Zinc

Gerald

nutrition
1-3
P. Butrimovitz,4

and
Ph.D. and

growth
William

in a childhood
Ph.D.

C. Purdy,5

ABSTRACT humans. income This diet and

Plasma study rapid

zinc growth.

concentrations to evaluate Plasma zinc

are a useful plasma concentrations zinc

indicator levels of an

of the zinc in a population inner city

nutritional stressed

status population

in

was designed

by a lowfor of that

childhood

are analyzed by polynominal male and female subjects rapid are lowered growth. growth, calculated plasma Am. infancy and zinc and mirror

regression are markedly puberty. the Nutr. The variation result 3 1 : 1409-14

analysis. different. growth of from

The resultant Concentrations velocities (growth zinc zinc

age-related plasma zinc curves are lowest during the years indices) nutrition of these The during two data populations suggest

plasma

concentrations.

concentrations

inadequate

periods

of rapid

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J. Clin.

12, 1978.

The trace element zinc only recently has been established as a nutrient essential for health and growth in humans. On a cellular level, zinc is involved in nearly all aspects of metabolism (1), in protein, DNA, and RNA synthesis (2-4), in the activity of some 70 enzymes (5, 6), and in the mobilization of vitamin A from the liver (7). Zinc deficiency in the adolescent is characterized by failure to undergo rapid sexual maturation and by a low plasma zinc concentration. Administration of zinc to dwarfed and sexually retarded male individuals has been shown to result in dramatic growth and sexual development (8, 9). In 1972, Hambidge et al. (10) reported that middle-class children from Denver with objective hypogeusia recovered their taste acuity through zinc supplementation. In a later study, an increase in growth of male infants and a rise in plasma zinc levels were associated with supplementation (1 1). Moynahan (12) administered zinc sulfate to a group of children suffering from acrodermatitis enteropathica, a fatal genetic disease. Complete resolution of symptoms resulted, accompanied by an increase in the childrens rate of growth. Others have suggested that zinc deficiency may lead to greater susceptibility to infection ( 13, 14). A recent paper reports the change in adult zinc levels in healthy and acutely ill patients (15). Sandstead et al. (8) suggest that the effects of zinc insufficiency may be most apparent
The American Journal ofClinical Nutrition 3 1 : AUGUST

in infancy and adolescence due to rapid growth and a high zinc requirement. The recommended dietary allowances for zinc in humans increases from 3 mg/day at infancy to 15 mg/day during adulthood (16). There is no differentiation in this RDA between sexes for periods of rapid growth and sexual development. In light of previous studies, it is probable that segments of our population may benefit at times from higher zinc intake or supplementation (17). Plasma zinc levels are of demonstrated value in the assessment of zinc nutritional status in humans (18). Butrimovitz and Purdy (19) reported that plasma zinc concentrations of inner city children from Baltimore, Md., were markedly lower than those reported for a middle-income population (20). Concentrations were generally higher in the male than in female children and were lowest during infancy and puberty. Because periods of rapid growth and zinc retention in the male
1

From

the

Department

of Chemistry,

University Center,

of

Maryland, College Park, Maryland 20742. 2 Supported in part by the Computer Science University 3 Taken University 4 Senior Laboratory Washington,

of Maryland. in part from the Ph.D. Dissertation of G.P.B., of Maryland, 1977. Fellow in Clinical Chemistry, Department of Medicine, University Hospital, University of Seattle, Washington 98195. Professor

of Chemistry and Associate in Medicine. McGill University, 801 Sherbrcoke Street West, Montreal, Quebec, Canada H3A 2K6.

1978,

pp.

1409-

1412.

Printed

in U.S.A.

1409

1410

BUTRIMOVITZ

AND

PURDY

5 80 4 70
C 4,
.

3 60 2 50 1

C .C 0

0 2 4 6 8 10 12 14 16 18 Age (years)

FIG. 1. Mean plasma zinc concentrations for females (6 weeks to 19 years, index throughout childhood. Solid curve is the mean plasma zinc concentration. human volunteer study for which age, height and weight data are available. curve for this population. Minima, maxima, and points of inflection in the growth plasma zinc by about 1 year. The increase in concentration at the end of childhood growth indices.

N = 68) as related to the growth 0 represents individuals in the approximates the mean growth index precede inverse changes in appears to be related to decreasing

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and female plasma zinc within each Materials

differ (21), an investigation concentrations in relation group was undertaken. and methods

of to age

Blood samples were collected midday (10 AM to 4 PM) on 156 nonfasting human volunteer subjects (88 male, 68 female) residing in the inner city of Baltimore, Md. These children were seen during routine clinical visits and were in good general health. None of the subjects was judged to be growth or sexually retarded. Plasma samples diluted 5-fold with deionized water were analyzed by atomic absorption spectrophotometry (22). Polynomial regression analysis (23) was used to produce polynomial equations describing mean zinc concentrations as a function of age. The equations were expressed through a curve-fitting routine (24) as polynomial curves defusing the continual change in the concentration. Solution of the second derivative of these equations (points of inflection of the curves) yielded ages where a major increase or decrease in plasma zinc occurred.

childhood. The steepest decline occurred at age 12.9 years. The pattern for females was quite different. The decline occurred two years earlier at age 10.8 years and increased again at age 16.9. The two periods of lowered concentration paralleled ages where the onset and end of puberty would occur in each group. Because high zinc requirements during infancy and puberty have been related to growth, it is probable that the age-related plasma zinc patterns reported here reflect the changes in zinc body stores as an outcome of growth. In order to inferentially test this hypothesis on these populations, growth indices
height (inches) x weight (pounds)
=

growth

index

age (years) x 350

Results The entire male by a second-degree male population mial.7 The results are shown as the 1 and 2. Points Table 1. Concentrations and then declined population was described polynomial and the feby a third-degree polynoof the curve-fitting routines solid line curves in Figures of inflection are given in in the male rose with through the duration age of

are calculated for the populations and plotted against age as indicators of relative growth velocity (25). The growth patterns for the male and female populations are similar (dashed line curves in Figs. 1 and 2) except for an earlier rise at age 10 and a decline at
6

Although

I I subjects

(six

male,

five

female)

were

below levels

the third percentile in growth, their plasma zinc were normal for this group. 7 The polynomial expression for males was of lower significance than that for the females due to a very high variance among the youngest members of the male population.

ZINC

NUTRITION

AND

GROWTH

IN

CHILDREN

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Age (years) FIG. 2. Mean plasma zinc concentrations for males (4 months to 18 years, throughout childhood. (Solid line, 0 and described in legend for inversely related to the growth index. Continuously decreasing concentrations growth indices during latter childhood. N = 88) as related to the growth Fig. 1). Concentrations appear appear to be related to constantly index to be high

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TABLE 1 Maxima, minima, and inflection points age-related plasma zinc polynomial regression analysis curves for male and female subjects
Subjects No. Maxima/minima age yr

Discussion
for

Inflection points age

Female Male

(68) (88)

6.5/15.1 7.7

3.3, 3.9,

10.8, 12.9

16.9

a Polynomial expressions utilized in this analysis: Male population, F (zinc) = 1.29 (age) 0.08 (age)2 + 68.56 . . . . F = 1.3 (2, 85 DF). Female population, F (zinc) = 5.64 (age) 0.62 (age)2 + 0.02 (age)3 + 59.32 . . . . F = 4.4 (3, 64 DF).

age 16 in females. The growth indices and plasma zinc concentrations for the females and males are plotted against age and presented in Figures 1 and 2. Plasma zinc concentrations mirror the growth indices in that low concentrations are associated with high growth indices. Further, it appears that the lowest concentrations during puberty in the female occur at age 15, approximately a year beyond the maximum in the growth index curve. The physiological effect at the end of female puberty is reflected at age 17 by an upward return of plasma zinc concentrations and reduced growth indices. Although the plasma zinc growth index pattern is less pronounced for the male population, the extended growth period during puberty is paralleled by continually decreasing plasma zinc concentrations.

The data suggest that variations in plasma zinc concentrations reflect the continual utilization and depletion of body stores of zinc and is depicted briefly following periods of rapid growth. The lowered concentrations that occur in the infant and teenage indigent populations may result from high zinc requirements and low zinc intakes from protein sources. Teenage males ha a high inc requirement and an extended grovav Lii period that is reflected in a contii.sal decrease of concentrations throughout later childhood. Because the female puberty period has a lower requirement for zinc and a shorter growth period, the plasma concentrations are not severely reduced. It is likely that segments of our population on low protein diets would benefit from higher zinc intake, especially during periods of rapid growth. U References
physiology and pathol39: 443, 1959. 2. FERNANDEZ-MADRID, E., A. S. PRASAD AND D. OBERLEA5. Effect of zinc deficiency in nucleic acids, collagen, and non-collagen protein of connective tissue. J. Lab. Chin. Med. 82: 951, 1973. 3. PRA5AD, A. S., AND D. OBERLEAS. Thymidine kinase activity and incorporation of thymidine into DNA in zinc deficient tissue. J. Lab. Chin. Med. 83: 634, 1974. 4. STEPHAN, J. K., AND J. M. H5U. Effect of zinc deficiency and wounding on DNA synthesis in rat
VALLEE,

1.

ogy

B. L. Biochemistry, of zinc. Physiol. Rev.

1412 skin.

BUTRIMOVITZ J. Nutr. 103: 548, 1973. H. A. Review of Physiological Chemistry, (14th ed). Los Altos, Calif.: Lange Medical Publishers, 1973, p. 145. VALLEE, B. L. Recent advances in zinc biochemistry. In: Biological Aspects oflnorganic Chemistry, edited by D. Dolphin. New York: Wiley-Interscience, 1977, pp. 37-70. SMITH, J. E., E. D. BROWN AND J. C. SMITH, JR. The effect of zinc deficiency on the metabolism of the retinol-binding protein in the rat. J. Lab. Chin. Med. 84: 692, 1974. SANDSTEAD, H. H., A. S. PRASAD, A. R. SCHULERT, Z. FARID, A. M1ALE, JR., S. BASS1LLY AND W. J. DARBY. Human zinc deficiency, endocrine manifestations and response to treatment. Am. J. Chin. Nutr. 20: 422, 1967. HALSTED, J. A., H. A. RONAGHY, P. ABADI, J., HAGHSHENASS, G. H. AMIRHAKEMI, R. M. BARAKAT AND J. G. REINHOLD. Zinc deficiency in man. The Shiraz experiment. Am. J. Med. 53: 277, 1972. HAMBIDGE, K. M., C. HAMBIDGE, M. JACOBS AND J. D. BAUM. Low levels of zinc in hair, anorexia, poor growth, and hypogeusia in children. Pediat. Res. 6: 878, 1972. WALRAVENS, P. A., AND K. M. HAMBIDGE. Growth of infants fed a zinc supplemented formula. Am. J. Chin. Nutr. 29: 1 1 14, 1976. MOYNAHAN, E. J. Acrodermatitis enteropathica: A lethal inherited human zinc deficiency disorder. Lancet 2: 399, 1974. HALSTED, J. A., AND J. C. SMITH, JR. Plasma zinc in health and disease. Lancet I: 322, 1970. SMITH, J. C., JR., E. G. MCDANIEL, L. D. MCBEAN, F. S. Dovr AND J. A. HALSTED. Effects of microorganisms upon zinc metabolism using germ-free and conventional rats. J. Nutr. 102: 711, 1972. FALCHUK, K. H. Effect of acute disease and ACTH on serum zinc proteins. New Engl. J. Med. 296: 1129,
HARPER,

AND

PURDY

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1977. 16. Recommended ington, tional D.C.: Research

Dietary

Allowances,

(8th

ed).

Wash-

6.

17.

18.

7.

19.

8.

9.

20.

10.

21. 22.

1 1.

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24. 25.

15.

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