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

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.

2020 ◽  
Vol 111 (4) ◽  
pp. 919-926 ◽  
Author(s):  
Melissa F Young ◽  
Junjie Guo ◽  
Anne Williams ◽  
Kyly C Whitfield ◽  
Sabiha Nasrin ◽  
...  

ABSTRACT Background Vitamin B-12 and folate deficiencies in women and children have important public health implications. However, the evidence is conflicting and limited on whether the influence of inflammation on biomarker concentrations may be sufficiently and consistently influenced by inflammation to require adjustment for interpreting concentrations or estimating population prevalence of deficiencies. Objective We examined correlations between concentrations of the inflammation biomarkers C-reactive protein (CRP) and α1-acid glycoprotein (AGP) and serum vitamin B-12 and serum and RBC folate among nonpregnant women of reproductive age (WRA; 15–49 yr) and preschool children (PSC; 6–59 mo). Methods We analyzed cross-sectional data from 16 nationally representative nutrition surveys conducted in WRA (n = 32,588) and PSC (n = 8,256) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Spearman correlations between CRP or AGP and vitamin B-12 or folate concentrations were examined, taking into account complex survey design effects. Results Correlations between inflammation and vitamin B-12 or folate were weak, with no clear pattern of association in either WRA or PSC. Correlation coefficients between CRP and vitamin B-12 for WRA and PSC ranged from −0.25 to 0.16, and correlations between AGP and vitamin B-12 ranged between −0.07 and 0.14. Similarly, correlations between CRP and serum folate ranged from −0.13 to 0.08, and correlations between AGP and serum folate between −0.21 and 0.02. Only 3 surveys measured RBC folate, and among them, correlations for WRA ranged from −0.07 to 0.08 for CRP and −0.04 for AGP (1 country). Conclusions Based on the weak and inconsistent correlations between CRP or AGP and vitamin B-12 or folate biomarkers, there is no rationale to adjust for inflammation when estimating population prevalence of vitamin B-12 or folate deficiencies in WRA or PSC.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Nico S Rizzo ◽  
Karen Jaceldo-Siegl ◽  
Gary Fraser

Objective: To describe the associations between dietary patterns with nutrient intakes differentiated by sex and race. Methods: Cross-sectional study of 71751 subjects (mean age 59 years, 65% female, 76% white) from the Adventist Health Study 2. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Five dietary patterns were established: non vegetarian, semi vegetarians, pesco vegetarians, lacto ovo vegetarians and strict vegetarians. ANCOVA and linear regression analysis were used to determine differences of nutrient intakes by dietary patterns. Non-dietary variables, such as age, smoking and physical activity were taken into account and associations between dietary pattern and BMI were compared. Analysis was repeated by stratifying for sex and race. Results: Strict vegetarians had the lowest BMI, with graded higher BMI levels for dietary patterns with greater fractions of animal plant protein, total fat and saturated fatty acids but similar total caloric intakes. Mean nutrient intake was more dissimilar across dietary pattern than between the sexes or blacks and whites. In general nutrient intakes were more similar between males and females than between blacks and whites with blacks revealing a strikingly higher percentage of non vegetarians than whites. Supplement intakes were often markedly higher in females than in males and higher in whites than in blacks with mean micronutrient intakes for all dietary patterns being well above the estimated average requirements for American adults in both sexes and blacks and whites. Conclusions: All groups met current American nutrient requirements. Nutrient intakes varied more markedly between dietary pattern than between sex or race. Lower BMI levels were associated with dietary patterns characterized by higher plant food intake despite generally similar caloric intake across dietary patterns warranting further investigation.


2011 ◽  
Vol 94 (2) ◽  
pp. 552-561 ◽  
Author(s):  
Regan L Bailey ◽  
Ralph Carmel ◽  
Ralph Green ◽  
Christine M Pfeiffer ◽  
Mary E Cogswell ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ekaterina Mineva ◽  
Maya Sternberg ◽  
Renee Storandt ◽  
Regan Bailey ◽  
Christine Pfeiffer

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.


2019 ◽  
Vol 110 (1) ◽  
pp. 158-168 ◽  
Author(s):  
Ekaterina M Mineva ◽  
Maya R Sternberg ◽  
Mindy Zhang ◽  
Yutaka Aoki ◽  
Renee Storandt ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1824-1824
Author(s):  
Ekaterina Mineva ◽  
Maya Sternberg ◽  
Christine M Pfeiffer

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.


2013 ◽  
Vol 98 (2) ◽  
pp. 460-467 ◽  
Author(s):  
Regan L Bailey ◽  
Ramon A Durazo-Arvizu ◽  
Ralph Carmel ◽  
Ralph Green ◽  
Christine M Pfeiffer ◽  
...  

2009 ◽  
Vol 79 (56) ◽  
pp. 297-307 ◽  
Author(s):  
Laila Hussein ◽  
Sahar Abdel Aziz ◽  
Salwa Tapouzada ◽  
Boehles

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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