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.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3738-3738
Author(s):  
A. Majid Shojania
Keyword(s):  
Celiac Disease ◽  
Folic Acid ◽  
Folate Deficiency ◽  
Tropical Sprue ◽  
Malabsorption Syndrome ◽  
Folate Intake ◽  
Serum Folate ◽  
Red Cell ◽  
B12 Deficiency ◽  
Grain Products

Abstract 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)(> 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 (<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.

Folate Assays Are No Longer Useful Diagnostic Tools in Medical Practice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3739-3739
Author(s):  
A. Majid Shojania ◽  
Kenneth von Kuster
Keyword(s):  
Celiac Disease ◽  
Medical Practice ◽  
Medical Records ◽  
Folate Deficiency ◽  
The Other ◽  
Deficiency Anemia ◽  
Red Cell ◽  
B12 Deficiency ◽  
The Mean ◽  
Low Serum

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.

Folate Intake of Older Adults Before and After Fortification of Grain Products

2007 ◽  
Vol 68 (4) ◽  
pp. 218-220 ◽  
Author(s):  
Judy DeWolfe
Keyword(s):  
Older Adults ◽  
At Risk ◽  
Folic Acid ◽  
Folate Intake ◽  
Serum Folate ◽  
Convenience Sample ◽  
Dietary Folate ◽  
Before And After ◽  
Grain Products ◽  
Age Range

Purpose: To determine whether fortification allowed older adults in the Kingston, Frontenac, and Lennox & Addington (KFL&A) Public Health area to obtain adequate amounts of food folate, and the proportion at risk of consuming more than the upper limit (UL) of folic acid (1,000 mcg). Methods: Dietary intake of a convenience sample of 103 healthy, active older adults (age range: 65 to 95 years) was measured using three 24-hour recalls. Dietary folate preand post-fortification was estimated. Results: Mean dietary folate increased from pre- to postfortification, but 43.4% of women and 20% of men still consumed less than the Estimated Average Requirement of 320 mcg dietary folate equivalent. No intakes exceeded the UL. Participants whose diet met grain products and vegetable and fruit recommendations of Canada's Food Guide to Healthy Eating consumed significantly more folate. Conclusions: Despite fortification, some older adults in the KFL&A area may not be obtaining enough folate to meet their nutritional needs, and may be at risk for health problems associated with folate deficiency. However, without concomitant serum folate measurements, the proportion is not known. Dietitians need to continue promoting foods naturally rich in folate, along with folic acid-fortified foods. While none of the older adults consumed more than the UL, some could exceed this amount if folic acid supplements were added to a folic acid-rich diet.

Reticulocyte Folate Concentration: A Tool To Monitor Immediate Folate Availability

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4655-4655
Author(s):  
Peter J. Miller ◽  
Elizabeth B. Agnew ◽  
Mary Ann Knovich ◽  
Andrew M. Farland ◽  
Johanna Waldron ◽  
...  
Keyword(s):  
Folic Acid ◽  
Magnetic Beads ◽  
Conflicts Of Interest ◽  
Binding Protein ◽  
Megaloblastic Anemia ◽  
Folate Deficiency ◽  
Serum Folate ◽  
Red Cell ◽  
Folate Binding Protein ◽  
Folate Concentration

The utilization of folic acid during erythropoiesis is widely known and accepted in medical literature and deficiency is known to cause a characteristic megaloblastic anemia resulting from the inhibition or ineffective synthesis of DNA. Although the resultant megaloblastic anemia may take considerable time before evidence or symptoms present, there are more acute changes visualized on peripheral smear that are representative of a functional folate deficiency. In addition to erythrocyte macrocytosis, hypersegmentation of neutrophils can also be seen. Often times, despite these visualized changes measurement of serum folate and/or total red cell folate yields a result within the accepted “normal” range of the assay. It has been demonstrated that these visualized characteristics represent a functional folate deficiency and can be overcome with folic acid supplementation regardless of the measured folic acid levels indicating a yet to be understood mechanism of folate utilization. Here, we sought to measure the folic acid levels in the earliest erythrocyte progenitors in peripheral circulation, the reticulocytes. Methods Reticulocytes were isolated using anti-CD71 (the transferrin receptor) coated magnetic beads. After separation, a sample slide was made utilizing methylene blue for visual confirmation of reticulocyte isolation. The reticulocytes were then lysed with citric acid and a Nanodrop-1000 spectrophotometer was used to determine absorbance at 413 nanometers. This absorbance was used to determine the sample hemoglobin concentration from a simple calibration curve. The sample folic acid level was then determined using the lysing method utilizing mouse monoclonal anti-folate binding protein, paramagnetic particles coated in anti-mouse IgG, human serum albumin and milk folate binding protein. Results were calculated as nanogram of folate per gram of hemoglobin. Results Twenty-five samples from normal individuals, not taking folate supplements, were analyzed. The range of results was 2.51 to 17.38 with a mean level of 9.61. Conclusion This protocol effectively and efficiently allows for isolation of reticulocytes in numbers high enough for measurement of folate in nanogram per gram of hemoglobin. By this method we show the normal reticulocyte folate level to be approximately 3-15 ng/g of Hgb. This figure is consistent with the normal red cell folate concentration. Further analysis is planned for comparing these results in patients with a suspected functional folate deficiency but “normal” red cell folate levels. Efficient isolation of reticulocytes and measurement of folate levels will allow us to probe the underlying cause of acute folate deficiency seen in very sick patients. Disclosures: No relevant conflicts of interest to declare.

Folate Nutritional Status among Psoriasis Patients not Exposed to Antifolate Drug

2020 ◽  
Vol 16 (4) ◽  
pp. 543-553
Author(s):  
Luciana Y. Tomita ◽  
Andréia C. da Costa ◽  
Solange Andreoni ◽  
Luiza K.M. Oyafuso ◽  
Vânia D’Almeida ◽  
...  
Keyword(s):  
Folic Acid ◽  
Linear Regression ◽  
Multiple Linear Regression Model ◽  
Folate Intake ◽  
Serum Folate ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Folic Acid Fortification ◽  
Plasma Folate ◽  
Psoriasis Severity

Background: Folic acid fortification program has been established to prevent tube defects. However, concern has been raised among patients using anti-folate drug, i.e. psoriatic patients, a common, chronic, autoimmune inflammatory skin disease associated with obesity and smoking. Objective: To investigate dietary and circulating folate, vitamin B12 (B12) and homocysteine (hcy) in psoriatic subjects exposed to the national mandatory folic acid fortification program. Methods: Cross-sectional study using the Food Frequency Questionnaire, plasma folate, B12, hcy and psoriasis severity using the Psoriasis Area and Severity Index score. Median, interquartile ranges (IQRs) and linear regression models were conducted to investigate factors associated with plasma folate, B12 and hcy. Results: 82 (73%) mild psoriasis, 18 (16%) moderate and 12 (11%) severe psoriasis. 58% female, 61% non-white, 31% former smokers, and 20% current smokers. Median (IQRs) were 51 (40, 60) years. Only 32% reached the Estimated Average Requirement of folate intake. Folate and B12 deficiencies were observed in 9% and 6% of the blood sample respectively, but hyperhomocysteinaemia in 21%. Severity of psoriasis was negatively correlated with folate and B12 concentrations. In a multiple linear regression model, folate intake contributed positively to 14% of serum folate, and negative predictors were psoriasis severity, smoking habits and saturated fatty acid explaining 29% of circulating folate. Conclusion: Only one third reached dietary intake of folate, but deficiencies of folate and B12 were low. Psoriasis severity was negatively correlated with circulating folate and B12. Stopping smoking and a folate rich diet may be important targets for managing psoriasis.

scholarly journals Epidemiology and (Patho)Physiology of Folic Acid Supplement Use in Obese Women before and during Pregnancy

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 331
Author(s):  
Melissa van der Windt ◽  
Sam Schoenmakers ◽  
Bas van Rijn ◽  
Sander Galjaard ◽  
Régine Steegers-Theunissen ◽  
...  
Keyword(s):  
Folic Acid ◽  
Scientific Evidence ◽  
Folate Deficiency ◽  
Folate Intake ◽  
Low Grade ◽  
Obese Women ◽  
Folic Acid Supplement ◽  
Physiological Uptake ◽  
Supplement Use ◽  
Acid Supplement

Preconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status, lifestyle, and medical conditions.

scholarly journals Aleurone flour increases red-cell folate and lowers plasma homocyst(e)ine substantially in man

2005 ◽  
Vol 93 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Michael Fenech ◽  
Manny Noakes ◽  
Peter Clifton ◽  
David Topping
Keyword(s):  
Folic Acid ◽  
Folate Intake ◽  
Red Cell ◽  
Healthy Individuals ◽  
Free Living ◽  
Folate Status ◽  
Placebo Tablet ◽  
Wet Weight ◽  
Baseline Values ◽  
Randomised Controlled

Aleurone flour (ALF) is a rich source of natural folate (>500 μg/100 g wet weight). Our objective was to establish whether intake of ALF in man can significantly improve folate status and reduce plasma homocyst(e)ine. We performed a randomised, controlled intervention, of 16 weeks duration, in free-living healthy individuals (mean age 46–52 years). Participants were assigned to one of three groups: ALF, 175 g bread made with ALF and placebo tablet each day; PCS, 175 g bread made with pericarp seed coat (PCS) flour and placebo tablet each day (low-folate control); or FA, 175 g bread made with PCS flour and tablet containing 640 μg folic acid each day (high-folate control). The daily folate intake contributed by the bread and tablet was 233 μg in the PCS group, 615 μg in the ALF group and 819 μg in the FA group. The number of participants completing all phases of the PCS, ALF and FA interventions was twenty-five, twenty-five and eighteen, respectively. Plasma and red-cell folate increased significantly (P<0·0001) and plasma homocyst(e)ine decreased significantly (P<0·0001) in the ALF and FA groups only. Plasma folate and red-cell folate in the ALF group (mean, 95 % CI) increased from baseline values of 12·9 (9·9, 15·7) nmol/l and 509 (434, 584) nmol/l to 27·1 (22·5, 31·7) nmol/l and 768 (676, 860) nmol/l, respectively. Plasma homocyst(e)ine in the ALF group decreased from 9·1 (8·2, 10·0) μmol/l at baseline to 6·8 (6·2, 7·5) μmol/l after 16 weeks. In conclusion, moderate dietary intake of ALF can increase red-cell folate and decrease plasma homocyst(e)ine substantially.

scholarly journals A Novel Review of Homocysteine and Pregnancy Complications

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Chuce Dai ◽  
Yiming Fei ◽  
Jianming Li ◽  
Yang Shi ◽  
Xiuhua Yang
Keyword(s):  
Folic Acid ◽  
Pregnancy Complications ◽  
Methylenetetrahydrofolate Reductase ◽  
Normal Pregnancy ◽  
Positive Outcome ◽  
Mthfr Gene ◽  
Folate Intake ◽  
Daily Diet ◽  
B12 Deficiency ◽  
Work Done

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

scholarly journals Severe folate deficiency anemia associated with the use of a PARP inhibitor (olaparib) in a patient with fallopian tube cancer

2018 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Binoy Yohannan ◽  
Kristi McIntyre ◽  
Mark Feldman
Keyword(s):  
Folic Acid ◽  
Fallopian Tube ◽  
Complete Blood Count ◽  
Parp Inhibitor ◽  
Folate Deficiency ◽  
Serum Folate ◽  
Deficiency Anemia ◽  
Folic Acid Deficiency ◽  
Fallopian Tube Cancer ◽  
Increased Risk

Treatment of cancer patients with olaparib (PARP inhibitor) is associated with an increased risk of anemia, which is seen in a majority of treated patients. However, symptomatic anemia requiring transfusion is rare. Olaparib-induced anemia can be secondary to bone marrow suppression, hemolysis or folate deficiency. We report a case of new onset severe folic acid deficiency anemia in a patient with breast and relapsed fallopian tube cancer being treated with olaparib. Complete blood count on admission showed a hemoglobin of 4.2 g/dl and serum folate was undetectable (< 1.6 ng/ml; reference range 7-31.4 ng/ml). This is the second report of olaparib-induced folate deficiency anemia. She received three units packed red cell transfusion and parenteral folic acid supplementation and improved symptomatically. This case highlights the importance of recognizing folate deficiency as a reversible cause of anemia with PARP inhibitor therapy.

An underinvestigated toxicity of sunitinib: Red cell macrocytosis.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 371-371
Author(s):  
D. J. Hands ◽  
B. Eccles ◽  
T. R. Geldart
Keyword(s):  
Kinase Inhibitor ◽  
Haematological Toxicity ◽  
Significant Proportion ◽  
Case Series ◽  
Folate Deficiency ◽  
Serum Folate ◽  
Red Cell ◽  
Contributing Factors ◽  
Duration Of Treatment ◽  
Mean Cell Volume

371 Background: Sunitinib, a multitargeted receptor tyrosine kinase inhibitor represents a standard firstline therapy for advanced renal cell carcinoma. Red blood cell (RBC) macrocytosis (with or without anaemia) is a recognized haematological toxicity but its aetiology remains uncertain. Methods: The medical records of 73 patients (55 male, 18 female) patients treated with sunitinib between 2007 and 2010 at Poole and Bournemouth NHS Trusts, UK were reviewed. Patient demographics, length of treatment, response, RBC mean cell volume (MCV) indices, and known causes of macrocytosis including B12 and folate deficiency and hypothyroidism were examined. Results: Median duration of treatment was 6 months (range 0-30). 38 (51%) have died. 24 (32%) received 2 or less cycles of treatment with the majority stopping due to early progression or death. 30 patients (41%) developed macrocytosis on treatment, but a trend to macrocytosis was identified in most patients positively correlating to time on treatment. 26 (87%) had a macrocytic anaemia. Median time to onset of macrocytosis was 4 months (range 1-11 months). Of the 30 macrocytic patients; 5 were hypothyroid, 7 had untreated borderline hypothyroidism and 13 were euthryoid throughout. Of patients tested to date 1 patient was found to be serum folate deficient at 2.5 ug/L (3-17). Supplementation corrected the macrocytosis. 1 patient was found to be serum B12 deficient; 53 ng/L (180-900) without any obvious comorbid cause. Further retrospective evaluation of other parameters such as red cell folate and reticulocyte count are currently being carried out. Conclusions: A significant proportion of patients on sunitinib (41%) develop macrocytosis. On the basis of this case series, the largest to date, underlying causes of macrocytosis (with or without anaemia) appear multifactorial. Biochemical hypothyrodism is common following sunitinib treatment and is likely to represent one of several possible contributing factors. B12 and folate deficiency should not be forgotten as a potentially reversible cause of macrocytosis secondary to sunitinib. C-kit inhibition by sunitinib is a potential mechanism, paralleling the potential C-kit mediated macrocytosis commonly recognised in imatinib therapy. No significant financial relationships to disclose.

scholarly journals Absorption of Physiologic Doses of Folic Acid in Subjects with Tropical Sprue Responding to Tetracycline Therapy

Blood ◽  
1969 ◽  
Vol 34 (2) ◽  
pp. 191-203 ◽  
Author(s):  
FREDERICK A. KLIPSTEIN
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Day Treatment ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Tropical Sprue ◽  
Response To Therapy ◽  
Serum Folate ◽  
Fecal Excretion ◽  
Hematologic Response

Abstract The response to therapy with oral tetracycline has been assessed in three subjects with tropical sprue, all of whom presented with a megaloblastic anemia due to combined folate and vitamin B12 deficiency, and all of whom were shown to have normal absorption prior to treatment of a physiologic dose of 25 µg. of folic acid, as tested by assay of the fecal excretion of a tritium-labeled test dose. Treatment was associated with clinical and intestinal improvement and a hematologic response in all three subjects. The serum folate concentration rose to normal in one subject and the absorption of a pharmacologic dose of folic acid was normal when tested by microbiologic assay at the termination of the 20 day treatment period in all three. In contrast, both the absorption and serum concentrations of vitamin B12 remained subnormal. These observations confirm the fact that folate deficiency can be present in some subjects with tropical sprue in whom the absorption of a physiologic dose of folic acid is normal. They suggest that in this circumstance folate repletion and the hematologic response secondary to tetracycline therapy in tropical sprue is mediated by a factor other than the absorption of crystalline folic acid; it is likely that this factor is increased absorption of dietary polyglutamate forms of folate.

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