The chemistry of the cobalt corrinoids - Recent advances and emerging themes. Part 3. Cobalamins and health.

Vitamin B12 (cobalamin) is an essential micronutrient whose biological importance extends beyond its traditional classification as a haematinic vitamin. This third and final part of a review covering work published between 2020 and 2025 synthesises selected illustrative studies that have advanced understanding of B12 physiology, nutrition, deficiency, delivery, and systems-level biology. At the molecular level, B12 functions as a cofactor in one‑carbon metabolism and mitochondrial pathways, influencing DNA synthesis, methylation capacity, and energy metabolism. These biochemical roles translate into organism-level consequences, particularly in the nervous system, where deficiency may cause irreversible neurological injury even in the absence of overt haematological abnormalities.Population-level analyses show that B12 status reflects the interaction of didetary intake, absorption efficiency, life stage, and food-system dynamics. Although animal-source foods remain the most reliable sources, shifts towards plant-based diets and inconsistent fortification practices are altering risk profiles. Clinical evidence further indicates that B12 deficiency is heterogeneous, frequently under-recognised, and complicated by the limitations of conventional biomarkers. Advances in delivery science point towards more controlled and targeted interventions, including encapsulation technologies, alternative administration routes, and receptor-mediated transport strategies. Emerging evidence also suggests biological activities for cobalamin derivatives beyond classical cofactor function, while microbiome research increasingly implicates corrinoid metabolism in host-microbe interactions relevant to immune and metabolic regulation. These developments support an integrated systems-level view of B12 biology spanning dietary supply, physiology, microbial ecology, and therapeutic innovation. SYNOPSIS: The final part of this review examines recent advances in vitamin B12 biology, spanning physiology, nutrition, deficiency, biomarker limitations, therapeutic delivery, and microbiome-linked corrinoid metabolism. These developments support an integrated systems-level view linking molecular function, dietary ecology, population health, and emerging therapeutic opportunities.