Anasayfa / Bilimsel Yayınlar / Telogen Effluvium’da Çinko Tedavisi

Telogen Effluvium’da Çinko Tedavisi

Çinko saç ve tırnak gelişiminin olmazsa olmaz elementlerindendir. Çinko eksikliği saç dökülmesi yanı sıra saçta ve tırnaklarda kalite kaybına sebep olmaktadır. Tedaviye çinko eklenmesi sorunun hızla düzelmesini sağlar.

Bilimsel yayın 1

Oral zinc therapy for zinc deficiency-related telogen effluvium.

Karashima T, Tsuruta D, Hamada T, Ono F, Ishii N, Abe T, Ohyama B, Nakama T, Dainichi T, Hashimoto T.


Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.


Zinc is crucial for maintaining human body homeostasis and is one of the major components of hormones, signal molecules, and enzymes. Zinc deficiency is caused by insufficient uptake of zinc from food, or caused by malabsorption syndromes, increased gastrointestinal and urinary losses, and administration of various medications. In order to test whether oral zinc administration can successfully improve zinc deficiency-related alopecia, we treated five patients with zinc deficiency-related telogen effluvium with oral zinc administration in the form of polaprezinc (Promac®). In all patients, hair loss was cured or improved. The administration of zinc for zinc deficiency-related alopecia may recover appropriate activities of metalloenzymes, hedgehog signaling, and immunomodulation, all of which are required for normal control of hair growth cycle.

© 2012 Wiley Periodicals, Inc.

Bilimsel yayın 2

Relation Zinc and Calcium Concentrations in Hair to Zinc Nutrition in Rats


Department of Biochemistry, American University of Beirut,

Beirut, Lebanon

ABSTRACT Zinc concentration decreased substantially in newly grown hair of

nearly all rats depleted of zinc by being fed diets containing approximately 2 ppm

zinc. Lowered zinc concentrations in hair occurred with significantly greater fre

quency than decreased growth rates. Some rats with markedly decreased zinc concen

trations in hair, however, maintained growth rates that did not differ from those of

pair-fed controls consuming the same diet but supplemented with 20 ppm of zinc. It

is concluded that zinc concentrations in hair are dependent upon zinc intake, but that

they do not necessarily reflect the severity of the metabolic effects of zinc deficiency

as manifested by impaired growth rates. Lowered concentrations of zinc in the hair

of zinc-depleted rats were associated with elevated concentrations of calcium.

The concentration of zinc in hak is

about 10 times that in visceral organs and

about 200 times that in plasma. A previ

ous study ( 1) showed that zinc concentra

tions decreased significantly in the hair of

rats when zinc intake in the diet was low.

Miller et al. (2) observed a decline in the

zinc concentrations in the hair of calves

fed diets containing minimal concentra

tions of zinc. Studies of human hak also

have shown that changes in zinc concen

tration may occur. Lowered concentra

tions of zinc were found by Strain et al.

(3) in the hak of Egyptian youths exhib

iting the syndrome of arrested growth, en

largement of liver and spleen and anemia,

attributed by Prasad et al. (4) to zinc de

ficiency. A study of the hak of Iranian

villagers (5) demonstrated a prevalence

of decreased concentrations of zinc com

pared with the hak of well-nourished ur

ban residents. The difference was attri

buted to the lower intake of available zinc

by the villagers. Evidence provided by

these studies suggests that the concentra

tion of zinc in hak depends upon zinc

intake, although the nature and degree of

the dependence have not been established.

The signs of zinc deficiency are non

specific and often equivocal. Proof that

zinc is a limiting factor in nutrition may

be difficult to obtain, and examination of

hak for its zinc concentration has poten

tialities as an aid to the detection of zinc

deficiency. The purpose of this study was

to learn more about the relationship be

tween zinc nutrition and zinc in hair. In

particular, it seemed necessary to estab

lish whether the lowered concentrations of

zinc in hak are closely related to the

metabolic disturbances associated with

zinc deficiency, or whether they are a

largely passive response to the lowered

intake of zinc in the diet.


Rats of a local Sprague-Dawley strain

weighing 40 to 60 g were fed a diet similar

to that described by Forbes and Yohe (6),

modified in that 2 parts casein and 1 part

gelatin supplied protein at a level of

14.8%. The casein was extracted with

0.1% disodium ethylenediaminetetraacetate (EDTA) solution several times to re

move most of the zinc, and then with

water to remove the EDTA. The diet con

tained all other essential constituents and

supported a satisfactory rate of growth

when zinc was added. The diet included

1% by weight of CaHPU4. Zinc concen

trations in the diets were measured, follow

ing digestion with nitric and perchloric

acids, either by extraction with dithizone

in carbon tetrachloride according to Wolff

Received for publication April 1, 1968.

i Supported in part by Public Health Service Re

search Grants nos. AM-09622 and AM-05285 (to

Columbia University) from the National Institute of

Arthritis and Metabolic Diseases.

îSome of the studies here presented were described

in a preliminary report published in the Proceedings

of The Third Symposium on Human Nutrition and

Health in the Near East held in Beirut May 15, 1967.

J. NUTRITION,96: 519-524.


by guest on November 12, 2012 Downloaded from 520 JOHN G. REINHOLD, GEORGE A. KFOURY AND MICHAEL ARSLANIAN

(7) or by atomic absorption spectrophotometry. They varied between 1.5 and 2.6

ppm (table 1 ). Control rats from the same

litter paired according to sex and weight

were fed the low zinc diet supplemented

with zinc carbonate to provide in four of

five experiments a zinc concentration ap

proximating 20 ppm. This amount is

nearly twice the estimated minimal re

quirements of the rat (6) but well below

toxic concentrations. It approximates the

dietary zinc level at which zinc concentra

tions in hair remain stable. In series 9,

the control diet contained 30 ppm. The

food consumption of the controls was ad

justed each day to that of the experimental

rats. Rats were housed in stainless steel

cages. Deionized water was provided ad


Hair was sheared with electric clippers

from the ventral surface within 1 to 11

days after the rats were started on the

diets. A second shearing confined to the

same area provided hair grown during the

experimental period. Under “periods of

study” (table 1), the numbers designate

the times of the first and second shearings

(as number of days after start of experi

ment). In series 9, a second harvest of

hair was obtained from 12 of the original

24 rats. The initial shearings were delayed

in four experiments for 5 to 11 days to

enable hair “in process” to be extruded

and removed.

The hair was washed with a sulfonated

fatty acid detergent (Lux Liquid) in water

(approximately 0.1% solution, v/v), and

rinsed with deionized water until no evi

dence of foaming was detected. Two wash

ings with 95% ethanol and one with ethyl

ether followed. The hair was then allowed

to equilibrate with air at room tempera

ture for several days. Duplicate samples

of 50 to 100 mg were digested with nitric

acid followed by perchloric acid until the

digests were colorless. The acids were

fumed off, and the residue was dissolved

in 2 ml deionized water. Care was taken

to avoid loss of zinc through overheating

or prolonged heating of the residue during

the fuming-off.

»Perkin-Elmer Model 303 Atomic Absorption SpectrophotomrttT, Perldn-Elmer Corporation, Norwalk, Con


by guest on November 12, 2012 Downloaded from ZINC CONCENTRATIONS IN HAIR 521

The zinc concentration in the digest was

measured with an atomic absorption spectrophotometer3 equipped with a zinc-cal

cium hollow cathode emission lamp. Meas

urements were made at 213.8 mu using an

acetylene-compressed air mixture in pro

portions that formed a blue flame which

became white when fuel flow was slightly

increased or auxiliary air flow slightly de

creased. The readings were recorded on a

Moseley chart recorder and corrected for

a blank which had been carried through

the digestion procedure. Comparison was

made with zinc standards prepared from

zinc sulfate heptahydrate crystals dissolved

in water.

Zinc concentrations in hair and growth

rates were considered to be significantly

decreased when they differed from the

means of the controls by more than two

standard deviations.


Table 1 summarizes the studies made of

five groups of rats. The expected decrease

in growth rate occurred when diets low in

zinc were fed. Growth rates of deficient

and control rats were lower than those

previously reported (1) in which the defi

cient diets had contained more zinc. No

close correlation, however, between zinc

content of the diet within the range used

in these experiments and rate of growth

or other signs of zinc deficiency was evi

dent. The occurrence of lesions of the skin

on the paws and around the eyes, bleeding

into stomach and intestine, and suscepti

bility to other effects of low zinc intake

varied considerably. Litter size was a no

ticeably important determinant; pups from

litters of 11 or more were more vulnerable

than those from litters of 6 to 10. Growth

rates of control rats also were subnormal

because of the curtailed intake of food

resulting from paired feeding.

In agreement with previous observa

tions (1), the concentration of zinc in

hair decreased substantially in the rats

consuming the low zinc diets. A new and

interesting observation was the prompt

ness with which the changes in zinc con

centrations of hair occurred. In series 9

and 11, these declined by 20 and 25% in

20- and 17-day periods, in series 10 and

17, by more than 40% in 33 to 35 days.

Longer periods of zinc deprivation, how

ever, were accompanied by only moderate

additional changes, as a third shearing in

series 9 demonstrates.

Zinc concentrations in the hair of con

trol rats receiving 20 ppm of zinc tended

to decrease slightly during the experi

mental period. This contrasts with the in

crease that occurred in series 9 in the hair

of control rats that were fed diets contain

ing 30 ppm of zinc. A similar result with

the higher intake was observed previously


Significantly decreased concentrations of

zinc in hair occurred in 43 of the 52 rats

fed low zinc diets. The frequency of de

creased concentrations, however, varied be

tween groups. All rats in series 17 showed

a decrease (table 1). In series 9, however,

only 8 of 12 had significantly lowered

zinc concentrations after 20 days on the

diet, although eventually all fell below the

2 SD limit.

Significantly decreased zinc concentra

tions in hair occurred more consistently

than decreased growth rates in the zincdepleted rats (table 2). Only half of the

depleted rats gained weight at rates sig

nificantly lower than those of the controls.

Generally, the rats undergoing the great

est losses of zinc from hair were those

that made the poorest weight gains. Coef

ficients of correlation between rate of gain

and decrease in zinc concentration in hair

per day were significant in two experi

ments. In series 16, r = —0.69 was sig

nificant at P < 0.02, and in series 17 a

significant correlation (r = —0.61, P<

0.02) was demonstrated when controls

and deficient rats were included in calcu

lations. Correlations between zinc con

centration in hair and growth were not

significant in the remaining groups. Simi

lar tests applied to the longer term experi

ments with higher zinc intakes described

in our preceding report (1) also failed to

demonstrate a significant correlation. The

variability of the effect of low zinc intake

upon growth was mainly responsible.

Again, zinc concentrations in hair were

more consistently changed in the longer

experiments than growth rates.

The relation between concentrations of

zinc and calcium in hair. Like zinc, little

is known about the calcium content in

by guest on November 12, 2012 Downloaded from 522 JOHN G. REINHOLD, GEORGE A. KFOURY AND MICHAEL ARSLANIAN


Statistical summary



Weight gain Decrease in zinc

No. of rats


Total < 2 SDi Total < 2 SDi

910111617126101012803710441261010128869998< 0.05ns


All series 52 26 52 43 < 0.001

i The number of rats among those fed low zinc diets differing from the means of the controls

by more than 2 so. (See footnote 1 to table 1.)

z Probability that the frequency of significant change in rate of weight gain or decrease of zinc

in hair differed. Tested by the chi-square method.




A Zn mM

Fig. 1 Changes in calcium concentration in

newly grown hair compared with changes in

zinc concentration in rats fed diets containing

low or normal concentrations of zinc. A Ca and

A Zn are expressed as inmoles per day.

hair, the extent of its dependence upon

calcium metabolism, or correlation with

concentrations of zinc. Figures 1 and 2

show typical results in two experiments

in which calcium and zinc concentrations

were measured. Concentrations of calcium

increased, at times substantially, as those

of zinc decreased in hak of depleted rats.

Coefficients of correlation calculated in

three of five experiments (series 11, 9,

and eight deficient rats in series 16) were

—0.53, —0.65 and —0.94. These are sig

nificant at P < 0.05, < 0.001 and < 0.01

levels, respectively. No correlation was

demonstrated in series 10, however, which

differed from the others in that calcium

concentrations in hair decreased during

the experiment. This trend was, however,

less marked in the zinc-depleted rats than

in the controls.


The concentration of zinc in most of the

visceral organs and tissues studied under

goes little change in young rats fed diets


Fig. 2 Results of an experiment similar to

that shown in figure 1. Note the large increment

of calcium in some zinc-deficient rats.

by guest on November 12, 2012 Downloaded from ZINC CONCENTRATIONS IN HAIR 523

low in zinc for 8 to 10 weeks (1). By

contrast, the present study shows that the

concentration of zinc in hair decreases rap

idly and extensively. The zinc concentra

tion decreased by 40 to 50% within 17

days in one experiment and within 20, 26

and 32 days in other experiments. Sub

sequently, zinc concentrations became

stable at approximately half of the con

centrations found in control samples of

hair sheared from the same rat before the

deficient diets took effect. Occasionally,

further declines occurred as the experi

ments continued during a second month.

The lower concentrations of zinc in the

hair of depleted rats observed in these ex

periments are explained by the lowered

zinc concentrations in the diets. These

were less than 2 ppm in four of five ex

periments, whereas in the earlier experi

ments (1) the diets contain about double

this amount. The importance of zinc in

take as a determinant of zinc concentra

tion in hair also is supported by analyses

of the hair of the control rats. When con

trols were fed diets containing 30 ppm of

zinc, the concentration of zinc in hair rose

substantially, whereas at 20 ppm zinc con

centrations in the hair remained stable. It

may be inferred that the intake of 20 ppm

in the diet was equivalent to that during

the first weeks of life, since the hair re

moved at the first shearing had grown

during the neonatal period.

The relationship of the changes occur

ring in the zinc concentrations in hair in

the zinc-depleted rats to the effects of zinc

depletion upon growth rates is of some

interest, since growth failure is one of the

earlier and more prominent manifestations

of zinc deficiency (8). Decreased concen

trations of zinc in hair occurred with a

much higher frequency (83% of the rats)

than did depressed growth rates (50% ).

The difference is highly significant when

tested by the chi-square method (P <


Some rats in each experimental group

were able to maintain growth approximat

ing that of the controls when fed diets

containing less than 2 ppm of zinc. Zinc

concentrations in the hair of such rats

decreased to the same extent as in the

rats that developed signs of deficiency, an

indication that they were not obtaining

zinc from extradietary sources. It must

be concluded, therefore, that the concen

tration of zinc in hair depends mainly

upon the quantity of zinc consumed in the

diet, but that it does not necessarily define

the state of zinc nutrition. A similar con

clusion concerning the significance of the

concentration of zinc in serum was reached

by Mills et al. (9).

No correlation between zinc concentra

tion in hair and that in liver could be dem

onstrated in the rats of series 16 and 17.

Coefficients of correlation were less than


The mechanism by which zinc or other

metals enters hair is unknown. Bates (10)

suggests that this may be by adsorption, a

proposal that is supported by observations

of Kennington (11) on the uptake of so

dium from dilute solutions by hair. The

dependence of zinc concentration in hair

upon dietary intake of zinc would then be

governed by the concentration of zinc

available to the hair follicle. However, hair

contains as much calcium as zinc. The

reciprocal relationship between zinc and

calcium in the hair of zinc-depleted rats

demonstrated in these studies indicates

that the concentration of zinc in hak may

depend upon not only the concentration

of zinc available to the follicle but also the

concentration of calcium. Calcium is

known to aggravate the severity of zinc de

ficiency; Forbes and Yohe (6) believed

this effect to occur at the cellular level,

although Forbes later attributed it to a

depressant effect on intestinal absorption

(12). It appears probable that a competi

tion between zinc and calcium for certain

chemical groupings in hair may exist. It

is conceivable that a similar competition

may exist elsewhere and that this could

affect movement of zinc within the tissues.

Follis (13) observed atrophy of hair

follicles and extensive skin changes as

manifestations of zinc deficiency. It is

possible that the onset of deterioration was

responsible for the lowered zinc concentra

tions. This explanation, however, seems

less satisfactory than one based on a de

creased concentration of zinc in skin.


The authors thank Miss Aznive Saboundjian for technical assistance and Miss

by guest on November 12, 2012 Downloaded from 524 JOHN G. REINHOLD, GEORGE A. KFOURY AN0 MICHAEL ARSLANIAN

Madeleine Basmadjian for performing the

statistical calculations and for aid with

the preparation of the manuscript.


1. Reinhold, J. G., G. A. Kfoury and T. A.

Thomas 1967 Zinc, copper, and iron con

centrations in hair and other tissue: Effects

of low zinc and low protein intakes in rats.

J. Nutr., 92: 173.

2. Miller, W. J., G. W. Powell, W. J. Pitts and

H. F. Perkins 1965 Factors affecting zinc

content of bovine hair. J. Dairy Sci. 48-


3. Strain, W. H., L. T. Steadman, C. A. Lankau,

W. P. Berliner and W. J. Pories 1966

Analysis of zinc levels in hair for the diag

nosis of zinc deficiency in man. J. Lab.

Clin. Med., 68: 244.

4. Prasad, A. S., A. Miale, Z. Farid, H. H.

Sandstead, A. R. Schulert and W. J. Darby

1963 Biochemical studies on dwarfism, hypogonadism, and anemia. Arch. Intern. Med.,

Ill: 407.

5. Reinhold, J. G., G. A. Kfoury, M. A. Ghalambor and J. C. Bennett 1966 Zinc and cop

per concentrations in hair of Iranian vil

lagers. Amer. J. Clin. Nutr., 18: 294.

6. Forbes, R. M., and M. Yohe 1960 Zinc re

quirement and balance studies in the rat.

J. Nutr., 70: 53.

7. Wolff, H. 1954 Determination of zinc in

biological specimens. Biochem. Z., 325: 267.

8. Miller, J. K., and W. J. Miller 1962 Ex

perimental zinc deficiency and recovery of

calves. J. Nutr., 76: 467.

9. Mills, C. F., A. C. Dalgarno, R. B. Williams

and J. Quarterman 1967 Zinc deficiency and

the zinc requirement of calves. Brit J

Nutr., 21: 751.

10. Bates, L. C. 1966 Adsorption and elution

of trace elements on human hair. Int. J.

Appi. Radiât.Isotop., 17: 417.

11. Kennington, G. S. 1967 Activation anal

ysis of soluble and fixed sodium in mammal

ian hair. Science, 155: 588.

12. Forbes, R. M. 1967 In: Newer Methods

of Nutritional Biochemistry, vol. 3, éd.,A. A.

Albanese. Academic Press, New York, p. 339.

13. Follis, R. H. 1948 The Pathology of Nu

tritional Disease. C. C Thomas, Springfield,


by guest on November 12, 2012 Downloaded from