Folate is a vital component of a healthy diet, being essential for numerous bodily functions. Deficiency of folate is common, with studies suggesting prevalence of deficiencyas high as 85.5% as was shown in women between the ages of 16 and 49, living in the UK. Causes of folate deficiency range from diet and lifestyle, to pathological and pharmacological processes. Because of the well-known role of folate in prevention of neural tube defects, numerous countries have implemented strategies to increase folate intake, with programs such as mandatory grain fortification. As a result, the intake of folate in these countries is often higher than the recommended dietary allowance for many groups of people. Although folate is believed to be non-toxic, the potential adverse effects of excessive intake of folic acid (synthetic form of folate) have not been highlighted well by authorities to people taking supplements; despite this, many studies have addressed this issue. However, the results of these studies provide discrepant results, leading to confusion as to whether mandatory folic acid fortification should be introduced in other countries. The purpose of this review was to provide a summary of evidence related to high folic acid ingestion and to look at the unwanted effects it may have on the certain groups within the general population.
Folate (vitamin B) plays a crucial role in fundamental cellular processes, including nucleic acid biosynthesis, methyl group biogenesis and amino acid metabolism. The detection and correction of folate deficiency prevents megaloblastic anaemia and reduces the risk of neural tube defects. Coexisting deficiencies of folate and vitamin B are associated with cognitive decline, depression and neuropathy. Folate deficiency and excess has also been implicated in some cancers. Excessive exposure to folic acid, a synthetic compound used in supplements and fortified foods, has also been linked to adverse health effects. Of at least three distinct laboratory markers of folate status, it is the total abundance of folate in serum/plasma that is used by the majority of laboratories. The analysis of folate in red cells is also commonly performed. Since the folate content of red cells is fixed during erythropoiesis, this marker is indicative of folate status over the preceding ~4 months. Poor stability, variation in polyglutamate chain length and unreliable extraction from red cells are factors that make the analysis of folate challenging. The clinical use of measuring specific folate species has also been explored. 5-Methyltetrahydrofolate, the main form of folate found in blood, is essential for the vitamin B-dependent methionine synthase mediated remethylation of homocysteine to methionine. As such, homocysteine measurement reflects cellular folate and vitamin B use. When interpreting homocysteine results, age, sex and pregnancy, specific reference ranges should be applied. The evaluation of folate status using combined markers of abundance and cellular use has been adopted by some laboratories. In the presence of discordance between laboratory results and strong clinical features of deficiency, treatment should not be delayed. High folate status should be followed up with the assessment of vitamin B status, a review of previous results and reassessment of folic acid supplementation regime.
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