Upload
marcos-andres-munoz-garcia
View
212
Download
0
Embed Size (px)
Citation preview
8/19/2019 Bioinorganica del zinc
1/34
A CONSPECTUS OF RESEARCH ON ZINC
REQUIREMENTS OF MAN
JA MES A. H ALSTED
Albany Medica l Co ll ege
A lb an y, N ew Yor k 1 22 08
J. CECIL SM ITH, JR.
Trace Elemen t Research Labora tory
Veterans Administ rat ion Hospital
Wash ington, D . C . 20422
an d
M. ISABEL IRWIN
Nutrit ion Insti tute
Agricultural Research Service
Unit ed S ta te s Departmen t o f Agri cu lt ure
Beltsviüe,Maryland 20705
Pages 345-378
THE JOURNAL OF NUTRITION
VO LUM E 1 4 N UM BER 3 MARC H 1974
8/19/2019 Bioinorganica del zinc
2/34
TABLE OF CONTEN TS
Introduction 347
Zinc in nature 347
Development of knowledge about zinc 348
Early discovery-uses in metallurgy 348
Chemistry 348
Biological essentiality 348
Biological functions 349
M ethods of measuring zinc 350
Zinc in food 350
Content in classes of foods 350
Content of typical meals or diets 351
Factors influencing content 352
M anufacturing techniques 352
Preparation of foods 352
M etabolic aspects of zinc in human nutrition 352
Distribution in the body 352
Plasma and serum 352
Red blood cells 352
Leucocytes 354
Hair 354
Absorption of zinc 354
Availability of zinc 355
Excretion of zinc 356
Binding of zinc to serum protein 357
Factors influencing the concentration of zinc in plasma .... 357
Relationship of zinc to endocrine functions 359
Interrelationships with other minerals 359
Calcium 359
Cadmium 359
Copper 360
Others 360
Interrelationships with vitamins 360
V itamin A 360
V itamin D 361
Riboflavin 361
Zinc deficiency 361
Animals 361
M an—clinical and metabolic features 362
Parameters for assessing zinc status in man 363
Zinc toxicity 364
Human requirements for zinc 365
Conclusions 367
Acknowledgments 368
Literature cited . 368
8/19/2019 Bioinorganica del zinc
3/34
INTRODUCTION
The 1934 report by Todd et al. (300)
that zinc was necessary for l if e in animals
suggested that it was probably an essential
nutrient for man also. N evertheless the
ubiqui ty of zinc made i t seem unl ikely that
al terations in zinc metabol ism could lead
to significant problems in human nutrition
or clinical medicine. For example, in 1962
Underwood (303) stated that an uncom
plicated dietary deficiency of zinc has never
been observed in man. Since then, zinc
def iciency has been observed in man, and
thus, in 1971 Underwood (304) included
man among the species in whom a de
ficiency syndrome had been demonstrated.
This was the result of reports of primary
zinc deficiency in Egypt by Prasad et al.
(224, 226, 228) and in I ran by H alsted et
al. (80, 84). I n addition, Caggiano et al.
(27), in the U nited States, observed zinc
def iciency secondary to intestinal malab-
sorption. M ore recently, also in the United
States, Hambidge et al . ( 87) reported cases
of low hair zinc concentration and low
taste acuity that were responsive to zinc
supplementation.
The l iterature on the metabol ic aspects
of zinc is extensive (223) and is grow ing.
M uch of our knowledge of zinc has
stemmed however f rom cl inical observa
tions in plant, animal and, most recently,
human pathology. I t is still necessary to
rely on indirect information in estimating
human requirements for zinc and in de
lineating those factors that may accentuate
requi rements. This indi rect information
comes from all branches of available knowl
edge including geochemistry and the zinc
content of the earth's crust. Many bits of
information gleaned from widely disparate
experimental approaches, including those
from the few reported metabolic balance
studies and from cultural eating practices,
shed some light on the role of zinc in
human nutrition.
T he objective of this conspectus is to
bring together the information that bears
on human requirements for zinc, to show
how the information was obtained, and to
point out areas where research is needed.
ZIN C IN N ATURE
Z inc has been estimated to rank 25th in
abundance ( 305 ) and to make up 0.004 to
0.01% of the earth's crust (216, 305).
However, it is less abundant than titanium,
barium, zirconium, or vanadium (264) , ele
ments not yet shown to be essential to man.
A lthough zinc is ubiqui tous i t is unevenly
distributed in the earth's crust, ranging
from 10 to 300 ppm with a mean of 50
ppm (264). Rocks average 16 to 95 ppm
( 21 ). Shales have the highest concentration
and sandstone has the lowest.
Analysis of moon samples brought back
by the astronauts of A pollo 11, 12, and 14
revealed a much lower concentration of
zinc in both the rocks and soils than in
materials found on earth (39, 253, 254).
Specifically, igneous rock samples (basalt
and gabbro ) contained f rom 0.2 to 3.0 ppm
zinc (Apollo 11). E ight rocks returned by
A pollo 12 contained between 0.2 and 4.3
ppm zinc w ith a mean of slightl y less than
4.0 ppm. Lunar soil samples showed a
range of 4.0 to 8.2 ppm with a mean of
6.7 ppm zinc, l ess than 15% the mean con
centration of earth soil.
T he zinc content of certain land plant
species grown in the U nited States has
been summarized (100) . The contents vary
widely around a mean of 23 ppm. Some
land plants reportedly accumulate up to
16% of their ash weight as zinc (330).
Marine animals have a wide range of zinc
concentrations w ith oysters having the
highest level (21).
As an inorganic element, zinc is not de
stroyed but remains in cycle. This cycle
in its simplest form is from the rock ( soil)
-^plants—»animals—»soilr ocean. T here is
however a net loss of elemental zinc from
the soi l due to natural leaching and erosion
Received for puhllrntion February 7. 1972.
Requests (or reprints should be addressed to M .
Isabel Irwin.
7
8/19/2019 Bioinorganica del zinc
4/34
34 8
J. A . HALSTED, J. C . SMITH, JR. AND M. I. IRW IN
and because sewage is directed toward the
oceans. Thus, it is theoretically possible
that zinc and other trace elements may be
depleted from the soil. In a like manner,
c on sta nt remo va l o f c ro ps w ith ou t re ple tio n
results in deficiency of zinc in the soil.
M itchell (172) has calculated that the up
take of zinc by plants is relatively high
com pared w ith soil concentration. That is,
when a crop containing 100 ppm zinc is
removed from the soil, 1 ppm zinc is lost
from the surface soil (assuming a yield of
10 tons/acre). The feasibility of zinc-
enriched fertilizers as a method for soil
reple tion has bee n discussed by V iets (310).
DEVELOPM ENT OF KNOW LEDGE
ABOUT ZINC
Early d iscovery—uses in me ta llurgy
Zinc does not occur naturally in a free,
uncom bined state. It was discovered by ac
cident in the fourth century A .D . that brass
was produced when a certain earth (zinc
bearing) was heated with copper. In India
during the 13th century, m etallic zinc was
produced by reducing calamine (zinc
oxide plus a small percentage of ferric
oxide) with organic substances such as
w oo l (8 8). E be ne r o f N ü rn be rgis re po rte d
to have recognized zinc as a discrete ele
ment in 1509 (223). In 1746 Marggraf re
discovered the metal in Europe (88). Zinc
as a bipositive ion is com bined w ith sulfide
in the mineral sphalerite which contains
67 zinc. O ther na turally occurring zinc -
containing m inerals of the earth's crust in
clude zincite, ZnO; smithsonite ZnCO3;
willem ite, Zn2SiO4; and hem im orphite,
Zn4(OH)(Si2O7)-H2O.
Cliemistry
Zinc has an atomic number of 30 and an
atomic weight of 65.4. It has a relatively
low meltin g p oin t o f 4 19°.F ifte en iso to pe s
of zinc have been described ranging from
80Zn to 72Zn. Ten of these isotopes are not
stable. Their half-lives vary from 1.48
m inutes (61Zn) to 245 days (8SZn) (98).
Metallic zinc is a good reducing agent, is
amphoteric and will dissolve in m ineral
acids and strong bases. Zinc exists in solu
tion only in the oxidized state of Zn2t. The
soluble salts of zinc include chloride, bro
m ide, iodide , form ate, a cetate, su lfate, an d
nitrate (98). The insoluble salts include
carbona te, sulfide, hydroxide, a mm onium
phosphate, ox alate, and p hytate (98).
Today elemental zinc is obtained by
heating ores containing zinc to form zinc
oxide, reducing the oxide with carbon and
then distilling the metal. M etallic zinc is
b lu is h wh it e.
Biological essentiality
O ver 100 years ago (1869) R aulin (236),
a pupil of Pasteur, discovered that zinc w as
indispensable for the growth of a black
bread m old, A spe rgillus n iger. T his finding
was confirmed in 1911, 40 years later, by
Bertrand and Javillier (16). According to
B ertrand and de W olf ( 1 2-15 ) A spergillus
niger requires zinc in order to synthesize
phenylala nine, tryptopha n, and ty rosine as
w ell as sev eral enzym es. G ro wth of penicillin-producing fungi is greatly retarded by
zinc deficiency of the culture m edium ( 60 ).
E vidence in dicating that zinc is essential to
the growth of m icroorganisms has been
s ummariz ed re ce ntly ( 3 30 ).
In 1919 Birckner ( 18 ) reported that egg
yolk, human milk, and cow 's m ilk con
tained zinc and suggested that zinc was of
n utritiv e v alu e. S ho rtly th ere afte r, S ommer
and Lipman (278) demonstrated that zinc
was essential for plant life. Lutz (137)
noted that there had been reports from
time to time indicating that zinc was a
com mon and nearly universal constituent
of animal as well as plant tissues. He em
phasized that zinc was not present in
traces but in am ounts not greatly differ
ent from that found for other heavy m etals
such as iron. Analyses of many foods at
that time showed amounts somewhat
greater than in present day analyses, pre
sumably the result of contamination of
samp le s a nd le ss p re cise a na ly tic al m eth od s
than those used at present. A fter extensive
and meticulous analyses of tissues from
rats, cats, and m an, Lutz (137) calculated
that the human body contained a total of
2.2 g of zinc, an amount about half that of
iron. This value has been widely quoted.
The only other sim ilar work is that ofW iddowson et al. (325), who reported
human body zinc content to be between
1.4 and 2.3 g.
Som e plant diseases have been traced to
zinc deficiency, such as leaf rosette in
8/19/2019 Bioinorganica del zinc
5/34
RESEA RCH ON Z IN C REQU IREM EN TS OF M A N
349
apples, mottle leaf in citrus crops and prob
ably dwarf ing of trees. Agronomists have
traced zinc deficiency in plants to deficient
soils in parts of Californi a and Texas and
in the Ninety M ile Desert in South Aus
tral ia. These lands have been reclaimed for
productivity by zinc supplementation (305).
A lthough many attempts were made to
provide a controlled zinc-deficient diet, this
was not accomplished until 1934 when
Todd et al. (300) were successful in dem
onstrating that zinc is essential for growth
and development of rats. The disease of
swine, porcine parakeratosis, which had
been long recognized in animal husbandry,
was shown to be the result of zinc defi
ciency by Tucker and Salmon (302) in
1955. Their f indings led to the general prac
tice of supplementing animal feeds w ith
zinc. O 'Del l and Savage ( 193) showed that
zinc was essential for growth in birds also.
A t present, at least 15 animal species, man
included, have been shown to require
zinc.
A dwarfism syndrome in man was first
described by Lemann in 1910 (129). T his
syndrome was reported subsequently in
Turkey by Reimann (237) in 1956 and bv
Okcuoglu et al. (195) in 1968, in Portugal
by LeCour ( 128 ) , and in Morocco by Faure
(53). I n 1960 and 1961 Prasad et al. (224)
and H alsted and Prasad (83) published a
detai led cl inical description of 11 dwarfs
w ith extreme iron deficiency anemia who
were studied in a hospital at Palliavi Uni
versi ty, Shi raz, I ran. They suggested that
the endocrinopathies (growth and sexual
retardation) observed in the dwarfs
might be caused by zinc deficiency. Sub
sequent biochemical investigations (225,
226, 257) in similar dwarfs residing in
the Nile delta of Egypt demonstrated
abnormalities of zinc metabolism. Dai ly
oral supplementation with zinc sulfate
resulted in signif icantly more rapid growth
and sexual development. These findings
were confirmed in I ran by Halsted et
al. (80, 84) in a study on 17 nutritional
dwarfs. I n this study sexual function oc
curred in 224  ±72 days (mean  ±so) innine dwarfs who were fed a wel l-balanced
hospital diet. In contrast, seven dwarfs, fed
the same diet plus 100 mg of zinc sulfate
dai ly, developed sexual function in 59 ±40
days. In 6 months the mean growth incre
ment in the nine dwarfs fed the hospital
diet alone was 4.2 Â ±1.9 cm, whereas in
dwarfs who were fed the same diet plus
zinc sulfate, the growth increment was
10.5 ±3.7 cm.The extreme degree of dwarfism and
total l ack of sexual development noted in
the above reports probably represent one
end of a spectrum, the other end being
represented by outwardly healthy but short
adolescents with delayed puberty and mild
anemia. Two studies have been publ ished
designed to determine whether oral zinc
supplementation of such mildly growth re
tarded individuals would cause a growth
response. Carter et al. (31) in Egypt gave
daily zinc supplementation for 5 months
with negative resul ts. Ronaghy et al . ( 251 )
in I ran administered a complete supple
ment that provided al l essential trace elements and vitamins with and without
added zinc to each of two groups. Those
receiving zinc developed sexually more
rapidly than those who did not (P < 0.02).
I t thus appears that zinc, in addition to
other essential nutrients and calories, may
be a limiting factor in normal growth and
well-being of certain populations in under
developed regions of the world.
B io l o gi c a l fu n c ti o n s
The biochemical functions in which zinc
has been implicated as necessary include:
1) enzymes and enzymatic function, 2) pro
tein synthesis, and 3) carbohydrate metab
olism.
K eilin and Mann in 1939 (116) and 1940
(117) f irst showed that zinc was an integral
and necessary component of carbonic an-
hydrase of red blood cells. Since then, at
least 18 metal loenzvmes have been shown
to contain zinc (202). Several enzvmes
necessary for cel lular oxidation, such as
human alcohol dehydrogenase, are zinc
dependent. M ore complete information on
the importance of zinc in enzymatic func
tion may be found in recent revi ews (160,
202).
Zinc has been shown to be related to
protein synthesis in microorganisms, ani
mals, and animal tissues. The synthesis of
both DNA (63, 132) and RNA (315, 321,
327) is inhibited when zinc is lacking.
Protein synthesis appears to be reduced or
altered in zinc-deficient rats (295, 326).
8/19/2019 Bioinorganica del zinc
6/34
35 0
J. A. HALSTED, J. C. SMITH, JR. AND M. I. IRWIN
Somers and Underwood (277), in a con
trolled study, found that the output of uri
nary nitrogen and sulfur w as significantly
higher in zinc-deficient lam bs than in con
trol anim als. This observation suggestedim paired protein or am ino acid utilization.
The data did not show whether the defect
was due to impaired tissue synthesis or to
increased catabol ism.
H su et al. ( 1 04 -107 ) recently elabo rated
on the relationship of zinc to protein syn
thesis. They showed that, in vivo, the in
corporation of 35S a mino acids into organ
and skin protein w as significantly altered
in z in c-d efic ie nt ra ts .
The role of zinc in carbohydrate m etab
olism is controversial. In 1937 Hove et al.
( 1 03 ) and m ore recently Quarterm an et al.
( 2 35 ) re po rte d d ec re as ed g lu co se to le ra nc e
in rats that w ere zinc defic ient. In c ontrast,
Macapinlac et al. (139) could find no dif
ference in fasting bloo d sugar, or in glucose
and insulin tolerance curves betw een zinc-
deficient rats and ad libitum controls.
Studies by M ills et al. (169) indicated that
zinc influences the membrane transport
and utilization of glucose. A lthough H ard
ing et al. (89) showed that the insulin
molecule contains 2 zinc atoms, it has not
been demonstrated that these are neces
sary for th.e biological activity of insulin.
K inetic studies by W eil et al. (322) have
indicated, however, that the stability of
zinc-free insulin is less than that of zinc
insulin. It is evident that the exact role of
zinc in carbohvdrate m etabolism has yet
to b e e lu cid ate d.
METHODS OF MEASURING ZINC
B ecause of the lack of precise analytical
procedures for the determ ination of zinc by
the earliest workers, zinc was assigned to
the category of a t race elem ent. The ele
m ent could be detected but not accurately
quantitated. As m ethods becam e m ore sen
sitive, the problem of contamination due
to the ubiquitous nature of zinc became
evident. For exam nle, blood for zinc analv-
sis is easilv contaminated bv the needles
and svringes used for venepuncture. V acu-
tainers, now widelv used to draw venous
blood, have been shown to be a source of
contamination (86, 91). The use of all-
plastic polyethy lene syring es 1 and certa in
sta in le ss ste el n ee dle s,2 h ow ev er, p re ve nts
contamination from these sources (81).
Anticoagulants also may be a source of
e xt ra neou s z in c.
Early analytical determ inations of zinc
relied upon gravim etric and volum etric
m ethods that were relatively insensitive.
Beam ish and W estland (7) have reviewed
such me thod s.
Am ong the m ore m odern techniques are
a tom ic abs orp tio n s pe ctro ph otometry , em is
sion spectrochem ical m ethods (173), and
X -ra y emis sio n sp ec tro gra ph y ( 1 ). O f th ese ,
atom ic absorption spectrophotom etry is at
present the most popular method for ana
lyzing zinc in biological sam ples (76, 249,
271). W alsh (318), an A ustralian physicist,
developed the method in 1955 and since
then several com mercial instrum ents have
becom e a vailable. T he general ad vantages
of this m ethod include: 1) simplicity and
ease of ope ration, 2 ) sensitivity, precision
and accuracy, and 3) cost. In its simplest
form the instrumentation consists of a
hollow cathode lamp (light source), a
flame atomizer, grating or prism , and a
photo detector. S am ple prep aration is a per
sistent problem in this m ethod because the
sample must be aspirated into the instru
ment. Dry ashing may result in losses of
zinc, presumably due to volatilization
( 2 96 ). A t presen t, the m ost popular m ethod
of preparing biological solid m aterial for
atom ic absorption analysis of zinc is acid
(w et) d ig estio n (2 74 ).
A lthough m any of the techniques for the
analysis of zinc are extrem ely sensitive,
each method is no better than the stan
dards available. The sam e standards rarely
have been used by different laboratories.
B iological reference standards are now
available from the U . S. N ational B ureau of
Standards.3 For an accurate com parison of
zinc analyses betw een laboratories it is im
p era tiv e th at a u niv ersa l re fe re nc e sta nd ard
b e u se d.
ZIN C IN FO OD
Con te nt in c la sse s o f fo od s
Classes of foods cannot be rigidly cate
gorized acco rding to zinc concentration be-
iP ee l-A -W ay S cien tific. S o. E l M onte , C aliforn ia
91733.
*Mono je ct -2 50 , She rwood Medi ca l I ndus tr ie s, I nc .,
Delano. Flor ida 32720 .
 »U .S . N ati on al B ur ea u o f S ta nd ar ds , Wa sh in gt on ,
D . C . 2 0204 .
8/19/2019 Bioinorganica del zinc
7/34
RESEARCH ON Z INC REQUI REM ENTS OF M AN
351
TABLE 1
Z in c c on ten ts o f selecte d fo od s1
Food i tem
Zinc
Meat p ro du cts
R oa st b ee f
B eef patty (raw )
Ch ic ken b re as t
C hi ck en th ig h
Da ir y p ro du ct s
Milk
C ream (half and half)
ma/100 g
wet w t
6.4
4.7
1.1
2.8
o «
4
BreadsWhiteRyeWhole
WheatVegetables
an druitsPeasPotatoesGreen
beansCarrotsTomatoesApricotsPeachesPearsApplesauceOrange
juiceApple
juice
GrapefruituiceBeveragesTeaCoffeeDecaf
coffee0.571.341.04O.fi )0.2(10.210.250.200.120.070.080.080.110.07
0.100.020.030.04
1 T ak en f rom Osi s et al. 197) .
cause of the variability of the zinc contents
of foods within each class. There is a wide
range of values published in the literature
for the same food because of the differ
ences in analysis, source, and variety. In
general, meat, eggs, m ilk products, and
shellfish ( o ysters in particular ) are the best
sources of zinc. Fruits and vegetables usu
ally are poor sources. Berfenstam ( 1 1 ) re
ported human m ilk to contain 3 to 5 ppm
( w et w eight ) w hich is com parable to cow 's
m ilk ( 1 89 ). M ore recent analyses of infant
foods showed that 22 mature human milk
sam ples contained a m ean zinc concentra
tion of 1.34 ppm and four commercially
prepared infant formulas, as consum ed,
contained 1.47 to 3.99 ppm (180). These
concentrations are markedly lower than
that of 20 ppm previously reported for
hum an colostrum (147). The im portance
of zinc in colostrum was demonstrated by
Nishim ura ( 1 84 ) who showed that zinc de
ficiency developed in suckling mice de
priv ed o f colo strum . O ral adm inistratio n of
zinc prevented the deficiency. M utch andHurley4 reported that dietary zinc de
ficiency in lactating fem ale rats resulted in
zinc deficiency in the suckling young due
to a lowered zinc content of the m ilk.
These studies suggest that consideration
be given to the adequacy of zinc in infant
formulas.
Content of typical m ea ls or diets
During the course of m etabolic balance
stu die s, O sis e t a l. (1 97 ) a na ly ze d n um ero us
diets. The average total zinc content of 138
diets used in metabolic balance studies
sam pled and analyzed over a 4-year period
was 12.2 mg/day. The zinc contents of a
standard hospital diet according to indi
vidual meals were: breakfast, 2.2 mg;
lunch, 4.7 mg; and dinner, 4.4 mg. Thus
the total zinc content of the daily standard
hospital diet was 11.3 m g, very sim ilar to
the m ean of the experim ental diets. M urph y
et al. (178) published analyses of trace
minerals in Type A school lunches col
lected from 300 schools in 19 states. The
average zinc content of these lunches,
served to sixth grade children, was 3.91
mg. The zinc content of selected foods as
reported by Osis et al. (197) is shown in
table 1.
An estimation of the zinc content of
several diets from other cultures was sum
marized by Eggleton in 1938 (47). The
diet of native sailors in the Dutch East
Indian Navy prior to 1874 was estim ated to
contain 7.3 m g of zinc. The diet consisted
mainly of meat (beef, pork, or fish) and
rice. (Its caloric content was not known.)
The Steffanssen all-meat diet (lean beef,
fatty tissue, liver, m arrow ) eaten by A rctic
explorers in the 1920's contained about 24
m g/day. The zinc content of a North China
diet was estimated as 9.5 mg/day. Grain
products and legumes furnished most of
the protein. Eggleton (47) estim ated that
the daily zinc intake of the poorest class of
Chinese in South China at that time was
«M utch, P . B. H ur ley. L . S. 1971) Z inc de
ficiency i n suck ling r at a. F ei l. Pr oc. 30, 043 Abstr .) .
Complete paper to be published in T he Journal of
Nutr i tion 1074.
8/19/2019 Bioinorganica del zinc
8/34
352
J. A. HA LSTED, J. C. SM ITH , JR. AN D M . I . IRW IN
l ess than 6 mg/day. He suggested that zinc
might be limiting at this level. The southern
China diet consisted mainly of polished
rice, sea fish, and cooked cabbage.
F a cto rs in flu en cin g zin c c on te nt o f fo od s
Ma nufa ctu ring tech niques. The r efining
of foods usual ly results in a decrease in the
zinc content. For example, Czerniejewski et
al. (40) found that during the milling
process of wheat for f lour, up to 80% of the
zinc may be lost. Schroeder et al. (263,
264) reported similar data. Thus, bread
made from white flour has a lower zinc
content than whole wheat bread (197).
Cornstarch contains much less zinc than
the whole corn kernel (165) . The possibly
deleterious ef fects of ref ining foods have
been discussed by M ertz (157) and
Schroeder (263).
P repa ra tion of foods. F ood pr epa ra tion
methods also affect zinc concentration. For
example, water added for cooking purposes
w il l vary markedly in zinc content among
di fferent regions, thus changing the zinc
level of the prepared food. Kopp ( 123 )
analyzed 380 samples of tap (finished)
water and reported the average zinc con
centration to be 79.2 /ig/liter. T he range
was from 3 to 2010 fig/liter. T he zinc con
tent of foods will also be affected by the
equipment and utensils used to prepare
and store the food. For instance, the cor
rosive action of acid foods in contact with
galvanized metal increases the zinc con
centration. This source of contamination,
however, has decreased with the increased
use of stainless steel , plastic, and plastic-
coated cooking utensils.
M ET ABOL IC A SPECT S OF Z IN C
IN H UM AN N UTRITION
D istr ib utio n in th e b od y
Several studies have been publ ished on
the distribution of zinc in tissues. Extensive
work on trace-element concentration in the
tissues of man has been carried out by
Tipton et al. (298). They analyzed, by
emission spectrography, 24 trace elements,
including zinc, in 10 different tissues of 162
adult subjects from various countries out
side the continental Uni ted States. About
half of the subjects had died from acci
dental causes, but the remainder had died
of various diseases. The tissues were col
lected from primitive A frican cultures,
L ebanon, I ndia, the Far East and Europe
(Switzerland and Scandinavia). T hese
samples represented people of a wide geographical distribution as well as with a
variety of dietary habits. Surprisingly, l ittle
variation was found in the zinc content.
The resul ts were simi lar to data obtained
by Perry et al. (211) from 150 healthy
A merican adults who died suddenly of
accidents.
Other data have been reported by Netsky
et al. (182), T ipton and Cook (297), Butt
et al. (25), Eggleton (47, 49), Galin et al.
(66), Schrodt et al. (262), and M cBean et
al. (148). T he results are summarized in
table 2. The distribution of stable zinc in
various tissues of rats (231) , calves (163) ,
and pigs (232) is included for comparisonin this table.
A highly signi ficant correlation among
dietary, plasma, and bone zinc contents
has been demonstrated in rats (274) . Often
the zinc concentrations of the k idney and
liver are not decreased when there is zinc
deficiency.
The concentrations of zinc in plasma or
serum, blood cells, and hair have been
extensively studied and will be considered
in more detail.
P la sma a nd ser um. Althoug h pla sma a nd
serum have usual ly been regarded as pos
sessing similar zinc concentrations (305,
311), Foley et al . (55) reported that seruminvariably has a higher zinc content than
plasma (about 16%). Thev attributed the
greater serum content to the l iberation of
zinc by disintegrated platelets, to a dilu
tion factor and to invisible hemolysis which
always occurs (268). I n a sense, serum is
always slightly contaminated by the zinc
contained in platelets and by hemolysis of
red cells.
Values for the concentrations of zinc in
plasma under normal conditions obtained
by di fferent laboratories using di fferent
methods are, with a few exceptions, in rea
sonably good agreement (table 3). T he
constancy of most estimates since 1965coincides with better methods for avoiding
contamination and with more precise ana
lytical methods.
Red blood cells. The r epor ted zinc con
tent of red blood cells varies from about
8/19/2019 Bioinorganica del zinc
9/34
RESEARCH ON ZINC REQUIREM ENTS OF M AN
&5i gSe
1^
8/19/2019 Bioinorganica del zinc
10/34
5
J. A . HALSTED, J. C. SMITH, JR. AND M. I. IRWIN
10 to 14 /tg/m l. Ross et al. (256) using the
dithizone method found that the red cells
of 48 norm al subjects contained 11.8 Â ±1.8
/x g zin c/g . A lso u sin g th e d ith iz on e m eth od ,
Prasad et al. (229) found a mean red cell
z in c c on te nt o f 1 3.7 Â ±1 .2 /Â ¿g /m lin a s tu dy
with 14 normal subjects. W hen samples of
the same blood were analyzed by atomic
absorption spcctrophotometry, a mean
value of 14.0 Â ±1.5 /Â ¿g/m lw as obtained.
Mansouri et al. (144) also using atomic
absorption spectrophotometry found a
m ean zinc content of 11.8  ±1.7 j «.g/m ln
the red blood cells of 51 normal subjects.
In the same laboratory, M cBean and
Halsted (149) obtained a mean value of
10.1 ±1.2 /ug/m l in 10 fasting controls.
After a meal, the mean value (10.1 ±1.0
/ag/m l) w as not sig nificantly changed. D if
ferences in techniq ue, for instance in sp eed
of centrifugation, m ay account for part of
t he d if fe re nc e in e stima te s.
Leucocytes. The zinc content of leuco
cytes has been determ ined (44, 170, 214,
306) with general agreement that these
cells a re rich in zinc.
Hair. Hair zinc concentration has been
reported to be affected by zinc intake in
rats (242), swine (130), cattle and goats
(164,168), and in m an (87).
Abs orp tio n o f Z in c
As with iron, apparently only a small
percentage of ingested zinc is absorbed.
Abs orp tio n is d iffic ult to a sc erta in p re cis ely
and intake-output studies are not valid
TABLE 3
P la sma o r s er um ti ne c on ce nt ra ti on in n orma l a du lt s1
( ng /1 00 m l)
Investigator
R efer ence Y ear
M e an  ± SD
Range
Method
Not«
WolffVikbladhBerfenstamKoch
etl.Vallee
etl.SmitFuwa
etl.Gofman
etl.Butt
etl.Prasad
etl.Kahn
etl.Sullivan
&ankfordOlehy
etl.Helwig
etl.Parker
etl.Rosner
&orfienHalsted
etl.Mahanand
etl.Davies
etl.Halsted
&mithSinha
&abrieliMeret
&ankinLindeman
etl.Kurz
etl.Pekarek
et al.(328)(311)(11)(122)(308)(272)(65)(67)(26)(229)(115)(292)(196)(92)(205)(255)(81)(143)(41)(85)(269)(156)(134)(125)(20
±(P)»120±23(P)121±19(S)139±29(S)122±
3(8)98±
2(S)5140±
6(S)5104±14(P)103
±(P)84
±30(8)94±12(S)93
±(P)91±17(S)90±10(S)138±13(P)96±13(P)94
(P)95±13(P)96±12(P)120±20(S)92±
3(S)696
(P)119(8)102±17(S)84-16370-170101-139—72-11287-23486-10276-12572-11576-1
fo ralesand
femalesNewborn,
125±5Males,
12 1±2955
adultsAdults39
adults170
adults64
adults23
adultsChildren,
108±15Males,
95±13Females,
16±11Children,
89±13Males,
96±13Females,
97±11100
m ale s 1 21±18100
females18±2145
females0±337
m ales 9 4±3Males,
96Females,
8811
adults10±2137
children28±1799
males
1 Z inc con cen tr at ion h as been f ou nd t o b e 16 h igher i n ser um t han i n p lasm a i n on e st ud y (21)8).
p lasm a. 4 A .A .S. ; at om ic ab sor pt ion sp ect rop hot om et ry. > SE .
(S) ; ser u m .
8/19/2019 Bioinorganica del zinc
11/34
RESEARCH ON ZINC REQUIREM ENTS OF M AN
355
indicators because excretion of zinc is
nearly al l v ia the gut. Thus data indicating
an increased absorption may also be inter
preted as indicating a decreased excretion
and vice versa.Data on the site or sites of absorption in
man and on the mechanism(s) of absorption,
whether this be by active, passive or facul
tative transport, are meager. Pearson et al .
( 2 07 ) using the everted gut sac of the rat
provided evidence that zinc is actively ab
sorbed into the intestinal mucosa against a
concentration gradient. They reported that
zinc was most efficiently absorbed from the
distal gut segments. M ore recently, M eth-
fessel and Spencer (159) using 65ZnClo,
studied specific absorption sites in rats by
means of l igated intestinal sacs. They con
cluded that the absorption of 65Znwas sig
nificantly greater f rom the duodenum than
f rom the more distal segments of the smal l
intestine. Over a 2-hour observation period,
absorption was much less from the mid-
jejunum and i leum. Only minimal amounts
were observed f rom the stomach, cecum
and colon. These data suggest that si tes of
zinc absorption may be simi lar to those of
iron.
Becker and H oekstra (9) recently re
viewed the available information on intesti
nal absorption of zinc. They concluded that
zinc absorption is variable in extent and
is highly dependent upon a variety of fac
tors.' A mong the factors that they sug
gested might af fect zinc absorption were
body size, the level of zinc in the diet, and
the presence in the diet of other potentially
interfering substances such as calcium,
phytate, other chelating agents, and vi ta
min D .
Ava i la b il it y o f zi nc
Edwards (46) using chicks studied the
availability of zinc from various com
pounds and ores. H e reported that zinc
was most avai lable f rom zinc sul fate, zinc
metal and zinc oxide, and least available
from sphalerite and franklinitc. Later
Roberson and Schaible (247) confirmed
these observations.
Other factors inf luence the absorption
and retention of zinc and thus its avail
abi li ty . Phytate ( inositol hexaphosphate ) ,
which is present in cereal grains, markedly
impairs the availability (absorption) of
zinc. This was f irst shown in 1960 by O'Del l
and Savage (194). Later Oberleas et al.
( 186 ) showed that phytic acid added to an
animal protein diet depressed growth in
swine. U sing rats, Oberleas and Prasad( 190) demonstrated a close relationship
between zinc and the utilization of soybean
protein. Without zinc supplementation, rats
fed a 12% soybean diet gained less than
half as much as rats that were supple
mented with zinc. O'D ell (192) reported
that autoclaving soybeans destroyed most
of the phytic acid. In contrast, Lease ( 127)
autoclaved sesame meal and found no re
duction in phytate despite the fact that
there was a marked increase in zinc avail
ability to the chick. L ikuski and Forbes
( 133) showed that phytic acid depressed
the avai labi li ty of zinc whether the protein
source was pure amino acids or casein.
Such studies have a close relationship to
zinc in human nutrition because there is
strong evidence that phytate exerts a simi
lar effect in man. Reinhold (238, 239)
found that unleavened bread, consumed in
large amounts by the I ranian villagers
(often providing the major source of pro
tein) , contains significantly more phytate
than urban breads which are leavened and
al lowed to ferment (P < 0.001) . Leavening
results in destruction of phytate. The omis
sion of the leavening process in I ranian
village breadmaking is presumably respon
sible for the high content of phytate.
T he data suggesting that phytate en
hances the possibi li ty of zinc def iciency in
man were strengthened by the reports f rom
Egypt (225, 226, 257) and Iran (83, 84)
that zinc def iciency occurred under condi
tions where unleavened bread was con
sumed in great amounts. Reinhold et al.
( 244) tested the hypothesis that phytate
ingestià ³n may result in zinc defi ciency.
Three adult subjects were studied. During
an initi al 16-day control period a diet pro
viding approximately 0.7 g phytic acid was
fed. Fol lowing the control period, sodium
phytate (4.5 g/day) was added to the diet
for 28 days yielding a total intake of about
2.5 g phytic acid/day. Then during the
next 32 days, no sodium phytate was fed,
but tanok replaced the low phytate bread
in the experimental diet. The tanok, a bread
consumed by vill agers of Southern I ran,
provided 2.6 to 3.4 g of phytate dai ly . Dur-
8/19/2019 Bioinorganica del zinc
12/34
356
J. A. HALSTED, J. C. SM ITH, JR. AND M . I . IRW IN
ing the sodium phytate period (28 days)
zinc balances became significantly less posi
tive. Occasionally, negative balances were
observed. D uring the tanok period (32
days), zinc balances became more nega
tive. After these two experimental periods,
a white bread low in phytate was given to
two of the subjects for 32 days. During this
period of low phytate ingestion, zinc bal
ances became positive again in both sub
jects.
The avai labi li ty of z inc from foodstuf fs,
w ith major emphasis on the effect of phv-
tate, was rev iewed by Oberleas et al . ( 188)
in 1966. M ore recently Oberleas (185),
studying phytate-mineral complexes, sug
gested that the chelating properties of
phytate may induce a w ide variety of min
eral def iciencies depending on which ele
ment first becomes limiting. Chemical
studies indicate that phytate decreases zinc
avai labi li ty by forming an extremely insol
uble calcium-zinc-phytate salt at the pH
ranges found in the upper smal l intestine
where most minerals are absorbed (141,
187, 313). Judging from the information
now available on the deleterious effect of
phytate in cereals on optimum growth and
protein uti li zation, some amino acid sup
plementation programs may not be fully
successful without careful consideration of
the possibility of abnormal zinc metabolism
associated with cereal diets.
O ther factors that possibly may affect
the availability of zinc include the zinc
status of the organism, geophagia, the pres
ence of chelating agents (other than phy
tate) , and vi tamin D.
Zinc sta tus. H eth et a l. 96), wor kin g
with rats, and Prasad (222), studying hu
man subjects, observed that the proportion
of oral ly administered zinc lost in the feces
decreased when the animals or human sub
jects were zinc def icient. Prasad et al . ( 225 )
suggested, however, that this increased ap
parent absorption was probably due to de
creased excretion of zinc rather than to the
increased true absorption.
G eoph a gia . Minnich et a l. 171) found
that clay from T urkey inhibited iron ab
sorption in human subjects. Nearly al l sub
jects with severe nutritional dwarfism
studied in I ran gave a history of eating
large amounts of clay for many years. Be
cause the evidence indicated that zinc de
f iciency was the basic cause of this dwarf -
ism syndrome, it was logical to suspect that
Iranian clay might hinder zinc absorption.
Furthermore, when a solution of 6BZnwas
mixed with this clay, 97% of the radio
activity was removed from the solution.
W hen, however, I ranian clay was fed to
zinc-deficient rats, it proved to be a life-
saving source of zinc (274). A plausible
deduction, therefore, is that the subjects in
I ran may have sought zinc through the
ingestion of clay.
C hela ting a gents. C on sider able wor k ha s
been reported on the effect of chelating
agents on zinc absorption. Most of these
studies were carried out in animals and
have been summarized by V ohra and
K ratzer (314) and Maddaiah et al. (141).
The ability of EDTA(ethylenediaminetetra-
acetic acid) to complex readily with zinc
has led to i ts use in removing radioactive
zinc f rom the body (279 ) .
Vita min D . Wor ker a nd Mig icovsky 32 9)
found that the movement of zinc into the
bones of chicks was enhanced by vi tamin
D. They suggested that the site of the
vitamin's ef fect on zinc metabol ism might
be in the absorption mechanism. Later
Becker and Hoekstra (8) observed in
creased absorption of dietary zinc in rats
treated with vi tamin D. Addi tional studies
with 65Zn convinced them that the in
creased absorption of zinc was not the pri
mary response but rather was the resul t of
an increased need for zinc secondary to in
creased skeletal growth.
E xc re tio n o f zin c
McCance and Widdowson (153) found
that regardless of whether zinc enters the
body oral ly or parenteral ly, i t is excreted
almost whol ly via the feces. Animal experi
ments have shown that fecal excretion is
chiefly by way of the pancreatic juice re
gardless of the route of zinc intake. Negl i
gible amounts are excreted by the liver
into bi le (153, 267) . Urinary zinc excretion
in normal individuals and those with dis
eases was summarized by Roman (250).
I n normal subjects, most of published
means ranged between 400 and 600 /¿g/24
hours.
Steele (284) recently reported data sug
gesting that renal handling of zinc is dif
f erent f rom that of other divalent cations.
8/19/2019 Bioinorganica del zinc
13/34
RESEA RCH ON Z IN C REQU IREM EN TS OF M A N
357
For instance, when saline-loaded subjects
were infused with a NaCl solution, zinc ex
cretion decreased, whereas that of calcium
and magnesium increased. Furthermore,
when a diureti c, either ethacrynic acid orfurosemide, was administered, urinary zinc
concentration decreased significantly while
the concentrations of calcium and mag
nesium increased. The mechanism govern
ing renal excretion of zinc is not clear.
Increased urinary zinc excretion (zinc-
uria) has been reported to accompany
nephrosis (52), diabetes (36, 154, 215),
postalcohol ic hepatic cirrhosis (229, 291,
307), and porphyria (213, 267). McCance
and Widdowson (153) found the urinary
zinc excretion in two patients with albu
minuria to be 3.3 and 2.0 mg/day—about
seven times the amount excreted by thei r
healthy subjects.Spencer and Samachson (282) noted
that urinary zinc excretion rose to high
levels during total starvation in extreme
obesi ty. They found a tenfold increase in
dai ly excretion during thei r ten 6-day bal
ance periods. Despi te the urinary losses,
plasma zinc levels did not change.
Recently Fel l et al . ( 54) studied urinary
zinc excretion by two patients after surgery
for total hip replacement. They adminis
tered 05Znto the patient in suf ficient time
before surgery to al low i ts incorporation
into the muscles. They found large in
creases in urinary excretion of 66Zn, total
zinc and nitrogen af ter surgery. The excre
tions rose to a maximum about 10 days
postoperation. The close correlation be
tween the excretion of 65Znand total zinc
suggested that the zinc was being with
drawn mainly from the skeletal muscles.
Because urinary total zinc was also closely
correlated with urinary nitrogen, Fel l et al .
(54) suggested that urinary zinc may pro
vide an index by which to estimate muscle
catabolism.
Bin din g o f zin c to ser um p ro tein
Early work by Laurel on zinc binding
was summarized and amplified by Vikbladh
in 1951 (312). T he portion of plasma zincbound to albumin was described as loosely
bound, whereas that associated with the
globulin fractions was more tightly bound
(312) . The relative amounts of loosely and
tightly bound zinc are at present some
what controversial, but it appears that most
is in a tightly bound form. The loosely
bound zinc complex according to Vikbladh
(312) is concerned with zinc transport.
These f indings on zinc binding with serumproteins have been confirmed by others
(22, 203, 305). The identi ty of the fraction
to which zinc is f irmly bound has been the
subject of several studies. Surgenor et al .
(293) reported that zinc could combine
w ith a ß iglobul in ( transferrin ) in vitro.
Later Boyett and Sul livan (22) f rom studies
of the distribution of protein-bound zinc
suggested that transferrin and alpha-2
macroglobulin may have an important role
in internal zinc exchange. Parisi and V allee
(203) isolated alpha-2 macroglobul in and
found that it contained 30 to 40% of the
total serum zinc. They suggested that
alpha-2 macroglobulin is the principal zinc
metalloprotein in human serum.
Prasad and Oberleas (227) using 86Z n
incubated serum found that from 2 to 8%
of the total serum zinc was ultraf il terable.
In their in vitro studies they found also that
several amino acids, specifically histidine,
glutamine, threonine, cystine, and lysine,
when added to predialyzed serum, in
creased the amount of ul traf il terable 65Zn
several fold. They suggested that this amino
acid bound fraction of zinc may play a
significant role in biological transport.
F a c to r s i nfl ue nc in g t he c on ce nt ra t io n
of zinc in pla sma
As noted in table 3 the mean plasma
zinc concentration reported in recent years
has been reasonably constant. M ost of these
results were derived by atomic absorption
spectrophotometry, but the neutron acti
vation, f luorometric, and dithizone meth
ods have given similar values. The use of
polyethylene materials, which became
avai lable in the 1960's, has undoubtedly
aided in el iminating sources of contami
nation.
L ittle work has been done on the ef fects
of age or sex differences on plasma zinc
levels. Somewhat higher levels have been
found in newborn infants and children
than in adults (11, 143), but another report
showed contradictory data (85). N o sig
nificant differences between males and
females have been reported (85) .
I nconclusive data exist on the effect of
8/19/2019 Bioinorganica del zinc
14/34
358
J. A . HALSTED, J. C. SM ITH, JR. AN D M . I . IRW IN
meals on plasma zinc concentration. Davies
et al. (41) reported that the zinc level de
creased fol lowing intravenous or oral glu
cose loading, but this has not been con
firmed. In another study (149), the effectof a meal containing 3.92 mg of zinc on the
plasma zinc level was negl igible in 10 nor
mal individuals who had tasted 12 hours
prior to eating the meal. There are few
data on the ef fect of fasting on the plasma
zinc levels of man. A s noted previously,
Spencer and Samachson (282) reported no
change in plasma level in one obese patient
treated by total starvation despite a tenfold
increase in urinary zinc excretion.
Many factors, including pregnancy and
oral contraceptives, various diseases, and
stress, induce the lowering of the plasma
zinc concentration (41, 85). Whether this
ref lects zinc def iciency, a redistribution ofzinc, or an emergency cal l on avai lable ci r
culating zinc loosely bound to albumin is
not clear. Wacker et al. (316) in 1956
noted that serum zinc concentration was
lowered af ter an acute myocardial infarcì.
L indeman et al. (134) also noted that the
zinc level fel l rapidly after extensive sur
gery, myocardial infarcì,and acute infec
tions. I t rose to normal during convales
cence. Similarl y, after injection of endo-
toxin in man5 and rats (208) a sharp fall
in serum zinc level was noted. A s the in
fection subsided, the serum zinc level re
turned toward normal (208, 210, 319). I n
pulmonary tuberculosis and in varioustypes of chronic l iver diseases the plasma
zinc level was usual ly depressed, rising
toward normal as the patient recovered
(85).
Observations with burned and wounded
rats suggested to Strain et al. (288, 289)
that zinc was essential for wound heal ing.
O ther investigators using rats (258, 126,
191), cattle (166) , and hamsters (289) also
observed improved heal ing when zinc was
administered. Sandstead et al . ( 258) sug
gested that collagen formation is impaired
in conditions of zinc def iciency. Recently
Stephan and Hsu (285) found that in zinc-
defi cient rats, there was decreased DNAsynthesis as indicated by reduced thymi -
dine-methyl-3H incorporation into the DNA
of skin. They suggested that this observa
tion of impaired skin D NA synthesis to
gether with a previous observation of de
creased incorporation of 14C-labeled amino
acids in skin proteins of zinc deficient rats
( 105) might indicate a molecular basis for
the relationship of zinc to heal ing (285).
At present there is conf licting evidenceon the effect of zinc on wound healing in
human subjects. Pories and Strain (219)
in 1966 reported that, with oral administra
tion of zinc sul fate heptahydrate, heal ing
time was apparently decreased. Thei r ob
servations included the measurement of
wound volume during the healing of piloni-
dal sinus tract excision wounds in two
unsupplemented patients and one zinc-
supplemented patient. When the work was
extended to include 20 young men (217,
218), 10 of whom received zinc supple
ments, healing time was significantly re
duced in the supplemented group (45.8 vs.
80.1 days) . Studies on heal ing of leg ulcers
(72, 77, 78, 113, 266) also indicated sig
nificantly higher rates of healing in pa
tients to whom zinc was administered as
compared with nonsupplemented controls.
Other investigators, however, failed to find
that healing was accelerated after zinc
supplementation. Brewer et al. (23), for
instance, in a double blind study with 14
patients with decubitus ulcers did not f ind
any difference in healing time between
zinc-treated and control patients. Likewise,
M yers and Cherry (181), studying 51
patients, 36 to 80 years old, w ith chronic
leg ulcers, and Barcia (5), w ith 20 young
men who underwent surgical treatment forchronic pilonidal disease, failed to show an
improvement in healing time in those pa
tients who were treated w ith zinc. Pories
and Strain (220) in reviewing these studies,
suggested that the patient's initial zinc
status may inf luence his response to zinc-
therapy. Holböökand Lanner (78), for
instance, observed significant differences in
heal ing time between zinc treated and un
treated patients in a group whose indi
vidual serum zinc levels were less than
110 /ig/100 ml but not in a group whose
serum zinc levels were 110 /¿g/100ml or
higher.
For many years there has been interestin a possible relationship of zinc to mal ig-
6 Smith, J. C., Jr., M cDaniel, E. G., M cBean, L. D.,
Doft, F. S. & Halsted, J. A . (1971) Effect of micro
organisms upon zinc metabolism. Proc. W estern
Hemisphere Nutr. Cong., Bal Harbour, Florida
(Abstr.).
8/19/2019 Bioinorganica del zinc
15/34
RESEA RCH ON Z IN C REQU IREM EN TS OF M A N
359
nant disease. Ross et al. (256), using 65Zn
in patients with neoplastic disease, found
that uptake of z inc in leukemia leucocytes
was about one-half that of normal sub
jects. The zinc content of blood consti tu
ents in Hodgkin's disease has been reported
to be low (4). Davies et al. (42) and
M organ (176) reported low plasma or
serum zinc levels in patients treated for
bronchogenic carcinoma. Smith et al. (275),
however, found no differences in serum
zinc levels between patients with untreated
bronchogenic carcinoma and normal con
trols. DeWys et al. (45) found that Walker
256 sarcoma implanted in zinc-def icient
rats grew at a markedly reduced rate com
pared with ones implanted in control , pair-
fed rats. These results suggest an increased
zinc requirement for tumor growth.
The wide variety of pathological statesin which plasma zinc concentration has
been found to be depressed suggests that
there may be several mechanisms involved
whereby zinc metabolism is altered in
disease. On the other hand, there also may
be a fundamental mechanism common to
all. I t is attractive to speculate that zinc is
required rapidly for enzyme formation or
protein synthesis when bodily insults occur,
and that the zinc that is loosely bound to
albumin is immediately avai lable for these
purposes. Of interest is the fact that the
zinc level rarely falls below 30 to 35% of
the normal. T his may correspond to that
amount loosely bound to albumin.
Re la tio ns hip o f zin c to e nd oc rin e fu nc tio ns
Endocrine abnormal ities in human zinc
def iciency have been studied only in cases
of nutritional dwarfism reported from
Egypt (34, 226) . Somewhat ambiguous re
sults were obtained in assessing growth
hormone, gonadotropin, adrenocortical, and
testicular function. In human pregnancy,
plasma zinc concentration is usuall y de
pressed to about two- thirds that of normal
(114). I n a study with rats, M cBean et al.
( 151) conf irmed the f indings, previously
observed in women (82) , that depression
of plasma zinc concentration occurs when
contraceptive hormones are fed. McBean
et al. (151) found that the estrogen com
ponent of the contraceptive compounds
was responsible for the plasma zinc lower
ing effect. A dditional work is needed to
establish more precisely the interrelation
ships between zinc and endocrine function.
In te rr ela tio ns hip s with o th er m in er a ls
C a lcium. Tu cker a nd Sa lmon 302) fir st
demonstrated that increasing the calcium
content of practical diets for swine en
hanced zinc-deficiency symptoms (skin
lesions and growth retardation) . Because
the basal diets fed were rel atively high in
zinc, 34 to 44 ppm, this was an apparent
demonstration of the antagonism of cal
cium to zinc. Numerous investigations with
swine using diets containing plant protein
have conf irmed the calcium-zinc antago
nism (35, 130, 131, 135, 136, 183, 286). I n
contrast, when swine were fed animal pro
tein diets the deleterious ef fect of calcium
on zinc uti li zation was not demonstrable
(10, 324). I n 1960 (57) Forbes reviewedthe interrelationship of zinc and calcium.
As pointed out by Forbes (58, 59) and
more recently by O'D ell (192), the con
flicting results regarding the antagonistic
effect of calcium toward zinc can be ex
plained by the presence of phytate. That
is, excess calcium in the presence of phytate
(which accompanies plant but not animal
protein) results in decreased zinc absorp
tion, enhancing zinc def iciency. The inter
relationships of calcium, zinc, and phytic
acid in promoting growth of pigs are
shown in figure 1.'
I t is doubtful whether the calcium an
tagonism to zinc absorption plays an important role in a well-balanced diet con
taining animal protein. Spencer et al . (283)
could not demonstrate a calcium-zinc an
tagonism in human subjects fed meat as a
protein source when calcium was varied in
the diet tenfold. However, the antagonism
may be a factor in diets high in plant pro
tein, i.e., beans, peas, and cereal grains.
C a dmium. C a dmium a nd zinc ha ve sev
eral similar chemical properties, including
a usual coordination number of 4, tetra-
hedral conf iguration, and isoelectronic
valence shells. In 1957 Pafizek (204)
showed that the destructive effect of in
jected cadmium upon testicular tissue
could be al leviated by zinc, and suggested
that the injury was due to interference with
9 By permission of the author B. L. O'D ell and the
publ isher American Journal of C linical Nutri tion.
8/19/2019 Bioinorganica del zinc
16/34
36 0
J. A. HALSTED..J. C . SMITH, JR. AND M. I. IRW IN
zinc function. Gunn et al. (74, 75), and
Mason and Young (146) confirmed the
antagonistic zinc-cadm ium effects on tes-
t icu lar function .
In hum an nutrition, the zinc-cadm ium
interrelationship has not been demon
strated. Schroeder et al. (264) have elab
orated on the close association between
cadm ium and zinc. Cadm ium , a nonessen-
tial elem ent, is invariably associated w ith
zinc in both geological and biological
matter.
Copper. In animal studies, excessively
high levels of zinc resulted in interference
w ith copper m etabolism (70, 142). Studies
such as those by Hoefer et al. (101) and
Wallace et al. (317) indicated that the
severity of parakeratosis in sw ine could be
alleviated by either zinc or copper, al
though zinc was usually more effective.
Ritchie et al. (246) reported that, in addi
tion to preventing parakeratosis in swine,
zinc gave protection against copper
toxicity.
The plasma zinc concentration was de
creased but copper concentration was in
creased in pregnant women (114) and in
those taking oral contraceptives (82). A t
present the significance of these observa
tio ns is n ot u nd ers to od .
W hen a diet composed entirely of meat
was fed to rodents, an anemia developed
that was responsive to copper (73, 174,
175). It was proposed that this meat
anem ia resulted not only from a relative
excess of zinc over copper present in m eat
but also from the lower calcium levels
found in m eat. The m eat anem ia, however,
could be reduced or prevented by cook
ing the meat (174). This suggests that it
was not due sim ply to a high zinc-copper
ratio but that a heat labile factor may have
been involved. Hoekstra (102) has re
v iewe d th is su bje ct b rie fly .
Others. In 1958 Sivarama Sasty and
Sarma (270) suggested that iron metab
olism was affected by toxic levels of zinc.
In addition, decreased concentrations of
iron in the liver were reported by Cox and
Harris (37), Magee and Matrone (142),
and Kinnamon (120) when rats were fed
to xic le ve ls o f z in c.
A n interaction of zinc and m olybdenum
was suggested by the investigations of
Gray and Ellis (71).
80 070 0
•600-Cn-¿
500-2
400-1
300-200-100-il1
†”Protein
S CCP.A.,
added, 0 0 0 1.4nmiJ^i>ifiC
C1.4
1.4Ça,
1.5 1.5 0.8 0.8 1.5.5Zn,
ppm 25 14 141414
11 4
Fig. I Effect of phytic acid on growth rate of
pigs fed diets based on soybean (S) or casein
(C) with varying levels of calcium and zinc.
Phytic acid (P.A .) was added to the casein diet.
Reproduced from Amer. J. Clin. Nutr. (1969)
22, 1316, by permission of the author and pub
lisher.
T he interrela tionships of zinc w ith oth er
m inera ls are obviously not lim ited to single
elements, i.e., zinc-copper or zinc-cad
mium . There have been some reports in
volving a sim ultaneous interaction of sev
eral m inerals (99, 136, 177, 243, 287). No
inform ation on su ch m ultiple in teractionsin hu mans w as found.
I nt er re la ti on sh ip s i ci th v it am ins
Vitamin A. Early studies on dark adap
tation indicated that ano ther nutrient m ight
be nece ssary fo r vitam in A u tilization (206).
Observations of reduced plasm a zinc con
centration in cirrhotic patients (85) sug
gested that this necessary nutrient m ight
be zinc. Studies with animals tended to
support this hypothesis. S tevenson and
Earle (286), for instance, reported that
zinc-deficient sw ine had depressed serum
vitam in A levels. These levels did not re
turn to normal even after massive oraldoses of vitam in A. Later, Saraswat and
A rora (260) reported that zinc supplem en
tation was necessary for maximum effi
ciency of vitam in A therapy in lambs that
were deficient in both zinc and vitam in A.
8/19/2019 Bioinorganica del zinc
17/34
RESEA RCH ON Z IN C REQU IREM EN TS OF M A N
361
M ore recently, Smith et al. (276) found in
rats that zinc was necessary for the mobili
zation of vitamin A from the liver into the
plasma. I n addition, retinal reductase, an
alcohol dehydrogenase of the retina in
volved in the metabolism of vitamin A , is
most probably a zinc metalloenzyme (307).
Vita min D . In 1 9 58 Whitin g a n d Be zea u
(324) reported that vitamin D decreased
the absorption and retention of zinc when
diets low in zinc were fed to pigs. W asser-
man (320) observed no significant change
in 8SZn absorption from the ligated du
odenum when rachitic chicks were fed
vitamin D .̂ As noted previously (page 356),
however, W orker and M igicovskv (329)
with chicks and Becker and I loekstra (8)
with rats observed that 7,inc absorption
and zinc uptake in the bones were en
hanced when vitamin D . ¡was fed. A posi
tive effect of vitamin D on zinc metabolism
was observed by others also (33, 118, 145).
Becker and Hoekstra (8) suggested that
the effect of vitamin D was primarily on
calcification and skeletal growth and that
the increased uptake of zinc bv the bone
was only a secondary effect. Chang et al.
(33), however, concluded from studios in
which bone growth and calcification of
rats were stimulated by either vitamin D
or protein that vitamin D probably exerts
an effect on zinc metabolism that is not
related to calci fi cation or bone growth.
Ribo fla vin. In 1 9 4 1, F o llis et a l. 5 6)
reported histological corneal lesions in
zinc-deficient rats and suggested that they
were apparently similar to lesions de
scribed by Bessey and Wolbach (17) in
uncompli cated ri bof lavin defi ciency in rats.
This was the f irst suggestion of an apparent
similarity in the effect of riboflavin and
zinc def iciencies upon speci fi c tissues. More
recently, French investigators noted a
similarity in the effects of riboflavin and
zinc deficiency in rats (221). Specifically,
in deficiencies of either zinc or riboflavin,
simi lar bony mal formations were observed.
In addition, fetuses from riboflavin-de-
ficient females had lower body zinc con
tents than fetuses from ribof lavin-sufficient
mothers.
Z INC DEFICIENCY
Animals
I n animals, zinc deficiency has been de
scribed in rats (300), mice (43), swine
(302), chickens (193), turkeys (124),
cattle (162), goats (167), lambs (200),
dogs (248), Japanese quail (62), rabbits
(69), squirrel monkeys (138), hamsters
(20), and guinea pigs (152).
The signs and svmptoms of zinc de
ficiency are markedly similar in different
animals. T hey include dermatitis, emaci
ation, alopecia, ocular lesions, testicular
atrophy, retarded growth, and anorexia.
A ll of these conditions with the possible
exception of testicular lesions are reversed
by zinc supplementation (6,161).
Mal formati ons of embryos and/or f etuses
due to zinc deficiency were reported for a
number of species. Blamberg et al. (19)
reported gross malformati ons involving the
brain, vertebrae, limbs, beak, and head of
chick embryos produced from eggs laid
by zinc-def icient hens. K ienhol z et al. ( 119)
confirmed these findings. H urlev and co-
workers (108-111) demonstrated congeni
tal malformations in rat fetuses delivered
f rom zinc-defi cient f emales. The malforma
tions included a high incidence of short or
missing mandibles, clubbed feet, fused or
missing digits, cleft palate, and brain ab
normalities. Related studies bv A pgar (3)
and Hurley and Sw enerton (112) indicated
that female rats fed a zinc-deficient diet
during pregnancy cannot mobilize zinc
from tissue stores in amounts sufficient to
supply the needs of normal fetal develop
ment. Swenerton et al. (294) suggested
that the high incidence of gross congenital
malformations resulting from zinc defi
ciency may be caused by impaired DNA
synthesis. The evidence of a relationship
between zinc deficiency and congenital
malformations in the rat was reviewed in
1967 (2). T o our knowledge no congenital
malformations due to zinc deficiency have
been reported in humans. I t is of interest,
nevertheless, that a brother of one patient
with the dwarfism syndrome originally re
ported in 1961 (224) had pronounced bony
abnormal ities as well as extreme dwarf ism.
J
8/19/2019 Bioinorganica del zinc
18/34
362
J. A. HALSTED, J. C. SM ITH, JR. A ND M . I . IRW IN
Behavioral impai rment was reported in
zinc-def icient adult rats (28, 29) . Perform
ance tests indicated that zinc-deficient rats
were inferior to zinc-suf ficient animals in
both learning ability and emotional sta
bility.
M a nâ € ” c li ni ca l a n d m et a bo li c fe a tu r es
I n man, the clinical aspects of zinc de
ficiency are similar to those described
above for animals. In summary, they consist
of severe iron def iciency anemia, hepato-
splenomegaly, short stature, infantile testes,
open epiphyses, spoon nai ls, f requently a
history of geophagia, and rough skin with
hyperpigmentation.
An interesting feature of the syndrome
is the rather prolonged rise in alkaline
phosphatase (a zinc-dependent enzyme)
which occurs when zinc is administered.
This could be due ei ther to a regeneration
of enzyme activity or to an increase in
bone grow th. I t was at first thought that
the syndrome was limited to males be
cause considerably higher concentrations of
zinc have been found in the testes than in
the ovaries. H owever, two well-docu
mented cases in females were included in
a recent report f rom Iran (84).
Ronaghy et al . ( 252) conducted a 6-year
follow-up study on the I ranian dwarfs in
whom zinc deficiency had first been sus
pected (224) . They found that the patients
remained well if they continued to eat a
wel l-balanced diet including meat. I f , how
ever, they resumed the vil lage diet in which
unleavened bread was predominant, their
symptoms of zinc deficiency reappeared.
Reinhold et al. (240) measured zinc,
calcium, phosphorus, and nitrogen intake
and output of 13 Iranian apparently healthy
vi llagers in a metabol ic ward ( table 4) . The
subjects were studied over a 6- to 7-day
period during which a well-balanced diet
was fed. The zinc data showed a wide
range of retention (—6.7 to 61.4%) . More
than half of the group had positive reten
tions greater than 25%. This observation
suggested to Reinhold et al. (240) that
these villagers had been depleted of zinc
previously.
Sandstead et al. (259) and Smit and
Pretorius (273 ) found very low serum zinc
levels in kwashiorkor. The latter workers
also found low urinary zinc excretion. A l-
TABLE 4
Zi nc b al an ce s tu di es o f a d ult I ra n ia n vil la ge rs 1
Subject
number12345678910111213SexM M M FM M FM FM FM FAgeVr3225382535473030243722
aiakg/dayN.A.0.070.070.18-0.060.03N.A.0.240.080.
15.4%-6.7-9.712.413.014.923.125.226
From Reinhold et al . (240) . ' AI weresufficiently healthy
to carry out normal activi ties of a v il lager . >Not avai lable
Alean for a 6 - to 7 -day period during which intakes in food
andiosses in excreta were measured. The hospital diet provided
2 400 calories, 75g ofprotein (15% from pulses, 21% from meat,¿8%from bread, and 36% from milk and cheese) , 80 to 120 e
of f at f rom butter and corn oi l, 24.6 mg of z inc, 1,031 mg of
calcium, and 1,513 mg of phosphorus.
though kwashiorkor is an extreme example
of protein-calori e malnutrition, zinc de
ficiency may be a secondary factor. To
date, littl e account of this possibili ty has
been taken.
Zinc deficiency, secondary to intestinal
malabsorption, recurrent infection and hy-
pogammaglobulinemia, has been reported
by Caggiano et al . ( 27) . One suspects that
zinc deficiency might be implicated in
growth retardation that may occur in cystic
f ibrosis, inf lammatory bowel disease, and
other malabsorption states, but these have
not yet been adequately investigated.
Reports by Henkin et al. (93-95) and
Schechter et al. (261) indicated that a de
crease in acuity of taste and/or smell may
occur spontaneously (idiopathic hypo-
geusia, hyposmia) or af ter the administra
tion of i/-penicillamine. These investigators
reported that this disorder may be cor
rected by the administration of ei ther cop
per or zinc.
Recently Hambidge et al . ( 87) reported
that 10 children over 4 years old in the
Denver area had hair zinc concentrations
of less than 70 ppm—a level simi lar to that
reported for Egyptian adolescents suffering
f rom symptomatic zinc def iciency (290) .
Seven of the 10 children had a history of
poor appetite and eight had heights that
8/19/2019 Bioinorganica del zinc
19/34
RESEARCH ON ZINC REQUIREM ENTS OF M AN
6
fell on or below the 10th percentile when
plotted on growth charts based on data
compi led by the Harvard School of Publ ic
Health and the Iowa Child W elfare Re
search Station. O f six children whose
taste acuity was measured, five showed
evidence of lowered acuity. A fter 1 to 3
months with dai ly dietary zinc supplemen
tation ( 1 to 2 mg ZnSO4/kg body weight ),
the taste acuity returned to normal and hair
zinc concentrations increased in the five
chi ldren. These chi ldren were from a group
of 338 subjects who were apparently
healthy Caucasians in the upper and mid
dle socioeconomic class.
Eggleton in 1938 (47) commenting on
a possible role of zinc defi ciency in beri
beri, said: A ttention is drawn, however,
to the fact that a diet producing beriberi
may supply minimal quantities of zinc,
and presumably also copper and manga
nese. To what extent shortage of minor ele
ments may be the cause of certain symp
toms usually associated with beriberi
remains to be shown, but i t is considered
possible that this shortage may account, in
part at least, for the pecul iar appearance of
the hair, the dry skin and the abnormal
f inger and toe nails . . . The integumentary
changes to which Eggleton referred also
are found in zinc-def icient dwarfs as wel l
as in animals with experimental or spon
taneous zinc def iciency. I t seems possible
that spoon nails (koilonychia) , long attrib
uted to chronic iron deficiency, might
actually be the result of associated zinc
deficiency.
PA RA M ET ERS FOR A SSESSI NG
ZINC STATUS IN M AN
Parameters that have been used in as
sessing zinc status in man are as fol lows:
1) plasma or serum concentration, 2) hai r
zinc concentration, 3) metabol ic balance
of zinc, 4) isotope turnover studies, 5) ex
cretion of urinary sulfate, and 6) response
of growth and sexual development to zinc
supplementation.
The simplest method is measurement of
plasma zinc concentration. As discussed
previously (pages 357-359), there are many
factors that influence the plasma zinc
level so that a lower than normal value
cannot be said to be more than suggestive
of zinc deficiency. I n some instances di
rectly after a stressful situation, such as the
injection of endotoxin, a myocardial infarct,
surgery, and other trauma, a very rapid
drop in the plasma zinc level occurs. I t ap
pears unl ikely that such a transiently low
level occurring so rapidly is a sign of zinc
deficiency. Nevertheless, demonstrable zinc
def iciency in man is accompanied by a low
plasma zinc concentration.
M easurement of a specif ic zinc-binding
protein, alpha-2 macroglobul in, possibly
may become a useful tool in assessment of
zinc def iciency. Boyett and Sul livan (22)
found a slight increase in this globulin
fraction in patients with alcoholic cirrhosis
as compared with normals. McBean et al .,7
studying a variety of diseases, found no
significant correlation, however, between
serum zinc and alpha-2 macroglobulin.
Hair zinc concentration has been studied
by several i nvestigators w ith varying re
sults (table 5). McBean et al. (150) could
find no correlation between plasma and
hair zinc concentration in growth-retarded
6- to 11-year-old chi ldren. These subjects
had lower than normal plasma zinc levels,
but hair zinc concentrations were normal .
T hey concluded that the zinc content of
hair was not a reliable indicator of body
zinc metabolism at the time of sampling.
Others ( 121, 212 ) have shown that various
factors, including age, af fect the zinc con
centration in hair.
Reinhold's zinc balance studies on Iranian
villagers (240) point to the value of thebalance method (table 4). H is data indi
cate that a zinc balance study, cumbersome
though it may be, is likely to shed light on
possible subclinical zinc deficiency.
Isotope turnover studies in man are
scarce, probably because the half-life of
65Znis 245 days making it an unacceptable
procedure except in patients with a l imited
lif e expectancy. Richmond et al. (245) re
ported that the biological half-life of this
isotope in human subjects averaged 154
days. Z inc isotope turnover studies have
been carried out by Ross et al. (256),
Prasad (225), and Spencer et al. (280, 281,
283) . Ross et al . ( 256) injected 65Zn intra-
7 McBean, L. D., Smith, J. C, Bernard, B. H. &
Halsted, J. A . (1972) Serum zinc and alpha-macro-
globulin concentration in patients with varimi«dis,
orders. Proc. I X I nt. Congr. N utr., M exico City,
M exico, September 2-9, 1972 (Abstr.).
8/19/2019 Bioinorganica del zinc
20/34
36 4
J. A . HALSTED, J. C . SMITH, JR. AND M. I. IRWIN
TABLE 5
Ha ir z in c concent ra ti on a s r epor te d b y var ious i nv es ti ga to rs
InvestigatorEggletonReinhold
etl.Strain
etl.Eininians
etl.KlevayMcBean
etl. 'MeanisD.
'Reference(48)(241)(290)(50)(121)(150)Mean
±SE.Year193819661966196719701971»E.S.;Subjects11
Chinesedults19
m ale a du lt Iran ian v illag ers
2 0 m ale co ntro l ad ult s ub jec ts
(Shiraz,ran)10
z in c d eficien t E gy ptian m ale d wa rfs
16 to 20 years
8 zinc-treated dw arfs 16 to 20 years
12 norm al Egyptians 27 to 40 years
6 norm al R ochester residents 23 to 37ears12
h ealth y villa ge ch ild ren 1 1 y ea rsld31
Panam anian males 6 to 10ears14
norm al adults (W ashington, D . C .)
75 Iranian village children 6 to 12 years
(g rowth retarded )Ha ir
zincppm255139Ü6.41
181±36.3 '54
±2121
±5s
103±42
120±s163±222127
±49'176±37l
199±22'MethodDithizoneZincon
ZinconE.S.»E.S.
E.S.
E.S.A.A.S.«A.A.S.A.A.S.A.A.S.emission
s pec tr og raphy. ' A .A .S. ; a tomic abs orpt io n s pec tr opho tomet ry .
venously into patients with m alignancy,
finding that it disappeared rapidly from
th e p lasm a. P rasad's stu dies indicated that,
in zinc deficiency, plasma zinc turnover
w as increased, the 24-hour exchangeable
zinc p ool w as decrease d, cum ula tive e xcre
tion of 66Zn was low , and 6-hour plasma
65Zn disappearance was rapid. Spencer's
reports w ere lim ited to m etabolic aspects
of zinc without consideration of zinc de
ficiency.
Hsu and Anthony (104) shewed that, in
zinc-deficient rats, urinary sulfate is
markedly increased after an injection of
cystine-35 S. S om ers a nd U nderw ood (277)
co nfirm ed the significantly ele vated su lfur
excretion in zinc-deficient lambs. The
m echanism suggested by H su and A nthony
( 1 04 ) w as th e in ab ility o f th e z in c-d efic ie nt
anim al to utilize sulfur-containing am ino
acids for protein synthesis, w ith conse
quent excretion of sulfate. No reports of
sim ila r w ork in m an w ere found .
At present the critical test for zinc de
ficiency in man or anim als is a definitive
response to oral supplem entation w ith zinc
under controlled conditions. The data for
p rim ary z in c d efic ie nc y in th e c ere al-e atin g
populations of Iran and Egypt now appear
unequivocal. N o reports of sim ilar studies
in other geographic locations have been
found.
Z IN C T OX IC IT Y
In comparison with the trace elements
lead, cadm ium , arsenic, and antim ony, zinc
is relatively nontoxic. Many of the toxic
effects ascribed to zinc by early investi
gators may be due actually to other con
taminating elements such as lead, cad
m ium , or arsenic (90). Zinc is noncum ula
tive, and the proportion absorbed is
thought to be inversely related to the
amount ingested (64, 96). Vomiting, a
protective m echanism , occurs after inges
tion of large quantities or after extended
exposure to fum es containing zinc. In fact,
an oral dose of 2 g of zinc sulfate (454 mg
of zinc) has been recommended as an
em etic (155). In addition to severe vom it
ing, the symptoms of zinc toxicity in hu
m ans include dehydration, electrolyte im
balance, stom ach pain, nausea, lethargy,
dizziness, and m uscular incoordination.
A cute renal failure caused by zinc chloride
poisoning was reported by Csata et al.
(38). The symptoms occurred within 3
hours after large quantities of zinc were
ingested.
There are reports in the literature indi
cating that the zinc content of acidic food
in contact w ith zinc-coated (galvanized)
containers for long periods possibly may
rise to toxic levels (24, 30). Toxic symp
toms were observed also after the volun
tary ingestion of 12 g of elemental zinc
8/19/2019 Bioinorganica del zinc
21/34
RESEARCHON ZINC REQUIREM ENTSOF M AN
365
over a 2-day period (179). Death is re
ported to have occurred after the ingestion
of 45 g of zinc sulfate ( 1 99 ). T oxic symp
toms, such as pulmonary distress, chi lls,
and fever, may be caused also by inhalation
of fumes or dust containing high levels of
zinc (201). T his so-called metal-fume
fever usually has been seen in industrial
workers such as welders of galvanized
metal.
Numerous studies on the toxici ty of zinc
in lower animals have been summarized
by Van Keen (309).
H UM A N REQU IREM EN TS FOR Z IN C
(T ABL E 6)
The apparent enteroenteric circulation of
zinc makes precise estimation of absorption
and excretion impossible by a simple mea
surement of intake and output. Neverthe
less, the balance method has been the prin
cipal technique used in estimating zinc re
quirements of man. A dult subjects and
school chi ldren have been most studied.
There have been a few observations on
infants and preschool children. No reports
were found on zinc requirements of healthy
adolescents, pregnant or lactating women,
or of the elderly. A ll of the balance studies
with presumably healthy subjects indicated
that urinary zinc excretion was low and
not apparently related to intake. Fecal zinc
excretion tended to fluctuate with intake.
I n the studies with adults, the intakes
varied from relatively low (about 5 mg/
day) to relatively high (about 22 mg/day) .
M cCance and W iddowson (153), for in
stance, reported data on two men and one
woman eating a special ly formulated diet
that provided 4.9 to 6.1 mg of zinc/day.
Zinc analysis was carried out by the
method described by Keilin and M ann(116). D uring dietary periods of about a
fortnight, balances of —0.8to 0.0 mg zinc/
day were observed. When the zinc intake
was raised to 9.1 or 13.8 mg/day by add
ing zinc salts or by providing 40 to 50%
of the calories f rom whi te f lour, balances
rose slightly to range from —0.1to 2.7 mg/
day. For two subjects, the zinc intake was
increased to 19.6 and 22.0 mg/day by re
placing the white flour with 90% extrac
tion f lour. With these intakes, retentions of
1.1 and 2.6 mg/day were observed. The
possible effect of phytate in the high ex
traction flour on zinc absorption was not
discussed in this report.
I n other studies in which moderate zinc
intakes (about 9 to 14 mg/day) were re
corded, retentions ranged from —4.0to 8.8
mg/day. The highest retentions w ith this
range of intake were recorded by T ribble
and Scoular (301). T hey studied a group
of 13 young women, 17 to 27 years old,
eating self-selected diets that were sampled
and analyzed for zinc by H ibbard's dithi-
zone method (97) . Wi th mean intakes that
ranged from 11.8 to 14.1 mg/day, the
young women retained f rom 5.1 to 8.8 mg/
day. Osis et al. (198) on the other hand,
observed much smaller retentions with
simi lar intakes. They studied one subject
whose mean zinc intake during four 6-day
periods ranged f rom 11.7 to 13.1 mg/day.
TABLE 6
C on tr oll ed s tu di es o n h um an r eq uir em en ts fo r zi nc
SubjectsInfante
5 to 8 daysldPreschool
3 to 6 yearsldSchool
children
7 to 12yearsldAdolescentsNumber
of
subjects10
368
0Xumber
of
studies1
13
0Daily
intake10.20
to.19mg/kii3.80
to.874.6
to 9.2
13.85 to 18.35Daily
retention1-0.85
to 0.08
mg/kg-2.70
to.390.5
to 3.8
4.92 ±2.94Estimated
daily
requirement10.300
to 0.307
mg/kg6.2Reference(32)
(265)(51,
234)
(140)
Adults
men and women6164.9
9.018.0to
6.1
to 14.1
to 22.0-0.8
-4.0
1.0to
0.0
to 8.8
to 8.3(153.(153)
198, 299, 301,
(68, 153, 299)323)
>In rag/day except where otherwise stated.
8/19/2019 Bioinorganica del zinc
22/34
36 6
J. A. HALSTED, J. C. SMITH, JR. AND M. I. IRWIN
W ith these i