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1. A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

Author

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

Subjects
Biological Sciences, Genetics, Pediatric, Prevention, Nutrition, Perinatal Period - Conditions Originating in Perinatal Period, Reproductive health and childbirth, Good Health and Well Being, Infant, Newborn, Pregnancy, Child, Female, Humans, DNA Methylation, Epigenome, Birth Weight, Vitamin B 12, Epigenesis, Genetic, Fetal Blood, Vitamin B12, DNA methylation, epidemiology, cohort study, meta-analysis, PACE consortium, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Developmental Biology, Biochemistry and cell biology
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 (n = 2,420) or cord blood (n = 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 P-value

Published
2023

2. Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity

Author

Raju, Sajan C., Molinaro, Antonio, Awoyemi, Ayodeji, Jørgensen, Silje F., Braadland, Peder R., Nendl, Andraz, Seljeflot, Ingebjørg, Ueland, Per M., McCann, Adrian, Aukrust, Pål, Vestad, Beate, Mayerhofer, Cristiane, Broch, Kaspar, Gullestad, Lars, Lappegård, Knut T., Halvorsen, Bente, Kristiansen, Karsten, Hov, Johannes R., and Trøseid, Marius

Published
2024
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6. A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium

Author

Midttun, Øivind, Ulvik, Arve, Meyer, Klaus, Zahed, Hana, Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Behndig, Annelie F., Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loïc, Weinstein, Stephanie J., Cai, Qiuyin, Arslan, Alan A., Chen, Yu, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Robbins, Hilary A., Brennan, Paul, Johansson, Mattias, and Ueland, Per M.

Published
2023
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16. Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12 months post‐treatment.

Author

Holthuijsen, Daniëlle D. B., van Roekel, Eline H., Bours, Martijn J. L., Ueland, Per M., Breukink, Stéphanie O., Janssen‐Heijnen, Maryska L. G., Keulen, Eric T. P., Brezina, Stefanie, Gigic, Biljana, Peoples, Anita R., Ulrich, Cornelia M., Ulvik, Arve, Weijenberg, Matty P., and Eussen, Simone J. P. M.

Subjects
FALSE discovery rate, COLORECTAL cancer, CANCER fatigue, MASS spectrometry, TRYPTOPHAN
Abstract

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health‐related quality of life (HRQoL). Inflammation‐induced activation of the kynurenine pathway may play a role in cancer‐related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post‐treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post‐treatment were performed in 249 stage I‐III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography‐tandem mass spectrometry (LC/MS–MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder‐adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid‐to‐quinolinic acid ratio (KA/QA), were associated with less fatigue and better functioning, while a higher kynurenine‐to‐tryptophan ratio (KTR) and 3‐hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12 months post‐treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Lifestyle, metabolite, and genetic determinants of formate concentrations in a cross-sectional study in young, healthy adults

Author

Brosnan, John T, Mills, James L, Ueland, Per M, Shane, Barry, Fan, Ruzong, Chiu, Chi-Yang, Pangilinan, Faith, Brody, Lawrence C, Brosnan, Margaret E, Pongnopparat, Theerawat, and Molloy, Anne M

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Clinical Research, Genetics, Nutrition, Prevention, Complementary and Integrative Health, Good Health and Well Being, Adolescent, Adult, Choline, Cross-Sectional Studies, Female, Formates, Genotyping Techniques, Humans, Incidence, Life Style, Male, Methionine, Methylenetetrahydrofolate Reductase (NADPH2), Polymorphism, Single Nucleotide, Serine, Tryptophan, Young Adult, folate, vitamin B-12, methylenetetrahydrofolate reductase, one-carbon metabolism, Trinity Student Study, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundFormate is an important metabolite that serves as a donor of one-carbon groups to the intracellular tetrahydrofolate pool. However, little is known of its circulating concentrations or of their determinants.ObjectiveThis study aimed to define formate concentrations and their determinants in a healthy young population.DesignSerum formate was measured in 1701 participants from the Trinity Student Study. The participants were men and women, aged 18 to 28 y, enrolled at Trinity College, Dublin. Formate concentrations were compared with other one-carbon metabolites, vitamin status, potential formate precursors, genetic polymorphisms, and lifestyle factors.ResultsSerum formate concentrations ranged from 8.7 to 96.5 µM, with a mean of 25.9 µM. Formate concentrations were significantly higher in women than in men; oral contraceptive use did not further affect them. There was no effect of smoking or of alcohol ingestion, but the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) polymorphism was associated with a significantly decreased formate concentration. Formate was positively associated with potential metabolic precursors (serine, methionine, tryptophan, choline) but not with glycine. Formate concentrations were positively related to serum folate and negatively related to serum vitamin B-12.ConclusionsFormate concentrations were sensitive to the concentrations of metabolic precursors. In view of the increased susceptibility of women with the TT genotype of MTHFR to give birth to infants with neural tube defects as well as the effectiveness of formate supplementation in decreasing the incidence of folate-resistant neural tube defects in susceptible mice, it will be important to understand how this genotype decreases the serum formate concentration. This trial was registered at www.clinicaltrials.gov as NCT03305900.

Published
2018

19. Inflammation-Related Marker Profiling of Dietary Patterns and All-cause Mortality in the Melbourne Collaborative Cohort Study

Author

Li, Sherly X, Hodge, Allison M, MacInnis, Robert J, Bassett, Julie K, Ueland, Per M, Midttun, Øivind, Ulvik, Arve, Rinaldi, Sabina, Meyer, Klaus, Navionis, Anne-Sophie, Shivappa, Nitin, Hébert, James R, Flicker, Leon, Severi, Gianluca, Jayasekara, Harindra, English, Dallas R, Vineis, Paolo, Southey, Melissa C, Milne, Roger L, Giles, Graham G, and Dugué, Pierre-Antoine

Published
2021
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20. Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes: the Maastricht Study

Author

Bakker, Lieke, Ramakers, Inez H. G. B., van Boxtel, Martin P. J., Schram, Miranda T., Stehouwer, Coen D. A., van der Kallen, Carla J. H., Dagnelie, Pieter C., van Greevenbroek, Marleen M. J., Wesselius, Anke, Midttun, Øivind, Ueland, Per M., Verhey, Frans R. J., Eussen, Simone J. P. M., and Köhler, Sebastian

Published
2021
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21. Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer : a cohort study

Author

Kok, Dieuwertje E., van Duijnhoven, Fränzel J.B., Lubberman, Floor J.E., McKay, Jill A., van Lanen, Anne-Sophie, Winkels, Renate M., Wesselink, Evertine, van Halteren, Henk K., de Wilt, Johannes H.W., Ulrich, Cornelia M., Ulvik, Arve, Ueland, Per M., Kampman, Ellen, Kok, Dieuwertje E., van Duijnhoven, Fränzel J.B., Lubberman, Floor J.E., McKay, Jill A., van Lanen, Anne-Sophie, Winkels, Renate M., Wesselink, Evertine, van Halteren, Henk K., de Wilt, Johannes H.W., Ulrich, Cornelia M., Ulvik, Arve, Ueland, Per M., and Kampman, Ellen

Abstract

Background: Capecitabine is an oral chemotherapeutic drug showing antitumor activity through inhibition of thymidylate synthase, an enzyme involved in folate metabolism. There are concerns about the high intake of certain vitamins, and specifically folate, during chemotherapy with capecitabine. Whether folate or folic acid, the synthetic variant of the vitamin, impact treatment toxicity remains unclear. Objective: We studied associations between intake and biomarkers of folate as well as folic acid and toxicities in patients with colorectal cancer (CRC) receiving capecitabine. Methods: Within the prospective COLON (Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence recurrence, survival, and quality of life) cohort, 290 patients with stage II to III CRC receiving capecitabine were identified. Dietary and supplemental intake of folate and folic acid were assessed at diagnosis and during chemotherapy using questionnaires (available for 280 patients). Plasma folate and folic acid levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and were available for 212 patients. Toxicities were defined as toxicity-related modifications of treatment, including dose reductions, regimen switches, and early discontinuation. Associations of intake and biomarkers of folate and folic acid with toxicities were determined using Cox proportional hazards regression adjusted for age and sex. Results: In total, 153 (53%) patients experienced toxicities leading to modification of capecitabine treatment. Folate intake and plasma folate levels were not associated with risk of toxicities. However, use of folic acid-containing supplements during treatment (hazard ratio (HR) 1.81 and 95% confidence interval (CI) 1.15-2.85) and presence of folic acid in plasma at diagnosis (HR 2.09, 95% CI: 1.24, 3.52) and during treatment (HR 2.31, 95% CI: 1.29, 4.13) were associated with an increased risk of toxicities. Conclusions

Published
2024

22. Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV

Author

Trøseid, Marius, Molinaro, Antonio, Gelpi, Marco, Vestad, Beate, Kofoed, Klaus Fuglsang, Fuchs, Andreas, Køber, Lars, Holm, Kristian, Benfield, Thomas, Ueland, Per M., Hov, Johannes R., Nielsen, Susanne Dam, Knudsen, Andreas Dehlbæk, Trøseid, Marius, Molinaro, Antonio, Gelpi, Marco, Vestad, Beate, Kofoed, Klaus Fuglsang, Fuchs, Andreas, Køber, Lars, Holm, Kristian, Benfield, Thomas, Ueland, Per M., Hov, Johannes R., Nielsen, Susanne Dam, and Knudsen, Andreas Dehlbæk

Abstract

Background The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. Methods Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). Results Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1–7.2; P = .048). Conclusions PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events., Background. The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. Methods. Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). Results. Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1–7.2; P = .048). Conclusions. PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.

Published
2024

23. Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV

Author

Trøseid, Marius, primary, Molinaro, Antonio, additional, Gelpi, Marco, additional, Vestad, Beate, additional, Kofoed, Klaus Fuglsang, additional, Fuchs, Andreas, additional, Køber, Lars, additional, Holm, Kristian, additional, Benfield, Thomas, additional, Ueland, Per M, additional, Hov, Johannes R, additional, Nielsen, Susanne Dam, additional, and Knudsen, Andreas Dehlbæk, additional

Published
2024
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25. Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer: a cohort study

Author

Kok, Dieuwertje E., primary, van Duijnhoven, Fränzel J.B., additional, Lubberman, Floor J.E., additional, McKay, Jill A., additional, van Lanen, Anne-Sophie, additional, Winkels, Renate M., additional, Wesselink, Evertine, additional, van Halteren, Henk K., additional, de Wilt, Johannes H.W., additional, Ulrich, Cornelia M., additional, Ulvik, Arve, additional, Ueland, Per M., additional, and Kampman, Ellen, additional

Published
2023
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27. Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults

Author

Zahed, Hana, Johansson, Mattias, Ueland, Per M., Midttun, Øivind, Milne, Roger L., Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Grankvist, Kjell, Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loic, Wilkens, Lynne R., Weinstein, Stephanie J., Albanes, Demetrius, Cai, Qiuyin, Blot, William J., Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Muller, David, Brennan, Paul, Guida, Florence, and Robbins, Hilary A.

Published
2021
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30. The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial

Author

Ulak, Manjeswori, primary, Kvestad, Ingrid, additional, Chandyo, Ram K, additional, Schwinger, Catherine, additional, Basnet, Sudha, additional, Shrestha, Merina, additional, Ranjitkar, Suman, additional, Nguyen, Linda Vy, additional, Corona-Pérez, Diana, additional, De Vivo, Immaculata, additional, Ueland, Per M, additional, McCann, Adrian, additional, and Strand, Tor A, additional

Published
2023
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32. Parental Smoking and Risk of Childhood-onset Type 1 Diabetes

Author

Magnus, Maria C., Tapia, German, Olsen, Sjurdur F., Granstrom, Charlotta, Mårild, Karl, Ueland, Per M., Midttun, Øivind, Svensson, Jannet, Johannesen, Jesper, Skrivarhaug, Torild, Joner, Geir, Njølstad, Pål R., Størdal, Ketil, and Stene, Lars C.

Published
2018

37. Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation

Author

Agudelo, Leandro Z., Ferreira, Duarte M.S., Cervenka, Igor, Bryzgalova, Galyna, Dadvar, Shamim, Jannig, Paulo R., Pettersson-Klein, Amanda T., Lakshmikanth, Tadepally, Sustarsic, Elahu G., Porsmyr-Palmertz, Margareta, Correia, Jorge C., Izadi, Manizheh, Martínez-Redondo, Vicente, Ueland, Per M., Midttun, Øivind, Gerhart-Hines, Zachary, Brodin, Petter, Pereira, Teresa, Berggren, Per-Olof, and Ruas, Jorge L.

Published
2018
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42. Abstract 1010: Circulating biomarkers of vitamin B1, B2, and B3 status and their associations with clinical outcomes among non-metastatic colorectal cancer patients: results from the FOCUS Consortium

Author

Gigic, Biljana, primary, Ose, Jennifer, additional, Brezina, Stefanie, additional, Geijsen, Anne JMR, additional, Ulvik, Arve, additional, van Roekel, Eline H., additional, Holowatyj, Andreana N., additional, Kok, Dieuwertje E., additional, van Duijnhoven, Fränzel JB, additional, Damerell, Victoria, additional, Li, Christopher I., additional, Habermann, Nina, additional, Ulrich, Alexis B., additional, Weijenberg, Matty P., additional, Gsur, Andrea, additional, Ueland, Per M., additional, Kampman, Ellen, additional, Schneider, Martin, additional, and Ulrich, Cornelia M., additional

Published
2023
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45. A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

Author

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

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 (n = 2,420) or cord blood (n = 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 P-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 (P FDR<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.

Published
2023

49. Effects of vitamin B.sub.12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial

Author

Strand, Tor A., Ulak, Manjeswori, Hysing, Mari, Ranjitkar, Suman, Kvestad, Ingrid, Shrestha, Merina, Ueland, Per M., McCann, Adrian, Shrestha, Prakash S., Shrestha, Laxman S., and Chandyo, Ram K.

Subjects
Infants -- Growth -- Food and nutrition -- Physiological aspects, Vitamin B12 -- Physiological aspects, Neurogenesis -- Nutritional aspects, Company growth, Biological sciences
Abstract

Background Vitamin B.sub.12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B.sub.12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B.sub.12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. Methods and findings This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 [mu]g of vitamin B.sub.12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B.sub.12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B.sub.12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): -0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: -1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: -0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B.sub.12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B.sub.12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B.sub.12 supplementation might not have covered a critical window for infant growth or brain development. Conclusions In this study, we observed that vitamin B.sub.12 supplementation in young children at risk of vitamin B.sub.12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B.sub.12 supplementation in marginalized infants from low-income countries. Trial registration ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information)., Author(s): Tor A. Strand 1,2,*, Manjeswori Ulak 2,3, Mari Hysing 4, Suman Ranjitkar 3, Ingrid Kvestad 5, Merina Shrestha 3, Per M. Ueland 6, Adrian McCann 6, Prakash S. Shrestha [...]

Published
2020
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50. Plasma methylmalonic acid predicts risk of acute myocardial infarction and mortality in patients with coronary heart disease: A prospective 2‐cohort study

Author

Dhar, Indu, primary, Lysne, Vegard, additional, Ulvik, Arve, additional, Svingen, Gard F. T., additional, Pedersen, Eva R., additional, Bjørnestad, Espen Ø., additional, Olsen, Thomas, additional, Borsholm, Robert, additional, Laupsa‐Borge, Johnny, additional, Ueland, Per M., additional, Tell, Grethe S., additional, Berge, Rolf K., additional, Mellgren, Gunnar, additional, Bønaa, Kaare H., additional, and Nygård, Ottar K, additional

Published
2023
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