B12 deficiency & fatigue: new research explains why

Groundbreaking research from Cornell University, published in January 2026, has uncovered the molecular reason why so many people feel exhausted, heavy-limbed, and foggy even when their doctors say their B12 levels are fine.

What the study found

Led by Dr Martha Field at Cornell’s Division of Nutritional Sciences, this study reveals that vitamin B12 is essential for maintaining your muscle cells’ ‘power plants’  called mitochondria. The research, titled ‘Vitamin B12 supports skeletal muscle oxidative phosphorylation capacity in male mice,’ demonstrates that B12 is far more than just a tool for making red blood cells; it is the literal gatekeeper of our cellular energy production.

The researchers discovered several critical findings:

● When B12 is deficient, uracil (a component normally found only in RNA) begins to accumulate in mitochondrial DNA, causing damage to the genetic material that controls energy production. This DNA damage leads to impaired function of the electron transport chain, reducing muscle energy production capacity by up to 25%.

●  Most importantly, these problems begin during a marginal deficiency, which is before blood tests show abnormal results.

● In aged mice, B12 supplementation improved muscle energy capacity by 2-fold, suggesting significant potential benefits for older adults experiencing age-related muscle decline.

The Grey Zone problem: why you can feel terrible with ‘normal’ test results

For decades, patients with Pernicious Anaemia and B12 absorption issues have reported feeling wiped out, heavy-limbed, and experiencing brain fog, even when their B12 blood tests come back within normal ranges. This research provides the molecular evidence that validates these patients’ lived experiences.

The study shows that mitochondrial damage and energy production problems start during a marginal deficiency.  This ‘grey zone’ is where many patients are currently told by doctors that they are fine.  However, your muscles need energy constantly, so they fail first, long before anaemia shows up in blood tests.

This explains a fundamental disconnect in current mainstream medical practice.  Muscle fatigue, heavy limbs, and brain fog happen long before anaemia develops. The classic ‘wait for anaemia’ approach means people suffer unnecessarily for years while their muscles are already starving for energy.

Why one-size-fits-all treatment may not work

Current B12 treatment protocols typically follow rigid schedules, which consist of B12 injections every 8 to 12 weeks, regardless of individual’s specific needs. However, this research reveals why such fixed schedules may be inadequate for many patients.

Because B12 is required for constant mitochondrial repair and energy production, a fixed-interval regimen ignores the reality that different individuals have vastly different metabolic demands. Many patients with Pernicious Anaemia report experiencing a ‘crash’ weeks before their next scheduled injection.  This is when their mitochondria are once again entering a state of energy crisis.

Dr Field writes, “This is the first study that shows B12 deficiency affects skeletal muscle mitochondrial energy production. It’s highly relevant because muscles have high energy demands.” If your cellular ‘power plants’ are damaged, you may need a more consistent supply of B12 to keep them functioning.

The case for symptom-led treatment

This research supports a shift toward symptom-led treatment rather than calendar-based protocols. When a patient reports the return of neurological or muscular symptoms, it is a direct signal that their mitochondria are once again entering a state of energy crisis, regardless of what a serum B12 blood test might suggest.

Because every individual has a unique metabolic rate and level of existing cellular damage, injection frequency must be personalised based on symptoms rather than dictated by a predetermined schedule.

Your symptoms are real & measurable

Perhaps most importantly, this research validates that brain fog and muscle weakness in B12 deficiency are the result of measurable mitochondrial dysfunction.

The study provides concrete evidence that can help patients advocate for appropriate treatment. When symptoms persist despite ‘normal’ test results, it isn’t your imagination as it is because your mitochondria struggling to produce the energy your body needs.

Who should pay particular attention

This research has particular relevance for:

Older adults: both because B12 deficiency becomes more common with age and because the ageing process naturally impairs mitochondrial function. The 2-fold improvement in muscle energy capacity seen with B12 supplementation in aged mice suggests significant potential benefits.

Vegans & vegetarians: these groups are at higher risk for B12 deficiency since B12 is primarily found in animal products.

People with Pernicious Anaemia or absorption issues: those whose bodies cannot properly absorb B12 through the digestive system.

Anyone with unexplained fatigue or muscle weakness: low B12 might be a contributing factor worth investigating, even if initial blood tests appear normal.

The way forward

This groundbreaking research provides the molecular evidence needed to support a shift in how B12 deficiency is diagnosed and treated. Rather than relying solely on blood tests and fixed treatment schedules, healthcare providers should consider:

● Testing for B12 deficiency earlier, before anaemia develops.

● Taking patient-reported symptoms seriously, even when blood tests appear normal.

● Personalising treatment schedules based on individual symptoms and metabolic needs.

● Recognising that muscle and neurological symptoms indicate real cellular dysfunction.

For patients, this research provides powerful evidence to support advocacy for symptom-led treatment. If you are experiencing symptoms of B12 deficiency, do not accept dismissal based solely on blood test numbers or rigid scheduling. Your mitochondria and your quality of life depend on adequate B12 supplementation tailored to your individual needs.

Reference

Castillo, L.F., Heyden, K.E., Williamson, A.R., Ma, W., Malysheva, O.V., Vacanti, N.M., Thalacker-Mercer, A.E., & Field, M.S. (2026). Vitamin B12 supports skeletal muscle oxidative phosphorylation capacity in male mice. The Journal of Nutrition.

About this article

This blog post summarises current research and is intended for educational purposes. It should not be considered medical advice. If you suspect you have B12 deficiency, please consult with a member of our Clinical Team or other healthcare provider for proper diagnosis and treatment.