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Psychological factors in iron absorption
Journal of Psychosomatic Research, 1959, Vol. 4, pp. 129 to 131. Pergamon Press Ltd. Printed in Northern Ireland
PSYCHOLOGICAL
FACTORS
IN IRON
ABSORPTION
I. C. LODGE PATCH, M.D.* THE absorption of iron is governed by many variables, as shown by the recent reviews of JOSEPHS (1958) and BOTHWELL et al. (1958). Amongst such factors, NORDENSEN et al. (1949) included the psychological, for in studying the absorption of different iron compounds, they examined their patients for the presence of ‘neurosis’. This seems to have been on empirical grounds, for neither criteria nor reasons are given, but they implied that their results might in some way be affected by this factor. Support for this view seems to come from the work of GRACE and DOIG (1954). These workers made twenty-six observations on a subject with a gastric fistula and found that ‘absorption (of iron) was optimal on days of good spirits, and below Such a claim merits further investigation, optimal on days of conflict and indecision’. since measurable metabolic changes which can be correlated with the mental state are few, but may have important implications. GRACE and DOIG give neither clinical nor technical details, but imply that their subject was psychiatrically normal, and that the mood changes were transient. Despite their importance, such observations are difficult to confirm on normal subjects, because different observers may easily disagree about the prevailing mood at a given time. It therefore seemed worth examining whether in a group of depressed patients, changes were present corresponding with those of GRACE and DOIG. In such patients one might reasonably expect the same psychophysical correlations as were present in a normal group. In addition, all could agree on the state of the mood at the time of the experiment, and the change after recovery would be unequivocal. Obviously such an experiment should be made on a group of patients. BOTHWELL et al. (1955) showed that investigation of iron absorption in a single case yielded no consistent results, and this criticism may be levelled at the study of GRACE and DOIG. In a group, however, these inconsistencies would tend to be eliminated, as BOTHWELL et al. agree. Such a study might show that the prevailing mental state was consistently related to iron absorption or that the relationship existed only where specific psychiatric features could be found. Finally, no evidence whatever might emerge in favour of such a relationship. MATERIAL The patients selected were a group of women, between the ages of 34 and 56, who were admitted to hospital suffering from depressive illnesses of moderate or great severity. Their illnesses varied from 1 month to 3 years in duration (average 13.7 months). Patients concurrently suffering from physical illnesses or minor infections were excluded from the series, and investigations were deferred during menstruation. Ultimately, however, no significant differences were found to exist between the post-menopausal and the younger group of women. METHOD The technique employed was that described by BOTHWELL and trial yielded results of an accuracy comparable with their own.
MALLETT (1955).
* Senior Registrar, Bethlem Royal and the Maudsley Hospitals, London S.E.5. 5-W
PP.)
129
A preliminary
130
I.C. LODGE PATCH
For 24 hr before the test no eggs were given, and milk was restricted to half a pint. No drugs were given on the day of the test, and in any case only barbiturate sedation on the previous days. Each patient was examined personally, in collaboration with the clinician responsible; the consistency of the depression was confirmed. The following morning, after a fasting specimen of blood had been taken (7.30 a.m.), a dose of ferrous sulphate (2 mg per kg body weight) was given, dissolved in half a glass of tap water. Specimens of blood were subsequently taken at 1, 3 and 5 hr after the dose, the patient remaining in bed and fasting throughout. The serum was later separated and refrigerated, the estimations being carried out within a few days. After recovery was complete, and shortly before discharge, the procedure was repeated: each patient thus served as her own control. On each occasion the haemoglobin was estimated: no correlations were found to exist between these levels and the nutritional status on the one hand, and the curves of iron absorption on the other. TABLE I.--SERUMIRON VALUES,MICROGRAMS, (FASTING 1,3 AND 5 HR SAMPLES), FOLLOWING AN ORAL DOSE 0F FERROUS~ULPHATE.ESTIMATIONS BEFOREANDAFTERRE~OVERY FROM DEPRESSION.
Pre-recovery 1 3 5 hr hr hr
Case
Age
F
(1) (2)
34 34 36 46 56 47 56 45 44 41 44
60 33 113 126 125 84 115 48 100 207 211
(3) (4) (5) (6) (7) (8) (9) (10) (11)
184 110 227 204 137 128 295 84 173 280 240
328 171 388 233 162 136 222 82 214 295 280
322 165 365 171 142 113 169 98 191 283 258
Post-recovery F 1 3 5 hr hr hr 66 12 183 75 57 18 151
170 147 217 132 147 86 241
234 412 294 225 136 148 211
219 425 265 245 122 141 164
RESULTS Table 1 presents the values of serum iron obtained in micrograms per 100 ml. In the last four cases, no ‘post-recovery’ test was carried out: examination of the earlier cases had already shown that nothing would be gained by a second test in those who followed. Because of the wide degree of variance, stabilization of these figures was carried out by taking their square roots. DISCUSSION
Examining the curves obtained, highly significant differences were found to exist between the fasting and the 1, 3 and 5 hr values, showing that the serum iron rose significantly in all cases after the oral dose (P < 0.01). A second analysis of variance was carried out to test whether differences existed between the ‘pre-recovery’ and the ‘post-recovery’ groups. This allowed the testing of possible interaction between the factors of recovery (pre- and post-) and of differences in the timing of samples. No significant differences were found to exist ; the patients behaved similarly, whether or not they were depressed. Comparing these findings with those of GRACE and DOIG it may be asked whether Their patient’s predominant symptoms were the mental state was comparable. In the present series, only case (2) ‘conflict and indecision’: these showed depression. showed a relationship similar to theirs, but she presented no clinical features unique
Psychological
factors
131
in iron absorption
in the series, although tension and anxiety were conspicuous.
The possibility that
specific symptoms, such as these, are related to differences in iron absorption, might be tested in patients with anxiety states. Otherwise, so far as these results apply to the finding of GRACE and DOUG, it seems that the relationship fact be due to a technical artefact.
they claim may in
250
0
I
2
3
4
5
hr Frc;.l.pCurves
of the mean values of strum iron from seven patients, recovery from depression.
before
and after
CONCLUSION In a group of depressed patients, no evidence was found that the levels of serum
iron, following
an oral dose, arc related to the mental state. The implications of
this finding arc discussed. ~cknow/ed~~~~enrs---l wish to thank examine
their cases,
the physicians at Bethlem Royal Hospital, who allowed me to Mr. A. E. MAXWELL for the statistical analysis and Mr. G. KING for technical
advice. REFERENCES BOTHWELLT. H., MALLETI. B., OLIVER R. and
SMITH M. D. (1955) Inability to assess absorption of iron from plasma radioiron curves. Brif. J. Haemafol. 1, 352. BOTHWELLT. H. and MAI.I.ETT B. (1955) The determination of iron in plasma or serum. Biochem. J.
59, 599. Bo-IHWELLT. H., PIRZIO-BIROLIG. and
FIXCH C. A. (1958) Iron absorption-l. Factors influencing Clin. Med. 51, 24. GRACE W. J. and DOUG R. K. (1954) Studies of absorption of iron from the gastro-intestinal tract. Clin. Res. Proc. 2, 53. JOSEI~HS H. W. (1958) Absorption of iron as a problem in human physiology: a critical review. Bloorl. 13, I. NOKIIENSENN. G., RYDIN H. and SANUELL E. (1949) Absorption experiments with different preparations of ferrous tartrate and ferrous chloride. Acta Phorm. Toxic., Kbh. 5, 363.
absorption.
J. Lab.
PSYCHOLOGICAL
FACTORS
IN IRON
ABSORPTION
I. C. LODGE PATCH, M.D.* THE absorption of iron is governed by many variables, as shown by the recent reviews of JOSEPHS (1958) and BOTHWELL et al. (1958). Amongst such factors, NORDENSEN et al. (1949) included the psychological, for in studying the absorption of different iron compounds, they examined their patients for the presence of ‘neurosis’. This seems to have been on empirical grounds, for neither criteria nor reasons are given, but they implied that their results might in some way be affected by this factor. Support for this view seems to come from the work of GRACE and DOIG (1954). These workers made twenty-six observations on a subject with a gastric fistula and found that ‘absorption (of iron) was optimal on days of good spirits, and below Such a claim merits further investigation, optimal on days of conflict and indecision’. since measurable metabolic changes which can be correlated with the mental state are few, but may have important implications. GRACE and DOIG give neither clinical nor technical details, but imply that their subject was psychiatrically normal, and that the mood changes were transient. Despite their importance, such observations are difficult to confirm on normal subjects, because different observers may easily disagree about the prevailing mood at a given time. It therefore seemed worth examining whether in a group of depressed patients, changes were present corresponding with those of GRACE and DOIG. In such patients one might reasonably expect the same psychophysical correlations as were present in a normal group. In addition, all could agree on the state of the mood at the time of the experiment, and the change after recovery would be unequivocal. Obviously such an experiment should be made on a group of patients. BOTHWELL et al. (1955) showed that investigation of iron absorption in a single case yielded no consistent results, and this criticism may be levelled at the study of GRACE and DOIG. In a group, however, these inconsistencies would tend to be eliminated, as BOTHWELL et al. agree. Such a study might show that the prevailing mental state was consistently related to iron absorption or that the relationship existed only where specific psychiatric features could be found. Finally, no evidence whatever might emerge in favour of such a relationship. MATERIAL The patients selected were a group of women, between the ages of 34 and 56, who were admitted to hospital suffering from depressive illnesses of moderate or great severity. Their illnesses varied from 1 month to 3 years in duration (average 13.7 months). Patients concurrently suffering from physical illnesses or minor infections were excluded from the series, and investigations were deferred during menstruation. Ultimately, however, no significant differences were found to exist between the post-menopausal and the younger group of women. METHOD The technique employed was that described by BOTHWELL and trial yielded results of an accuracy comparable with their own.
MALLETT (1955).
* Senior Registrar, Bethlem Royal and the Maudsley Hospitals, London S.E.5. 5-W
PP.)
129
A preliminary
130
I.C. LODGE PATCH
For 24 hr before the test no eggs were given, and milk was restricted to half a pint. No drugs were given on the day of the test, and in any case only barbiturate sedation on the previous days. Each patient was examined personally, in collaboration with the clinician responsible; the consistency of the depression was confirmed. The following morning, after a fasting specimen of blood had been taken (7.30 a.m.), a dose of ferrous sulphate (2 mg per kg body weight) was given, dissolved in half a glass of tap water. Specimens of blood were subsequently taken at 1, 3 and 5 hr after the dose, the patient remaining in bed and fasting throughout. The serum was later separated and refrigerated, the estimations being carried out within a few days. After recovery was complete, and shortly before discharge, the procedure was repeated: each patient thus served as her own control. On each occasion the haemoglobin was estimated: no correlations were found to exist between these levels and the nutritional status on the one hand, and the curves of iron absorption on the other. TABLE I.--SERUMIRON VALUES,MICROGRAMS, (FASTING 1,3 AND 5 HR SAMPLES), FOLLOWING AN ORAL DOSE 0F FERROUS~ULPHATE.ESTIMATIONS BEFOREANDAFTERRE~OVERY FROM DEPRESSION.
Pre-recovery 1 3 5 hr hr hr
Case
Age
F
(1) (2)
34 34 36 46 56 47 56 45 44 41 44
60 33 113 126 125 84 115 48 100 207 211
(3) (4) (5) (6) (7) (8) (9) (10) (11)
184 110 227 204 137 128 295 84 173 280 240
328 171 388 233 162 136 222 82 214 295 280
322 165 365 171 142 113 169 98 191 283 258
Post-recovery F 1 3 5 hr hr hr 66 12 183 75 57 18 151
170 147 217 132 147 86 241
234 412 294 225 136 148 211
219 425 265 245 122 141 164
RESULTS Table 1 presents the values of serum iron obtained in micrograms per 100 ml. In the last four cases, no ‘post-recovery’ test was carried out: examination of the earlier cases had already shown that nothing would be gained by a second test in those who followed. Because of the wide degree of variance, stabilization of these figures was carried out by taking their square roots. DISCUSSION
Examining the curves obtained, highly significant differences were found to exist between the fasting and the 1, 3 and 5 hr values, showing that the serum iron rose significantly in all cases after the oral dose (P < 0.01). A second analysis of variance was carried out to test whether differences existed between the ‘pre-recovery’ and the ‘post-recovery’ groups. This allowed the testing of possible interaction between the factors of recovery (pre- and post-) and of differences in the timing of samples. No significant differences were found to exist ; the patients behaved similarly, whether or not they were depressed. Comparing these findings with those of GRACE and DOIG it may be asked whether Their patient’s predominant symptoms were the mental state was comparable. In the present series, only case (2) ‘conflict and indecision’: these showed depression. showed a relationship similar to theirs, but she presented no clinical features unique
Psychological
factors
131
in iron absorption
in the series, although tension and anxiety were conspicuous.
The possibility that
specific symptoms, such as these, are related to differences in iron absorption, might be tested in patients with anxiety states. Otherwise, so far as these results apply to the finding of GRACE and DOUG, it seems that the relationship fact be due to a technical artefact.
they claim may in
250
0
I
2
3
4
5
hr Frc;.l.pCurves
of the mean values of strum iron from seven patients, recovery from depression.
before
and after
CONCLUSION In a group of depressed patients, no evidence was found that the levels of serum
iron, following
an oral dose, arc related to the mental state. The implications of
this finding arc discussed. ~cknow/ed~~~~enrs---l wish to thank examine
their cases,
the physicians at Bethlem Royal Hospital, who allowed me to Mr. A. E. MAXWELL for the statistical analysis and Mr. G. KING for technical
advice. REFERENCES BOTHWELLT. H., MALLETI. B., OLIVER R. and
SMITH M. D. (1955) Inability to assess absorption of iron from plasma radioiron curves. Brif. J. Haemafol. 1, 352. BOTHWELLT. H. and MAI.I.ETT B. (1955) The determination of iron in plasma or serum. Biochem. J.
59, 599. Bo-IHWELLT. H., PIRZIO-BIROLIG. and
FIXCH C. A. (1958) Iron absorption-l. Factors influencing Clin. Med. 51, 24. GRACE W. J. and DOUG R. K. (1954) Studies of absorption of iron from the gastro-intestinal tract. Clin. Res. Proc. 2, 53. JOSEI~HS H. W. (1958) Absorption of iron as a problem in human physiology: a critical review. Bloorl. 13, I. NOKIIENSENN. G., RYDIN H. and SANUELL E. (1949) Absorption experiments with different preparations of ferrous tartrate and ferrous chloride. Acta Phorm. Toxic., Kbh. 5, 363.
absorption.
J. Lab.