The keynote manuscript by Ralph Green, MD, PhD, from the University of California, Davis, provides a comprehensive overview of the causes and risk factors of Vitamin B12 deficiency across the lifespan. It begins by acknowledging the historical significance of Vitamin B12 in curing pernicious anemia. This condition previously had a dire prognosis and highlights the Nobel Prize-winning work that led to this discovery. Contrary to earlier beliefs that B12 deficiency was mainly a concern for the elderly, Green points out that it can affect individuals at any age and is a significant cause of morbidity among children and young adults in certain regions.
Figure 1. Kaplan-Meier survival curve of 321 patients with pernicious anemia, generated from the publication by Cabot (1908).5 The median survival was less than 20 months, and the 5-year survival was less than 10 percent.
A special tribute is paid to Dorothy Crowfoot Hodgkin, a Nobel Prize laureate for her work on the structure of the B12 molecule. Her personal struggle with rheumatoid arthritis and her determination to continue her research despite severe physical limitations are described, underscoring the human element behind scientific discovery.
The manuscript delves into the complex mechanisms involved in B12 absorption, protection, and metabolism, emphasizing the importance of understanding these processes to grasp how B12 deficiency can occur. It is noted that B12 is essential for only two biochemical reactions in humans but is crucial for health, influencing homocysteine and methylmalonate levels in the plasma, which are linked to various health issues, including cardiovascular disease and cognitive decline.
Various factors determining B12 adequacy are discussed, such as dietary intake, the integrity of the absorption mechanism, and the role of the microbiome. The causes of B12 deficiency are categorized into inadequate intake, malabsorption, and miscellaneous causes, with specific attention to the impact of diet, particularly in vegetarian and vegan populations, and the various diseases and conditions that can impair B12 absorption.
Green also highlights the wide range of clinical manifestations of B12 deficiency, from hematological to neurological complications, and the shift in the frequency of these manifestations over time. The narrative includes intriguing case studies that illustrate the atypical and diverse presentations of B12 deficiency, emphasizing the importance of maintaining a high index of suspicion for this condition.
In conclusion, the manuscript stresses the complexity of B12 deficiency, its varied etiologies, and its potential impact on health across the lifespan. It calls for heightened awareness and a proactive approach to diagnosis and treatment to mitigate the consequences of this deficiency.