Risk of persistent cobalamin deficiency in adolescents fed a macrobiotic diet in early life.
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BACKGROUND: Cobalamin deficiency has been described in children consuming macrobiotic diets. OBJECTIVE: We investigated whether moderate consumption of animal products is sufficient for achieving normal cobalamin function in 73 adolescents who had received a macrobiotic diet until 6 y of age and had then switched to a lactovegetarian, lactoovovegetarian, or omnivorous diet (macrobiotic adolescents). DESIGN: Hematologic indexes and serum concentrations of methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured. Current consumption frequency of animal products and cobalamin intake from dairy products were assessed by questionnaire. Data from 94 age-matched adolescents who received an omnivorous diet from birth were used as a reference. RESULTS: Serum cobalamin concentrations were significantly lower and concentrations of MMA and folate and mean corpuscular volume (MCV) were significantly higher in macrobiotic adolescents than in control adolescents: of macrobiotic adolescents, 21% had abnormal MMA concentrations (>0.41 micromol/L), 37% had abnormal cobalamin concentrations (<218 pmol/L), 10% had abnormal tHcy concentrations (> 12.8 micromol/L), and 15% had abnormal MCV (> 89 fL). In macrobiotic adolescents, dairy products (200 g milk or yogurt and 22 g cheese/d) supplied on average 0.95 microg cobalamin/d; additionally, these adolescents consumed fish, meat, or chicken 2-3 times/wk. In girls, meat consumption contributed more to cobalamin status than the consumption of dairy products, whereas in boys these food groups were equally important. CONCLUSIONS: A substantial number of the formerly strict macrobiotic adolescents still had impaired cobalamin function. Thus, moderate consumption of animal products is not sufficient for restoring normal cobalamin status in subjects with inadequate cobalamin intake during the early years of life. (+info)
Stabilized polynuclear iron hydroxide is an efficient oral phosphate binder in uraemic patients.
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BACKGROUND: There is a continuing need for non-aluminium and non-calcium-containing oral phosphate binders. A novel product, i.e. stabilized polynuclear iron hydroxide, has experimentally been shown to be an effective phosphate binder. The purpose of the study was to test the efficacy and tolerability of the compound in hyperphosphataemic patients with stable preterminal renal failure. METHODS: In an open uncontrolled study we examined a total of 13 patients with stable preterminal renal failure (median serum-creatinine 5.4 mg/dl, range 4.2-7.3 mg/dl) and hyperphosphataemia (median fasting plasma-Pi 2.2 mmol/l, range 1.95 3.0 mmol/l). Patients were given dietary advise to maintain a constant intake of phosphate and this was verified by measuring urinary Pi excretion. After 2 weeks on no oral phosphate binders, patients were given daily 3 x 2.5 g stabilized polynuclear iron hydroxide with meals for 4 weeks. In a blinded fashion plasma-Pi and urinary-Pi as well as 1,84 i-PTH, vitamin D metabolites, serum-iron and ferritin were measured in a central laboratory. RESULTS: Compared to baseline (no oral phosphate binders), the median per cent decrease of fasting plasma-Pi at day 14 was 20% (7.2-41%) (P<0.001 by Wilcoxon test) and the median per cent decrease of urinary P excretion was 37% (9.6-56.6%) (P<0.0003 by Wilcoxon test for paired differences). Ferritin levels did not differ significantly during the study. Apart from a certain laxative action and black discolouration of the faeces, no side effects were noted in this short-term study. CONCLUSION: Stabilized polynuclear iron hydroxide is a promising, efficaceous and well tolerated phosphate binder. (+info)
School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls.
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BACKGROUND: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. OBJECTIVE: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. DESIGN: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B were randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. RESULTS: By the end of the study, 2% of the girls had dropped out and > 96% had taken > or = 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. CONCLUSION: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls. (+info)
Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in a Peruvian population.
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BACKGROUND: Maternal zinc deficiency during pregnancy may be widespread among women in developing countries, but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status. OBJECTIVE: We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima, Peru. DESIGN: Beginning at gestation week 10-24, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate, with or without 15 mg Zn. Venous blood and urine samples were collected at enrollment, at gestation week 28-30, and at gestation week 37-38. At birth, a sample of cord vein blood was collected. We measured serum zinc concentrations in 538 women, urinary zinc concentrations in 521 women, and cord zinc concentrations in 252 neonates. RESULTS: At 28-30 and 37-38 wk, mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc (8.8 +/- 1.9 compared with 8.4 +/- 1.5 micromol/L and 8.6 +/- 1.5 compared with 8.3 +/- 1.4 micromol/L, respectively). Urinary zinc concentrations were also higher in mothers who received supplemental zinc (P < 0.05). After adjustment for covariates and confounding factors, neonates of mothers receiving zinc supplements had higher cord zinc concentrations than neonates of mothers who did not receive zinc (12.7 +/- 2.3 compared with 12.1 +/- 2.1 micromol/L). Despite supplementation, maternal and neonatal zinc concentrations remained lower than values reported for well-nourished populations. CONCLUSION: Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status, but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population. (+info)
10-Formyl-dihydrofolic acid is bioactive in human leukemia cells.
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The bioactivity of 10-formyl-7,8-dihydrofolic acid and 10-formyl-folic acid was determined in human leukemia (CCRF-CEM) cells grown in a folate-depleted medium containing methotrexate. Excess 10-formyl-7,8-dihydrofolic acid, (but not 10-formyl folic acid) supported the growth of these cells, but it was less potent than5-formyl-5,6,7,8-tetrahydrofolic acid (a control). 10-formyl-7, 8-dihydrofolic acid (not 10-formyl folic acid) was active as substrate for aminoimidazole carboxamide ribotide transformylase and dihydrofolate reductase. This is the first experimental evidence that 10-formyl-7,8-dihydrofolic acid is a bioactive folate in mammalian cells. These experiments and several other lines of evidence in the literature suggest that 10-formyl-folic acid must be metabolized to bioactive folate by enteric bacteria before it can be utilized by the vertebrate host. (+info)
The antimalarial triazine WR99210 and the prodrug PS-15: folate reversal of in vitro activity against Plasmodium falciparum and a non-antifolate mode of action of the prodrug.
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We have studied the reversal of activity against Plasmodium falciparum of WR99210, a triazine antimalarial drug, and of the pro-drug PS-15 by folic acid (FA) and folinic acid (FNA). Folic acid and FNA inhibit the growth of P. falciparum in vitro at concentrations > 10(-4.5) and 10(-3.5) mol/L, respectively. The activity of pyrimethamine against Kenyan strains M24 and K39 is reduced 10-12-fold by 10(-5) mol/L of FA, and virtually eliminated by 10(-5) mol/L of FNA. Folates do not antagonise the action of WR99210 against Kenyan strains, and only partially antagonize the action of WR99210 action against the Southeast Asian strains V1/S and W282. Similarly, FA and FNA exerted weak or no antagonism of the action of PS-15. The inability of folates to antagonize the action of WR99210 can be explained in terms of high drug-enzyme affinity, but this does not account for the inability of FA and FNA to antagonize PS-15. These results suggest that action of PS-15 against P. falciparum is primarily due to a non-folate mechanism. (+info)
Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.
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Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC. (+info)
Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial.
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BACKGROUND: Folates have been suggested to be of benefit in reducing cardiovascular risk. The present study was designed to examine whether oral folic acid supplementation could improve endothelial function as an intermediate end point for cardiovascular risk in patients with increased risk of atherosclerosis due to familial hypercholesterolemia (FH). METHODS AND RESULTS: In a prospective, randomized, double-blind, placebo-controlled study with crossover design, we evaluated the effects of 4 weeks of treatment with oral folic acid (5 mg PO) on endothelial function in FH. In 20 FH patients, forearm vascular function was assessed at baseline, after 4 weeks of folic acid treatment, and after 4 weeks of placebo treatment by venous occlusion plethysmography, with serotonin and sodium nitroprusside used as endothelium-dependent and -independent vasodilators. In addition, we examined the vasoconstrictor response to the NO synthase inhibitor N(G)-monomethyl-L-arginine to assess basal NO activity. In FH patients, folic acid supplementation restored the impaired endothelium-dependent vasodilation, whereas it did not significantly influence endothelium-independent vasodilation or basal forearm vasomotion. There was a trend toward improvement in basal NO activity. CONCLUSIONS: These data demonstrate that oral supplementation of folic acid can improve endothelial function in patients with increased risk of atherosclerotic disease due to hypercholesterolemia, without changes in plasma lipids. (+info)