FUNCTIONAL VITAMIN B12 DEFICIENCY WITHOUT ANEMIA: CLINICAL IMPLICATIONS, DIAGNOSTIC CHALLENGES, AND EVIDENCE FROM THE LITERATURE

Functional vitamin B12 deficiency without anemia represents an underrecognized clinical condition in which biochemical and tissue-level cobalamin insufficiency occurs despite normal hemoglobin levels and, in many cases, normal mean corpuscular volume. This narrative literature review aimed to synthesize current evidence on the pathophysiology, clinical manifestations, diagnostic limitations, and management strategies of functional vitamin B12 deficiency in the absence of anemia. A comprehensive search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, Cochrane Library, SciELO, and LILACS, including studies published between 2005 and 2025. The findings demonstrate that neurological, psychiatric, and subtle hematological abnormalities may precede overt anemia, leading to frequent underdiagnosis. Serum vitamin B12 levels alone showed limited sensitivity, while biomarkers such as methylmalonic acid and homocysteine provided greater diagnostic accuracy. The literature highlights significant heterogeneity in clinical presentation and diagnostic thresholds, contributing to delayed treatment. Early recognition of functional deficiency is essential to prevent irreversible neurological damage. This review underscores the need for a broader diagnostic approach and increased clinical awareness of non-anemic vitamin B12 deficiency in internal medicine practice.