• Nutrition Research and Practice
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• v.14 no.4
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• pp.309-321
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• 2020

BACKGROUND/OBJECTIVES: The present study aimed to evaluate the effects of folic acid supplementation in high-fructose-induced hepatic steatosis and clarify the underlying mechanism of folic acid supplementation. MATERIALS/METHODS: Male SD rats were fed control, 64% high-fructose diet, or 64% high-fructose diet with folic acid for eight weeks. Plasma glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lipid profiles, hepatic lipid content, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS: The HF diet significantly increased hepatic total lipid and triglyceride (TG) and decreased hepatic SAM, SAH, and SAM:SAH ratio. In rats fed a high fructose diet, folic acid supplementation significantly reduced hepatic TG, increased hepatic SAM, and alleviated hepatic steatosis. Moreover, folic acid supplementation in rats fed high fructose enhanced the levels of phosphorylated AMP-activated protein kinase (AMPK) and liver kinase B (LKB1) and inhibited phosphorylation of acetyl coenzyme A carboxylase (ACC) in the liver. CONCLUSIONS: These results suggest that the protective effect of folic acid supplementation in rats fed high fructose may include the activation of LKB1/AMPK/ACC and increased SAM in the liver, which inhibit hepatic lipogenesis, thus ameliorating hepatic steatosis. The present study may provide evidence for the beneficial effects of folic acid supplementation in the treatment of non-alcoholic fatty liver disease.

• Journal of Nutrition and Health
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• v.38 no.3
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• pp.211-218
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• 2005

Elevated homocysteine concentration is known to be related to placental abruption, spontaneous abortion, and many adverse pregnancy outcomes. The purpose of this study was to investigate the effects of folic acid supplementation ($1000{\cal}ug$ per day) and 5, 10 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype on serum homocysteine and B vitamin levels in 50 infertile women ($31.2{\pm}3.2\;years$). Blood sampling was performed at baseline and at the end of folic acid supplementation period. In infertile women, serum folate and vitamin $B_{12}$ concentrations were significantly higher in post-supplementation than those in pre-supplementation. Serum homocysteine concentration was significantly lower in post-supplementation than that in pre-supplementation. However, serum homocysteine levels were still higher in the T/T genotype than those in the C/C or C/T even after folic acid supplementation. Serum homo-cysteine was inversely related to serum folate in T/T homozygotes at baseline and at the end of folic acid supplementation. These results suggest that folic acid supplementation is needed for infertile women to improve their vitamin status and also to reduce the risk of hyperhomocysteinemia. These effects were different according to their MTHFR C677T genotypes. Therefore, further studies are necessary to determine the optimal level of supplementation of folic acid by MTHFR genotypes.

• Journal of Preventive Medicine and Public Health
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• v.52 no.4
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• pp.205-213
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• 2019

Objectives: Maternal folic acid supplementation is considered mandatory in almost every country in the world to prevent congenital malformations. However, little is known about the association of maternal folic acid intake with the occurrence of childhood cancer. Hence, this study aimed to determine the effects of maternal folic acid consumption on the risk of childhood cancer. Methods: A total of 158 related articles were obtained from PubMed, Google Scholar, Scopus, and ProQuest using standardized keywords, of which 17 were included in the final review. Results: Eleven of the 17 articles showed a significant protective association between maternal folic acid supplementation and childhood cancer. Using a random-effects model, pooled odds ratios (ORs) showed a protective association between maternal folic acid supplementation and childhood acute lymphoblastic leukaemia (OR, 0.75; 95% confidence interval [CI], 0.66 to 0.86). However, there was no significant association between maternal folic acid supplementation and acute myeloid leukaemia (OR, 0.70; 95% CI, 0.46 to 1.06) or childhood brain tumours (OR, 1.02; 95% CI, 0.88 to 1.19). Conclusions: Maternal folic acid supplementation was found to have a protective effect against childhood acute lymphoblastic leukaemia. Thus, healthcare professionals are recommended to provide regular health education and health promotion to the community on the benefits of folic acid supplementation during pregnancy.

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.495-502
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• 2005

This study was performed to investigate effects of dietary folic acid supplementation on plasma homocysteine levels, thiobarbituric acid reactive substance s (TBARS) level s and liver SAM/SAH ratio in hyperhomocysteinaemia-induced pregnant rats. Forty-two female Sprague-Dawley rats were divided three groups (C: control diet, HFD: $0.3\%$ homocystine and 0 mg folic acid diet, HFS: $0.3\%$ homocystine and 8 mg/kg folic acid diet) according to homocystine and folic acid levels in the diet. They were fed experimental diets for 5 weeks prior to the mating and also during the entire period of pregnancy till gestational day 20. Dietary folic acid supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine-diet, with a concomitant increase in plasma and liver folate levels. Liver TBARS levels in homocysteine-folic acid-deficient group (HFD) were higher than those in control group. Dietary folic acid supplementation increased hepatic SAM/SAM ratio in homocysteine-folic acid- sopplemetantion group (HFS) when compared to the HFD (p < 0.05). These data suggest that folate depletion and elevated plasma homocysteine may promote oxidative stress in rat livers and influence the remethylation cycle of the homocysteine metabolism detrimentally. In conclusion, dietary folic acid supplementation was found to be effective for lowering plasma homocysteine levels, relieving oxidative stress, and improving the methylation status in the body.

• 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.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.327-333
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• 2017

BACKGROUND/OBJECTIVES: Complications of diabetes, such as cardiovascular disease, are associated with increased mortality among type 2 diabetes mellitus patients. Homocysteine has been recently identified as a predictor of cardiovascular disease-related complications in diabetes. We investigated whether or not supplementation with folic acid tablets can lower homocysteine levels and improve parameters related with vascular complications. SUBJECTS/METHODS: We conducted a non-randomized 8-week trial involving postmenopausal diabetic women (n = 25) supplemented with $800{\mu}g$ of folic acid ($400{\mu}g$ twice a day) daily. Subjects' serum levels of folate, homocysteine, and vitamin $B_{12}$ were measured, along with vascular function and brachial-ankle pulse wave velocity. RESULTS: Folic acid supplementation significantly increased serum folate levels (P < 0.0001), reduced homocysteine levels (P < 0.0001), and increased vitamin $B_{12}$ levels (P = 0.0063). There were significant decreases in low-density lipoprotein cholesterol levels as well as the ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein cholesterol. Brachial-ankle pulse wave velocities were not altered by supplementation. Changes in serum vitamin $B_{12}$ after folic acid supplementation were negatively correlated with changes in brachial-ankle pulse wave velocity. CONCLUSIONS: In this study on postmenopausal Korean women with type 2 diabetes mellitus, folic acid supplementation reduced serum homocysteine levels, increased serum folate and vitamin $B_{12}$ levels, and lowered lipid parameters.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.240-246
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• 2017

BACKGROUND/OBJECTIVES: Folic acid supplementation before pregnancy is known to significantly reduce the risk of having a baby with neural tube defects (NTDs). Therefore, it is important for women to be aware of the effects of folic acid supplementation before pregnancy. The purpose of this study was to investigate the awareness and preconceptional use of folic acid and to assess the current knowledge about folic acid among low-income pregnant women in Korea. SUBJECTS/METHODS: A questionnaire survey was conducted in 2012. Five hundred pregnant women were selected from the waiting list for the Nutriplus program implemented in public health centers using a multistage clustered probability sampling design. Data from 439 women were analyzed after excluding ones with incomplete answers. RESULTS: Among women who responded to the questionnaire, 65.6% had heard of folic acid before pregnancy, and 26.4% reported on the preconceptional use of folic acid. Women with a university degree or higher education were more likely to be aware of folic acid and to take folic acid in the preconception period. In a multivariate logistic regression, when age, education level, household income, employment status, gravidity, parity, and folic acid awareness were included in the model, folic acid awareness was a strong predictor of preconceptional folic acid use. As of interview, 85.4% and 77.7% of women were aware of the NTD-preventive role of folic acid and the appropriate time to take folic acid, respectively. The main sources of information on folic acid were healthcare professionals (41.2%), friends and family members (31.2%), and the media (26.5%). CONCLUSIONS: Our results suggest that public health strategies are needed to increase the preconceptional use of folic acid among Korean women.

• Korean Journal of Poultry Science
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• v.22 no.4
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• pp.213-221
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• 1995

Five experiments were conducted to evaluate the effect of dietary supplemental folic acid(FA) in starting broiler chicks. In the first two experiments, basal diets based on corn and soybean meal contained 0.6 mg/kg FA but no supplemental methionine or choline. At 18 d of age, chicks showed curvilinear responses to folic acid supplementation with maximum growth and feed efficiencies at 1.45 mg/kg FA diet. The liver FA response was also curvilinear but reached a plateau at 1.70 mg/kg FA diet. The basal diet for 3 additional experiments contained soybean meal that had been washed with methanol to remove most of the choline. The diet contained only 0.6 mg /kg folic acid and 754 mg /kg choline. Chicks exhibited a larger growth response to folic acid at low choline levels as evidenced by a significant FA x choline interaction. FA supplementation increased but then decreased valgus leg deformity. Choline supplementation also decreased the incidences of valgus and varus leg deformities and decreased bone ash and increased the incidence of tibial dyschondroplasia. It is concluded that chicks fed diets based on practical ingredients require from 1.45 to 1.70 mg /kg FA diet and also 1.60 mg/kg FA when choline is offered near the NRC recommended level of 1,300 mg/kg.

• 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.

• Women's Health Nursing
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• v.29 no.4
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• pp.291-301
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• 2023

Purpose: This study aimed to investigate the current status of effective folic acid intake and the level of folic acid knowledge of Chinese pregnant women and to analyze the relationship between effective folic acid intake and folic acid knowledge. Methods: From November 2021 to May 2022, 140 pregnant women at Yantai Yuhuangding Hospital in the Chinese province of Shandong, answered questions about their general characteristics, folic acid intake, and folic acid knowledge. The data were analyzed using the t-test, chi-square test, and logistic regression analysis, and were presented with frequency with percentage or mean±standard deviation. Results: Only 16.4% of the pregnant women (n=23) took folic acid effectively, using the following four criteria. Of all pregnant women who took folic acid, 72.2% took folic acid starting 1 month before pregnancy, 70.8% took folic acid up to 3 months after pregnancy, 36.8% took 400 ㎍ every time, and 78.6% took folic acid more than 24 days every month. The score for folic acid knowledge was relatively high (5.61±2.18 on a scale of 0-9). A higher folic acid knowledge score correlated with more effective folic acid intake (t=4.10, p<.001). Conclusions: Our study shows that the current recommendations to prevent neural tube defects through effective folic acid intake supplementation are not being fully implemented in China. Furthermore, folic acid knowledge was positively correlated with the effectiveness of its intake. Future education related to effective folic acid intake should emphasize the four methods of effective folic acid intake, especially regarding the recommended dose of 400 ㎍ every time.