“Folate participates in the transfer and utilization of one-carbon units important in amino acid metabolism and in biosynthetic pathways leading to DNA, RNA, membrane lipids, and neurotransmitters. The clinical effects of folate deficiency are the result of impaired synthesis of DNA. Causes of folate deficiency are increased physiological requirement (e.g., pathological conditions and drugs) and decreased availability (reduced dietary intake and impaired folate absorption). Research has shown that optimal blood folate concentrations can play a role in maintaining health throughout the lifecycle. While study results for maternal health in pregnancy (prevention of megaloblastic anemia and preeclampsia) and fetal development (prevention of neural tube defects) are conclusive, there is early evidence for positive effects of folate on cognitive health in childhood. Convincing findings suggest preventive effects in heart disease and promising results in cancer prevention. In addition, it has been suggested that folate plays a possible role in bone health and cognitive function in aging.
Folate, along with metabolically related B vitamins, is required for the metabolism of homocysteine. When folate status is low or deficient, plasma homocysteine concentration is invariably elevated, thereby providing a sensitive functional biomarker of folate status. Elevated homocysteine concentration in blood has been suggested as a risk factor for cardiovascular disease (CVD), of similar magnitude as elevated cholesterol. Apart from having an established role in preventing neural tube disorders (NTDs), the strongest evidence to support the health benefits of improving folate status (and/or lowering homocysteine) is in the primary prevention of stroke (1,2).
Evidence supporting a causal relationship between sub-optimal folate status and CVD also comes from genetic studies. The most important genetic determinant of homocysteine in the general population is the common 677C->T variant in the gene encoding the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR). People homozygous for this polymorphism (TT genotype) - about 10% of populations worldwide - typically have higher plasma homocysteine concentrations and a 14 to 21% higher risk of cardiovascular disease (3). Another B-vitamin, riboflavin (vitamin B2), is required as a co-factor for MTHFR. New evidence shows that intervention with supplemental riboflavin results in marked lowering of blood pressure specifically in people with the TT genotype (4,5), an effect that appears to be independent of the homocysteine-lowering effect of riboflavin also seen only in individuals with the TT genotype.
Strong and consistent evidence from epidemiological and animal studies has linked low folate status to increased cancer risk, with strongest evidence for colorectal cancer. As possible mechanism for this relationship it has been suggested that low folate leads to reduced availability of S-adenosyl methionine (SAM) for DNA methylation and/or abnormal DNA synthesis and repair. However, some researchers have raised concerns regarding potential cancer-promoting effects of long-term exposure to high doses of folic acid (6,7).
There are three routes to achieve optimal folate status: natural food sources, fortified foods and supple-ments. While natural food folates show incomplete bioavailability and poor stability, folic acid (the synthetic form of folate) can offer a very stable and highly bioavailable vitamin form. Recent evidence indicates that the supplemental dose of folic acid required to have potential beneficial effects – due to a decrease in homo-cysteine concentrations – is much lower than previously estimated as interventions were too short (8).”
Based on: McNulty H. Nutrition throughout life: folic acid. Symposium “100 years of vitamins – Past, present, future: Micronutrients – Macro impact”. November 2012. Basel, Switzerland.
