Vitamin B12 is long understood as a vital nutrient required for red blood cell formation and nerve function, but a new Cornell study suggests its role in human biology is far more intricate, with implications for aging, metabolism and disease prevention.
The research, published Jan. 19 in the Journal of Nutrition, reports previously unrecognized pathways by which B12 influences cellular metabolism and uncovers biomarkers that may identify early nutritional stress far before classic deficiency symptoms appear.
"This is the first study that shows B12 deficiency affects skeletal muscle mitochondrial energy production," said corresponding author Martha Field, Ph.D. '07, associate professor in the Division of Nutritional Sciences and in the College of Human Ecology. "It's highly relevant because muscles have high energy demands. More importantly, my co-author, Anna Thalacker-Mercer from the University of Alabama at Birmingham, wondered if B12 supplementation in aged mice would improve muscle mitochondrial function - and it did."
Up until now, most research has focused on B12 deficiency and the resulting clinical syndromes - megaloblastic anemia, neuropathy and cognitive decline - rather than its deeper mechanistic roles.
At Cornell, a team including Field and two of her former lab members, first authors Luisa Castillo, Ph.D. '25, and Katarina Heyden, B.S. '18, Ph.D. '24, set out to probe those mechanisms, mapping how B12 interacts with lipid metabolism, organelle stress pathways and epigenetic regulation. What emerged was startling: The vitamin appears to act as a gatekeeper of multiple "hub" pathways, meaning that its insufficiency may ripple far beyond the classic symptoms.
"Another thing we observed in mice is that B12 deficiency seemed to inhibit growth or maintenance of muscle mass," Field said. "It seems that low B12 status is associated with lower muscle mass and maybe muscle strength."
B12 deficiency remains common worldwide, especially among older adults and in low-income settings where meat consumption (a major B12 source) is limited. According to one estimate, one in four older adults in developed countries may show suboptimal B12 status. This new insight underscores the urgency of screening and intervention.
This work also intersects with a growing body of evidence that micronutrient insufficiency - not complete deficiency - contributes significantly to chronic disease. Global public-health data indicate that while many developed countries see little outright B12 deficiency, suboptimal status remains widespread in older adults and among vegans, vegetarians or individuals with malabsorption. The study suggests that even "marginal" B12 status may compromise resilience to metabolic stress, immune challenge and accelerated aging.
From a clinical-science perspective, the authors propose that B12-based biomarkers could inform more personalized nutrition strategies. Instead of one-size-fits-all supplement guidelines, future nutrition guidance might tailor B12 intake to individual metabolic and lifestyle profiles - a shift toward precision nutrition. Such an approach aligns with the broader vision of integrating nutrient science with systems biology.
The findings are based on cell models and require confirmation in humans, Field said.
"We want to understand the whole causal pathway - understanding the molecules and mechanisms," Field said. "This sets the stage for a future controlled human trial."
