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

Background: No consensus exists about which cutoff point should be applied for serum vitamin B-12 (SB-12) concentrations to define vitamin B-12 status in population-based research.

Objective: The study's aim was to identify whether a change point exists at which the relation between plasma methylmalonic acid (MMA) and SB-12 changes slope to differentiate between inadequate and adequate vitamin B-12 status by using various statistical models.

Design: We used data on adults (≥19 y; n = 12,683) from NHANES 1999-2004-a nationally representative, cross-sectional survey.

Diagnosis and management of clinical and subclinical cobalamin deficiencies: why controversies persist in the age of sensitive metabolic testing.

In the past two decades, sensitive biochemical tests have uncovered cobalamin deficiency much more frequently than ever before. Almost all cases involve mild, biochemical changes without clinical manifestations (subclinical cobalamin deficiency; SCCD), whose health impact is unclear. Because the causes of SCCD are most often unknown, nonmalabsorptive, and seldom documented, controversy and confusion surround the diagnostic criteria and, inevitably, consequences and management of SCCD.

Subclinical cobalamin deficiency.

Purpose Of Review: This review focuses on recent developments and controversies in the diagnosis, consequences, and management of subclinical cobalamin deficiency (SCCD), which affects many elderly persons.

Recent Findings: Diagnosis of SCCD depends exclusively on biochemical tests whose individual limitations suggest that combinations of tests are needed, especially in epidemiologic research. The causes of SCCD are unknown in more than 60% of cases, which limits prognostic predictions and identification of health consequences.

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

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 cross-sectional survey, were examined for adults aged >19 y (mean ± SD age: 45 ± 1 y) from 1999 to 2004 (n = 12,612).

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES--serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)--and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES.

Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II.

Cobalamin deficiency is relatively common, but the great majority of cases in epidemiologic surveys have subclinical cobalamin deficiency (SCCD), not classical clinical deficiency. Because SCCD has no known clinical expression, its diagnosis depends solely on biochemical biomarkers, whose optimal application becomes crucial yet remains unsettled. This review critically examines the current diagnostic concepts, tools, and interpretations.

Biomarkers of folate status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999-2002.

Mandatory fortification of the food supply with cobalamin: an idea whose time has not yet come.

The success of folic acid fortification has generated consideration of similar fortification with cobalamin for its own sake but more so to mitigate possible neurologic risks from increased folate intake by cobalamin-deficient persons. However, the folate model itself, the success of which was predicted by successful clinical trials and the known favorable facts of high folic acid bioavailability and the infrequency of folate malabsorption, may not apply to cobalamin fortification. Cobalamin bioavailability is more restricted than folic acid and is unfortunately poorest in persons deficient in cobalamin.

Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels.

Transcobalamin (TC) I deficiency, like the function of TC I itself, is incompletely understood. It produces low serum cobalamin levels indistinguishable from those of true cobalamin deficiency. Diagnosis is especially elusive when TC I deficiency is mild.

Nutritional anemias and the elderly.

Nutritional anemias are important because they are easily reversed and because their underlying causes, most often unrelated to dietary intake, require individualized assessment. Iron-deficiency anemia (IDA) usually results from iron losses accompanying chronic bleeding, including loss to intestinal parasites, or from gastric disorders or malabsorption in the elderly. Cobalamin-deficiency anemia, the only nutritional anemia with predilection for the elderly, nearly always stems from failure of intrinsic factor (IF)-related absorption.

Efficacy and safety of fortification and supplementation with vitamin B12: biochemical and physiological effects.

Long known as an uncommon but serious medical disorder requiring medical management, vitamin B12 deficiency is now seen to be common worldwide, but it is in a quite different form than traditionally envisioned. Most of the newly recognized deficiency is subclinical in nature, its health impact and natural history are uncertain, and its prevalence has been greatly inflated by also including persons with "low-normal" vitamin B12 levels, few of whom are deficient. The spread of folic acid fortification has also introduced concerns about folate's potentially adverse neurologic consequences in persons with undetected vitamin B12 deficiency.

How I treat cobalamin (vitamin B12) deficiency.

The challenges in medical management of cobalamin deficiency lie in attention to the unique pathophysiology that underlies cobalamin deficiency, more than in the mechanics of therapy. The central physiologic principles are that clinically important deficiency is more likely to occur (and progress) when intrinsic factor-driven absorption fails than when diet is poor and that most causes take years to produce clinically obvious deficiency. Transient defects have little clinical impact.

Diagnosis and management of clinical and subclinical cobalamin deficiency: advances and controversies.

Major recent developments in cobalamin deficiency include issues such as the nature of food-cobalamin malabsorption, sensitivities and specificities of diagnostic tests, and emerging data on oral therapy. These have been heavily influenced by studies of subclinical deficiency, which has a much slower progression (which may be nonlinear), arises from different causes, and poses different, more public health-oriented management considerations than the less frequent but much more medically important entity of clinically expressed deficiency. Distinguishing carefully between the two deficiency states is helpful because clinical lessons and strategies derived from one may not apply equally to the other, as illustrated by controversial decisions about clinical issues such as the serum cobalamin level diagnostic of deficiency.

Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II.

Background: Cobalamin attached to transcobalamin II (TC II), known as holo-TC II, is the active cobalamin fraction taken up by tissues. Holo-TC II is also the form in which absorbed cobalamin enters the circulation from the ileum. Therefore, holo-TC II has been proposed variously as a marker of cobalamin adequacy, cobalamin absorption, or both, including even its advocacy as a surrogate Schilling test.

Mild hyperhomocysteinemia in adult patients with sickle cell disease: a common finding unrelated to folate and cobalamin status.

Homocysteine has associations with both vitamin insufficiency and vascular complications, and its status is therefore of interest in sickle cell disease (SCD). However, information is limited, especially in adults. We studied plasma total homocysteine (tHcy) and three of its major modifiers, cobalamin, folate, and creatinine, in 90 adult patients with SCD and 76 control subjects.

Update on cobalamin, folate, and homocysteine.

Three topics affecting cobalamin, folate, and homocysteine that have generated interest, activity, and advances in recent years are discussed. These are: (I). the application of an expanded variety of tools to the diagnosis of cobalamin deficiency, and how these affect and are affected by our current understanding of deficiency; (II).