7 Utilization of Zinc by Humans
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S. J. RITCHEY and L. JANETTE TAPER Virginia Polytechnic Institute and State University, Department of Human Nutrition and Foods, Blacksburg, VA 24061
The u t i l i z a t i o n and retention of zinc has been studied i n several groups of human subjects, including preadolescent children, young adult women, pregnant women, and elderly adults. Studies, ranging i n length from 18 to 42 days, were conducted under controlled conditions, including regulation of food and water intake, collection of all excreta, and careful monitoring of a c t i v i ties of subjects. Experimental diets were comprised of commonly consumed foods with supplements of zinc and/or other nutrients to achieve the objective of the study or to obtain desired intakes of critical nutrients. Apparent absorption of zinc ranged from about 2 percent i n elderly adults to about 60 percent i n one group of children. However, the usual range of apparent absorption was between 20 and 30 percent of intake. Average zinc excretion through feces, as a percentage of intake, ranged from 73.0 percent i n preadolescent children to 97.4 percent i n the elderly adults. Urinary zinc was between 0.3 and 0.4 mg/day for most subjects. In the elderly, urinary excretion was about 0.8 mg/day. These studies provide the basis for estimating losses of zinc i n relation to dietary intake and for assessing physiological needs of human subjects. During the past several years we have investigated the u t i l i z a t i o n of zinc i n several different age groups of human subjects. Work with growing préadolescent children, young adults, pregnant women, and elderly adults has been reported. Our goal through this work has been to provide reasonable estimates of zinc needs of the human at different ages and during normal physiological events. This paper i s not intended to be a comprehensive review, but focuses on work accomplished at laboratories within this institution. 0097-615 6/ 83/0210-0107$06.00/0 © 1983 American Chemical Society In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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Experimental Approach The balance study technique has been used i n a l l of these s t u d i e s . Although there a r e d i f f i c u l t i e s and c e r t a i n problems w i t h balance s t u d i e s , n u t r i t i o n researchers have not y e t found a reasonable and r e a l i s t i c a l t e r n a t i v e to estimate n u t r i e n t needs of human s u b j e c t s . Continued development and increased s o p h i s t i c a t i o n of methods and a n a l y t i c a l techniques may provide a l t e r n a t i v e s i n the f u t u r e , but these a r e not c l e a r l y a v a i l a b l e a t the present time. Throughout our s t u d i e s we employed the same general approach and techniques. We placed c o n s i d e r a t i o n emphasis on the e n l i s t ment of c o o p e r a t i v e s u b j e c t s who have an a p p r e c i a t i o n f o r the research and who understand the need f o r complete adherence to the g u i d e l i n e s of the s p e c i f i c study. I n a d d i t i o n , we emphasized the need f o r s t r i c t c o n t r o l of a l l p o t e n t i a l sources of contamin a t i o n , an absolute e s s e n t i a l f o r s t u d i e s w i t h the t r a c e m i n e r a l s . We were s u c c e s s f u l i n both of these concerns w i t h minor deviations. The general approach to our s t u d i e s has been described i n d e t a i l (1). We u t i l i z e d an adjustment p e r i o d ranging from f i v e to t e n days dependent upon the s p e c i f i c experiment. Commonly consumed foods were used to develop a s e r i e s of menus ( T a b l e . . I ) » u s u a l l y three to s i x , to a v o i d boredom and because we wanted to have r e s u l t s as c l o s e l y r e p r e s e n t a t i v e of the general p o p u l a t i o n as f e a s i b l e . Menus were developed and t e s t e d , key n u t r i e n t s were analyzed f o r , and m o d i f i c a t i o n s were made as necessary p r i o r to the beginning of an experiment. Supplements of n u t r i e n t s were u t i l i z e d to achieve the d e s i r e d experimental i n t a k e s and/or to meet the d a i l y recommended allowances of other e s s e n t i a l n u t r i e n t s (3) f o r the p a r t i c u l a r age group. U r i n e and f e c a l e x c r e t i o n s were c o l l e c t e d throughout the study. Appropriate composites of food and e x c r e t a were prepared and samples were taken f o r a n a l y t i c a l work. R e t e n t i o n , apparent a b s o r p t i o n , and other c a l c u l a t i o n s were based on the e n t i r e study except the adjustment p e r i o d , although i n some s t u d i e s the c a l c u l a t i o n s were made f o r d i s c r e t e p e r i o d s w i t h i n the experiment when there appeared t o be changes i n n u t r i e n t r e t e n t i o n s as a f u n c t i o n of an experimental treatment. D i e t a r y P r o t e i n and Zinc Zinc r e c e i v e d a t t e n t i o n i n our i n s t i t u t i o n as e a r l y as 1956 i n s t u d i e s w i t h préadolescent c h i l d r e n . A s e r i e s of experiments were done under completely c o n t r o l l e d c o n d i t i o n s (1) w i t h the g o a l of d e f i n i n g n u t r i e n t needs of the growing c h i l d . S e v e r a l i n v e s t i g a t o r s , r e p r e s e n t i n g a g r i c u l t u r a l experiment s t a t i o n s i n the southern r e g i o n and working under the r e g i o n a l research concept, p a r t i c i p a t e d i n these s t u d i e s . Engel e t a l . (4) and
In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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Table I . Example menu p a t t e r n used i n human s t u d i e s . 3
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Breakfast Orange j u i c e Bran f l a k e s Toast Margarine Coffee Milk Sugar
122 28 23 5 2 122 7
Apple j u i c e Bran f l a k e s Hard cooked egg Toast Margarine Coffee Milk Sugar
122 28 44 23 10 2 122 7
60 26 11 75 244 14
Cottage cheese Tomato wedges Lettuce Crackers Cantaloupe Lemonade
90 75 26 11 100 244
90 100 100 40 26 10 100 2 7 244 28
Baked f i s h Baked potato Peas Carrots Roll Margarine Sherbet Coffee Sugar Lemonade Graham c r a c k e r s
90 100 50 50 26 10 100 2 7 244 28
Lunch Tuna s a l a d Lettuce Crackers Apple dumpling Punch Mayonnaise Dinner Turkey b r e a s t Potatoes Green beans Cranberry j e l l y Roll Margarine Fruit cocktail Coffee Sugar Punch, f r u i t Graham c r a c k e r s
^ i s t of menu items and weights ( g ) . Analyzed v a l u e s f o r key n u t r i e n t s were done p r i o r to and throughout the experiment. Zinc contents were 6.10 and 5.98 mg, r e s p e c t i v e l y . The mean p r o t e i n content was 56 g and the mean energy content was 2000 k c a l s . Adapted from ( 2 ) .
In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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P r i c e e t a l . (5) measured the r e t e n t i o n of z i n c and other minor elements i n s t u d i e s i n which the major v a r i a b l e s were source and l e v e l of d i e t a r y p r o t e i n . Comparison of p r o t e i n sources from p l a n t and mixed sources i n d i c a t e d t h a t the apparent a b s o r p t i o n was somewhat lower from the d i e t s w i t h only p l a n t p r o t e i n s than that from mixed sources. A lower l e v e l o f p r o t e i n (25 g/day) caused a lower r e t e n t i o n of z i n c than the moderate p r o t e i n (46 g/day) d i e t , although c o n c l u s i o n s were complicated because of other v a r i a b l e s . In a recent study (6) w i t h young a d u l t s , the e f f e c t of l e v e l of d i e t a r y p r o t e i n on z i n c u t i l i z a t i o n was examined. Two l e v e l s of p r o t e i n , 49.2 and 94.9 g/day, and two l e v e l s of z i n c , 9.78 and 19.20 mg/day, were v a r i a b l e s i n a 24-day study. Zinc r e t e n t i o n s were not s i g n i f i c a n t l y a f f e c t e d by the l e v e l of p r o t e i n . However, u r i n a r y e x c r e t i o n of z i n c was s i g n i f i c a n t l y (p < 0.05) higher f o r s u b j e c t s consuming the higher p r o t e i n d i e t . This was true only d u r i n g the l a s t 6-day p e r i o d and r a i s e s the question of approp r i a t e l e n g t h o f human balance s t u d i e s . The very high f e c a l e x c r e t i o n s f o r s u b j e c t s on the higher p r o t e i n , high z i n c t r e a t ment may have been a o d d i t y . These e x c r e t i o n s r e s u l t e d i n a negative n e t r e t e n t i o n and may be m i s l e a d i n g i n our e v a l u a t i o n of these data. Reports from other l a b o r a t o r i e s have c o n f l i c t e d w i t h regard to the e f f e c t s o f p r o t e i n on z i n c u t i l i z a t i o n . Greger and Snedeker (7) reported t h a t apparent a b s o r p t i o n of z i n c was a f f e c t e d by the l e v e l of d i e t a r y p r o t e i n , phosphorus i n t a k e and the i n t e r a c t i o n between p r o t e i n and phosphorus. Apparent r e t e n t i o n of z i n c was highest w i t h the high p r o t e i n , moderate phosphorus d i e t compared to other treatments, i n c l u d i n g low prot e i n and e i t h e r low o r moderate phosphorus v a r i a b l e s . U r i n a r y z i n c was higher i n s u b j e c t s consuming the high p r o t e i n d i e t s . Based on a lengthy metabolic study w i t h men, Sandstead e t a l . (8) have reported that the d i e t a r y requirement f o r z i n c increased as the l e v e l o f p r o t e i n i n t a k e increased. A l l o f these i n v e s t i g a t i o n s suggest that a higher amount of p r o t e i n i n the d i e t r e s u l t s i n poorer u t i l i z a t i o n and/or increased metabolic need f o r z i n c . The s i t u a t i o n may prove t o be s i m i l a r t o that f o r other m i n e r a l s , such as calcium. O r a l Contraceptive Use and Pregnancy i n Adult Women A l t e r a t i o n s i n blood l e v e l s of z i n c during pregnancy and during the use of o r a l c o n t r a c e p t i v e agents a r e w e l l documented (9, 10). However, the u t i l i z a t i o n and need f o r z i n c during pregnancy and when women a r e using hormonal c o n t r a c e p t i v e agents have r e c e i v e d l i t t l e a t t e n t i o n . U t i l i z a t i o n of z i n c during the use o f o r a l c o n t r a c e p t i v e s was not a f f e c t e d (11). Contraceptive users were compared t o c o n t r o l s (non-users) i n an 18-day balance study. Retentions and f e c a l e x c r e t i o n s were s i m i l a r f o r the two groups - both groups were i n negative balance on a mean z i n c
In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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i n t a k e of 9.12 mg/day. Apparent absorptions could not be c a l c u l a t e d s i n c e f e c a l e x c r e t i o n s exceeded i n t a k e . U r i n e e x c r e t i o n s were not d i f f e r e n t f o r the treatments. A recent study (12) focused on the z i n c needs during the second t r i m e s t e r of pregnancy. This study was d i f f e r e n t from most i n our l a b o r a t o r y because we permitted s u b j e c t s to consume t h e i r normal d i e t s , thus the balance and e x c r e t i o n data represent a range of i n t a k e s . We found z i n c i n t a k e s f a l l i n g a t two l e v e l s , 6.7 and 22.0 mg/day. The higher i n t a k e s r e s u l t e d from supplements of z i n c . We measured r e t e n t i o n s i n two weeks during the 4.5 month to the 5.5 month of pregnancy. The study design r e s u l t e d i n v a r y i n g l e v e l s of i n t a k e and r e t e n t i o n s , p a r t i c u l a r l y f o r the lower, non-supplemented group of women. Both groups of s u b j e c t s were i n net p o s i t i v e balance, although the lower l e v e l was marg i n a l a t best when a l l p o t e n t i a l l o s s e s of z i n c were accounted f o r i n e s t i m a t i n g r e t e n t i o n s . Apparent z i n c a b s o r p t i o n ranged from 9.6 to 23.79 percent w i t h no e f f e c t r e s u l t i n g from l e v e l of dietary intake. Taper et a l . (13) i n v e s t i g a t e d the e f f e c t s of z i n c i n t a k e on copper u t i l i z a t i o n i n a d u l t women. The experiment i n v o l v e d feedi n g three l e v e l s of z i n c , ranging from 8.0 to 24.0 mg/day. Copper r e t e n t i o n was not a f f e c t e d by z i n c i n t a k e . U r i n e l o s s e s of z i n c were from 0.4 to 0.6 mg/day and f e c a l e x c r e t i o n s p a r a l l e l e d the i n t a k e . Percent apparent absorptions of z i n c were 7.75, 9.13, and 11.50 percent when i n t a k e s were 8.0, 16.0 and 24.0 mg/day. U t i l i z a t i o n i n Growing C h i l d r e n In a d d i t i o n to the study of Engel et a l . (4) and P r i c e et a l . (5), two other experiments have been conducted i n our l a b o r a t o r i e s . Examining the e f f e c t of z i n c supplementation on p r o t e i n u t i l i z a t i o n i n the growing c h i l d , Meiners et a l . (14) fed z i n c l e v e l s of e i t h e r 5.5 mg/day, the amount present i n d i e t s t y p i c a l of low-income p o p u l a t i o n s i n the Southern r e g i o n , or 10.5 mg/day. Retentions were b o r d e r l i n e e q u i l i b r i u m f o r s u b j e c t s on the lower i n t a k e , but were p o s i t i v e f o r those c h i l d r e n consuming 10.5 mg/ day. U r i n e e x c r e t i o n s were i n the range of 0.45 to 0.79 mg/day. Losses were higher than f o r most a d u l t s t u d i e s i n our l a b o r a t o r y . The apparent absorptions ranged from 7.1 to 21.2 percent. Préadolescent g i r l s were provided z i n c l e v e l s ranging from 5.61 to 14.61 mg/day to evaluate the needs f o r z i n c by t h i s age group (15). Percent apparent a b s o r p t i o n ranged from 26.1 to 43.7 percent w i t h most s u b j e c t s i n the more narrow range of 25 to 30 percent. Losses of Zinc The c o n s i d e r a t i o n of z i n c u t i l i z a t i o n i s i n l a r g e measure an assessment of z i n c l o s s e s or e x c r e t i o n under any given set of circumstances, i n c l u d i n g d i e t a r y v a r i a b l e s , p h y s i o l o g i c a l s t a t e ,
In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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p a t h o l o g i c a l i n s u l t , s t r e s s , and other c o n d i t i o n s which may a f f e c t u t i l i z a t i o n . Major routes of z i n c e x c r e t i o n a r e f e c a l and u r i n a r y , w i t h p o t e n t i a l l o s s e s through sweat, and probably some s l i g h t l o s s e s through other routes. Studies from our l a b o r a t o r i e s and from others a r e now such that we can begin to have some general n o t i o n o f l e v e l s o f e x c r e t i o n by human subjects and can p r e d i c t i n a general f a s h i o n the u t i l i z a t i o n of z i n c . U r i n a r y l o s s e s of z i n c represent s m a l l , and apparently f a i r l y constant amounts. Using the data from s e v e r a l s t u d i e s i n our l a b o r a t o r y , we made c a l c u l a t i o n s of average l o s s e s by groups of subjects (Table I I ) . Urine e x c r e t i o n was u s u a l l y i n the range of 0.3 to 0.4 mg/day w i t h c o n s i d e r a b l e v a r i a b i l i t y around those average v a l u e s . However, we have a reasonable b a s i s f o r suggesting that u r i n a r y l o s s e s w i l l be c o n s i s t e n t l y w i t h i n the 0.3 to 0.5 mg/day range when subjects a r e consuming commonly used foods. From our data, e l d e r l y a d u l t s a r e the c l e a r exception to t h i s g e n e r a l i z a t i o n , but there a r e l i m i t e d numbers of i n d i v i d u a l s i n t h i s pool of data. F e c a l e x c r e t i o n s were c a l c u l a t e d as a percentage of i n t a k e s i n c e t h i s l o s s almost always i n our experience c l o s e l y f o l l o w s i n t a k e (Table I I ) . Percentages of i n t a k e excreted through feces ranged from 73.0 i n the préadolescent c h i l d t o 97.4 i n the e l d e r l y a d u l t s . D i e t a r y f a c t o r s may have more impact on the l o s s of z i n c through the g a s t r o i n t e s t i n a l t r a c t , thus a wide range of excret i o n s from study to study might be a n t i c i p a t e d . I t i s i n t e r e s t ing that the lowest percentages occur i n those groups that would have the higher p h y s i o l o g i c a l needs f o r z i n c , préadolescent c h i l d r e n and pregnant women. Losses of z i n c through sweat can be s i g n i f i c a n t , p a r t i c u l a r l y i n hot, humid c l i m a t e s . Data from a few s t u d i e s , i n c l u d i n g those of Jacob e t a l . (16) and Ritchey e t a l . (15), suggest that l o s s e s through t h i s route a r e i n the range from 0.5 to 1.0 mg/day, perhaps somewhat higher i n t r o p i c a l areas. Summary In most of the i n d i v i d u a l s studied i n our l a b o r a t o r y , z i n c i s absorbed w i t h i n the range of 20 to 30 percent of i n t a k e , although there a r e s i g n i f i c a n t d e v i a t i o n s from that apparently normal response. Losses, i n c l u d i n g e x c r e t i o n s and sweat l o s s , from commonly consumed d i e t s can be p r e d i c t e d i n a general way a t the present time, thus u t i l i z a t i o n of z i n c by human subjects can be estimated under most circumstances. A d d i t i o n a l information and refinements a r e needed f o r some p o p u l a t i o n groups, such as the e l d e r l y and pregnant women.
In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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Table I I . E x c r e t i o n s of z i n c through u r i n e and feces by groups of s u b j e c t s .
Group
No. of Subj e c t s
U r i n e (mg/day) Mean Range
Feces (% of i n t a k e ) Mean Range
Ref.
Préadolescent children
70
0.38
0.20-0.79
73.0
56.3-92.9
(15)
Adult females
57
0.37
0.27-0.57
93.2
82.3-104.7
(6,11, 13)
Pregnant women
24
0.30
0.25-0.34
82.9
76.2-90.5
(12)
Elderly adults
10
0.78
0.46-1.09
97.4
96.3-98.5
(2)
In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.
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Literature Cited 1. 2. 3. 4.
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5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
Ritchey, S. J.; Korslund, M. K. Home Econ. Res. J. 1976, 4, 248-252. Burke, D. M.; DeMicco, F. J.; Taper, L. J.; Ritchey, S. J. J. Gerontology 1981, 36, 558-563. Food and Nutrition Board. "Recommended Dietary Allowances"; National Academy of Sciences: Washington, 1980, 9th ed. Engel, R. W.; Miller, R. F.; Price, N. O. In: Zinc Metabolism (Prasad, A, S., ed. C. C. Thomas, Springfield, Ill., 1956). Price, N. O.; Bunce, G. E.; Engel, R. W. Am. J. Clin. Nutr. 1970, 23, 258-260. Colin, M. A. M.S. Thesis, Virginia Polytechnic Institute and State University, Blacksburg, VA, 1982. Greger, J. L.; Snedeker, S. M. J. Nutr. 1980, 110, 22432253. Sandstead, H. H.; Klevay, L.; Mahalko, J.; Johnson, L.; Milne, D. Am. J. Clin. Nutr. 1981, 34, 617 (Abs.). Prasad, A. S.; Oberleas, D.; Lei, K. Y . ; Moghissi, M. D.; Stryker, J. C. Am. J. Clin. Nutr. 1975, 20, 377-391. Margen, S.; King, J. C. Am. J. Clin. Nutr. 1975, 28, 392402. Crews, M. G.; Taper, L. J.; Ritchey, S. J. Am. J. Clin. Nutr. 1980, 33, 1940-1945. Oliva, J. T. M.S. Thesis, Virginia Polytechnic Institute and State University, Blacksburg, VA, 1981. Taper, L. J.; Hinners, M. L.; Ritchey, S. J. Am. J. Clin. Nutr. 1980, 33, 1077-1082. Meiners, C. R.; Taper, L. J.; Korslund, M. K.; Ritchey, S. J. Am. J. Clin. Nutr. 1977, 30, 879-882. Ritchey, S. J.; Korslund, M. K.; Gilbert, L. M.; Fay, D. C.; Robinson, M. F. Am. J. Clin. Nutr. 1979, 32, 799-803. Jacob, R. Α.; Sandstead, Η. H.; Munoz, J. M.; Klevay, L. M.; Milne, D. B. Am. J. Clin. Nutr. 1981, 34, 1379-1383.
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In Nutritional Bioavailability of Zinc; Inglett, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1983.