Evidence map›Paper›PMID 21593511›Full record

ReviewThe American journal of clinical nutrition2011

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.

Ralph Carmel

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The American journal of clinical nutrition, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 4 pooled it
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 4 syntheses or guidelines pooled it, 250 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Association ofThe American journal of clinical nutrition · 2017
    Pooled it
  5. Trial
  6. Assessment of vitamin A, vitamin BEuropean journal of nutrition · 2025
    Trial
  7. Trial
  8. Monitoring Vitamin BNutrients · 2019
    Trial
  9. Trial
  10. Trial
  11. Associations between Biomarkers of Vitamin BThe Journal of nutrition · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Ralph CarmelDepartment of Medicine, New York Methodist Hospital, Brooklyn, NY 11215, USA. rac9001@nyp.org
NewYork–Presbyterian Brooklyn Methodist Hospital · US

Funding

SUBTLE DISTURBANCES OF COBALAMIN STATUSR01DK032640 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CARMEL, RALPH · 1988 to 2007
$2.1M
NIDDK NIH HHS DK32640
6 · The paper itself

Abstract

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. Their exploration begins with understanding that SCCD differs from clinical deficiency not just in degree of deficiency but in fundamental pathophysiology, causes, likelihood and rate of progression, and known health risks (the causation of which by SCCD awaits proof by randomized clinical trials). Conclusions from SCCD data, therefore, often may not apply to clinical deficiency and vice versa. Although many investigators view cobalamin testing as unreliable, cobalamin, like all diagnostic biomarkers, performs satisfactorily in clinical deficiency but less well in SCCD. The lack of a diagnostic gold standard limits the ability to weigh the performance characteristics of metabolic biomarkers such as methylmalonic acid (MMA) and holotranscobalamin II, whose specificities remain incompletely defined outside their relations to each other. Variable cutoff selections affect diagnostic conclusions heavily and need to be much better rationalized. The maximization of reliability and specificity of diagnosis is far more important today than the identification of ever-earlier stages of SCCD. The limitations of all current biomarkers make the combination of ≥2 test result abnormalities, such as cobalamin and MMA, the most reliable approach to diagnosing deficiency in the research setting; reliance on one test alone courts frequent misdiagnosis. Much work remains to be done.

Indexed as

BiomarkersHomocysteineHumansMethylmalonic AcidPublic HealthTranscobalaminsVitamin B 12Vitamin B 12 DeficiencyBiomarkersHomocysteineMethylmalonic AcidTranscobalaminsVitamin B 12

Identifiers

PMID21593511
PMCPMC3174853
OpenAlexW2111467130

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.