• Journal of Nutrition and Health
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• v.40 no.1
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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.

• Clinical and Experimental Pediatrics
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• v.49 no.5
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• pp.475-481
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• 2006

Purpose : As the prevalence of childhood obesity is increasing, hypertension, hyperlipidemia, insulin resistance and diabetes mellitus have become problems. High homocysteine levels and low vitamin $B_{12}$ supplementation are acknowledged to have a role in coronary artery disease, but there are few studies on homocysteine, insulin and vitamin $B_{12}$ levels in obese children. We aimed to study whether homocysteine, insulin, vitamin $B_{12}$, folic acid levels could have any difference and relation in obese children. Methods : The disease group consisted of 27 children from 8 to 11 years old, whose obesity index was over 130. The control group consisted of 30 healthy children of the same age group. Obesity index and body mass index were calculated by height and body weight of the children, and their systolic and diastolic blood pressures at resting state were checked. Total cholesterol, triglyceride, homocysteine, insulin, vitamin $B_{12}$, folic acid levels were studied after 10 hours of fasting. Intracellular fluid, extracellular fluid, protein, mineral, muscle mass, lean body fat, fat mass and fat percentages were checked by bioelectrical impedance. Results : Homocysteine levels were higher in obese children($8.1{\pm}2.1{\mu}mol/mL$ vs. $4.9{\pm}1.0{\mu}mol/mL$). Insulin levels were also higher in obese children($26.8{\pm}11.2{\mu}IU/mL$ vs. $12.5{\pm}5.24{\mu}IUl/mL$). Vitamin $B_{12}$ was lower in obese children($798.6{\pm}174.3pg/mL$ vs. $967.8{\pm}405.0pg/mL$). But there was not a difference in the folic acid levels between the two groups. In obese children, systolic blood pressure (r=0.535), triglyceride(r=0.517), total cholesterol(r=0.408), folic acid(r=0.408), vitamin $B_{12}$(r=0.338) and abdomoanl fat %(r=0.306) had a positive correlation. Conclusion : We found definite differences of insulin, homocysteine, and vitamin $B_{12}$ plasma levels in obese children, but we need more study to use those parameters as risk factors of metabolic syndrome in pediatric obese patients.

• The Journal of Internal Korean Medicine
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• v.33 no.3
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• pp.243-256
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• 2012

Objectives : This clinical study was done to examine metabolic syndrome (MS) and plasma homocysteine (HCY) level in patients with silent lacunar infarction (SLI) and in normal controls. Methods : A total of 154 patients, who were over 20 years of age and visited the stroke prevention check-up center of a university hospital from December 2006 to December 2010, were examined by brain CT or brain MRI, and classified into two groups. We compared the components of MS and HCY levels between patients with SLI (n=74) and normal controls (n=80). Modified ATP III definition was used for diagnosis of MS while Korean standard for waist circumference was used. Results : Prevalence of MS was significantly higher in the SLI group than the normal group. HCY was also significantly higher in the SLI group than the noraml, and the odds ratio (OR) for SLI, comparing high HCY level (${\geq}10{\mu}mol/L$) with low HCY level ($<10{\mu}mol/L$), was 3.64 (95% confidence interval (CI); 1.81-7.29, p<.0001). However, there was no correlation between MS and HCY in the SLI group. Prevalence of diabetes and hypertension (HT) was higher in the SLI group than the normal group, but there was no significant difference in blood lipids level between the SLI and normal groups. Of note, HT itself was enough to be an independent risk factor for SLI (OR; 4.58, 95% CI; 1.91-11.01, p=0.001). Body mass index, waist circumference, waist-hip ratio and visceral fat area were significantly higher in the SLI than normal group, and visceral fat area was enough to be an independent risk factor for SLI (OR; 2.41, 95% CI; 1.04-5.59, p=0.040). Conclusions : SLI is shown to have significant correlation with HCY and prevalence of MS, however there is no relationship between HCY and prevalence of MS in patients with SLI.

• Nutrition Research and Practice
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• v.7 no.2
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• pp.109-114
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• 2013

We compared the preventive capacity of high intakes of vitamin C (VC) and vitamin E (VE) on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet. Thirty-two Wistar rats received the low fat (10% of total calories) Lieber-DeCarli liquid diet as follows: either ethanol alone (Alc group, 36% of total calories) or ethanol in combination with VC (Alc + VC group, 40 mg VC/100 g body weight) or VE (Alc + VE group, 0.8 mg VE/100 g body weight). Control rats were pair-fed a liquid diet with the Alc group. Ethanol administration induced a modest increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), conjugated dienes (CD), and triglycerides but decreased total radical-trapping antioxidant potential (TRAP) in plasma. VE supplementation to alcohol-fed rats restored the plasma levels of AST, CD, and TRAP to control levels. However, VC supplementation did not significantly influence plasma ALT, AST, or CD. In addition, a significant increase in plasma aminothiols such as homocysteine and cysteine was observed in the Alc group, but cysteinylglycine and glutathione (GSH) did not change by ethanol feeding. Supplementing alcohol-fed rats with VC increased plasma GSH and hepatic S-adenosylmethionine, but plasma levels of aminothiols, except GSH, were not influenced by either VC or VE supplementation in ethanol-fed rats. These results indicate that a low-fat ethanol diet induces oxidative stress and consequent liver toxicity similar to a high-fat ethanol diet and that VE supplementation has a protective effect on ethanol-induced oxidative stress and liver toxicity.

• Tuberculosis and Respiratory Diseases
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• v.62 no.3
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• pp.211-216
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• 2007

Hyperhomocysteinemia is an independent risk factor for cardiovascular, cerebrovascular and peripheral vascular diseases that are complicated by atherosclerosis and a thromboembolism. An increased level of plasma homocysteine develops from a genetic defect in the of enzyme for the homocysteine metabolism or a vitamin deficiency. Hyperhomocysteinemia has direct toxic effect on the vascular endothelium and causes damages to the antithrombotic action of vascular endothelial cells. Most cases of hyperhomocysteinemia are asymptomatic, but cardiopulmonary or cerebrovascular incidents developin rare cases. In the case of a thromboembolism with an unknown cause, hyperhomocysteinemia should be considered in a differential diagnosis. The authors report a case of pulmonary thromboembolism in a patient with hyperhomocysteinemia with a review of the relevant literature.

• Food Science of Animal Resources
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• v.34 no.1
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• pp.106-114
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• 2014

Folic acid, one of the B group of vitamins, is an essential substance for maintaining the functions of the nervous system, and is also known to decrease the level of homocysteine in plasma. Homocysteine influences the lowering of the cognitive function in humans, and especially in elderly people. In order to determine the strains with a strong capacity to produce folic acid, 190 bacteria were isolated from various kinds of jeotgal and chungkuk-jang. In our test experiment, JA71 was found to contain $9.03{\mu}g/mL$ of folic acid after 24 h of incubation in an MRS broth. This showed that JA71 has the highest folic acid production ability compared to the other lactic acid bacteria that were isolated. JA71 was identified as Lactobacillus plantarum by the result of API carbohydrate fermentation pattern and 16s rDNA sequence. JA71 was investigated for its physiological characteristics. The optimum growth temperature of JA71 was $37^{\circ}C$, and the cultures took 12 h to reach pH 4.4. JA71 proved more sensitive to bacitracin when compared with fifteen different antibiotics, and showed most resistance to neomycin and vancomycin. Moreover, it was comparatively tolerant of bile juice and acid, and displayed resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus with restraint rates of 60.4%, 96.7%, and 76.2%, respectively. These results demonstrate that JA71 could be an excellent strain for application to functional products.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1478-1487
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• 2019

Ulcerative colitis (UC), a chronic inflammatory bowel disease, substantially impacts patients' health-related quality of life. In this study, an effective strategy for discovering high-efficiency probiotics has been developed. First, in order to survive in the conditions of the stomach and intestine, high bile salt-resistant and strong acid-resistant strains were screened out from the fecal flora of healthy adults. Next, the probiotic candidates were rescreened by examining the induction ability of IL-10 (anti-inflammatory factor) production in dextran sodium sulfate (DSS)-induced colitis mice, and Lactobacillus sakei 07 (L07) was identified and selected as probiotic P. In the end, fourteen bifidobacterium strains isolated from stools of healthy males were examined for their antimicrobial activity. Bifidobacterium bifidum B10 (73.75% inhibition rate) was selected as probiotic B. Moreover, the colonic IL-6 and $TNF-{\alpha}$ expression of the DSS-induced colitis mice treated with L. sakei 07 (L07) - B. bifidum B10 combination (PB) significantly decreased and the IL-10 expression was up-regulated by PB compared to the DSS group. Furthermore, Bacteroidetes and Actinobacteria decreased and Firmicutes increased in the DSS group mice, significantly. More interestingly, the intestinal flora biodiversity of DSS colitis mice was increased by PB. Of those, the level of B. bifidum increased significantly. The Bacteriodetes/Firmicutes (B/F) ratio increased, and the concentration of homocysteine and LPS in plasma was down-regulated by PB in the DSS-induced colitis mice. Upon administration of PB, the intestinal permeability of the the DSS-induced colitis mice was decreased by approximately 2.01-fold. This method is expected to be used in high-throughput screening of the probiotics against colitis. In addition, the L. sakei 07 - B. bifidum B10 combination holds potential in UC remission by immunomodulatory and gut microbiota modulation.

• Clinical and Experimental Pediatrics
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• v.53 no.3
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• pp.329-334
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• 2010

Purpose : The neonatal screening test for homocystinuria primarily measures methionine by using a dried blood specimen. We investigated the incidence and clinical manifestations of homocystinuria, isolated hypermethioninemia, and transient hypermethioninemia among patients with hypermethioninemia on a neonatal screening test. Methods : We performed a retrospective study of 58 patients transferred to Shoonchunhyang Hospital because of hypermethioninemia on a neonatal screening test between January 1996 and August 2009. We analyzed the level of amino acid from plasma and urine, as well as blood homocysteine.Results : Almost half of the 58 patients were identified as normal. Whereas only 3 (5.1%) patients were identified as having homocystinuria, about 20.7% (12 cases) of the patients had isolated hypermethioninemia. The ages of these two groups at initial detection of hypermethioninemia on plasma amino acid analysis were $50.0{\pm}22.5$ days and $34.9{\pm}13.5$ days, respectively. Both groups were put on diets, and they showed a normal developmental course as a result of early diagnosis and treatment. Conclusion : Hypermethioninemia without homocystinuria, referred to as isolated hypermethioninemia, was also detected. Thus, the impact of hypermethioninemia on a neonatal screening test should be carefully evaluated through analysis of amino acid levels from blood and urine, and we need to detect and treat an early stage of isolated hypermethioninemia as well as homocystinuria.

• 대한예방의학회:학술대회논문집
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• 2005.10a
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• pp.359-359
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• 2005

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4383-4386
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• 2015

Background: The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for natural methylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folate metabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectal cancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatous polyp occurrence. Materials and Methods: 164 controls and 38 adenomatous polyp cases were analysed to determine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, synthetic pteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype. Results: In controls and cases, 7.3 and 18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatous polyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intake and the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp. However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPII CT genotype subjects (p=0.037). Conclusions: The findings suggest that C1561T-GCPII variation may be associated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variant gene, its expression product and/or folate substrates.