What test checks for the ability to process B vitamins in the stomach?

Testing for Intrinsic Factor Deficiency and B12 Malabsorption

The primary test to check if you are missing the ability to process B vitamins (specifically B12) in your stomach is intrinsic factor antibody testing, which identifies pernicious anemia—the most common cause of impaired B12 absorption due to lack of intrinsic factor. 1

Initial Diagnostic Approach

First-Line Blood Tests

• Serum B12 measurement is the standard initial screening test, with levels <150 pmol/L (<203 pg/mL) confirming deficiency 1

• Intrinsic factor antibodies should be tested in patients with confirmed B12 deficiency to identify pernicious anemia, which requires lifelong B12 supplementation 1

• Active B12 (holotranscobalamin) measures the biologically active form available for cellular use and is more sensitive than total B12, though not routinely performed 1

Confirmatory Metabolic Testing

• Methylmalonic acid (MMA) should be measured when B12 levels are indeterminate (180-350 pg/mL) or when clinical suspicion remains high despite normal B12 levels 1

• MMA has 98.4% sensitivity for detecting functional B12 deficiency and identifies an additional 5-10% of patients with deficiency who have low-normal B12 levels 1

• MMA is more specific than homocysteine for B12 deficiency, being elevated in only 12.2% of folate-deficient patients versus 91% for homocysteine 1

Historical Test: The Schilling Test

• The Schilling test was historically used to directly measure B12 absorption through the terminal ileum by administering radioactive B12 and measuring urinary excretion over 24-48 hours 2

• A two-stage approach was used: Stage I with crystalline radioactive B12 alone, followed by Stage II with intrinsic factor added to distinguish intrinsic factor deficiency from other causes of malabsorption 2, 3

• This test has largely fallen out of use with the advent of serum B12 binding assays and antibody testing 2

• Important limitation: The crystalline B12 used in standard Schilling tests does not reproduce the physiologic process of separating B12 from food proteins, potentially missing protein-bound B12 malabsorption 4, 5

Clinical Context and Risk Factors

Conditions Affecting B12 Absorption

• Pernicious anemia (autoimmune destruction of gastric parietal cells) eliminates intrinsic factor production, requiring lifelong B12 supplementation 6, 7

• Atrophic gastritis affecting the gastric body impairs B12 absorption even in early stages 1

• Gastric surgery and simple gastric achlorhydria can impair food-bound B12 absorption while crystalline B12 absorption remains normal 4

• Patients with autoimmune hypothyroidism have 28-68% prevalence of B12 deficiency and should be screened at diagnosis and annually 1

Medications Impairing B12 Absorption

• Metformin use >4 months poses significant risk, with annual screening recommended after 4 years of use 1, 8

• H2 receptor antagonists and proton pump inhibitors reduce gastric acid needed to separate B12 from food proteins 1

• Colchicine and para-aminosalicylic acid produce malabsorption with prolonged use 6, 7

Diagnostic Algorithm

1. Measure serum B12 as first-line test 1

   • If <150 pmol/L: Diagnose deficiency and proceed to step 2
   • If 180-350 pg/mL: Proceed to step 3 for MMA testing
   • If >350 ng/L: Deficiency unlikely

2. Test intrinsic factor antibodies in confirmed deficiency to identify pernicious anemia requiring lifelong treatment 1

3. Measure MMA when B12 results are indeterminate to confirm functional deficiency 1

   • MMA >271 nmol/L confirms functional B12 deficiency 9
   • Up to 50% of patients with "normal" serum B12 have metabolic deficiency by MMA 1, 9

4. Consider additional testing based on clinical context:

   • Complete blood count for megaloblastic anemia (though absent in one-third of cases) 1
   • Gastrin levels if pernicious anemia suspected (markedly elevated >1000 pg/ml) 10

Critical Pitfalls to Avoid

• Do not rely solely on serum B12 to rule out deficiency, especially in patients >60 years where metabolic deficiency is common despite normal serum levels 1

• Avoid giving folic acid before confirming B12 status, as doses >0.1 mg daily may correct anemia while allowing irreversible neurologic damage to progress 6, 7

• MMA and homocysteine can be falsely elevated in hypothyroidism, renal insufficiency, and hypovolemia—interpret cautiously in these conditions 1

• Neurologic symptoms often present before hematologic changes and can become irreversible if untreated, including cognitive difficulties, memory problems, and peripheral neuropathy 1

Treatment Implications

• Patients with confirmed intrinsic factor antibodies require lifelong B12 supplementation, typically via intramuscular injections (1000 mcg monthly) 1, 6

• Oral B12 (1000-2000 mcg daily) is as effective as intramuscular administration for most patients without severe neurologic manifestations or confirmed malabsorption 1, 9

• Treatment should begin immediately when B12 <150 pmol/L to prevent permanent degenerative spinal cord lesions that can develop after 3 months of untreated deficiency 6, 7