01/24/2026
New research article from Cornell University
Vitamin B12 clues offer hope for new therapies
By Laura Reiley, Cornell Chronicle
January 20, 2026
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.”
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My Summary
Pat Kornic, January 24, 2026
We all know that cyanocobalamin and hydroxocobalamin convert to both active forms of B12 in the body. The active forms are methylcobalamin and adenosylcobalamin. Methylcobalamin is the form that floats around the plasma. It does not store but it is needed as it comprises a huge 93% of all B12 in the body. Adenosylcobalamin comprises juts 4% of the amount of B12 in the body but is a very important per centage because this is the form that stores in the liver, kidneys and the mitochondria. It is also the form that gives us energy.
In my daughter's case I don't think she converts enough adenosylcobalamin from cyanocobalamin so in addition to injections she also supplements with an Adenosylcobalamin sublingual. A sublingual works, remember that 4%, so one does absorb enough adenosylcobalamin from a 3000mcg sublingual.
This article discusses B12 in the mitochondria.
How this research matters for Pernicious anemia sufferers as well as B12 malabsorption sufferers
Pernicious anemia and B12 malabsorption isn’t about not eating B12 — it’s about not being able to absorb it.
Normally, B12 needs:
stomach acid
intrinsic factor (made by the stomach)
and a healthy intestine
In pernicious anemia, intrinsic factor is missing and B12 can’t get into cells properly, even if blood levels look “okay.” In B12 Malabsorption, a number of other medical conditions can interfere with the process of getting into the cells, despite having blood levels that look okay.
The study suggests:
Cells can be functionally B12-deficient even when blood tests don’t scream “deficiency”
Some tissues (muscle, energy-producing cells) suffer earlier and silently
This strongly supports what many patients experience:
“My B12 looks fine on labs, but I still feel weak, tired, or unwell.”
This research helps explain why.
Why standard B12 blood tests can miss problems
Most doctors check serum B12, which only shows:
How much B12 is floating in the blood
❌ Not how much is actually working inside cells
The Cornell researchers point out:
B12 has hidden roles in energy production (mitochondria)
Damage can happen before anemia or nerve symptoms appear
Better markers (still underused)
These are often more meaningful:
Methylmalonic acid (MMA)
Homocysteine
Functional symptoms (fatigue, weakness, brain fog)
This matters a LOT for pernicious anemia and B12 Deficiency Malabsorption patients.
Muscle weakness & energy — a big clue
The Cornell study showed:
Low or poorly functioning B12 → mitochondria do not work well
Muscles lose strength and mass over time
This is very relevant if you experience:
Weakness that doesn’t match lab results
Fatigue out of proportion to anemia levels
Poor recovery or stamina
This is not “just aging” — and the research supports that.
What this means practically (and this is not medical advice)
Based on this research, many experts now believe:
✔ B12 needs are individual
✔ “Normal range” isn’t always normal for you
✔ People with:
pernicious anemia
digestive issues
B12 Malabsorption conditions such as Colitis, Crohn’s, Ileitis, autoimmune gastritis, Coeliac, short bowel syndrome, surgery to the stomach or small intestine, destruction of the parietal cells that was caused by long term use of PPI’s or a long term undiagnosed SIBO (small intestinal bacterial overgrowth) and I may have missed some,
may need ongoing, lifelong, and functional monitoring
And importantly:
Treat the person, not just the lab number.
Big takeaway (plain language)
This Cornell study supports something patients have been saying for years:
You can have enough B12 on paper —
but still not have enough B12 where your cells actually need it.
That’s especially true if:
you can’t absorb B12 properly
you feel weak or fatigued without a clear explanation
and this has just reminded me to give myself an injection.
End of summary...this is just what I get from the article. This is a link to the article.
https://news.cornell.edu/stories/2026/01/vitamin-b12-clues-offer-hope-new-therapies?fbclid=IwY2xjawPiGPBleHRuA2FlbQIxMABicmlkETFTUHZOOFlYb09zTkZCYmJoc3J0YwZhcHBfaWQQMjIyMDM5MTc4ODIwMDg5MgABHvYKrlCHRz2i3OkKxzmakMAuItBEn13OWXKz7B35cemYp_tupN4x1XS4t8ab_aem_JfANeLrItctx6WdJiEOtOA
And this is a link to the actual research paper but not much information provided in the abstract. When it has been out longer, I will see if I can get the full article and will place in our file section
This is the conclusion from the paper
Conclusions
Exposure to a B12-deficient diet led to uracil accumulation in mtDNA and impaired maximal oxidative capacity in skeletal muscle. B12 supplementation improved complex IV maximal capacity in gastrocnemius from aged mice, a model of age-related skeletal muscle decline.
https://jn.nutrition.org/article/S0022-3166(26)00016-7/abstract
My thanks to Molly McLaren Craig for finding this article.
Vitamin B12 is a cofactor in folate-mediated one-carbon metabolism (FOCM), which generates nucleotides (thymidylate (dTMP) and purines) and methionine. Depressed de novo thymidylate (dTMP) synthesis leads to uracil accumulation in DNA.
