Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities

Carmel, Ralph; Green, Ralph; Jacobsen, Donald W.; Rasmussen, Karsten; Florea, Mircea; Azen, Colleen

doi:10.1093/ajcn/70.5.904

Cited by 142 publications

(103 citation statements)

References 33 publications

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“…The general outcome supports the hypothesis that an elevated homocysteine plasma concentration leads to an increased risk of ischemic heart disease and to increased mortality [5]. In this context, the role of vitamin B12 remains unclear [6,7].…”

Section: Introductionsupporting

confidence: 73%

Gastric Status and Vitamin B12 Levels in Cardiovascular Patients

et al. 2007

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Proper absorption of vitamin B12 requires gastric corpus mucosa that functions appropriately and secretes intrinsic factor needed as an essential cofactor for the absorption of dietary vitamin B12 in the small bowel. Here we describe the prevalence of vitamin B12 deficiency and atrophic corpus gastritis (ACG) in patients with coronary heart disease. Fasting serum was obtained from patients who were admitted for cardiovascular diseases at the Coronary Care Unit in Nijmegen, the Netherlands. The status of gastric mucosa was assessed by using the serum levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori IgG antibodies and analyzed over vitamin B12 level subgroups. The study population consisted of 376 patients (mean age, 65 years [SD, 13 years], 227 [60%] males). Low vitamin B12 levels (<150 pM) were detected in 28 patients (7%). Of these 28 patients, 5 (18%) had ACG according to the biomarker assays. Altogether, another 140 patients (37%) had vitamin B12 levels between 150 and 250 pM, of whom 10 (7%) had ACG.Professor Pentti Sipponen is scientific advisor for Biohit Plc, the company that developed the H. pylori, serum pepsinogen, and gastrin-17 assays. Of the remaining patients, five (2%) had ACG. Deficiency of vitamin B12 is common among subjects with coronary heart disease. Up to 20% of these deficiencies are related to ACG. M. G. H. van Oijen

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Section: Introductionsupporting

confidence: 73%

Gastric Status and Vitamin B12 Levels in Cardiovascular Patients

et al. 2007

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“…Profile 3 was characterized by a high MMA concentration alone; serum vitamin B-12 concentrations were within the defined normal range. This group may have reflected the superior sensitivity of MMA to vitamin B-12 in mild, purely biochemical vitamin B-12 deficiency (44), which may predominate in profile 3, as also suggested by the demographic similarities of profile 3 to profile 1; the significantly lower MMA elevation than in profile 1 suggests that the vitamin B-12 deficiency, if present, was milder. However, others in profile 3 may also have represented falsely elevated MMA concentrations for reasons not related to vitamin B-12 status (5).…”

Section: Discussionmentioning

confidence: 95%

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

Bailey¹,

Carmel²,

Green³

et al. 2011

The American Journal of Clinical Nutrition

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136

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Background: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects. Objective: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency. Design: Data from NHANES, a nationally representative crosssectional survey, were examined for adults aged .19 y (mean 6 SD age: 45 6 1 y) from 1999 to 2004 (n = 12,612). Results: Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of .148 pmol/L for vitamin B-12 and of 210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency. Conclusions: These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal.Am J Clin Nutr 2011;94:552-61.

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“…In the same way, none of the studies included different cut-offs for Hcy depending on age. Only Carmel et al [27] and Gamble et al [28] reported values for males (m) and females (f) separately: 17.1 μmol/L (m) and 16.8 μmol/L (f), and 11.4 μmol/L (m) and 0.4 μmol/L (f). Age and gender did not seem to influence the choice of cut-offs values for both sFolate and RBC folate.…”

Section: Discussionmentioning

confidence: 99%

A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population

Aparicio‐Ugarriza¹,

Palacios²,

Alder

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

105

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Vitamin B 12 deficit is one of the most common vitamin deficiencies. However, there is no consensus on the cut-off points for vitamin B 12 and its co-markers, such as folate, holotranscobalamin, methylmalonic acid and homocysteine. In order to establish the state of the art about cut-off points used to determine vitamin B 12 deficiency in the last decades, the database MEDLINE was used for searching studies published in adults between December 1992 and May 2014 (69 articles), using search terms like 'vitamin B 12 ', 'cobalamin', 'cut-off', 'deficiency' alone or in combinations. Broad ranges of cut-off points for vitamin B 12 and its biomarkers were identified: vitamin B 12 ranged between 100 pmol/L and 350 pmol/L, holotranscobalamin 20-50 pmol/L, methylmalonic acid 0.210-0.470 μmol/L, homocysteine 10-21.6 μmol/L, serum folate 3.7-15.9 nmol/L and red blood cell 124-397 nmol/L. For the majority of studies, the potential influence of age, analytical methods, gender and fortified food consumption was not taken in account when choosing cut-off values. This could explain the discrepancies between studies on vitamin B 12 and folate deficiency prevalences. We conclude that there is inconsistency in the literature regarding vitamin B 12 cut-offs. It would be necessary to establish different reference cut-offs according to age, considering the analytical methods used.

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Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities

Cited by 142 publications

References 33 publications

Gastric Status and Vitamin B12 Levels in Cardiovascular Patients

Gastric Status and Vitamin B12 Levels in Cardiovascular Patients

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

A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population

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