Folate deficiency reduces the GPI-anchored folate-binding protein in rat renal tubules.
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A folate-binding protein (FBP) anchored to cell membranes by a glycosyl phosphatidylinositol (GPI) adduct is constitutively expressed in some transformed and cultured cell lines. Its expression is upregulated when these cells are grown in medium containing low folate, but whether this occurs in vivo with nutritional folate deficiency is unknown. To address this question, the GPI-FBP in the liver, kidney, and brain of rats on control and folate-deficient (FD) diets was measured. The GPI-FBP in the kidney of FD rats decreased significantly in contrast to the upregulation of this protein in cultured cells. Northern blot analysis and nuclear run-on assays indicated that transcription of the GPI-FBP gene in the kidney was not reduced by folate deficiency. This decrease of the GPI-FBP appears to result from its proteolysis, similar to the enzymatic degradation of the apoprotein that occurs in vitro. Because the GPI-FBP is on the brush borders of the proximal renal tubules and provides for the reabsorption of folate, this function diminishes when the protein decreases in folate deficiency. (+info)
The plasma homocysteine concentration is better than that of serum methylmalonic acid as a marker for sociopsychological performance in a psychogeriatric population.
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BACKGROUND: Cobalamin/folate deficiency in elderly subjects may lead to psychiatric symptoms, but more often it increases the severity of various organic and nonorganic mental diseases. A major clinical problem, however, is the uncertainty and controversy concerning biochemical markers of cobalamin/folate deficiency to be used in the diagnostic evaluation of suspected cobalamin/folate deficiency. METHODS: We measured plasma homocysteine (tHcy), blood folate, serum methylmalonic acid, and serum cobalamin in 80 psychogeriatric patients (age, 77.3 +/- 8.6 years) and 50 controls (age, 76.1 +/- 8. 0 years). We assessed associations of these tests with measures of cognitive and behavior performance by use of regression analyses. RESULTS: Plasma tHcy was increased in 45% of the psychogeriatric population (mean, 20.5 +/- 9.2 micromol/L vs 15.3 +/- 4.7 micromol/L for controls; P <0.01). Plasma tHcy correlated with severity of dementia (r = 0.36; P <0.01), the Katz ADL index (r = 0.29; P <0.05), the Berger scale (r = 0.29; P <0.05), and the score of symptoms (r = 0.39; P <0.001) in the psychogeriatric population. Similarly, blood folate was significantly correlated with these measures, but the concentrations of serum cobalamin and methylmalonic acid were not. In a stepwise multiple regression analysis including the biochemical markers, tHcy was the only significant predictor of the severity of dementia (r(2) = 0.11; P <0.01) and the score of symptoms (r(2) = 0.16; P <0.001). CONCLUSION: Plasma tHcy is the best marker of those measured to investigate suspected tissue deficiency of cobalamin/folate. (+info)
Folate status of elderly women following moderate folate depletion responds only to a higher folate intake.
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Dietary Reference Intakes (DRI) for folate for elderly women have been based primarily on data extrapolated from studies in younger women. This study was conducted to provide the first age-specific data in elderly women (60-85 y) from a controlled metabolic study on which to base folate intake recommendations. Subjects (n = 33) consumed a moderately folate-deplete (118 microg/d) diet for 7 wk, followed by repletion diets providing either 200 or 415 microg folate/d as diet plus folic acid (FA) or a combination of FA and orange juice (OJ) for 7 wk (n = 30). Comparisons among and within groups were made for serum folate (SF), RBC folate and plasma total homocysteine (tHcy) concentrations. SF concentrations decreased significantly (P < 0.001) during depletion (65 +/- 15%). Postrepletion, the adjusted SF concentration for subjects consuming 415 microg folate/d was significantly greater (P = 0.003) than for subjects consuming 200 microg folate/d. RBC folate concentrations decreased (P < 0.001) during depletion (21 +/- 10%) and further (P < 0.001) during repletion (5 +/- 14%). During depletion, plasma tHcy concentrations increased significantly (P < 0.001) and an inverse relationship between SF and plasma tHcy concentrations was observed in 94% of subjects (P < 0.001). Reversal of this inverse relationship was significant only for subjects consuming 415 microg folate/d (P < 0.001). Postrepletion, subjects consuming 200 microg folate/d had a significantly higher (P = 0.009) adjusted plasma tHcy concentration than subjects consuming 415 microg folate/d. These data in elderly women indicate that 415 microg/d folate, provided as a combination of diet, FA and OJ, or diet and FA, normalizes folate status more effectively than does 200 microg/d, thus providing age-specific data for future folate intake recommendations. (+info)
Etiology of anemia in pregnancy in south Malawi.
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BACKGROUND: Anemia in pregnancy is a major public health problem in developing countries. In sub-Saharan Africa, such anemia is generally accepted as resulting from nutritional deficiencies, particularly iron deficiency. OBJECTIVE: We comprehensively assessed the full spectrum of nutritional and nonnutritional factors associated with pregnancy anemia. DESIGN: Iron, folate, vitamin B-12, and vitamin A were measured in serum in a cross-sectional study of 150 pregnant women in Blantyre, Malawi. Bone marrow aspirates were evaluated, peripheral blood films were examined for malaria parasites, stool and urine samples were examined for helminthic infection, and tests were done for genetic disorders and for HIV infection. C-reactive protein (CRP) concentrations and erythrocyte sedimentation rates were measured as markers of inflammation. RESULTS: Of the 150 anemic women, 23% were iron deficient with no evidence of folate, vitamin B-12, or vitamin A deficiencies; 32% were deficient in iron and one or more of the other micronutrients; 26% were not iron deficient but had evidence of one of the other micronutrient deficiencies, most often vitamin A; and 19% were not deficient in any of the micronutrients studied. CRP concentrations were notably high in 54% of the anemic women with no nutritional deficiencies and in 73.5% of the anemic women who were iron replete by bone marrow assessment. CONCLUSION: The role of chronic inflammation as a possible contributing factor to anemia in pregnancy has important implications for the clinical evaluation and treatment of women. (+info)
Homocysteine, folate, methylation, and monoamine metabolism in depression.
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OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. METHODS: In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. RESULTS: Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. CONCLUSIONS: Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement. (+info)
Folate status in Italian blood donors: relation to gender and smoking.
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BACKGROUND AND OBJECTIVES: Folate deficiency in the general population is associated with a risk of cardiovascular disease and various cancers. The aim of this study was to evaluate folate status in Italian blood donors and its relationship with gender and smoking habit. DESIGN AND METHODS: A prospective study of 201 first visit donors (99 males and 102 females) was undertaken to evaluate folate status by measuring serum folate (SF) and red blood cell folate (RCF) levels and relating those with gender and smoking habit (100 smokers and 101 non-smokers). RESULTS: The rates of SF level less than 6.8 nmol/L and RCF less than 340 nmol/L were 9.9% and 25.3%, respectively in Italian blood donors. Mean RCF level was significantly lower (p<0.05) in females than in males and in smokers compared to non-smokers (p<0.001). The risk of reduced RCF levels in smokers was related to the number of cigarettes smoked per day, more than nine cigarettes increased the relative risk (RR) of low RCF level to 2.93 (95% C.I.: 1.34-6.41). INTERPRETATION AND CONCLUSIONS: This study suggests that folate deficiency, evaluated by RCF and SF levels, is widespread in Italian blood donors. Moreover, RCF values seem related to gender in non-smokers and modified by smoking habit, according to the cigarettes number smoked per day. (+info)
Oral contraceptive hormones, folate metabolism, and the cervical epithelium.
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The currently available evidence concerning disorders of folate metabolism in women taking oral contraceptives has been reviewed. A disturbance in folate balance serious enough to cause symptoms (i.e., megaloblastic anemia) occurs very rarely. In some series, but not in others, serum and/or red cell folate concentrations have been reduced in oral contraceptive users. It is doubtful whether sex steroids affect polyglutamate folate absorption. About 20 percent of women taking contraceptive hormones manifest mild megaloblastic changes on Papanicolaou smears of the cervicovaginal epithelium which disappear after folic acid therapy. The current evidence, however, would not indicate that any significant benefit would ensue from routine folate supplementation in women on oral contraceptives. (+info)
Is there a metabolic basis for dietary supplementation?
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To be efficacious, dietary supplements must either provide a nutrient that is normally undersupplied to cells or exert a pharmacologic effect on cellular processes. In the first case, optimal function is achieved when a nutrient required by the organism reaches a specific concentration within the cell. A supplement has benefit only when the normal intake of a bioavailable form of a nutrient is lower than the amount that would provide maximum benefit as judged from all biological perspectives. Metabolic, environmental, and genetic factors can make individual nutrient requirements differ from the estimated needs calculated from population-based data. For example, under certain circumstances intracellular antioxidants may be depleted and a dietary supplement might restore optimal antioxidant protection. In the second case, the dietary supplement contains a constituent that is normally not required by the cell, but this substance is capable of altering normal cell function. For example, herbal preparations may contain ephedrine (a drug), which might alter heart rate so that the amount of blood pumped by the heart is enhanced. An understanding of how the variation in nutrient requirements comes about and of the pharmacologic actions of nutrient supplements can help to identify which individuals are most likely to benefit from dietary supplements. (+info)