The antimegaloblastic effect of cooked folic acid-fortified maize meal was tested by feeding the meal to 5 lactating patients with folate-deficient megaloblastic anaemia. The dose of folic acid in the meal before cooking varied from 100 to ·500 µg daily. One patient who received 100 µg daily had a suboptimal haematological response. Meal containing 300 µg and 500 µg daily produced optimal haematological response in all 4 patients so treated, and there was no secondary reticulocyte response in the 2 patients subsequently given pharmacological doses of folic acid. It is concluded that the fortified meal after cooking is an effective antimegaloblastic agent.S. Afr. Med. J., 48, 1795 (1974)

Colman, N.

Green, R.

Metz, J.

Stevens, K.

English

AJOL - African Journals Online

3l AlIgllstus 1974 S.-A. MEDIESE TVDSKRIF 1795Prevention of Folate Deficiency by FoodFortificationVI. THE ANTIMEGALOBLASTIC EFFECT OF FOLICACID-FORTIFIED MAIZE MEALN. COLMAN, R. GREEN, K. STEVENS, J. METZSUMMARYThe antimegaloblastic effect of cooked folic acid-fortifiedmaize meal was tested by feeding the meal to 5 lactatingpatients with folate-deficient megaloblastic anaemia. Thedose of folic acid in the meal before cooking varied from100 to ·500 p..g daily. One patient who received 100 p..gdaily had a suboptimal haematological response. Mealcontaining 300 p..g and 500 p..g daily produced optimalhaematological response in all 4 patients so treated, andthere was no secondary reticulocyte response in the 2patients subsequently given pharmacological doses offolic acid. It is concluded that the fortified meal aftercooking is an effective antimegaloblastic agent.S. Afr. Med. J., 48, 1795 (1974).There is much interest in food fortification to preventnutritional deficiencies. As maize, which is poor in folate,lis a staple item of the diet of millions of people indeveloping countries, and as folate deficiency is commonin these peoples, we are investigating the use of folicacid-fortified maize meal (FAMM) in the prevention offolate deficiency. Feeding FAMM to pregnant subjectsresults in a rise in the Lactobacillus casei folate activityin their serum and red cells.' This indicates that theFAMM provides a form of folate which can be utilisedby bacteria, but while this is suggestive, it does not provethat this folate is biologically available to man. For thisreason, the efficacy of FAMM as a therapeutic agent inpatients with folate-deficient megaloblastic anaemia hasbeen evaluated.PATIENTS AND METHODSThe antimegaloblastic effect of the cooked meal wastested by means of a conventional therapeutic trial carriedDepartment of Haematology, School of Pathology, SouthAfrican Institute for Medical Research, and University ofthe Witwatersrand, JohannesburgN. COLMANR. GREENK. STEVENSJ. METZDate received: 26 April 1974.13out in 5 patients with folate-deficient megalobla ticanaemia. All were adult females who were admitted tohospital with severe anaemia occurring during lactation,and they continued to breast-feed throughout their stayin hospital. The mean period between parturition andadmission to hospital was 114 days (range 49 - 189 days).The laboratory findings on admission are summarised inTable I.On admission to hospital, the patients received theusual hospital diet for periods of 3 - 8 days until thediagnosis of folate deficiency was established by appro-priate laboratory investigations. The diet was free ofuncooked' green leafy vegetables and contained copiousquantities of maize meal. This diet did not inducehaematological response in patients with folate-deficientmegaloblastic anaemia, who were followed for periods ofup to 30 days.'"Patients 2 and 3, who were the most severely anaemic.were given transfusions of whole blood at the time ofadmission to hospital.After the diagnosis of folate deficiency had beenestablished, the maize meal in the hospital diet wassupplemented with the FAMM. The daily dose of folicacid added to the maize meal before cooking was 100 pgin the case of patient 1, 300 I~g in the case of patients2 and 3, and 500p..g in the case of patients 4 and 5.The maize meal was fortified with pteroylglutamic acid inproportions of one daily dose for each 30 g of maize meal(dry weight). The mixture was cooked in boiling waterfor 30 - 45 minutes to form a stiff paste, and was eatenwith the usual hospital meals each day. We have foundthat folic acid resists destruction by boiling in waterfor two hours:In patients 4 and 5, an attempt was made to elicita secondary reticulocyte response when the reticulocytecounts had returned to stable levels after feeding theFAMM. These patients were given 15 mg folic acidand 240 mg elemental iron (as ferrous sulphate) daily bymouth.Standard laboratory methods were used. Haemoglobin.cell counts and red cell indices were measured with aCoulter S counter. Serum folate'" and red cell folate'were assayed with L. casei, and serum vitamin RIOmeasured by a radio-isotope dilution method.'·['(96 S A. MEDICAL JOURNAL 31 August 1974TABLE I. RESULTS OF HAEMATOLOGICAL INVESTIGATIONS IN 5 PATIENTS ON ADMISSION TO HOSPITAL (IN ALLPATIENTS THE BLOOD SMEAR. SHOWED OVAL MACROCYTES AND HYPERSEGMENTED NEUTROPHILS, AND THE BONEMARROW WAS MEGALOBLASTIC)The daily red cell and reticulocyte counts of the 5 patientsare depicted graphically in Figs I - 5. None of the patientshad a reticulocyte response while receiving the hospitaldiet only, but all showed haematological response afterfeeding with FAMM. In order for a haematologicalresponse in a patient with megaloblastic anaemia to berated as optimal, three criteria should be satisfied, viz.the reticulocyte peak should occur between days 5 and8," reach certain levels," and the red cell count mustrise at a specified rate." The height of the reticulocytepeak and the rate of rise in red cell count are relatedto the severity of anaemia. According to these criteria,all the patients in the present study showed an optimalresponse, except for patient 1 who received the lowestdose of folic acid in FAMM (100 ,ug/day). In this patientthe height of the reticulocyte peak and the rate of risein the red cell count were suboptimal.Neither of the 2 patients who received pharma-cological doses of folic acid and iron showed a secondaryreticulocyte response, after the initial response to theFAMM.Four patients were thrombocytopenic at the start ofthe trial, and all had normal platelet counts by day 8.The single patient with a leucoPenia on day 0 had anormal white cell count on day 3 of the trial.Meal containing 1000gPGA doilyPatient No.2 3 4 53,4 3,7 5,1 4,40,79 1,00 1,25 1,2510,1 11,8 15,3 13,7128 118 122 10743,0 37,0 40,8 34,433,7 31,4 33,3 32,15000 2700 9800 740040000 54000 85000 1880002,8 0,6 1,0 3,41,0 1,2 0,6 0,6100 116 12 84134 216 195 241175 57 77 31505 554 1205 10684565 3110 2490 2630~'E<: 'it-~ ..0 Clu >.uCi 0"3u.~-c "iCl Ql:Ql:5 50Haemoglobin (g/100 ml) ...Red cell count (million/,ul)Haematocrit (%)Mean cell volume (,urn') ...Mean cell haemoglobin (pg)Mean cell haemoglobin concentration (0{,)Leucocyte count/,ul ...Platelet count/,uLReticulocyte count (%)Serum folate (ng/ml) ...Red cell folate (ng/ml)Serum iron (,ug/loo ml)Serum unsaturated iron-binding capacity (,ug/l00ml)Serum vitamin B I2 (pg/ml) (normal range 400-1 020 pg/mI) ...Serum lactic dehydrogenase (units) (normal range90 - 200)RESULTS4,71,3015,311836,230,74800300003,00,7488612740261303240302010/ -~ ,, ,I , ,,, ,, ,,,, ,,, ,,,,, \,, ,,\- ......,,-,-5 0 5 10 15DISCUSSIONNone of the patients in the present study showed a risein reticulocyte count during the period in hospital beforeDaysFig. 1'. Reticulocyte response (broken line) and rise in redcell count (solid line) in a patient with folate-deficientmegaloblastic anaemia after eating maize meal fortifiedwith lOO /lg folic acid/day.31 Augustus 1974 S.-A. MEDIESE TYDSKRIF 1797DoysFig. 2. Reticulocyte response (broken line) and rise in redcell count (solid line) in a patient with folate-deficientmegaloblastic anaemia after eating maize meal fortifiedwith 300 /lg folic acid/day. 201515mg PGA+240mg iron10.,\,,,,,-- -... .......,5,", .,, ,, ,, I,.,I,,,,Meal containing SOOugPGA dailyo~--......../',I,I,,,_-- "'1-4~·e <f?.~'E 4>:> >.0 uu .E:>"'ii .~v 'i"tl '"Cl 60-er:5 50-4 403 302 20102015"-. - --...105. Meal containing 300ugPGA daily,-'. 'o,'....... _---650 Bloodl!....>..uo"5.!!..'"102 203 30"tlCl'"DaysFig. 3. Reticulocyte response (broken line) and rise in redcell count (solid line) in a patient with folate-deficientmegaloblastic anaemia after eating maize meal fortifiedwith 300 /lg folic acid/day.~::::-'E'E ~..:> •0 >.u v.. .E:>v ~ Meal containing 300ug1 'iGl: PGA dailyGl:6 60 Blood11110 504 403 30DaysFig. 4. Reticulocyte response (broken line) and rise in redcell count (solid line) in a patient with folate-deficientmegaloblastic anaemia after eating maize meal fortifiedwith 500 /lg folic acid per day. There was no secondaryreticulocyte response to pharmacological doses (IS mg/day)of folic acid.they received FAMM. This is in accord with previousexperience with the hospital diet;·, which contains in-sufficient amounts of folate to induce a haematologicalresponse.Patient 1, in whom the haematological response wassuboptimal, received FAMM containing 100 p.g folicacid daily before it was cooked. Failure to induce optimalhaematological response reflects the fact that this doseis inadequate to meet the folate requirement of thelactating patient, which has been estimated to be approxi-mately 300 j.Lg/day."The failure to induce a secondary reticulocyte responsewith pharmacological doses of folic acid in the 2 patientsso studied (Nos. 4 and 5) is further evidence of the optimalnature of the response induced by the FAMM containing500 j.Lg folic acid daily.In patients 2 and 3, the therapeutic trial followed theadministration of blood transfusions. It has been suggestedthat transfusions may induce a 'spontaneous' responsein a patient with megaloblastic anaemia." However, in aprevious study, 3 lactating patients with folate-deficientmegaloblastic anaemia who were transfused did not havereticulocyte responses when followed for periods of upto 17 days!The results of these trials indicate that cooking folicacid in the presence of maize meal does not alter itsbiological efficacy as an antimegaloblastic factor in man.15105'.I'I .,I ,/_... \,I ,'--IIIo-8 -510202We wish to thank Professors H. C. Seftel, F. Segal, and DrA. Dubb and their staff for their assistance and for their per-mission to study the patients under their care; and Mr M.Kaplan of Upjohn (Pty) Lld who prepared the fortified meal.Due acknowledgement is made to the South African MedicalResearch Council and the Atomic Energy Board for assistanceand support enabling the research to be undertaken.Fig. 5. Reticulocyte response (broken line) and rise in redcell connt (solid line) in a patient with folate-deficientmegaloblastic anaemia after eating maize meal fortifiedwith 500 fJ.g folic acid per day. There was no secondaryreticulocyte response to pharmacological doses (15 mgjday) of folic acid.S.A. MEDICAL JOURNALIMeal containing SOOug PGAJ'dail31 August 19742. Colman, N., Barker, M., Green, R. and Metz, J. (1974): AIDer. J.C1in. Nutr., 27, 339.3. Metz, J. (1959): M.D. thesis, University of the Witwatersrand,Johannesburg.4. Stevens, K. (1964): M.D. thesis, University of the Witwatersrand,Johannesburg.5. Baurnslag, N. and Metz, J. (1964): S. Afr. Med. J., 38, 611.REFERENCES1. Metz, J., Lurie, A. and Konidaris, M. (1970): S. Afr. Med. 1., 44,539.12. Sturgis, C. C. and Isaacs, R. in Downey, H., ed. (1938): Handbookof Haematology. vol. 3, p. 2231. London: Hamish Hamilton.13. Bethell, F. H. (1935): Personal communication - quoted by Sturgisand Isaacs.].26. Colman, N., Green, R. and Metz., J: Unpublished data.7. Waters, A. H. and Mollin. D. L. (1961): J. Clin. Path., 14, 335.8. Herbert, V. (1961): J. Clin. Invest., 40, 81.9. Hoffbrand, A. V., Newcombe, B. F. A. and Mollin, D. L. (1966):J. Clin. Path .• 19, 17.10. Green, R., Newmark, P. A., Musso, A. M. and MoUin, D. L.(1974): Brit. J. Haemat., 27, 507.11. Chanarin, I. (1969): The Megaloblastic Anaemias. Oxford: Black-well Scientific Publications.14. Metz, J. (1970): AIDer. J. Clin. Nutr., 23, 843.15. Herbert, V. (1963): New Engl. J. Med., 268, 201.201515mg PGA+240mg iron--- - ........ _---- -10Days,,,,.,5", \I ,I ,. ,. ,.//.I.IIo------"-31798~.-EC If::>Cl0u"&Cl ..Qu ::>""tl.~Cl QitJ< 0<5 504 403 302 2010

Prevention of folate deficiency by food fortification

The antimegaloblastic effect of cooked folic acid-fortified maize meal was tested by feeding the meal to 5 lactating patients with folate-deficient megaloblastic anaemia. The dose of folic acid in the meal before cooking varied from 100 to 500 µg daily. One patient who received 100 µg daily had a suboptimal haematological response. Meal containing 300 µg and 500 µg daily produced optimal haematological response in all 4 patients so treated, and there was no secondary reticulocyte response in the 2 patients subsequently given pharmacological doses of folic acid. It is concluded that the fortified meal after cooking is an effective antimegaloblastic agent.S. Afr. Med. J., 48, 1795 (1974)

Prevention of folate deficiency by food fortification

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online

AJOL - African Journals Online