Expert Perspectives on Diagnosis and Management of Vitamin B₁₂ Deficiency in Adults

There is no universally accepted definition of vitamin B₁₂ deficiency despite the severity of its medical consequences if not properly diagnosed and treated. Vitamin B₁₂ deficiency can arise either from inadequate dietary intake, or various causes of impaired absorption or availability. The latter include Helicobacter pylori and autoimmune gastritis, other causes of malabsorption, and drug side effects. Vitamin B₁₂ deficiency can display diverse clinical signs and symptoms, including hematological, neurological, psychiatric, and thromboembolic manifestations. The minutes and conclusions of 3 workshops at the Federation of American Societies of Experimental Biology (FASEB) "B-vitamins and One-Carbon Metabolism" Scientific Research Conferences (2022 and 2024) and the 2025 International Conference on One-Carbon Metabolism, B-Vitamins and Homocysteine, the examination of the literature and the National Institute for Health and Care Excellence/DELPHI guidelines allowed us to identify gaps and issues on diagnostic criteria and definition, evaluation of causation, and treatment strategies of vitamin B₁₂ deficiency across different health care settings in adults (>18 y). Our aim is to address these gaps and issues in global guidelines to be reviewed and disseminated by the International Union of Nutritional Sciences. We identified 4 main goals: 1) definition of vitamin B₁₂ deficiency; 2) assessment of causality; 3) differential diagnosis and evaluation of nutritional and metabolic comorbidities; and 4) treatment and follow-up. The objective of such guidelines should be to reduce both underdiagnosis and overdiagnosis of vitamin B₁₂ deficiency by integrating clinical biomarker assessment and considering cause-specific treatment pathways. This should ultimately improve patient outcomes worldwide and, by arriving at uniform diagnostic criteria, facilitate the conduct, interpretation, and integration of research observations to inform clinical guidelines.