Zinc Balances in Humans During Different Intakes of Calcium and

16 Zinc Balances in Humans During Different Intakes of Calcium and Phosphorus H E R T A S P E N C E R , LOIS K R A M E R , and D A C E OSIS Downloaded by IOWA STATE UNIV on March 23, 2017 | http://pubs.acs.org Publication Date: January 20, 1983 | doi: 10.1021/bk-1983-0210.ch016

Veterans Administration Hospital, Metabolic Section, Hines, IL 60141

Animal studies indicate that calcium and phosphorus inhibit the availability of zinc for absorption. In the present study the effect of calcium and phosphorus on zinc metabolism was investigated in adult men by determining metabolic balances of zinc during different intakes of calcium and phosphorus. Three intake levels of calcium, ranging from 200 to 2000 mg/day, and two intake levels of phosphorus (800 and 2000 mg/day) were used during a constant dietary zinc intake of 14.5 mg/day. Increasing the calcium intake from 200 to 2000 mg and increasing the phosphorus intake from 800 to 2000 mg/day had no effect on urinary or fecal zinc excretion nor on zinc retention. Zn absorption studies confirmed these results. The observations made in man are in contrast with results obtained in animal studies. 65

Interaction between zinc and calcium has been demonstrated in several animal studies (1-6)· It has been shown that calcium antagonizes the biological effects of zinc and that calcium reduces the availability of zinc for absorption. This decrease in zinc absorption resulted in severe malnutrition and parakeratosis (.1-7)· Several studies have conclusively shown that the calcium-zinc antagonism studied in animals is due to excess phytic acid in the diet (8, 9). However, in the absence of phytic acid, excess dietary calcium per se has also been shown to decrease the intestinal absorption and the retention of zinc in rats (10). This inhibitory effect on zinc absorption, induced by calcium, was further enhanced by the addition of phosphorus to the high calcium intake (11). Little information is available in man on the effect of either calcium or of phosphorus on zinc metabolism and specifically l i t t l e is known on the effect of these minerals on the intestinal absorption of zinc in humans. In a study carried out by 0097-6156/ 83/0210-0223$06.00/0 © 1983 American Chemical Society Inglett; Nutritional Bioavailability of Zinc ACS Symposium Series; American Chemical Society: Washington, DC, 1983.

224

NUTRITIONAL BIOAVAILABILITY OF ZINC

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this group, using ^Zn as the tracer, a high calcium intake of 2000 mg calcium per day did not decrease the intestinal absorp tion of zinc i n man compared with the absorption during a calcium intake of 200 mg per day (12). However, metabolic balances of stable zinc were not determined at that time. In a study carried out by others, using dairy products with the breakfast meal, namely, milk and cheese, both of which contain calcium and phos phorus, a decrease of the intestinal absorption of zinc was ob served which was estimated by zinc plasma levels; however, zinc absorption studies were not carried out (13). This same study has also demonstrated that phosphate per se had a similar effect in decreasing the intestinal absorption of zinc. It should be mentioned that this same study also reported that other sub stances, such as coffee, decrease the intestinal absorption of zinc i n man. In the present study complete metabolic balances of zinc, calcium, and phosphorus were determined i n adult males under s t r i c t l y controlled dietary conditions i n the Metabolic Research Ward i n order to determine the effect of these minerals, which were used singly and combined, on the a v a i l a b i l i t y of zinc for absorption. The metabolic diet and the daily f l u i d Intake were kept constant and the diet was analyzed for zinc, calcium, and phosphorus throughout a l l study phases. The basal diet contained an average of 14.5 mg zinc, 850 mg phosphorus, and 230ragc a l c i um. The calcium Intake was adjusted to appropriate levels by the addition of calcium gluconate tablets to the constant diet. Com plete collections of urine and stool were obtained for several weeks from the start of the study. Metabolic balances of zinc, calcium, and phosphorus were determined i n each 6-day metabolic study period by analyzing the diet and the excreta for these ele ments. Calcium and zinc were analyzed by atomic absorption spec troscopy (14, 15) and phosphorus by a modification of the method of Fiske and SubbaRow (16). The net or apparent absorption of zinc during the different intakes of phosphorus and calcium was determined by relating the fecal zinc excretion to the zinc i n take according to the following formula: Zinc Intake - Fecal Zinc Net absorption, % «

χ 100 Zinc Intake

Several zinc absorption studies, using oral doses of 6 5 z d 2 were carried out. 65zn plasma levels were determined s e r i a l l y on the day of the oral administration of the $Zn tracer, urinary and fecal 65z excretions were determined for approximately 15 days. The subjects studied were f u l l y ambulatory males who were in good nutritional state. They were normal according to a l l c l i n i c a l and laboratory c r i t e r i a , including the serum levels of zinc, calcium, and phosphorus. The effect of three intake levels of calcium on the zinc balance was studied, namely, of 200, 900, n

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Inglett; Nutritional Bioavailability of Zinc ACS Symposium Series; American Chemical Society: Washington, DC, 1983.

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Zinc Balances During Intake of Ca and Ρ

and 2000 mg calcium per day. In studies of the effect of phos phate on zinc metabolism the Increased Intake of phosphorus was due to the addition of sodium glycerophosphate to the constant diet. The high phosphorus Intake was 2000 mg per day compared to a dietary intake of 800 mg per day i n the control study. During the addition of either calcium or phosphorus a l l other dietary constituents remained unchanged. The duration of each study phase was several weeks both i n control studies and during the higher intakes of calcium or phosphorus.


Effect of Calcum on the Zinc Balance Table I shows data of the effect of different intake levels of calcium on the zinc balance i n three patients. During a low calcium intake of approximately 200 mg per day the major pathway of zinc excretion i s via the intestine, the urinary zinc excre tion i s low ranging from 0.7 to 0.9 mg per day. Increasing the calcium Intake from 200 to 900 mg per day did not result i n any appreciable changes of the fecal zinc excretion. These excre tions reflected the slightly lower zinc intake during the higher calcium intake. There was no change of the urinary zinc excre tion nor of the zinc balance (Patient 1). This lack of change of the fecal zinc excretion was observed i n the presence of a marked increase of the fecal calcium excretion. The lack of change of the urinary zinc excretion was observed i n the presence of an i n crease i n urinary calcium excretion. When the calcium Intake was Increased further, from 200 mg to 2000 mg per day (Patient 2), there was again no change of the fecal or urinary zinc excretion nor of the zinc balance. During this high calcium intake of 2000 mg calcium per day (Patient 2), the fecal calcium excretion was even higher than during the 900 mg calcium intake and the presence of these large amounts of calcium i n the intestine did not affect the fecal zinc excretion. In the third study carried out i n a patient with idiopathic hypercalciuria (urinary calcium 370 mg per day during a calcium intake of approximately 800 mg per day), the increase of the calcium intake from 800 to 2000 mg per day again did not result i n any change of the urinary or fecal zinc excretions nor of the zinc balance, despite the fact that the urinary and fecal calcium excretions increased, partic ularly the l a t t e r . The net absorption of zinc during the d i f ferent calcium intakes varied and these values ranged from -1% of the intake during a 2000 mg calcium intake to 16% on the same calcium intake. The phosphorus intake during a l l three studies was constant, 800 mg/day. These studies, as well as additional studies carried out i n this Research Unit, have shown that increasing the calcium Intake up to 2000 mg per day does not affect the excretions or retention of zinc i n man. These observations are i n contrast to results obtained i n animal studies (10) which have shown that a high c a l cium intake per se, i n the absence of phytic acid, can decrease


225


48 48

36 42

60 42

STUDY DAYS

15.3 14.6

17.2 16.0

13.8 11.9

Intake

0.9 0.9

0.9 0.7

0.7 0.5

Urine

13.6 12.2

16.3 16.1

13.2 11.8

Stool

ZINC, mg/day

Phosphorus intake * 800 mg/day i n a l l studies

Normal Calcium High Calcium

Patient 3

Low Calcium High Calcium

Patient 2

Low Calcium Normal Calcium

Patient 1

PATIENT AND STUDY

+0.8 +1.5

0 -0.8

-0.1 -0.4

Balance

11 16

5 -1

4 1

Zn, NET ABSORPTION %

838 1903

212 2022

198 947

Intake

370 407

57 176

102 149

Urine

562 1209

197 1772

220 637

Stool

CALCIUM, mg/day

EFFECT OF DIFFERENT INTAKE LEVELS OF CALCIUM ON THE ZINC BALANCE

TABLE I


- 94 +287

- 42 + 74

-124 +161

Balance

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the Intestinal absorption of zinc. I t should be stated that the type of diet used i n our studies had a low phytate content* The difference i n results obtained i n animals and man i s most l i k e l y due to the fact that the amount of calcium used i n animal studies, r e l a t i v e to the total body weight, was considerably higher than the calcium Intake levels used i n our studies i n humans* I t should also be pointed out that i n terms of a high calcium intake in man i t would be most unlikely that the human diet would con tain more than 2000 mg calcium per day* No data are available, to our knowledge, on the effect of calcium intakes greater than 2000 mg per day on the zinc balance i n man* Effect of Phosphorus on the Zinc Balance Table II shows data of the effect of a high phosphorus i n take on the zinc balance* The phosphorus supplements were given to three patients during different calcium intakes, namely, dur ing a low calcium intake of 200 mg per day and during higher c a l cium intakes of 800 mg and 2000 mg calcium per day. The phos phorus intake of the subjects studied was approximately 900 mg per day i n the control study and was 2000 mg per day during the high phosphorus intake* In the control study, during a low c a l cium intake and a normal phosphorus intake of 900 mg per day and a dietary zinc intake of 17 mg per day, the urinary zinc excre tion was relatively high, 1.6 mg/day, the fecal zinc excretion was i n the expected range and the zinc balance was positive, +1.6 mg/day. In the experimental study, when the phosphorus i n take was increased by approximately 1000 mg per day, there was l i t t l e change of the urinary or fecal zinc excretions and, there fore, the zinc balance also did not change. In the study carried out during a calcium intake of 800 mg per day and a dietary zinc intake of 13.6 mg per day, the urinary zinc excretion was normal, the fecal zinc excretion reflected the zinc intake, and the zinc balance was slightly negative, -0.7 mg per day. With the addi tion of 1000 mg of phosphorus the urinary zinc excretion r e mained unchanged, the fecal zinc excretion decreased slightly, and the zinc balance became slightly positive during this high phosphorus intake* In the study carried out during a high c a l cium Intake of 2000 mg per day and a high phosphorus Intake of 2000 mg per day, and a dietary zinc intake of 14.6 mg per day, the following observation was made. In the high calcium control study the urinary zinc excretion was slightly higher than normal, 0.9 mg per day, the fecal zinc excretion reflected the dietary zinc intake and the zinc balance was positive, +1.5 mg per day. During the addition of 1000 mg phosphorus to the high calcium i n take of 2000 mg per day, there was no change of the urinary zinc excretion and the fecal zinc excretion increased s l i g h t l y ; how ever, the dietary zinc intake was also somewhat higher than i n the control study. The zinc balance remained unchanged during the high phosphorus intake which was given during a high calcium



2000 2000

3

48 48

14.6 15.2

0.9 0.8

12.2 13.0

+1.5 +1.4

-0.7 +0.4

13.5 12.0

0.8 0.7

13.6 13.1

18 36

800 800

2

+1.6 +1.9

13.6 13.8

1.6 1.5

16.8 17.2

18 30

200 200

1

Balance

Urine

Stool

ZINC, mg/day

Intake

STUDY DAYS

CALCIUM INTAKE mg/day

PATIENT

443 887

472 941

+ 22 +205

- 79 +102

380 542 529 1337

830 1981

1 8

937 2033

+ 90 +130 203 296 637 1578 930 2004

19 20

16 15

Balance Stool Urine

PHOSPHORUS , mg/day Intake

Zn, NET ABSORPTION %

EFFECT OF DIFFERENT INTAKE LEVELS OF PHOSPHORUS ON THE ZINC BALANCE

TABLE II



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intake of 2000 mg per day. The studies have shown that the addi tion of phosphorus to the diet did not change the net absorption of zinc during the different phosphorus intakes and this lack of change was independent of the calcium intake. Even during the concomitant use of a high calcium and a high phosphorus intake there was no change of the intestinal absorption of zinc and the net absorption of zinc was similar during the calcium intakes of 200 mg and 2000 mg per day. The phosphorus balance data (Table II) show that the urinary phosphorus excretion increased approximately two- to three-fold in a l l three high phosphorus studies, while the fecal phosphorus excretion increased to a considerably lesser extent. The phos phorus balance of a l l three patients became more positive during the high phosphorus intake. These studies have shown that i n creasing the phosphorus intake up to 2000 mg/day did not affect the excretions of zinc nor the zinc balance, despite the fact that there were marked changes i n phosphorus metabolism, primari l y a marked increase of the urinary phosphorus excretion, while the fecal phosphorus excretion increased to a lesser extent. This lack of change of the zinc excretions during the addition of phosphorus was observed irrespective of the calcium intake. A l though i t has been claimed frequently that the American diet has a high phosphorus content, i t i s not expected that the usual diet would reach or exceed 2000 mg phosphorus per day. This amount of phosphorus i s higher than that o f f i c i a l l y recommended (17). I t i s noteworthy that i n none of the studies i n man reported here did the zinc balance become more negative during the high phos phorus intake i n contrast to results obtained i n animals (11). A review of the zinc requirement i n man elaborates on various fac tors which Influence the intestinal absorption of zinc, including the effect of phosphorus and of calcium (18). Studies of the effect of both calcium and phosphorus on the zinc balance which have been carried out i n this Research Unit (19, 20) have shown that the zinc balance varies during a normal dietary calcium and phosphorus intake and ranges from slightly negative to positive values and that the net or apparent absorp tion of zinc, calculated from zinc balance data, remained un changed during the addition of the amounts of calcium or phos phorus used i n these studies. The zinc balances i n the present study have to be considered as maximal balances as the loss of zinc i n sweat has not been considered as part of the excretory losses. I t has been estimated that the loss of zinc i n sweat i s quantitatively as great as the urinary zinc excretion (21). The results obtained i n zinc balance studies during d i f f e r ent intake levels of calcium and phosphorus were i n agreement i n 65zn absorption studies. Figure 1 shows data of 65zn plasma levels and of the fecal 6$Zn excretions following a single oral dose of 65zn chloride during the Intake of different levels of calcium and phosphorus. The 65zn plasma levels were quite simi lar during the different study conditions as were the fecal 65zn


229


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NUTRITIONAL BIOAVAILABILITY OF ZINC

Zn

ABSORPTION DURING DIFFERENT INTAKES OF CALCIUM AND PHOSPHORUS

65

Figure 1. A single tracer dose of ZnCl was given orally in each study. Fecal Zn excretions are cumulative for 12 days. 2

65


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excretions, thus confirming the zinc balance data, i . e . , the lack of effect of the amounts of calcium and phosphorus, used singly or combined, on the a v a i l a b i l i t y of zinc for absorption. The results obtained with calcium and phosphorus on the zinc balance and on the a v a i l a b i l i t y of zinc for absorption i n the present study are i n contrast to results obtained i n animals. These observations point out the d i f f i c u l t y i n extrapolating r e sults obtained i n animal studies to humans.


Acknowledgment This study was supported by a grant from the U. S. Department of Agriculture, CSRS, S&E.

Literature Cited 1. Berry, R. K.; Bell, M. C.; Grainger, R. B.; Buescher, R. G. J. Animal Sci. 1961, 20, 433-9. 2. Forbes, R. M. Fed. Proc. 1960, 19, 643-7. 3. Forbes, R. M.; Yohe, M. J. Nutr. 1960, 70, 53-7. 4. Hoekstra, W. G.; Lewis, P. K.; Phillips, P. H.; Grummer, R. H. J. Animal Sci. 1956, 15, 752-64. 5. Lewis, P. K.; Hoekstra, W. G.; Grummer, R. H. J. Animal Sci. 1957, 16, 578-88. 6. Newland, H. W.; Ullrey, D. Ε.; Hoefer, J. Α.; Luecke, R. W. J. Animal Sci. 1958, 17, 886-92. 7. Bell, M. C.; Lloyd, M. K. Fed. Proc. 1963, 22, 492. 8. Oberleas, D.; Muhrer, M. E.; O'Dell, B. L. J. Animal Sci. 1962, 21, 57-61. 9. O'Dell, B. L; Savage, J. E. Proc. Soc. Exp. Biol. Med. 1960 103, 304-6. 10. Heth, D. Α.; Hoekstra, W. G. J. Nutr. 1965, 85, 367-74. 11. Heth, D. Α.; Becker, W. M.; Hoekstra, W. G. J. Nutr. 1966, 88, 331-7. 12. Spencer, H.; Vankinscott, V.; Lewin, I.; Samachson, J. J. Nutr. 1965, 86, 169-77. 13. Pecoud, Α.; Donzel, P.; Schelling, J. L. Clin. Ρharm. Therap. 1975, 17, 469-74. 14. Willis, J. B. Spectrochim. Acta 1960, 16, 259-72. 15. Willis, J. B. Analyt. Chem. 1971, 33, 556-9. 16. Fiske, C. H.; SubbaRow, Y. T. J. Biol. Chem. 1925, 66, 375-400. 17. "Recommended Dietary Allowances"; 9th ed.; National Academy of Sciences; Washington, DC, 1980. 18. Halsted, J. Α.; Smith, J. C. Jr.; Irwin, M. I. J. Nutr. 1974, 104, 345-78. 19. Spencer, H.; Osis, D.; Kramer, L . ; Norris, C. "Trace Ele ments in Human Health and Disease;" Prasad, A. S., Ed.; Academic Press, Inc.; 1976; Vol. 1, New York; pp. 345-61.


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20.

ZINC

Spencer, Η.; Gatza, C.; Kramer, L . ; Osis, D. "Zinc in the Environment." Part II.; Nriagu, J . O., Ed.; John Wiley & Sons, Inc.; New York, 1980, pp. 105-19. 21. Prasad, A. S.; Schulert, A. R.; Sandstead, H. H.;Miale,Α.; Farid, Z. J . Lab. Clin. Med. 1963, 62, 84-9. August 23,1982


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Zinc Balances in Humans During Different Intakes of Calcium and

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