Skip to main content
Back to Research Library
B
Good Confidence
Review ArticlePMC Full Text2011

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

Carmel R • American Journal of Clinical Nutrition

Key Finding

Serum B12 <148 pmol/L: 95-97% sensitivity for clinical deficiency but only 38-39% for SCCD; MMA >270 nmol/L more sensitive; reliance on single test is risky

Key Findings

  • 1Serum B12 <148 pmol/L: 95-97% sensitive for clinical deficiency, only 38-39% for SCCD
  • 2MMA >270 nmol/L: >95% sensitivity, more frequently elevated than low B12
  • 3Reliance on single diagnostic test is risky - combined testing recommended
  • 4Most B12 deficiency in population surveys is subclinical (SCCD)

Original title: “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”

Plain English Summary

Review examining B12 biomarkers for epidemiologic research. Distinguishes subclinical cobalamin deficiency (SCCD) from clinical deficiency. Most cases in population surveys are SCCD.

In-Depth Analysis

Study Details

Author: Ralph Carmel, MD
Institutions: New York Methodist Hospital; Weill Medical College of Cornell University
Journal: Am J Clin Nutr, 2011; 94(1):348S-358S
PMCID: PMC3174853

Key Points (from original paper)

Main Finding

"Cobalamin deficiency is relatively common, but the great majority of cases in epidemiologic surveys have subclinical cobalamin deficiency (SCCD), not classical clinical deficiency."

Diagnostic Thresholds

Serum Cobalamin:

  • •Standard cutoff: <148 pmol/L (<200 ng/L)
  • •Sensitivity for clinical deficiency: 95-97%
  • •Sensitivity for SCCD: 38-39% (55-84% with higher cutoffs)

Methylmalonic Acid (MMA):

  • •Common cutoffs: 210-480 nmol/L
  • •Typical threshold: ~270 nmol/L
  • •Sensitivity for clinical deficiency: >95%
  • •More frequently elevated than low cobalamin in population surveys

Holotranscobalamin II (holo-TC II):

  • •Cutoff ranges: 11-50 pmol/L (varies by laboratory)
  • •Commercial assay: 19 pmol/L
  • •Performs marginally better than total cobalamin
Critical Recommendation

"Reliance on any single diagnostic test is risky in epidemiologic research and public health surveys."

Combined testing using abnormalities in both cobalamin and MMA recommended for reliable diagnosis.

Source: PMC full text (PMC3174853)

Paradigm Relevance

How this study applies to different clinical perspectives:

Standard Medical

Relevant

Conventional clinical guidelines used by most doctors

Why it matters:

Explains limitations of standard serum B12 testing used in routine practice.

Research Consensus

Relevant

Current scientific understanding, often ahead of guidelines

Why it matters:

Provides evidence basis for optimal testing strategies and cutoff interpretation.

Metabolic Optimization

Relevant

Proactive targets for optimal health, not just disease absence

Why it matters:

Supports using multiple markers (B12 + MMA) for confident identification of true deficiency.

Study Details

Type
Review Article
Methodology
Critical review of B12 biomarkers including serum cobalamin, MMA, and holotranscobalamin II for epidemiologic applications.

Evidence Quality

Review from PMC3174853. Author Ralph Carmel from New York Methodist Hospital/Cornell.

Topic

vitamin b12biomarkersdiagnostics

Related Biomarkers

VITAMIN B12METHYLMALONIC ACIDHOMOCYSTEINE

Calculate & Evaluate on Metabolicum

🔴

Vitamin B12

Evaluator

Assess B12 status with metabolic context

Original Source

View on PubMedView DOIFull Text (Open Access)

DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.

Related Studies