• Nutrition Research and Practice
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• 제1권3호
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• pp.163-174
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• 2007

Folate has received international attention regarding its role in the risk-reduction of birth defects, specifically neural tube defects (NTDs). In 1998 health officials in Canada, like the United States, mandated the addition of folic acid to white flour and select grain product's to increase the folate intake of reproductive-aged women. Subsequent to this initiative there has been an increase in blood folate concentrations in Canada and a 50% reduction in NTDs. Many countries, including Korea, have not mandated folic acid fortification of their food supply. Reasons vary but often include concern over the masking of vitamin $B_{12}$ deficiency, a belief that folate intakes among womenare adequate, low priority relative to other domestic issues, and the philosophy that individuals have the right not to consume supplemental folic acid if they so choose. Prior to folic acid fortification of the food supply in Canada, the folate intakes of women were low, and their blood folate concentrations while not sufficiently low to produce overt signs of folate deficiency (eg. anemia) were inconsistent with a level known to reduce the risk of an NTD-affected pregnancy. The purpose of this article is to describe the role of folate during the periconceptional period, pregnancy, and during lactation. The rationale for, and history of recommending folic acid-containing supplements during the periconceptional period and pregnancy is described as is folic acid fortification of the food supply. The impact of folic acid fortification in Canada is discussed, and unresolved issues associated with this policy described. While the incidence of NTDs in Canada pre-folic acid fortification were seemingly higherthan that of Korea today, blood folate levels of Korean women are strikingly similar. We will briefly explore these parallels in an attempt to understand whether folic acid fortification of the food supply in Korean might be worth consideration.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.247-260
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• 2014

The impact of folate on health and disease, particularly pregnancy complications and congenital malformations, has been extensively studied. Mandatory folic acid fortification therefore has been implemented in multiple countries, resulting in a reduction in the occurrence of neural tube defects. However, emerging evidence suggests increased folate intake may also be associated with unexpected adverse effects. This literature review focuses on contemporary issues of concern, and possible underlying mechanisms as well as giving consideration the future direction of mandatory folic acid fortification. Folate fortification has been associated with the presence of unmetabolized folic acid (PteGlu) in blood, masking of vitamin $B_{12}$ deficiency, increased dosage for anti-cancer medication, photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the pathoaetiology of colorectal cancer. Increased folate intake has also been associated with twin birth and insulin resistance in offspring, and altered epigenetic mechanisms of inheritance. Although limited data exists to elucidate potential mechanisms underlying these issues, elevated blood folate level due to the excess use of PteGlu without consideration of an individual's specific phenotypic traits (e.g. genetic background and undiagnosed disease) may be relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to inhibition of dihydrofolate reductase and other enzymes. Concerns notwithstanding, folic acid fortification has achieved enormous advances in public health. It therefore seems prudent to target and carefully monitor high risk groups, and to conduct well focused further research to better understand and to minimize any risk of mandatory folic acid fortification.

• Journal of Nutrition and Health
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• 제49권2호
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• pp.72-79
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• 2016

Purpose: The initiation of mandatory folic acid fortification using pteroylmonoglutamic acid (PteGlu) has reduced the rate of congenital malformations. However, it also appears to be responsible for several adverse effects, including increased cancer incidence. This may be related to physicho-chemical characteristics of PteGlu. This study examines the potential effect of high concentrations of PteGlu on a population subjected to mandatory folic acid fortification using an in vitro model. Methods: Caco-2 (colorectal cancer) and MCF7 (breast cancer) cell lines were cultured at 6 different PteGlu concentrations (0, 0.1, 1, 50, 250, and $500{\mu}g/ml$) for 6 days. Cell growth was determined using thiazolyl blue tetrazolium bromide assay. The genotype of dihydrofolate reductase 19bp deletion/insertion (DHFR 19-del) was also scored in cell lines using a restriction fragment length polymorphism technique to examine whether genetic variations may factor in cell proliferation. Results: PteGlu exhibited differential growth promoting properties between cell lines. Caco-2 cells did not show a significant growth difference at low concentrations compared to control, however, at higher concentrations, the growth showed a contrasting trend in the early experimental period, while MCF7 showed enhanced cell growth at all concentrations. The DHFR 19-del genotype differed in the two cell lines. Conclusions: Altered response to PteGlu by Caco-2 and MCF7 may reflect a tissue specific disease aetiology or genotype specific differential enzyme activity, for example by DHFR, to critical levels of PteGlu. As folic acid fortification is a blanket intervention, and DHFR and other enzyme activities vary between individuals, PteGlu intake may have an as yet undefined effect on health. These findings may be relevant when considering mandatory folic acid fortification for disease prevention.

• Nutrition Research and Practice
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• 제7권4호
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• pp.315-325
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• 2013

We evaluated folate status of child-bearing age women diagnosed with abnormal pap smear in the US post-folic acid (FA) fortification era and assessed the determinants of NTD-protective and supra-physiologic (SP) concentrations of folate. The distribution of 843 women according to NTD-protective concentrations of RBC folate, plasma folate and SP concentrations of plasma folate were tested in relation to demographic and life-style factors. Logistic regression models specified NTD-protective concentrations of RBC and plasma folate or SP concentrations of plasma folate as dependent variables and demographic and life-style factors as independent predictors of interest. More than 82% reached NTD-protective concentrations of RBC and plasma folate and ~30% reached SP concentrations of plasma folate. FA supplement use was associated with having SP concentrations of plasma folate rather than NTD-protective concentrations of folate. African American (AA) women and smokers were significantly less likely to achieve NTD-protective concentrations of RBC and plasma folate. A large majority of women reached NTD-protective concentrations of folate with the current level of FA fortification without using supplementary FA. Therefore, the remaining disparities in AA women and in smokers should be addressed by targeted individual improvements in folate intake.

• Journal of Nutrition and Health
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• 제39권7호
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• pp.692-698
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• 2006

The voluntary addition of vitamins and minerals to the appropriate foods may help reduce the risks associated with low intakes of these micronutrients, yet the potential of excessive intake, particularly for persons consuming very large amount of foods needs to be addressed. Using the Flynn's model to estimate the level of each vitamins and minerals that can be added safely to foods, maximum levels of fortification to conventional foods per 100 kcal portion were estimated. Critical factors in the Flynn's model included tolerable upper intake level (UL), each micronutrient intake at the $95^{th}$ percentile, the proportion of fortified foods in the diets of individuals, the proportion of foods to which micronutrients could be practically added, and a range of estimates for fractions of foods which might be actually fortified in each nutrient. Food vehicles included all foods except for fresh foods and alcoholic beverages, in general. With fortification of 50% of all potentially fortifiable foods, micrornutrients could be added safely to foods at levels per 100 kcal 1) > 100% Recommended Intake (RI) for vitamin $B_12$, 2) 1,200% RI for vitamin $B_1$ and niacin, 3) 1,000% $B_1$ for vitamins $B_2$ and $B_6$, 4) 400% RI for vitamin E, 5) 30% RI for calcium, 6) 20% RI for folic acid, iron and zinc, 7) 10% RI for manganese, 8) no fortification for magnesium, phosphorous and vitamin A, and 8) further consideration of vitamin D, copper and selenium due to insufficient evidence. Results of this study suggests a wide range of vitamins and minerals that can be added safely to foods in current diets of Koreans.

• 한국식품조리과학회지
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• 제18권5호
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• pp.487-494
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• 2002

This study was conducted to investigate the thermal stability of water-soluble and fat-soluble vitamins dissolved in water and milk by various heat treatments. Vitamin samples were prepared by dissolving them in water and milk at various concentrations, and were heat treated for 30 min at 65$\^{C}$, 15 sec at 85$\^{C}$, 5 sec at 100$\^{C}$, 121$\^{C}$ at 15 min, the levels of residual vitamin were measured by using HPLC. Milk samples were fortified with vitamins before and after UHT treatment. As heating over 100$\^{C}$, riboflavin in water were destructed more than 92% but fortified in milk showed less than 20% destruction, suggesting that riboflavin was protected by milk components. Also retinol heated ever 100$\^{C}$ was more stable in milk than in water. L-Ascorbic acid and cholecalciferol(D$_3$) showed a similar destruction rate in water and in fortified milk. L-ascorbic acid was easily destructed by UHT treatment. Destruction of thiamin and tocopherol was increased in fortified milk. Among tour capsulated water-soluble vitamins, L-ascorbic acid was much more stable compared with powder form. Nicotinic acid and folic acid either in capsule or powder form showed a slight destruction by heat treatment. The results suggested that the fortification of unstable vitamins such as L-ascorbic acid, thiamin, tocopherol and cholecalciferol(D$_3$) should be made in milk after heat treatment.