Age and Ageing (1975), 4, 195
THE RELATIONSHIP BETWEEN LOW LEUCOCYTE ASCORBIC-ACID LEVELS AND TYROSINE METABOLISM IN THE ELDERLY *Manor Park Hospital, Bristol and -[Royal United Hospital, Bath Summary Twenty-seven elderly men aged 69-94 years had tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g daily for four days. There was a significant rise in the fasting and half-hourly mean plasma tyrosine levels after ascorbic acid administration in those subjects with an initial leucocyte ascorbic-acid level (LAA) below 15 ng/108 w.c.c. The peak of the tyrosine tolerance curve was also advanced following administration of ascorbic acid in those subjects with an initial LAA below 15 ^g/108 w.c.c. A further ten elderly men aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma cortisol and plasma tyrosine levels before and after receiving ascorbic acid 1 g daily for four days. All ten subjects showed a peak LAA level at 5 p.m. when saturated with vitamin C but there was no significant correlation between plasma cortisol changes and plasma tyrosine changes. Possible explanations for the results are discussed. INTRODUCTION
A Panel on Nutrition of the Elderly survey (1972) showed that 30 per cent of women and 25 per cent of men aged 75 + ingested less than 30 mg of ascorbic acid per day. The survey indicated a highly significant correlation between leucocyte ascorbic acid levels (LAA) and recorded intake of vitamin C. In the survey, 26 per cent of the men and 12 per cent of the women had LAA levels of less than 10 ^.g/108 w.c.c. Andrews (1973) recorded low levels of vitamin C white-cell concentration in the elderly living in large hospitals, and has suggested that this is associated with low dietary vitamin C intake rather than the result of multiple pathology causing an increased demand for vitamin C. One of the main problems is to determine whether the low LAA levels in the elderly are associated with any biochemical or clinical disturbance. Windsor & Williams (1970) suggested that there is an alteration of hydroxyproline metabolism in the elderly who have LAA levels below 15 /xg/108 w.c.c. Krasner et al. (1974) have shown that with increased levels of LAA the rate of ethanol clearance from the blood is enhanced. They suggested that alcohol dehydrogenase activity is dependent on ascorbic acid saturation. It is well know that animals and man, deficient in ascorbic acid, metabolize tyrosine incompletely when given extra amounts of this amino acid. Light et al. (1966) have shown that the elevated serum phenylalanine and elevated serum tyrosine levels found in premature infants can be reversed with administration of high doses of ascorbic acid. Although to date the role of ascorbic acid in tyrosine metabolism is considered nonspecific, merely acting as a reducing agent, it was thought well worth ascertaining whether there is a relationship between the low LAA levels found in the elderly and tyrosine metabolism. 24
Downloaded from http://ageing.oxfordjournals.org/ at University of Tennessee ? Knoxville Libraries on June 7, 2016
A. C. M. WINDSOR,* C. B. HoBBS.f D. A. TREBYf and C. B. GUPTA*
196
A. C. M. Windsor, C. B. Hobbs, D. A. Treby and C. B. Gupta Method
RESULTS
Amongst the 27 subjects who had tyrosine tolerance tests, 18 had initial LAA levels below 15 /xg/108 w.c.c., and nine had levels above 15 ^ig/108 w.c.c. All subjects showed a rise in LAA following treatment with ascorbic acid. It can be seen from Fig. 1 that
TPre- treatment 60 Post- treatment 50
40
8 30
20
10
F
"2 Initial
LAA
I I
I l'/2 hourly
15 /ig / IO8 wcc.
Fig. 1. Mean and range of plasma tyrosine levels following administration of ascorbic acid 1 g per day for four days in subjects with high and low leucocyte ascorbic-acid levels.
Downloaded from http://ageing.oxfordjournals.org/ at University of Tennessee ? Knoxville Libraries on June 7, 2016
Twenty-seven elderly men, all volunteers, aged 69-94 years had LAA levels and tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g per day for four days. All subjects had fasting, half-hour, one-hour, and one-and-a-half-hour plasma tyrosine levels following the ingestion of 3.5 g of tyrosine. Subjects with abnormal tyrosine metabolism resulting from thyroid disease, Parkinsonism, liver disease, or depression were excluded from the survey. Windsor et al. (1972) have shown that tetracycline reduces LAA levels and therefore it was confirmed that no subject in the.survey had recently received tetracycline. Plasma tyrosine levels were measured by a fluorimetric method (Waalkes & Udenfriend, 1957) and LAA levels by the method of Denson & Bowers (1961). A further ten elderly men, all volunteers, aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma tyrosine and plasma cortisol levels. The blood samples were taken at 9 a.m., 12 noon, 5 p.m. and 10.45 p.m. The criteria for selection of subjects was the same as stated in the above paragraph. Also the same methods of measuring LAA levels and plasma tyrosine levels were used. The plasma cortisol was measured by the method of Mattingly (1962). During the investigations all subjects were on a normal ward diet, they had no evidence of clinical scurvy, were on no drug therapy, and had no clinical or biochemical evidence of an endocrine disturbance.
Low Leucocyte Ascorbic-acid Levels and Tyrosine Metabolism
197
Table I. Mean change and standard error of mean change in fasting and half-hour plasma tyrosine levels following treatment with ascorbic acid 1 g per day for four days Plasma tyrosine (^ig/ml) £ hour
Fasting
All subjects 1st Subdivision -11
12 + 2nd Subdivision -14
15 + 3rd Subdivision -15
16 +
No.
Mean change
S.E.
P
THE RELATIONSHIP BETWEEN LOW LEUCOCYTE ASCORBIC-ACID LEVELS AND TYROSINE METABOLISM IN THE ELDERLY *Manor Park Hospital, Bristol and -[Royal United Hospital, Bath Summary Twenty-seven elderly men aged 69-94 years had tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g daily for four days. There was a significant rise in the fasting and half-hourly mean plasma tyrosine levels after ascorbic acid administration in those subjects with an initial leucocyte ascorbic-acid level (LAA) below 15 ng/108 w.c.c. The peak of the tyrosine tolerance curve was also advanced following administration of ascorbic acid in those subjects with an initial LAA below 15 ^g/108 w.c.c. A further ten elderly men aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma cortisol and plasma tyrosine levels before and after receiving ascorbic acid 1 g daily for four days. All ten subjects showed a peak LAA level at 5 p.m. when saturated with vitamin C but there was no significant correlation between plasma cortisol changes and plasma tyrosine changes. Possible explanations for the results are discussed. INTRODUCTION
A Panel on Nutrition of the Elderly survey (1972) showed that 30 per cent of women and 25 per cent of men aged 75 + ingested less than 30 mg of ascorbic acid per day. The survey indicated a highly significant correlation between leucocyte ascorbic acid levels (LAA) and recorded intake of vitamin C. In the survey, 26 per cent of the men and 12 per cent of the women had LAA levels of less than 10 ^.g/108 w.c.c. Andrews (1973) recorded low levels of vitamin C white-cell concentration in the elderly living in large hospitals, and has suggested that this is associated with low dietary vitamin C intake rather than the result of multiple pathology causing an increased demand for vitamin C. One of the main problems is to determine whether the low LAA levels in the elderly are associated with any biochemical or clinical disturbance. Windsor & Williams (1970) suggested that there is an alteration of hydroxyproline metabolism in the elderly who have LAA levels below 15 /xg/108 w.c.c. Krasner et al. (1974) have shown that with increased levels of LAA the rate of ethanol clearance from the blood is enhanced. They suggested that alcohol dehydrogenase activity is dependent on ascorbic acid saturation. It is well know that animals and man, deficient in ascorbic acid, metabolize tyrosine incompletely when given extra amounts of this amino acid. Light et al. (1966) have shown that the elevated serum phenylalanine and elevated serum tyrosine levels found in premature infants can be reversed with administration of high doses of ascorbic acid. Although to date the role of ascorbic acid in tyrosine metabolism is considered nonspecific, merely acting as a reducing agent, it was thought well worth ascertaining whether there is a relationship between the low LAA levels found in the elderly and tyrosine metabolism. 24
Downloaded from http://ageing.oxfordjournals.org/ at University of Tennessee ? Knoxville Libraries on June 7, 2016
A. C. M. WINDSOR,* C. B. HoBBS.f D. A. TREBYf and C. B. GUPTA*
196
A. C. M. Windsor, C. B. Hobbs, D. A. Treby and C. B. Gupta Method
RESULTS
Amongst the 27 subjects who had tyrosine tolerance tests, 18 had initial LAA levels below 15 /xg/108 w.c.c., and nine had levels above 15 ^ig/108 w.c.c. All subjects showed a rise in LAA following treatment with ascorbic acid. It can be seen from Fig. 1 that
TPre- treatment 60 Post- treatment 50
40
8 30
20
10
F
"2 Initial
LAA
I I
I l'/2 hourly
15 /ig / IO8 wcc.
Fig. 1. Mean and range of plasma tyrosine levels following administration of ascorbic acid 1 g per day for four days in subjects with high and low leucocyte ascorbic-acid levels.
Downloaded from http://ageing.oxfordjournals.org/ at University of Tennessee ? Knoxville Libraries on June 7, 2016
Twenty-seven elderly men, all volunteers, aged 69-94 years had LAA levels and tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g per day for four days. All subjects had fasting, half-hour, one-hour, and one-and-a-half-hour plasma tyrosine levels following the ingestion of 3.5 g of tyrosine. Subjects with abnormal tyrosine metabolism resulting from thyroid disease, Parkinsonism, liver disease, or depression were excluded from the survey. Windsor et al. (1972) have shown that tetracycline reduces LAA levels and therefore it was confirmed that no subject in the.survey had recently received tetracycline. Plasma tyrosine levels were measured by a fluorimetric method (Waalkes & Udenfriend, 1957) and LAA levels by the method of Denson & Bowers (1961). A further ten elderly men, all volunteers, aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma tyrosine and plasma cortisol levels. The blood samples were taken at 9 a.m., 12 noon, 5 p.m. and 10.45 p.m. The criteria for selection of subjects was the same as stated in the above paragraph. Also the same methods of measuring LAA levels and plasma tyrosine levels were used. The plasma cortisol was measured by the method of Mattingly (1962). During the investigations all subjects were on a normal ward diet, they had no evidence of clinical scurvy, were on no drug therapy, and had no clinical or biochemical evidence of an endocrine disturbance.
Low Leucocyte Ascorbic-acid Levels and Tyrosine Metabolism
197
Table I. Mean change and standard error of mean change in fasting and half-hour plasma tyrosine levels following treatment with ascorbic acid 1 g per day for four days Plasma tyrosine (^ig/ml) £ hour
Fasting
All subjects 1st Subdivision -11
12 + 2nd Subdivision -14
15 + 3rd Subdivision -15
16 +
No.
Mean change
S.E.
P
