scholarly journals Prevalence of Vitamin B-12 Deficiency in US Adults Using the Combined Indicator of Vitamin B-12 status, cB12

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1824-1824
Author(s):  
Ekaterina Mineva ◽  
Maya Sternberg ◽  
Christine M Pfeiffer
Keyword(s):  
Mexican Americans ◽  
Methylmalonic Acid ◽  
Age Groups ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Us Congress ◽  
Funding Sources ◽  
Plasma Thcy ◽  
Younger Age ◽  
Vitamin B 12

Abstract Objectives High blood methylmalonic acid (MMA) and homocysteine (tHcy) and low serum B-12 and holotranscobalamin (holoTC) concentrations indicate vitamin B-12 deficiency. The diagnosis is often contradictory when using any test independently. A mathematical model including all 4 biomarkers, named combined indicator of vitamin B-12 status (cB12), has been proposed. Our goal was to describe cB12 in US adults and estimate the prevalence of low or transitional vitamin B-12 status compared to conventional single biomarkers. Methods We assessed cB12 in persons ≥20 y participating in NHANES from 1999 to 2004 from 3 biomarkers: serum vitamin B-12, MMA, and plasma tHcy. Results The following groups had significantly lower cB12: persons ≥70 y compared with younger age groups, males compared with females, non-Hispanic whites compared with non-Hispanic blacks and Mexican Americans, and non-users of vitamin B-12 containing supplements compared with users. Shorter fasting times and impaired renal function also resulted in lower cB12. There was a strong significant association of cB12 with serum vitamin B-12 (Spearman r = 0.75), MMA (r = −0.70), and tHcy concentrations (r = −0.59). The prevalence of vitamin B-12 deficiency varied with the biomarker and cutoff used: 2.2% and 13% for serum vitamin B-12 < 148 and 148 − 222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff between 250 and 320 nmol/L; and 8.4% for tHcy > 13 μmol/L. Using the proposed cB12 cutoff of < −0.5, 2.7% of adults had “low or transitional vitamin B-12 status”. Conclusions Based on the new combined indicator using 3 biomarkers a larger portion of US adults had adequate vitamin B-12 status (97%) compared to conventional single biomarkers (between 85% and 94%), likely indicating the higher specificity of cB12. It is unclear whether the availability of holoTC data would change these findings. Funding Sources This work was supported by direct appropriations from US Congress.

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.

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 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 <148 pmol/L, holoTC <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 <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.

Effect of Age on Plasma Homocysteine Concentrations in Young and Elderly Subjects Considering Serum Vitamin Concentrations and Different Lifestyle Factors

2004 ◽  
Vol 74 (2) ◽  
pp. 129-136 ◽  
Author(s):  
Straßburg ◽  
Krems ◽  
Lührmann ◽  
Hartmann ◽  
Neuhäuser-Berthold
Keyword(s):  
Young Adults ◽  
Linear Regression Analysis ◽  
Serum Vitamin ◽  
Lifestyle Factors ◽  
Elderly Subjects ◽  
Vitamin B ◽  
Serum Concentrations ◽  
Plasma Thcy ◽  
Vitamin B 12 ◽  
Young And Elderly Subjects

Objectives: The aim of this study was to investigate whether an increase in total homocysteine (tHcy) concentration with increasing age is due to diminishing serum concentrations of pyridoxal-5-phosphate (PLP), vitamin B-12, and folate. The possible influence of different lifestyle factors on tHcy concentration was considered. Methods: Plasma tHcy, serum concentrations of pyridoxal-5-phosphate, vitamin B-12, and folate, intake of coffee and tea, alcohol, and methionine, as well as cigarette smoking, were determined in 252 elderly subjects (60–87 years old) of the longitudinal study on nutrition and health status in an aging population in Gießen (GISELA) and 99 young adults (20–34 years old) of the study on health and nutrition of young adults (GEJE). Results: Mean plasma tHcy concentrations were significantly higher in elderly than in young female subjects (9.7 ± 1.9 mumol/L vs. 9.0 ± 1.6 mumol/L, p < 0.05), but there was no difference between elderly and young men (10.6 ± 2.1 mumol/L vs. 10.7 ± 2.6 mumol/L). No differences in tHcy were observed between young and elderly subjects after adjustment for serum concentrations of PLP, vitamin B-12, and folate. Multiple linear regression analysis revealed a significant influence of age only in elderly, but not in younger subjects. Conclusion: Higher tHcy concentrations in the elderly, in comparison to younger women, are due to lower serum concentrations of PLP, vitamin B-12, and folate, whereas within the age group of elderly subjects alone tHcy concentrations increase with age irrespective of serum vitamin concentrations.

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.

scholarly journals Modeling a methylmalonic acid–derived change point for serum vitamin B-12 for adults in NHANES

2013 ◽  
Vol 98 (2) ◽  
pp. 460-467 ◽  
Author(s):  
Regan L Bailey ◽  
Ramon A Durazo-Arvizu ◽  
Ralph Carmel ◽  
Ralph Green ◽  
Christine M Pfeiffer ◽  
...  
Keyword(s):  
Change Point ◽  
Methylmalonic Acid ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Vitamin B 12

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.

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