Does oral iron cause false-positive stool guaiac test?

The general agreement in the literature is that oral iron supplementation does not cause a false-positive guaiac-based fecal occult blood test (GFOBT).

GFOBT is based on rapid oxidization of α-guaiaconic acid to “guaiacum blue”, with hemoglobin serving as a catalyst through a non-enzymatic or “pseudoperoxidase” action. Although in vitro Fe3+ may serve as an oxidizing agent, this reaction is possible only under acidic conditions not found in the stool (pH ≥ 6-7)1.  Also, in the absence of a catalyst, Fe3+ alone would not be expected to cause rapid (within 30 seconds) conversion of α-guaiaconic acid to guaiacum blue1

Although a number of earlier clinical studies reported false-positive GBFOBT because of oral iron supplementation, subsequent investigations have uniformly failed to confirm these findings2. Potential reasons for earlier false-positive GBFOBT results include false interpretation of the color change—eg, green instead of blue— particularly when the discoloration is weakly positive, and non-standardized method of stool collection with the possibility of stool sample contamination by toilet water.

Other fascinating facts: Did you know that guaiac plant extract was used for centuries for treatment of syphilis and that the earliest application of guaiac testing was in forensic medicine in 1800s?


  1. McDonnell WM, Ryan JA, Seeger DM, Elta GH. Effect of iron on the guaiac reaction. Gastroenterology. 1989 Jan;96(1):74-8.
  2. Anderson GD, Yellig TR, Krone RE. An investigation into the effects of oral iron supplementation on in vivo hemoccult stool testing. Am J Gastroenterol 1990;85:558-561.

Contributed by Brian Li, Medical Student, Harvard Medical School

Does oral iron cause false-positive stool guaiac test?

How should I interpret a positive Treponema serology by enzyme immunoassay (EIA) in my elderly patient with dementia?

A positive EIA treponema-specific test (e.g. Trep-Sure) suggests either current or prior syphilis.  It should be followed by an RPR to better assess disease activity (1).  If the RPR is positive, syphilis can be assumed and further evaluation for neurosyphilis with lumbar puncture may be necessary in this elderly patient with neurological symptoms.

If the RPR is negative, a more specific treponema test (e.g. fluorescent tryponemal antibody [FTA], or  Treponema pallidum particle agglutination [TP-PA]) should be performed for confirmation of the treponema-specific test (1). 

Recall that the treponema-specific antibody tests by EIA  are much more sensitive and specific than RPR, especially during the primary and late stages of syphilis.   Also remember that serum RPR may be negative in about 30% of patients with neurosyphilis (2); so a negative serum RPR should not rule out neurosyphilis.

1. Binnicker MJ, Jespersen DJ, Rollins LO. Treponema-specific tests for serodiagnosis of syphilis: comparative evaluation of seven assays 2011;49:1313-1317.

2. Whitefield SG, Everett As, Rein MF. Case 32-1991;tests for neurosyphilis. N Engl J Med 1992;326:1434.

How should I interpret a positive Treponema serology by enzyme immunoassay (EIA) in my elderly patient with dementia?