Homocysteine, vitamins, and coronary artery disease. Comprehensive review of the literature.
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OBJECTIVE: To summarize results of clinical trials investigating the role of homocysteine (tHcy) as a risk factor for coronary artery disease (CAD) and the role of vitamin therapy (folic acid and vitamins B6 and B12) in primary and secondary prevention of CAD. QUALITY OF EVIDENCE: MEDLINE was searched from January 1976 to January 1999 to locate cross-sectional, retrospective and prospective cohort studies and meta-analyses on CAD using the MeSH words homocysteine, folic acid, vitamins B6 and B12, and coronary artery or heart disease. MAIN MESSAGE: Elevated tHcy levels are prevalent; most retrospective and cross-sectional studies show an association with increased risk of CAD. Results from recent prospective studies are less consistent. Folic acid, alone or with vitamins B6 and B12, reduces tHcy concentrations in the blood. Results from ongoing randomized controlled trials could determine the effect of vitamins B6 and B12 and folic acid supplementation on CAD-related morbidity and mortality and could indicate whether routine supplementation with these vitamins should be advocated. Before mass screening for tHcy can be done, the tHcy assay must be standardized. CONCLUSION: The role of homocysteine and vitamins B6 and B12 in managing CAD is unclear. Routine screening is not recommended. (+info)
Urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythrocyte aminotransferase levels in oral contraceptive users receiving controlled intakes of vitamin B6.
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Fifteen women who had used combination type oral contraceptives (estrogen plus progestogen) and 9 control women who had never used these agents were given a diet deficient in vitamin B6. After 1 month, this diet was supplemented daily with 0.8, 2.0 or 20.0 mg of pyridoxine hydrocholride for an additional month. At weekly intervals, measurements were made of urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythocyte alanine and aspartate aminotransterases. No significan differences were observed between oral contraceptive users and controls in any of the above measured indices. The data suggest that if the use of oral contraceptives of the combined estrogen-progestogen type does alter the requirement for vitamin B6, the effect is a mild one and of doubtful clinical significance to the majority of women taking these steroid preparations. The amount of vitamin B6 (as pyridoxine) needed to maintain normal levels of the above indices of vitamin B6 nutrition in these subjects were between 0.8 and 2.0 mg/day. (+info)
Functional capacity of the tryptophan-niacin pathway in the premenarchial phase and in the menopausal age.
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Studies on the interrelationship between female hormones associated with reproduction and the vitamin B6-dependent enzymes along the kynurenin pathway of trytophan metabolism were carried out in girls with an age less, and more than 10 years (just before the onset of the first menstrual cycle), and in postmenapausal women with and without relative (excess) production of estradioll from the adrenal cortex. It is found that most of the determined metabolites are retained by the girls with age less than 10 years after tryptophan loading without and with vitamin B6 supplementation. Estradiol from either the ovaries (in girls just before menarch), or the adrenal cortex-in postmenopausal women with relative (excess) production of this hormone-interferes with the further degradation of 3-hydroxyanthranilic acid. However, this interference could be completely restored by vitamin B6 supplementation. The extra presence of a partial impairment in the kynureninase enzyme is also suggested in these postmenopausal women. In the latter case, this enzymatic activity could be partially resored by vitamin B6 supplementation. On the contrary, the enzymes: kynureninases and adrenocortical estradio. Pyridoxine supplementation partially corrected the inhibition especially that of 3-hydroxykynurenine transaminase enzyme. (+info)
Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore.
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BACKGROUND: Epidemiologic studies have identified the plasma homocysteine concentration as a risk factor for atherothrombotic vascular disease. There is little information on the distributions and determinants of homocysteine concentrations in Asian populations. OBJECTIVE: The present study was designed to examine the relations between genetic and lifestyle factors and plasma homocysteine concentrations among Chinese in Singapore. DESIGN: Plasma total homocysteine, folate, vitamin B-12, and vitamin B-6 concentrations and genetic variation at the methylenetetrahydrofolate reductase (MTHFR) locus were measured in 486 Chinese men and women aged 45-74 y in Singapore. Data on dietary and other lifestyle factors were collected in face-to-face interviews. RESULTS: Men had higher plasma concentrations of total homocysteine than women (P = 0.0001). Age was positively associated with plasma homocysteine in both sexes (P for trend = 0.0001). Plasma concentrations of folate, vitamin B-12, and vitamin B-6 were inversely associated with homocysteine concentrations. Among individuals with low plasma folate, those possessing 2 copies of MTHFR mutant alleles had significantly higher homocysteine concentrations than did those with > or = 1 copy of the wild-type allele. Cigarette smoking, daily coffee consumption, and physical inactivity were positively related to plasma homocysteine concentrations in both sexes (P < 0.05). However, these associations disappeared after adjustment for plasma folate concentrations. CONCLUSIONS: Age, sex, plasma folate, vitamin B-12 and B-6 concentrations, and MTHFR genotype are independent determinants of plasma homocysteine in middle-aged and older Chinese in Singapore. These factors combined could account for up to 40% of the total variation in homocysteine concentrations in this Asian population. (+info)
Supplementation of atherogenic diet with B vitamins does not prevent atherosclerosis or vascular dysfunction in monkeys.
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BACKGROUND: Hyperhomocysteinemia is associated with increased risk of atherosclerotic and thrombotic vascular disease. In many patients, hyperhomocysteinemia can be treated or prevented by dietary supplementation with B vitamins, but the clinical benefit of B vitamins for the prevention of vascular disease has not been proven. METHODS AND RESULTS: Using an atherogenic diet that produces both hyperhomocysteinemia and hypercholesterolemia, we tested the hypothesis that dietary supplementation with B vitamins (folic acid, vitamin B(12), and vitamin B(6)) would prevent hyperhomocysteinemia, vascular dysfunction, and atherosclerotic lesions in monkeys. After 17 months, plasma total homocysteine increased from 3.6+/-0.3 to 11.8+/-1.7 micromol/L in monkeys fed an unsupplemented atherogenic diet (P<0.01) but did not increase in monkeys fed an atherogenic diet supplemented with B vitamins (3.8+/-0.3 micromol/L). Serum cholesterol increased from 122+/-7 to 550+/-59 mg/dL in the unsupplemented group (P<0.001) and from 118+/-5 to 492+/-55 mg/dL in the supplemented group (P<0.001). Responses to endothelium-dependent vasodilators, both in resistance vessels in vivo and in the carotid artery ex vivo, were impaired to a similar extent in groups that did and did not receive vitamin supplements. Anticoagulant responses to the infusion of thrombin were also impaired to a similar extent in both groups. Vitamin supplementation failed to prevent intimal thickening in the carotid or iliac arteries. CONCLUSIONS: These findings demonstrate that supplementation with B vitamins prevents hyperhomocysteinemia but is not sufficient to prevent the development of vascular dysfunction or atherosclerotic lesions in monkeys with marked hypercholesterolemia, even in the absence of preexisting atherosclerosis. (+info)
Effect of ethynodiol diacetate and mestranol on serum folic acid and vitamin B12 levels and on tryptophan metabolism in baboons.
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The effect of an oral contraceptive agent on serum folate and vitamin B12 levels and on some aspects of tryptophan metabolism in the baboon has been investigated. Folate levels were not affected by this treatment. Vitamin B12 levels were lowered during oral contraceptive treatment (P smaller than 0.1) and increased during a 30-day period of pyridoxine supplementation (P smaller than 0.01). Trends indicating deterioration of glucose tolerance and abnormal tryptophan metabolism were also observed. Definite conclusions concerning the effect of oral contraceptive agents on nutritive parameters could not be made. This is in keeping with the vast volume of literature published on the effects of oral contraceptive agents in humans and other species. It is concluded that perhaps, due to the biologically variable responses to oral contraceptive agents by individuals of any species, studies of serum levels of vitamins and other superficial biochemical parameters. Further, we conclude that the baboon could be a useful model for the study of endocrine influences on nutritive parameters, first because endocrine parameters resemble those of humans and second, because experimental protocols can be rigidly adhered to. (+info)
Effects of oral contraceptive steroids on vitamin and lipid levels in serum.
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The results of a comprehensive study to determine the effects of oral contraceptive agents on nutrient metabolism have been reported. The group of women using oral contraceptive agents was found to have significantly higher levels of hemoglobin, packed cell volume, serum vitamin A, total lipids, triglycerides, vitamin E, and alpha1-protein and significantly lower levels of serum and red cell folacin, vitamin B12 and albumin. The biological significance of many of these differences has not been elucidated satisfactorily. (+info)
Effects of methionine loading on plasma and erythrocyte sulphur amino acids and sulph-hydryls before and after co-factor supplementation in haemodialysis patients.
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BACKGROUND: Hyperhomocysteinaemia, which is potentially atherogenic, is common in chronic haemodialysis (HD) patients but the reason for this is not yet known. The methionine (Met) loading test (MLT) is used to test the capacity of homocysteine (Hcy) disposal by the trans-sulphuration pathway and thus may provide information on the metabolism of sulphur amino acids. The availability of vitamin B(6) and folic acid, as co-factors for Hcy metabolism may affect the response to MLT. In the present study, we compared the effect of Met loading on plasma and erythrocyte (RBC) sulphur amino acids and sulph-hydryls before and after co-factor supplementation in healthy subjects and HD patients. METHODS: In 10 HD patients and 10 healthy subjects the effect of Met loading, 0.1 g/kg BW, on plasma and RBC methionine metabolites was studied over 7 h, before and after 4 weeks supplementation with high daily doses of vitamin B(6) (200 mg) and folic acid (15 mg). RESULTS: MLT before vitamin supplementation in HD patients, compared to the healthy subjects, caused significantly greater increases in plasma Hcy levels (43+/-12 vs 15+/-5 micromol/l), cysteinesulphinic acid (CSA) (1.34 vs 0.36 micromol/l) and gamma-glutamylcysteine (0.98+/-0.83 vs -01+/-0.42 micromol/l) and no decline in plasma cysteine (Cys) (0.5+/-33.9 vs -31+/-26 micromol/l), but no significant differences in plasma taurine, cysteinylglycine, and glutathione concentrations. In RBCs there was a small increase in Hcy levels and a more marked increase in Tau levels, with no difference between the healthy subjects and HD patients. Vitamin supplementation in pharmacological doses failed to correct the abnormal responses to MLT in the HD patients. CONCLUSIONS: Oral methionine loading in HD patients leads to higher accumulation of Hcy and other Met metabolites in plasma and RBCs than in healthy subjects, indicating impaired metabolism of sulphur amino acids via the trans-sulphuration pathway. Supplementation with high doses of vitamin B(6) and folic acid does not correct this impairment, suggesting that it most probably is not due to lack of these co-factors. (+info)