Serum Vitamin B12 Concentrations among Mothers and Newborns and Follow-up Study to Assess Implication on the Growth Velocity and the Urinary Methylmalonic Acid Excretion

2009 ◽  
Vol 79 (56) ◽  
pp. 297-307 ◽  
Author(s):  
Laila Hussein ◽  
Sahar Abdel Aziz ◽  
Salwa Tapouzada ◽  
Boehles
Keyword(s):  
Early Diagnosis ◽  
Growth Velocity ◽  
Methylmalonic Acid ◽  
Post Partum ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Postnatal Life ◽  
Negative Consequences ◽  
Metabolic Marker ◽  
Biochemical Measurement

Objective:Cobalamin (B12) deficiency has been reported in infants born to mothers with low cobalamin intake. Early diagnosis of vitamin B12 deficiency in infants is critical for the prevention of neurobehavioral disorders. We investigated the relationship between serum vitamin B12 level in newborns and in their healthy mothers who consumed an omnivorous diet. Anthropometry was studied longitudinally to assess the growth velocity of the infants. Urinary methylmalonic acid (MMA) excretion of 6-month old infants was compared retrospectively as the biomarker correlated with the initial serum vitamin B12 concentrations. Methods: Serum cobalamin and blood hemoglobin were determined in 84 pairs of newborns and their mothers. Urinary MMA excretion was measured in the same subjects during the first 6 months of the post partum period. Results: At birth, median serum cobalamin levels were 152.0 pmol/L in the mothers and 296.6 pmol/L in the newborns. Maternal and neonatal serum cobalamin levels had no effect on growth velocity during the first six months of postnatal life. Serum maternal and neonatal cobalamin levels were inversely associated with urinary MMA excretion. Conclusion: Early diagnosis of vitamin B12 status in neonates and infants is crucial, particularly in nutritionally deprived areas. Biochemical measurement of plasma cobalamin or its metabolic marker MMA is highly recommended. Urinary MMA measurement in cobalamin diagnostics provides an advantage in that blood sampling is not required. A vitamin B12 taskforce should be created to alleviate vitamin deficiency and its negative consequences.

scholarly journals Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies

2012 ◽  
Vol 108 (11) ◽  
pp. 1948-1961 ◽  
Author(s):  
Fiona O'Leary ◽  
Margaret Allman-Farinelli ◽  
Samir Samman
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Cognitive Decline ◽  
Quality Assessment ◽  
Prospective Cohort ◽  
Methylmalonic Acid ◽  
Serum Vitamin ◽  
Assessment Tools ◽  
Vitamin B ◽  
Prospective Cohort Studies

Poor vitamin B12 status may lead to the development of cognitive decline and dementia but there is a large variation in the quality, design of and results reported from these investigations. We have undertaken a systematic review of the evidence for the association between vitamin B12 status and cognitive decline in older adults. A database search of the literature to 2011 was undertaken, using keywords related to vitamin B12 and cognition. All prospective cohort studies assessing the association of serum vitamin B12 or biomarkers were included. Quality assessment and extraction of the data were undertaken by two researchers. The quality assessment tool assigns a positive, neutral or negative rating. Of 3772 published articles, thirty-five cohort studies (n 14 325 subjects) were identified and evaluated. No association between serum vitamin B12 concentrations and cognitive decline or dementia was found. However, four studies that used newer biomarkers of vitamin B12 status (methylmalonic acid and holotranscobalamin (holoTC)) showed associations between poor vitamin B12 status and the increased risk of cognitive decline or dementia diagnosis. In general, the studies were of reasonable quality (twenty-one positive, ten neutral and four negative quality) but of short duration and inadequate subject numbers to determine whether an effect exists. Future studies should be of adequate duration (at least 6 years), recruit subjects from the seventh decade, choose markers of vitamin B12 status with adequate specificity such as holoTC and/or methylmalonic acid and employ standardised neurocognitive assessment tools and not screening tests in order to ascertain any relationship between vitamin B12 status and cognitive decline.

The Effect of Cobalt Deficiency in the Pregnant Ewe on Lamb Viability

1988 ◽  
Vol 1988 ◽  
pp. 27-27
Author(s):  
G.E.J. Fisher ◽  
A. MacPherson
Keyword(s):  
Methylmalonic Acid ◽  
Clinical Symptoms ◽  
Post Partum ◽  
Acquired Immunity ◽  
Vitamin B ◽  
Treatment Groups ◽  
Turbidity Test ◽  
Term Trial ◽  
Cobalt Deficiency ◽  
Pregnant Ewe

Experiments were designed to investigate the effect of sub-clinical cobalt deficiency in pregnant hill sheep, on lamb viability. This form of the deficiency is not characterised by clinical symptoms. The disease is therefore difficult to detect, and may be of economic importance to farms on land of marginal cobalt status.In each of two trials, both with sixty Scottish Blackface x Swaledale ewes, animals were randomly assigned to three treatment groups: A. Cobalt-deficient intake throughout pregnancy; B. Initially cobalt-sufficient intake, but deficient from mid-pregnancy (Trial 1) or initially cobalt-deficient intake, but repleted from mid-term (Trial 2); C. Cobalt-sufficient intake throughout pregnancy. A cobalt-deficient ration (<0.06 mg Co/kg DM) of Timothy hay, micronised maize and maize gluten, was fed from tupping in Trial 1, and from two months before tupping in Trial 2. Treated animals received a weekly oral dose of 0.7 mg Co/head.Vitamin B12 (microbiological and radio-immuno assays) and methylmalonic acid (capillary gas chromatography) were analysed in ewe and lamb sera, as indicators of cobalt status. Levels of passively acquired immunity were measured by analysis of lamb sera, sampled at two and four weeks post-partum, for immunoglobulin G (IgG) and by the zinc sulphate turbidity test (ZSTT).

scholarly journals The experimental production of vitamin B12 deficiency in the baboon (Papio cynocephalus). A 2-year study

1974 ◽  
Vol 32 (2) ◽  
pp. 219-228 ◽  
Author(s):  
R. C Siddons
Keyword(s):  
Methylmalonic Acid ◽  
Daily Intake ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
Vegetarian Diet ◽  
Vitamin B ◽  
Papio Cynocephalus ◽  
Experimental Production ◽  
Deficient Diet ◽  
Liver Vitamin

1. The development of vitamin B12 deficiency, as indicated by the serum and liver vitamin B12 levels and the excretion of methylmalonic acid, was studied over a 2-year period in baboons (Papio cynocephalus) given a diet deficient in vitamin B12. The effects of partial hepatectomy and the inclusion of either ampicillin or sodium propionate in the diet on the rate of development of the deficiency were also studied.2. The baboons had previously been fed on a mainly vegetarian diet. Their serum vitamin B12 levels were less than 100 ng/l and the mean liver vitamin B12 concentration was 0·56 μ/g. Similar serum and liver vitamin B12 levels were found in baboons given a purified diet supplemented with 1 μg vitamin B12/d, and marked increases in the serum and liver vitamin B12 levels occurred when the daily intake was increased to 2 μg.3. The serum vitamin B12 levels decreased to less than 20 ng/l in all baboons given a vitamin B12-deficient diet.4. The liver vitamin B12 concentration also decreased in all baboons given a deficient diet. At 9 months the lowest levels (0·20 μ/g) were found in partially hepatectomized baboons but subsequently baboons given the diet containing ampicillin had the lowest levels (0·11 μ/g).5. The excretion of methylmalonic acid after a valine load was found to be inversely related to the liver vitamin B12 concentration. In the early part of the study, partially hepatectomized baboons excreted the highest amount but subsequently baboons given a diet containing ampicillin excreted the highest amount.6. Increased formiminoglutamic acid excretion after a histidine load was observed in two baboons given a vitamin B12-deficient diet and in both baboons the liver folic acid concentration was low.7. No haematological or neurological symptoms of the vitamin B12 deficiency were observed.

Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid

2003 ◽  
Vol 9 (3) ◽  
pp. 239-245 ◽  
Author(s):  
M Vrethem ◽  
E Mattsson ◽  
H Hebelka ◽  
K Leerbeck ◽  
A Österberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Methylmalonic Acid ◽  
Haemoglobin Concentration ◽  
Serum Vitamin ◽  
High Serum ◽  
Plasma Homocysteine ◽  
Cobalamin Deficiency ◽  
Vitamin B ◽  
Plasma Thcy

Objective: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. Methods: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (C SF) MMA and tHcy in 72 patients with MS and 23 controls. Results: The mean plasma tHcy level was significantly increased in MS patients (11.6 mmol/L) compared with controls (7.4 mmol/L) (P =4-0.002). Seven patients showed low serum vitamin B12levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MC V), haemoglobin concentration, C SF tHcy or C SF MMA between patients and healthy subjects. There were no correlations between C SF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, C SF Hcy or C SF MMA were not correlated to disability status, activity of disease, duration of disease or age. Conclusions:The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. O ur findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. A nalysis of C SF MMA and C SF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.

scholarly journals Effects of cobalt deficiency in pregnant and post-parturient ewes and their lambs

1981 ◽  
Vol 46 (2) ◽  
pp. 337-344 ◽  
Author(s):  
W. R. H. Duncan ◽  
E. Rona Morrison ◽  
G. A. Garton
Keyword(s):  
Perinatal Mortality ◽  
Methylmalonic Acid ◽  
Post Partum ◽  
Acid Synthesis ◽  
Urinary Concentration ◽  
Vitamin B ◽  
Deficient Diet ◽  
Cobalt Deficiency ◽  
Group A ◽  
Group B

1. Two groups of ewes were fed on a cobalt-deficient diet throughout pregnancy; one group (group A) was given the diet from the beginning of pregnancy, whilst the other (group B) received the diet for 16 weeks before mating. The ewes in group A continued to receive the diet for 12 weeks post-partum.2. The vitamin B12 content of serum was estimated on three occasions before parturition and, for group A ewes, at 12 weeks post partum. Urinary concentration of methylmalonic acid was also determined at intervals before the lambs were born.3. Serum values for vitamin B12 indicated that the ewes in both groups were depleted of the vitamin, though those in group B were more severely affected, as was evidenced by the high incidence of perinatal mortality among the lambs born to these ewes. Perinatal mortality appeared to be associated with abnormally-high values for urinary concentration of methylmalonic acid.4. Analysis of liver lipids and adipose tissue triacylglycerols of some of the vitamin B12-deprived lambs which died before, or within 1 d of, birth showed that, compared with the corresponding tissues of control lambs, these lipids contained unusually high proportions of odd-numbered fatty acids (mostly 15:0, 17:0 and 19:0). This observation is discussed in relation to the likelihood that, in vitmain B12-deprived lambs, propionate becomes available as a primer unit for fatty acid synthesis when the metabolism of its carboxylation product, methylmalonic acid, is impaired due to partlal lack of a vitamin B12-containing enzyme system.

scholarly journals Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12

2011 ◽  
Vol 94 (2) ◽  
pp. 552-561 ◽  
Author(s):  
Regan L Bailey ◽  
Ralph Carmel ◽  
Ralph Green ◽  
Christine M Pfeiffer ◽  
Mary E Cogswell ◽  
...  
Keyword(s):  
United States ◽  
Nutritional Status ◽  
Methylmalonic Acid ◽  
Serum Vitamin ◽  
The United States ◽  
Vitamin B ◽  
Vitamin B 12

scholarly journals Associations of Circulating Methylmalonic Acid and Vitamin B-12 Biomarkers Are Modified by Vegan Dietary Pattern in Adult and Elderly Participants of the Adventist Health Study 2 Calibration Study

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Ella H Haddad ◽  
Karen Jaceldo-Siegl ◽  
Keiji Oda ◽  
Gary E Fraser
Keyword(s):  
Dietary Pattern ◽  
Methylmalonic Acid ◽  
Serum Vitamin ◽  
Health Study ◽  
Vitamin B ◽  
Limited Information ◽  
Cross Sectional ◽  
Fortified Food ◽  
Vitamin B 12 ◽  
Adventist Health Study

ABSTRACT Background Elevated plasma methylmalonic acid (MMA) is a functional biomarker of vitamin B-12 status but limited information is available on its prevalence in US vegetarians. Objectives The study examines the prevalence of plasma MMA ≥0.27 µmol/L in those consuming vegetarian diets, its associations with vitamin B-12 intake and biomarkers, and the modifying effect of vegetarian patterns on these associations. Methods In this cross-sectional study (n = 785), concentrations of MMA, vitamin B-12, holotranscobalamin (holoTC), and homocysteine (Hcy) were determined in participants of the calibration substudy of the Adventist Health Study 2 (AHS-2). Vitamin B-12 intake from food, fortified food, and supplements was assessed by six 24-h recalls. Regression models were used to estimate ORs of having high MMA as related to vitamin B-12 status biomarkers, vitamin B-12 intake, and dietary pattern. Results The prevalence of low vitamin B-12 status defined by serum vitamin B-12 &lt;148 pmol/L, holoTC &lt;35 pmol/L, MMA ≥0.27 and ≥0.37 μmol/L, or Hcy ≥15 μmol/L, and the OR of having high MMA did not differ by dietary pattern, possibly due to intake from fortified food and supplements. Total daily vitamin B-12 intake in the second tertile range of 4.4–14.5 μg/d reduced the likelihood of elevated MMA by 69%; and a doubling of vitamin B-12 intake was associated with a 4.3% decrease in plasma MMA. The association between log plasma MMA and biomarkers was modified by diet, with the vegan pattern showing an ∼3-fold stronger association with log serum vitamin B-12 and Hcy than did the nonvegetarian pattern. Conclusions The prevalence of vitamin B-12 intake &lt;2.0 μg/d was 15.2% in vegans, 10.6% in lacto-ovo-vegetarians, and 6.5% in nonvegetarians. Given the irreversible neurological consequences of vitamin B-12 inadequacy, the importance of regular supplemental vitamin B-12 intake in adult and elderly individuals is stressed.

Vitamin B12 Deficiency in Children With Infantile Spasms: A Case-Control Study

2018 ◽  
Vol 33 (12) ◽  
pp. 767-771 ◽  
Author(s):  
Mahender K. Meena ◽  
Suvasini Sharma ◽  
Himani Bhasin ◽  
Puneet Jain ◽  
Seema Kapoor ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Developmental Delay ◽  
Methylmalonic Acid ◽  
Case Reports ◽  
Serum Vitamin ◽  
Infantile Spasms ◽  
Global Developmental Delay ◽  
P Value ◽  
Vitamin B ◽  
Serum Homocysteine

There have been few case reports showing association of vitamin B12 deficiency with infantile spasms. We planned this study to see if there was an association of serum vitamin B12 deficiency in children with development of infantile spasms. Cases included children with infantile spasms of ages 6 months to 3 years. The controls were children in the same age group who had global developmental delay but no history of epileptic spasms. Mean serum vitamin B12, serum homocysteine, and urinary methylmalonic acid levels were measured in both groups and compared. Children with infantile spasms had lower mean serum vitamin B12 levels (354.1 pg/mL; standard deviation 234.1 pg/mL) as compared to children with global developmental delay without spasms (466.7 pg/mL; standard deviation 285.5 pg/mL) ( P value < .05). Mean serum homocysteine level (13.9 vs 7.8 μmol/L, P = .02) and mean urinary methylmalonic acid level (68.1 mmol/mol of creatinine vs 26.1 mmol/mol of creatinine, P = .03) were elevated in children with infantile spasms than in controls. Fourteen children (35.0%) with infantile spasms were vitamin B12 deficient compared with 3 (7.50%) controls ( P = .005). Thus, vitamin B12 deficiency may have an association with infantile spasms. More studies are needed before recommending routine measurement of serum B12 levels in children with infantile spasms.

scholarly journals Age-specific Serum Methylmalonic Acid Reference Ranges for More Accurate Interpretation of Vitamin B-12 Status in U.S. Adults (P24-030-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ekaterina Mineva ◽  
Maya Sternberg ◽  
Renee Storandt ◽  
Regan Bailey ◽  
Christine Pfeiffer
Keyword(s):  
Renal Function ◽  
Normal Renal Function ◽  
Impaired Renal Function ◽  
Methylmalonic Acid ◽  
Age Groups ◽  
Serum Vitamin ◽  
Reference Intervals ◽  
Vitamin B ◽  
Younger Age ◽  
Vitamin B 12

Abstract Objectives To evaluate vitamin B-12 status of U.S. adults. High serum methylmalonic acid (MMA) is a specific functional indicator of low vitamin B-12 status, but it is not sensitive because concentrations also increase with impaired renal function. Our goal was to describe the distribution of serum vitamin B-12 and MMA in U.S. adults, and estimate age-specific reference intervals for serum MMA in a subpopulation with replete vitamin B-12 status and normal renal function. Methods We examined cross-sectional data for serum vitamin B-12 and MMA in U.S. adults participating in the National Health and Nutrition Examination Survey from 2011–2014. Vitamin B-12 was assessed by electrochemiluminescence assay and MMA by isotope-dilution LC-MS/MS. Results In both bivariate and multivariate analysis age, race/Hispanic origin, and vitamin B-12 supplementation were generally significantly associated with serum vitamin B-12 and MMA concentrations before and after controlling for additional covariates. We observed higher serum vitamin B-12 and MMA concentrations in persons ≥60 y compared with younger age groups. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations compared with non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were wider for persons ≥60 y compared with younger age groups. Compared with the overall population, the central 95% reference interval for serum MMA concentrations was considerably narrower for a vitamin B-12 replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, while serum MMA showed notable increases with impaired renal function. Conclusions The higher serum MMA concentrations throughout the entire distribution in older persons who are vitamin B-12 replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret the vitamin B-12 status in clinical and epidemiologic research. Funding Sources This work was supported by direct appropriations from U.S. Congress.

scholarly journals Age-specific reference ranges are needed to interpret serum methylmalonic acid concentrations in the US population

2019 ◽  
Vol 110 (1) ◽  
pp. 158-168 ◽  
Author(s):  
Ekaterina M Mineva ◽  
Maya R Sternberg ◽  
Mindy Zhang ◽  
Yutaka Aoki ◽  
Renee Storandt ◽  
...  
Keyword(s):  
Renal Function ◽  
Normal Renal Function ◽  
Impaired Renal Function ◽  
Methylmalonic Acid ◽  
Serum Vitamin ◽  
Reference Intervals ◽  
Specific Reference ◽  
Vitamin B ◽  
Reference Ranges ◽  
Vitamin B 12

ABSTRACTBackgroundSerum vitamin B-12 is measured to evaluate vitamin B-12 status. Serum methylmalonic acid (MMA) is a specific functional indicator of vitamin B-12 status; however, concentrations increase with impaired renal function.ObjectiveThe aim of this study was to describe the distribution of serum vitamin B-12 and MMA in US adults, and estimate age-specific reference intervals for serum MMA in a healthy subpopulation with replete vitamin B-12 status and normal renal function.MethodsWe examined cross-sectional data for serum vitamin B-12 and MMA in adults participating in the NHANES from 2011 to 2014. Vitamin B-12 was measured by electrochemiluminescence assay and MMA by isotope-dilution liquid chromatography–tandem mass spectrometry.ResultsIn both bivariate and multivariate analyses, age, race/Hispanic origin, and vitamin B-12 supplement use were generally significantly associated with serum vitamin B-12 and MMA concentrations. Serum MMA concentrations increased with age, particularly in persons aged ≥70 y. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations than non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were widest for persons aged ≥70 y compared with younger age groups. Compared with the overall population, the central 95% reference intervals for serum MMA concentrations were considerably narrower for a vitamin B-12–replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, whereas serum MMA showed notable, increases with impaired renal function.ConclusionsThe higher serum MMA concentrations throughout the entire distribution in older persons (especially persons aged ≥70 y) who are vitamin B-12–replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret vitamin B-12 status in epidemiologic research.

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