Importance, Sources, and Forms of Vitamin B12- A Review

A recent comprehensive review published in Cureus compared these forms and examined the role of vitamin B12 in various health conditions, including megaloblastic anemia.

The review, authored by Christopher R. Behringer from the Clinical Education Department at Lake Erie College of Osteopathic Medicine, Erie, USA, and colleagues, provides an in-depth overview of vitamin B12 physiology, dietary sources, absorption mechanisms, and clinical implications of deficiency. The authors highlight that vitamin B12, present as cyanocobalamin, methylcobalamin, and adenosylcobalamin, is a crucial micronutrient primarily obtained through the diet, especially from animal-derived foods such as meat, dairy products, eggs, and fish.

Despite adequate availability in many diets, vitamin B12 deficiency remains surprisingly common. Older adults, individuals following vegetarian or vegan diets, and patients with gastrointestinal disorders or malabsorption syndromes are particularly vulnerable. Deficiency can manifest as megaloblastic anemia, neurological symptoms such as numbness and cognitive changes, and adverse pregnancy outcomes, underscoring the vitamin’s wide-ranging physiological importance.

The review explains that in healthy individuals, dietary intake and supplementation are generally equally effective in raising serum B12 levels. However, in disease states—especially conditions like megaloblastic anemia or disorders affecting absorption—diet alone may be insufficient. In such cases, supplementation becomes necessary to restore adequate vitamin levels and prevent complications.

A key focus of the review is the comparison between natural and synthetic forms of vitamin B12. Natural forms, particularly methylcobalamin, are biologically active and directly involved in cellular processes such as DNA synthesis and neurological function. Cyanocobalamin, the most commonly used synthetic form in supplements and fortified foods, must first be converted in the body into active forms. According to the authors, methylcobalamin appears to offer better bioavailability and effectiveness, especially in individuals with impaired absorption or altered methylation pathways.

The authors suggest that targeted screening for vitamin B12 deficiency may be beneficial in high-risk populations, including the elderly, individuals with chronic gastrointestinal conditions, and those following strict plant-based diets. Early identification and timely supplementation may help prevent irreversible neurological damage and long-term hematologic consequences.

However, the review also acknowledges its limitations. As a narrative literature review rather than a clinical trial, the findings rely on previously published studies with varying methodologies and populations. This limits the ability to draw firm conclusions about superiority between different B12 forms across all patient groups. The authors emphasize the need for large-scale comparative studies and meta-analyses to better understand long-term outcomes of supplementation and the role of genetic and metabolic differences.

"The review reinforces vitamin B12’s critical role in human health and supports the use of both natural and synthetic forms for correcting deficiency. While supplementation has shown benefits in improving neurological and psychiatric symptoms related to deficiency, important questions remain regarding optimal formulation, long-term safety, and the potential role of preventive supplementation in susceptible populations," the authors concluded.

Reference:

Behringer C R, Kulkarni A, Weinstein A (November 06, 2025) Vitamin B12: A Comprehensive Review of Natural vs Synthetic Forms of Consumption and Supplementation. Cureus 17(11): e96258. doi:10.7759/cureus.96258