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, particularly among vegans/vegetarians, 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 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 aged >18 y. Our aim is to address these gaps and issues in global guidelines to be evaluated 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 scoring and biomarker algorithms 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.