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      Nutritional 1C Imbalance, B12 Tissue Accumulation, and Pregnancy Outcomes: An Experimental Study in Rats

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      , , *
      Nutrients
      MDPI
      vitamin B12, cobalamin, cyano-B12, hydroxo-B12, pregnancy, rats, 1C metabolism

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          Abstract

          Vitamin B12 deficiency during pregnancy has been associated with poor fetal outcome. Here we investigate the influence of a one-carbon (1C) imbalanced diet (low B12, high folate, high methionine) on maternal B12 status, fetal outcome, B12 distribution, and on the 24-h distribution of synthetic cyano-B12 (CN-B12) and natural hydroxo-B12 (HO-B12). Female Wistar rats were mated while on a 1C balanced ( n = 12) or imbalanced diet starting two weeks ( n = 10) or four weeks ( n = 9) prior to pregnancy and continuing throughout pregnancy. At gestation day 18 (out of 21), all rats received an oral dose of labeled CN-B12 or HO-B12. After 24 h, the rats were sacrificed. Fetuses were inspected, and maternal tissues and fetuses were measured for endogenous and labeled B12. Pregnancy caused a redistribution of B12 from the kidneys to the liver and fetal compartment (uterus, placenta, fetuses). The 1C imbalanced diet reduced maternal kidney B12 and gave rise to lower-weight fetuses with visual malformations. In contrast, fetal B12 did not reflect fetal outcome. This suggests that maternal B12 is more important for fetal outcome than fetal B12. The 24-h distribution of labeled B12 in the rats on the 1C imbalanced diet showed a higher fetal accumulation of CN-B12 than HO-B12, while the opposite was seen in the maternal tissues.

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          Effects of vitamin B12 and folate deficiency on brain development in children.

          Folate deficiency in the periconceptional period contributes to neural tube defects; deficits in vitamin B12 (cobalamin) have negative consequences on the developing brain during infancy; and deficits of both vitamins are associated with a greater risk of depression during adulthood. This review examines two mechanisms linking folate and vitamin B12 deficiency to abnormal behavior and development in infants: disruptions to myelination and inflammatory processes. Future investigations should focus on the relationship between the timing of deficient and marginal vitamin B12 status and outcomes such as infant growth, cognition, social development, and depressive symptoms, along with prevention of folate and vitamin B12 deficiency.
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            Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

            Background Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. Objective To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. Data sources Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. Key recommendations We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early. Electronic supplementary material The online version of this article (doi:10.1007/s10545-016-9991-4) contains supplementary material, which is available to authorised users.
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              Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects.

              Blood was taken at the first antenatal clinic from 56,049 pregnant women. Neural tube defect (NTD) pregnancies (81) were compared to controls (247) for plasma vitamin B12 (B12) (ng/l), plasma folate (microgram/l), and red cell folate (RCF) (microgram/l). Median values were significantly different and were, respectively, 243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269 and 338 (p < 0.001). There was a significant correlation between plasma B12 and RCF in cases (r = 0.31, p = 0.004) but not in controls (r = 0.02, p = 0.725). In cases only, multiple regression showed that both plasma B12 and plasma folate influenced the maternal RCF (multiple r = 0.68, p < 0.001). Plasma folate and plasma B12 were independent risk factors for NTDs, suggesting that the enzyme methionine synthase is involved directly or indirectly in the aetiology. The levels of folate and B12 where increased risk occurred were not those usually associated with deficiency, calling for a re-evaluation of their recommended daily allowances. Whether the aetiology is purely nutritional or a metabolic defect, this study suggests that consideration should be given to including B12 as well as folic acid in any programme of supplementation or food fortification to prevent NTDs.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                26 October 2018
                November 2018
                : 10
                : 11
                : 1579
                Affiliations
                Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; au335591@ 123456post.au.dk (O.N.); ebbanexo@ 123456rm.dk (E.N.)
                Author notes
                [* ]Correspondence: greibe@ 123456clin.au.dk ; Tel.: +45-263-910-09
                Author information
                https://orcid.org/0000-0002-0417-1195
                Article
                nutrients-10-01579
                10.3390/nu10111579
                6265706
                30373131
                77ef2bd1-78f2-4755-b860-0d3d645b1c11
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 September 2018
                : 24 October 2018
                Categories
                Article

                Nutrition & Dietetics
                vitamin b12,cobalamin,cyano-b12,hydroxo-b12,pregnancy,rats,1c metabolism
                Nutrition & Dietetics
                vitamin b12, cobalamin, cyano-b12, hydroxo-b12, pregnancy, rats, 1c metabolism

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