Homocysteine lowering interventions for preventing cardiovascular events

Iberoamerican Cochrane Network, Valencia, Edo. Carabobo, Venezuela, 2001.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2009; 1(4):CD006612. DOI: 10.1002/14651858.CD006612.pub2
Source: PubMed

ABSTRACT 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, and may have a high risk for developing myocardial infarction, angina pectoris, stroke (ischaemic, haemorrhagic or both). 'Emergent or new risk factors' for cardiovascular disease have been recently added to the established risk factors (diabetes mellitus, high blood pressure, active smoker, adverse blood lipid profile). One of these risk factors is elevated circulating total homocysteine levels. Homocysteine is an amino acid, and its levels in 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. Hence, it has been suggested that B vitamin supplementation might reduce the risk of myocardial infarction, stroke, and angina pectoris. Preventive strategies might include healthy people with low or high risk for developing cardiovascular disease (primary prevention) and people with an established cardiovascular disease (secondary prevention). In this updated review, we included 12 randomised clinical trials involving 47,429 participants living in countries with or without mandatory fortification. We 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, stroke, or reduce total mortality in participants at risk or with established cardiovascular disease. Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer).

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    • "IL-6- knockout mice exhibit impaired immune and acute-phase responses [15]. Homocysteineis an í µí»¼-amino acid [16]. It is not obtained from the diet; it is biosynthesized from methionine [17]. "
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    ABSTRACT: Background. Chronic inflammation may play a role in psoriasis pathogenesis. Lipocalin 2, clusterin, soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6, homocysteine, and uric acid are inflammatory and/or biochemical markers. However, both the roles of these markers and the pathogenesis of psoriasis are unknown. Objective. The aim of this study was to investigate serum levels of lipocalin 2, clusterin, sTNFR-1, interleukin-6, homocysteine, and uric acid in patients and controls groups. Methods. Fifty-six patients with psoriasis and 33 healthy controls were included in the study. Serum concentrations of the markers were evaluated by ELISA. The Psoriasis Area and Severity Index (PASI) was evaluated in all psoriasis patients. Body mass index (BMI) was calculated by dividing weight (kg) by height (m) squared. Results. The serum value of lipocalin and sTNFR-1 were significantly higher in psoriasis patients than in controls (resp., P < 0.001, P < 0.05). The others showed no significant differences between psoriasis and the control groups (all of them P > 0.05). The mean PASI score in the patient group was 8.3 ± 6.5. Conclusions. These findings suggest that lipocalin 2 and sTNFR-1 might play a role in the pathogenesis of psoriasis and can be used as markers of the disease.
    Disease markers 04/2014; 2014:541709. DOI:10.1155/2014/541709 · 2.17 Impact Factor
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    • "Similarly, HS-indomethacin and HS-naproxen are more GI sparing than their traditional counterparts [12,14]. HS-mesalamin exhibits a marked increase in antiinflammatory activity and potency in a murine model of colitis, compared to mesalamine [15] [16], while GYY4137, a slow-releasing H 2 S donor, has anti-inflammatory properties in a mouse model of endotoxic shock [17]. "
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    ABSTRACT: Hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (HS-NSAIDs) are an emerging novel class of compounds with significant anti-inflammatory properties. They consist of a traditional NSAID to which an H(2)S-releasing moiety is covalently attached. We examined the effects of four different HS-NSAIDs on the growth properties of eleven different human cancer cell lines of six different tissue origins. Human colon, breast, pancreatic, prostate, lung, and leukemia cancer cell lines were treated with HS-aspirin, -sulindac, -iburofen, -naproxen, and their traditional counterparts. HS-NSAIDs inhibited the growth of all cancer cell lines studied, with potencies of 28- to >3000-fold greater than that of their traditional counterparts. HS-aspirin (HS-ASA) was consistently the most potent. HS-NSAIDs inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle block. Metabolism of HS-ASA by colon cells showed that the acetyl group of ASA was hydrolyzed rapidly, followed by hydrolysis of the ester bond linking the salicylate anion to the H(2)S releasing moiety, producing salicylic acid and ADT-OH from which H(2)S is released. In reconstitution studies, ASA and ADT-OH were individually less active than the intact HS-ASA towards cell growth inhibition. Additionally, the combination of these two components representing a fairly close approximation to the intact HS-ASA, was 95-fold less active than the intact HS-ASA for growth inhibition. Taken together, these results demonstrate that HS-NSAIDs have potential anti-growth activity against a wide variety of human cancer cells.
    Biochemical pharmacology 03/2012; 83(6):715-22. DOI:10.1016/j.bcp.2011.12.018 · 4.65 Impact Factor
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    • "It is well known that low folate intake, low folate status, or high plasma homocysteine concentrations are independent risk factors for a number of adverse health outcomes including, among others: cardiovascular diseases, some cancers, cognitive decline in the elderly, adverse pregnancy outcomes, and congenital malformations. Although it is well known that an FA supplementation effectively lower the homocysteine concentration [1], up to date, the expected risk decrease of the cardiovascular events, cancers, adverse pregnancy outcomes, or other adverse health outcomes has not been supported by the available studies [2] [3] [4] [5] [6] [7] [8] [9] [10]. The only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies including pre–post evaluation after mandatory fortification, is the risk reduction of neural tube defects (NTDs). "
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    ABSTRACT: In recent years, a number of studies have been performed to evaluate the possible health benefits of an increased intake of folic acid (FA) on human health. However, the only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies is the risk reduction of neural tube defects (NTDs). NTDs are congenital malformations that include anencephaly, encephalocele, and spina bifida caused by the failure of fusion of the neural tube that normally closes between 22nd and 28th day since conception (on an average 40-42th day after the first day of last menstrual period). The occurrence of NTDs varies among population between 0.8 and 3 per 1,000, and it is estimated that 324,000 pregnancies are affected every year worldwide. More FA can decrease the NTDs risk up to 0.6 per 1,000 births. Other malformations as congenital heart defects, cleft lip, and limb deficiencies can be most probably also reduced. To decrease the NTDs risk, it is recommended that all women capable of becoming pregnant should have more FA. The goal is that every woman could start her pregnancy with an optimal folate status, estimated today to be as more than 906 nmol/L of red blood cell folate concentration. More FA can be obtained through a strict Mediterranean pattern of nutrition and healthy life style, fortified food, supplements. Women and health authorities can choose the most appropriate strategy. Monitoring folate status of women during the periconceptional period is an essential way to evaluate the success of the preferred strategy.
    BioFactors 07/2011; 37(4):272-9. DOI:10.1002/biof.172 · 3.00 Impact Factor
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