Txansfus. Sci. 1992; 13:255-259 0955-3886192 $5.00+0.00 Printed in Great Britain. All rights reserved Copyright @ 1992 Pergamon Press Ltd

The Effect of Iron Depletion on the Mental Performance of Non-

anaemic Healthy Blood Donors Wayne Mackintosh, MB, MMedPath(Haem)*

Peter Jacobs, MB,PhDt

n The mental performance of 7 healthy non-anaemic but iron-depleted male blood donors was assessed psychometri- cally, both before and after iron replen- ishment, and compared with controls. Despite a sign&ant increase in body stores, as determined by serum ferritin, no deleterious effects of iron depletion on mental performance could be demons- trated in the test group or when com- pared with their normal counterparts. It remains possible that failure to show any difference may be related to the small numbers of subjects tested. n

INTRODUCTION

In an otherwise healthy male population the donation of multiple units of blood on an annual basis can lead to reduction in body iron stores, eventual depletion, and the subsequent emergence of hypochromic microcytic anaemia; iron status is known to depend on the fre- quency of donation rather than the cumulative total.1~2 Investigators in recent years have demonstrated a good correlation between serum ferritin con- centration and the size of body iron

From The University of Cape Town Leukaemia Centre and the Department of Haematolofl, Groote Schmu Hoapital, Obmvatory, Cape., South Africa. Received S/91; Accepted 9/91. ‘Resent addrem 102 Lancet Medical Center, 74, Lome sueet, Durban 4001, south Africa tAutho? to whom all correspondence should be addressed.

stores.334 The effects of iron deficiency are wide-ranging, both in human and animal studies; good evidence is avail- able that when iron deficiency is severe enough to cause anaemia, exercise toler- ance is impaired. 5~6 Rat studies have shown that there is a deterioration of physical performance under these cir- cumstances, not necessarily related to the level of haemoglobin but rather to the degree of iron deficiency.7-9 In a human study, productivity increased signi- ficantly when women workers on a tea plantation were given iron supplementa- tiOllj this improvement in performance occurred before there was a substantial rise in haemoglobin concentration and it was concluded that the beneficial effects of iron supplementation reflected a replenishment of tissue iron rather than a correction of anaemia.lO The effects of iron lack are not limited to skeletal muscle function since changes in behaviour have been reported in infants and young childrerPJ2 and this signi- ficantly improved by iron supplementa- tion in those with iron deficient erythro- poiesis but who were not yet anaemic.13

In view of these controversial obser- vations it was considered important to examine the mental status of male blood donors who, although maintaining a haemoglobin of at least 135 g/L, had minimal iron stores. This study was designed to test the hypothesis that a decrease in body iron stores could inter- fere with cerebral function when this was evaluated psychometrically; in addi-

256 Transfus. Sci. Vol. 13, No. 2

tion, anticipating this to be a possibility, to document any changes in the cogni- tive tests that followed replacement of body iron stores whilst haemoglobin levels remained unaltered. To exclude the placebo effect, control individuals starting off with normal iron stores were assessed under comparable conditions.

DONOR POPULATION

Healthy males who had each donated a minimum of 4 units of whole blood in the preceding 12 months volunteered for this study. All were asymptomatic adults who were assessed by a health question- naire completed immediately before the study and who fulfilled acceptable inter- national criteria for donation.14

The protocol was approved by the Ethics and Research Committee at the University of Cape Town and Groote Schuur Hospital, and participation required informed consent.

HAEMATOLOGIC STUDIES

Under standard conditions 5 mL of venous blood was collected into EDTA for haemoglobin estimation15 and from a further 10 mL haemoglobin-free serum was separated within 4 h of collection and stored at -20°C for subsequent determination of ferritin by radioimmu- noassay (Amersham Fe&tin Radioim- munoassay, Amersham, 1984).

TRIAL DESIGN

19 individuals (Group 1) with a haemo- globin above 135 g/L and a serum ferritin less than 20 clg/L were rando- mixed to receive either 100 mg elemental iron (Ferrimed DS chewable tablets. Hausmann Laboratories Inc., St Gallen, Switzerland) as ferric polymaltose twice daily with meals (Group la; n=8) or an identical but iron-free placebo tablet (Group lb, II= 11) for 56 days, in a single blind study.

15 individuals (Group 2) with a com- parable haemoglobin but serum ferritin between 50 and 150 pg/L were simi-

larly randomized to the equivalent dose of the iron salt (Group 2a; n=7) or placebo (Group 2bj n=8).

Prior to taking oral iron or placebo each subject was required to complete 6 cognitive tests.

After the 56th day of therapy a repeat blood haemoglobin and serum ferritin was performed, as well as the same 6 cognitive tests at a similar time of day. The BMDP statistical package was used for the t-tests and the ANOVAS.*6J7

CONSTRUCTION OF THE 6 COGNITIVE TESTS

6 cognitive tests, prepared by Verster,‘* were used in this study. These were non- verbal but visual and were presented on an Apple IIe cathode-ray-tube display screen. Responses were recorded on a modified keyboard and no computer or typing skills were necessary for their completion. There was no time limit on the tests; the subject worked uninter- rupted and continuously at his own maximum speed.

Prior to starting each of the tests full instructions were displayed on the screen, followed by several practice examples, at which stage the subject could refer back to the screen instruc- tions if necessary. The tests were aimed at three cognitive levels, sensory, percep- tual and conceptual, with 2 tests for each comprising a variable number of items (Table 1).

Tests of lowest complexity were presented first, at each cognitive level and within each measurement. For the items, accuracy was measured in terms of right or wrong responses regardless of time taken, with subjects in some tests required to produce the correct response before being allowed to proceed to the next item. Speed was measured by the computer in terms of item-response latencies, to an accuracy of milliseconds. The time taken for each of the four subject groups to complete each test battery, as well as the number of errors, was compared with the values obtained after treatment, whether iron or placebo.

Iron Depletion and Mental Pafonrmrnee 257

Table 1. The Cognitive Tests

CogaWe Level Test Items

Sensory Intensity 50

Symbols 60

Perceptual Pattern Matching 50

Matrix Scarming 40

Description

2-choice luminosity intensity discrimination 3-choice symbol recognition

2-choice same-or-different pattern decision Search of 4 columns of figures for 2 specific numbers and a decision comment as to whether either, both or neither of the latter were found in the columns

Conceptual Analogy 25

Rule Induction 25

4-choice geometric analysis decision 9-choice geometric progression rule inference

6 non-verbal but visual tests were presented on an Apple IIe cathode-ray-tube display screen, aimed at three cognitive levels.

ANOVA was also carried out using the deficiency of iron or lack of deficiency and treatment with iron or non- treatment with iron (placebo) to create the variables for dividing the data. Stu- dent t-tests were performed with the experimental group la put against the three controls, namely, groups lb, 2a and 2b.

RESULTS (Table 2)

The donors with the lowest ferritin levels (Group la; n=8) responded to oral iron polymaltose, with an expansion in body iron stores reflected in an increase in serum ferritin (P=O.Ol J. In the corres- ponding group receiving placebo (Group lb; n=ll) there was a small but signi- ficant rise in serum ferritin (P= 0.05>P>O.O2), probably reflecting enhanced absorption of dietary iron. There was no sign&ant change in iron status in group 2a or group 2b. In none of the four groups did the marginal rise in haemoglobin achieve statistical signi- ficance (PaO.05).

The time taken for each group to complete the individual tests, as well as the number of errors, was compared with the pretreatment @ures; a positive dif- ference indicating an improvement and a

negative value a failure of benefit. No trend was demonstrable in the test group la when compared with the other three control groups; both positive and nega- tive values were randomly distributed throughout all four groups. The positive difference in group la, when present, did not vary significantly when compared to the other three groups. ANOVA, using iron deficiency or repletion and supple- mentation or placebo were similar for each variable before treatment in the four groups. However, on time taken to com- plete the tests, symbols and matrix scan- ning showed some significance of the amount of iron in the blood prior to treatment. The t-tests did not show any improvement between the experimental and control groups.

DISCUSSION

The object of the study was to determine whether decreased body iron stores inter- fered with cognitive function and, if so, whether the demonstrable psychometric effect could be reversed by replacing body iron stores with or without altering the haemoglobin level. The experimental group, la, with minimal iron stores, showed a sign&ant increase in serum ferritin. Psychometrically, however, no

258 Transfus. Sci. Vol. 13, No. 2

Table 2. The Effect of Iron or Placebo on Haemoglobin and Ferritin Levels

Group II Therapy Mean SD Mean SD t-value D.P. P-value Pre- Post-

Haemoglobin

la 8 + 14.38 0.88 15.11 0.67 -1.88 14 O.l>P>O.O5

lb 11 - 14.30 0.68 14.95 0.86 -1.97 20 O.l>P>O.O5

2a P>O.5

7 -I- 14.96 0.55 15.16 0.71 -0.59 12

2b 8 - 14.59 0.65 15.25 0.85 -1.77 14 O.l>P>O.O5

Ferritin

la 8 + 16.13 1.46 47.37 29.74 -2.97 14 P=O.Ol

lb 11 - 16.73 2.05 26.64 4.81 -2.20 20 0.05>P>O.O2

2a P>O.5

7 + 74.0 30.35 77.14 34.96 -0.18 12

2b P>O.S

8 - 67.63 33.58 70.63 47.18 -0.15 14

+ = oral iron replacement. - = placebo.

difference was documented by replace- ment therapy in these subjects, Three control groups were considered; group lb, like the experimental group la, had minimal iron stores and was treated with placebo, whilst groups 2a and 2b had normal ferritin and received polymaltose and placebo respectively in a single blind study. No significant psychometric dif- ference was documented in the control groups.

The number of test subjects is, unfortunately, too small and psychomet- ric differences might well have been missed; larger groups, as well as an alternative battery of tests, are needed to exclude any psychometric disadvantage of minimal iron stores in an otherwise healthy adult population.

The importance of a more compre- hensive study to the blood banking world

is considerable. Heavy reliance has to date been placed on an arbitrary haemo- globin level rather than the iron stores of blood donors as a minimum criterion for their disqualification and hence subtle degrees of psychometric morbidity might well be unrecognized. If such a disadvantage in higher cerebral function can be correlated with the possession of minimal iron stores, this knowledge will contribute positively to the ongoing dia- logue between the two opinions within the blood banking fraternity; on the one hand, there is a group advocating prophy- lactic iron therapy to speed the recovery of haemoglobin levels or maintain iron stores and in contrast there are those who maintain that blood donation is a wholly physiologic process, with any treatment therefore being inappropriate. The prac- tice of using the haemoglobin level as the

Iron Ih&tioa and Mental Pahmuance 259

sole determinant of blood donation cur- rently appears to be a reasonable crite- rion and only if additional information becomes available, suggesting that iron status is an independent variable which affects mental function, would this need to be considered further.

Acknowledgements

Council, the National Cancer Association and the Michael Chanani and Kaliski Bequests.

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