Vitamin B-12 Status Differs among Pregnant, Lactating, and Control Women with Equivalent Nutrient Intakes.

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 ∼8.6 µg/d [mixed diet (∼6 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 ∼30% (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 ∼20% 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 (∼3 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.

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

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 (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, 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 (rs = 0.574) 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.

Vitamin supplementation reduces the level of homocysteine in the urine of autistic children.

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.

[Measurement of methylmalonic acid, homocysteine and methionine in cobalamin and folate deficiencies and homocysteinuria]. / Måling av metylmalonsyre, homocystein og metionin ved kobalamin- og folatmangel og homocystinuri.

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.

Plasma cobalamin and folate and their metabolic markers methylmalonic acid and total homocysteine among Egyptian children before and after nutritional supplementation with the probiotic bacteria Lactobacillus acidophilus in yoghurt matrix.

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.

Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh.

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 (

Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study.

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.

Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure.

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.