Folate Assays Are No Longer Useful as Screening Tests for Malabsorption Syndrome. Now, Iron and B12 Deficiency Are More Common Than Folate Deficiency in Adults with Untreated Celiac Disease.
Authors: Shojania A. Majid 
Published: April 2020

In the past, before immunological tests for celiac disease became available, many authors advocated the use of red cell folate (RFA) as a screening test for celiac disease. That is, if the red cell folate were normal, then celiac disease was considered very unlikely. Low red cell folate was found in all 24 cases of celiac disease reported by Hoffbrand et al (J Clin Pathol1966;19:17–28). Since Patients with celiac disease and tropical sprue absorb the folic acid used in the fortification of grain products much better than folate polyglutamates present in food, I decided to investigate whether serum or red cell folate is still useful for screening malabsorption syndrome.

Methods: Serum folate (SFA) and red cell folate at St. Boniface General Hospital (SBGH) were determined by L. Casei microbilogical assay. During the 30-month period of July 1,1999 – Dec 31, 2001, the search of Laboratory Information System (LIS) at SBGH, revealed 29 patients with strong laboratory evidence of celiac disease (strongly positive gliadin antibody with positive endomysial and or t-transglutaminase antibodies) who also had SFA or RFA results. LIS was searched for the results of complete blood count (CBC), SFA, RFA, serum ferritin (SFer) and serum B12 (SB12).

Results: Five out of 29 patients (17.2%) with laboratory evidence of celiac disease had low SFA. Of these 5 patients with low SFA, 4 also had RFA. Only one of these 4 with low SFA had a low RFA. Eleven of the 29 patients also had RFA and only 2 of these 11 (18%) had low RFA. One of the two with low RFA had a normal SFA; and the other had a low SFA, a low SB12 and a low SFer. Twelve of 29 (41.3%) with celiac disease had low SFer and 6 of 29 (20.6%) had low SB12. Four out of 29 (13.8%) had high mean corpuscular volume (MCV)(&gt; 98 fL). All of the four with high MCV had normal RFA, but had low SB12, indicating that macrocytosis in these 4 cases was due to B12 deficiency. Ten out of 12 with low serum ferritin had low MCV (&lt;80 fL).

Discussion: The mandated fortification of grain products in USA and Canada (0.14 mg of folic acid per 100 g of grain) was estimated to add about 0.1 mg of folic acid to the daily folate intake of the average adult. However, some studies have shown that the actual increase in daily folate intake, through folic acid fortification, is about 0.2 mg (J Nutr2002;132:2792–8 and Am J Clin Nutr2003;77:221–5). Patients with celiac disease or tropical sprue can absorb this folic acid much better than the folate polyglutamates present in food. Sheehy et al (Blood1961;18:623–36) have demonstrated that many patients with tropical sprue who had developed folate deficiency megaloblastic anemia, despite consuming more than 1 mg of food folates daily, responded to as little as 0.025 mg of folic acid daily. It is for this reason than most of our celiac patients had normal serum folate but were either iron deficient or B12 deficient. In the past, B12 deficiency was considered to be uncommon in untreated adults with celiac disease.

Conclusion: As the result of fortification of grain products with folic acid, red cell folate is no longer a useful test as a screening test for malabsorption syndrome. Now, as our data demonstrate, B12 deficiency is more common than folate deficiency in adults with untreated celiac disease. A patient with celiac disease and macrocytic anemia is more likely to be B12 deficient than folate deficient.