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Ebba Nexo - One of the best experts on this subject based on the ideXlab platform.
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Metformin Lowers Serum Cobalamin without Changing Other Markers of Cobalamin Status: A Study on Women with Polycystic Ovary Syndrome
Nutrients, 2013Co-Authors: Eva Greibe, Birgitta Trolle, Mustafa Vakur Bor, Finn Friis Lauszus, Ebba NexoAbstract:Treatment with the anti-diabetic drug metformin is followed by a decline in plasma Cobalamin, but it is unsettled whether this denotes an impaired Cobalamin status. This study has explored changes in the markers of Cobalamin status in women with Polycystic Ovary Syndrome treated with metformin (1.5-2.5 g per day) (n = 29) or placebo (n = 23) for six months. Serum samples were collected before and after two, four, and six months of treatment. We found serum Cobalamin to decline and reach significant lower levels after six months of treatment (p = 0.003). Despite the decline in serum Cobalamin, we observed no reductions in the physiological active part of Cobalamin bound to transCobalamin (holotransCobalamin), or increase in the metabolic marker of Cobalamin status, methylmalonic acid. Instead, the non-functional part of circulating Cobalamin bound to haptocorrin declined (p = 0.0009). Our results have two implications: The data questions whether metformin treatment induces an impaired Cobalamin status in PCOS patients, and further suggests that serum Cobalamin is a futile marker for judging Cobalamin status in metformin-treated patients.
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Cobalamin and haptocorrin in human milk and Cobalamin-related variables in mother and child: a 9-mo longitudinal study
The American journal of clinical nutrition, 2013Co-Authors: Eva Greibe, Dorte L. Lildballe, S. Streym, Peter Vestergaard, Lars Rejnmark, Leif Mosekilde, Ebba NexoAbstract:Background: Measurement of milk Cobalamin is hampered by the high content of the Cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk Cobalamin to Cobalamin status in healthy mothers and their children. Objectives: The objectives were to explore the concentration of Cobalamin and haptocorrin in foremilk and hindmilk during the first 9 mo of lactation and to relate these results to biomarkers of an impaired Cobalamin status of mother and child. Design: Milk samples from 25 mothers were collected at 2 wk, 4 mo, and 9 mo postpartum for the measurement of Cobalamin and haptocorrin. Plasma samples from a larger cohort of lactating mothers (n = 107) and their infants (n = 108) were collected at the same time points for the measurement of Cobalamin, holotransCobalamin, total transCobalamin, total haptocorrin, and methylmalonic acid. Results: Median (range) concentrations of Cobalamin in hindmilk were 760 (210‐1880), 290 (140‐690), and 440 (160‐1940) pmol/L at 2 wk, 4 mo, and 9 mo, respectively; the respective haptocorrin concentrations were 25 (9‐102), 22 (4‐100), and 180 (30‐460) nmol/L. We found slightly lower values in foremilk. A decrease in milk Cobalamin at 4 mo was associated with decreases in plasma Cobalamin (P , 0.0001) and holotransCobalamin (P , 0.0001) in the infants. Strong positive associations in paired maternal-infant Cobalamin concentrations were found at all time points. Conclusions: Foremilk and hindmilk contained comparable amounts of Cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk Cobalamin mirrored biochemical changes in infants, which suggests an impaired Cobalamin status and indicates that nutrition from only mother’s milk may not be sufficient for the supply of Cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 200841-2185. Am J Clin Nutr doi: 10.3945/ajcn.113.058479.
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Cobalamin and haptocorrin in human milk and Cobalamin-related variables in mother and child: a 9-mo longitudinal study
The American journal of clinical nutrition, 2013Co-Authors: Eva Greibe, Dorte L. Lildballe, S. Streym, Peter Vestergaard, Lars Rejnmark, Leif Mosekilde, Ebba NexoAbstract:Measurement of milk Cobalamin is hampered by the high content of the Cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk Cobalamin to Cobalamin status in healthy mothers and their children. The objectives were to explore the concentration of Cobalamin and haptocorrin in foremilk and hindmilk during the first 9 mo of lactation and to relate these results to biomarkers of an impaired Cobalamin status of mother and child. Milk samples from 25 mothers were collected at 2 wk, 4 mo, and 9 mo postpartum for the measurement of Cobalamin and haptocorrin. Plasma samples from a larger cohort of lactating mothers (n = 107) and their infants (n = 108) were collected at the same time points for the measurement of Cobalamin, holotransCobalamin, total transCobalamin, total haptocorrin, and methylmalonic acid. Median (range) concentrations of Cobalamin in hindmilk were 760 (210-1880), 290 (140-690), and 440 (160-1940) pmol/L at 2 wk, 4 mo, and 9 mo, respectively; the respective haptocorrin concentrations were 25 (9-102), 22 (4-100), and 180 (30-460) nmol/L. We found slightly lower values in foremilk. A decrease in milk Cobalamin at 4 mo was associated with decreases in plasma Cobalamin (P , 0.0001) and holotransCobalamin (P , 0.0001) in the infants. Strong positive associations in paired maternal-infant Cobalamin concentrations were found at all time points. Foremilk and hindmilk contained comparable amounts of Cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk Cobalamin mirrored biochemical changes in infants, which suggests an impaired Cobalamin status and indicates that nutrition from only mother's milk may not be sufficient for the supply of Cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 2008-41-2185.
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Cobalamin analogues in humans: a study on maternal and cord blood.
PloS one, 2013Co-Authors: Tore Forsingdal Hardlei, Rima Obeid, Wolfgang A. Herrmann, Ebba NexoAbstract:Background Haptocorrin (HC) carries Cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All Cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transCobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin of CorA.
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A single rainbow trout Cobalamin-binding protein stands in for three human binders.
The Journal of biological chemistry, 2012Co-Authors: Eva Greibe, Boe Sandahl Sorensen, Sergey N. Fedosov, Steen Seier Poulsen, Peter Højrup, Ebba NexoAbstract:Cobalamin uptake and transport in mammals are mediated by three Cobalamin-binding proteins: haptocorrin, intrinsic factor, and transCobalamin. The nature of Cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim of this study was to characterize the Cobalamin-binding proteins of the rainbow trout (Oncorhynchus mykiss) and to compare their properties with those of the three human Cobalamin-binding proteins. High Cobalamin-binding capacity was found in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and plasma (2500 nmol/liter). In all cases, it appeared to be the same protein based on analysis of partial sequences and immunological responses. The trout Cobalamin-binding protein was purified from roe fluid, sequenced, and further characterized. Like haptocorrin, the trout Cobalamin-binding protein was stable at low pH and had a high binding affinity for the Cobalamin analog cobinamide. Like haptocorrin and transCobalamin, the trout Cobalamin-binding protein was present in plasma and recognized ligands with altered nucleotide moiety. Like intrinsic factors, the trout Cobalamin-binding protein was present in the stomach and resisted degradation by trypsin and chymotrypsin. It also resembled intrinsic factor in the composition of conserved residues in the primary Cobalamin-binding site in the C terminus. The trout Cobalamin-binding protein was glycosylated and displayed spectral properties comparable with those of haptocorrin and intrinsic factor. In conclusion, only one soluble Cobalamin-binding protein was identified in the rainbow trout, a protein that structurally behaves like an intermediate between the three human Cobalamin-binding proteins.
Eva Greibe - One of the best experts on this subject based on the ideXlab platform.
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Metformin Lowers Serum Cobalamin without Changing Other Markers of Cobalamin Status: A Study on Women with Polycystic Ovary Syndrome
Nutrients, 2013Co-Authors: Eva Greibe, Birgitta Trolle, Mustafa Vakur Bor, Finn Friis Lauszus, Ebba NexoAbstract:Treatment with the anti-diabetic drug metformin is followed by a decline in plasma Cobalamin, but it is unsettled whether this denotes an impaired Cobalamin status. This study has explored changes in the markers of Cobalamin status in women with Polycystic Ovary Syndrome treated with metformin (1.5-2.5 g per day) (n = 29) or placebo (n = 23) for six months. Serum samples were collected before and after two, four, and six months of treatment. We found serum Cobalamin to decline and reach significant lower levels after six months of treatment (p = 0.003). Despite the decline in serum Cobalamin, we observed no reductions in the physiological active part of Cobalamin bound to transCobalamin (holotransCobalamin), or increase in the metabolic marker of Cobalamin status, methylmalonic acid. Instead, the non-functional part of circulating Cobalamin bound to haptocorrin declined (p = 0.0009). Our results have two implications: The data questions whether metformin treatment induces an impaired Cobalamin status in PCOS patients, and further suggests that serum Cobalamin is a futile marker for judging Cobalamin status in metformin-treated patients.
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Cobalamin and haptocorrin in human milk and Cobalamin-related variables in mother and child: a 9-mo longitudinal study
The American journal of clinical nutrition, 2013Co-Authors: Eva Greibe, Dorte L. Lildballe, S. Streym, Peter Vestergaard, Lars Rejnmark, Leif Mosekilde, Ebba NexoAbstract:Background: Measurement of milk Cobalamin is hampered by the high content of the Cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk Cobalamin to Cobalamin status in healthy mothers and their children. Objectives: The objectives were to explore the concentration of Cobalamin and haptocorrin in foremilk and hindmilk during the first 9 mo of lactation and to relate these results to biomarkers of an impaired Cobalamin status of mother and child. Design: Milk samples from 25 mothers were collected at 2 wk, 4 mo, and 9 mo postpartum for the measurement of Cobalamin and haptocorrin. Plasma samples from a larger cohort of lactating mothers (n = 107) and their infants (n = 108) were collected at the same time points for the measurement of Cobalamin, holotransCobalamin, total transCobalamin, total haptocorrin, and methylmalonic acid. Results: Median (range) concentrations of Cobalamin in hindmilk were 760 (210‐1880), 290 (140‐690), and 440 (160‐1940) pmol/L at 2 wk, 4 mo, and 9 mo, respectively; the respective haptocorrin concentrations were 25 (9‐102), 22 (4‐100), and 180 (30‐460) nmol/L. We found slightly lower values in foremilk. A decrease in milk Cobalamin at 4 mo was associated with decreases in plasma Cobalamin (P , 0.0001) and holotransCobalamin (P , 0.0001) in the infants. Strong positive associations in paired maternal-infant Cobalamin concentrations were found at all time points. Conclusions: Foremilk and hindmilk contained comparable amounts of Cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk Cobalamin mirrored biochemical changes in infants, which suggests an impaired Cobalamin status and indicates that nutrition from only mother’s milk may not be sufficient for the supply of Cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 200841-2185. Am J Clin Nutr doi: 10.3945/ajcn.113.058479.
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Cobalamin and haptocorrin in human milk and Cobalamin-related variables in mother and child: a 9-mo longitudinal study
The American journal of clinical nutrition, 2013Co-Authors: Eva Greibe, Dorte L. Lildballe, S. Streym, Peter Vestergaard, Lars Rejnmark, Leif Mosekilde, Ebba NexoAbstract:Measurement of milk Cobalamin is hampered by the high content of the Cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk Cobalamin to Cobalamin status in healthy mothers and their children. The objectives were to explore the concentration of Cobalamin and haptocorrin in foremilk and hindmilk during the first 9 mo of lactation and to relate these results to biomarkers of an impaired Cobalamin status of mother and child. Milk samples from 25 mothers were collected at 2 wk, 4 mo, and 9 mo postpartum for the measurement of Cobalamin and haptocorrin. Plasma samples from a larger cohort of lactating mothers (n = 107) and their infants (n = 108) were collected at the same time points for the measurement of Cobalamin, holotransCobalamin, total transCobalamin, total haptocorrin, and methylmalonic acid. Median (range) concentrations of Cobalamin in hindmilk were 760 (210-1880), 290 (140-690), and 440 (160-1940) pmol/L at 2 wk, 4 mo, and 9 mo, respectively; the respective haptocorrin concentrations were 25 (9-102), 22 (4-100), and 180 (30-460) nmol/L. We found slightly lower values in foremilk. A decrease in milk Cobalamin at 4 mo was associated with decreases in plasma Cobalamin (P , 0.0001) and holotransCobalamin (P , 0.0001) in the infants. Strong positive associations in paired maternal-infant Cobalamin concentrations were found at all time points. Foremilk and hindmilk contained comparable amounts of Cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk Cobalamin mirrored biochemical changes in infants, which suggests an impaired Cobalamin status and indicates that nutrition from only mother's milk may not be sufficient for the supply of Cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 2008-41-2185.
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A single rainbow trout Cobalamin-binding protein stands in for three human binders.
The Journal of biological chemistry, 2012Co-Authors: Eva Greibe, Boe Sandahl Sorensen, Sergey N. Fedosov, Steen Seier Poulsen, Peter Højrup, Ebba NexoAbstract:Cobalamin uptake and transport in mammals are mediated by three Cobalamin-binding proteins: haptocorrin, intrinsic factor, and transCobalamin. The nature of Cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim of this study was to characterize the Cobalamin-binding proteins of the rainbow trout (Oncorhynchus mykiss) and to compare their properties with those of the three human Cobalamin-binding proteins. High Cobalamin-binding capacity was found in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and plasma (2500 nmol/liter). In all cases, it appeared to be the same protein based on analysis of partial sequences and immunological responses. The trout Cobalamin-binding protein was purified from roe fluid, sequenced, and further characterized. Like haptocorrin, the trout Cobalamin-binding protein was stable at low pH and had a high binding affinity for the Cobalamin analog cobinamide. Like haptocorrin and transCobalamin, the trout Cobalamin-binding protein was present in plasma and recognized ligands with altered nucleotide moiety. Like intrinsic factors, the trout Cobalamin-binding protein was present in the stomach and resisted degradation by trypsin and chymotrypsin. It also resembled intrinsic factor in the composition of conserved residues in the primary Cobalamin-binding site in the C terminus. The trout Cobalamin-binding protein was glycosylated and displayed spectral properties comparable with those of haptocorrin and intrinsic factor. In conclusion, only one soluble Cobalamin-binding protein was identified in the rainbow trout, a protein that structurally behaves like an intermediate between the three human Cobalamin-binding proteins.
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The Cobalamin-binding protein in zebrafish is an intermediate between the three Cobalamin-binding proteins in human.
PloS one, 2012Co-Authors: Eva Greibe, Sergey N. Fedosov, Ebba NexoAbstract:In humans, three soluble extracellular Cobalamin-binding proteins; transCobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are involved in the uptake and transport of Cobalamin. In this study, we investigate a Cobalamin-binding protein from zebrafish (Danio rerio) and summarize current knowledge concerning the phylogenetic evolution of kindred proteins. We identified a Cobalamin binding capacity in zebrafish protein extracts (8.2 pmol/fish) and ambient water (13.5 pmol/fish) associated with a single protein. The protein showed resistance toward degradation by trypsin and chymotrypsin (like human IF, but unlike human HC and TC). The Cobalamin analogue, cobinamide, bound weaker to the zebrafish Cobalamin binder than to human HC, but stronger than to human TC and IF. Affinity for another analogue, adenosyl-pseudo-Cobalamin was low compared with human HC and TC, but high compared with human IF. The absorbance spectrum of the purified protein in complex with hydroxo-Cobalamin resembled those of human HC and IF, but not TC. We searched available databases to further explore the phylogenies of the three Cobalamin-binding proteins in higher vertebrates. Apparently, TC-like proteins are the oldest evolutionary derivatives followed by IF and HC (the latter being present only in reptiles and most but not all mammals). Our findings suggest that the only Cobalamin-binding protein in zebrafish is an intermediate between the three human Cobalamin binders. These findings support the hypothesis about a common ancestral gene for all Cobalamin-binding proteins in higher vertebrates.
Emmanuel Andrès - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of oral Cobalamin (vitamin B12) therapy
Expert opinion on pharmacotherapy, 2010Co-Authors: Emmanuel Andrès, Helen Fothergill, Mustapha MeciliAbstract:Cobalamin (vitamin B12) deficiency is particularly common in the elderly (> 15%). Management of Cobalamin deficiency with Cobalamin injections is well codified at present, but new routes of Cobalamin administration (oral and nasal) are being studied, especially oral Cobalamin therapy for food-Cobalamin malabsorption. The objective of this review is to evaluate the efficacy of oral Cobalamin treatment in elderly patients. To reach this objective, PubMed data were systematically searched for English and French articles published from January 1990 to July 2008. Data from our research group on Cobalamin deficiency (Groupe d'Etude des CAREnce vitamine B12 - CARE B12) were also analyzed. Three prospective randomized studies, a systematic review by the Cochrane group and five prospective cohort studies were found and provide evidence that oral Cobalamin treatment may adequately treat Cobalamin deficiency. The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters, for example hemoglobin level, mean erythrocyte cell volume and reticulocyte count. The effect of oral Cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. Oral Cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections. Our experience and the present analysis support the use of oral Cobalamin therapy in clinical practice.
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efficacy of oral Cobalamin vitamin b12 therapy
Expert Opinion on Pharmacotherapy, 2010Co-Authors: Emmanuel Andrès, Helen Fothergill, Mustapha MeciliAbstract:Importance of the field: Cobalamin (vitamin B12) deficiency is particularly common in the elderly (> 15%). Management of Cobalamin deficiency with Cobalamin injections is well codified at present, but new routes of Cobalamin administration (oral and nasal) are being studied, especially oral Cobalamin therapy for food-Cobalamin malabsorption.Areas covered in this review: The objective of this review is to evaluate the efficacy of oral Cobalamin treatment in elderly patients. To reach this objective, PubMed data were systematically searched for English and French articles published from January 1990 to July 2008. Data from our research group on Cobalamin deficiency (Groupe d’Etude des CAREnce vitamine B12 – CARE B12) were also analyzed.What the reader will gain: Three prospective randomized studies, a systematic review by the Cochrane group and five prospective cohort studies were found and provide evidence that oral Cobalamin treatment may adequately treat Cobalamin deficiency. The efficacy was particularl...
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Cobalamin Deficiency in Older Adults
2009Co-Authors: Emmanuel Andrès, Thomas Vogel, Laure Federici, Helen Fothergill, Mustapha Mecili, Hôpitaux Univer, Hôpitaux Universitaires De Strasbourg, Jacques ZimmerAbstract:Cobalamin (vitamin B12) deficiency is particularly common in among older adults, although it is frequently undiagnosed as the clinical presentations may be subtle. However, serious complications do occur, in particular neuropsychiatric and hematolog- ical disorders. In older adults, the main causes of Cobalamin deficiency are food-Cobalamin malabsorption (50-60%) and pernicious anemia (30-40%). Food-Cobalamin malab- sorption syndrome is a disorder characterized by the inability to release Cobalamin from food or its binding proteins. This syndrome is frequently associated with atrophic gas- tritis, which may be a result of Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. The management of Cobalamin deficiency with Cobalamin injections is currently well documented, however new routes of Cobalamin administra- tion (including via oral and nasal passages) are being studied. Oral Cobalamin therapy is of particular interest in the management of food-Cobalamin malabsorption syndrome.
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An update on Cobalamin deficiency in adults
QJM : monthly journal of the Association of Physicians, 2008Co-Authors: Nassim Dali-youcef, Emmanuel AndrèsAbstract:Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age), but is often unrecognized because of its subtle clinical manifestations; although they can be potentially serious, particularly from a neuropsychiatric and hematological perspective. In the general population, the main causes of Cobalamin deficiency are pernicious anemia and food-Cobalamin malabsorption. Food-Cobalamin malabsorption syndrome, which has only recently been identified, is a disorder characterized by the inability to release Cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Besides these syndromes, mutations in genes encoding endocytic receptors involved in the ileal absorption and cellular uptake of Cobalamin have been recently uncovered and explain, at least in part, the hereditary component of megaloblastic anemia. Management of Cobalamin deficiency with Cobalamin injections is currently well codified, but new routes of Cobalamin administration (oral and nasal) are being studied, especially oral Cobalamin therapy for food-Cobalamin malabsorption.
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Cobalamin deficiency in elderly patients: a personal view
Current gerontology and geriatrics research, 2008Co-Authors: Emmanuel Andrès, Thomas Vogel, Laure Federici, Jacques Zimmer, Ecaterina Ciobanu, Georges KaltenbachAbstract:Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age) but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of Cobalamin deficiency are pernicious anemia and food-Cobalamin malabsorption. Food-Cobalamin malabsorption syndrome is a disorder characterized by the inability to release Cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of Cobalamin deficiency with Cobalamin injections is currently well documented but new routes of Cobalamin administration (oral and nasal) are being studied, especially oral Cobalamin therapy for food-Cobalamin malabsorption.
Dorte L. Lildballe - One of the best experts on this subject based on the ideXlab platform.
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Cobalamin and haptocorrin in human milk and Cobalamin-related variables in mother and child: a 9-mo longitudinal study
The American journal of clinical nutrition, 2013Co-Authors: Eva Greibe, Dorte L. Lildballe, S. Streym, Peter Vestergaard, Lars Rejnmark, Leif Mosekilde, Ebba NexoAbstract:Background: Measurement of milk Cobalamin is hampered by the high content of the Cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk Cobalamin to Cobalamin status in healthy mothers and their children. Objectives: The objectives were to explore the concentration of Cobalamin and haptocorrin in foremilk and hindmilk during the first 9 mo of lactation and to relate these results to biomarkers of an impaired Cobalamin status of mother and child. Design: Milk samples from 25 mothers were collected at 2 wk, 4 mo, and 9 mo postpartum for the measurement of Cobalamin and haptocorrin. Plasma samples from a larger cohort of lactating mothers (n = 107) and their infants (n = 108) were collected at the same time points for the measurement of Cobalamin, holotransCobalamin, total transCobalamin, total haptocorrin, and methylmalonic acid. Results: Median (range) concentrations of Cobalamin in hindmilk were 760 (210‐1880), 290 (140‐690), and 440 (160‐1940) pmol/L at 2 wk, 4 mo, and 9 mo, respectively; the respective haptocorrin concentrations were 25 (9‐102), 22 (4‐100), and 180 (30‐460) nmol/L. We found slightly lower values in foremilk. A decrease in milk Cobalamin at 4 mo was associated with decreases in plasma Cobalamin (P , 0.0001) and holotransCobalamin (P , 0.0001) in the infants. Strong positive associations in paired maternal-infant Cobalamin concentrations were found at all time points. Conclusions: Foremilk and hindmilk contained comparable amounts of Cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk Cobalamin mirrored biochemical changes in infants, which suggests an impaired Cobalamin status and indicates that nutrition from only mother’s milk may not be sufficient for the supply of Cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 200841-2185. Am J Clin Nutr doi: 10.3945/ajcn.113.058479.
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Cobalamin and haptocorrin in human milk and Cobalamin-related variables in mother and child: a 9-mo longitudinal study
The American journal of clinical nutrition, 2013Co-Authors: Eva Greibe, Dorte L. Lildballe, S. Streym, Peter Vestergaard, Lars Rejnmark, Leif Mosekilde, Ebba NexoAbstract:Measurement of milk Cobalamin is hampered by the high content of the Cobalamin-binding protein haptocorrin, and limited data are available relating trustworthy measures of milk Cobalamin to Cobalamin status in healthy mothers and their children. The objectives were to explore the concentration of Cobalamin and haptocorrin in foremilk and hindmilk during the first 9 mo of lactation and to relate these results to biomarkers of an impaired Cobalamin status of mother and child. Milk samples from 25 mothers were collected at 2 wk, 4 mo, and 9 mo postpartum for the measurement of Cobalamin and haptocorrin. Plasma samples from a larger cohort of lactating mothers (n = 107) and their infants (n = 108) were collected at the same time points for the measurement of Cobalamin, holotransCobalamin, total transCobalamin, total haptocorrin, and methylmalonic acid. Median (range) concentrations of Cobalamin in hindmilk were 760 (210-1880), 290 (140-690), and 440 (160-1940) pmol/L at 2 wk, 4 mo, and 9 mo, respectively; the respective haptocorrin concentrations were 25 (9-102), 22 (4-100), and 180 (30-460) nmol/L. We found slightly lower values in foremilk. A decrease in milk Cobalamin at 4 mo was associated with decreases in plasma Cobalamin (P , 0.0001) and holotransCobalamin (P , 0.0001) in the infants. Strong positive associations in paired maternal-infant Cobalamin concentrations were found at all time points. Foremilk and hindmilk contained comparable amounts of Cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk Cobalamin mirrored biochemical changes in infants, which suggests an impaired Cobalamin status and indicates that nutrition from only mother's milk may not be sufficient for the supply of Cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 2008-41-2185.
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Uptake of Cobalamin and markers of Cobalamin status: a longitudinal study of healthy pregnant women.
Clinical chemistry and laboratory medicine, 2011Co-Authors: Eva Greibe, Anne L Morkbak, Dorte L. Lildballe, Birgitte Horst Andreasen, Anne-mette Hvas, Ebba NexoAbstract:BACKGROUND Currently, it is unknown whether the decline in plasma Cobalamin observed during pregnancy is caused by malabsorption of the vitamin. This study examined Cobalamin absorption and markers of Cobalamin status during normal pregnancy. METHODS Twenty-seven pregnant Danish women were examined at gestation weeks 13, 24 and 36. The absorption test CobaSorb was performed in all women implying measurement of holotransCobalamin or cyanoCobalamin bound to transCobalamin before and after 2 days intake of 3 × 9 μg Cobalamin. Serum Cobalamin and the two Cobalamin binding proteins transCobalamin and haptocorrin, including haptocorrin saturated with Cobalamin or analogues, were measured, and so was plasma methylmalonic acid and homocysteine. RESULTS No change in the uptake of Cobalamin was observed throughout pregnancy. Serum Cobalamin displayed a gradual decline during pregnancy (p
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Uptake of Cobalamin and markers of Cobalamin status: a longitudinal study of healthy pregnant women.
Clinical chemistry and laboratory medicine, 2011Co-Authors: Eva Greibe, Anne L Morkbak, Dorte L. Lildballe, Birgitte Horst Andreasen, Anne-mette Hvas, Ebba NexoAbstract:Currently, it is unknown whether the decline in plasma Cobalamin observed during pregnancy is caused by malabsorption of the vitamin. This study examined Cobalamin absorption and markers of Cobalamin status during normal pregnancy. Twenty-seven pregnant Danish women were examined at gestation weeks 13, 24 and 36. The absorption test CobaSorb was performed in all women implying measurement of holotransCobalamin or cyanoCobalamin bound to transCobalamin before and after 2 days intake of 3 × 9 μg Cobalamin. Serum Cobalamin and the two Cobalamin binding proteins transCobalamin and haptocorrin, including haptocorrin saturated with Cobalamin or analogues, were measured, and so was plasma methylmalonic acid and homocysteine. No change in the uptake of Cobalamin was observed throughout pregnancy. Serum Cobalamin displayed a gradual decline during pregnancy (p<0.0001), while holotransCobalamin remained unchanged, despite an increase in total transCobalamin (p<0.0001). In accord with these results, total haptocorrin showed a decline from the 1st to 3rd trimester (p=0.007) and Cobalamin bound to haptocorrin declined (p<0.0001). Interestingly, the amount of Cobalamin analogues attached to haptocorrin remained unchanged. Methylmalonic acid (p=0.002) and homocysteine (p<0.0001) increased during pregnancy. Cobalamin absorption remains unchanged during normal pregnancy, as judged by the CobaSorb test. No change was observed in the biological active holotransCobalamin during pregnancy. Thus, the pregnancy-related decline in Cobalamin is caused by alternations in haptocorrin-bound Cobalamin. Surprisingly, no pregnancy-related change was observed in the amount of analogues attached to haptocorrin.
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High concentrations of haptocorrin interfere with routine measurement of Cobalamins in human serum and milk. A problem and its solution.
Clinical chemistry and laboratory medicine, 2009Co-Authors: Dorte L. Lildballe, Tore Forsingdal Hardlei, Lindsay H. Allen, Ebba NexoAbstract:Background: Human milk and occasional serum samples contain high concentrations of unsaturated haptocorrin, which influence accurate measurement of Cobalamins. Methods: Cobalamins in serum samples spiked with increasing amounts of unsaturated haptocorrin were measured employing the Centaur, Cobas and Architect analysers. Cobinamide-coated EAH sepharose was employed for pretreatment of the samples. Human milk samples were collected from 24 healthy mothers. Haptocorrin was measured by ELISA. Results: The measured concentration of Cobalamins either increased (Centaur analyser) or decreased (Architect, Cobas analysers) significantly for haptocorrin >10 nM, and was 220%, 52% or 45% of the expected values in a serum sample containing 50 nM haptocorrin. Following pretreatment with cobina-mide-sepharose, the expected Cobalamin concentration was obtained (Centaur). The milk samples contained 4.5-180 nM haptocorrin. In samples containing > 10 nM haptocorrin (n=19), the median concentration of Cobalamins decreased from 1.3 nM to 0.67 nM after pretreatment with cobinamidesepharose. Conclusions: Haptocorrin in concentrations above 10 nM influences measurement of Cobalamins giving rise to falsely elevated or decreased results. Removal of unsaturated haptocorrin by pretreatment with cobinamide-sepharose solves the problem.
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Low Cobalamin Levels as Predictors of Cobalamin Deficiency: Importance of Comorbidities Associated with Increased Oxidative Stress.
The American journal of medicine, 2015Co-Authors: Lawrence R SolomonAbstract:Cobalamin (B12) deficiency can lead to irreversible neurocognitive changes if unrecognized. Screening involves measurement of serum Cobalamin levels, but the sensitive metabolic indicators of Cobalamin deficiency, methylmalonic acid (MMA) and homocysteine (HCys), may be normal when Cobalamin values are low and elevated when Cobalamin values are normal. Because Cobalamin is inactivated by oxidation, the relationship between these metabolites and comorbidities associated with increased oxidative stress (oxidant risks) in subjects with low and low-normal Cobalamin levels was studied. A retrospective record-review was conducted of community-dwelling adults evaluated for Cobalamin deficiency during a 12-year period with serum Cobalamin values in the low (≤ 200 pg/mL; n = 49) or low-normal (201-300 pg/mL; n = 187) range and concurrent measurement of MMA. When "No" oxidant risk was present, elevated MMA (>250 nmol/L) and HCys (>12.1 μmol/L) values occurred in 50% and 30% of subjects, respectively (P <.01). In contrast, when "Three or More" oxidant risks were present, mean MMA and HCys values were significantly higher, and elevated MMA and HCys values occurred in 84% and 78% of these subjects, respectively (P ≤.012). Pharmacologic doses of cyanoCobalamin significantly decreased metabolite values in ≥ 94% of treated subjects. In subjects with low or low-normal Cobalamin values, metabolic evidence of Cobalamin deficiency is more frequent when 3 or more oxidant risks are present. Thus, defining a low serum Cobalamin level to screen for Cobalamin deficiency may be a "moving target" due to the variable presence and severity of often subtle, confounding clinical conditions in individual subjects. Copyright © 2016 Elsevier Inc. All rights reserved.
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Low Cobalamin Levels as Predictors of Cobalamin Deficiency: Importance of Comorbidities Associated with Increased Oxidative Stress
The American Journal of Medicine, 2015Co-Authors: Lawrence R SolomonAbstract:Abstract Background Cobalamin (B12) deficiency can lead to irreversible neurocognitive changes if unrecognized. Screening involves measurement of serum Cobalamin levels, but the sensitive metabolic indicators of Cobalamin deficiency, methylmalonic acid (MMA) and homocysteine (HCys), may be normal when Cobalamin values are low and elevated when Cobalamin values are normal . Because Cobalamin is inactivated by oxidation, the relationship between these metabolites and comorbidities associated with increased oxidative stress (oxidant risks) in subjects with low and low-normal Cobalamin levels was studied. Methods A retrospective record-review was conducted of community-dwelling adults evaluated for Cobalamin deficiency during a 12-year period with serum Cobalamin values in the low (≤ 200 pg/mL; n = 49) or low-normal (201-300 pg/mL; n = 187) range and concurrent measurement of MMA. Results When "No" oxidant risk was present, elevated MMA (>250 nmol/L) and HCys (>12.1 μmol/L) values occurred in 50% and 30% of subjects, respectively ( P P ≤.012). Pharmacologic doses of cyanoCobalamin significantly decreased metabolite values in ≥ 94% of treated subjects. Conclusion In subjects with low or low-normal Cobalamin values, metabolic evidence of Cobalamin deficiency is more frequent when 3 or more oxidant risks are present. Thus, defining a low serum Cobalamin level to screen for Cobalamin deficiency may be a "moving target" due to the variable presence and severity of often subtle, confounding clinical conditions in individual subjects.
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disorders of Cobalamin vitamin b12 metabolism emerging concepts in pathophysiology diagnosis and treatment
Blood Reviews, 2007Co-Authors: Lawrence R SolomonAbstract:Although Cobalamin (vitamin B12) was isolated almost 60 years ago, its biochemical, physiologic and neurologic effects remain incompletely defined. New observations suggest renal regulation of Cobalamin metabolism; actions of Cobalamin on nucleic acid and protein function; and a role for Cobalamin in cytokine and growth factor regulation. Clinically, no gold standard has emerged for the diagnosis of Cobalamin deficiency. Moreover, Cobalamin resistance may occur in diabetes, renal insufficiency and advanced age, leading to functional Cobalamin deficiency despite adequate Cobalamin nutriture. Finally, high-dose Cobalamin therapy may have salutary pharmacologic effects on neurologic function in a variety of disorders. Many studies lacked appropriate control groups. However, at this time, therapeutic trials with pharmacologic doses of Cobalamin are suggested when findings consistent with Cobalamin deficiency are present regardless of the results of diagnostic tests. While oral Cobalamin immediate-release is adequate for many patients, its effectiveness in reversing neurologic abnormalities has yet to be established.