The effect of a subnormal vitamin B-6 status on homocysteine metabolism.

Ubbink, Johan B.; Merwe, Anita van der; Delport, Rhena; Allen, Robert H.; Stabler, Sally P.; Riezler, Reiner; Vermaak, W. J. H.

doi:10.1172/jci118763

Cited by 228 publications

(132 citation statements)

References 50 publications

(48 reference statements)

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“…Previous studies have reported increased cystathionine concentrations in patients with asthma, a condition known to be related to systemic inflammation 29. Accordingly, in our study, plasma cystathionine concentration was directly associated with CRP, a marker of inflammation 30.…”

Section: Discussionsupporting

confidence: 63%

“…Alternatively, high plasma cystathionine may reflect suboptimal nutritional status 20, 21. In this regard, previous studies showed that low serum concentrations of B‐vitamins, in particular vitamin B6, were strongly associated with high cystathionine levels 21, 29. However, any influence by poor nutrition status seems unlikely, because plasma levels of B‐vitamins neither attenuated the association between plasma cystathionine and stroke events nor introduced any significant effect modification.…”

Section: Discussionmentioning

confidence: 98%

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Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

Dhar

Svingen

Ueland

et al. 2018

JAHA

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BackgroundCystathionine is an intermediate product in the transsulfuration pathway and formed during the B6‐dependent conversion of methionine to cysteine. Elevated plasma cystathionine has been related to atherosclerosis, which is a major etiological factor for ischemic stroke. However, the role of cystathionine in stroke development is unknown. Therefore, we prospectively assessed the association of circulating levels of cystathionine with risk of total and ischemic stroke.Methods and ResultsTwo‐thousand thirty‐six patients (64% men; median age, 62 years) undergoing coronary angiography for suspected stable angina pectoris were included. Stroke cases were identified by linkage to the CVDNOR (Cardiovascular Disease in Norway) project. Hazard ratios with confidence intervals (95% confidence interval) were estimated by using Cox‐regression analyses. During 7.3 years of median follow‐up, 124 (6.1%) incident strokes were ascertained, which comprised 100 cases of ischemic stroke. There was a positive association of plasma cystathionine with risk of total stroke and ischemic stroke. Comparing the fourth versus the first cystathionine quartiles, age‐ and sex‐adjusted hazard ratios (95% confidence interval) were 2.11 (1.19–3.75) and 2.56 (1.31–4.99) for total and ischemic stroke, respectively. Additional adjustment for major stroke risk factors only slightly attenuated the associations, which tended to be stronger in patients without previous or existing atrial fibrillation at baseline (hazard ratio [95% confidence interval], 2.43 [1.27–4.65] and 2.88 [1.39–5.98] for total and ischemic stroke, respectively).ConclusionsIn patients with suspected stable angina pectoris, plasma cystathionine was independently related to increased risk of total stroke and, in particular, ischemic stroke.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 98%

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

Dhar

Svingen

Ueland

et al. 2018

JAHA

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“…A possible explanation has been attributed to the role of Sadenosylmethionine in the regulation of homocysteine metabolism. S-adenosylmethionine (an activator for the enzyme cystathionine b-synthase) favors folate and vitamin B 12 -dependent homocysteine remethylation to methionine in the fasting state; vitamin B 6 deficiency does not affect Sadenosylmethionine Ubbink et al, 1996). Homocysteine is only directed to the trans-sulfuration pathway when methionine is in excess.…”

Section: Discussionmentioning

confidence: 99%

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

et al. 2004

Eur J Clin Nutr

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Objective: To investigate whether vitamin B 6 supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. Design: A single-blind intervention study. Setting: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. Subjects: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. Interventions: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n ¼ 8), 5 mg vitamin B 6 (n ¼ 8), 10 mg vitamin B 6 (n ¼ 8), 50 mg vitamin B 6 (n ¼ 9), or 5 mg folic acid combined with 0.25 mg vitamin B 12 (n ¼ 9) for 12 weeks. Main outcome measures: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B 6 status was assessed by direct measures (plasma pyridoxal 5 0 -phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B 12 were measured. Results: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B 6 when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B 12 supplementation (P ¼ 0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B 6 supplemented groups, respectively; whereas folic acid combined with vitamin B 12 supplementation significantly reduced fasting plasma homocysteine concentration by 32% (Po0.001). Conclusions: Our results indicate that vitamin B 6 supplementation alone is less effective than folic acid combined with vitamin B 12 in lowering plasma homocysteine concentrations in CAD patients.

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“…In certain studies, interlaboratory imprecision with immunoassay methods has been reported. 21 In addition, fluorescence immunoassay reagents are relatively very expensive. 15 As stated by Refsum et al in their comprehensive 2004 review coauthored by a group of the world's leading experts in this field, many analytical methods afford results that do not fulfill baseline bias and imprecision criteria.…”

Section: Homocysteine and Cysteine In Human Healthmentioning

confidence: 99%

Detection of Homocysteine and Cysteine

et al. 2005

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At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular diseases, Alzheimer's disease, neural tube defects, and osteoporosis. Both 1 and cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by which 1 and 3 are involved in disease states are relatively unclear. Herein, we describe simple methods for detecting either Hcy or Cys in the visible spectral region with the highest selectivity reported to date without using biochemical techniques or preparative separations. Simple methods and readily available reagents allow for the detection of Cys and Hcy in the range of their physiologically relevant levels. New HPLC postcolumn detection methods for biological thiols are reported. The potential biomedical relevance of the chemical mechanisms involved in the detection of 1 is described.

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The effect of a subnormal vitamin B-6 status on homocysteine metabolism.

Cited by 228 publications

References 50 publications

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

Detection of Homocysteine and Cysteine

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