Understanding Vitamin B12 Deficiency

Vitamin B12 is primarily absorbed in the stomach and the terminal part of the small intestine, known as the ileum. This process relies on a protein called intrinsic factor, which is secreted by the stomach lining. Factors such as chronic gastritis, autoimmune disorders, surgical removal of parts of the stomach or small intestine, and certain medications can impair the body’s ability to absorb B12, leading to deficiency.

Common symptoms of vitamin B12 deficiency include anemia, numbness or tingling in the hands and feet, pale skin, unsteady movements, memory problems, and mood disturbances. While these symptoms are non-specific and may overlap with those of cancer or its treatments, emerging data suggest that in some cases, vitamin B12 deficiency might not just accompany cancer; it may point to its presence.

Is There a Higher Rate of B12 Deficiency in Cancer Patients?

Multiple studies have shown that vitamin B12 deficiency is notably more common among cancer patients compared to the general population, even in those who have not yet started treatment.

A cross-sectional study involving 311 newly diagnosed cancer patients found that 47% of those who were anemic also had vitamin B12 deficiency. Importantly, this group had not yet received chemotherapy or radiotherapy, suggesting that the deficiency may be linked to the cancer itself, not just its treatment.

Another study focusing on patients with esophagogastric cancer reported that 16% had a confirmed B12 deficiency before undergoing surgery. The rates were even higher among those with gastric adenocarcinoma, where 27% were deficient. These figures are significantly above the estimated 5% deficiency rate seen in the general elderly population of similar age.

The elevated rates in cancer patients suggest a deeper connection between malignancy and B12 metabolism. While poor nutrition and age-related malabsorption can play a role, they do not fully explain the observed patterns.

Biological Mechanisms That May Explain the Link

Several medical mechanisms can account for why vitamin B12 deficiency may be more common in people with certain cancers:

• Gastrointestinal cancers such as stomach and esophageal tumors can interfere directly with the production of intrinsic factor or damage the stomach lining, impairing B12 absorption.
• Autoimmune gastritis and pernicious anemia, both of which reduce intrinsic factor secretion, are associated with a higher risk of developing gastric cancer. This means that B12 deficiency and cancer could stem from the same underlying process.
• Tumor-induced inflammation and weight loss, common in advanced cancers, can further disrupt nutrient intake and absorption.

Interestingly, some patients with cancer and B12 deficiency show no signs of malnutrition or weight loss. This indicates that mechanisms beyond simple dietary insufficiency may be at work, possibly linked to the cancer’s location or biochemical effects on the body.

When Deficiency Mimics Disease

In certain cases, vitamin B12 deficiency can produce symptoms and laboratory results that resemble blood cancers. For instance, severe B12 deficiency can cause bone marrow changes and blood abnormalities similar to those seen in leukemia or myelodysplastic syndromes. This has led to misdiagnoses and unnecessary treatments in some patients.

One case report described a patient initially believed to have acute myeloid leukemia due to abnormal findings on bone marrow examination. Upon further investigation, the cause was found to be a severe B12 deficiency. Once treated with supplementation, the patient’s blood counts and bone marrow returned to normal, underscoring the importance of screening for nutritional deficiencies before making a cancer diagnosis.

In another documented case, a patient being monitored for breast cancer relapse showed a sustained elevation in the CA 15-3 tumor marker, which typically indicates recurrence. However, the marker normalized after the patient received vitamin B12 supplementation, highlighting how deficiency can influence diagnostic biomarkers and mimic disease progression.

Is There a Risk of Cancer from B12 Deficiency?

Beyond being a possible sign of cancer, could vitamin B12 deficiency contribute to cancer development itself? Some evidence suggests this may be the case.

A prospective epidemiological study found that postmenopausal women with low serum B12 levels had a significantly increased risk of developing breast cancer. At a molecular level, vitamin B12 is essential for DNA methylation and repair. A deficiency can lead to DNA damage, impaired gene regulation, and abnormal cell growth. All hallmarks of cancer.

Supporting this idea, a study of 200 cancer patients revealed that those with low B12 levels had increased expression of DNA methyltransferases and abnormal DNA methylation patterns. These epigenetic changes were observed in cancers such as hepatocellular carcinoma, breast, colon, and lung cancer.

The Impact of Cancer Treatment on B12 Levels

Even if B12 deficiency is not present before cancer treatment, it often develops afterward due to surgery or therapy. Surgical procedures involving the stomach or intestines can significantly reduce the body’s ability to absorb B12.

A systematic review and meta-analysis found that nearly 49% of patients who underwent total gastrectomy for gastric cancer later developed vitamin B12 deficiency. These patients commonly experienced symptoms such as anemia, fatigue, dizziness, and numbness. Another study found that 18% of patients who had esophagectomy with gastric tube reconstruction developed deficiency within a year of surgery.

Radiotherapy, especially to the abdomen or pelvis, can also damage the intestinal lining, leading to malabsorption of B12. Additionally, chemotherapy-induced changes to the gut microbiome and nutritional status can further reduce B12 levels over time.

These treatment-related factors highlight the importance of monitoring B12 levels in cancer survivors, particularly those who have undergone gastrointestinal surgeries or intensive therapies.

What Patients and Doctors Should Know

Given the growing body of research, vitamin B12 deficiency should not be dismissed as a minor nutritional issue in patients with or at risk for cancer. Its presence can:

• Precede the diagnosis of cancer, especially in gastrointestinal malignancies
• Mimic symptoms and laboratory findings of hematologic cancers
• Interfere with the interpretation of tumor markers
• Reduce quality of life and impair recovery following surgery or chemotherapy

Doctors should consider checking vitamin B12 levels in patients who present with unexplained anemia, fatigue, or neurologic symptoms, especially if these patients are older or have other risk factors for malignancy. Likewise, cancer survivors who have undergone gastrointestinal surgery or radiation should have their B12 levels monitored regularly to prevent long-term complications.