Severe deficiency in either folate or vitamin B12 can lead to megaloblastic anemia, which causes fatigue, weakness, and shortness of breath. Improper treatment of vitamin B12-dependent megaloblastic anemia with high dose supplemental folic acid can potentially delay the diagnosis of vitamin B12 deficiency and thus leave the individual at risk of developing irreversible brain damage. (More information)
Folate status is influenced by the presence of genetic variations in folate metabolism, particularly those found in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. (More information)
Inadequate folate status during early pregnancy increases the risk of congenital anomalies. The introduction of mandatory folic acid fortification of refined grain products in the US in 1998 has reduced the prevalence of neural tube defects (NTDs) in newborns. Yet, folate status is considered inadequate in a majority of women of childbearing age worldwide. Moreover, genetic factors might modify the risk of NTDs by increasing the susceptibility to folate deficiency during pregnancy. Several studies are currently investigating the role of folic acid supplementation in the prevention of congenital anomalies other than NTDs. (More information)
Folate deficiency and elevated concentrations of homocysteine in the blood are associated with increased risk of cardiovascular disease (CVD). Although folic acid supplementation has been proven effective to control circulating homocysteine concentrations, the effect of homocysteine lowering on the incidence of CVD is still debated. (More information)
Low folate status has been linked to increased cancer risk. However, intervention trials with high doses of folic acid have not generally shown any benefit on cancer incidence. (More information)
Prospective cohort studies have reported an inverse association between folate status and colorectal cancer (CRC) risk, especially among men. The relationship between folate status and cancer risk is however complex and requires further research. (More information)
Folate is essential for brain development and function. Low folate status and/or high homocysteine concentrations are associated with cognitive dysfunction in aging (from mild impairments to dementia). Whether supplemental B-vitamins, including folic acid, will have long-term benefits in maintaining cognitive health is not yet known. (More information)
