Homocysteine and methylmalonic acid levels in pregnant Nepali women. Should cobalamin supplementation be considered?
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OBJECTIVE: The aim of this study was to investigate homocysteine and methylmalonic acid levels as markers of functional cobalamin and folate status in pregnant Nepali women. DESIGN: Cross-sectional study. SETTING: Patan Hospital, Kathmandu, Nepal. SUBJECTS: A sub-sample (n=382) of all pregnant women (n=2856) coming for their first antenatal visit in a 12 month period, 1994-1995. The selection of the sub-sample was based on maternal haematocrit values, categorised into three groups: severely, moderately and non-anaemic women. As serum levels of total homocysteine (s-tHcy) and methylmalonic acid (s-MMA) were similar in the three groups, pooled data are presented. Women who had already received micronutrient supplementation (n=54) were excluded. The remaining women (n=328) were included in the statistical analysis. RESULTS: Overall mean values (+/-s.d.) of s-tHcy and s-MMA were 9.5 (+/-4.2) micromol/l and 0.39 (+/-0.32) micromol/l, respectively. Elevated s-tHcy (>7.5 micromol/l) was found in 68% of the women, while 61% had elevated s-MMA (>0.26 micromol/l). Low s-cobalamin values (<150 pmol/l) were observed in 49% of the women, while only 7% had low s-folate values (< or =4.5 nmol/l). s-tHcy was significantly correlated with s-MMA (r=0.28, P<0.001), s-cobalamin (r=-0.30, P<0.001) and s-folate (r=-0.24, P<0.001). s-MMA was significantly associated with s-cobalamin (r=-0.40, P<0.001), but not with s-folate. CONCLUSIONS: Functional cobalamin deficiency was very common in the study population, while functional folate deficiency was rather uncommon. We suggest considering cobalamin supplementation to pregnant Nepali women. SPONSORSHIP: The Norwegian Research Council and the Norwegian Universities Committee for Development, Research and Education. (+info)
In what extent anemia coexists with cognitive impairment in elderly: a cross-sectional study in Greece.
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BACKGROUND: A project aimed at studying the frequency of dementia and depression in the catchment area of the Health Centre of Chrissoupolis (HCCh), Northern Greece, was carried out. This paper reports the association between AD and anemia among the elderly participants in this Greek study. METHODS: Eligible participants were people 65 years or over who were (a) living in the Elderly People's Home (all 48 subjects included); (b) visiting the Open Center for Elderly People during a 20 workday period (75 subjects) and (c) visiting the HCCh for routine medical care. The Mini Mental State Examination (MMSE) was used in assessing the cognitive capacity of the participants. Blood was drawn for serum hematocrit, vitamin B12 and folate determination. RESULTS: The prevalence proportions of possible cognitive impairment among anemic and non-anemic males were 55.6% and 34.4%, respectively (X2 = 5.8, d.f. = 1, p = 0.016). The corresponding proportions in females were 47.5% and 40.1 % (X2 = 1.1, d.f. = 1, p = 0.305). Using logistic regression analysis, age-group (>or= 80 yrs), type of Institute, vitamin B12 and anemia had significant independent associations with possible cognitive impairment. CONCLUSIONS: Anemia is a frequent finding in elderly and it may be a risk factor for dementia, but the extent of the associated deterioration of cognitive impairment or the relation with AD is not known. GPs should be aware of this coexistence and recommend for screening, assaying and treating elderly people. (+info)
Thymidylate synthetase activity in bone marrow cells in pernicious anemia.
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The tritium release assay for the demonstration of thymidylate synthetase activity has been applied to the measurement of enzyme activity in the bone marrow of four patients with pernicious anemia and nine normal subjects. On the average, an approximately ninefold increase in enzyme activity was observed in patients with pernicious anemia. In the absence of 5, 10-methylene-tetrahydrofolate, enzyme activity was reduced in both normal and in pernicious anemia cells. Addition of 5, 10-methylene-tetrahydrofolate to the assay medium resulted in a far greater activation of thymidylate synthetase activity in megaloblastic bone marrow cells than in the cells of control subjects. (+info)
Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores.
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Mild hyperhomocysteinemia is an independent risk factor for cardiovascular disease and may result from a deficiency of folate, vitamin B-6 or vitamin B-12. Because vitamin B-12 deficiency is often associated with vegetarianism, this study was designed to examine the effect of Taiwanese vegetarian diets on B-vitamin status and plasma homocysteine levels. Female Buddhist lacto-vegetarians (n = 45; 31-45 y) and matched omnivores (n = 45) recruited in Hualien, Taiwan, were investigated. Taiwanese vegetarians consumed normal amount of folate, but only 21% of Taiwan Recommended Daily Nutrient Allowances (RDNA) values of vitamin B-12. Compared with the omnivores, the vegetarians had significantly higher levels of plasma folate (14.79 +/- 7.70 vs. 11.98 +/- 8.29 nmol/L), but lower levels of vitamin B-12 (207.7 +/- 127.1 vs. 403.5 +/- 138.9 pmol/L). Fasting plasma homocysteine levels were significantly higher in vegetarians than in omnivores (mean: 11.20 +/- 4.27 vs. 8.64 +/- 2.06 micromol/L; median: 10.5 vs. 8.5 micromol/L). Fasting plasma homocysteine was inversely correlated with plasma folate and vitamin B-12 in the vegetarian group. Multiple regression analysis revealed that plasma folate, vitamin B-12 and creatinine were independent determinants of homocysteine variation and contributed to 38.6% of homocysteine variation in the vegetarians. Compared with the omnivores, vegetarians also had significantly lower serum levels of valine, isoleucine, leucine, lysine, alanine and arginine, but higher levels of glycine. In the vegetarian group, fasting plasma homocysteine correlated negatively with serum threonine, lysine, histidine, arginine and cystine, and these amino acids contributed to 38.7% of homocysteine variation. In conclusion, the Buddhist nuns who consumed a lacto-vegetarian diet had mildly elevated fasting plasma homocysteine levels presumably due to lower levels of plasma vitamin B-12. (+info)
The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people.
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Hyperhomocysteinemia is considered a risk factor for cardiovascular disease and is prevalent in the elderly. Supplementation with folic acid, vitamin B-6 and B-12 lowers homocysteine levels. In January 2000, the Chilean government initiated a flour folic acid fortification program to decrease the occurrence of neural tube defects. The aim of this study was to evaluate the effect of this program on serum homocysteine and folate levels in elderly subjects after 6 mo. A total of 108 elderly people were studied. We measured serum folate, homocysteine and vitamin B-12 levels before the fortification started and 6 mo later. At baseline, folate deficiency (<6.8 nmol/L) was present in 1.8%, vitamin B-12 deficiency (<165 pmol/L) in 27.6% and hyperhomocysteinemia (>14 micromol/L) in 31% of the sample. Six months later, serum folate levels increased from 16.2 +/- 6.2 to 32.7 +/- 7.1 nmol/L (P < 0.001), homocysteine levels decreased from 12.95 +/- 3.7 to 11.43 +/- 3.6 micromol/L (P < 0.001) and vitamin B-12 levels were unchanged. Flour fortification with folic acid had a moderate lowering effect on homocysteine levels. Given that vitamin B-12 deficiency was more common than folate deficiency, it may be more appropriate to add vitamin B-12 to food, at least in foods for this age group. (+info)
Hyperhomocysteinaemia, folate and vitamin B12 in unsupplemented haemodialysis patients: effect of oral therapy with folic acid and vitamin B12.
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BACKGROUND: Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition). B-complex vitamin supplements have been shown to lower plasma total homocysteine (tHcy) concentrations, but the respective effectiveness of folate and oral vitamin B12 is not yet known. Our objectives were: (i) to determine the status of folate and vitamin B12 in a cohort of unsupplemented dialysis patients (ii) to assess the homocysteine-lowering effect of a folate supplement and then of a folate supplement with added vitamin B12. The responses were analysed for the C677T genotypes of MTHFR. METHODS: Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC). All patients were then given daily supplements of 15 mg of folic acid for 2 months. They were given daily supplements of 1 mg of vitamin B12 in addition to the folate supplements for a further 2 months. Plasma tHcy, folate and vitamin B12 were monitored after each intervention. RESULTS: At baseline folate and vitamin B12 deficiencies were found in 10% and 6% of the patients. Initial plasma tHcy concentrations were high in all patients (mean 38.1+/-15 micromol/l). CC patients tended to have a lower tHcy concentration than pooled CT and TT patients. After 2 months of folate therapy, tHcy concentration decreased significantly to 20.2+/-7 micromol/l (P<0.001) and no significant differences were observed between the different genotype subgroups (19.4+/-6 for CC, 21.3+/-8 for CT, 18.5+/-4 for TT). A significant positive relationship was found between the reduction of tHcy and its initial value (rho=0.615, P<0.0001). The impact of the added vitamin B12 was negligible since tHcy concentrations did not change for the patients as a whole (19.8+/-7 micromol/l, NS) or in any subgroup (19.1+/-5 for CC, 20.3+/-9 for CT and 20+/-7 micromol/l for TT). CONCLUSIONS: (i) Folate and vitamin B12 deficiencies were observed in 10% and 6% respectively of our unsupplemented dialysis patients. (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups. (iii) Vitamin B12 supplements are useful in folate treated patients to prevent cobalamin deficiency and its neurological consequences but they did not lower tHcy plasma levels for the patients as a group or for any of the MTHFR subgroups. (+info)
Megaloblastic erythropoiesis and macrocytosis in patients on anticonvulsants.
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The results of deoxyuridine suppression tests on the bone marrow cells of 14 patients on anticonvulsant drugs, 11 of whom had evidence of megaloblastic erythropoiesis, indicated that the megaloblastic changes and macrocytosis encountered in treated epileptics are often not caused either by folate deficiency or by drug-induced impairment of the 5, 10-methylenetetrahydrofolate-dependent methylation of deoxyuridylate to thymidylate. A folate-related abnormality in the methylation of deoxyuridylate was found in only two of the 11 patients with megaloblastic erythropoiesis. (+info)
Cardiac structure and function in vitamin B-12-deprived rats.
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The effect of prolonged vitamin B-12 deprivation in rats on the histological structure of heart and on cardiac linoleic acid oxidation has been investigated. Offspring from pregnant females fed vitamin B-12-deficient diets were fed the deprivation diet for up to 16 months, and the development of B-12 deficiency was monitored by determination of urinary methylmalonic acid levels. These levels averaged 4.2 mg/day by 9 months of B-12-deprivation diet, and 142 mg/day after 16 months. The hearts of these animals were characterized by extensive fibrosis, and electron microscopy revealed cardiac mitochondria that were grossly enlarged and distorted. The metabolic defect of B-12 deprivation in heart muscle was determined in isolated hearts during recirculating perfusion of labeled propionic acid. Both the uptake and oxidation of propionic acid were markedly reduced in hearts from B-12-deprived rats (16 months) compared with controls, and the site of the metabolic block, i.e., accumulation of labeled methylmalonate, was established. Vitamin B-12 deprivation did not affect the extraction of recirculating labeled linoleic acid by perfused hearts, in contrast to the effect on propionic extraction. Furthermore, the oxidation of the extracted fatty acid was markedly increased over controls. Analysis of the circulating media after 45-minute perfusions showed no accumulation of labeled methylmalonate but did contain significantly less succinate than perfusion media from control hearts. The results are discussed with respect to cardiac structure and to the oxidative pathway(s) for polyunsaturated fatty acids. (+info)