Cobalamin and folate status in 6 to 35 months old children presenting with acute diarrhea in Bhaktapur, Nepal

Background: Cobalamin and folate are essential micronutrients and are important in DNA and RNA synthesis, cell proliferation, growth, hematopoiesis, and cognitive function. However, data on cobalamin and folate status are lacking particularly from young children residing in low and middle income countries. Objective: To measure cobalamin and folate status and identifies their predictors among 6 to 35 months old children presenting with acute diarrhea. Design: This was a cross-sectional study in 823 children presenting with acute diarrhea. We measured plasma cobalamin, folate, methylmalonic acid and total homocysteine who sought treatment for acute diarrhea between June 1998 and August 2000. Results: The mean (SD) plasma concentrations of cobalamin, folate, total homocysteine and methylmalonic acid were 206 (124) pmol/L, 55 (32) nmol/L, 11.4 (5.6) mmol/L and 0.79 (1.2) mmol/L, respectively. The prevalence of low plasma cobalamin (,150 pmol/L) was 41% but less than 2% (15) children had low folate concentration (,10 nmol/L). Plasma homocysteine and methylmalonic acid concentrations were negatively associated with cobalamin concentration but not associated with folate status. The prevalence of cobalamin deficiency was higher in breastfed than non-breastfed children (44% vs 24%; p =,0.001). The prevalence of hyperhomocysteinemia (.10 mmol/L) and elevated methylmalonic acid (.0.28 mmol/L) were 73% and 52%, respectively. In the regression analyses, the plasma cobalamin concentration was positively associated with age, and introduction of animal or formula milk. Conclusions: Our study indicated that poor cobalamin status was common particularly among breastfed children. Folate deficiency was virtually none existent. Possible consequences of cobalamin deficiency in young children need to be explored

Cobalamin and folate status in infants and young children in a low-to-middle income community in India

Background: Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking. Objective: The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India. Design: Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial. Results: The median (interquartile range; IQR) cobalamin concentration in 6-11-mo-old children was substantially lower in breastfed (183; 120-263 pmol/L) than in nonbreastfed (334; 235-463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6-11-mo-old group were higher in breastfed (20.3; 11.7-34.4 nmol/L) than in nonbreastfed (5.3; 3.4-7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001). Conclusions: In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered

Vitamin B12 concentrations in milk from Norwegian women during the six first months of lactation

Background: Human milk vitamin B12 (B12) concentrations depend on maternal status and intake; only few data are available in high-income countries. Objective: We assessed human milk B12 concentrations during the first 6 months postpartum in Norwegian women and its association with maternal dietary B12 intake and maternal urinary methylmalonic acid (MMA) concentration. Methods: In this cross-sectional study, 175 mothers, exclusively (80%) or partially (20%) breastfeeding, were included. Milk B12 was measured by IMMULITE®/IMMULITE® 1000 B12 competitive protein binding assay and urinary MMA relative to creatinine (MMA/Cr) by liquid chromatography-tandem-mass spectrometry. Maternal habitual B12 intake and supplement use were estimated using a food frequency questionnaire. Results: Mean human milk B12 concentration was 327 pmol/L (range 140-1089), with 402 pmol/L at 1 month (n = 21), 333 pmol/L at four months (n = 32), and 299 pmol/L at 6 months (n = 21). Maternal B12 intake was 5 µg/d, 89% met the Estimated Average Requirement, and supplement use did not affect milk B12 concentrations. MMA/Cr was low in all women compared with published data. In exclusively breastfeeding women, MMA/Cr (beta (95% CI) -42.5 (-82.5, -2.5) and time since birth (-4.9 (-9.6, -0.3)) were significant predictors of human milk B12 concentrations. There was no association between total B12 intake and milk B12 concentration or between total B12 intake and MMA/Cr. Conclusions: Maternal B12 status and human milk B12 concentrations are likely sufficient, based on adequate maternal B12 dietary intake combined with low urinary MMA concentrations. Nevertheless, milk B12 concentration fell during 6 months postpartum while maternal B12 status did not change.publishedVersio

Folate, but not vitamin B-12 status, predicts respiratory morbidity in north Indian children

Background: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections. Objective: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity. Design: A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo. Results: We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31). Conclusions: Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk

Plasma free choline, betaine and cognitive performance: the Hordaland Health Study

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P= 0·004), m-DST (10·5 v. 9·8, P= 0·005) and m-MMSE (11·5 v. 11·4, P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12 ( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12 or high MMA on cognitive performance.publishedVersio

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.Objective: To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Methods and Findings: Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B₆ and B₁₂ in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B₁₂ (0.5 mg/d) and vitamin B₆ (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.Results: A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P=0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine &gt; 13μmol/L was 53% lower in the active treatment group (P=0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.Conclusions and significance: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.</p