Detection, isolation, and characterization of a novel impurity from several folic acid products / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Folic acid belongs to the group of water-soluble B vitamins and naturally exists in multiple forms in a wide variety of foods such as legumes, vegetables, liver, and milk (Iyer and Tomar, 2009; Lyon et al., 2020). It is involved in many biochemical reactions critical for cell division, such as purine and pyrimidine biosynthesis, DNA/RNA biosynthesis, and amino acid metabolism (Iyer and Tomar, 2009). Mammals cannot synthesize folic acid and thus they must acquire it from food. Although folic acid is ubiquitous in foods, folic acid deficiency still often occurs due to various causes such as unhealthy diet (Hildebrand et al., 2021; Iimura et al., 2022), disease-related malabsorption (Arcot and Shrestha, 2005), medication-related depletion (Arcot and Shrestha, 2005), or vitamin B12 deficiency (Fishman et al., 2000). Folic acid deficiency has been associated with several health problems, such as anemia (Carmel, 2005; Bailey and Caudill, 2012), cancer (Duthie, 1999), cardiovascular diseases (Wald et al., 2002), neural tube defects in newborns (van der Put et al., 2001), neuropsychiatric dysfunction (Shea et al., 2002), depression (Falade et al., 2021), inflammatory diseases (Suzuki and Kunisawa, 2015; Jones et al., 2019), and eye diseases (Sijilmassi, 2019). To prevent folic acid deficiency, its daily intake (400 μg/d) has been recommended for adults in the European Union, and its increased intake (600 μg/d) is advised for women before and during pregnancy (FAO/WHO, 2002; IOM, 2004). The New Zealand government mandated the fortification of non-organic wheat flour with folic acid in July 2021, and the UK government mandated the fortification of non-wholemeal wheat flour with folic acid in September 2021 (Haggarty, 2021).

Do Japanese take more folate from traditional Japanese dish than is conventionally estimated?-Actual folate contents in hospital diets and marketed lunch boxes.

Folic acid deficiency is very rare in Japan. However, recent concerns in relation to causal relationships between cancer and low folic acid levels necessitate information on actual folate intake by Japanese, which has hitherto not been well studied. We therefore evaluated folate contents of a hospital diet for 7 consecutive days and of 16 lunch boxes purchased at convenience stores. Dietary intake was assessed for weighed food items after cooking using our previously published data on folate contents of various foods and also by using Standard Tables of Food Composition in Japan (STFCJ). Mean daily folate intake from the hospital diet was 723.9 microg/day using our data but only 359.2 microg/day if calculated using the STFCJ. Twenty-nine % of the total daily folate intake was through rice. Mean folate intake through lunch boxes was 491.7 microg/day by our tabulation and 139.5 microg/day with the STFCJ. Folic acid intake of Japanese is far above the levels taken in other countries and over half of this amount is taken from rice. Levels of folic acid contents (especially in rice) listed in the STFCJ are too low and revision is strongly suggested.

Folate supplementation and neural tube defects: a review of a Public Health issue

Folate deficiency is one of today's most common vitamin deficiencies in women. Women who consume a low level of folate during pregnancy are at risk for poor pregnancy outcomes including neural tube defects (NTD). However, other factors such as heredity, social class, maternal age, birth order, maternal diet, length of time between pregnancies, maternal zinc deficiency, use of anticonvulsant drugs, abnormal homocysteine metabolism and the use of oral contraceptives, have also been implicated as causes of NTD. Animal studies have shown that fetuses are highly dependent on the folate status of the mother. In addition, several retrospective and prospective human studies have provided evidence that folate lowers the incidence of NTD