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. B12 deficiency can arise either from inadequate dietary intake, in particular in vegans/vegetarians, or various causes of impaired uptake/availability. The latter include H. pylori and auto-immune gastritis, other causes of malabsorptions 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 three workshops at the FASEB "B-Vitamins and One Carbon Metabolism" Scientific Research Conferences (2022, 2024) and the 2025 International Conference on One-Carbon Metabolism, B-Vitamins and Homocysteine, the examination of the literature and the NICE/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 perspective is to address these gaps and issues in global guidelines to be evaluated by the IUNS (International Union of Nutrition Societies). We identified 4 main goals: 1) definition of vitamin B12 deficiency; 2) assessment of causality; 3) differential diagnosis and evaluation of nutritional and metabolic co-morbidities; and 4) treatment and follow-up. The objective of such guidelines should be to reduce both under- and over- diagnoses of vitamin B12 deficiency by integrating clinical scoring, biomarker algorithms, and to consider 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. STATEMENT OF SIGNIFICANCE: This work is the first effort to design globally applicable clinical guidelines for adult vitamin B12 deficiency that explicitly integrate clinical scoring, biomarker algorithms, and systematic assessment of causality and co-morbid nutritional states. Unlike existing regional guidelines, it proposes a combine use of the GRADE and Delphi frameworks to develop global guidelines for diagnosis and management of vitamin B12 deficiency.