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.