(b) Folic acid meets the specifications of the Food Chemicals Codex, 9th edition, as updated by the Third Supplement, with effect from December 1, 2015, pp. 495-496, which is incorporated by reference. The Director of the Office of the Federal Register approves this entry by reference pursuant to 5 U.S.C. 552(a) and 1 CFR Part 51. Copies of the United States Pharmacopeial Convention, 12601 Twinbrook Pkwy., Rockville, MD 20852 (Internet address www.usp.org). Copies may be viewed at the Food and Drug Administration Main Library, 10903 New Hampshire Ave., Bldg. 2, Third Floor, Silver Spring, MD 20993, 301-796-2039, or from the National Archives and Records Administration (NARA). For more information on the availability of this equipment at NARA, call 202-741-6030 or www.archives.gov/federal-register/cfr/ibr-locations.html. (c) Folic acid may be added to foods that are subject to a standard of identity under section 401 of the federal Food, Drugs and Cosmetics Act (the Act) if the standard of identity specifically provides for the addition of folic acid. In 2006, the Scientific Advisory Committee on Nutrition (SACN) of the UK FSA recommended that mandatory folic acid fortification should continue, as well as controls on folic acid intake from voluntarily fortified foods [90]. In 2007, the SACN was convened at the request of the UK FSA to examine the possible adverse effects of folic acid on colorectal cancer risk based on two papers published earlier this year.
In 2009, following a comprehensive review, the Panel concluded that there was currently insufficient evidence to support concerns that folic acid fortification promotes cancer and announced its decision to support its previous recommendation regarding mandatory folic acid fortification [94]. Canada, Costa Rica, Chile, Argentina, Brazil and South Africa have also reported a decrease in NTDs (19% to 55%) since folic acid fortification began [33,34,35,36,41,42,43,44,45,46]. The extent of the decline in NTD prevalence observed in each country depended on a number of factors. The largest decrease in NTD prevalence was observed in countries with the highest background prevalence. Other variables that influenced the decline in NTD prevalence after fortification included the pre-fortification population folate status, the number of people consuming fortified foods, and the ability of congenital anomalies surveillance systems to effectively determine the decline in NTD prevalence following folic acid fortification. Although there were differences in NTD rates between countries prior to enrichment (10.6 to 17.0 cases per 10,000 live births), reduced rates since folic acid fortification were less variable (6.3 to 10.0 cases per 10,000 live births), as previously verified [32]. These data suggest that a prevalence of 5-6 cases per 10,000 pregnancies is the lowest prevalence possible by current folic acid fortification practices, and that some of the remaining NTDs are not sensitive to folic acid [23,32]. Recent evidence suggests that low maternal vitamin B12 levels are an important (folic acid-independent) predictor of NTD risk [47]. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants.7 This review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF did not review the evidence on folic acid supplementation in women with a history of pregnancy affected by neural tube defects or other high-risk factors. Evidence on folic acid fortification, advice on increasing dietary intake of folic acid or natural dietary folate, or screening for neural tube defects are also outside the scope of this review. Genetic predisposition and environmental influences are believed to contribute to neural tube defects.
These environmental influences are studied. A significant environmental impact is the consumption of folic acid. The mechanism of action of folate in preventing neural tube defects is unknown. Folate acts as a coenzyme in nucleic acid synthesis and amino acid metabolism. An important function of folate is its role in direct carbon transfer, which are important in methylation reactions and in the synthesis of purine and pyrimidine. NHANES 2007-2012 found that 48% of respondents of childbearing age reported consuming folic acid only from compulsorily fortified foods. Only 29% of all respondents reported taking a folic acid supplement daily.9 Among women who took a daily folic acid supplement, about half (14.6% of all women) took a supplement containing less than the recommended daily intake of 0.4 mg (400 μg).1, 9 Folic acid is usually reduced to tetrahydrofolate after ingestion by the liver [80]. When the body`s ability to reduce folic acid is exceeded, unmetabolized folic acid circulates in the blood. One experimental study suggested that unmetabolized folic acid would be found after consuming a bolus of >200 μg of folic acid [81].
Intake above this threshold would be common through the use of supplements or fortified foods such as breakfast cereals [82], but is unlikely to be achieved by mandatory U.S. folic acid intake. Only the mounting steps [81,83,84,85,86,87]. Because folic acid has long been a component of over-the-counter supplements and prenatal vitamins, unmetabolized folic acid has reportedly been found in much of the U.S. population for decades. It is only recently that the laboratory equipment needed to measure circulating unmetabolized folic acid has become available.