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Cited by 184Folate and B Vitamins ResearchPorphyrin Metabolism and DisordersHematological disorders and diagnostics

The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.

Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points

Fedosov, Sergey N., Brito, Alex, Miller, Joshua W., Green, Ralph, Allen, Lindsay H.·2015·Clinical Chemistry and Laboratory Medicine (CCLM)
DOI 10.1515/cclm-2014-0818
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Abstract

BACKGROUND: A novel approach to determine vitamin B12 status is to combine four blood markers: total B12 (B12), holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy). This combined indicator of B12 status is expressed as cB12=log10[(holoTC·B12)/(MMA·Hcy)]-(age factor). Here we calculate cB12 in datasets with missing biomarkers, examine the influence of folate status, and revise diagnostic cut-points. METHODS: We used a database with all four markers (n=5211) plus folate measurements (n=972). A biomarker Z (assumed missing) was plotted versus X (a combination of other markers) and Y (age). Each chart was approximated by a function Ztheor, which predicted the potentially absent value(s). Statistical distributions of cB12 were aligned with physiological indicators of deficiency and used to determine cut-offs. RESULTS: The predictive functions Ztheor allowed assessment of the "incomplete" indicators, 3cB12 (three markers known) and 2cB12 (two markers known). Predictions contained a systematic deviation associated with dispersion along two axes Z and X (and unaccounted by the least squares fit). Increase in tHcy at low serum folate was corrected (cB12+Δfolate) based on the function of Δfolate=log10(Hcyreal/Hcytheor) versus folate. Statistical distributions of cB12 revealed the boundaries of groups with B12 deficiency, i.e., cB12<-0.5. CONCLUSIONS: We provide equations that combine two, three or four biomarkers into one diagnostic indicator, thereby rescaling unmatched data into the same coordinate system. Adjustment of this indicator is required if serum folate is <10 nmol/L and tHcy is measured. Revised cut-points and guidelines for using this approach are provided.

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Research works printed but not linked: 36

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Metadata

Authors
Fedosov, S. N., Brito, A., Miller, J. W., Green, R., & Allen, L. H.
Affiliations
  • Aarhus University (DK)
  • University of California, Davis (US)
  • Western Human Nutrition Research Center (US)
Corresponding author
Fedosov, Sergey N.
ORCID
Venue
Clinical Chemistry and Laboratory Medicine (CCLM)
Publisher
Walter de Gruyter GmbH
Published
2015-01-01
Volume
53
Issue
8
Pages
1215-25
ISSN
  • 1434-6621 (ISSN-L)
  • 1437-4331
DOI
10.1515/cclm-2014-0818
OpenAlex
W2323150136
Cited by
184
References
37
Citations by year
2026: 13 · 2025: 19 · 2024: 16 · 2023: 19 · 2022: 9 · 2021: 19 · 2020: 20 · 2019: 20 · 2018: 17 · 2017: 15 · 2016: 10 · 2015: 7
FWCI
13.55
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Chemistry and Laboratory Medicine (CCLM) (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
  • Health Sciences › Medicine › Hematology › Hematological disorders and diagnostics
Keywords
vitamin B12 status, holotranscobalamin, methylmalonic acid, total homocysteine, serum folate, diagnostic thresholds
MeSH terms
Folic Acid, Homocysteine, Humans, Methylmalonic Acid, Transcobalamins, Vitamin B 12, Biomarkers, Healthy Volunteers

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