Plasma tHcy Concentrations Research Articles

Trends in Circulating Concentrations of Total Homocysteine among US Adolescents and Adults: Findings from the 1991–1994 and 1999–2004 National Health and Nutrition Examination Surveys

The National Health and Nutrition Examination Survey (NHANES) has monitored total homocysteine (tHcy) concentrations in a nationally-representative sample of the US population since 1991. Until recently, however, data could not be compared across survey periods because of changes in analytical methods and specimen matrices. Such an analysis of these data could supplement current knowledge regarding whether the US folic acid fortification program has modified national plasma tHcy concentrations. We examined tHcy data in the prefortification NHANES III survey (phase II, 1991-1994) and in 3 postfortification survey periods (1999-2000, 2001-2002, and 2003-2004). We applied method adjustment equations to the survey data based on method comparison studies of separate samples. Persons with chronic kidney disease were excluded from the analyses. Mean plasma tHcy concentrations decreased by 8%, 9%, and 10% for adolescent, adult, and older men and by 6%, 3%, and 13% for women, respectively, from before to after fortification. Concentrations remained unchanged between the first and third postfortification survey periods. Prevalence estimates of increased plasma tHcy concentrations (>13 micromol/L) for older men and women decreased from prefortification (32% and 20%, respectively) to postfortification (14% and 5%, respectively) but remained unchanged thereafter (16% and 14%, respectively [males] and 5% and 9%, respectively [females]). After adjusting for method changes, we quantified a prefortification to postfortification decrease in circulating tHcy concentrations of about 10% in a national sample of the US population. This change is similar to effects seen in intervention trials with folic acid and in smaller observational studies.

Plasma lipoprotein (a), homocysteine, and other cardiovascular disease (CVD) risk factors in Nigerians with CVD

Elevated plasma lipoprotein (a) (Lp(a)) and total homocysteine (tHcy) concentrations, as well as fat distributions, are associated with cardiovascular disease (CVD) risk. The purpose of this study was to evaluate plasma Lp(a), tHcy, percentage body fat, anthropometric indices, and blood pressure (BP) and their relationships with each other in well-defined, hospital-based, CVD patients in a Nigerian African community. One hundred seventy patients suffering from hypertensive heart disease, hypertension, ischaemic heart disease, and myocardial infraction with the mean age of 45.3 +/- 1.3 years and 58 apparently healthy volunteers with the mean age of 44.8 +/-1.2 years were selected. Anthropometric indices and BP were measured. Percentage body fat, body mass index, and waist-to-hip ratio (WHR) were calculated. Plasma Lp(a) and tHcy concentrations were determined. The results showed significant increases in BP, skinfold thickness (SFT) variables, and WHR in all of the CVD patients. Plasma Lp(a) was also significantly increased (p < 0.001), whereas the slight increase in the mean tHcy was not statistically significant. Positive significant correlations were found between systolic BP, triceps, SFT, and percentage body fat (p < 0.01), whereas significant correlations were found between some body composition variables, tHcy, and systolic BP (p < 0.05). Our findings provide supportive evidence for altered plasma Lp(a) concentration in addition to some other traditional CVD risk factors in Nigerians. The role of homocysteine is not well defined.

Plasma S-Adenosylhomocysteine Is a Better Biomarker of Atherosclerosis Than Homocysteine in Apolipoprotein E-Deficient Mice Fed High Dietary Methionine ,

Homocysteine (Hcy) and S-adenosylhomocysteine (AdoHcy) are critical intermediates of methionine metabolism. To investigate which, if either, of these compounds is more closely related to atherosclerosis, we fed 5 groups of apolipoprotein E (apoE)-deficient mice different diets for 8 wk to induce changes in their plasma Hcy and AdoHcy concentrations. These included an AIN-93G control diet (C), this C diet supplemented with methionine (M), the M diet deficient in folates, vitamin B-6, and vitamin B-12 (M−V), this M diet supplemented with these B vitamins (M+V), and a C diet deficient in B vitamins (C−V). Compared with controls, mice fed the C−V diet had a moderate elevation in their plasma total Hcy (tHcy) levels; however, their plasma AdoHcy concentration and atherosclerotic lesion areas were not different. In contrast, the mice fed the M+V diet had larger atherosclerotic lesion areas and elevated plasma AdoHcy concentrations but their plasma tHcy concentration did not differ from that of the group C mice. The plasma AdoHcy concentration and aortic sinus lesion areas were positively correlated (r = 0.866; P < 0.001). We observed a negative correlation between the plasma AdoHcy concentration and both the DNA methyltransferase activity (r = −0.792; P < 0.001) and global DNA methylation status (r = −0.824; P < 0.001) in the aortic tissue. Hence, our study suggests that plasma AdoHcy is a better biomarker of atherosclerosis than Hcy and may accelerate the development of atherosclerotic lesions in apoE-deficient mice that have been fed a high methionine diet. The mechanisms underlying this effect may be related to the AdoHcy-mediated inhibition of DNA methylation in the aortic tissue.

Plasma homocysteine and vascular disease in elderly patients with mental illness

Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness compared to control subjects. There are many different determinants of plasma tHcy concentration, including the presence of vascular disease. The presence of vascular disease may contribute to cognitive impairment. Clarification of the role of vascular risk factors in mental illness is important because most are modifiable, in contrast to other risk factors, such as age and genetics. In this review, we summarize the findings of our investigations of vascular disease and plasma tHcy level in elderly patients with mental illness. Elevated plasma tHcy concentration in elderly patients with mental illness was mainly associated with the presence of vascular disease and was not related to the specific psychogeriatric diagnosis. Furthermore, it seems possible that the control of conventional vascular risk factors could be guided by the level of plasma tHcy, serum cystatin C, serum N-terminal pro-brain natriuretic peptide, and serum C-reactive protein.

Dietary Folate Intake, Blood Folate Status, and Urinary Folate Catabolite Excretion in Korean Women of Childbearing Age

This study assessed folate intake, folate concentrations in plasma and erythrocytes, plasma total homocysteine (tHcy) concentrations, and urinary excretion of folate metabolites in Korean women of childbearing age. A total of 36 women voluntarily participated in this study. Precise dietary intake for 3 consecutive days was determined by weighing all foods consumed, and folate intake was calculated with a computer-aided dietary analysis system. Folate concentrations in plasma and erythrocytes were determined via microbiological methods and in plasma by HPLC. Urine excreted over the same period of time was collected and assayed for folate catabolites, para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG) by reverse-phase HPLC after affinity chromatography. The mean folate intake was 206.9+/-90.8 microg DFE/d, and the mean concentrations in plasma and erythrocytes were 10.5+/-3.7 and 249.9+/-77.8 ng/mL, respectively. Erythrocyte folate concentration was low in 2.8% of the subjects (<140 ng/mL) and was marginal in 5.5% (140-156 ng/mL). The mean plasma tHcy concentration was 12.7+/-0.2 nmol/mL, and 11% of the subjects evidenced hyperhomocysteinemia (>or=15 nmol/mL). The mean urinary excretion levels of pABG and ApABG were 10.7+/-3.8 and 89.1+/-19.5 nmol/d, respectively. The means of folate reserve and folate turnover rate were 26.2+/-11.6 and 10.5+/-3.9, respectively. We noted positive relationships between folate intake and the folate concentrations in plasma and erythrocytes, as well as the urinary excretions of ApABG and total folate catabolites. In addition, the erythrocytic folate concentrations were positively associated with the urinary excretions of ApABG and total folate catabolites. In conclusion, the folate status of Korean women of childbearing age was marginally deficient with inadequate concentrations of erythrocyte folate and elevated plasma tHcy, largely due to insufficient folate intake. The marginally deficient folate status was confirmed by the low excretion of folate catabolites in urine.

Effects of orange juice and proline betaine on glycine betaine and homocysteine in healthy male subjects

Proline betaine (PB), a glycine betaine (GB) analogue found in citrus foods, increases urinary GB loss and plasma total homocysteine (tHcy) concentrations in rats. Its presence in human plasma is associated with increased GB excretion. To compare the effects of dietary levels of PB on GB excretion, and on plasma tHcy and GB concentrations in healthy volunteers. In a randomized crossover study, eight healthy males (18-50 years) ingested either 750 mL orange juice (containing 0.545 g PB), a PB supplement (0.545 g PB dissolved in 750 mL apple juice), or 750 mL apple juice (control). Plasma PB, GB and tHcy, and urine PB, GB and creatinine concentrations were measured hourly for 6 h and at 24 h post-treatment. Plasma tHcy concentrations were not increased (relative to control) following ingestion of either orange juice or PB supplement. Both treatments produced a significant increase in plasma PB concentrations (P < 0.001), this effect being greater following orange juice compared with PB supplement (P < 0.05, 1-2 h). Urinary excretion of PB was greater than the control following both orange juice (P < 0.001) and PB supplement (P < 0.001), from 2 to 24 h post-treatment. This increase in PB excretion was significantly greater following orange juice compared with PB supplement with higher peak excretion (Cmax difference, P = 0.008). GB excretion was significantly greater following ingestion of orange juice compared with PB in apple juice (P = 0.007) and apple juice control (P < 0.001) in the first 2 h post-ingestion. PB administered in dietary doses had little effect on plasma tHcy concentrations in healthy humans. Ingestion of PB in orange juice compared with PB alone resulted in greater increases in the urinary excretion of PB and GB.

Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects

We have previously reported six novel mutations in the 5'-UTR of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations we screened patients, referred for investigation of suspected dementia (DGM subgroup) by SSCP and DNA sequencing from the end of exon 1 to the first bases of intron 3. We found 4 sequence variations, FOLR1 g.1314G>A, g.1816delC, g.1841G>A, and g.1928C>T. Pyrosequencing genotyping assays were developed for all of them, and 389 active seniors (AS subgroup) and the 202 DGM patients were genotyped for these mutations. The frequency q of the mutated allele was, among the AS subjects, 0.068, 0.0026, 0.0026, and 0.024 respectively, and among the DGM subjects, 0.067, 0.0076, 0.0078, and 0.023. The g.1816delC and g.1841G>A mutations thus were more frequent in the DGM than in the AS subgroup, but the difference did not reach statistical significance. The mutated alleles, FOLR1 1816(-) and 1841A, always occurred together in the same subjects, suggestive of a rare double-mutant haplotype. The two common polymorphisms, FOLR1 g. 1314G>A and g.1928C>T seemed not to raise tHcy plasma levels, whereas the double-mutated g.1816(-)-g.1841A haplotype may possibly have a slight tHcy-raising effect. Thus, so far 8 novel rare FOLR1 mutations with a combined prevalence of approximately 1.3% in Whites as well as two common polymorphisms with 5% and 13%, respectively, have been demonstrated. Only a few of the rare mutations may potentially be associated with raised plasma tHcy concentrations. No association with dementia was found.

High-throughput and simultaneous measurement of homocysteine and cysteine in human plasma and urine by liquid chromatography–electrospray tandem mass spectrometry

Total homocysteine (tHcy) and cysteine (tCys) concentrations in biological fluids are routinely used in the clinical diagnosis of genetic and metabolic diseases, and this necessitates the development of rapid and sensitive methods for quantification. Liquid chromatography–electrospray tandem mass spectrometry (LC–MS/MS) was used to measure tHcy and tCys in 23 plasma and 21 urine samples from healthy adults and 14 urine samples from healthy children. The results were compared with a standard high-performance liquid chromatography (HPLC) method. The coefficient of variation (CV) for the LC–MS/MS method ranged from 2.9% to 6.1% for the intraassay and 4.8% to 6.4% for the interassay. Mean recoveries were close to 100% for both plasma and urinary tHcy and tCys. The mean plasma tHcy and tCys concentrations in healthy adults were 8.62 and 261.40μmol/L, respectively. The mean urinary tHcy and tCys in adults were 0.98 and 22.60μmol/mmol creatinine, respectively. The mean urinary tHcy and tCys in children were 1.17 and 27.43μmol/mmol creatinine, respectively. Bland–Altman difference plots of method comparison between LC–MS/MS and HPLC showed good agreement in plasma and urinary tHcy and tCys concentrations. Our method is suitable for rapid measurements, and the reported urinary values in children will help to develop a pediatric reference range for clinical use.

Relations of glutamate carboxypeptidase II (GCPII) polymorphisms to folate and homocysteine concentrations and to scores of cognition, anxiety, and depression in a homogeneous Norwegian population: the Hordaland Homocysteine Study

Background: Glutamate carboxypeptidase II (GCPII) encodes for intestinal folate hydrolase and brain N-acetylated α-linked acidic dipeptidase. Previous studies provided conflicting results on the effect of the GCPII 1561C→T polymorphism on folate and total homocysteine (tHcy) concentrations.Objective: We aimed to determine the potential effects of 2 polymorphisms of GCPII on plasma folate and tHcy concentrations, cognition, anxiety, and depression in a large aging cohort of Norwegians enrolled in the Hordaland Homocysteine Study.Design: DNA samples were genotyped for the GCPII 1561C→T and 484A→G polymorphisms, and the results were linked to plasma folate and tHcy concentrations and to scores for cognition, anxiety, and depression.Results: The 2 polymorphisms were in linkage disequilibrium and were associated with concentrations of tHcy. After adjustment for covariates, persons in the CT or combined CT and TT groups of the 1561C→T polymorphism had higher plasma folate concentrations and lower tHcy concentrations than did those in the CC group. Subjects with the TT genotype had lower Symbol Digit Modalities Test (SDMT) scores than did subjects with the CC genotype. Compared with abstainers, moderate alcohol drinkers had higher plasma folate concentrations and higher scores on the Mini Mental State Examination. However, women abstainers with the CT genotype had lower SDMT scores than did abstainers with the CC genotype or moderate drinkers with the CT genotype.Conclusions: The 1561C→T polymorphism is associated with higher plasma folate and lower tHcy concentrations and with lower SDMT cognitive scores in women who abstain from alcohol.

Dietary fat and plasma total homocysteine concentrations in 2 adult age groups: the Hordaland Homocysteine Study

Background:The intake of n−3 (formerly called omega-3) fatty acids (FAs) may be inversely associated with plasma total homocysteine (tHcy) concentrations, but the epidemiologic data are sparse.Objective:We examined the association between dietary fat and tHcy in a Norwegian population.Design:A cross-sectional, population-based study of 5917 subjects in 2 age groups (47–49 and 71–74 y old) was conducted with the use of food-frequency questionnaires and measurement of plasma tHcy concentrations.Results:The intake of saturated FAs (SFAs) was positively and significantly (Pfor trend < 0.001) associated with tHcy concentrations; the difference in plasma tHcy concentrations between the highest and lowest quartiles of SFAs was 8.8%. The intake of marine very-long-chain n−3 FAs was inversely associated with tHcy concentrations; the difference in plasma tHcy concentrations between the lowest and the highest quartiles was −5.0% (Pfor trend < 0.001). Intakes of total and monounsaturated fat also were positively associated with plasma tHcy concentrations (Pfor trend < 0.001 and < 0.005, respectively), whereas the intake of polyunsaturated fat was positively associated with tHcy concentrations only in the younger subjects (Pfor trend = 0.03). The associations were weakened by additional adjustment for B vitamin intake but remained significant for SFA intake (P< 0.001). When stratified for total B vitamin intake, the inverse association between tHcy concentrations and very-long-chain n−3 FAs was significant only in the highest quartile of B vitamin intake (Pfor trend = 0.001), regardless of supplement use.Conclusions:High intakes of SFAs are associated with high plasma concentrations of tHcy. The inverse association between dietary intakes of very-long-chain n−3 FAs and plasma tHcy concentrations is apparent only at high B vitamin intakes.

Homocysteine and Cardiovascular Risk: Considering the Evidence in the Context of Study Design, Folate Fortification, and Statistical Power

The hypothesis that moderately increased plasma total homocysteine (tHcy) concentrations are causally related to cardiovascular disease (CVD) originated from observations of vascular disease in patients with homocystinuria (1). tHcy concentrations are ∼10-fold higher in patients with untreated homocystinuria than in the general population, and these patients often suffer from CVD in early life. Homocystinuria may arise from one of several rare defects in genes involved in methionine metabolism, resulting in high tHcy concentrations, with cystathionine β-synthase ( CBS gene) deficiency being the most common. In responsive cases of homocystinuria, dietary supplementation with B-vitamins and betaine is remarkably effective at lowering plasma tHcy concentrations and decreasing the risk of CVD (2). In addition to suggesting that extremely high tHcy concentrations may be causally related to CVD in affected individuals with homocystinuria, McCully also suggested that moderately increased tHcy concentrations may be related to CVD risk in the general population (1). A single discrete mechanism of vascular injury has not been identified, but high homocysteine may have adverse effects on platelet function and clotting factors and may increase vascular smooth muscle cell proliferation. Furthermore, increased homocysteine concentrations provoke endothelial dysfunction, possibly mediated by oxidative stress or interference with nitric oxide function (3)(4). Over the last 3 decades, many observational epidemiological studies have reported associations between increased tHcy concentrations and risk of coronary heart disease (CHD) and stroke (5). Although results of prospective cohort studies (in which blood for tHcy determination was collected before the onset of disease) have been weaker and more inconsistent than those of retrospective studies (in which the blood was collected after the onset of disease), prospective studies are more reliable because they are not vulnerable to bias due to the effect of disease on tHcy (“reverse causality”) and because they control for confounding from established …

Plasma Homocysteine Is Elevated in Elderly Patients with Memory Complaints and Vascular Disease

Background: There is an association between elevated plasma total homocysteine (tHcy) and vascular disease in elderly patients suffering from organic and non-organic mental disease. The main objective of the present study was to investigate the relationship between plasma tHcy concentration and vascular disease in elderly patients with memory complaints. Methods: In 108 patients with memory complaints the concentration of plasma tHcy was related to the presence of vascular disease. Furthermore, different determinants of plasma tHcy concentration were measured. Results: Patients with confirmed memory complaints (CMC, n = 86) which fulfilled the criteria of mild cognitive impairment were divided into two categories, with and without vascular disease. The CMC group without vascular disease showed similar biochemical and brain imaging findings to patients with subjective memory complaints (SMC, n = 22). The group of CMC patients with vascular disease had higher age, higher plasma tHcy, lower serum folate and lower renal function than patients without vascular disease. Conclusion: The finding of two subgroups of patients with CMC supports the notion that mild cognitive impairment is a heterogenous clinical entity with multiple aetiological factors. The elevated plasma tHcy in the group of CMC patients with vascular disease is likely to be associated with vascular disease.

High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status.

Elevated plasma total homocysteine (tHcy) concentrations are associated with lower folate, vitamin B-12, and vitamin B-6 status and are considered an independent risk factor for cardiovascular disease in developed countries, but data in developing countries are limited. We conducted a cross-sectional study to explore tHcy status and its association with plasma B vitamin status in 2471 Chinese men and women aged 35 to 64 y, living in the urban and rural areas of the northern and the southern regions of China. Blood samples were also collected in 2 seasons (spring and fall). The geometric mean plasma tHcy concentration was significantly higher in the north (adjusted geometric mean, 95% CI; 13.0 micromol/L, 12.6-13.3) than in the south (9.1, 8.9-9.4) after controlling for gender, area (urban and rural), age, and season (spring and fall). Twenty-eight percent of northerners and 7% of southerners had plasma tHcy concentrations>or=16.0 micromol/L, a level used to define hyperhomocysteinemia. Within each region, men had higher plasma tHcy concentrations than women (16.1 vs. 10.6 micromol/L in the north, and 10.7 vs. 7.9 micromol/L in the south) and 40% of the northern men had hyperhomocysteinemia. Generally, individuals living in the urban areas had 30% (95% CI, 1.0-1.6) greater odds of having high tHcy levels (>or=16 micromol/L) than those living in the rural areas. Low plasma concentrations of folate, vitamins B-12 and B-6, older age, being male, and living in urban areas were all independently associated with elevated tHcy, with low folate as the strongest determinant.

Plasma Total Homocysteine, Folate, and Vitamin B12 Status and Hospitalizations for Cardiovascular Disease

Abstract Elevated plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular disease (CVD). Also known is that plasma folate and vitamin B12 influence homocysteine metabolism as cosubstrate and cofactor, respectively. This population-based study was conducted to evaluate the plasma concentrations of tHcy, folate, and vitamin B12 in 54 older patients aged ≥51 years (40 males; 14 females) of Nice hospital cardiology service. After excluding cases with a serum creatinine &gt;120 mmol/L, we established the test properties of a plasma tHcy concentration &lt;15 μmol/L (Group 1) or ≥15 μmol/L (Group 2). In the population aged ≥51 years, plasma tHcy was higher in women (18.0 μmol/L) than in men (15.5 μmol/L; not significant), conversely, serum vitamin B12 was higher in men (376.9 pg/ml) than in women (340.7 pg/ml; not significant). Average plasma tHcy was 11.5 μmol/L in Group 1 and 21.6 μmol/L in Group 2. Vice versa, serum vitamin B12 was higher in Group 1 (419.5 pg/ml) than in Group 2 (307.2 pg/ml) (p &lt;0.05). Correlation analysis (Pearson's r) in the total study population (20-84 years) indicated an inverse correlation between serum folate and age (r = -0.231, p &lt;0.05). In the subjects, aged ≥51 years, there was a significant negative correlation between age and tHcy levels (r = -0.283, p &lt;0.05) and serum vitamin B12 concentrations (r = -0.326, p &lt;0.01) but not with serum folate. However, in subjects with tHcy &lt;15 μmol/L, a significant inverse correlation existed between plasma tHcy and serum folate (r = -0.455; p &lt;0.05). In conclusion, these results highlight the relevance of the vitamin status and particularly of folate levels in the modulation of fasting tHcy levels in the patients with clinical hyperhomocysteinemia, defined as plasma tHcy &gt;15 μmol/L.

Childbearing women of twenty and under are at greater risk than those of twenty-five and over for compromised folate status

This study assessed folate intakes, folate concentrations in plasma and erythrocytes, plasma total homocysteine (tHcy) concentration, and urinary excretion of folate metabolites in Korean women with childbearing potential. A total of 23 women voluntarily participated in this study. Precise dietary intakes for 3 consecutive days were determined by weighing all foods consumed and folate intake was calculated using a computer-aided dietary analysis system. Folate concentration of plasma and erythrocytes was determined by a microbiological method. Plasma tHcy concentration was assayed using an HPLC analysis method. Urine excreted over the same period of time was collected and folate catabolites, para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG), were evaluated using a reverse-phase HPLC method after affinity chromatography. Young women of 20 and under were likely to consume less folate with low energy intake, had lower folate concentration in plasma and erythrocytes, and excreted a lesser amount of ApABG and total folate catabolites than women of 25 years and over. The results of this study confirmed that young Korean women with childbearing potential, especially those under 21 years of age, might be at risk for compromised folate status due to insufficient folate intakes from inadequate energy consumption.

Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India.

People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (<150 pmol/L) and 24 had hyperhomocysteinemia (>15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p <0.05) and reduced tHcy concentration (18.0 to 13.0 micromol/L, p <0.05) within first 2 weeks, both of which remained stable for the next 4 weeks. Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12, and there was no change in plasma folate concentration in any of the groups. Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 (by 3 g/L, p <0.05) and the number of women with macrocytosis decreased from 2 to zero. There was no change in vibration sensory threshold during the period of the study. High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks. People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations.

Serum sex hormone and plasma homocysteine levels in middle-aged and elderly men

To investigate whether circulating levels of testosterone (total, bioavailable), estradiol (total, bioavailable), and DHEA sulfate (DHEAS) are associated with fasting plasma homocysteine (tHcy) levels in middle-aged and elderly men. A population-based sample of 400 independently living men between 40 and 80 years of age in a cross-sectional study. Total testosterone, sex hormone binding globulin (SHBG), and total estradiol were measured by RIA methods and bioavailable testosterone and estradiol were calculated. DHEAS was measured using an immunometric technique. Fasting homocysteine was measured by fluorescence polarization immunoassay. Anthropometric characteristics were also measured and two standardized questionnaires completed, including life-style factors and diet. Linear regression analysis adjusted for age, body mass index (BMI), creatinine clearance, and mean visceral fat was used to assess the association of endogenous sex hormones and fasting plasma homocysteine levels. After adjustment for age, BMI, creatinine clearance, and mean visceral fat no statistically significant association was observed between testosterone (total, bioavailable), DHEAS, and estradiol (total, bioavailable)levels with natural log tHcy (beta = -2 x 10(-3); 95% confidence intervals (CI) -9 x 10(-3); 5 x 10(-3)), (beta = -4 x 10(-3); 95% CI -18 x 10(-3); 9 x 10(-3)), (beta = 3 x 10(-3); 95% CI -6 x 10(-3); 12 x 10(-3)), (beta = -9.3 x 10(-5); 95% CI -1 x 10(-3); 1 x 10(-3)), and (beta = 0.00; 95% CI -3 x 10(-3); 2 x 10(-3)) respectively. Additional adjustment for smoking, alcohol intake, daily physical activity, diabetes mellitus, and hypertension did not change these findings. The results of our study do not support a direct role for circulating sex hormone levels in the regulation of fasting plasma tHcy concentrations in middle-aged and elderly men.

Population reference values for plasma total homocysteine concentrations in US adults after the fortification of cereals with folic acid1,2

Folic acid fortification has resulted in a dramatic increase in folate intake in the United States. Folate intake is inversely associated with circulating total homocysteine (tHcy). Elevated tHcy is directly associated with cardiovascular disease risk. The aim of this study was to present the distribution of plasma concentrations of tHcy in US adults by using data from nationally representative sample surveys conducted since folic acid fortification was implemented. Data from the National Health and Nutrition Examination Surveys from 1999-2001 and 2001-2002 were used to study tHcy distribution by age, sex, and race-ethnicity in 9196 persons. Plasma concentrations of tHcy were higher in men than in women and in older persons than in younger persons. In those aged 19-30, 31-50, and 51-70 y but not in those aged >70 y, men had significantly (P < 0.0001) higher mean plasma concentrations of tHcy than did women. A race-ethnicity difference in plasma tHcy existed only in persons aged >70 y. Non-Hispanic blacks aged >70 y had significantly (P < 0.05) higher tHcy concentrations than did non-Hispanic white or Mexican American or Hispanic subjects in the same age group. Age-adjusted plasma tHcy concentrations did not differ significantly between non-Hispanic white (8.39 micromol/L), non-Hispanic black (8.92 micromol/L), and Mexican American or Hispanic (8.12 micromol/L) subjects. The rate of increase in plasma tHcy was greater in non-Hispanic blacks aged >/=50 y than in persons of similar age but of other races-ethnicities. These plasma tHcy data reflect the effects of folic acid fortification. Sex, age, and race-ethnicity differences persist in plasma tHcy concentrations.

Elevated plasma homocysteine levels: Risk factor or risk marker for the development of dementia and Alzheimer's disease?

Elevated plasma homocysteine (tHcy) concentrations have been associated with an increased risk of developing dementia and Alzheimer's disease (AD). It is not clear, however, if an elevation in tHcy concentration is a "risk factor" with a direct pathophysiological role in the development of the disease or merely a "risk marker" reflecting an underlying process such as oxidative stress responsible for both the high tHcy concentrations and the development of AD. Epidemiological studies have confirmed that elevations in plasma tHcy temporally precede the development of dementia and that there is a continuous, inverse linear relation between plasma tHcy concentrations and cognitive performance in older persons. Several potential biological pathways that could mediate the observed association are briefly reviewed. In light of these data and the growing parallel interest in plasma tHcy as an emerging vascular risk factor there was considerable hope that vitamin therapy with folate, B12 and B6, shown to lower plasma tHcy levels, could significantly reduce the risk of stroke and dementia permitting healthy brain aging. The results from recent trials addressing the secondary prevention of stroke and myocardial infarction trials have been disappointing. However, the role of vitamins and other homocysteine lowering treatments in the primary prevention of stroke and dementia, as well as their role in preserving cognition among persons with mild cognitive impairment and early dementia deserves to be fully pursued.

Hyperhomocysteinaemia, methylenetetrahydrofolate reductase polymorphism and risk of coronary artery disease

Hyperhomocysteinaemia is an independent, graded risk factor for coronary artery disease (CAD). The methylenetetrahydrofolate reductase (MTHFR) polymorphism is associated with hyperhomcysteinaemia and may therefore influence individual susceptibility to CAD. We have investigated this risk factor in a Tunisian Arab population. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the C677T and A1298C variants of the MTHFR gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed as the number of affected vessels. Plasma total homocysteine (tHcy) concentration was determined using a direct chemiluminescence assay. MTHFR CC, CT and TT genotype frequencies in the CAD group were significantly different from those observed in the control group (49%, 35% and 16% versus 48.3%, 45.8% and 5.8%, respectively; P = 0.031). However, MTHFR AA, AC and CC genotypes frequencies in the CAD group were not significantly different from the control group ( P = 0.568). Patients with CAD showed higher plasma tHcy concentrations than patients without CAD (15.86 +/- 8.63 micromol/L versus 11.90 +/- 3.25 micromol/L, P < 0.001). There was no association between the MTHFR polymorphisms and the number of stenosed vessels. Patients with the MTHFR TT genotype had higher plasma tHcy, serum creatinine, cholesterol and triglyceride concentrations than patients with the MTHFR CC genotype. The C677T polymorphism of the MTHFR gene is associated with hyperhomocysteinaemia, lipid dysregulation and the presence of CAD in this Tunisian Arab population.