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

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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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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: Fedosov, Sergey N.
Miller, Joshua W.
Green, Ralph
Allen, Lindsay H.
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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Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points

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