22: Vitamin B12 (Chapter 22b)
- Page ID
- 117166
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Dietary deficiencies of vitamin B12 in industrialized countries are relatively rare and usually arise from food-bound malabsorption, particularly in the elderly. Secondary B12 deficiency may also develop from certain disease states or medications that interfere with B12 absorption. In low or middle-income countries, however, dietary vitamin B12 deficiency may occur among children and pregnant and lactating women who exclude or consume low amounts of animal-source foods. Absorption of B12 occurs via passive or active absorption, the latter a complex process during which the bioavailability of dietary B12 in healthy adults is assumed to be about 40‑50%. Dietary requirements for B12 vary across countries, with some establishing adequate intakes (AIs) but not requirements per se. There is no Tolerable Upper Intake Level (UL) for vitamin B12 because high intakes have not been associated with any adverse health effects.
There are two major metabolic roles for vitamin B12: (a) synthesis of methionine from homocysteine and (b) conversion of methylmalonyl coenzyme A to succinyl coenzyme A. Vitamin B12 has an important role in cellular metabolism, especially in DNA-synthesis, methylation and mitochondrial metabolism. Deficiency of B12 predominantly affects hematological and neurological systems, although neuropsychiatric symptoms are often the first clinical manifestation. Notably, the full spectrum of clinical features associated with B12 deficiency is much broader, is nonspecific, and may occur as a consequence of other diseases.Risk of B12 insufficiency can be assessed through measurement of dietary vitamin B12 intake, a biomarker of exposure. Currently, no gold standard exists to define deficiency of vitamin B12. Total B12 concentration in serum is most frequently used, despite its poor sensitivity and specificity. Consequently, a combination of biomarkers is preferred to define and classify B12 status. If subclinical vitamin B12 is suspected, then circulating total vitamin B12 or transcobalamin (TC)-bound B12 (i.e., holo TC) in serum should be measured first, followed by methylmalonic acid (MMA) or homocysteine in serum, both more sensitive functional biomarkers that reflect B12 stores rather than intake. Algorithms based on all or some of these biomarkers measured either sequentially or concurrently are often applied, with concurrent biomarkers combined into a single indicator termed cB12. For all B12 biomarkers, information should be collected on age, gender, ethnicity, pregnancy, folate status, and presence of possible bacterial overgrowth because all these factors impact B12 biomarkers. There is no consensus on the interpretive criteria used to define inadequate B12 status with these B12 biomarkers. For some, statistically defined reference limits are used, whereas for others "true" cutoffs" based on a known relationship between the B12 biomarker and low body stores, functional impairment, or clinical signs of deficiency, are applied.
Often in clinical patients, once B12 deficiency is diagnosed, the next step is to establish whether malabsorption is the cause. In the past, the Schilling test was used, but is rarely conducted today because this test uses radioactive B12. Instead, the CobaSorb test that measures change in serum holoTC concentrations following an oral dose of unlabeled B12 can be used. Under development is the 14C or 13C-labeled absorption test, each of which measures enrichment of 14C or 13C, respectively in blood, urine, or stool following oral ingestion of microbiologically-produced B12 labeled with 14Carbon or 13Carbon.
- 22.1: Introduction (22b.1)
- This page discusses Vitamin B12, its various forms, roles in metabolism, and absorption processes involving dietary sources and complex mechanisms. It highlights the importance of holo-transcobalamin for cellular uptake and the liver's role in storage. The page notes the clinical impact of deficiency, associated risks, and factors like nitrous oxide exposure affecting B12 status. It also outlines international dietary intake recommendations and indicates the safety of high B12 consumption.
- 22.2: Biomarkers of vitamin B12 status (22b.2)
- This page summarizes an expert panel's review of vitamin B12 status biomarkers, emphasizing dietary assessment, biometric testing, and the influence of factors like age and pregnancy on B12 levels. Variability in serum B12 levels across different demographics, particularly among diet types, underscores the need for established reference intervals that respect ethnicity and age.