Part III: The Well-Appearing Patient: Laboratory Identification of Pro-Neoplastic Risk in Latent Iron, Vitamin B12, and Folate Deficiency
Main Article Content
Abstract
Background: A significant portion of the population harbors latent iron, vitamin B12, and folate deficiencies that are clinically silent and often missed by routine laboratory panels. These subclinical deficiencies can promote chronic oxidative stress and epigenetic disruption, increasing long-term cancer risk, yet a diagnostic gap remains for their early detection in asymptomatic individuals.
Objective: This review suggests a new, function-first diagnostic approach to uncover hidden micronutrient deficiencies in "well-appearing" patients. It offers a practical, evidence-based framework for clinicians to go beyond traditional screening cutoffs and detect pro-neoplastic metabolic risk before irreversible damage occurs.
Methods: We advocate for an updated diagnostic strategy that includes sensitive and functional biomarkers. This involves using a higher serum ferritin cutoff (<50 µg/L) to define early iron depletion, implementing a seven-step algorithm focusing on transferrin saturation (TSAT) and reticulocyte hemoglobin (Ret-He), and employing holotranscobalamin (holoTC) and renal-adjusted methylmalonic acid (MMA) to accurately assess vitamin B12 status, especially when total serum levels are indeterminate.
Findings: Using this advanced diagnostic approach can reveal a significant prevalence of non-anemic iron deficiency and functional B12 deficiency, which are typically overlooked. These functional markers provide a more accurate measure of tissue-level nutrient availability and metabolic effects, particularly in complex clinical settings such as chronic inflammation, heart failure, or kidney disease.
Conclusion: Transitioning to proactive, function-based laboratory evaluation is essential for modern preventive medicine. By detecting and addressing hidden micronutrient deficiencies early, clinicians can diminish the factors that lead to carcinogenesis, offering a genuine opportunity to intervene in the neoplastic process and potentially reduce cancer rates.
Article Details
How to Cite
TISMAN, Glenn.
Part III: The Well-Appearing Patient: Laboratory Identification of Pro-Neoplastic Risk in Latent Iron, Vitamin B12, and Folate Deficiency.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7183>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7183.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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4. Skjærven KH, Jakt LM, Fernandes JMO, et al. Parental micronutrient deficiency distorts liver DNA methylation and expression of lipid genes associated with a fatty-liver-like phenotype in offspring. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-21211-5
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12. Cancado RD, Leite LAC, Muñoz M. Defining global thresholds for serum ferritin: a challenging mission in establishing the iron deficiency diagnosis in this era of striving for health equity. Diagnostics. 2025;15(3):289. doi:10.3390/diagnostics15030289
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