@article{pmid37658825,

title = {Impaired glucose utilization in the brain of patients with delirium following hip fracture},

author = {Irit Titlestad and Leiv Otto Watne and Gideon A Caplan and Adrian McCann and Per Magne Ueland and Bjørn Erik Neerland and Marius Myrstad and Nathalie Bodd Halaas and Christian Thomas Pollmann and Kristi Henjum and Anette Hylen Ranhoff and Lene B Solberg and Wender Figved and Colm Cunningham and Lasse M Giil},

doi = {10.1093/brain/awad296},

issn = {1460-2156},

year  = {2024},

date = {2024-01-01},

journal = {Brain},

volume = {147},

number = {1},

pages = {215--223},

abstract = {Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and β-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, β-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37858724,

title = {Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study},

author = {Sol Maja G Bjørkevoll and Carolien Konijnenberg and Ingrid Kvestad and Adrian McCann and Per M Ueland and Synnøve Næss Sleire and Lisbeth Dahl and Marian Kjellevold and Tor A Strand and Maria W Markhus},

doi = {10.1016/j.tjnut.2023.10.013},

issn = {1541-6100},

year  = {2023},

date = {2023-12-01},

journal = {J Nutr},

volume = {153},

number = {12},

pages = {3543--3554},

abstract = {BACKGROUND: Vitamin B12 and folate are essential micronutrients important for normal infant growth and development.nnOBJECTIVES: The aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status.nnMETHODS: Pregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo.nnRESULTS: At gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 μmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 μmol/L or 3 combined indicator of vitamin B12 (cB12) < -0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 μmol/L, 59% and 66% had MMA concentrations >0.26 μmol/L, and 47% and 60% had cB12 > -0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants' cobalamin and t-Hcy concentrations.nnCONCLUSIONS: Subclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences. This trial was registered at clinicaltrials.gov as NCT02610959.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37264981,

title = {Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease},

author = {Anne-Brita Knapskog and Mari Aksnes and Trine Holt Edwin and Per Magne Ueland and Arve Ulvik and Evandro Fei Fang and Rannveig Sakshaug Eldholm and Nathalie Bodd Halaas and Ingvild Saltvedt and Lasse M Giil and Leiv Otto Watne},

doi = {10.1002/alz.13162},

issn = {1552-5279},

year  = {2023},

date = {2023-12-01},

journal = {Alzheimers Dement},

volume = {19},

number = {12},

pages = {5573--5582},

abstract = {INTRODUCTION: The kynurenine pathway's (KP) malfunction is closely related to Alzheimer's disease (AD), for antagonistic kynurenic acid (KA) and agonistic quinolinic acid act on the N-methyl-D-aspartate receptor, a possible therapeutic target in treating AD.nnMETHODS: In our longitudinal case-control study, KP metabolites in the cerebrospinal fluid were analyzed in 311 patients with AD and 105 cognitively unimpaired controls.nnRESULTS: Patients with AD exhibited higher concentrations of KA (β = 0.18, P < 0.01) and picolinic acid (β = 0.20, P < 0.01) than the controls. KA was positively associated with tau pathology (β = 0.29, P < 0.01), and a higher concentration of KA was associated with the slower progression of dementia.nnDISCUSSION: The higher concentrations of neuroprotective metabolites KA and picolinic acid suggest that the activation of the KP's neuroprotective branch is an adaptive response in AD and may be a promising target for intervention and treatment. Highlights Patients with Alzheimer's disease (AD) exhibited higher concentrations of kynurenic acid and picolinic acid than controls. Higher concentrations of kynurenic acid were associated with slower progression of AD. Potential neurotoxic kynurenines were not increased among patients with AD. Activation of the kynurenine pathway's neuroprotective branch may be an adaptive response in AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37093107,

title = {A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation},

author = {Giulietta S Monasso and Thanh T Hoang and Giulia Mancano and Sílvia Fernández-Barrés and John Dou and Vincent W V Jaddoe and Christian M Page and Laura Johnson and Mariona Bustamante and Kelly M Bakulski and Siri E Håberg and Per M Ueland and Thomas Battram and Simon K Merid and Erik Melén and Doretta Caramaschi and Leanne K Küpers and Jordi Sunyer and Wenche Nystad and Sandra G Heil and Rebecca J Schmidt and Martine Vrijheid and Gemma C Sharp and Stephanie J London and Janine F Felix},

doi = {10.1080/15592294.2023.2202835},

issn = {1559-2308},

year  = {2023},

date = {2023-12-01},

journal = {Epigenetics},

volume = {18},

number = {1},

pages = {2202835},

abstract = {Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy ( = 2,420) or cord blood ( = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate -value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37550593,

title = {A diet containing cod backbone proteins attenuated the development of mesangial sclerosis and tubular dysfunction in male obese BTBR ob/ob mice},

author = {Maria O'Keeffe and Åge Oterhals and Hrafn Weishaupt and Sabine Leh and Arve Ulvik and Per Magne Ueland and Alfred Halstensen and Hans-Peter Marti and Oddrun Anita Gudbrandsen},

doi = {10.1007/s00394-023-03227-4},

issn = {1436-6215},

year  = {2023},

date = {2023-12-01},

journal = {Eur J Nutr},

volume = {62},

number = {8},

pages = {3227--3240},

abstract = {PURPOSE: The obese black and tan, brachyuric (BTBR) ob/ob mouse spontaneously develops features comparable to human diabetic nephropathy. The primary aim of the present study was to investigate if a diet containing fish proteins would attenuate or delay the development of glomerular hypertrophy (glomerulomegaly), mesangial sclerosis and albuminuria in obese BTBR ob/ob mice.nnMETHODS: Obese BTBR.CgLep/WiscJ male mice were fed diets containing 25% of protein from Atlantic cod backbones and 75% of protein from casein (Cod-BB group), or casein as the sole protein source (control group). Kidneys were analysed morphologically, and markers for renal dysfunction were analysed biochemically in urine and serum.nnRESULTS: The Cod-BB diet attenuated the development of mesangial sclerosis (P 0.040) without affecting the development of glomerular hypertrophy and albuminuria. The urine concentration of cystatin C (relative to creatinine) was lower in mice fed the Cod-BB diet (P 0.0044).nnCONCLUSION: A diet containing cod backbone protein powder attenuated the development of mesangial sclerosis and tubular dysfunction in obese BTBR ob/ob mice, but did not prevent the development of glomerular hypertrophy and albuminuria in these mice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37852105,

title = {The role of the kynurenine pathway in cognitive functioning after stroke: A prospective clinical study},

author = {Lieke Bakker and Inez H G B Ramakers and Simone J P M Eussen and Kyonghwan Choe and Daniel L A van den Hove and Gunter Kenis and Bart P F Rutten and Robert J van Oostenbrugge and Julie Staals and Arve Ulvik and Per M Ueland and Frans R J Verhey and Sebastian Köhler},

doi = {10.1016/j.jns.2023.120819},

issn = {1878-5883},

year  = {2023},

date = {2023-11-01},

journal = {J Neurol Sci},

volume = {454},

pages = {120819},

abstract = {BACKGROUND: The kynurenine pathway is the main metabolic pathway of tryptophan degradation and has been associated with stroke and impaired cognitive functioning, but studies on its role in post-stroke cognitive impairment (PSCI) are scarce. We aimed to investigate associations between metabolites of the kynurenine pathway at baseline and post-stroke cognitive functioning over time.nnMETHODS: Baseline plasma kynurenines were quantified in 198 stroke patients aged 65.4 ± 10.8 years, 138 (69.7%) men, who were followed up over a period of three years after stroke. Baseline and longitudinal associations of kynurenines with PSCI and cognitive domain scores were investigated using linear mixed models, adjusted for several confounders.nnRESULTS: No evidence of associations between kynurenines and odds of PSCI were found. However, considering individual cognitive domains, higher plasma levels of anthranilic acid (AA) were associated with better episodic memory at baseline (β per SD 0.16 [0.05, 0.28]). Additionally, a linear-quadratic association was found for the kynurenic acid/ quinolinic acid ratio (KA/QA), a neuroprotective index, with episodic memory (Wald χ = 8.27, p = .016). Higher levels of KA were associated with better processing speed in women only (p = .008; β per SD 0.15 [95% CI 0.02, 0.27]). These associations did not change over time.nnCONCLUSIONS: Higher levels of KA, AA and KA/QA were associated with better scores on some cognitive domains at baseline. These associations did not change over time. Given the exploratory nature and heterogeneity of findings, these results should be interpreted with caution, and verified in other prospective studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37923499,

title = {Longitudinal associations of macronutrient and micronutrient intake with plasma kynurenines in colorectal cancer survivors up to 12 months posttreatment},

author = {Daniëlle D B Holthuijsen and Eline H van Roekel and Martijn J L Bours and Per M Ueland and Stéphanie O Breukink and Maryska L G Janssen-Heijnen and Eric T P Keulen and Andrea Gsur and Dieuwertje E Kok and Arve Ulvik and Matty P Weijenberg and Simone J P M Eussen},

doi = {10.1016/j.ajcnut.2023.08.003},

issn = {1938-3207},

year  = {2023},

date = {2023-11-01},

journal = {Am J Clin Nutr},

volume = {118},

number = {5},

pages = {865--880},

abstract = {BACKGROUND: The tryptophan-kynurenine pathway is increasingly recognized to play a role in health-related quality of life (HRQoL) after cancer. Because tryptophan is an essential amino acid, and vitamins and minerals act as enzymatic cofactors in the tryptophan-kynurenine pathway, a link between diet and kynurenines is plausible.nnOBJECTIVES: This study aimed to investigate the longitudinal associations of macronutrient and micronutrient intake with metabolites of the kynurenine pathway in colorectal cancer (CRC) survivors up to 12 mo posttreatment.nnMETHODS: In a prospective cohort of stage I-III CRC survivors (n = 247), repeated measurements were performed at 6 wk, 6 mo, and 12 mo posttreatment. Macronutrient and micronutrient intake was measured by 7-d dietary records. Plasma concentrations of tryptophan and kynurenines were analyzed using liquid chromatography tandem mass spectrometry (LC/MS-MS). Longitudinal associations were analyzed using linear mixed models adjusted for sociodemographic, clinical, and lifestyle factors.nnRESULTS: After adjustment for multiple testing, higher total protein intake was positively associated with kynurenic acid (KA) (β as standard deviation [SD] change in KA concentration per 1 SD increase in total protein intake: 0.12; 95% CI: 0.04, 0.20), xanthurenic acid (XA) (standardized β: 0.22; 95% CI: 0.11, 0.33), 3-hydroxyanthranilic acid (HAA) (standardized β: 0.15; 95% CI: 0.04, 0.27) concentrations, and the kynurenic acid-to-quinolinic acid ratio (KA/QA) (standardized β: 0.12; 95% CI: 0.02,0.22). In contrast, higher total carbohydrate intake was associated with lower XA concentrations (standardized β: -0.18; 95% CI: -0.30, -0.07), a lower KA/QA (standardized β: -0.23; 95% CI: -0.34, -0.13), and a higher kynurenine-to-tryptophan ratio (KTR) (standardized β: 0.20; 95% CI: 0.10, 0.30). Higher fiber intake was associated with a higher KA/QA (standardized β: 0.11; 95% CI: 0.02, 0.21) and a lower KTR (standardized β: -0.12; 95% CI: -0.20, -0.03). Higher total fat intake was also associated with higher tryptophan (Trp) concentrations (standardized β: 0.18; 95% CI: 0.06, 0.30) and a lower KTR (standardized β: -0.13; 95% CI: -0.22, -0.03). For micronutrients, positive associations were observed for zinc with XA (standardized β: 0.13; 95% CI: 0.04, 0.21) and 3-hydroxykynurenine (HK) (standardized β: 0.12; 95% CI: 0.03, 0.20) concentrations and for magnesium with KA/QA (standardized β: 0.24; 95% CI: 0.13, 0.36).nnCONCLUSIONS: Our findings show that intake of several macronutrients and micronutrients is associated with some metabolites of the kynurenine pathway in CRC survivors up to 12 mo posttreatment. These results may be relevant for enhancing HRQoL after cancer through potential diet-induced changes in kynurenines. Further studies are necessary to confirm our findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37498368,

title = {Exploratory analyses on the effect of time since last meal on concentrations of amino acids, lipids, one-carbon metabolites, and vitamins in the Hordaland Health Study},

author = {Åslaug Matre Anfinsen and Hanne Rosendahl-Riise and Ottar Nygård and Grethe Seppola Tell and Per Magne Ueland and Arve Ulvik and Adrian McCann and Jutta Dierkes and Vegard Lysne},

doi = {10.1007/s00394-023-03211-y},

issn = {1436-6215},

year  = {2023},

date = {2023-10-01},

journal = {Eur J Nutr},

volume = {62},

number = {7},

pages = {3079--3095},

abstract = {PURPOSE: Dietary intake may have pronounced effects on circulating biomarker concentrations. Therefore, the aim was to provide a descriptive overview of serum metabolite concentrations in relation to time since last meal, focusing on amino acids, lipids, one-carbon metabolites, and biomarkers of vitamin status.nnMETHODS: We used baseline data from the observational community-based Hordaland Health Study, including 2960 participants aged 46-49 years and 2874 participants aged 70-74 years. A single blood draw was taken from each participant, and time since last meal varied. Estimated marginal geometric mean metabolite concentrations were plotted as a function of time since last meal, up to 7 h, adjusted for age, sex, and BMI.nnRESULTS: We observed a common pattern for nearly all amino acids and one-carbon metabolites with highest concentrations during the first 3 h after dietary intake. Homocysteine and cysteine were lowest the 1st hour after a meal, while no patterns were observed for glutamate and glutamic acid. The concentrations of phylloquinone and triglycerides were highest 1 h after dietary intake. Thiamine and thiamine monophosphate concentrations were highest, while flavin mononucleotide concentrations were lowest within the first 2 h after a meal. No clear patterns emerged for the other fat-soluble vitamins, blood lipids, or B-vitamin biomarkers.nnCONCLUSION: Our findings suggest that distinguishing between "fasting" and "non-fasting" blood samples may be inadequate, and a more granular approach is warranted. This may have implications for how to account for dietary intake when blood sampling in both clinical and research settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37880581,

title = {B-vitamins, related vitamers, and metabolites in patients with quiescent inflammatory bowel disease and chronic fatigue treated with high dose oral thiamine},

author = {Palle Bager and Christian Lodberg Hvas and Mette Mejlby Hansen and Per Ueland and Jens Frederik Dahlerup},

doi = {10.1186/s10020-023-00741-3},

issn = {1528-3658},

year  = {2023},

date = {2023-10-01},

journal = {Mol Med},

volume = {29},

number = {1},

pages = {143},

abstract = {BACKGROUND: High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue.nnMETHODS: Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab.nnRESULTS: Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01).nnCONCLUSION: FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention.nnCLINICAL TRIAL REGISTRATION: ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37328069,

title = {Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation},

author = {Peder Rustøen Braadland and Annika Bergquist and Martin Kummen and Lars Bossen and Lise Katrine Engesæter and Henrik Mikael Reims and Ida Björk and Krzysztof Grzyb and Andreas Abildgaard and Milada Cvancarova Småstuen and Trine Folseraas and Marius Trøseid and Arve Ulvik and Per Magne Ueland and Espen Melum and Pål-Dag Line and Marte Lie Høivik and Henning Grønbæk and Tom Hemming Karlsen and Mette Vesterhus and Johannes Roksund Hov},

doi = {10.1016/j.jhep.2023.05.038},

issn = {1600-0641},

year  = {2023},

date = {2023-10-01},

journal = {J Hepatol},

volume = {79},

number = {4},

pages = {955--966},

abstract = {BACKGROUND AND AIMS: We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT).nnMETHODS: We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT.nnRESULTS: In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease.nnCONCLUSIONS: Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation.nnIMPACT AND IMPLICATIONS: We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36622937,

title = {The Influence of Preanalytical Biospecimen Handling on the Measurement of B Vitamers, Amino Acids, and Other Metabolites in Blood},

author = {Kara A Michels and Stephanie J Weinstein and Paul S Albert and Amanda Black and Michelle Brotzman and Norma A Diaz-Mayoral and Nicole Gerlanc and Wen-Yi Huang and Joshua N Sampson and Alaina Shreves and Per Magne Ueland and Kathleen Wyatt and Nicolas Wentzensen and Christian C Abnet},

doi = {10.1089/bio.2022.0053},

issn = {1947-5543},

year  = {2023},

date = {2023-10-01},

journal = {Biopreserv Biobank},

volume = {21},

number = {5},

pages = {467--476},

abstract = { Sample handling can influence biomarker measurement and introduce variability when combining data from multiple studies or study sites. To inform the development of blood collection protocols within a multisite cohort study, we directly quantified concentrations of 54 biomarkers in blood samples subjected to different handling conditions.  We obtained serum, lithium heparin plasma, and EDTA plasma from 20 adult volunteers. Tubes of chilled whole blood were either centrifuged and processed within 2 hours of collection (the "reference standard") or were stored with cool packs for 24 or 48 hours; centrifuged before and/or after this delay; or collected in tubes with/without gel separators. We used linear mixed models with random intercepts to estimate geometric mean concentrations and relative percent differences across the conditions.  Compared to the reference standard tubes, concentrations of many biomarkers changed after processing delays, but changes were often small. In serum, we observed large differences for B vitamers, glutamic acid (37% and 73% increases with 24- and 48-hour delays, respectively), glycine (12% and 23% increases), serine (16% and 27% increases), and acetoacetate (-19% and -26% decreases). Centrifugation timing and separator tube use did not affect concentrations of most biomarkers.  Sample handling should be consistent across samples within an analysis. The length of processing delays should be recorded and accounted for when this is not feasible.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37773439,

title = {Lower levels of the neuroprotective tryptophan metabolite, kynurenic acid, in users of estrogen contraceptives},

author = {Anne-Lise Bjørke-Monsen and Kristin Varsi and Sunniva Todnem Sakkestad and Arve Ulvik and Cathrine Ebbing and Per Magne Ueland},

doi = {10.1038/s41598-023-43196-6},

issn = {2045-2322},

year  = {2023},

date = {2023-09-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {16370},

abstract = {Changes in kynurenine metabolites are reported in users of estrogen containing contraception. We have assessed kynurenines, vitamin B6, vitamin B2 and the inflammation markers, C-reactive protein (CRP) and neopterin, in healthy, never-pregnant women between 18 and 40 years (n = 123) and related this to their use of hormonal contraception. The population included 58 women, who did not use hormonal contraceptives (non-users), 51 users of estrogen-containing contraceptives (EC-users), and 14 users of progestin only contraceptives (PC-users). EC-users had significantly lower plasma kynurenic acid (KA) and higher xanthurenic acid (XA) levels compared to non-users. Serum CRP was significantly higher and negatively associated with both vitamin B6 and B2 status in EC-user compared to non-users. No significant differences in any parameters were seen between PC-users and non-users (p > 0.1). The low KA and high XA concentration in users of estrogen containing contraception resemble the biochemical profile observed in vitamin B6 deficiency. The hormonal effect may result from interference with the coenzyme function of vitamin B6 and B2 for particular enzymes in the kynurenine metabolism. KA has been suggested to be neuroprotective and the significantly reduced concentration in EC-users may be of importance in the observed increased risk of mood disorders among users of oral contraceptives.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36916878,

title = {Impaired Adipocyte SLC7A10 Promotes Lipid Storage in Association With Insulin Resistance and Altered BCAA Metabolism},

author = {Regine Å Jersin and Divya Sri Priyanka Tallapragada and Linn Skartveit and Mona S Bjune and Maheswary Muniandy and Sindre Lee-Ødegård and Sini Heinonen and Marcus Alvarez and Kåre Inge Birkeland and Christian André Drevon and Päivi Pajukanta and Adrian McCann and Kirsi H Pietiläinen and Melina Claussnitzer and Gunnar Mellgren and Simon N Dankel},

doi = {10.1210/clinem/dgad148},

issn = {1945-7197},

year  = {2023},

date = {2023-08-01},

journal = {J Clin Endocrinol Metab},

volume = {108},

number = {9},

pages = {2217--2229},

abstract = {CONTEXT: The neutral amino acid transporter SLC7A10/ASC-1 is an adipocyte-expressed gene with reduced expression in insulin resistance and obesity. Inhibition of SLC7A10 in adipocytes was shown to increase lipid accumulation despite decreasing insulin-stimulated uptake of glucose, a key substrate for de novo lipogenesis. These data imply that alternative lipogenic substrates to glucose fuel continued lipid accumulation during insulin resistance in obesity.nnOBJECTIVE: We examined whether increased lipid accumulation during insulin resistance in adipocytes may involve alter flux of lipogenic amino acids dependent on SLC7A10 expression and activity, and whether this is reflected by extracellular and circulating concentrations of marker metabolites.nnMETHODS: In adipocyte cultures with impaired SLC7A10, we performed RNA sequencing and relevant functional assays. By targeted metabolite analyses (GC-MS/MS), flux of all amino acids and selected metabolites were measured in human and mouse adipose cultures. Additionally, SLC7A10 mRNA levels in human subcutaneous adipose tissue (SAT) were correlated to candidate metabolites and adiposity phenotypes in 2 independent cohorts.nnRESULTS: SLC7A10 impairment altered expression of genes related to metabolic processes, including branched-chain amino acid (BCAA) catabolism, lipogenesis, and glyceroneogenesis. In 3T3-L1 adipocytes, SLC7A10 inhibition increased fatty acid uptake and cellular content of glycerol and cholesterol. SLC7A10 impairment in SAT cultures altered uptake of aspartate and glutamate, and increased net uptake of BCAAs, while increasing the net release of the valine catabolite 3- hydroxyisobutyrate (3-HIB). In human cohorts, SLC7A10 mRNA correlated inversely with total fat mass, circulating triacylglycerols, BCAAs, and 3-HIB.nnCONCLUSION: Reduced SLC7A10 activity strongly affects flux of BCAAs in adipocytes, which may fuel continued lipogenesis during insulin resistance, and be reflected in increased circulating levels of the valine-derived catabolite 3-HIB.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36400946,

title = {Inflammation, sex, blood pressure changes and hypertension in midlife: the Hordaland Health Study},

author = {Ester Kringeland and Eva Gerdts and Arve Ulvik and Grethe S Tell and Jannicke Igland and Teresa R Haugsgjerd and Per Magne Ueland and Helga Midtbø},

doi = {10.1038/s41371-022-00772-z},

issn = {1476-5527},

year  = {2023},

date = {2023-08-01},

journal = {J Hum Hypertens},

volume = {37},

number = {8},

pages = {718--725},

abstract = {Our aim was to test sex-specific associations of circulating markers of inflammation with blood pressure (BP) and incident hypertension in midlife. Participants in the Hordaland Health study (n = 3280, 56% women, mean age 48 years) were examined at baseline and followed for 6 years. Circulating levels of inflammatory markers including high-sensitive C-reactive protein (hs-CRP), neopterin, and pyridoxic acid ratio (PAr) index were measured at follow-up. The associations with systolic/diastolic BP and incident hypertension were tested in sex-specific linear- or logistic-regression analyses adjusted for body mass index, serum triglycerides, creatinine, physical activity, smoking and diabetes. At follow-up, women had lower mean BP than men (124/72 vs. 130/78 mmHg, p < 0.001). Higher hs-CRP was significantly associated with greater systolic and diastolic BP (standardized β = 0.07 and β = 0.09, both p < 0.01) in women, but not in men. Higher neopterin was associated with higher diastolic BP in women and higher PAr index was associated with higher diastolic BP in women and higher systolic and diastolic BP in men (all p < 0.01). Compared to hs-CRP < 1 mg/l, higher levels of hs-CRP 1-<3 mg/l and hs-CRP ≥ 3 mg/l were associated with new-onset hypertension only in women (odds ratio (OR) 1.74, 95% CI 1.20-2.53 and OR 1.87, 95% CI 1.20-2.90). Sex-interactions were found for hs-CRP and neopterin in models on incident hypertension and diastolic BP, respectively (both p < 0.05). Higher levels of circulating markers of inflammation were associated with higher BP and incident hypertension in a sex-specific manner. Our results suggest a sex-specific interaction between cardiovascular inflammation and BP in midlife.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37630687,

title = {Vitamin B12 Status before and after Outpatient Treatment of Severe Acute Malnutrition in Children Aged 6-59 Months: A Sub-Study of a Randomized Controlled Trial in Burkina Faso},

author = {Victor Nikièma and Suvi T Kangas and Cécile Salpeteur and André Briend and Leisel Talley and Henrik Friis and Christian Ritz and Ebba Nexo and Adrian McCann},

doi = {10.3390/nu15163496},

issn = {2072-6643},

year  = {2023},

date = {2023-08-01},

journal = {Nutrients},

volume = {15},

number = {16},

abstract = {Severe acute malnutrition (SAM) is treated with ready-to-use therapeutic foods (RUTF) containing a vitamin-mineral premix. Yet little is known about micronutrient status in children with SAM before and after treatment. We aimed to investigate vitamin B12 status in children with uncomplicated SAM, aged 6-59 months in Burkina Faso, before and after treatment with a standard or a reduced dose of RUTF. Blood samples were collected at admission and discharge. Serum B12 was determined with microbiological assay and serum methylmalonic acid (MMA) and total homocysteine (tHcy) were analyzed with gas chromatography-tandem mass spectrometry. B12 status was classified using the combined indicator (3cB12). Among 374 children, the median [interquartile range] age was 11.0 [7.7-16.9] months, and 85.8% were breastfed. Marked or severe B12 deficiency, as judged by 3cB12, decreased from 32% to 9% between admission and discharge ( < 0.05). No differences in B12 status following treatment with either standard ( = 194) or reduced ( = 180) doses of RUTF were observed. Breastfed children showed a lower B12 status (3cB12) than non-breastfed ones (-1.10 vs -0.18,  < 0.001 at admission; -0.44 vs 0.19;  < 0.001 at discharge). In conclusion, treatment of SAM with RUTF improved children's B12 status but did not fully correct B12 deficiency.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37149106,

title = {Correlations between kynurenines in plasma and CSF, and their relation to markers of Alzheimer's disease pathology},

author = {Lieke Bakker and Sebastian Köhler and Simone J P M Eussen and Kyonghwan Choe and Daniel L A van den Hove and Gunter Kenis and Bart P F Rutten and Arve Ulvik and Per M Ueland and Frans R J Verhey and Inez H G B Ramakers},

doi = {10.1016/j.bbi.2023.04.015},

issn = {1090-2139},

year  = {2023},

date = {2023-07-01},

journal = {Brain Behav Immun},

volume = {111},

pages = {312--319},

abstract = {INTRODUCTION: Altered levels of kynurenines in blood and cerebrospinal fluid (CSF) have been reported in Alzheimer's disease (AD). However, it is still largely unknown whether peripheral kynurenine concentrations resemble those found in CSF and how they relate to AD pathology. We therefore studied correlations between kynurenines in plasma and CSF and their associations with CSF amyloid-beta (Aβ) and tau levels in patients from the memory clinic spanning the whole cognitive spectrum.nnMETHODS: The Biobank Alzheimer Center Limburg study is a prospective cohort study of consecutive patients referred to the memory clinic of the Alzheimer Center Limburg. Plasma and CSF concentrations of tryptophan (TRP), eight kynurenines and neopterin from 138 patients were determined by means of LC-MS/MS. Additionally, CSF Aβ, total-tau (t-tau) and phosphorylated tau (p-tau) concentrations were determined using commercially available single-parameter ELISA methods. Partial correlations were used to analyze cross-sectional associations between kynurenines in plasma and CSF and their relation to AD related CSF-biomarkers adjusted for age, sex, educational level, and kidney function.nnRESULTS: Moderate to strong correlations were observed between plasma and CSF levels for quinolinic acid (QA; r = 0.63), TRP (r = 0.47), anthranilic acid (r = 0.59), picolinic acid (r = 0.55), and the kynurenine (KYN)/TRP ratio (KTR; r = 0.55; all p < 0.0001), while other kynurenines correlated only weakly with their corresponding CSF values. No correlations were found between plasma and CSF levels of KA/QA. Several kynurenines were also weakly correlated with Aβ, t-tau or p-tau. Plasma levels of KA/QA were negatively correlated with Aβ (r = -0.21, p < 0.05). Plasma levels of TRP were negatively correlated with t-tau (r = -0.19) and levels of KYN with p-tau (r = -0.18; both p < 0.05). CSF levels of KYN (r = 0.20, p < 0.05), KA (r = 0.23, p < 0.01), and KTR (r = 0.18, p < 0.05) were positively correlated with Aβ. Finally, TRP and KYN were negatively (r = -0.22 and r = -0.18, respectively), and neopterin positively (r = 0.19) correlated with p-tau (all p < 0.05).nnCONCLUSIONS: Plasma concentrations of TRP, KP metabolites, KTR, and neopterin all significantly correlated positively with their corresponding CSF concentrations, but many correlations were weak. Additionally, our results suggest a relation between higher kynurenine levels and lower AD pathology load. These results need verification in future studies and require more research into (shared) underlying mechanisms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37121550,

title = {B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study},

author = {Indu Dhar and Gard Ft Svingen and Espen Ø Bjørnestad and Arve Ulvik and Sahrai Saeed and Ottar K Nygård},

doi = {10.1016/j.ajcnut.2023.04.033},

issn = {1938-3207},

year  = {2023},

date = {2023-07-01},

journal = {Am J Clin Nutr},

volume = {118},

number = {1},

pages = {77--84},

abstract = {BACKGROUND: Calcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker.nnOBJECTIVE: We explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B, and/or B) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial.nnMETHODS: Patient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included CVD risk factors, medical histories, and the use of CVD medications.nnRESULTS: A total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.7% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels, and erythrocyte sedimentation rate (all P<0.001). Furthermore, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15,1.57], 1.35 [1.08,1.70], and 1.33 [1.09,1.64] for total, CVD, and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25, 1.88], 1.69 [1.25, 2.30], and 1.41 [1.06, 1.86] for total, CVD deaths, and non-CVD deaths, respectively), whereas no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91, 1.46], 1.09 [0.76, 1.57], and 1.20 [0.88, 1.65]).nnCONCLUSIONS: In patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37444500,

title = {Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium},

author = {Jennifer Ose and Biljana Gigic and Stefanie Brezina and Tengda Lin and Anita R Peoples and Pauline P Schobert and Andreas Baierl and Eline van Roekel and Nivonirina Robinot and Audrey Gicquiau and David Achaintre and Augustin Scalbert and Fränzel J B van Duijnhoven and Andreana N Holowatyj and Tanja Gumpenberger and Petra Schrotz-King and Alexis B Ulrich and Arve Ulvik and Per-Magne Ueland and Matty P Weijenberg and Nina Habermann and Pekka Keski-Rahkonen and Andrea Gsur and Dieuwertje E Kok and Cornelia M Ulrich},

doi = {10.3390/cancers15133391},

issn = {2072-6694},

year  = {2023},

date = {2023-06-01},

journal = {Cancers (Basel)},

volume = {15},

number = {13},

abstract = {Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates Absolute p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I-III) colon ( = 394) or rectal cancer ( = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23-1.72, p = 0.03; but not colon cancer: p = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37084480,

title = {Metabolic role of the hepatic valine/3-hydroxyisobutyrate (3-HIB) pathway in fatty liver disease},

author = {Mona Synnøve Bjune and Laurence Lawrence-Archer and Johnny Laupsa-Borge and Cathrine Horn Sommersten and Adrian McCann and Robert Clay Glastad and Iain George Johnston and Matthias Kern and Matthias Blüher and Gunnar Mellgren and Simon N Dankel},

doi = {10.1016/j.ebiom.2023.104569},

issn = {2352-3964},

year  = {2023},

date = {2023-05-01},

journal = {EBioMedicine},

volume = {91},

pages = {104569},

abstract = {BACKGROUND: The valine (branched-chain amino acid) metabolite 3-hydroxyisobutyrate (3-HIB), produced by 3-Hydroxyisobutyryl-CoA Hydrolase (HIBCH), is associated with insulin resistance and type 2 diabetes, but implicated tissues and cellular mechanisms are poorly understood. We hypothesized that HIBCH and 3-HIB regulate hepatic lipid accumulation.nnMETHODS: HIBCH mRNA in human liver biopsies ("Liver cohort") and plasma 3-HIB ("CARBFUNC" cohort) were correlated with fatty liver and metabolic markers. Human Huh7 hepatocytes were supplemented with fatty acids (FAs) to induce lipid accumulation. Following HIBCH overexpression, siRNA knockdown, inhibition of PDK4 (a marker of FA β-oxidation) or 3-HIB supplementation, we performed RNA-seq, Western blotting, targeted metabolite analyses and functional assays.nnFINDINGS: We identify a regulatory feedback loop between the valine/3-HIB pathway and PDK4 that shapes hepatic FA metabolism and metabolic health and responds to 3-HIB treatment of hepatocytes. HIBCH overexpression increased 3-HIB release and FA uptake, while knockdown increased cellular respiration and decreased reactive oxygen species (ROS) associated with metabolic shifts via PDK4 upregulation. Treatment with PDK4 inhibitor lowered 3-HIB release and increased FA uptake, while increasing HIBCH mRNA. Implicating this regulatory loop in fatty liver, human cohorts show positive correlations of liver fat with hepatic HIBCH and PDK4 expression (Liver cohort) and plasma 3-HIB (CARBFUNC cohort). Hepatocyte 3-HIB supplementation lowered HIBCH expression and FA uptake and increased cellular respiration and ROS.nnINTERPRETATION: These data implicate the hepatic valine/3-HIB pathway in mechanisms of fatty liver, reflected in increased plasma 3-HIB concentrations, and present possible targets for therapeutic intervention.nnFUNDING: Funding was provided by the Research Council of Norway (263124/F20), the University of Bergen, the Western Norway Health Authorities, Novo Nordisk Scandinavia AS, the Trond Mohn Foundation and the Norwegian Diabetes Association.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37031691,

title = {The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial},

author = {Ram K Chandyo and Ingrid Kvestad and Manjeswori Ulak and Suman Ranjitkar and Mari Hysing and Merina Shrestha and Catherine Schwinger and Adrian McCann and Per M Ueland and Sudha Basnet and Laxman Shrestha and Tor A Strand},

doi = {10.1016/S0140-6736(23)00346-X},

issn = {1474-547X},

year  = {2023},

date = {2023-05-01},

journal = {Lancet},

volume = {401},

number = {10387},

pages = {1508--1517},

abstract = {BACKGROUND: Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment.nnMETHODS: In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666.nnFINDINGS: 800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0·57 (SD 1·03) in the B12 group and -0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group.nnINTERPRETATION: Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy.nnFUNDING: Research Council of Norway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}