ABSTRACT
BACKGROUND: Limited data are available from controlled studies on biomarkers of maternal vitamin B-12 status. OBJECTIVE: We sought to quantify the effects of pregnancy and lactation on the vitamin B-12 status response to a known and highly controlled vitamin B-12 intake. METHODS: As part of a 10-12 wk feeding trial, pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant, nonlactating; n = 21) women consumed vitamin B-12 amounts of â¼8.6 µg/d [mixed diet (â¼6 µg/d) plus a prenatal multivitamin supplement (2.6 µg/d)]. Serum vitamin B-12, holotranscobalamin (bioactive form of vitamin B-12), methylmalonic acid (MMA), and homocysteine were measured at baseline and study-end. RESULTS: All participants achieved adequate vitamin B-12 status in response to the study dose. Compared with control women, pregnant women had lower serum vitamin B-12 (-21%; P = 0.02) at study-end, whereas lactating women had higher (P = 0.04) serum vitamin B-12 throughout the study (+26% at study-end). Consumption of the study vitamin B-12 dose increased serum holotranscobalamin in all reproductive groups (+16-42%; P ≤ 0.009). At study-end, pregnant (vs. control) women had a higher holotranscobalamin-to-vitamin B-12 ratio (P = 0.04) with â¼30% (vs. 20%) of total vitamin B-12 in the bioactive form. Serum MMA increased during pregnancy (+50%; P < 0.001) but did not differ by reproductive state at study-end. Serum homocysteine increased in pregnant women (+15%; P = 0.009) but decreased in control and lactating women (-16-17%; P < 0.001). Despite these changes, pregnant women had â¼20% lower serum homocysteine than the other 2 groups at study-end (P ≤ 0.02). CONCLUSION: Pregnancy and lactation alter vitamin B-12 status in a manner consistent with enhanced vitamin B-12 supply to the child. Consumption of the study vitamin B-12 dose (â¼3 times the RDA) increased the bioactive form of vitamin B-12, suggesting that women in these reproductive states may benefit from vitamin B-12 intakes exceeding current recommendations. This trial was registered at clinicaltrials.gov as NCT01127022.
Subject(s)
Energy Intake , Micronutrients/administration & dosage , Vitamin B 12/blood , Adult , Biomarkers/blood , Breast Feeding , Choline/administration & dosage , Choline/blood , Dietary Supplements , Dose-Response Relationship, Drug , Double-Blind Method , Female , Healthy Volunteers , Homocysteine/blood , Homocysteine/urine , Humans , Lactation/blood , Methylmalonic Acid/blood , Postpartum Period , Pregnancy , Recommended Dietary Allowances , Vitamin B 12/administration & dosage , Young AdultABSTRACT
BACKGROUND: Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. AIM: Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. STUDY DESIGN AND METHODS: Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. RESULTS: Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rsâ=â0.676) and RCF (rsâ=â0.649) than apABG (rsâ=â0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rsâ=â0.574) after 12 weeks. CONCLUSION: Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics.
Subject(s)
Dietary Supplements , Folic Acid/metabolism , Folic Acid/urine , Adult , Dietary Supplements/analysis , Folic Acid/administration & dosage , Folic Acid/blood , Glutamates/blood , Glutamates/metabolism , Glutamates/urine , Homocysteine/blood , Homocysteine/urine , Humans , Male , Urinalysis , Vitamin B 12/blood , Vitamin B 12/urine , Vitamin B 6/blood , Vitamin B 6/urine , Young AdultABSTRACT
Significant differences in homocysteine levels in the urine of autistic children are observed. We hypothesized that vitamin supplementation might reduce the level of urinary homocysteine. To rationalize such a hypothesis, analyses were performed using the gas chromatography/mass spectrometry method. The homocysteine level in the urine of autistic children was measured twice: (1) before vitamin supplementation (group C, 30 autistic children) and (2) after supplementation, with either folic acid and vitamins B(6) and B(12) (group A1, 24 autistic children) or vitamins B(6) and B(12) alone (group A2, 6 autistic children). The homocysteine level in the urine of autistic children before vitamin supplementation was 2.41 ± 1.10 mmol/mol creatinine (mean ± SD difference). After treatment, the homocysteine level was reduced to 1.13 ± 0.44 and 1.33 ± 0.39 mmol/mol creatinine for A1 and A2 groups, respectively. The intake of vitamins B(6) and B(12), together with folic acid, was found to be more effective in lowering the levels of urinary homocysteine than the intake of vitamins B(6) and B(12) alone. Our findings may lead to the recommendation of including vitamins B(6) and B(12) together with folic acid supplementation in the diets of children with autism.
Subject(s)
Autistic Disorder/diet therapy , Dietary Supplements , Folic Acid/administration & dosage , Homocysteine/urine , Vitamin B 12/administration & dosage , Vitamin B 6/administration & dosage , Child , Child, Preschool , Creatinine/administration & dosage , Female , Gas Chromatography-Mass Spectrometry , Humans , MaleABSTRACT
BACKGROUND: Deficiencies of cobalamin (vitamin B12) or folate are common conditions that predispose for anemia and chronic diseases. An elevated concentration of methylmalonic acid in plasma/serum is an indicator of cobalamin deficiency, whereas an increased concentration of total homocysteine in plasma occurs with deficiency of both cobalamin and folate. The biomarkers methylmalonic acid and homocysteine are therefore complementary, and the combination is often requested when conventional tests fail to provide an unambiguous diagnosis. MATERIAL AND METHODS: This article summarizes publications, retrieved through Medline, describing novel strategies for laboratory diagnostics of cobalamin and folate deficiencies. RESULTS AND INTERPRETATION: Adverse health effects of food fortification and uncritical supplementation with folic acid are explanations for a renewed interest in individual diagnosis of B-vitamin deficiency. Interpretation of methylmalonic acid and homocysteine test results requires knowledge of kidney function, as renal failure causes an increase in the concentrations of both metabolites. Homocystinuria is a condition that also causes increased levels of plasma homocysteine. This condition is an inborn error with a higher prevalence (1 : 6400) than previously recognized; which usually responds favourably to homocysteine-lowering therapy. Patients with homocysteinuria have high levels of methionine in plasma and knowledge of plasma methionine concentration may therefore distinguish these patients from those with conditions like B-vitamin deficiencies or renal failure, which are accompanied by normal or low to normal methionine concentrations. Complementarity, logistics, small sample volumes and costs therefore favour a combined analysis of methylmalonic acid, homocysteine and methionine in a single sample. Such an approach also allows assessment of cobalamin status in small volume capillary blood samples drawn from newborns and infants.
Subject(s)
Biomarkers/blood , Folic Acid Deficiency/blood , Homocysteine/blood , Methionine/blood , Methylmalonic Acid/blood , Vitamin B 12 Deficiency/blood , Amino Acid Metabolism, Inborn Errors/blood , Amino Acid Metabolism, Inborn Errors/complications , Amino Acid Metabolism, Inborn Errors/diagnosis , Diagnosis, Differential , Folic Acid/administration & dosage , Folic Acid/adverse effects , Folic Acid Deficiency/complications , Folic Acid Deficiency/diagnosis , Food, Fortified/adverse effects , Homocysteine/urine , Humans , Infant , Infant, Newborn , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/diagnosisABSTRACT
OBJECTIVE: To evaluate the biopotency of the viable probiotic Lactobacillus acidophilus (La1) in yoghurt matrix consumed by Egyptian children on their plasma vitamin B12 and folate levels, and their metabolic markers methylmalonic acid (MMA) and total homocysteine (t-Hcy). METHODS: A randomized nutritional supplementation trial (42 days duration) was performed in free-living children of both sexes (11 years old). The La1 in yoghurt matrix was administered to provide 1012 colony-forming units/subject/day. Blood sampling for the analysis of plasma vitamin B12, folate and t-Hcy was performed by standardized methods. Five-hour urine collection was used for the analysis of MMA and t-Hcy. RESULTS: Initially 33.3% of the children presented with biochemical vitamin B12 deficiency (<208 pg/ml), while one-fifth (21%) were biochemically deficient in folate (<3 ng/ml folate/ml plasma or 0.68 nmol/l). Fifty percent of the children presented with high plasma t-Hcy (>15.0 micromol/l). The daily consumption of the probiotic La1 yoghurt for 42 days significantly improved the mean levels of plasma vitamin B12 (P<0.05) and folate (P<0.01) among the studied children compared with the respective baseline data. On the other hand, the average levels of plasma t-Hcy and urinary MMA decreased significantly (P<0.05) at the termination of the 42-day nutritional supplementation, compared with the respective initial mean levels. The consumption of the probiotic yoghurt was also associated with a significant (chi2=8.0; P<0.01) reduction in the percentage prevalence of anemia (hemoglobin <120 g/l). CONCLUSION: The long-term ingestion of viable probiotic La1 potentially promoted the overall nutritional status of the studied children.
Subject(s)
Folic Acid/blood , Homocysteine/blood , Lactobacillus acidophilus , Methylmalonic Acid/blood , Probiotics/administration & dosage , Vitamin B 12/blood , Chi-Square Distribution , Child , Dietary Supplements , Egypt , Female , Homocysteine/urine , Humans , Male , Methylmalonic Acid/urine , Treatment Outcome , Vitamin B 12 Deficiency/blood , Vitamin B 12 Deficiency/diet therapy , Vitamin B 12 Deficiency/urine , YogurtABSTRACT
BACKGROUND: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water. To various degrees, ingested inorganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one-carbon metabolism; impaired methylation is associated with adverse health outcomes. Consequently, folate nutritional status may influence arsenic methylation and toxicity. OBJECTIVE: The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation. DESIGN: Two hundred adults in a rural region of Bangladesh, previously found to have low plasma concentrations of folate (=9 nmol/L) were enrolled in a randomized, double-blind, placebo-controlled folic acid-supplementation trial. Plasma concentrations of folate and homocysteine and urinary concentrations of arsenic metabolites were analyzed at baseline and after 12 wk of supplementation with folic acid at a dose of 400 microg/d or placebo. RESULTS: The increase in the proportion of total urinary arsenic excreted as DMA in the folic acid group (72% before and 79% after supplementation) was significantly (P < 0.0001) greater than that in the placebo group, as was the reduction in the proportions of total urinary arsenic excreted as MMA (13% and 10%, respectively; P < 0.0001) and as InAs (15% and 11%, respectively; P < 0.001). CONCLUSIONS: These data indicate that folic acid supplementation to participants with low plasma folate enhances arsenic methylation. Because persons whose urine contains low proportions of DMA and high proportions of MMA and InAs have been reported to be at greater risk of skin and bladder cancers and peripheral vascular disease, these results suggest that folic acid supplementation may reduce the risk of arsenic-related health outcomes.
Subject(s)
Arsenic/metabolism , Environmental Exposure , Folic Acid/administration & dosage , Folic Acid/metabolism , Water Pollutants, Chemical/metabolism , Adult , Aged , Arsenic/administration & dosage , Arsenic/urine , Arsenicals/urine , Bangladesh , Creatine/biosynthesis , Creatinine/urine , Dietary Supplements , Double-Blind Method , Female , Folic Acid/blood , Homocysteine/blood , Homocysteine/urine , Humans , Male , Methylation/drug effects , Middle Aged , Skin Neoplasms/chemically induced , Urinary Bladder Neoplasms/chemically induced , Vitamin B Complex/administration & dosage , Vitamin B Complex/blood , Vitamin B Complex/metabolism , Water Pollutants, Chemical/administration & dosageABSTRACT
OBJECTIVE: The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. DESIGN: A randomized placebo-controlled double-blind intervention study with cross-over design. SETTING: Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. SUBJECTS: Eight female patients with chronic urinary tract infection and 12 healthy women (controls). INTERVENTIONS: After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks. MAIN OUTCOME MEASURES: Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. RESULTS: Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. CONCLUSIONS: Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.
Subject(s)
Amino Acids/blood , Homocysteine/blood , Methionine/pharmacology , Urinary Tract Infections/prevention & control , Adult , Aged , Amino Acids/urine , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Female , Folic Acid/blood , Homocysteine/metabolism , Homocysteine/urine , Humans , Methionine/blood , Methionine/urine , Middle Aged , Urinary Tract Infections/blood , Urinary Tract Infections/urine , Vitamin B 12/blood , Vitamin B 6/bloodABSTRACT
We investigated the elimination of total homocysteine (tHcy) from plasma after peroral homocysteine (Hcy) loading in eight patients with chronic renal failure. Data on bioavailability and distribution volume were obtained from two patients and two healthy controls by performing both intravenous and peroral Hcy loading. Response to high-dose folic acid was studied in six cases. Mean (SD) basal plasma tHcy was 27.4 (11.0) microM at inclusion. The half-life and the area under the curve were about four times higher, and clearance was reduced to 29.8% compared to controls. High-dose folic acid had no influence on half-life for tHcy, but the basal tHcy level declined by 26.8%. The reduction in tHcy was particularly pronounced in three patients with low-normal serum folate, and the enhanced methionine response to Hcy loading after folic acid suggested improved Hcy remethylation in tissues. In conclusion, patients with renal failure had markedly reduced clearance of tHcy from plasma, which probably accounts for their hyperhomocysteinemia. High-dose folic acid reduces fasting tHcy by improving tissue Hcy remethylation without affecting the low renal clearance of tHcy.