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      Variations in the lipid profile of patients with chronic renal failure treated with pyridoxine

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          Abstract

          Background

          Hyperhomocysteinemia and lipid abnormalities are commonly found in patients with chronic renal failure; both are recognized as risk factors for atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial. This study was performed to determine the effect of a high dose of pyridoxine (300 mg i.v. three times a week) on plasma and red blood cell lipid profile and plasma homocysteine concentration in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (basal 1), after 30 and 60 days of treatment and 4 months after withdrawal (basal 2).

          Results

          Pyridoxine supplementation induced a significant decrease in total plasma homocysteine level and also a lowering effect in plasma total cholesterol and triglycerides. These biochemical data increased when the samples were taken at basal 2, reaching the levels obtained at the beginning of the experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl-hexatriene.

          Conclusions

          We conclude that high doses of pyridoxine represent an effective strategy to ameliorate both plasma homocysteine levels and lipid profiles in chronic renal failure patients, protecting them from atherosclerosis. Further research using a long-term treatment would be necessary in an attempt to restore the fatty acid pattern and the fluidity of red cell membranes.

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          Most cited references41

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          Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

          Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. Case-control study. Nineteen centers in 9 European countries. A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.
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            Homocysteine and vascular disease.

            For more than 20 years, moderately raised concentrations of total homocysteine (tHcy) have been associated with an increased risk of atherothrombotic vascular events but only recently has evidence mounted to suggest that the association may be causal. The association is independent of other factors, it is fairly consistent across many studies, it is strong and dose-related, and it is biologically plausible. However, the evidence needs to be strengthened by a systematic review of all comparable studies and the demonstration, in randomised trials, that lowering tHcy is followed by a significant reduction in atherothrombotic vascular disease. In addition, the measurement of tHcy needs to be standardised. If these can be achieved then tHcy measurement will become another useful marker of vascular risk, multivitamin therapy will be another therapeutic option for people at risk of atherothrombotic vascular disease, and fortification of food with folic acid will rise high on the political and public health agenda.
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              The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function.

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                Author and article information

                Journal
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                2003
                18 September 2003
                : 2
                : 7
                Affiliations
                [1 ]Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP-CONICET-UNLP)
                [2 ]Cátedra de Medicina Interna, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900, La Plata, Argentina. Fax: 54:221 4258988
                Article
                1476-511X-2-7
                10.1186/1476-511X-2-7
                222990
                14575530
                2a414e80-fb4e-4e24-b967-9991357e4463
                Copyright © 2003 de Gómez Dumm et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
                History
                : 28 August 2003
                : 18 September 2003
                Categories
                Research

                Biochemistry
                chronic renal failure,cholesterol,homocysteine,pyridoxine,triglyceride,polyunsaturated fatty acids

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