False-Negative Fecal Occult Blood Test
Excess vitamin C (more than 250 mg from supplements or citrus fruits) is the most likely cause of a false-negative FOBT among the options listed, as it blocks the peroxidase reaction in guaiac-based tests. 1
Understanding False-Negative Results
The key mechanism for false-negative results in guaiac-based FOBT involves interference with the peroxidase reaction that detects blood:
- Vitamin C (ascorbic acid) in excess of 250 mg acts as a reducing agent that blocks the peroxidase reaction, preventing detection of actual blood in the stool 1
- Patients should avoid vitamin C supplements and citrus fruits for 3 days before testing to minimize this risk 2, 1
- Inadequate specimen collection or improper test development can also lead to false negatives 1
Why the Other Options Are Incorrect
Oral Iron Therapy (Option A)
Oral iron does NOT cause false-negative results. Multiple prospective studies have definitively shown that:
- Ferrous sulfate and ferrous gluconate in therapeutic doses (324 mg three times daily) do not cause false-positive, true-positive, or false-negative Hemoccult tests 3
- In a study of 84 stool specimens during oral iron therapy, all were appropriately negative on Hemoccult testing 3
- A separate double-blind crossover study of 78 participants found zero positive results after iron ingestion 4
Coumadin Therapy (Option B)
While anticoagulation could theoretically cause gastrointestinal bleeding leading to a true-positive result (not a false-negative), this represents actual pathology rather than a test artifact. 5
Iron Deficiency Anemia (Option C)
Iron deficiency anemia is associated with false-negative results in clinical practice, but this reflects the poor sensitivity of FOBT rather than a direct interference mechanism:
- FOBT has a sensitivity of only 0.58 (95% CI 0.53-0.63) in patients with iron deficiency anemia 6, 7
- 42% of patients with identifiable causes of IDA had false-negative FOBT 7
- Guidelines specifically recommend against using FIT in patients with iron deficiency anemia due to poor performance 6
- However, this is not a "cause" of false-negatives in the same mechanistic sense as vitamin C interference
Dietary Peroxidases (Option D)
Dietary peroxidases from fruits, vegetables, grains, and red meat cause false-positive results (not false-negatives) due to pseudoperoxidase activity 5
Clinical Implications
The correct answer is vitamin C (dietary peroxidases), though this option is poorly worded in the question. The parenthetical note about "false +ve" appears to be an error, as dietary peroxidases cause false-positives, while vitamin C causes false-negatives. 1, 5
Key Practice Points:
- Instruct patients to avoid vitamin C supplements exceeding 250 mg for 3 days before guaiac-based FOBT 2, 1
- Consider using fecal immunochemical tests (FIT) instead, as they are not affected by vitamin C and have better specificity 1
- Do not withhold oral iron therapy based on concerns about FOBT interference—this is not supported by evidence 3, 4
- Recognize that FOBT has inherently poor sensitivity (only 37.1% for non-rehydrated Hemoccult II), meaning many cancers will be missed even with proper testing 5