Vitamin B12 (cobalamin) is a water-soluble nutrient vital for several fundamental bodily processes. It maintains the health of the nervous system, assists in the formation of red blood cells, and supports DNA synthesis. While deficiency affects an estimated 6% of the general population under 60, the risk increases substantially with age. Approximately 20% of adults over 60 may experience B12 deficiency. This elevated risk is typically due to a disruption of the biological mechanisms required to extract and absorb B12 from food, rather than poor diet alone.
The Crucial Role of Stomach Acid in B12 Absorption
The absorption of B12 from food is a multi-step digestive process beginning in the stomach. B12 in animal products is initially bound tightly to food proteins. To be utilized, the vitamin must be released from this complex, which requires the highly acidic environment of the stomach. Hydrochloric acid and the enzyme pepsin work together to cleave the B12 molecule from the food protein.
Once freed, B12 binds to haptocorrin, a protective protein that shields it from degradation. Simultaneously, specialized parietal cells in the stomach lining secrete Intrinsic Factor (IF). The B12-haptocorrin complex travels into the small intestine where pancreatic enzymes break down the haptocorrin. This release allows B12 to bind to Intrinsic Factor, forming a complex absorbed in the terminal section of the small intestine.
Age-Related Changes in Gastric Function
The most common reason for B12 deficiency in older adults is atrophic gastritis (AG). This physiological change involves the chronic inflammation and thinning of the stomach lining, and its prevalence increases significantly with age. AG is estimated to affect 8% to 9% of adults over 65, with rates reaching 40% in individuals over 80.
The deterioration of the stomach lining in AG decreases the number of parietal cells. Since these cells produce hydrochloric acid, their reduction results in hypochlorhydria, or low stomach acid production. This lack of sufficient acid prevents the initial, acid-dependent separation of B12 from its food proteins.
If B12 remains bound to food protein, it cannot efficiently bind with Intrinsic Factor later in the digestive tract. This failure to release the food-bound vitamin is a form of malabsorption termed “food-cobalamin malabsorption.” This mechanism, caused by the progression of atrophic gastritis, is the primary non-dietary cause of B12 deficiency in the elderly.
Medication Impact on Absorption Efficiency
Beyond age-related changes, certain common medications prescribed to older adults can induce similar malabsorption issues. Proton Pump Inhibitors (PPIs) and H2 blockers (H2RAs) are widely used to treat gastroesophageal reflux disease (GERD) and heartburn. These drugs function by suppressing the production of gastric acid.
By drastically reducing the acidity of the stomach, these acid-suppressing medications effectively replicate the hypochlorhydria caused by atrophic gastritis. This lack of acid and pepsin impairs the necessary first step of digestion: the cleavage of B12 from its protein carrier in food. Long-term use of these medications, often exceeding two years, is associated with a greater risk of developing B12 deficiency due to this interference.
Metformin, a first-line drug for managing Type 2 Diabetes, also interferes with B12 status. Unlike acid suppressors, Metformin does not primarily affect the stomach. Instead, it interferes with B12 absorption in the small intestine. The drug disrupts the critical calcium-dependent mechanism required for the B12-Intrinsic Factor complex to bind to receptors in the terminal ileum.
Autoimmune Factors Affecting Intrinsic Factor
A distinct cause of B12 deficiency that increases with age is the autoimmune condition Pernicious Anemia (PA). While AG reduces acid, PA represents an immune-mediated failure in the production of Intrinsic Factor. This condition is responsible for an estimated 15% to 25% of B12 deficiency cases in older populations.
Pernicious Anemia occurs when the immune system produces auto-antibodies that attack the stomach’s parietal cells. The destruction of these cells eliminates the source of Intrinsic Factor, the glycoprotein required to carry B12 through the small intestine for absorption. The immune attack may also involve antibodies that directly bind to Intrinsic Factor, preventing it from attaching to B12.
The absence of functional Intrinsic Factor means that B12 cannot be properly transported or absorbed in the terminal ileum, leading to a severe deficiency regardless of how much B12 is consumed in the diet. This autoimmune mechanism is separate from the generalized gastric thinning of atrophic gastritis.