Review questionWe reviewed homocysteine-lowering interventions for preventing cardiovascular events. Background
Cardiovascular disease is the number one cause of death worldwide. The most common causes of cardiovascular disease leading to both morbidity and mortality are ischaemic heart disease, stroke and congestive heart failure. Many people with cardiovascular diseases may be asymptomatic, but may have a high risk of developing myocardial infarction, angina pectoris or stroke (ischaemic, haemorrhagic or both). 'Emergent' or new risk factors for cardiovascular disease have recently been added to the established risk factors (which are diabetes mellitus, high blood pressure, active smoking and an adverse blood lipid profile). One of these risk factors is elevated circulating total homocysteine levels. Homocysteine is an amino acid and its levels in the blood are influenced by blood levels of B-complex vitamins: cyanocobalamin (B12), folic acid (B9) and pyridoxine (B6). High plasma total homocysteine levels are associated with an increased risk of atherosclerotic diseases (where there is a build-up of plaque in the arteries). Study characteristicsIn this second update, we included 12 studies involving 47,429 participants living in countries with or without mandatory fortification of foods. These studies compared different regimens of B-complex vitamins (cyanocobalamin (B12), folic acid (B9) and pyridoxine (B6)) with a control or any other comparison. The studies were published between 2002 and 2010. Key resultsWe found no evidence that homocysteine-lowering interventions, in the form of supplements of vitamins B6, B9 or B12 given alone or in combination, at any dosage compared with placebo or standard care, prevent myocardial infarction or stroke, or reduce total mortality in participants at risk of or with established cardiovascular disease. Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer). Quality of evidenceOur confidence in the results of this review is high because the included trials we synthesised were of high quality and conducted with a large number of participants.
"Vitamins B The association of vitamins B6 (pyridoxin), B9 (folic acid) and B12 (cyanocobalamine) reduces the production of homocysteine (Gariballa et al., 2012) and DNA methylation , but there are contradictory reports regarding the protection against cognitive decline (De Jager et al., 2012; Nachum-Biala & Troen, 2012), vascular disease (Saposnik et al., 2009; Marti-Carvajal et al., 2015) or death (Towfighi et al., 2014). It has been documented that the regular intake of these vitamins B prevents brain shrinkage, and the resulting dementia, among persons with a high homocysteine concentration in blood (Douaud et al., 2013), whereas folate intake below the recommended daily allowance was associated with increased risk of cognitive impairment (Agnew-Blais et al., 2015). "
[Show abstract][Hide abstract] ABSTRACT: The long-term intake of a judiciously composed nutriceutical containing low-dose vitamins, antioxidants, minerals and particular herbal preparations seems justified for older persons who take medication, or who consume an unbalanced diet, or who are exposed to environmental toxins. Recent reports suggest these nutriceuticals may delay age-related diseases and the occurrence of cancer, and reduce mortality in apparently healthy ageing men. Food supplementation with a nutriceutical that was formulated particularly for ageing men should result in an increase of at least one quality-adjusted life year and may lower the financial and social burden of disease in elderly people.
"It has been shown that the nutritional status of stroke patients is closely related to their long term clinical outcome . Though a large number of studies have investigated the effect of specific nutrients on the recurrence of stroke such as vitamin B, folic acid ( , antioxidants   , and fat    ), none have shown significant improvements in mortality and recurrence of stroke. There is no evidence to support the timing or choice of nutritional method which should be used in stroke patients. "
"Subsequently, numerous cross-sectional and case control studies have demonstrated a clear association between total serum homocysteine and the presence of coronary, carotid, and peripheral vascular disease23456. However, a systemic review of 12 randomized controlled trials involving 47,429 participants showed that homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction, stroke or death by any cause313233. Clinical benefit of homocysteine lowering therapy is very controversial topics. "
[Show abstract][Hide abstract] ABSTRACT: Hyperhomocystemia has been reported to be associated with cardiovascular disease, especially stroke. The resistive index (RI) estimated by carotid ultrasound is an established variable for estimating the risk of cerebral infarction. The aim of this study was to evaluate the relationship between homocysteine concentration and carotid RI, a marker of cerebral vascular resistance in essential hypertensive patients. We measured serum total homocysteine and carotid RI in 261 patients. Multiple linear regression analysis was used to determine the association of homocysteine with carotid RI and intima media thickness (IMT). Age, sex, BMI, systolic blood pressure (SBP), homocysteine, total cholesterol, high density lipoprotein-cholesterol (HDL-C), uric acid, CRP, HbA1c, estimated glomerular filtration rate, and use of antihypertensive agents were included as independent variables. Age, sex, use of antihypertensive agents, HDL-C and homocysteine levels were shown to be significant predictors of carotid RI, but not IMT. Multiple regression analysis in men older than 65 years showed homocysteine and SBP were associated significantly with carotid RI. In elderly male patients, homocysteine was the strongest predictor of carotid RI (B = 0.0068, CI = 0.0017-0.0120, P = 0.011) in the multivariate model. In conclusion, hyperhomocysteinemia is associated with carotid RI, a surrogate marker of cerebral vascular resistance, especially in elderly men.
Marko Boban, Damir Raljevic, Vesna Pehar Pejcinovic, Viktor Persic
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