• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.130-136
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• 2005

The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-28 gestational weeks; 20-40 years old) women were analyzed for the MTHFR genotype and serum levels of folate and homocysteine, and were then followed for gestational age and infant birthweight. The mean infant birthweight was highest in mothers carrying MTHFR CC and with a normal folate range, and they were followed by mothers carrying MTHFR CT or TT and a normal range of folate or a folate deficiency. Birthweight was the lowest in mothers whose carrying MTHFR CC with folate deficiency. Using two way ANOVA, we found that folate level and the MTHFR polymorphism interacted to affect birth-weight of infants (p=0.05). Among those mothers carrying MTHFR CC, those with folate deficiency showed a 543 g reduction in infant birthweight compared with those with normal folate levels. However, infant birthweight was no different for mothers, those who with folate deficiency compared to those with normal range of folate among mothers carrying the MTHFR CT or TT genotypes. This study suggests an interaction between maternal serum folate and the MTHFR polymorphisms of the mother on the risk of delivering reduced birthweight offspring. Folate supplementation of folate deficient pregnant women with the MTHFR wild type is suggested to reduce the risk of low birthweight.

• Nutrition Research and Practice
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• 제7권4호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9313-9317
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• 2014

Fragile histidine triad (FHIT) is a suppressor gene related to cervical cancer through CpG island hypermethylation. Folate is a water-soluble B-vitamin and an important cofactor in one-carbon metabolism. It may play an essential role in cervical lesions through effects on DNA methylation. The purpose of this study was to observe effects of folate and FHIT methylation and HPV 16 on cervical cancer progression. In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101). There were significant differences in HPV16 status (${\chi}^2=36.64$, P<0.001), CpG island methylation of FHIT (${\chi}^2=71.31$, P<0.001) and serum folate level (F=4.57, P=0.011) across the cervical histologic groups. Interaction analysis showed that the ORs only with FHIT methylation (OR=11.47) or only with HPV 16 positive (OR=4.63) or with serum folate level lower than 3.19ng/ml (OR=1.68) in SCC group were all higher than the control status of HPV 16 negative and FHIT unmethylation and serum folate level more than 3.19ng/ml (OR=1). The ORs only with HPV 16 positive (OR=2.58) or with serum folate level lower than 3.19ng/ml (OR=1.28) in CIN group were all higher than the control status, but the OR only with FHIT methylation (OR=0.53) in CIN group was lower than the control status. HPV 16 positivity was associated with a 7.60-fold increased risk of SCC with folate deficiency and with a 1.84-fold increased risk of CIN. The patients with FHIT methylation and folate deficiency or with FHIT methylation and HPV 16 positive were SCC or CIN, and the patients with HPV 16 positive and FHIT methylation and folate deficiency were all SCC. In conclusion, HPV 16 infection, FHIT methylation and folate deficiency might promote cervical cancer progression. This suggests that FHIT may be an effective target for prevention and treatment of cervical cancer.

• Journal of Nutrition and Health
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• 제31권4호
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• pp.708-715
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• 1998

Chronic abuse of alcohol can lead to the development of folate deficiency due to inadequate folate intaike, excessive urinary excretion and from effects of ethanol on folate absorption and metabolism . To investigate the effects of alcohol and folate intake on folate metabolism, the rates were raised for 4 and 10 weeks on experimental diets containing 0, 2 8mg folate/kg diet, and were administered 50% ethanol(1.8$m\ell$/kg body weight) three times a week intragastrically. Plasma and tissue folate concentrations were found to be significantly influenced by dietary folate level. In animals fed on folate-deficient diet, concentrations of folate in the plasma, liver and kidney were decreased by 60-89% compared to those on folate-adequate diet, and ther values were further decreased with experimental period. Folate supplementation increased plasma and tissue folate levels significantly by 16-78% compared to those on folate-adequate diet, and the folate levels in the plasma and liver were affected most by the supplementation. Alcohol administration did not seem to influence folate status in the body significantly when animals were raised on folate-deficient diet. However, when rats were fed folate-adequate or folate-supplemented diet, alcohol was shown to decrease plasma and tissue folate concentrations. Among the animals receiving alcohol, folate concentrations in the plasma and tissues were significantly higher when animals fed folate-supplemented diet compared to folate adequate diet. Alcohol seems to exert differential effects on urinary foalte excretion by experimental period it increased urinary folate in the 4-week period, but lowered foalte excretion in the urine when the experimental period was extended to 10 weeks. Alcohol did not seem to influence folate excretion in the feces. These results indicate that folate supplementation might be beneficial in ameliorating the inadequate folate status that might occur with chronic alcoholism.

• Journal of Nutrition and Health
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• 제40권1호
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• pp.14-23
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• 2007

Elevated plasma homocysteine (Hcy) is a risk factor for cognitive dysfunction and Alzheimer disease, although the mechanism is still unknown. Both folate and betaine, a choline metabolite, play essential roles in the remethylation of Hcy to methionine. Choline deficiency may be associated with low folate status and high plasma Hcy. Alterations in DNA methylation also have established critical roles for methylation in development of the nervous system. This study was undertaken to assess the effect of choline and folate deficiency on Hcy metabolism and genomic DNA methylation status of the liver and brain. Groups of adult male Sprague Dawley rats were fed on a control, choline-deficient (CD), folate-deficient (FD) or choline/folate-deficient (CFD) diets for 8 weeks. FD resulted in a significantly lower hepatic folate (23%) (p<0.001) and brain folate (69%) (p<0.05) compared to the control group. However, plasma and brain folate remained unaltered by CD and hepatic folate reduced to 85% of the control by CD (p<0.05). Plasma Hcy was significantly increased by FD $(18.34{\pm}1.62{\mu}M)$ and CFD $(19.35{\pm}3.62{\mu}M)$ compared to the control $(6.29{\pm}0.60{\mu}M)$ (p<0.001), but remained unaltered by CD. FD depressed S-adenosylmethionine (SAM) by 59% (p<0.001) and elevated S-adenosylhomocysteine (SAM) by 47% in liver compared to the control group (p<0.001). In contrast, brain SAM levels remained unaltered in CD, FD and CFD rats. Genomic DNA methylation status was reduced by FD in liver (p<0.05) Genomic DNA hypomethylation was also observed in brain by CD, FD and CFD although it was not significantly different from the control group. Genomic DNA methylation status was correlated with folate stores in liver (r=-0.397, p<0.05) and brain (r = -0.390, p<0.05), respectively. In conclusion, our data demonsoated that genomic DNA methylation and SAM level were reduced by folate deficiency in liver, but not in brain, and correlated with folate concentration in the tissue. The fact that folate deficiency had differential effects on SAM, SAH and genomic DNA methylation in liver and brain suggests that the Hcy metabolism and DNA methylation are regulated in tissue-specific ways.

• Nutrition Research and Practice
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• 제1권2호
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• pp.120-125
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• 2007

Folate is important for multiple metabolic processes such as nucleic acid synthesis and interconversions, and cell division. Folate deficiency may be a risk factor for several pathologies, such as neural tube birth defects, dementia, and cardiovascular diseases. The objectives of this study were to estimate folate intakes and plasma concentrations of young children living in Kwangju, Korea. Three consecutive 24-h food recalls and fasting blood samples were obtained from 24 boys and 30 girls, aged 2-6 y, living in Kwangju, Korea. The daily folate intake ($mean{\pm}SD$) of the children was $146.7{\pm}73.6{\mu}g$ dietary folate equivalents. No differences in folate intakes were observed by gender ($p{\geq}0.05$). The mean folate intakes of the 2 and 3 y old groups were significantly lower (p<0.05) than those of 5 and 6 y old groups. Over half of subjects consumed $mean{\pm}SD$) of all subjects was $19.2{\pm}8.7nmol/L$, and there was no significant difference by age nor gender ($p{\geq}0.05$). No significant correlation was observed between folate intakes and plasma folate concentrations. One subjeci (1.9%) in this study had a plasma folate concentration <6.8 nmol/L, which is indicative of folate deficiency. Approximately 24% of subjects had plasma folate concentrations of 6.8-13.4 nmol/L, which is representative of marginal folate status. In conclusion, some young children may have less than adequate folate status in Korea.

• Journal of Nutrition and Health
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• 제26권1호
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• pp.67-75
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• 1993

Folate and iron nutrition was studied in a total of 122 pregnant, lactaging, and non-pregant, non-lactating Korean women, Serum folate levels were determined microbiologically using Lactobacillus casei(ATCC 7469), and serum iron levels was analyzed colormetrically. The average folate values of pregnant and lactating women were 5.42ng/ml and 4.14ng/ml, which were significantly lower than that of the non-pregnant, non-lactating women(7.06ng/ml). More than 1/3 of the total subjects were found to have serum folate levels lower than 3ng/ml, at which folate nutrition status can be considered inadequate. Serum iron values of pregnant(96.9ug/dl)and lactating women(93.9ug/dl) were not significantly different from that of the non-pregnant, non-lactating women (97.1ug/dl). There were however, more iron-deficient subjects in the pregnant gorup(17%) and the lactating group(19%) than in the non-pregnant, non-lactating group (8%). A statistically significant positive correlation was shown between the levels of serum folate and iron in lactating women(r=.9694, p<0.05). The results of our study document that folate deficiency is a nutritional problem as prevalent as iron deficiency in Korean women, especially during pregnancy and lactation. For these women a routine folate and iron supplementation might be necessary.

• 한국식품영양과학회지
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• 제26권5호
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• pp.983-992
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• 1997

During pregnancy and lactation, folate status is important because folate requirements increase during the periods as well as maternal folate status influences on pregnancy outcome and human milk folate; especially folate deficiency around periconceptional period may induce neural tube defects(NTDs) of fetus. There have been a plenty of evidences that maternal folate status deteriorates during pregnancy of fetus. There have been a plenty of evidences that maternal folate status deteriorates during pregnancy and lactation if folate needed is not sufficiently provided. The Public health Service of the United States recommends all child-bearing is not sufficiently provided. The Public Health Service of the United States recommends all child-bearing women to intake 0.4mg of folate daily, and the Food and Drug Administration the folate status of child-bearing women and to reduce the rate of occurrence of NTDs. Many authors have insisted that the current recommended dietary allowances of folate for Americans are too low to maintain good folate status. There are little data about Korean folate status including pregant and lactating women. A couple of reports indicated that the folate intakes of Korean pregant and lactating women are below the Korean RDAs of folate and serum folate levels of them are subnormal. The authors pregnant and lactating women. Therefore, it is worth to review the assessment methods of folate status of pregnant and lactating women, folate RDAs for them, the relationships between maternal folate status and pregnancy outcome as well as human milk folate, the methods to increase folate intake, and the problems of large dose of folic acid supplementatiion.

• 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.

• 대한두개안면성형외과학회지
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• 제22권1호
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• pp.33-37
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• 2021

Background: Children with cleft lip and/or palate can be undernourished due to feeding difficulties after birth. A vicious cycle ensues where malnutrition and low body weight precludes the child from having the corrective surgery, in the absence of which the child fails to gain weight. This study aimed to identify the proportion of malnutrition, including the deficiency of major micronutrients, namely iron, folate and vitamin B12, in children with cleft lip and/or palate and thus help in finding out what nutritional interventions can improve the scenario for these children. Methods: All children less than 5 years with cleft lip and/or cleft palate attending our institute were included. On their first visit, following were recorded: demographic data, assessment of malnutrition, investigations: complete blood count and peripheral blood film examination; serum albumin, ferritin, iron, folate, and vitamin B12 levels. Results: Eighty-one children with cleft lip and/or palate were included. Mean age was 25.37±21.49 months (range, 3-60 months). In 53% of children suffered from moderate to severe wasting, according to World Health Organization (WHO) classification. Iron deficiency state was found in 91.6% of children. In 35.80% of children had vitamin B12 deficiency and 23.45% had folate deficiency. No correlation was found between iron deficiency and the type of deformity. Conclusion: Iron deficiency state is almost universally present in children with cleft lip and palate. Thus, iron and folic acid supplementation should be given at first contact to improve iron reserve and hematological parameters for optimum and safe surgery.