• Nutrition Research and Practice
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• v.1 no.3
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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.

• Journal of Nutrition and Health
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• v.40 no.2
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• pp.130-137
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• 2007

Myelin basic protein (MBP), a major structural protein of the myelin, is thought to be important for the maintenance of myelin in the central nervous system (CNS). We investigated the effect of maternal folic acid nutritional status on the folate level and the synthesis of MBP in the offspring. In order to test this hypothesis, female Sprague-Dawley rats were fed either folic acid sufficient (8 mg/kg diet) or deficient (0 mg/kg diet) diet from 2 wks prior to the mating throughout the entire pregnancy, lactation and weaning period. We examined plasma folate level by the radioimmunoassay and homocysteine level by HPLC, respectively. The MBP expression was measured by the western blot analysis. The maternal folic acid deficiency decreased plasma folate level with a concomitant increase in plasma homocysteine level in their offspring. The maternal folic acid deficiency decreased hepatic levels of SAM and SAM/SAH ratio with a concomitant increase in hepatic levels of SAH and the MBP expression of spinal cord in their offspring at 7 wks of age. These results suggest that maternal folic acid nutritional status affect plasma folate and homocysteine level in their offspring. Moreover, the maternal folic acid deficiency mi호t inhibit the MBP expression of the spinal cord and disrupt many other vital CNS reactions in their offspring.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.122-127
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• 2009

Folate is generally considered as a safe water-soluble vitamin for supplementation. However, we do not have enough information to confirm the potential effects and safety of folate supplementation and the interaction with vitamin $B_{12}$ deficiency. It has been hypothesized that a greater methyl group supply could lead to compensation for vitamin $B_{12}$ deficiency. On this basis, the present study was conducted to examine the effects of high-dose folic acid (FA) supplementation on biomarkers involved in the methionine cycle in vitamin $B_{12}$-deficient rats. Sprague-Dawley rats were fed diets containing either 0 or $100{\mu}g$ (daily dietary requirement) vitamin $B_{12}/kg$ diet with either 2 mg (daily dietary requirement) or 100 mg FA/kg diet for six weeks. Vitamin $B_{12}$-deficiency resulted in increased plasma homocysteine (p<0.01), which was normalized by dietary supplementation of high-dose FA (p<0.01). However, FA supplementation and vitamin $B_{12}$ deficiency did not alter hepatic and brain S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations and hepatic DNA methylation. These results indicated that supplementation of high-dose FA improved homocysteinemia in vitamin $B_{12}$-deficiency but did not change SAM and SAH, the main biomarkers of methylating reaction.

• Nutrition Research and Practice
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• v.5 no.6
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• pp.520-526
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• 2011

Folate deficiency and hyperhomocysteinemia are found in most patients with alcoholic liver disease. Oxidative stress is one of the most important mechanisms contributing to homocysteine (Hcy)-induced tissue injury. However it has not been examined whether exogenous administration of folic acid attenuates oxidative stress and hepatic toxicity. The aim of this study was to investigate the in vivo effect of folic acid supplementation on oxidative stress and hepatic toxicity induced by chronic ethanol consumption. Wistar rats (n = 32) were divided into four groups and fed 0%, 12%, 36% ethanol, or 36% ethanol plus folic acid (10 mg folic acid/L) diets. After 5 weeks, chronic consumption of the 36% ethanol diet significantly increased plasma alanine transaminase (ALT) (P < 0.05) and aspartate transaminase (AST) (P < 0.05), triglycerides (TG) (P < 0.05), Hcy (P < 0.001), and low density lipoprotein conjugated dienes (CD) (P < 0.05) but decreased total radical-trapping antioxidant potential (TRAP) (P < 0.001). These changes were prevented partially by folic acid supplementation. The 12% ethanol diet had no apparent effect on most parameters. Plasma Hcy concentration was well correlated with plasma ALT (r = $0.612^{**}$), AST (r = $0.652^*$), CD (r = $0.495^*$), and TRAP (r = $-0.486^*$). The results indicate that moderately elevated Hcy is associated with increased oxidative stress and liver injury in alcohol-fed rats, and suggests that folic acid supplementation appears to attenuate hepatic toxicity induced by chronic ethanol consumption possibly by decreasing oxidative stress.

• Preventive Nutrition and Food Science
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• v.19 no.4
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2199-2206
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• 2012

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.

• Nutrition Research and Practice
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• v.7 no.4
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• pp.281-286
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• 2013

We examined the effect of parental folate deficiency on the folate content, global DNA methylation, folate receptor-alpha (FR${\alpha}$), insulin-like-growth factor-2 (IGF-2) and -1 receptor (IGF-1R) in the liver and plasma homocysteine in the postnatal rat. Male and female rats were randomly fed a folic acid-deficient (paternal folate-deficient, PD and maternal folate-deficient, MD), or folic acid-supplemented diet (paternal folate-supplemented, PS and maternal-folate-supplemented, MS) for four weeks. They were mated and grouped accordingly: $PS{\times}MS$, $PS{\times}MD$, $PD{\times}MS$, and $PD{\times}MD$. Pups were killed on day 21 of lactation. The hepatic folate content was markedly reduced in the $PD{\times}MD$ and $PS{\times}MD$ and $PD{\times}MS$ as compared with the $PS{\times}MS$ group. The hepatic global DNA methylation was decreased in the $PD{\times}MS$ and $PS{\times}MD$ groups as much as in the $PD{\times}MD$ group, and all the three groups were significantly lower as compared to the $PS{\times}MS$ group. There were no significant differences in the hepatic FR${\alpha}$, IGF-2 and IGF-1R expressions among the groups. Positive correlations were found between the hepatic folate content and global DNA methylation and protein expressions of FR${\alpha}$, IGF-2 and IGF-1R, whereas an inverse correlation was found between hepatic folate content and plasma homocysteine level in the 3-week-old rat pup. The results of this study show that both paternal and maternal folate deficiency at mating can influence the folate content and global DNA methylation in the postnatal rat liver.

• The Journal of Internal Korean Medicine
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• v.21 no.5
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• pp.877-881
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• 2000

Anemia is present in adult if the hematocrit is less than 41%(hemoglobin <13.5g/dL) in males or 37%(hemoglobin <12g/dL) in females. In taking the history, congenital anemia may be suggested by the patient's personal and family history. Poor diet results in folic acid deficiency and may contribute to iron deficiency. Bleeding should always be considered in iron deficiency. Object : The symptoms of this patient are easy fatigability, dizziness, anorexia and paleness of the face. This women is the patient of iron deficiency anemia, cerebral hemorrhage and hypertension. Medication : Gwibitang(歸脾湯) plus(合) Samultang(四物湯) and feroba are dispensed for 30 days. Result : After 30 days, HCT Hb Iron of the laboratory findings are increased and TIBC of the laboratory findings is decreased.

• Nutrition Research and Practice
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• v.5 no.2
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• pp.112-116
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• 2011

We investigated the effect of paternal folate status on folate content and expression of the folate transporter folate receptor ${\alpha}$ ($FR{\alpha}$) in rat placental tissues. Rats were mated after males were fed a diet containing 0 mg of folic acid/kg of diet (paternal folate-deficient, PD) or 8 mg folic acid/kg of diet (paternal folate-supplemented, PS) for 4 weeks. At 20 days of gestation, the litter size, placental weight, and fetal weight were measured, and placental folate content (n=8/group) and expression of $FR{\alpha}$ (n=10/group) were analyzed by microbiological assay and Western blot analysis, respectively. Although there was no difference observed in litter size or fetal weight, but significant reduction (10%) in the weight of the placenta was observed in the PD group compared to that in the PS group. In the PD group, placental folate content was significantly lower (by 35%), whereas $FR{\alpha}$ expression was higher (by 130%) compared to the PS group. Our results suggest that paternal folate status plays a critical role in regulating placental folate metabolism and transport.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.146-151
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• 2005

Purpose: We have preoperatively and postoperatively investigated the characteristics of anemia in patients with gastric cancer in order to provide optimal medical care for the patients. Materials and Methods: Preoperative hemoglobin, serum iron, serum ferritin, serum vitamin $B_{12}$, and serum folic acid were measured for 321 patients with gastric cancer. These were measured again for 287 patients 6 months postoperatively. Results: Ninety-four patients (29.3%) had preoperative anemia. Preoperative hemoglobin, serum iron, and serum vitamin $B_{12}$ levels were higher in the patients with early gastric cancer than in patients with advanced gastric cancer. Preoperative hemoglobin, serum iron, and serum ferritin levels were higher in male patients than in female patients. The patients who had preoperative anemia showed a high probability of having postoperative anemia (P<0.001), and the patients who had low serum ferritin levels preoperatively showed a high probability of having low serum ferritin levels and iron deficiency anemia postoperatively (P<0.004). Conclusion: Preoperative ferritin deficiency should be improved by iron supplement, even though the patient may not be anemic at that time. Periodic postoperative measurements of the hemoglobin, serum iron, serum ferritin, serum vitamin $B_{12}$, and serum folic acid levels are highly recommended because postgastrectomy anemia is not rare. Finally, if any low hemoglobin, serum iron, serum ferritin, serum vitamin $B_{12}$, or serum folic acid levels are found, they should be treated in an appropriate way.