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

Kynurenine pathway metabolites in Alzheimer's disease.

Background Metabolites of tryptophan, produced via the kynurenine pathway (kynurenines) have been linked to Alzheimer’s disease (AD) in small cohorts with conflicting results. Objective To compare differences in plasma kynurenine levels between AD and controls and identify potential associations with cognition. Methods The study included 65 histopathologically-confirmed AD patients and 65 cognitively-screened controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. Cognition was assessed using the Cambridge Cognitive Examination (CamCog). Tryptophan, kynurenines, neopterin and vitamin B6 forms were measured in plasma by liquid chromatography-tandem mass spectrometry. Non-parametric statistics, logistic regression and standardized robust regressions were applied with a false discovery rate of 0.05. Results Tryptophan, xanthurenic acid, 3-hydroxyanthranilic acid and quinolinic acid were lower in AD (Odds ratios (ORs) 0.24 – 0.47; p-values < 0.001 – 0.01). Pyridoxal 5’phosphate did not differ between AD and controls. Kynurenine, anthranilic acid, quinolinic acid and markers of immune activation (neopterin, kynurenine/tryptophan ratio and the PAr index (Pyridoxic acid/(Pyridoxal 5’phosphate + Pyridoxal)) increased with age (β 0.31 – 0.51; p-values < 0.001 – 0.006). Xanthurenic acid decreased with age (β: -0.42, p < 0.001). Elderly AD patients with high quinolinic acid performed worse on the CamCog test, indicated by a significant age*quinolinic acid interaction (β 0.21, p < 0.001). Conclusion Plasma concentrations of several kynurenines were lower in patients with AD compared to controls. Low xanthurenic acid occurred in both AD and with ageing. Inflammation-related markers were associated with age, but not AD. However, elevated QA was associated with poor cognition in older AD patients

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 &lt; 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 (&lt;150 pmol/L) were were detected in 36% of breastfed and 9% of nonbreastfed children (P &lt; 0.001). The proportions of children with plasma folate concentrations &lt;5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P &lt; 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

Acute effects of oral mesna administration on the full amino acid profile and 3-methylhistidine: secondary results from the CYLOB dose-finding study

Plasma total cysteine (tCys) is strongly associated with fat mass in humans. Mesna lowers plasma tCys in a dose-dependent manner, but it is not known whether it interferes with metabolism of other amino acids or protein. In this Phase-1 study, we show that a single dose of mesna administered at 400, 800, 1200 or 1600 mg to 6–7 individuals per dose only slightly affects amino acid profiles, with increases in plasma valine across dose levels. There were no effects of mesna on 3-methylhistidine, a marker of protein breakdown

Branched-chain amino acid metabolism, insulin sensitivity and liver fat response to exercise training in sedentary dysglycaemic and normoglycaemic men

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.Aims/hypothesis: Obesity and insulin resistance may be associated with elevated plasma concentration of branched-chain amino acids (BCAAs) and impaired BCAA metabolism. However, it is unknown whether the insulin-sensitising effect of long-term exercise can be explained by concomitant change in BCAAs and their metabolism. Methods: We included 26 sedentary overweight and normal-weight middle-aged men from the MyoGlu clinical trial, with or without dysglycaemia, for 12 weeks of supervised intensive exercise intervention, including two endurance and two resistance sessions weekly. Insulin sensitivity was measured as the glucose infusion rate (GIR) from a hyperinsulinaemic−euglycaemic clamp. In addition, maximum oxygen uptake, upper and lower body strength and adipose tissue depots (using MRI and spectroscopy) were measured, and subcutaneous white adipose tissue (ScWAT) and skeletal muscle (SkM) biopsies were harvested both before and after the 12 week intervention. In the present study we have measured plasma BCAAs and related metabolites using CG-MS/MS and HPLC-MS/MS, and performed global mRNA-sequencing pathway analysis on ScWAT and SkM. Results: In MyoGlu, men with dysglycaemia displayed lower GIR, more fat mass and higher liver fat content than normoglycaemic men at baseline, and 12 weeks of exercise increased GIR, improved body composition and reduced liver fat content similarly for both groups. In our current study we observed higher plasma concentrations of BCAAs (14.4%, p = 0.01) and related metabolites, such as 3-hydroxyisobutyrate (19.4%, p = 0.034) in dysglycaemic vs normoglycaemic men at baseline. Baseline plasma BCAA levels correlated negatively to the change in GIR (ρ = −0.41, p = 0.037) and VO2max (ρ = −0.47, p = 0.015) after 12 weeks of exercise and positively to amounts of intraperitoneal fat (ρ = 0.40, p = 0.044) and liver fat (ρ = 0.58, p = 0.01). However, circulating BCAAs and related metabolites did not respond to 12 weeks of exercise, with the exception of isoleucine, which increased in normoglycaemic men (10 μmol/l, p = 0.01). Pathway analyses of mRNA-sequencing data implied reduced BCAA catabolism in both SkM and ScWAT in men with dysglycaemia compared with men with normoglycaemia at baseline. Gene expression levels related to BCAA metabolism correlated positively with GIR and markers of mitochondrial content in both SkM and ScWAT, and negatively with fat mass generally, and particularly with intraperitoneal fat mass. mRNA-sequencing pathway analysis also implied increased BCAA metabolism after 12 weeks of exercise in both groups and in both tissues, including enhanced expression of the gene encoding branched-chain α-ketoacid dehydrogenase (BCKDH) and reduced expression of the BCKDH phosphatase in both groups and tissues. Gene expression of SLC25A44, which encodes a mitochondrial BCAA transporter, was increased in SkM in both groups, and gene expression of BCKDK, which encodes BCKDH kinase, was reduced in ScWAT in dysglycaemic men. Mediation analyses indicated a pronounced effect of enhanced SkM (~53%, p = 0.022), and a moderate effect of enhanced ScWAT (~18%, p = 0.018) BCAA metabolism on improved insulin sensitivity after 12 weeks of exercise, based on mRNA sequencing. In comparison, plasma concentration of BCAAs did not mediate any effect in this regard. Conclusion/interpretation: Plasma BCAA concentration was largely unresponsive to long-term exercise and unrelated to exercise-induced insulin sensitivity. On the other hand, the insulin-sensitising effect of long-term exercise in men may be explained by enhanced SkM and, to a lesser degree, also by enhanced ScWAT BCAA catabolism.publishedVersionInstitutt for fysisk prestasjonsevne / Department of Physical Performanc

Does Lifestyle Intervention After Gastric Bypass Surgery Prevent Weight Regain? A Randomized Clinical Trial

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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