Testosterone regulation of renal cystathionine β-synthase: implications for sex-dependent differences in plasma homocysteine levels

2007 ◽  
Vol 293 (2) ◽  
pp. F594-F600 ◽  
Author(s):  
Victor Vitvitsky ◽  
Anna Prudova ◽  
Sally Stabler ◽  
Sanjana Dayal ◽  
Steven R. Lentz ◽  
...  
Keyword(s):  
Independent Risk Factor ◽  
Important Determinant ◽  
Epidemiological Studies ◽  
Plasma Homocysteine ◽  
Elevated Plasma ◽  
Lower Plasma ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine ◽  
Expression And Activity

Elevated plasma total homocysteine (tHcy) is an independent risk factor for ischemic heart disease and stroke. Epidemiological studies reveal that men have higher tHcy levels than women, but the mechanism underlying this sex-dependent difference is unknown. One route for intracellular disposal of homocysteine is catalyzed by cystathionine β-synthase (CBS). Renal function is known to be an important determinant of tHcy, and, in this study, we demonstrate that renal CBS expression and activity in mice diminished approximately twofold after castration, whereas ovariectomization was without effect. The higher renal CBS activity in males (22.7 ± 3.1 mmol cystathionine·h−1·kg kidney−1) vs. females (8.4 ± 3.4 mmol cystathionine·h−1·kg kidney−1, P ≤ 10−6) in C57Bl/6J mice was associated with lower plasma tHcy levels in males vs. females, and this difference was exacerbated in Cbs+/− mice (7.7 ± 1.9 μmol/l in males vs. 13.8 ± 6.4 μmol/l in females, P = 0.005). Surprisingly, mammals exhibit a diversity of regulatory patterns for kidney CBS, with females exhibiting lower CBS activity in mice, higher in rats and humans, and being indistinguishable from males in rabbit, hamster, and guinea pig. Our data suggest that testosterone-dependent regulation of human CBS in kidney may contribute to sex-dependent differences in homocysteine transsulfuration.

Assessing Plasma Total Homocysteine in Patients with End-Stage Renal Disease

2007 ◽  
Vol 27 (5) ◽  
pp. 476-488 ◽  
Author(s):  
Bradley L. Urquhart ◽  
Andrew A. House
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Elevated Plasma ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Stage Renal Disease ◽  
End Stage ◽  
Plasma Total Homocysteine

Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease; however, in light of several recent randomized trials, the issue of causality has been cast into doubt. Patients with end-stage renal disease are particularly interesting as they consistently have elevated tHcy and their leading causes of morbidity and mortality are related to cardiovascular disease. In the present article, we review the early evidence for the homocysteine theory of atherosclerosis, homocysteine metabolism, mechanisms of toxicity, and pertinent available clinical investigations. Where appropriate, the sparse evidence of homocysteine in peritoneal dialysis is reviewed. We conclude by addressing the difficulties associated with lowering plasma tHcy in patients with end-stage renal disease and suggest some novel methods for lowering tHcy in this resistant population. Finally, to address the issue of causality, we recommend that clinicians and scientists await the results of the FAVORIT trial before abandoning homocysteine as a modifiable risk factor for cardiovascular disease, as this study has recruited patients from a population with consistently elevated plasma tHcy who are known to respond to vitamin therapy.

scholarly journals Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis

2013 ◽  
Vol 109 (5) ◽  
pp. 785-794 ◽  
Author(s):  
Derek Obersby ◽  
David C. Chappell ◽  
Andrew Dunnett ◽  
Amalia A. Tsiami
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Elevated Plasma ◽  
Cross Sectional ◽  
Animal Products ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B12can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B12deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B12levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B12of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12, from which it can be concluded that the usual dietary source of vitamin B12is animal products and those who choose to omit or restrict these products are destined to become vitamin B12deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.

scholarly journals Association of Elevated Plasma Total Homocysteine With Dementia With Lewy Bodies: A Case-Control Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Guili Zhang ◽  
Shuai Liu ◽  
Zhichao Chen ◽  
Zhihong Shi ◽  
Wenzheng Hu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Dementia With Lewy Bodies ◽  
Case Control Study ◽  
Lewy Bodies ◽  
Case Control ◽  
Elevated Plasma ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine ◽  
Control Study

Background: Elevated plasma total homocysteine (tHcy) level, a known risk factor for vascular disease, is reported to be an independent risk factor for cognitive impairment and Alzheimer’s disease (AD) in most studies. tHcy may also be associated with dementia with Lewy bodies (DLB).Objective: To investigate the association between plasma tHcy levels and DLB or AD.Methods: This is a case-control study including 132 DLB patients, 264 AD patients, and 295 age-matched healthy controls. We used multivariate logistic regression model to analyze the data with adjustments for confounding variables.Results: The highest tHcy tertile (>13.9 μmol/L) was significantly independently associated with DLB [adjusted odds ratio (OR): 4.65, 95% confidence interval (CI): 1.95–11.10, P = 0.001] and AD (adjusted OR: 1.82, 95% CI: 1.02–3.23, P = 0.041) compared to the lowest tertile (<10.7 μmol/L). The cumulative frequency plots showed a shift in the distribution of the tHcy concentrations to higher values in patients with DLB compared to AD. The mean tHcy levels were stable and not altered by the duration of cognitive impairment prior to the collection of blood samples from DLB patients.Conclusion: Elevated plasma tHcy levels were independently associated with DLB, and the association was stronger for DLB than for AD. The lack of a relationship between tHcy levels and symptom duration may refute these observed associations being a consequence of DLB, and future longitudinal studies will be required to confirm whether tHcy plays a causative role in DLB.

Diet, total plasma homocysteine concentrations and mortality rates in broiler chickens

2003 ◽  
Vol 83 (3) ◽  
pp. 601-604 ◽  
Author(s):  
S. E. Samuels
Keyword(s):  
Cardiovascular Disease ◽  
Sudden Death ◽  
Broiler Chickens ◽  
Independent Risk Factor ◽  
Total Mortality ◽  
Mortality Rates ◽  
Plasma Homocysteine ◽  
Sudden Death Syndrome ◽  
Total Plasma ◽  
Elevated Plasma

The aim of this study was to determine if total plasma homocysteine (HCY) concentrations and mortality rates due to ascites syndrome and (AS) sudden death syndrome (SDS) in broiler chickens could be lowered by diet. Elevated plasma HCY is an independent risk factor for cardiovascular disease in humans. A total of 828 day-old male broiler chickens (Arbor Acre) were fed, for 6 wk, either a basal practical diet or one supplemented with excess vitamins B6 and B12, folic acid and betaine to stimulate the degradation of HCY. The supplemented diet decreased plasma HCY by 17% (P < 0.05; n = 16 per diet). Total mortality due to AS and SDS was 18% lower in the supplemented diet but this difference was not statistically significant. Key words: Homocysteine, folate, chickens, cardiovascular disease, ascites, sudden death syndrome

Oral and transdermal estrogens both lower plasma total homocysteine in male-to-female transsexuals

2003 ◽  
Vol 168 (1) ◽  
pp. 139-146 ◽  
Author(s):  
Erik J. Giltay ◽  
Petra Verhoef ◽  
Louis J.G. Gooren ◽  
Johanna M. Geleijnse ◽  
Evert G. Schouten ◽  
...  
Keyword(s):  
Lower Plasma ◽  
Total Homocysteine ◽  
Male To Female ◽  
Plasma Total Homocysteine

scholarly journals Polymorphisms in the Transcobalamin Gene: Association with Plasma Homocysteine in Healthy Individuals and Vascular Disease Patients

2002 ◽  
Vol 48 (9) ◽  
pp. 1383-1389 ◽  
Author(s):  
Karin JA Lievers ◽  
Lydia A Afman ◽  
Leo AJ Kluijtmans ◽  
Godfried HJ Boers ◽  
Petra Verhoef ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Vascular Disease ◽  
Vitamin B12 Deficiency ◽  
Potential Effect ◽  
Sequence Variants ◽  
Cvd Risk ◽  
Plasma Thcy ◽  
B12 Deficiency ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

Abstract Background: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD). Intracellular vitamin B12 deficiency may lead to increased plasma total homocysteine (tHcy) concentrations and because transcobalamin (TC) is the plasma transporter that delivers vitamin B12 to cells, genetic variation in the TC gene may affect intracellular vitamin B12 availability and, consequently, tHcy concentrations. Methods: We examined five sequence variants, i.e., I23V, G94S, P259R, S348F, and R399Q, in the TC gene as possible determinants of tHcy and, concordantly, as possible risk factors for CVD in 190 vascular disease patients and 601 controls. We also studied potential effect-modification of vitamin B12 by genotype. Results: In individuals with high vitamin B12, 259PP individuals had lower tHcy concentrations than 259PR and 259RR individuals. Homozygous 23VV individuals had lower fasting tHcy concentrations than their 23IV and 23II peers. None of the genotypes defined by the three other sequence variants showed an association with tHcy concentrations, nor was any TC genotype associated with an increased CVD risk. Conclusions: In individuals in the highest quartile of the vitamin B12 distribution (&gt;299 pmol/L), tHcy concentrations are lower in 259PP homozygotes than in 259PR and 259RR individuals. Therefore, 259PP individuals, who represent &gt;25% of the general population, may be more susceptible to reduction of plasma tHcy concentrations by increasing the vitamin B12 status.

scholarly journals Association between plasma total homocysteine level within normal range and bone mineral density in adults

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Zhongxin Zhu ◽  
Changhua Liu ◽  
Xiao’e Li ◽  
Xiaocong Yao
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Recursive Algorithm ◽  
Positive Trend ◽  
Mineral Density ◽  
Normal Range ◽  
Thcy Level ◽  
Plasma Thcy ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

Abstract Background Growing evidence indicates that homocysteine is a noteworthy marker for general health status. However, research regarding plasma total homocysteine (tHcy) levels and bone mineral density (BMD) is sparse and controversial. Hence, we aimed to investigate the association between plasma tHcy level within normal range and lumbar BMD in adults. Methods In this cross-sectional study, using the National Health and Nutrition Examination Survey database, data on 10748 adults aged between 30 and 85 years were analyzed. The weighted multiple logistic regression analyses were conducted to evaluate the association between plasma tHcy level and lumbar BMD. The fitted smoothing curves were performed to explore potential non-linear relationships. When non-linearity was detected, we further calculated the inflection point using a recursive algorithm and constructed a weighted two-piecewise linear regression model. Results After adjusting for all the covariates, the association between plasma tHcy and lumbar BMD was different in various age groups (adults aged 30–49 years: β = −0.0004, 95% CI −0.0025, 0.0018; adults aged 50–69 years: β = 0.0001, 95% CI −0.0025, 0.0026; adults aged 70–85 years: β = 0.0050, 95% CI 0.0008, 0.0092). In the subgroup analysis stratified by gender, this association also differed based on gender. There was a negative trend in females (aged 30–49 years: β = −0.0022, 95% CI −0.0054, 0.0011; aged 50–69 years: β = −0.0028, 95% CI −0.0062, 0.0007), and a positive trend in males (aged 30–49 years: β = 0.0018, 95% CI −0.0012, 0.0048; aged 50–69 years: β = 0.0027, 95% CI −0.0009, 0.0063) in both 30–49 years group and 50–69 years group. In the 70–85 years group, this association was significantly positive in males (β = 0.0136, 95% CI 0.0068, 0.0204), but was not significantly different in females (β = 0.0007, 95% CI −0.0046, 0.0060). Conclusion The correlation between plasma tHcy level within the normal range and lumbar BMD differs by age and gender.

The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases

2007 ◽  
Vol 45 (12) ◽  
Author(s):  
Rima Obeid ◽  
Andrew McCaddon ◽  
Wolfgang Herrmann
Keyword(s):  
Disease Risk ◽  
Epidemiological Studies ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Dependent Relationship ◽  
Total Homocysteine ◽  
B Vitamin ◽  
Dose Dependent ◽  
Plasma Total Homocysteine

AbstractHyperhomocysteinemia (HHcy) is related to central nervous system diseases. Epidemiological studies show a positive, dose-dependent relationship between plasma total homocysteine (tHcy) concentration and neurodegenerative disease risk. tHcy is a marker of B-vitamin (folate, BClin Chem Lab Med 2007;45:1590–606.

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