Homocysteine Levels In Postmenopausal Women Research Articles

Associations between B vitamin and amino acid intake, MTHFR genotype, atherogenic indices, and homocysteine levels in postmenopausal women

AbstractIt has been hypothesized that insufficiency of one-carbon metabolism may aggravate lipid metabolism disturbances. Lipid metabolism abnormalities and metabolic syndrome (MetS)—which is associated with abnormally high levels of triglycerides (TG) and low levels of high-density lipoproteins (HDL)—often occur in postmenopausal women. The purpose of this study was thus to determine the relationships between amino acid and B vitamin intake, MTHFR genotype, lipid profile, and atherogenic indices in postmenopausal women.131 postmenopausal women were enrolled for the study. The mean macronutrient, amino acid, and B vitamin intake was evaluated using dietary records. Lipid profile and concentrations of apolipoprotein A1 (ApoA1) and B (ApoB) in serum were measured using the colorimetric method. The total homocysteine (tHcy) and glutathione (GSH) level in plasma were measured using high-performance liquid chromatography. MTHFR genotype (rs1801133) was determined using a single tube TaqMan SNP Genotyping Assay. We calculated atherogenic indices, such as Castelli's risk index I and II (CRI-I and CRI-II), the atherogenic coefficient (AC), and the TG/HDL ratio.No association was found between MetS and tHcy or GSH concentrations. MTHFR genotype and folate intake also did not affect tHcy, GSH, lipid profile, or atherogenic indices. Subjects with tHcy levels over the median had lower total protein intake, lower animal protein/plant protein ratio, lower protein/carbohydrates ratio, and higher amino acid intake (methionine, lysine, arginine, glycine, and tryptophan) than did subjects with lower tHcy levels. Women who failed to meet their vitamin B12 intake needs had almost 40% higher levels of tHcy than women who did met those needs.MTHFR genotype, folate intake, and tHcy levels in plasma are not associated with lipid metabolism in postmenopausal women. tHcy levels may depend on the intake of vitamin B12, and of protein or particular amino acids.The project was financed by the National Science Centre, Poland (grant number 2015/17/N/NZ9/04133).

Does genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis

Objective: To perform a meta-analysis examining the effects of genistein on homocysteine and lipid levels in postmenopausal women.Methods: We systematically searched the PubMed, MEDLINE, and Cochrane Library databases and the ClinicalTrials.gov website for studies. We performed a meta-analysis using weighted mean differences (WMD) and 95% confidence intervals in a random-effects model. We assessed between-study heterogeneity using the Cochran’s Q and I2 statistics.Results: Eight randomized, controlled trials with a total of 476 subjects were included in the meta-analysis. Compared with placebos, genistein was effective in reducing plasma levels of homocysteine (WMD, −0.58 μmol/l; p = 0.001), and increasing high density lipoprotein (HDL) cholesterol levels (WMD, 4.9 mg/dl; p = 0.0002). Subgroup analyses revealed that genistein significantly decreased the levels of low density lipoprotein (LDL) cholesterol (WMD, −16.90 mg/dl; p = 0.01), total cholesterol (WMD, −15.83 mg/dl; p = 0.008), and triglycerides (WMD, −46.58 mg/dl; p = 0.03) in postmenopausal women with metabolic syndrome, but had no significant effects in those with no metabolic syndrome.Conclusions: Our meta-analysis demonstrates that genistein significantly reduces homocysteine levels and increases HDL cholesterol levels in postmenopausal women. Genistein also significantly decreases LDL cholesterol, total cholesterol and triglyceride levels in postmenopausal women with metabolic syndrome.

Beneficial effects of Lactobacillus plantarum on glycemia and homocysteine levels in postmenopausal women with metabolic syndrome

ObjectiveMetabolic syndrome (MetS) in postmenopausal women is an important risk factor for cardiovascular morbidity, especially stroke and coronary heart disease and mortality. Preventing and treating MetS would be useful in preventing disability and promoting normal aging. Previous human studies have found some beneficial effects of Lactobacillus species on some isolated parameters of MetS. Nevertheless, we are not aware, to date, of any study which has verified the influence of probiotics in patients with MetS. Therefore, the aim of the present study was to evaluate the influence of fermented milk with L. plantarum in the classical parameters related to MetS, as well as in other parameters related to cardiovascular risk in postmenopausal women. MethodsTwenty-four individuals were paired by age, ethnicity, and body mass index in two groups: Non-fermented milk (NFM = 12) 80 mL/d and fermented milk (FM = 12) 80 mL/d. Anthropometric and blood pressure measurements, biochemical, inflammatory, and immunologic biomarkers were measured. ResultsTotal cholesterol and γ-glutamyltranspeptidase had a significant reduction both in NFM (P = 0.043 and P = 0.036, respectively) and FM groups (P = 0.010 and P = 0.018, respectively) after 90 d, whereas low-density lipoprotein cholesterol showed a significant reduction in NFM group (P = 0.002) and trend in the FM group (P = 0.092). Glucose and homocysteine levels showed a significant reduction in the FM group compared with the NFM group (P = 0.037 and P = 0.019, respectively). In relation to inflammatory biomarkers, there was a significant decrease in interleukin-6 both in NFM (P = 0.032) and in FM (P = 0.001) groups. ConclusionFM with L. plantarum showed more favorable results than NFM in relation to cardiovascular risk factors in postmenopausal women with MetS.

Low calcium intake is associated with high plasma homocysteine levels in postmenopausal women

Nutritional interventions targeting homocysteine remain controversial, and further nutritional research is warranted. We thus sought to explore the determinants of plasma homocysteine other than B-group vitamins. This cross-sectional study surveyed the nutritional status of 713 Japanese postmenopausal women using a semiquantitative food frequency questionnaire. Associations between total energy, protein, fat, carbohydrate, and vitamin A and K intakes and homocysteine were insignificant. Mean homocysteine in the second (536.1 ± 34.7 mg/day) and third (712.9 ± 115.6 mg/day) tertiles of calcium intake were lower than in the first tertile (379.6 ± 76.6 mg/day) by -0.57 nmol/mL (95 % confidence interval, -1.10 to-0.04, p = 0.04) and -1.18 nmol/mL (-1.76 to -0.60, p<0.01), respectively, after adjustment for lifestyle and clinical factors (trend p\0.01). Mean homocysteine in those with dietary calcium intake above the median (>536 mg/day) were lower regardless of the folic acid concentration; the differences were -1.59 nmol/mL (-2.33 to -0.85, p = 0.02) and -0.75 nmol/mL (-1.37 to-0.12, p<0.01) for the high (<7.8 ng/mL) and low folic acid groups, respectively. There was no significant association between calcium and folic acid (p = 0.08). In conclusion, further prospective research to confirm our findings is needed for the development of nutritional inventions targeting homocysteine.

Intra-operative grading of coronary artery atherosclerosis associated with homocysteine levels in postmenopausal women undergoing elective off-pump CABG surgery

Background:Atherosclerosis is one of the common causes of morbidity and mortality, in postmenopausal women. Homocysteine, a sulfur-containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular diseases. This study was designed to evaluate the relationship between intra-operative grading of coronary artery atherosclerosis and homocysteine level in postmenopausal women who were candidates for off-pump coronary bypass graft surgery (CABG).Materials and Methods:In this cross-sectional study, 136 postmenopausal women (with the mean age of 54.9±4 years) were enrolled as candidates for elective off-pump CABG. For each patient the extent and severity of atherosclerosis was assessed by intra-operative grading (IOG) and Gensini score system. Total homocysteine was determined with ELISA method after 12 hours of fasting. The patients were classified into two groups (diffuse vs. discrete) based on intra-operative findings. Finally the relation between age, IOG, and Gensini score with homocysteine level was assessed by ANOVA, T-test, and Tukey HSD test.Results:There was a positive correlation between intra-operative grading and homocysteine level in both groups (P=0.005). The association between Gensini score and homocysteine was significant in higher levels of hyperhomocysteinemia (P<0.05). The homocysteine level also increased with age; therefore, patients were classified into two categories (<54 years and ≥54 years) by Levene test. Statistical analysis indicated no relationship between IOG, Gensini score, and homocysteine level in the patients who were younger than 54 years (P=0.3, P=0.2), but significant relation was detected between IOG, Gensini score, and homocysteine in the patients who were older than 54 years with diffuse or discrete lesions in coronary arteries (P=0.001, P=0.001).Conclusion:According to our findings, homocysteine level increases in post-menopausal women that can be an important risk factor for atherosclerosis and cardiovascular diseases.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Serum levels of monocyte chemoattractant protein-1 and C-reactive protein levels, as early signs of vascular damage and cardiovascular disease, were increased in young, lean patients with polycystic ovary syndrome. Serum monocyte chemoattractant protein-1 levels were positively correlated with serum LH, T, and C-reactive protein levels.

Intranasal 17β-estradiol treatment and homocysteine levels in postmenopausal women

Intranasal 17β-estradiol treatment and homocysteine levels in postmenopausal women

A comparison of the effects of sequential transdermal versus continuous orally administered hormone replacement therapies on plasma total homocysteine levels in postmenopausal women: A randomized, placebo-controlled study

Objective The objective was to determine the effects of transdermal and oral hormone replacement therapies on plasma total homocysteine levels in postmenopausal women. Material and methods One hundred and ten postmenopausal patients were enrolled in the study. Participants were randomized into three groups: in Group A ( n = 31) oral continuous combined therapy and in Group B ( n = 30) transdermal sequential hormone replacement therapy were given for 6 months. A placebo was administered orally to the control group (Group C, n = 30). Serum homocysteine levels were studied prior to and after 6 months of treatment in all groups. Results There were no statistical significant differences in mean serum homocysteine levels among the groups prior to the study. The mean homocysteine levels after 6 months in Groups A–C were also similar. Conclusions Serum homocysteine levels alter with neither oral continuous nor sequential transdermal hormone replacement therapy.

Effects of low- or high-dose hormone therapy on fasting and post-methionine homocysteine levels in postmenopausal women

Objective To evaluate the effect of two different hormone therapy (HT) doses on fasting and post-methionine homocysteine levels, an independent risk factor for cardiovascular and thromboembolic diseases.Methods Forty-eight women in natural postmenopause randomly received calcium 1 mg/day (control group; n = 12) or calcium plus low dose (1 mg estradiol plus 0.5 mg norethisterone; n = 18) or high dose (2 mg estradiol plus 1 mg norethisterone; n = 18) HT in a 6-month randomized, controlled, prospective study.Results Folate levels did not vary in any group, while levels of vitamin B12 significantly decreased after low- (−12.2 ± 6.6%; p < 0.04) or high-dose HT (−13.9 ± 6.1%; p < 0.01). Fasting homocysteine was reduced by either HT dose in a way that was inversely related to pretreatment homocysteine levels (−0.675x; r = 0.644; p < 0.0001). Modification of post-load homocysteine increase was influenced by the HT dose and inversely related to the homocysteine response to methionine observed at baseline. The regression slope observed with the low-dose HT (−1.637x; r = 0.57; p < 0.02) was significantly steeper (p < 0.001) than that observed with the high-dose HT (−0.304x; r = 0.554; p < 0.03) dose.Conclusions Low- or high-dose HT similarly influences fasting homocysteine levels. Low-dose HT seems to be more effective than high-dose HT in reducing the post-methionine homocysteine increase.

Effect of oral conjugated equine estrogen combined with medroxyprogesterone acetate on plasma homocysteine levels in postmenopausal women

Conjugated equine estrogen alone or combined with medroxyprogesterone acetate lowered homocysteine levels in postmenopausal women. Regardless of the dosage of progestin used, there was no impact on homocysteine metabolism after 3 years of therapy.

The effect of estradiol valerate and dienogest combination on serum homocysteine levels in postmenopausal women: A clinical trial

Several studies have verified that hormone replacement therapy (HRT) has protective effects on postmenopausal women's cardiovascular condition. However, highly significant recent studies have reported that women treated with HRT have more cardiovascular events than untreated women. An elevated homocysteine level is one important risk factor for cardiovascular disease (CVD). As a good indicator of CVD risk, we examined the changes in plasma homocysteine levels of postmenopausal women treated with HRT. In our study, we administered estradiol valerate (2 mg) and dionegest (2 mg) to 34 postmenopausal women recruited randomly from our menopause clinic, and measured plasma homocysteine levels of patients at baseline and after 3 and 6 months of therapy. The changes in plasma homocysteine levels of treated patients were not statistically significant (p = 0.241). Our results indicate that 6 months of estradiol valerate and dionegest therapy does not change homocysteine levels in postmenopausal women.

Plasma homocysteine levels after hormone therapy with and without folic acid supplementation: A randomized study

Sequential transdermal estrogen-progestin therapy induced a significant reduction in fasting serum homocysteine levels in postmenopausal women. The addition of folic acid supplementation for 6 months did not further lower the homocysteine concentrations.

Effect of hormone replacement therapy and tibolone on serum total homocysteine levels in postmenopausal women

Objective: To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. Study design: Ninety-five postmenopausal women aged 41–68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31) or tibolone 2.5 mg ( n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. Results: No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: −3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: −15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: −3.23%, NS). Conclusion: Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results.

Menopause rather than estrogen modifies plasma homocysteine levels

Objectives: To investigate the effects of transdermal estrogen replacement therapy (ERT) on plasma homocysteine levels in postmenopausal women who underwent total hysterectomy with bilateral oophorectomy. Methods: In two-phase open longitudinal prospective study we compared 28 premenopausal women and 35 healthy postmenopausal patients to evaluate the effect of transdermal estrogen treatment (TTS 50 twice-weekly) on plasma homocysteine levels after 6 and 12 months of therapy. Results: The study showed statistically relevant differences (P<0.05) in baseline plasma homocysteine concentration between the patients in premenopausal and in postmenopausal status. No difference in the plasma homocysteine levels was observed after 6 and 12 months of ERT on postmenopausal patients. Conclusions: Surgically postmenopausal women have higher plasma homocysteine concentrations than premenopausal women, but transdermal estrogen treatment for 12 months in postmenopausal women does not modify homocysteine levels.

Effect of raloxifene, estrogen, and hormone replacement therapy on serum homocysteine levels in postmenopausal women

Homocysteine (Hcy) is a sulfur-containing amino acid involved in the remethylation and transulfuration metabolic pathways (1). Genetic mutations and the deficiency in nutrients and micronutrients may disrupt Hcy metabolism and result in elevated serum levels. Furthermore, total Hcy (tHcy) levels may be determined by demographics, lifestyle, and state of health factors (1–4). Although tHcy levels are reported to be lower in premenopausal women compared with postmenopausal women (5), there is no consensus on whether they increase after menopause (5, 6). Furthermore, it is unclear whether the menopause-associated increase is related to age (2, 7) or to estrogen depletion (2, 5). In a previous study, we reported that the increase in tHcy levels among postmenopausal women appears to be age related (7).

Hormone Replacement Therapy Does Not Affect Plasma Homocysteine in Postmenopausal Women with Coronary Artery Disease

Objective: The objective was to evaluate the effect of hormone replacement therapy (HRT) on plasma homocysteine levels in postmenopausal women with coronary artery disease (CAD) and to investigate associations of homocysteine to other cardiovascular risk factors. Methods: The women in this single-center, controlled, and randomized study were examined at baseline, and after 3 and 12 months, after they had been recruited consecutively from patients referred for investigational coronary angiography. All analyses were performed examiner blind. They were randomized to HRT consisting of transdermal application of continuous 17β-estradiol with cyclic medroxyprogesterone acetate (MPA) tablets for 14 days every 3rd month, or to a control group. Results: After 3 months of unopposed 17β-estradiol, no significant effect on homocysteine was observed compared to the control group. The absolute decrease of 5% in median plasma homocysteine levels after 12-month HRT did not reach statistical significance. Plasma homocysteine seemed slightly higher in women with three- or four-vessel disease, but the difference was not significant. With increasing homocysteine levels, free tissue factor pathway inhibitor (TFPI) antigen increased, whereas E-selectin decreased. In women with diabetes or elevated blood glucose >6.0 mmol/l, plasma homocysteine was correlated to body mass index, C-peptide and insulin as well as age. Conclusion: Transdermal application of 17β-estradiol and sequential MPA do not affect plasma homocysteine in women with established CAD. Plasma homocysteine is stable in women with CAD over time, and unless special intervention is undertaken, repetitive measurements are not necessary in this particular group of high-risk individuals. The circulating anticoagulant TEPI is related to plasma homocysteine.

Effects of tibolone on plasma homocysteine levels in postmenopausal women

Objective: To investigate the effects of tibolone on levels of plasma homocysteine, an independent risk factor for cardiovascular disorders, in postmenopausal women. Design: Prospective, randomized clinical study. Setting: University hospital. Patient(s): Postmenopausal healthy women. Intervention(s): Tibolone (2.5 mg/d) or calcium (1250 mg/d) and conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (5 mg/d) were administered orally for 6 months. Blood samples were collected at the start and the end of therapy. Main Outcome Measure(s): Plasma homocysteine levels. Result(s): Administration of tibolone and calcium caused only a 4% decrease in plasma homocysteine levels compared with initial levels. In contrast, conjugated equine estrogens plus medroxyprogesterone acetate caused a 29% decrease in plasma homocysteine levels. Conclusion(s): Despite the reported beneficial effect of tibolone on the serum lipid profile, tibolone had no statistically significant effect on serum homocysteine levels in postmenopausal women. The possible cardiovascular protective role of tibolone might be unrelated to its effects on homocysteine levels.

Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women

Objective: The aim of our randomized, controlled trial was to verify the effect of folic acid supplementation on homocysteine levels in postmenopausal women. Study Design: Thirty-six women were divided randomly into 2 groups as follows: a placebo group (n = 18) and a group receiving 500 μg folic acid per day for 4 weeks (n = 18). To assess concentrations of plasma homocysteine, venous blood samples were taken on enrollment and after 4 weeks of treatment. Results: Mean plasma homocysteine levels were 10.9 ± 2.7 μmol/L in the placebo group and 7.8 ± 2.35 μmol/L ( P < .01) in the group receiving 500 μg folic acid per day for 4 weeks. The thirds (referred to as tertiles) of women with the highest baseline homocysteine plasma levels showed the greatest reduction in homocysteine, with a mean decrease of 4.35 μmol/L (32%; P < .01), in comparison with a decrease of 3.35 μmol/L (29%; P < .01) in the middle tertile and 1.3 μmol/L (22.4%; P = .09) in the lower tertile. Conclusions: The results show that low doses of folic acid are associated with a significant reduction in plasma concentrations of homocysteine. The highest initial levels of homocysteine showed the most important reduction after therapy. (Am J Obstet Gynecol 2000;183:945-7.)

Plasma total homocysteine levels in postmenopausal women with unstable coronary artery disease

An elevated plasma total homocysteine (tHcy) level is considered a risk factor for coronary artery disease (CAD), but the relationship between plasma tHcy and well-defined CAD in women is still unclear. Plasma tHcy concentrations and the covariates serum folate, vitamin B12, and creatinine were analysed in 157 angiographically examined postmenopausal women with unstable CAD and in 101 healthy controls. At coronary angiography, 16% had normal vessels and 84% had coronary atherosclerosis. Mean plasma tHcy concentration (μmol/l, 95% confidence interval) did not differ in patients compared to controls (13.1 (12.3–13.8) vs. 12.5 (11.6–13.5)) or in patients with or without coronary atherosclerosis (13.3 (12.4–14.1) vs. 12.0 (10.8–13.2)). A trend to an increasing plasma tHcy with increasing degree of coronary atherosclerosis was attenuated after adjustment for age and the previous mentioned covariates. Odds ratio for the risk of coronary artery disease and coronary atherosclerosis in hyperhomocysteinemic patients (≥90th percentile in controls) was approximately 3. However, the confidence interval included unity in half of the groups and the significance was therefore difficult to judge. Receiver operating characteristics showed age to be the only variable with a significant discriminatory ability regarding the presence of coronary atherosclerosis (area 0.77). Mild hyperhomocysteinemia seems not to be related to the risk of unstable CAD in postmenopausal women. The trend towards higher plasma tHcy with increasing degree of coronary atherosclerosis may be a marker of the disease. In future studies adjustment for age and the other three covariates should be considered.

Randomized, double-blind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women

Objective: To investigate the long-term effects of raloxifene on fasting plasma homocysteine levels in postmenopausal women compared with conjugated equine estrogen (CEE). Design: Randomized, double-blind, placebo-controlled study. Setting: Outpatient department of a university hospital. Patient(s): Fifty-two hysterectomized, healthy postmenopausal women. Intervention(s): Oral raloxifene in two dosages (60 mg/d [n = 13] and 150 mg/d [n = 13]), oral CEE (0.625 mg/d [n = 13], and placebo (n = 13) were given for 24 months. Main Outcome Measure(s): Fasting plasma homocysteine concentrations. Result(s): Plasma homocysteine levels were not altered in the placebo group. After 12 months, a significant reduction versus baseline in the mean plasma homocysteine level (−16%) was found only in the raloxifene 150-mg group. The mean change in plasma homocysteine levels within this group also was significantly different from the changes versus baseline found in the placebo group (+2%) and the raloxifene 60-mg group (−2%), but not different from those found in the CEE group (−8%). After 24 months, plasma homocysteine levels were decreased significantly in the raloxifene 150-mg and CEE groups compared with both baseline (−13% and −10%, respectively) and placebo values (−15% and −11%, respectively). No significant change in plasma homocysteine levels was observed in the raloxifene 60-mg group. Conclusion(s): Raloxifene has a favorable, dose-related effect on plasma homocysteine levels in postmenopausal women.