RELEVANT RESEARCH STUDIES AND ARTICLES
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- Wald, D et al. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.
British Journal of Medicine. 2002;325:1202
*Quick Summary of Study: Lower serum homocysteine levels reduces the risk of cardiovascular disease.
To assess whether the association of serum homocysteine concentration with ischaemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke is causal and, if so, to quantify the effect of homocysteine reduction in preventing them.
Meta-analyses of the above three diseases using (a) 72 studies in which the prevalence of a mutation in the MTHFR gene (which increases homocysteine) was determined in cases (n=16b) 20 prospective studies (3820 participants) of serum homocysteine and disease risk.
Main outcome measures
Odds ratios of the three diseases for a 5 Î¼mol/l increase in serum homocysteine concentration.
There were significant associations between homocysteine and the three diseases. The odds ratios for a 5 Î¼mol/l increase in serum homocysteine were, for ischaemic heart disease, 1.42 (95% confidence interval 1.11 to 1.84) in the genetic studies and 1.32 (1.19 to 1.45) in the prospective studies; for deep vein thrombosis with or without pulmonary embolism, 1.60 (1.15 to 2.22) in the genetic studies (there were no prospective studies); and, for stroke, 1.65 (0.66 to 4.13) in the genetic studies and 1.59 (1.29 to 1.96) in the prospective studies.
The genetic studies and the prospective studies do not share the same potential sources of error, but both yield similar highly significant resultsï¿½strong evidence that the association between homocysteine and cardiovascular disease is causal. On this basis, lowering homocysteine concentrations by 3 Î¼mol/l from current levels (achievable by increasing folic acid intake) would reduce the risk of ischaemic heart disease by 16% (11% to 20%), deep vein thrombosis by 25% (8% to 38%), and stroke by 24% (15% to 33%).
2.Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ. 1998;316(7135):894-898
*Quick Summary of Study: Folic acid,B-12 and B-6 were found to reduce serum levels of homocysteine.
Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6.
Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentrations. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6.
Subjects: Individual data on 1114 people included in 12 trials.
Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P<0.001) and at lower pretreatment blood folate concentrations (P<0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12
Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5
3. Al-Majed AA, Sayed-Ahmed MM, Al-Omar FA, Al-Yahya AA, Aleisa AM, Al-Shabanah OA (August 2006). "Carnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus". 2006; 33 (8): 725-733.
*Quick Summary of Study: Animal study shows that Acetyl-L-carnitine can help keep neurons intake against induced ischaemia neural damge.
1. The present study investigated whether propionyl-L-carnitine (PLC) has neuroprotective effects, similar to those reported for acetyl-L-carnitine (AC), against transient forebrain ischaemia-induced neuronal damage and biochemical derangement in the rat hippocampal CA1 region. 2. In total, 105 adult male Wistar albino rats were divided into seven groups of 15 animals each. The first three groups were injected i.p. with normal saline, AC (300 mg/kg) or PLC (300 mg/kg) for 7 successive days. The next three groups were injected i.p. with the same doses of normal saline, AC or PLC immediately after the induction of 10 min forebrain ischaemia and i.p. injections were continued for 7 successive days. Rats in the seventh group were subjected to sham-operated ischaemia and injected with normal saline for 7 successive days. 3. Seven days after treatment, animals were killed and their brains isolated for histopathological examination and biochemical studies. 4. Forebrain ischaemia resulted in a significant decrease in the number of intact neurons (77%), ATP concentration (51%) and glutathione content (32%), whereas there was a significant increase in the production of thiobarbituric acid-reactive substances (TBARS; 71%) and total nitrate/nitrite (NOx; 260%) in hippocampal tissues. 5. Administration of either AC or PLC attenuated forebrain ischaemia-induced neuronal damage, manifested by a greater number of intact neurons, ATP and glutathione, as well as a decrease in TBARS and NOx in hippocampal tissues. 6. Results from the present study suggest, for the first time, that PLC attenuates forebrain ischaemia-induced neuronal injury, oxidative stress and energy depletion in the hippocampal CA1 region. Propionyl-L-carnitine has neuroprotective effects similar to AC and could have a potential use in the treatment of neurodegenerative diseases. 7. The results of the present study will open up new perspectives for the use of PLC in the treatment of neurodegenerative diseases associated with, or secondary to, myocardial ischaemia-reperfusion injury and chronic circulatory failure.
4. Haleagrahara N, Julian V, Chakravarthi S. N-acetylcysteine Offers Cardioprotection by Decreasing Cardiac Lipid Hydroperoxides and 8-Isoprostane Level in Isoproterenol-Induced Cardiotoxicity in Rats. Cardiovasc Toxicol. 2011 Jul 28.
*Quick Summary of Study: Animal study shows that NAC can improve antioxidant enzymes levels and reduce the negative effects caused by induced cardiovascular toxicity.
This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague-Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P < 0.05) in LPO and IP levels in ISO-control group and NAC treatment reduced these changes. Antioxidant enzyme, SOD and GSH, level decreased significantly (P < 0.05) in ISO-control group, and treatment with NAC was able to reverse these changes significantly (P < 0.05). Histopathologically, ISO-control group showed morphological changes suggestive of cardiotoxicity with large areas of coagulative necrosis, with diffused interstitial edema. NAC treatment successfully reduced these histopathological changes. In conclusion, the study proves that NAC has a strong cardioprotective effect against isoproterenol-induced cardiac changes. NAC decreases isoproterenol-induced LPO and IP