitamin B12 deficiency: A recent study37 using zebra fish found that excessive folic acid can induce cardiac abnormality by disrupting the methylation level of cardiac marker genes, such as hand2, gata4, and nppa. Furthermore, excessive folic acid intake has been linked to an increased rate of de novo point mutations in DNA.38 Vitamin B12 deficiency and elevated homocysteine may amplify the association between high folate levels and CHD risk by worsening these pathogenesis pathways, which requires further investigation.