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CLINICAL EFFECTS OF VITAMIN C IN ELDERLY INPATIENTS WITH LOW BLOOD-VITAMIN-C LEVELS
403
relapses completely in
CLINICAL EFFECTS OF VITAMIN C IN ELDERLY INPATIENTS WITH LOW BLOOD-VITAMIN-C LEVELS
the risk, however, large series of children with gbmerulonephritis on long-term steroid treatment, 5% died of steroid side-effects.l0-13 The scarch for other methods of steroid treatment has thus continued,since steroids are still the first choice in the treatment of minimost cases, at
of serious side-effects. In
mal-change nephrotic syndrome. used interthe more effective and the steroid was rupted regimens more toxic. The answer to the first question was clear: a given amount of prednisone was more effective in preventing relapses of nephrotic syndrome when given on alternate days. Intermittent prednisone in the dosage we used did not prevent patients from relapsing while under therapy. This is in accord with the I.S.K.D.C.’s finding that 61 c of a group of patients on 6 months’ intermittent prednisone therapy relapsed.14 There is no doubt that intermittent prednisone in higher doses is more effective2,3 but this treatment increases the risk of serious side-effects and the cost of treatment. We suggest that the intermittent regimen should be abandoned since alternate-day treatment with the same total dosage of prednisone is more effective. Our second question was one of toxicity. Patients were observed for obesity, growth retardation, hypertension, cataracts, severe infections, and other severe complications but there were no differences between the two treatment groups. The question, however, cannot be answered completely: the length of observation was too short and the duration of the nephrotic syndrome before entering the study and the type of pretreatment during this period were too variable. Our study standardised treatment only during the year preceding entry into the BB’e asked which of the
two most
We know of no other direct comparison of alternateday and intermittent prednisone treatments in nephrotic syndrome. The different types of interrupted steroid treatment have been compared only with continuous steroid treatment or with non-treatment, and then only with regard to certain aspects of effectiveness and sideeffects. Growth was retarded in children with nephrotic syndrome treated with intermittent steroids compared with non-treated children,15 while alternate-day steroid therapy influences growth to a lesser degree than does intermittent therapy in various diseases and in kidney transplantation. 16-21 It has been claimed that the responsiveness and activity of the hypothalamic-pituitary-adrenocortical axis is depressed by intermittent22-26 but not by alternate-day steroids. 11,27,28 However, it is almost impossible to draw
definitive conclusions from those studies because different types of steroids were used in changing doses on patients with various diseases and in various clinical conditions who had different pre-treatment experiences. It thus seems mandatory to continue precise, controlled, and prospective studies on a cooperative basis, to obtain answers to the many outstanding questions within a reasonable period. ’.’’
e
thank Dr U.
Department of Chemical Pathology, University of Leeds,
widely
study.
Feldmann, department of biometry, Medizinische
Hannover, for statistical analyses.
Requests for reprints should be addressed to J. B., Medizinische Kinderklink D-3000 Hannover-61, West-Germany.
A. NEWILL D. B. MORGAN
C. J. SCHORAH D. L. SCOTT Leeds
The effect of oral vitamin C has been examined in elderly long-stay inpatients known to have low levels of vitamin C in their plasma and leucocytes. 1 g of vitamin C given daily for 28 days was shown to be associated with slight, but significant, clinical improvement and weight-gain when compared with placebo therapy.
Summary
Introduction THERE is
increasing concern with for
the nutrition of the
elderly. elderly patients in have low concentrations of vitamin C long-stay hospitals in their "leucocytes" (strictly a mixture of white-cell and platelet vitamin C),’-3 which has been attributed to a low intake of the vitamin.1.4 Scurvy is very unusual in elderly patients, but more subtle ill-effects due to lack of vitamin C have not been excluded. When elderly patients with low leucocyte-vitamin-C are given the vitamin daily in doses of 5 to 30 times the recommended minimum intake, the vitamin-C content of their leucoOne
cause
concern
is that
to normal.3,5,6, However, there has been of the effect of vitamin C on the general health and activity of these elderly patients. We have carried out a double-blind trial of the effect of large
cytes increases no assessment
Lange, K., Slobody, L., Strang, R. Proc. Soc. exp. Biol. Med. 1953, 82, 315. Lange, K., Strang, R., Slobody, L. B., Wenk, E. J. Archs intern. Med. 1957, 99, 760. 3. Lange, K., Wasserman, E., Slobody, L. B. J. Am. med. Ass. 1958, 168, 377. 4. Abramowicz, M., Arneil, G. C., Barnett, H. L., Barron, B. A., Edelmann, C. M., Jr., Gordillo P.-G., Greifer, I., Hallman, N., Kobayashi, O., Tiddens, H. A. Lancet, 1970, i, 959. 5. Reichling, G. H., Kligman, A. M. Archs Derm. 1961, 83, 980. 6. Harter, J. C., Reddy, W. J., Thorn, G. W. New Engl. J. Med. 1963, 269, 1. 2.
591. 7. 8. 9. 10.
Soyka, L. F., Saxena, K. M. J. Am. med. Ass. 1965, 192, 225. Soyka, L. F. m. J. Dis. Child. 1967, 113, 693. Abramowicz, C. M., Edelmann, C. M., Spitzer, A. J. Pediat. 1970, 76, 336. Cameron, J. S., Glasgow, E. F., Ogg, C. S., White, R. H. R. Br. med. J. 1970, iv, 7. 11. Habib, R., Gubler, M. C. Nephron, 1971, 8, 382. 12. White, R. H. R., Cameron, J. S., Trounce, J. R. Br. med. J. 1966, ii, 853. 13. White, R. H. R., Glasgow, E. F., Mills, R. J. Lancet, 1970, i, 1353. 14. International Study of Kidney Disease in Children. Lancet, 1974, ii, 423. 15. Fleisher, D. S., McCrory, W. W., Rapoport, M. J. Pediat. 1960, 57, 192. 16. Ansell, B. M., Bywaters, E. G. L. J. Rheumat. 1974, 1, 176. 17. Hoda, Q., Hasinoff, D. J., Arbus, G. S. Clin. Nephrol. 1975, 3, 6. 18. McEnery, P. T., Gonzalez, L. L., Martin, L. M., West, C. D. J. Pediat. 1973, 83, 806. 19. Potter, D., Holliday, M. A., Wilson, C. J., Salvatierra, O., Belzer, F. O. Transplant. Proc. 1975, 7, 79. 20. Reimold, E. W. Pediatrics, 1973, 52, 235. 21. Sadeghi-Nejad, A., Senior, B. ibid. 1969, 43, 277. 22. Adams, D. A., Gold, E. M., Gonick, H. C., Maxwell, M. H. Ann. intern. Med. 1966, 64, 542. 23. Leisti, S., Hallmann, N., Koskimies, O., Perheentupa, J., Rapola, R., Vilska, J. Lancet, 1977, ii, 795. 24. Leisti, S., Vilska, J., Hallman, N. Pediatrics, 1977, 60, 334. 25. Martin, M. M., Gaboardi, F., Podolsky, S., Raiti, S., Calcagno, P. L. New Engl. J. Med. 1968, 279, 273. 26. Zurbrügg, R. P., Zimmermann, E., Oetlicker, O. H. Helv. pœdiat. Acta.
1974, 29, 221. 27. Ackerman, G. C., Nolan, C. M. New Engl. 28. Fleisher, D.S. J. Pediat. 1967, 70, 54.
J. Med. 1963, 278, 405.
404
the clinical state and body-weight long-stay elderly patients in two geriatric hospitals.
doses of vitamin C
of
Results
on
Materials and Methods 118 long-stay patients, aged 59-97 years, in two geriatric hospitals were studied. They had been in the same geriatric hospital for 2 months to 23 years. Before the trial started, each patient was examined clinically, and the ward sister or charge-nurse completed a questionnaire which included their opinion on the potential for improvement in each patient. Each patient was weighed. The vitamin-C content of plasma was measured’ in all but 4 of the patients, and the vitamin C in the leucocytes was measured’ in 42 of them. Vitamin-C levels in plasma and leucocytes were also measured in a control group of 46 blood-donors, aged 19-55years. A sweetened flavoured solution was prepared, and vitamin added to half of it to make up a concentration of 50 mg/ml. The placebo and vitamin-C solutions were indistinguishable in taste, smell, or appearance. A pharmacist from another hospital allocated the patients by name to treatment or placebo groups by using random tables, and prepared individual bottles (labelled with the patient’s name) of either vitamin or placebo for each patient. Every morning for four weeks, each patient was given 20 ml of solution from his/her bottle, so that the dose of vitamin C was 1 g a day (30 times the recommended minimum intake). At the end of the trial, each patient was weighed and reassessed by the ward sister or charge-nurse, who recorded any clinical event during the trial and any change in living activities (such as mobility, dressing, feeding, social conversation), interest in surroundings, or appetite. Also, at the end of the trial, plasma-vitamin-C was measured in 64 of the 111 patients and leucocyte-vitamin-C was measured in 23 of the 42 patients who had had the measurement made initially.
C
was
Of the 118 patients who entered the trial, 1 died, 1 changed hospital, and the questionnaire for 1 was not completed, so that the final population was 115. None of these patients had xny features of scurvy. The average initial concentrations of vitamin C in and leucocytes were low compared with the values in the young controls, and the range of values overlapped those found in clinical scurvy8-11 (table r). The plasma-vitamin-C increased to normal values during the trial in all the patients in the vitamin-C group, whereas the increase in the mean value in patients in the placebo group was much smaller, but significant (table II). These results indicate that the patients were taking the treatments that they had been allocated. There were also significant increases in the leucocyte-vitamin-C levels in the patients in the vitamin-C group (table II), but the values did not reach normal despite the large daily dose of vitamin-C. The majority of patients did not show changes in living activities, interest in surroundings, and appetite, but more patients improved and fewer deteriorated in the vitamin-C group than in the placebo group (table m), and the probability that these differences arose by chance was less than 10%. The differences between the two groups were not significant for any of the variables, but the total number of changes in all three variables indicated that the probability that the vitamin-C group fared no better than the placebo group was less than 2-5% (table in). We have considered all these variables together because, although related, they do measure different aspects of clinical change. In the vitamin-C group only 2 patients showed a deterioration
plasma
TABLE I-INITIAL VALUES IN LONG-STAY GERIATRIC INPATIENTS COMPARED WITH THOSE IN YOUNG CONTROLS AND IN PATIENTS WITH
SCURVY
Mean values for both plasma and (P
leucocyte
vitamin C in the
geriatric patients
were
significantly
lower than
mean
values for the young
TABLE II-VITAMIN-C LEVELS IN GERIATRIC PATIENTS BEFORE AND AFTER VITAMIN-C OR PLACEBO THERAPY
Values significantly
higher after compared with before therapy *P<0-001,
‡P<0.02 (paired ttest).
subjects
405 TABLE III-CLINICAL CHANGES IN LONG-STAY GERIATRIC
INPATIENTS AFTER ONE MONTH OF VITAMIN C OR PLACEBO
-considerable improvement; +slight improvement; 0 no change; -slight deterioration. In the vitamin-C group the numbers of overall improvements compared with deteriorations and si,gnificantlv greater than in the placebo group (y2 analysis; P<0.025; P<0.05 respectively). -
of more than
one
compared
variable, whilst half those showing im-
than one, and some showed provement changed in all three. change Considering all variables collectively emphasises the greater magnitude of the improvement in the vitamin-C group. The variable which showed change most frequently was daily living activity, and most of the patients who showed change in one of the other variables also showed change in living activities. The number of patients who were thought unlikely to improve was similar in the two groups (placebo, 24, and vitamin C, 23) but the number who upset this prediction and improved was greater in the vitamin-C group (placebo, 1, and vitamin C, 7). The number thought to be capable of improvement was the same in the two groups (placebo, 35, and vitamin C, 33), but the number who upset this prediction and deteriorated was greater in the placebo group (placebo, 5, and vitamin C, 2). Weight-change was also different between the groups. The average weight increased in the vitamin-C group, but decreased in the placebo group, and this difference was more apparent in men (table IV). The distribution of patients between those who lost weight and those who gained weight was significantly different in the two in
more
groups (table v).
-
with deterioration
plus no change were
Discussion The patients we studied had been in hospital for many months for a variety of reasons. Most of them would be described as having little interest in their environment, and most were only partly mobile, so that no dramatic clinical improvement could have been expected in many of them. Instead, the placebo group tended to deteriorate during the trial. Nevertheless, there were significantly more clinical improvements and weight-gains in the vitamin-C groups than in the placebo groups. Unlike those in the placebo group, improvements in the vitamin-C group were not limited to those patients thought to have the potential for improvement. We suggest that these observations are particularly encouraging as, although the improvements are slight and do not all reach accepted levels of significance (<5%), the trial was short and the leucocyte-vitamin-C was still low at the end of the trial. Our results suggest the need for further and more detailed studies of the clinical and biochemical effects of vitamin C in small and large doses in elderly patients in and out of institutions. Similar studies would be justified in younger long-stay inpatients who also have low concentrations of vitamin C in plasma and leucocytes
(unpublished data). We thank the patients who participated in the trial, and Dr M. A. Dr C. Davidson, Dr A. Zaman. Dr M. Ahmed, Mr B. Harrison, Mrs J. Muirhead, Mrs A. Tomlinson, Mrs B. Rhodes, Mr G. Griffiths, Mr A. B. Miller, Miss M. Calender, and Miss H. Flavell for their
TABLE IV-WEIGHT-CHANGE
Sooltan,
help. Requests for reprints should be addressed of Chemical Pathology, The Martin Wing.
C. J. S., Department The General Infirmary
to
Leeds LS13EX. give en in parentheses. Stgmficance of difference Student’s s t test). s E
from
placebo--*p
‡p<0.025
TABLE V-NUMBERS SHOWING WEIGHT-CHANGE AFTER ONE
MONTH OF VITAMIN C OR PLACEBO
(by REFERENCES 1. Andrews, J., Brook, M., Allen, M. A. Geront. Clins. 1966, 8, 257. 2. Bates, J. F., Hughes, R. E., Hurley, R. J. Archs oral Biol. 1972, 17, 1017. 3. Brocklehurst, J. C., Griffiths, L. L., Taylor, G. F., Marks, J., Scott, D. L., Blackly, J. Geront. Clins. 1968, 10, 309. 4. Eddy, T. P. in Vitamins in the Elderly (edited by A. N. Exton-Smith and D. L. Scott); p. 86. Bristol, 1968. 5. Taylor, T. V., Rimmer, S., Day, B., Butcher, J., Dymock, I. N. Lancet,
1974, ii, 544.
magnificant at P<0.05. m parentheses are for males in the study.
C
6. Bnggs, M., Briggs, M. ibid. 1973, i, 998. 7. Denson, K. W., Bowers, E. F. Clin. Sci. 1961, 21, 157. 8. Goldberg, A. Q. Jl Med. 1963, 32, 51. 9. Hodges, R. E., Hood, J., Canham, J. E., Sauberlich, H. E., Baker, E. M. Am. J. clin. Nutr. 1971, 24, 432. 10. Bartley, W., Krebs, H. A., O’Brien, J. R. P. Medical Research Council Special Report Series, 1953, No. 280.
11. Crandon, J. H., Landau, B., Mikal, S., Balmanno, J., Jefferson, M., Mahoney, N. New Engl. J. Med. 1958, 258, 105.
relapses completely in
CLINICAL EFFECTS OF VITAMIN C IN ELDERLY INPATIENTS WITH LOW BLOOD-VITAMIN-C LEVELS
the risk, however, large series of children with gbmerulonephritis on long-term steroid treatment, 5% died of steroid side-effects.l0-13 The scarch for other methods of steroid treatment has thus continued,since steroids are still the first choice in the treatment of minimost cases, at
of serious side-effects. In
mal-change nephrotic syndrome. used interthe more effective and the steroid was rupted regimens more toxic. The answer to the first question was clear: a given amount of prednisone was more effective in preventing relapses of nephrotic syndrome when given on alternate days. Intermittent prednisone in the dosage we used did not prevent patients from relapsing while under therapy. This is in accord with the I.S.K.D.C.’s finding that 61 c of a group of patients on 6 months’ intermittent prednisone therapy relapsed.14 There is no doubt that intermittent prednisone in higher doses is more effective2,3 but this treatment increases the risk of serious side-effects and the cost of treatment. We suggest that the intermittent regimen should be abandoned since alternate-day treatment with the same total dosage of prednisone is more effective. Our second question was one of toxicity. Patients were observed for obesity, growth retardation, hypertension, cataracts, severe infections, and other severe complications but there were no differences between the two treatment groups. The question, however, cannot be answered completely: the length of observation was too short and the duration of the nephrotic syndrome before entering the study and the type of pretreatment during this period were too variable. Our study standardised treatment only during the year preceding entry into the BB’e asked which of the
two most
We know of no other direct comparison of alternateday and intermittent prednisone treatments in nephrotic syndrome. The different types of interrupted steroid treatment have been compared only with continuous steroid treatment or with non-treatment, and then only with regard to certain aspects of effectiveness and sideeffects. Growth was retarded in children with nephrotic syndrome treated with intermittent steroids compared with non-treated children,15 while alternate-day steroid therapy influences growth to a lesser degree than does intermittent therapy in various diseases and in kidney transplantation. 16-21 It has been claimed that the responsiveness and activity of the hypothalamic-pituitary-adrenocortical axis is depressed by intermittent22-26 but not by alternate-day steroids. 11,27,28 However, it is almost impossible to draw
definitive conclusions from those studies because different types of steroids were used in changing doses on patients with various diseases and in various clinical conditions who had different pre-treatment experiences. It thus seems mandatory to continue precise, controlled, and prospective studies on a cooperative basis, to obtain answers to the many outstanding questions within a reasonable period. ’.’’
e
thank Dr U.
Department of Chemical Pathology, University of Leeds,
widely
study.
Feldmann, department of biometry, Medizinische
Hannover, for statistical analyses.
Requests for reprints should be addressed to J. B., Medizinische Kinderklink D-3000 Hannover-61, West-Germany.
A. NEWILL D. B. MORGAN
C. J. SCHORAH D. L. SCOTT Leeds
The effect of oral vitamin C has been examined in elderly long-stay inpatients known to have low levels of vitamin C in their plasma and leucocytes. 1 g of vitamin C given daily for 28 days was shown to be associated with slight, but significant, clinical improvement and weight-gain when compared with placebo therapy.
Summary
Introduction THERE is
increasing concern with for
the nutrition of the
elderly. elderly patients in have low concentrations of vitamin C long-stay hospitals in their "leucocytes" (strictly a mixture of white-cell and platelet vitamin C),’-3 which has been attributed to a low intake of the vitamin.1.4 Scurvy is very unusual in elderly patients, but more subtle ill-effects due to lack of vitamin C have not been excluded. When elderly patients with low leucocyte-vitamin-C are given the vitamin daily in doses of 5 to 30 times the recommended minimum intake, the vitamin-C content of their leucoOne
cause
concern
is that
to normal.3,5,6, However, there has been of the effect of vitamin C on the general health and activity of these elderly patients. We have carried out a double-blind trial of the effect of large
cytes increases no assessment
Lange, K., Slobody, L., Strang, R. Proc. Soc. exp. Biol. Med. 1953, 82, 315. Lange, K., Strang, R., Slobody, L. B., Wenk, E. J. Archs intern. Med. 1957, 99, 760. 3. Lange, K., Wasserman, E., Slobody, L. B. J. Am. med. Ass. 1958, 168, 377. 4. Abramowicz, M., Arneil, G. C., Barnett, H. L., Barron, B. A., Edelmann, C. M., Jr., Gordillo P.-G., Greifer, I., Hallman, N., Kobayashi, O., Tiddens, H. A. Lancet, 1970, i, 959. 5. Reichling, G. H., Kligman, A. M. Archs Derm. 1961, 83, 980. 6. Harter, J. C., Reddy, W. J., Thorn, G. W. New Engl. J. Med. 1963, 269, 1. 2.
591. 7. 8. 9. 10.
Soyka, L. F., Saxena, K. M. J. Am. med. Ass. 1965, 192, 225. Soyka, L. F. m. J. Dis. Child. 1967, 113, 693. Abramowicz, C. M., Edelmann, C. M., Spitzer, A. J. Pediat. 1970, 76, 336. Cameron, J. S., Glasgow, E. F., Ogg, C. S., White, R. H. R. Br. med. J. 1970, iv, 7. 11. Habib, R., Gubler, M. C. Nephron, 1971, 8, 382. 12. White, R. H. R., Cameron, J. S., Trounce, J. R. Br. med. J. 1966, ii, 853. 13. White, R. H. R., Glasgow, E. F., Mills, R. J. Lancet, 1970, i, 1353. 14. International Study of Kidney Disease in Children. Lancet, 1974, ii, 423. 15. Fleisher, D. S., McCrory, W. W., Rapoport, M. J. Pediat. 1960, 57, 192. 16. Ansell, B. M., Bywaters, E. G. L. J. Rheumat. 1974, 1, 176. 17. Hoda, Q., Hasinoff, D. J., Arbus, G. S. Clin. Nephrol. 1975, 3, 6. 18. McEnery, P. T., Gonzalez, L. L., Martin, L. M., West, C. D. J. Pediat. 1973, 83, 806. 19. Potter, D., Holliday, M. A., Wilson, C. J., Salvatierra, O., Belzer, F. O. Transplant. Proc. 1975, 7, 79. 20. Reimold, E. W. Pediatrics, 1973, 52, 235. 21. Sadeghi-Nejad, A., Senior, B. ibid. 1969, 43, 277. 22. Adams, D. A., Gold, E. M., Gonick, H. C., Maxwell, M. H. Ann. intern. Med. 1966, 64, 542. 23. Leisti, S., Hallmann, N., Koskimies, O., Perheentupa, J., Rapola, R., Vilska, J. Lancet, 1977, ii, 795. 24. Leisti, S., Vilska, J., Hallman, N. Pediatrics, 1977, 60, 334. 25. Martin, M. M., Gaboardi, F., Podolsky, S., Raiti, S., Calcagno, P. L. New Engl. J. Med. 1968, 279, 273. 26. Zurbrügg, R. P., Zimmermann, E., Oetlicker, O. H. Helv. pœdiat. Acta.
1974, 29, 221. 27. Ackerman, G. C., Nolan, C. M. New Engl. 28. Fleisher, D.S. J. Pediat. 1967, 70, 54.
J. Med. 1963, 278, 405.
404
the clinical state and body-weight long-stay elderly patients in two geriatric hospitals.
doses of vitamin C
of
Results
on
Materials and Methods 118 long-stay patients, aged 59-97 years, in two geriatric hospitals were studied. They had been in the same geriatric hospital for 2 months to 23 years. Before the trial started, each patient was examined clinically, and the ward sister or charge-nurse completed a questionnaire which included their opinion on the potential for improvement in each patient. Each patient was weighed. The vitamin-C content of plasma was measured’ in all but 4 of the patients, and the vitamin C in the leucocytes was measured’ in 42 of them. Vitamin-C levels in plasma and leucocytes were also measured in a control group of 46 blood-donors, aged 19-55years. A sweetened flavoured solution was prepared, and vitamin added to half of it to make up a concentration of 50 mg/ml. The placebo and vitamin-C solutions were indistinguishable in taste, smell, or appearance. A pharmacist from another hospital allocated the patients by name to treatment or placebo groups by using random tables, and prepared individual bottles (labelled with the patient’s name) of either vitamin or placebo for each patient. Every morning for four weeks, each patient was given 20 ml of solution from his/her bottle, so that the dose of vitamin C was 1 g a day (30 times the recommended minimum intake). At the end of the trial, each patient was weighed and reassessed by the ward sister or charge-nurse, who recorded any clinical event during the trial and any change in living activities (such as mobility, dressing, feeding, social conversation), interest in surroundings, or appetite. Also, at the end of the trial, plasma-vitamin-C was measured in 64 of the 111 patients and leucocyte-vitamin-C was measured in 23 of the 42 patients who had had the measurement made initially.
C
was
Of the 118 patients who entered the trial, 1 died, 1 changed hospital, and the questionnaire for 1 was not completed, so that the final population was 115. None of these patients had xny features of scurvy. The average initial concentrations of vitamin C in and leucocytes were low compared with the values in the young controls, and the range of values overlapped those found in clinical scurvy8-11 (table r). The plasma-vitamin-C increased to normal values during the trial in all the patients in the vitamin-C group, whereas the increase in the mean value in patients in the placebo group was much smaller, but significant (table II). These results indicate that the patients were taking the treatments that they had been allocated. There were also significant increases in the leucocyte-vitamin-C levels in the patients in the vitamin-C group (table II), but the values did not reach normal despite the large daily dose of vitamin-C. The majority of patients did not show changes in living activities, interest in surroundings, and appetite, but more patients improved and fewer deteriorated in the vitamin-C group than in the placebo group (table m), and the probability that these differences arose by chance was less than 10%. The differences between the two groups were not significant for any of the variables, but the total number of changes in all three variables indicated that the probability that the vitamin-C group fared no better than the placebo group was less than 2-5% (table in). We have considered all these variables together because, although related, they do measure different aspects of clinical change. In the vitamin-C group only 2 patients showed a deterioration
plasma
TABLE I-INITIAL VALUES IN LONG-STAY GERIATRIC INPATIENTS COMPARED WITH THOSE IN YOUNG CONTROLS AND IN PATIENTS WITH
SCURVY
Mean values for both plasma and (P
leucocyte
vitamin C in the
geriatric patients
were
significantly
lower than
mean
values for the young
TABLE II-VITAMIN-C LEVELS IN GERIATRIC PATIENTS BEFORE AND AFTER VITAMIN-C OR PLACEBO THERAPY
Values significantly
higher after compared with before therapy *P<0-001,
‡P<0.02 (paired ttest).
subjects
405 TABLE III-CLINICAL CHANGES IN LONG-STAY GERIATRIC
INPATIENTS AFTER ONE MONTH OF VITAMIN C OR PLACEBO
-considerable improvement; +slight improvement; 0 no change; -slight deterioration. In the vitamin-C group the numbers of overall improvements compared with deteriorations and si,gnificantlv greater than in the placebo group (y2 analysis; P<0.025; P<0.05 respectively). -
of more than
one
compared
variable, whilst half those showing im-
than one, and some showed provement changed in all three. change Considering all variables collectively emphasises the greater magnitude of the improvement in the vitamin-C group. The variable which showed change most frequently was daily living activity, and most of the patients who showed change in one of the other variables also showed change in living activities. The number of patients who were thought unlikely to improve was similar in the two groups (placebo, 24, and vitamin C, 23) but the number who upset this prediction and improved was greater in the vitamin-C group (placebo, 1, and vitamin C, 7). The number thought to be capable of improvement was the same in the two groups (placebo, 35, and vitamin C, 33), but the number who upset this prediction and deteriorated was greater in the placebo group (placebo, 5, and vitamin C, 2). Weight-change was also different between the groups. The average weight increased in the vitamin-C group, but decreased in the placebo group, and this difference was more apparent in men (table IV). The distribution of patients between those who lost weight and those who gained weight was significantly different in the two in
more
groups (table v).
-
with deterioration
plus no change were
Discussion The patients we studied had been in hospital for many months for a variety of reasons. Most of them would be described as having little interest in their environment, and most were only partly mobile, so that no dramatic clinical improvement could have been expected in many of them. Instead, the placebo group tended to deteriorate during the trial. Nevertheless, there were significantly more clinical improvements and weight-gains in the vitamin-C groups than in the placebo groups. Unlike those in the placebo group, improvements in the vitamin-C group were not limited to those patients thought to have the potential for improvement. We suggest that these observations are particularly encouraging as, although the improvements are slight and do not all reach accepted levels of significance (<5%), the trial was short and the leucocyte-vitamin-C was still low at the end of the trial. Our results suggest the need for further and more detailed studies of the clinical and biochemical effects of vitamin C in small and large doses in elderly patients in and out of institutions. Similar studies would be justified in younger long-stay inpatients who also have low concentrations of vitamin C in plasma and leucocytes
(unpublished data). We thank the patients who participated in the trial, and Dr M. A. Dr C. Davidson, Dr A. Zaman. Dr M. Ahmed, Mr B. Harrison, Mrs J. Muirhead, Mrs A. Tomlinson, Mrs B. Rhodes, Mr G. Griffiths, Mr A. B. Miller, Miss M. Calender, and Miss H. Flavell for their
TABLE IV-WEIGHT-CHANGE
Sooltan,
help. Requests for reprints should be addressed of Chemical Pathology, The Martin Wing.
C. J. S., Department The General Infirmary
to
Leeds LS13EX. give en in parentheses. Stgmficance of difference Student’s s t test). s E
from
placebo--*p
‡p<0.025
TABLE V-NUMBERS SHOWING WEIGHT-CHANGE AFTER ONE
MONTH OF VITAMIN C OR PLACEBO
(by REFERENCES 1. Andrews, J., Brook, M., Allen, M. A. Geront. Clins. 1966, 8, 257. 2. Bates, J. F., Hughes, R. E., Hurley, R. J. Archs oral Biol. 1972, 17, 1017. 3. Brocklehurst, J. C., Griffiths, L. L., Taylor, G. F., Marks, J., Scott, D. L., Blackly, J. Geront. Clins. 1968, 10, 309. 4. Eddy, T. P. in Vitamins in the Elderly (edited by A. N. Exton-Smith and D. L. Scott); p. 86. Bristol, 1968. 5. Taylor, T. V., Rimmer, S., Day, B., Butcher, J., Dymock, I. N. Lancet,
1974, ii, 544.
magnificant at P<0.05. m parentheses are for males in the study.
C
6. Bnggs, M., Briggs, M. ibid. 1973, i, 998. 7. Denson, K. W., Bowers, E. F. Clin. Sci. 1961, 21, 157. 8. Goldberg, A. Q. Jl Med. 1963, 32, 51. 9. Hodges, R. E., Hood, J., Canham, J. E., Sauberlich, H. E., Baker, E. M. Am. J. clin. Nutr. 1971, 24, 432. 10. Bartley, W., Krebs, H. A., O’Brien, J. R. P. Medical Research Council Special Report Series, 1953, No. 280.
11. Crandon, J. H., Landau, B., Mikal, S., Balmanno, J., Jefferson, M., Mahoney, N. New Engl. J. Med. 1958, 258, 105.