We investigated the effects of dietary folate supplementation on plasma homocysteine, vitamin B12 and hepatic levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in diet-induced hyperhomocysteinemic rats. All animals were fed 0.3% homocysteine diet for 2 weeks, then they were placed either on a 0.3% homocystine or no homocystine with or without 8 mg/kg folate diet for 8 weeks. Homocystine diet induced hyperhomocysteinemia up to 3.5-fold at 10 weeks (28.0+/-4.8 micromol/l vs. 7.9+/-0.3 micromol/l). Dietary folate supplementation caused a significant decrease in plasma homocysteine levels which had been increased by a homocystine-diet. Also, dietary folate supplementation made them return to control levels at 4 wk when the diet was free of homocystine. Plasma folate levels were markedly decreased with homocystine diet with no folate supplementation. Plasma vitamin B12 did not differ between groups. Dietary homocystine increased hepatic levels of SAM in folate supplementation group at 10 weeks (p<0.05). Dietary folate supplementation increased hepatic levels of SAM/SAH ratios in homocystine group (p<0.05). In conclusion, dietary folate supplementation can effectively ameliorate the detrimental effects of hyperhomocysteinemia.mia.
Animals ; Diet ; Folic Acid* ; Homocysteine ; Homocystine* ; Hyperhomocysteinemia* ; Metabolism* ; Plasma ; Rats* ; S-Adenosylhomocysteine ; S-Adenosylmethionine* ; Vitamin B 12

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 B12 deficiency. It has been hypothesized that a greater methyl group supply could lead to compensation for vitamin B12 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 B12-deficient rats. Sprague-Dawley rats were fed diets containing either 0 or 100 microg (daily dietary requirement) vitamin B12/kg diet with either 2 mg (daily dietary requirement) or 100 mg FA/kg diet for six weeks. Vitamin B12-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 B12 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 B12-deficiency but did not change SAM and SAH, the main biomarkers of methylating reaction.
Animals ; Biomarkers ; Brain ; Compensation and Redress ; Diet ; Dietary Supplements ; DNA Methylation ; Folic Acid ; Homocysteine ; Hyperhomocysteinemia ; Methionine ; Plasma ; Rats ; Rats, Sprague-Dawley ; S-Adenosylhomocysteine ; S-Adenosylmethionine ; Vitamin B 12 Deficiency ; Vitamins

BACKGROUND/OBJECTIVE: The aim of this study was to examine the effect of high dietary methionine (Met) consumption on plasma and hepatic oxidative stress and dyslipidemia in chronic ethanol fed rats. MATERIALS/METHODS: Male Wistar rats were fed control or ethanol-containing liquid diets supplemented without (E group) or with DL-Met at 0.6% (EM1 group) or 0.8% (EM2 group) for five weeks. Plasma aminothiols, lipids, malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase were measured. Hepatic folate, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS: DL-Met supplementation was found to increase plasma levels of homocysteine (Hcy), triglyceride (TG), total cholesterol (TC), and MDA compared to rats fed ethanol alone and decrease plasma ALT. However, DL-Met supplementation did not significantly change plasma levels of HDL-cholesterol, cysteine, cysteinylglycine, and glutathione. In addition, DL-Met supplementation increased hepatic levels of folate, SAM, SAH, and SAM:SAH ratio. Our data showed that DL-Met supplementation can increase plasma oxidative stress and atherogenic effects by elevating plasma Hcy, TG, and TC in ethanol-fed rats. CONCLUSION: The present results demonstrate that Met supplementation increases plasma oxidative stress and atherogenic effects by inducing dyslipidemia and hyperhomocysteinemia in ethanol-fed rats.
Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Cholesterol ; Cysteine ; Diet ; Dyslipidemias* ; Ethanol ; Folic Acid ; Glutathione ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Male ; Malondialdehyde ; Methionine* ; Oxidative Stress* ; Plasma ; Rats* ; Rats, Wistar ; S-Adenosylhomocysteine ; S-Adenosylmethionine ; Triglycerides

BACKGROUND/OBJECTIVE: The aim of this study was to examine the effect of high dietary methionine (Met) consumption on plasma and hepatic oxidative stress and dyslipidemia in chronic ethanol fed rats. MATERIALS/METHODS: Male Wistar rats were fed control or ethanol-containing liquid diets supplemented without (E group) or with DL-Met at 0.6% (EM1 group) or 0.8% (EM2 group) for five weeks. Plasma aminothiols, lipids, malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase were measured. Hepatic folate, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS: DL-Met supplementation was found to increase plasma levels of homocysteine (Hcy), triglyceride (TG), total cholesterol (TC), and MDA compared to rats fed ethanol alone and decrease plasma ALT. However, DL-Met supplementation did not significantly change plasma levels of HDL-cholesterol, cysteine, cysteinylglycine, and glutathione. In addition, DL-Met supplementation increased hepatic levels of folate, SAM, SAH, and SAM:SAH ratio. Our data showed that DL-Met supplementation can increase plasma oxidative stress and atherogenic effects by elevating plasma Hcy, TG, and TC in ethanol-fed rats. CONCLUSION: The present results demonstrate that Met supplementation increases plasma oxidative stress and atherogenic effects by inducing dyslipidemia and hyperhomocysteinemia in ethanol-fed rats.
Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Cholesterol ; Cysteine ; Diet ; Dyslipidemias* ; Ethanol ; Folic Acid ; Glutathione ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Male ; Malondialdehyde ; Methionine* ; Oxidative Stress* ; Plasma ; Rats* ; Rats, Wistar ; S-Adenosylhomocysteine ; S-Adenosylmethionine ; Triglycerides

Folate and vitamin B12 are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin B12 deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folate-sufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin B12-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 +/- 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 +/- 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 +/- 9.6 nmol/L) compared with rats fed FD and FDH (21.1 +/- 1.4 nmol/L, 22.0 +/- 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin B12 deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin B12 deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.
Animals ; Biomarkers ; Brain ; Carbon ; Diet ; DNA Methylation ; Folic Acid ; Homocysteine ; Homocystine ; Humans ; Hyperhomocysteinemia ; Liver ; Male ; Methylation ; Neurodegenerative Diseases ; Plasma ; Rats ; S-Adenosylhomocysteine ; S-Adenosylmethionine ; Vitamin B 12 ; Vitamin B 12 Deficiency ; Vitamins

Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.
Aging ; Amino Acids, Sulfur ; Animals ; Child, Preschool ; Cystathionine ; Cysteine ; Down-Regulation ; Glutathione ; Homocysteine ; Humans ; Infant ; Male* ; Metabolism* ; Metabolomics ; Methionine ; Mice* ; Plasma ; S-Adenosylhomocysteine ; S-Adenosylmethionine ; Sulfur* ; Taurine ; Up-Regulation

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 un-dertaken 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 signi-ficantly increased by FD ( 18.34 +/- 1.62 micrometer) and CFD ( 19.35 +/-3.62 micrometer) compared to the control ( 6.29 +/-0.60 micrometer) ( p < 0.001) , but remained unaltered by CD. FD depressed S-adenosylmethionine ( SAM) by 59% ( p < 0.001) and ele-vated S-adenosylhomocysteine ( SAH) 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 signifi-cantly 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 demonstrated 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.
Adult ; Alzheimer Disease ; Animals ; Betaine ; Brain ; Choline ; Choline Deficiency ; Diet ; DNA Methylation* ; DNA* ; Folic Acid ; Homocysteine* ; Humans ; Liver ; Male ; Metabolism ; Methionine ; Methylation ; Nervous System ; Plasma* ; Rats* ; Rats, Sprague-Dawley ; Risk Factors ; S-Adenosylhomocysteine ; S-Adenosylmethionine

No abstract available.
Atherosclerosis* ; Homocysteine*

Background: Preeclampsia is a major cause of maternal and perinatal mortality and morbidity, affecting 5 - 6% of all pregnancies. Recently, homocysteine (Hcy), a metabolite of amino acid methionine has been postulated producing oxidative stress, endothelial cell dysfunction, and alterations associated with preeclampsia. It is unclear whether high concentration of circulating Hcy causes preeclampsia, or whether this is a secondary phenomenon of metabolic alterations resulting from the disorder. Objectives: (1) Determining blood Hcy concentration in pregnancies in various severities of preeclampsia. (2) Discover the relationships between serum Hcy and other biological markers in preeclampsia. Subjects and method: This descriptive cross-sectional study consisted of 3 groups of pregnancies admitted to Thanh Nhan Hospital: 24 normal pregnant women, 28 pregnancies with non-serious preeclampsia, and 27 pregnancies with serious preeclampsia. Concentrations of blood Hcy of all participants were assayed by a competition fluorescence immunoassay (FPIA). Results: The mean concentration of serum Hcy during normal pregnancy was 5.2+/-1.0micromol/L compared with 7.1+/-1.8micromol/L among pregnancies with non-serious preeclampsia, and 11.7+/-2.9micromol/L among pregnancies with serious preeclampsia. Serum Hcy increased in pregnancies with renal dysfunction, elevated serum uric acid, and injuries of liver cells. Conclusion: Concentration of the serum Hcy in pregnancies with serious preeclampsia is significantly higher than that of pregnancies with non-serious preeclampsia, and the serum Hcy in pregnancies with non-serious preeclampsia is significantly higher than that of normal pregnancies. There are relationships between elevated serum Hcy in preeclampsia with level of kidney failure, injury of liver and increased levels of serum uric acid.
Homocysteine ; Preeclampsia

68 patients with stroke treated at Hue Central Hospital from March to June 2004. Risk factors as hypertension, smoking were evaluated. Patients had clinical and paraclinical examination such as CT scanning of cerebral skull, blood formula. Blood level of homocystein was estimated: The prevalence of stroke in gender male/female was 1.64/1 with 61.76% men and 38.24 women. Hypertension 85.24%, men/women 1.64/1. Smoke 67.65%. Blood level of homocystein increases in stroke by the rate of 77.94%, as for hemorrhagic stroke was 65.63%, for ischemic stroke was 88.57%. Stroke rate increased by age, especially after 55 years old. A positive correlation between blood level of homocystein and hematocrite was notified
Stroke ; Homocysteine ; blood