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.