Folate Assays Are No Longer Useful Diagnostic Tools in Medical Practice.
Authors: Shojania A. Majid , von Kuster Kenneth 
Published: April 2020

Abstract
Since 1999, due to mandatory fortification of grain products with folic acid, folate deficiency has become very rare. We elected to find out whether there is still any justification in ordering folate assays in medical practice.
Methods: All the Red cell folates (RFA) at St. Boniface General Hospital (SBGH) for the period of January 1, 1996–Dec 31, 2001 and all of serum folates (SFA) and RFAs at Health Sciences Centre (HSC) for the period of January 1-December 31, 2001 were reviewed. The medical records of all patients who had low SFA or RFA were reviewed to find the cause of low folate results. At SBGH L. Casei microbiological assay and at HSC, a competitive binding assay of folates was used.
Results: Among 2153 SFAs performed at HSC 10 (0.46%) were below normal. All 10 were anemic but their SFAs were not as low as those seen in folate deficiency anemia. Only one case had a high mean corpuscular volume (MCV). This patient had ethanol induced pancreatitis and his macrocytosis was considered to be due to ethanol abuse. Two patients had celiac disease. In the other seven patients there was no evidence of folate deficiency anemia and no explanation could be found from the review of their medical records as to why their SFAs were low. Among 560 RFAs performed at HSC, 4 patients (0.7%) had low RFAs. In one case, the low RFA was due to B12 deficiency. The second case was the same patient with ethanol induced pancreatitis who also had low SFA. The other two had celiac disease. AT SBGH, there was a progressive increase in mean RFA and a decrease in percentage of those with low RFA during each year in the period between 1996 and 2001. In 1996 the mean RFA was 509 nmol/L and 95 out of 511 (18.5%) had low RFA. During the 3 year period of 1999–2001, the mean RFA was 947 nmol/L and 19 out of 991(1.6%) RFAs were low. Of these 19 patients, 9 were ethanol abusers with alcoholic liver disease, 7 had celiac disease, two had low RFA due to severe B12 deficiency and one was an AIDS patient who was admitted because of extreme malnutrition and had a low RFA, a low serum B12 (SB12) and a low serum ferritin. Of 7 patients with celiac disease, only one had had a high MCV.
Discussion: There are generally three reasons why physicians order folate assays. The most common reason is to detect folate deficiency as the cause of anemia. Our study shows that folate deficiency is now very rare. In none of the patients with low SFA or RFA could we attribute the anemia to folate deficiency. The second reason is for investigation of hyperhomocysteinemia. Since folate deficiency is now very rare and management of hyperhomocysteinemia is the same whether SFA or RFA are low or normal, having SFA or RFA result would not change the patient’s management. The third reason for ordering RFA is for screening for malabsorption syndrome. During 30 months period of July 1, 1999–December 31, 2001, the search of the Laboratory Information System at SBGH, revealed 29 patients with serological evidence of celiac disease, who also had SFA or RFA results. Of these 29, five had low SFAs and two had low RFAs.
Conclusion: We find very little support for the need to order serum or red cell folate in medical practice. In those rare occasions, when folate deficiency is suspected by the patient’s history or laboratory findings, it is simpler and more economical to treat the patient with folic acid (as long as one makes sure the SB12 is normal) than ordering folate assays and waiting for the results that most likely going to be normal.