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This paper reviews research published in recent years concerning the effects of zinc deficiency, its consequences, and possible solutions. Zinc is an essential trace element necessary for over 300 zinc metalloenzymes and required for normal nucleic acid, protein, and membrane metabolism. Zinc deficiency is one of the ten biggest factors contributing to burden of disease in developing countries. Populations in South Asia, South East Asia, and sub-Saharan Africa are at greatest risk of zinc deficiency. Zinc intakes are inadequate for about a third of the population and stunting affects 40% of preschool children. In Pakistan, zinc deficiency is an emerging health problem as about 20.6% children are found in the levels of zinc, below 60 μg/dL. Signs and symptoms caused by zinc deficiency are poor appetite, weight loss, and poor growth in childhood, delayed healing of wounds, taste abnormalities, and mental lethargy. As body stores of zinc decline, these symptoms worsen and are accompanied by diarrhea, recurrent infection, and dermatitis. Daily zinc requirements for an adult are 12-16 mg/day. Iron, calcium and phytates inhibit the absorption of zinc therefore simultaneous administration should not be prescribed. Zinc deficiency and its effects are well known but the ways it can help in treatment of different diseases is yet to be discovered. Improving zinc intakes through dietary improvements is a complex task that requires considerable time and effort. The use of zinc supplements, dietary modification, and fortifying foods with zinc are the best techniques to combat its deficiency.
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A Question Mark on Zinc Deficiency in 185 Million
People in Pakistan—Possible Way Out
Nauman Khalid a , Anwaar Ahmed b , Muhammad Shahbaz Bhatti b , Muhammad Atif
Randhawa c , Asif Ahmad b & Rabab Rafaqat b
a Department of Global Agriculture , Graduate School of Agriculture and Life Sciences, The
University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku , Tokyo , 113-8657 , Japan
b Department of Food Technology , PMAS-Arid Agriculture University , Rawalpindi , 36400 ,
Pakistan
c National Institute of Food Science & Technology , University of Agriculture , Faisalabad ,
38040 , Pakistan
Accepted author version posted online: 14 May 2013.Published online: 05 Feb 2014.
To cite this article: Nauman Khalid , Anwaar Ahmed , Muhammad Shahbaz Bhatti , Muhammad Atif Randhawa , Asif Ahmad &
Rabab Rafaqat (2014) A Question Mark on Zinc Deficiency in 185 Million People in Pakistan—Possible Way Out, Critical Reviews
in Food Science and Nutrition, 54:9, 1222-1240, DOI: 10.1080/10408398.2011.630541
To link to this article: http://dx.doi.org/10.1080/10408398.2011.630541
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Critical Reviews in Food Science and Nutrition, 54:1222–1240 (2014)
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ISSN: 1040-8398 / 1549-7852 online
DOI: 10.1080/10408398.2011.630541
A Question Mark on Zinc Deficiency
in 185 Million People in
Pakistan—Possible Way Out
NAUMAN KHALID,1ANWAAR AHMED,2MUHAMMAD SHAHBAZ BHATTI,2
MUHAMMAD ATIF RANDHAWA,3ASIF AHMAD,2and RABAB RAFAQAT2
1Department of Global Agriculture, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi,
Bunkyo-ku, Tokyo 113-8657, Japan
2Department of Food Technology, PMAS-Arid Agriculture University, Rawalpindi 36400, Pakistan
3National Institute of Food Science & Technology, University of Agriculture, Faisalabad 38040, Pakistan
This paper reviews research published in recent years concerning the effects of zinc deficiency, its consequences, and possible
solutions. Zinc is an essential trace element necessary for over 300 zinc metalloenzymes and required for normal nucleic
acid, protein, and membrane metabolism. Zinc deficiency is one of the ten biggest factors contributing to burden of disease
in developing countries. Populations in South Asia, South East Asia, and sub-Saharan Africa are at greatest risk of zinc
deficiency. Zinc intakes are inadequate for about a third of the population and stunting affects 40% of preschool children.
In Pakistan, zinc deficiency is an emerging health problem as about 20.6% children are found in the levels of zinc, below
60 μg/dL. Signs and symptoms caused by zinc deficiency are poor appetite, weight loss, and poor growth in childhood,
delayed healing of wounds, taste abnormalities, and mental lethargy. As body stores of zinc decline, these symptoms worsen
and are accompanied by diarrhea, recurrent infection, and dermatitis. Daily zinc requirements for an adult are 12–16 mg/day.
Iron, calcium and phytates inhibit the absorption of zinc therefore simultaneous administration should not be prescribed.
Zinc deficiency and its effects are well known but the ways it can help in treatment of different diseases is yet to be discovered.
Improving zinc intakes through dietary improvements is a complex task that requires considerable time and effort. The use
of zinc supplements, dietary modification, and fortifying foods with zinc are the best techniques to combat its deficiency.
Keywords Zinc, zinc deficiency, symptoms, recommended intake, Pakistan, government policies, possible solutions
BACKGROUND
Population of developing countries is on peak than world’s
average population growth rate of 1.8% (Population Division,
2009). There is a need of real hard effort and food revolution
in poor and developing countries to solve food scarcity (Huang
et al., 2002) but it require consistent and determined efforts.
In comparison of total population, about 65% of world’s to-
tal population is starving (Food Security Statistics, 2008) and
lives below poverty line. Malnutrition and under nutrition are
found among people where food supply and diet diversifica-
tion are lacking. Right now in 21st century developing world
is under severe threat of micronutrient malnutrition, because of
Address correspondence to Nauman Khalid Department of Global
Agriculture, Graduate School of Agriculture and Life Sciences, The Uni-
versity of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. E-mail:
aa127410@mail.ecc.u-tokyo.ac.jp
consumption of cereals that are rich in phytates and these limits
bioavailability of essential nutrients (Hussain et al., 2010).
The deficiency of essential vitamins and minerals are re-
garded as “hidden hunger” and it affects more than one-third of
the world’s population, threaten women and children, resulting
devastating consequences for public health, social development,
and future of country. It is estimated that as many as two bil-
lion people are at risk of zinc deficiency in this world so called
as “Global Village.” Zinc and other micronutrient deficiencies
(MNDs) contribute significantly to the burden of disease and
linked to adverse functional outcomes such as stunting, wast-
ing, increased susceptibility to infections during pregnancy, de-
creased IQ level, cognitive losses, blindness, and premature
mortality. Literature reviews estimates that 20% of the world’s
population may be at risk of inadequate dietary intake of zinc
and the populations at highest risk are located in South and
Southeast Asia, Sub-Saharan Africa, Central America, and the
Andean region. Premature and small-for-gestational-age infants,
1222
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1223
Figure 1 Causes of death among children less than five years of age worldwide
(Black et al., 2003; Muller and Krawinkle, 2005). (Color figure available online.)
and preschool children, mostly in between 6 and 23 months of
age comes in most vulnerable list and need extreme attention
from Non-governmental Organizations (NGOs) and Govern-
ment bodies (Boy et al., 2009).
Specialists have divided Malnutrition into protein energy
malnutrition (PEM) and MNDs; these two constitute to be the
majority of health burden in all developing countries covering
from Asia to Africa. Malnutrition typically result in inadequate
diet, and is easily diagnosable in children living in sub-Saharan
Africa and south Asia (Manary and Sandige, 2008). These de-
ficiencies covers whole developing world and creates an alarm-
ing situation in whole world. In developing world, people’s diet
lack both micronutrients (minerals, vitamin, and electrolytes)
and macronutrients (proteins, carbohydrates, and fats) resulting
in malnutrition and burden of diseases (Millward and Jackson,
2004; Muller and Krawinkle, 2005). Figure. 1 and Table 1 point
the threats of malnutrition in children of developing world and
confirm the degree of correlation among malnutrition and rate
of death in developing countries (Fernandez et al., 2002; Black
et al., 2003; FAO, 2004).
Pakistan is a developing country and since its birth malnu-
trition has recognized as a key factor that significantly affecting
infants, children, and women. Malnutrition affects the physical
growth in terms of body development, physical work capacity,
Tab le 1 Prevalence’s of protein–energy malnutrition among children under
5 years of age in developing countries (FAO, 2004), (NNS, 2002).
Region Stunting (%) Underweight (%) Wasting (%)
Africa 39 28 8
Asia 41 35 10
Latin America and
Caribbean
18 10 3
Oceania 31 23 5
Pakistan36.8 38 13.2
and producing risk for several chronic diseases in children. In
South-East Asia, it was estimated at 43% whereas in Pakistan
50% of children fewer than five were stunted, 40% were un-
der weight and 9% were wasted (Bellamy, 2000). This situation
has not changed much in the region; recent reports showed that
stunting is 37%, underweight 38%, while wasting is progres-
sively increased to 13%, indicating lack of proper nutritional
and health interventions at national level (Diaz et al., 2003).
Pakistan is suffering from high rate of childhood malnutrition
and has made little progress in the past 20 years due to bad
governess and less attention paid by NGOs. The burden of child
malnutrition in South Asia (India, Bangladesh, and Nepal) is
considered much higher than most of the countries in sub-Sahara
Africa. The situation is more serious in Pakistan that has long
been considered as self-sufficient in diverse agriculture produce
and refined foods. But lack of political commitment to systemat-
ically address the malnutrition, minimal investments in nutrition
interventions, and lack of clear, focused, and practical strategy
are some of the factors that contribute to the persistence of high
levels of child malnutrition (Ahmed and Farooq, 2010).
Pakistan is a developing country and the deficiencies of mi-
cronutrients exist in various segments of the population. Half of
its children aged five years or less are stunted, over a one third
is underweight, and a quarter of all births are low birth weight
(Bhutta, 2000). Iron, vitamin A and Zinc deficiency are prevalent
among infants, school going children, females, and especially
pregnant women indicated by several regional and national sur-
veys. The last National Nutrition Survey (National Nutrition
Survey, 2004) conducted in (2001–02), pointed out that 37%
of 0–5 year olds were found to be zinc deficient. Among preg-
nant women, 45% had zinc deficiency. In calculation, more than
50% people in Pakistan suffer from micronutrient deficiencies
that gives alarming call for urgent attention of Government, but
still is a question mark.
MNDs, like Zinc and vitamin A are responsible for 0.4 mil-
lion and 0.6 million deaths, respectively, in children with less
than five years of age whereas iron deficiency anemia is found in
40–50% of infant and children (Black et al., 2008). It is interest-
ing to note 50% of vitamin A deficiency cases are found in South
Asia, including India (35.5 million), Indonesia (12.6 million),
and (11.4 million) China (Diaz et al., 2003). In these countries,
ample amount of leafy vegetables are available that could be
utilized in a better way to eradicate this vitamin and other mi-
cronutrients deficiencies. According to World Bank suggestion
that the cost of MNDs forces country 5% gross national prod-
uct (GNP) whereas intervention and strategies might only cost
0.3% of the GNP (Hill et al., 2005). Zinc and Calcium deficien-
cies are also related to growth failure and increasing number
of patients with osteoporosis. Co-existing nutritional interven-
tions can prevent stunting by 36% and plummeting MNDs by
about 25% (Bhutta et al., 2008). Human Zn deficiency is the
fifth major cause of diseases and deaths in developing countries
(WHO, 2002). Around the world, 2.7 billion people are Zn defi-
cient (WHO, 2002; Muller and Krawinkle, 2005). About 50% of
world’s population is under risk of Zn deficiency and prevalence
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1224 N. KHALID ET AL.
Figure 2 World population (%) deficient in zinc (Brown et al., 2001; Hussian et al., 2010). (Color figure available online.)
is more in developing countries of Asia and Africa (Fig 2). In
Pakistan, every third child and 40% mothers are suffering from
Zn deficiency (Bhutta et al., 2007).
ZINC AS AN IMPORTANT NUTRIENT
FOR SUSTAINING LIFE
Zinc is an essential nutrient having a complex biological
role, including neuropsychological aspects. The human body
contains approximately 2 g zinc in total, with 60% found in
skeletal muscle and 30% in bone mass, although it is found in
all body tissues and fluids (Wahlqvist, 1997). Mostly, it is 10 mg
Zn per day for adult women and 12 mg Zn per day for adult men.
Women in pregnancy and lactation require up to 14 mg Zn per
day. These intake levels are generally not fulfilled in developing
countries due to diet rich in phytates and less calorie intake from
cereals and other staple food (Bouis, 2002; Beers and Berkow,
2003; Hussain et al., 2010). Lean body mass and tissues contain
approximately 30 μg/g of total available zinc. Plasma zinc has
a rapid turnover rate and it represents only about 0.l% of total
body zinc content. Higher concentrations of zinc are found in
the choroid of the eye 274 μg/g (Hambidge, 1987).
ZINC METABOLISM AND HOMEOSTASIS
Zinc absorption is influenced by many factors and adequate
dietary intake does not necessarily correlate with adequate zinc
status. High phytate content significantly reduce zinc absorp-
tion due to the formation of strong and insoluble complexes
(Lonnerdal, 2000). Concerns have also been raised over the cal-
cium, iron, copper, and cadmium to reduce zinc absorption. The
amount of animal protein in a meal positively correlates to zinc
absorption and the amino acids histidine and methionine, and
various organic acids present in foods, such as citric, malic, and
lactic acids, can also increase absorption (King, 2003). Under
normal circumstances, the absorption of zinc occurs through
small intestine, but the up take process is not fully saturated.
Zinc administered in aqueous solutions is considered to be effi-
ciently absorbed up to 60–70%, but absorption from solid diets is
less efficient and varies depending on zinc content and diet com-
position (Sandstr¨
om, 1997). Zinc is lost from the body through
the kidneys, skin, and intestine (King and Turnlund, 1989). The
endogenous intestinal losses can vary from 70.5 mg/day to more
than 3 mg/day, depending on zinc intake. Starvation and mus-
cle catabolism increase zinc losses in urine. Strenuous exercise
and elevated ambient temperatures could also lead to losses by
perspiration (King and Turnlund, 1989). The utilization of zinc
depends on the overall composition of the diet. Experimental
studies have identified a number of dietary factors as poten-
tial promoters or antagonists of zinc absorption (Sandstr¨
om and
L¨
onnerdal, 1989). Soluble low-molecular-weight organic sub-
stances, such as amino and hydroxy acids, facilitate zinc absorp-
tion. In contrast, organic compounds forming stable and poorly
soluble complexes with zinc can impair absorption (Sandstr¨
om
and L¨
onnerdal, 1989). Isotopic studies with humans identified
two factors which together with the total zinc content of the
diet are major determinants of absorption and utilization of di-
etary zinc in human body. The first is the content of inositol
hexaphosphate (phytate) and the second is the level and source
of dietary protein. Phytates are present in whole-grain cereals
and legumes and in smaller amounts in other vegetables. They
have a strong potential for binding divalent cations and their
depressive effect on zinc absorption has been demonstrated in
humans (Sandstr¨
om and L¨
onnerdal, 1989).
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1225
Zinc in Biochemical Reactions
Metalloenzymes
At the cellular level, the function of zinc can be divided
into three categories: catalytic, structural, and regulatory (King,
2003). As a constituent of over 300 metalloenzymes, zinc is
involved in numerous chemical reactions that are important
for normal body functioning, such as carbohydrate metabolism,
protein and DNA synthesis, protein digestion, bone metabolism,
and endogenous antioxidant systems (Wardlaw et al., 1994;
Wahlqvist, 1997; Beers and Berkow, 2003).
Maintenance of Biomembranes and Immunological Functions
Zinc is important for the formation of biomembranes and
zinc finger motifs found in DNA transcription factors (Semrad,
1999). Zinc is involved in many aspects of immunological func-
tions. It is essential for the normal development and function
of cells, mediating nonspecific immunity such as neutrophils
and natural killer cells and affecting development of acquired
immunity and T-lymphocyte function. Its deficiency rapidly di-
minishes antibody and cell-mediated responses in both humans
and animals, leading to increases in opportunistic infections and
mortality rates (Fraker et al., 2000). Animal models have shown
that suboptimal intake of zinc over 30 days can lead to 30–80%
loss in defense capacity. Investigation using a human model has
demonstrated that even mild deficiency in humans adversely
affects T-cell functions (Prasad, 1998). Conversely, high-dose
zinc supplementation (20-fold RDI) can also produce immune
dysfunction.
Controlling Body Coordination System
Zinc ions are unevenly distributed in the CNS, acting as neuro
secretory products or cofactors. Zinc is highly concentrated
in the synaptic vesicles of specific neurons, known as “zinc-
containing” neurons. Zinc containing neurons are a subset of
glutamatergic neurons and mostly located in the telencephalon.
Zinc is released from zinc-containing neurons in a calcium-
and impulse-dependent manner, producing a broad spectrum of
neuromodulatory effects. Additionally, zinc appears to stabilize
the storage of certain macromolecules in presynaptic vesicles
(Frederickson and Danscher, 1990; Frederickson and Moncrieff,
1994; Frederickson, 2000).
Functions in Reproductive System
In humans, zinc is necessary for the formation and matura-
tion of spermatozoa, for ovulation, and for fertilization (Favier,
1992). Zinc has multiple actions on the metabolism of andro-
gen hormones, oestrogen, and progesterone, and these, together
with the prostaglandins and nuclear receptors for steroids are
all zinc finger proteins. In adult males, zinc content is high in
the testis and prostate, which have the highest concentration of
zinc of any organ in the body (Bedwal and Bahuguna, 1994). In
women, zinc deficiency during pregnancy has been associated
with increased maternal morbidity, increased risk of abortion,
stillbirth, teratogenicity, and other unwanted outcomes (Bedwal
and Bahuguna, 1994).
Zinc as an Antioxidant Agent
Zinc limits oxidant-induced damage in a number of indirect
ways, such as protecting against vitamin E depletion, control-
ling vitamin A release, contributing to the structure of the an-
tioxidant enzyme extracellular superoxide dismutase, restricting
endogenous free radical production, maintaining tissue concen-
trations of metallothionein, a possible scavenger of free rad-
icals, and stabilizing membrane structure (DiSilvestro, 2000).
Furthermore, it was observed to decrease lipid peroxidation, and
protect mononuclear cells from TNF-alpha induced NF-kappa-
B activation associated with oxidative stress (Prasad, 2004).
One of the in vivo features of zinc is its insulin-like function,
which is mediated via inhibition of endogenous GSK-3 (Ilouz,
2002). This is important because GSK-3 inhibition appears es-
sential for normal function of the insulin-activated signaling
pathway.
DIETARY SOURCES OF ZINC
Nature has put solution for all types of deficiencies. The
solution of zinc can be found in all sectors of food choices
ranging from lean red meat, whole-grain cereals, pulses, and
legumes. All these products provide the highest concentrations
of zinc 25–50 mg/kg raw weight. As a common perception that
processing decrease the nutritional quality, similarly processed
cereals has low extraction rates, polished rice, and lean meat
or meat with high fat content have a moderate zinc content
10–25 mg/kg (fish, roots and tubers, green leafy vegetables, and
fruits are only modest sources of zinc <10 mg/kg (Sandstr¨
om
and L¨
onnerdal, 1989). Saturated fats, sugar, and alcohol have
very low zinc content.
ZINC REQUIREMENTS AND RECOMMENDED INTAKE
There is no specific index for zinc status limits for eval-
uating zinc requirements. Zinc requirements were estimated
by using factorial techniques (adding the requirements for tis-
sue growth, maintenance, metabolism, and endogenous losses)
(AO/IAEA/WHO, 1996; WHO/FAO, 2001). Experimental zinc
repletion studies with low zinc intakes have clearly demon-
strated that the body has a pronounced ability to adapt to dif-
ferent levels of zinc intakes by changing the endogenous zinc
losses through the kidneys, intestine, and skin (Milne et al.,
1983; Lukaski et al., 1984; Taylor et al., 1991). The normative
requirement for absorbed zinc was defined as the obligatory
loss during the early phase of zinc depletion before adaptive
reductions in excretion take place and was set at 1.4 mg/day
for men and 1.0 mg/day for women. In growing individuals,
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1226 N. KHALID ET AL.
the rate of accumulation and zinc content of newly formed tis-
sues were used to obtain the data required for tissue growth.
Similarly, the retention of zinc during pregnancy and the zinc
concentration in milk at different stages of lactation were used
to estimate the physiologic requirements in pregnancy and lac-
tation (AO/IAEA/WHO, 1996; WHO/FAO, 2001).
Infants, Children, and Adolescents
Endogenous losses of zinc in human-milk-fed infants were
assumedtobe20μg/kg/day whereas 40 μg/kg/day was assumed
for infants fed formula or weaning foods (AO/IAEA/WHO,
1996; WHO/FAO, 2001). Estimated zinc increases for infant
growth were set at 120 and 140 μg/kg/day for female and male
infants, respectively, for the first three months (AO/IAEA/WHO,
1996; WHO/FAO, 2001). These values decrease to 33 μg/kg/day
for ages 6–12 months. For ages 1–10 years, the requirements
for growth were based on the assumption that new tissue con-
tains 30 μg/g (AO/IAEA/WHO, 1996; WHO/FAO, 2001). For
adolescent growth, a zinc content of 23 μg/g increase in body
weight was assumed. Growth of adolescent males corresponds
to an increase in body zinc requirement of about 0.5 mg/day
(AO/IAEA/WHO, 1996; WHO/FAO, 2001).
Pregnancy
The total amount of zinc retained during pregnancy has been
estimated to be 100 mg (Swanson and King, 1987). During the
third trimester, the physiologic requirement of zinc is approx-
imately twice as high as that in women who are not pregnant
(AO/IAEA/WHO, 1996; WHO/FAO, 2001).
Lactation
Zinc concentrations in human milk are high in early lacta-
tion, 2–3 mg/L in the first month, and fall to 0.9 mg/L after
three months (WHO, 1998). From data on maternal milk vol-
ume and zinc content, it was estimated that the daily output
of zinc in milk during the first three months of lactation could
amount to 1.4 mg/day, which would theoretically triple the phys-
iologic zinc requirements in lactating women compared with
non-lactating, nonpregnant women. In setting the estimated re-
quirements for early lactation, it was assumed that part of this re-
quirement was covered by postnatal involution of the uterus and
from skeletal resorption (AO/IAEA/WHO, 1996; WHO/FAO,
2001).
Recommended Intake
The studies of (Hess et al., 1977; Milne et al., 1983; Baer and
King, 1984; Milne et al., 1987; Johnson et al., 1993) on factorial
technique have considered a relatively small number of subjects
and do not allow any estimate of inter-individual variations in
Tab le 2 Recommended intake of zinc among different age groups
Dietary Zn bioavailability (mg/day)
Population and age (years) High Medium Low
Infants
0–0.5a—— —
0.5–1 3.3 5.6 11.1
Children
1–3 3.3 5.5 11
3–6 3.9 6.5 12.9
6–10 4.5 7.5 15
Males
10–12 5.6 9.3 18.7
12–15 7.3 12.1 24.3
15–18 7.8 13.1 26.2
18–60 5.6 9.4 18.7
Females
10–12 5 8.4 16.8
12–15 6.1 10.3 20.6
15–18 6.2 10.2 20.6
18–60 4.0 6.5 13.1
Pregnant womenb6.0 10.0 20.0
lactating women (0–5 months) 7.3 12.2 24.3
Lactating women (>6 months) 5.8 9.6 19.2
aExclusive breastfeeding is recommended.
bMean for all trimesters.
Source: (WHO, 2001 and Brown et al., 2001).
obligatory losses of zinc at different intakes. The reason is that
zinc requirements are related to tissue turnover rate and growth,
it is reasonable to assume that variations in physiologic zinc
requirements are of the same magnitude as variations in protein
requirements (FAO/WHO/UNU, 1985). From the available data
from zinc absorption studies (N¨
avert et al., 1985; Sandstr¨
om and
L¨
onnerdal, 1989; Sandstr¨
om and Sandberg, 1992; Hunt et al.,
1995; Knudsen et al., 1995; Sian et al., 1996), it is suggested that
the variation in dietary zinc requirements, which covers varia-
tion in requirement for absorbed zinc (variations in metabolism
and turnover rate of zinc) and variation in absorptive efficiency,
corresponds to a coefficient of variance of 25%. The recom-
mended nutrient intakes derived from the estimates of average
individual dietary requirements are presented in Table 2.
SIGNS AND SYMPTOMS OF DEFICIENCY
Zinc deficiency is an important factor contributing to in-
creased morbidity, mortality, and impaired development of chil-
dren in underprivileged settings. Zinc deficiency is now widely
recognized as a leading risk factor for morbidity and mortality
and is estimated to be responsible for approximately 800,000
excess deaths annually among children fewer than five years
of age (Haider and Bhutta, 2009). Two types of zinc deficien-
cies are found, i.e., primary and secondary deficiency. Primary
deficiency can result from inadequate dietary intake of zinc;
however, inhibition of zinc absorption is a common causative
factor (Lonnerdal, 2000). Strict vegetarians are at risk of defi-
ciency if their major food staples are grains and legumes because
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1227
the phytic acid in these foods will impair dietary zinc absorp-
tion. Zinc chelating compounds have been identified in coffee
(Wen et al., 2005; Higdon and Frei, 2006) and coffee has been
found to inhibit the bioavailability of zinc in vitro by 21–32%
(Van Dyck et al., 1996; Higdon and Frei, 2006). Secondary de-
ficiency develops in some people with cirrhosis, mal-absorption
syndromes, sickle cell anemia, conditions of increased zinc loss,
such as severe burns or major surgery, chronic diarrhea or dia-
betes, HIV and AIDS, and during prolonged parenteral nutrition
(Prasad, 1999). Additionally, strenuous exercise and elevated
ambient temperatures increase zinc losses through perspiration.
A congenital disorder known as acrodermatitis enteropathica
causes severe zinc deficiency.
Zinc deficiency is also associated with impaired glucose tol-
erance. It is assumed that zinc may interact with the hormone in-
sulin in a way that influences the uptake of glucose by adipocytes
(Ganapathy and Volpe, 1999). In addition to this interaction
with insulin, zinc is known to interact with a number of other
hormones, including growth hormone, various sex hormones,
thyroid hormones, prolactin, and corticosteroids (Guthrie and
Picciano, 1995). The interactions between zinc and hormones
are double-edged because, where zinc influences the synthesis
and activities of hormones, various hormones also influence the
absorption and metabolism of zinc. Zinc appears to be required
for the normal development and maintenance of the immune
system. An adequate intake of zinc helps the body resist infec-
tion (Fraker et al., 1986; Keen and Gershwin, 1990; Ganapathy
and Volpe, 1999).
The major signs and symptoms of zinc deficiency are,
Anorexia and impaired sense of taste, slowed growth and de-
velopment, and delayed sexual maturation. More pronounced
are delayed sexual maturation, hypogonadism and hyposper-
mia, and menstrual problems. Skin rashes, alopecia, chronic
and severe diarrhea, immune system deficiencies, and increased
susceptibility to infection are also of major concern. Other prob-
lems include impaired wound healing due to decreased colla-
gen synthesis, night blindness; swelling and clouding of the
corneas, behavioral disturbances such as mental fatigue and
depression (King, 2003). Zinc deficiency during pregnancy is
associated with the defects like increased maternal morbidity,
preeclampsia and toxemia, prolonged gestation, inefficient la-
bor, atonic bleeding, increased risk of abortion, and stillbirths.
Teratogenicity, low birth weight infants, diminished attention in
the newborn, and poorer motor function at six months are also
reported (Bedwal and Bahuguna, 1994; Prasad, 1996; Higdon,
2003).
ZINC DEFICIENCY IN PAKISTAN
In Pakistan, despite an increase in per capita food avail-
ability and resultant rise in per capita calorie and protein in-
take, the prevalence of malnutrition has not improved over last
20 years (Pakistan Demographic and Health Survey, 2007). At
the time of the on-set of the Ninth Plan, i.e., 1997–98, the esti-
Tab le 3 Nutrition indicators of Pakistan
Nutrition indicators of Pakistan
Deficiencies
Vitamin A
(Indirect estimates) 12.50%
Bitot’s spot 1.20%
Low serum retinol 12%
Zinc 37%
IDD (iodine deficiency disorder)
Prevalence of clinical Goiter 6.50%
Biochemical Iodine Deficiency
Moderate 17%
Severe 22.90%
Iron 45%
Source: National Nutrition Program, 2011.
mated number of malnourished children was about eight million.
Nearly half of the children under five years of age were found
underweight of age at a level that corresponds to general mal-
nutrition of PEM. Approximately 5% of these were severely
underweight and 10% were moderately underweight. Recent
studies show that Pakistan is lacking to achieve its Millennium
targets goal to reduce malnutrition and it is clearly depicted from
Figure 3.
The nutritional and demographic surveys, conducted during
last two decades, indicate extremely poor state of female and
child nutrition. According to the National Nutrition Survey (Na-
tional Nutrition Survey, 1988), nearly 65% of the young children
and 45% of pregnant and lactating women suffered from anemia
due to iron deficiency. Nearly 28% of pregnant and 46% of lac-
tating women consumed less than 70% of recommended daily
allowance (RDA) of calories. This proportion has not changed
much in 1995 (Pakistan Demographic and Health Survey, 2007).
The NNS (National Nutrition Survey, 1988) observed a high in-
cidence of malnutrition among children under five years of age.
About 52% of children were found to have low weight for age
(underweight); 42% had low height for their age (stunted); and
11% had low weight for height (wasted). In recent years, the pro-
portion of children stunted declined to 36%, while the propor-
tion of children wasted increased to 14% during 1990–94 NHS
(Pakistan Demographic and Health Survey, 2007). NNS (Na-
tional Nutrition Survey, 1988) also observed low consumption
of protein, calories and iron among children. Almost 10–20%
children of age under five years, received less than 70% of the
RDA of protein, nearly 30–40% received less than 70% of the
RDA for calories and 25% children of the age group 4–5 years
received less than 70% of the RDA for iron. An overview of
Pakistan nutrition indicators are presented in Table 3.
Despite widespread stunting and the high dietary phytate con-
tent in the average diet, there are few data on the prevalence of Zn
deficiency in Pakistan. In this country, zinc deficiency has been
found in malnourished children and children suffering from per-
sistent diarrhea. The zinc deficiency has been reported in 54.2%
preschool children (Paracha and Jamil, 2000). The zinc defi-
ciency and sub-clinical infections in Pakistani preschool chil-
dren have been found alarmingly high and proper intervention to
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1228 N. KHALID ET AL.
Figure 3 Millennium target goal (MDG) on reduction in malnutrition (weight for age) (1990 =100%, target reduction to 50% of 1990 level by 2015).
Source: WDI 2006 & UNDP 2006. (Color figure available online.)
reduce zinc deficiency and sub-clinical infection in vulnerable
group of population is urgently required.
Bhutta (2007) evaluated serum-Zn concentrations on a na-
tionally representative sample of 5800 women of reproductive
age and children (age group: <5 years). The assessment revealed
that almost a third of children and 40% of mothers had serum-Zn
concentration below 60 μg/dL, and the prevalence was greater
in rural populations. Bhutta et al. (2000) evaluated prospectively
risk factors for Zn deficiency in two urban and rural cohorts of
weaned infants. Quantitative assessment of intake of Fe and Zn
from commonly consumed weaning diets indicated that dietary
Zn and Fe intakes were very low (1.2 mg/day in young infants,
1.9 mg/day in older infants). These values are below the RDAs
and are accompanied by a high phytate content of the diet and
high burdens of diarrhea and respiratory infections.
The zinc deficiency in humans in general is a serious global
issue particularly in the developing nations. In Pakistan, 54.2%
preschool children of KPK (Khyber Pakhtunkhwa) province
were reported to be zinc deficient (Paracha and Jamil, 2000).
Similarly in a population based study in urban and rural Sindh,
54% of all pregnant women were observed to be zinc defi-
cient (Bhutta, 2000). A comparable rate of sub-clinical zinc
deficiency was seen among adolescent girls and boys in upper
Sindh province. The National Nutritional Survey 2001–02 has
indicated that 37.1% preschool children and 41.4% mothers of
children under five years had sub-clinical zinc deficiency with
serum concentrations below 60 μg/dL. Approximately 61% of
people in developing countries are at risk of low dietary zinc
intake (Brown and Wuehler, 2000). Bhutta et al. (2007) reported
several traditional foods consumed by infants in Pakistan like
Khitchri (rice +lentil), Sago Dana (sabo grain), Kheer (rice
pudding), Suji Kheer (suji and milk), Suji Halwa (suji +sugar
and water), Banana Kheer (banana +milk and sugar), Potato
Kheer (potato +milk and sugar), and Mixed Diet (potato, lentils,
spinach, and oil). They reported a significant variation in average
daily intake and absorption of zinc from commonly consumed
complementary foods by young infants and envisaged that ab-
sorption of zinc was more in infants of age group 9–12 months as
compared to infants of 6–8 months. The most common comple-
mentary food consumed in Pakistan by Infants (6–12 months)
and uptake of iron and zinc form these complementary foods are
represented in Table 4. The higher Zn deficiency in Pakistani in-
fants occurs because of incomplete beast feeding practices. The
recent Pakistan demographic health survey indicates that only
23% people practice exclusive breastfeeding up to six month of
age (Global breastfeeding week, 2011). Figure. 4 clearly shows
that Pakistan and South Asia still follows one of the world lowest
breastfeeding practices in the world (UNICEF, 2011).
The recent WHO/UNICEF review on complementary feed-
ing in developing countries confirmed that iron and zinc require-
ment may be difficult to meet from nonfortified complementary
foods (WHO, 1998). Diarrheal illness and helminthiasis prob-
lem in Pakistan increases micronutrients requirements. Mothers
in Pakistan have very low iron and zinc status, hence delivering
low birth weight babies that are more prone toward different
diseases (Bhutta, 2007). A study conducted to check the plasma
levels for retinol-binding protein and zinc among young infants
presenting with diarrhea by Bhutta (2007) in Karachi and he
concluded that the plasma zinc concentration was significant
lower among those having low birth weight. The other rea-
sons for having low zinc concentration is low rate of exclusive
breastfeeding and delayed introduction of suitable complemen-
tary food (Kilbride et al., 1999).
The cereal flours are currently the most frequently used ve-
hicles for calcium, iron, and zinc fortification in many advanced
countries of the world. Unfortunately, the calcium, iron, and zinc
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1229
Tab le 4 Average complementary foods of Pakistani infants (modified from Bhutta, 2000)
Iron and zinc content of complementary foods in Pakistani infants (6–12 months of age)
Zinc Iron Phytate Phytate/Zn Phytate/Fe
Content per 100 g Energy density (mg) (mg) (mg) Molar ratio Molar ratio
Khitchri (rice-lentils) 1.2 1.9 2.8 291 15.08 8.81
Sago dana (sabo grains) 0.6 0.2 0.3 54 26.5 15.27
Dallia (wheat porridge) 0.9 0.3 0.7 61 20.0 7.39
Kheer or firni (rice porridge) 0.7 0.3 0.3 81 26.59 22.90
Suji kheer (suji and milk) 0.6 0.1 0.4 14 13.78 2.96
Suji halwa (suji, sugar, and oil) 1.8 0.4 0.6 46 11.32 6.50
Banana kheer (milk-based) 0.5 0.1 0.3 7 6.89 1.97
Potato kheer (milk-based) 0.6 0.1 0.3 16 15.75 4.52
Mixed diet (potato, lentils, spinach, and oil) 0.7 1.2 1.8 77 6.31 3.62
in cereal based foods are poorly bioavailable due to presence of
antinutritional factors like phytic acid that reduces their intesti-
nal absorption, resulting in high rates of iron and zinc deficiency,
especially in infants, children, and women of child-bearing age
(Sandstead, 2000). Several investigators reported that calcium
may interfere with the absorption of iron and zinc (Hallberg
et al., 1993). These elements can interact with each other, with
one element inhibiting the absorption of the other (Lonnerdal,
2000). The postabsorptive interactions between calcium, iron,
and zinc are yet not much known. There is need to understand
the interactions of these nutrients for assessing the effects of iron
or zinc supplementation on the nutritional status of the other nu-
trient. The information regarding micronutrient bioavailability
is vital for the planning of appropriate intervention strategies to
overcome the MNDs.
STRATEGIES AND SOLUTIONS TO COMBAT
THE DEFICIENCY
Foods with a high content of absorbable micronutrients are
considered the best means for preventing MNDs (Gibson and
Ferguson, 1998; IZiNCG, 2004). In countries like Africa where
supplies of such foods a++re unavailable, specific preventive
and healing interventions are needed (Adamson, 2003; Holmes
and Toole, 2005). There are few countries including Pakistan
that have adopted zinc supplementation (Fig. 5) as there na-
tional policy. Recently, it has been clearly understood that three
main factors are responsible for zinc deficiency in developing
world these includes, inadequate dietary consumption due to
the intake of largely plant-based diets, or suboptimal breast-
feeding practices; disease states that either disrupt zinc utiliza-
tion or induce excessive losses; and physiological stressors that
elevate zinc requirements, such as rapid growth during child-
hood and pregnancy (Hess et al., 2009). Three major nutrition-
related strategies have been proposed to control zinc deficiency
(Table 5). These include supplementation, fortification, and di-
etary diversification/modification. Right now there is growing
consensus on the importance of multiple micronutrient inter-
ventions in populations with a high prevalence of malnutrition
(Tontisirin et al., 2002; Shrimpton et al., 2005). For the for-
mulation of multiple micronutrient food strict synergistic and
antagonistic interactions between micronutrients have to be con-
sidered (Hurrell et al., 2004; Shrimpton et al., 2005).
Figure 4 Percentage of infants (0–5 months) exclusively breastfed, by region (2000–2007). Source: UNICEF Global Database, 2011. (Color figure available
online.)
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1230 N. KHALID ET AL.
Figure 5 Countries that have adopted zinc policy on zinc supplementation (zinc task force, data from UNICEF, WHO, and USAID). (Color figure available
online.)
Zinc Supplementation
Supplementation can be further divided into preventive sup-
plementation and therapeutic supplementation for treatment of
diarrhea and possibly other infections. According to WHO, sup-
plementation refers to the provision of additional nutrients, usu-
ally in the form of some chemical or pharmaceutical compounds
usually in the form of pills, capsules, and syrups, rather than
in food (WHO/FAO, 2006) but these supplements are highly
absorbable. Zinc supplementation has proven beneficial in the
treatment of acute child diarrhea and appears to enhance linear
growth (Louise and Villamor, 2010) and in fact zinc supple-
mentation has been studied most extensively with reference
to reducing diarrheal morbidity in young children. According
to Zinc Investigators’ Collaborative Group (IZiNCG), children
with acute diarrhea supplemented with zinc, results in 15%
lower probability of continuing diarrhea when compared to the
controlled group (Bhutta, 2000; Scrimgeour et al., 2011) and
recent meta-analysis studies supports their finding (Patro et al.,
2008). Supplementation programs are particularly useful for tar-
geting vulnerable population subgroups whose nutritional status
needs to be improved within a relatively short time period. For
this reason, such programs are often viewed as short-term strate-
gies. Most of the existing experience with zinc supplementation
Tab le 5 Possible solutions of combating zinc deficiency in world and in Pakistan (FAO/WHO, 1998; White and Broadley, 2005; Stein et al., 2007; Bouis and
Welch, 2010; Hussain et al., 2010; Scrimgeour et al., 2011)
Interventions and strategies Coverage Importance and economical aspects
Supplementation: include both preventive and
therapeutic strategy by giving minerals as
drugs in acute form.
This strategy covers from pregnancy to initial
developments of children up to 5 years.
Active response and immunity development but
costly.
Fortification: both single and multiple
fortification method including particular
element of interest (Zn and iron).
To all segments of population, but has disadvantages
like limits to urban areas and disliking among
people in term of color and taste.
Initial uneconomical and difficult to lunge but
give valuable aspects.
Food diversification and modification: change
eating habits and utilization of highly
nutritious food.
Only developed societies of countries and where
selection of food is available.
Economically feasible but less important only
concentrated to developed world.
Biofortification: increasing the bioavailable
micronutrients through plant breeding and
agronomic practices.
Especially in rural area, where food modification is
difficult and people reject fortification techniques.
Economically feasible and have value
importance deficiency.
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1231
is derived from research trials. Issues that must be considered
in the development of supplementation programs include (1)
the physical and chemical forms of the zinc compound; (2) the
dosage level and frequency of administration; (3) the possi-
ble inclusion of other micronutrients in the supplement; (4) the
administration of supplements with or without foods; (5) the
packaging and distribution system; and (6) any possible risk of
toxicity.
Preventive Supplementation
Preventive zinc supplementation reduces the incidence of
diarrhea by approximately 27% among young children over
12 months of age and decreases the incidence of acute lower
respiratory tract infections by approximately 15%. Zinc supple-
mentation reduces child mortality by approximately 6% (Brown
and Baker, 2009). Preventive zinc supplementation also in-
creases linear growth and weight gain of young children, hence
reduced rates of stunting and underweight. The current evidence
on the functional benefits of zinc is based mainly on findings
from preventive zinc supplementation trials (Baqui et al., 2002;
Brown et al., 2002; Brooks et al., 2005). Almost all preven-
tive zinc intervention trials are conducted by a randomized,
placebo-controlled efficacy trial design (Brown et al., 2002),
and little is known about the effectiveness of preventive zinc
supplementation when it is delivered under realistic program
conditions. All of these trails clearly demonstrated the effective
of preventive supplementation. For instance, of 12 studies that
examined the effect of zinc supplementation on acute diarrhea,
11 demonstrated a reduction in diarrhea duration, with eight
showing statistically significant reductions. Moreover, the pub-
lished information on zinc intervention trials completed among
children 6–35 months of age was derived from studies that used
a single daily dose of zinc, ranging from 3 to 20 mg/day in
individual studies, and mostly failed to monitor the possible
adverse effects. Only one study compared daily versus weekly
zinc supplementation and hardly any results are available from
dose-response studies. Thus, more information is needed on op-
timal dosing regimens and duration of zinc supplementation.
IZiNCG recommends daily intake of 3–5 mg of dietary zinc
for children of ages up to 6–47 months depending upon the
usual staple diet (IZiNCG, 2004). From all these frequent trails
and findings in May 2004, UNICEF and WHO issued a joint
statement recommending the use of zinc with oral rehydration
therapy to treat diarrhea in children. Twenty milligrams of zinc
are recommended for 10–14 days in children 12–59 months of
age; and 10 mg of zinc for infants less than six months of age
(WHO and UNICEF, 2004). It has been estimated that imple-
menting zinc supplementation as an adjunct treatment with oral
rehydration therapy to combat diarrhea, could prevent 88% of
deaths attributable to diarrhea (Jones et al., 2003).
A number of studies have examined the effects of zinc on
iron absorption and vice versa, using both tracer methods and
biochemical and functional responses to longer term supplemen-
tation. Longer term studies suggest that each mineral reduces
the magnitude of the biochemical response observed with single
nutrient supplementation (Dijkhuizen et al., 2001; Berger et al.,
2006), although nutritional status is still enhanced to a consider-
able extent despite the nutrient–nutrient interactions. Findings
regarding the impact of zinc supplementation with or without
iron on functional outcomes are less consistent. Simultaneous
delivery of iron and zinc may undermine the growth-enhancing
effect of zinc and possibly the benefits of zinc for reducing mor-
bidity and the benefits of iron for psychomotor development.
In contrast, positive effects on the incidence and duration of
diarrhea in infants and young children have been found with
concomitant iron and zinc supplementation compared with iron
supplementation alone (Rosado et al., 1997; Baqui et al., 2002).
However, studies of combined multiple micronutrient supple-
mentation (including iron and zinc as well as other micronutri-
ents) in Peru (Penny et al., 2004) and Bangladesh (Baqui et al.,
2002) failed to detect the morbidity reduction that was observed
when zinc alone was provided.
Bhutta et al. (2008) study the effect of zinc supplementation
in malnourished children with persistent diarrhea in Pakistan
and concluded that Supplemented children had a significant
improvement in plasma zinc levels and serum alkaline phos-
phatase after 14 days of therapy in comparison with controls.
Similarly, Fischer Walker et al. (2006) conduct randomized,
placebo-controlled trial in three countries (Pakistan, India, and
Ethiopia) to assess the safety and efficacy of 10 mg zinc supple-
mentation for the treatment of acute diarrhea in infants younger
than six months and they concluded that there was no signif-
icant difference of zinc supplementation in young infants for
treatment of diarrhea The importance of oral rehydration so-
lution (ORS) and continued breastfeeding for the treatment of
diarrhea, should continue in young infants where zinc may not
be as effective as in older children. The current WHO/UNICEF
recommendations for the treatment of diarrhea suggest zinc sup-
plementation in addition to ORS and continued feeding for all
children younger than 5 years (WHO and UNICEF, 2004). Their
finding suggests that WHO should consider reevaluating this
policy for infants younger than six months. Yakoob et al. (2011)
carried a detail review to optimize the performance of zinc sup-
plementation in developing countries and concluded that zinc
supplementation results in reduction in diarrhea and pneumo-
nia mortality. Imdad and Bhutta (2011), used meta-analysis tool
to check the effect of preventive zinc supplementation on lin-
ear growth in children especially under five years of age and
they comes with a positive result that Zinc supplementation has
a significant positive effect on linear growth, especially when
administered alone, and this strategy should be included in na-
tional programs to reduce stunting in children <5 years of age
in developing countries.
The challenges of zinc supplementation programs include
product availability, coverage, training, endorsement, and treat-
ment compliance (Scrimgeour et al., 2011). Zinc sulfate tablets
have most commonly been used in supplementation programs
because they are inexpensive, easy to transport and accepted by
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1232 N. KHALID ET AL.
mothers and children; however, for program sustainability, local
production or technology transfer is needed.
Therapeutic Supplementation
Many studies have evaluated the therapeutic effects of zinc
supplementation during acute or persistent diarrhea. In studies
conducted by Black (1998) on acute diarrhea, the illness dura-
tion has found to be 9–23% shorter in zinc supplemented than in
controlled children, same case is for the persistent diarrhea but
the results was less significant the reason behind this was less
number of children participate in studies. Therapeutic zinc sup-
plementation has been evaluated for the treatment of respiratory
infections and malaria. There is insufficient and inconsistent
information on the effect of zinc supplementation on the sever-
ity and duration of acute lower respiratory tract infections, and
the data are inconsistent with regard to upper respiratory tract
infections (Hulisz, 2004). There is little information on zinc
as a component of the therapeutic regimen for tuberculosis, and
there is no apparent benefit of zinc supplementation for the treat-
ment of malaria. Dietary supplementation with zinc and other
micronutrients for primary prevention of multiple MNDs that
are known to result from therapies used in the treatment of gas-
trointestinal inflammatory disorders (Scrimgeour and Condlin,
2009). WHO and UNICEF also recommended zinc regarding
the appropriate clinical management of acute diarrhea, which
urges the provision of ORS and home-available fluids, breast-
feeding, continued feeding of other foods, selective use of an-
tibiotics, and the administration of zinc supplements (20 mg/day
for children >12 months of age and 10 mg/day for infants) for
10–14 days with each episode of diarrhea. The significant het-
erogeneity of responses to zinc suggests the need to revisit the
strategy of universal zinc supplementation in the treatment chil-
dren with acute diarrhea in developing countries (Patel et al.,
2010). Following the publication of these recommendations by
WHO and UNICEF, several lower income countries have begun
incorporating zinc supplementation in their therapeutic regimen
for diarrhea.
According to International Zinc Nutrition Consultative
Group (IZiNCG, 2004) adequate zinc nutrition is necessary for
optimal child health, physical growth, and normal pregnancy
outcomes. Systematic trials have found that zinc supplemen-
tation decreases rates of diarrhea and acute lower respiratory
infections among young children, two of the most important
causes of child mortality in lower income countries. Several
studies have detected significantly reduced death rates among
children who receive supplemental zinc (Brooks et al., 2005)
and zinc supplements increased the linear growth and weight
gain of stunted or underweight children (Brown et al., 2002).
FORTIFICATION
Food fortification is a medium- to long-term solution to al-
leviate specific nutrient deficiencies in a population. Its method
involves the addition of measured amounts of a nutrient-rich
“premix,” which contains the required vitamins and minerals, to
commonly eaten foods during processing. Within an integrated
approach, micronutrient fortification of foods and condiments
allows for an inexpensive and highly cost effective strategy to
improve and protect the health and nutritional status of popu-
lations. The start-up cost for food fortification is relatively in-
expensive for the food industry, and recurrent costs are rapidly
passed on to the consumer. The benefits of fortification can ex-
tend over the entire life cycle of humans. It can thus be one of
the most cost-effective means of overcoming micronutrient mal-
nutrition. Although it is a fact that the first reason for fortifying
foods with essential vitamins and minerals is this approach is
safe and effective, the economics of food fortification has played
an important role in its implementation in public policy. Food
fortification is defined as “the deliberate addition of one or more
nutrients to particular foods so as to increase the intake of these
micronutrients and correct or prevent a demonstrated deficiency
and provide a health benefit” (Haider and Bhutta, 2009; Scrim-
geour et al., 2011). The WHO’s dietary goal of fortification is
defined as “the provision of most (97.5%) individuals in the
population group(s) at greatest risk of deficiency with an ade-
quate intake of specific micronutrients, without causing a risk of
excessive intakes in these or other groups” (WHO/FAO, 2006).
Food fortification most often involves the addition of nutrients
to food at the point of food processing or production; however,
fortification may also occur at the community or household level
(Hess and Brown, 2009). The WHO distinguishes three possi-
ble approaches to food fortification: mass, targeted, and market
driven fortification (WHO/FAO, 2006). Mass fortification is the
addition of micronutrients to foods consumed routinely by the
general population. Common mass fortification vehicles include
cereal flours, vegetable oils and fats, milk, and condiments. Tar-
geted fortification is intended to reach a specific population
subgroup that have an identified risk of deficiency, such as com-
plementary foods for young children or rations for internally
displaced populations, when normal food distribution channels
have been disrupted. Finally, market driven fortification is for-
tification of processed foods, initiated by a food manufacturers
(WHO/FAO, 2006; Scrimgeour et al., 2011).
Food fortification, especially multiple micronutrient fortifi-
cation, is often considered the most cost-effective approach to
address deficiencies if the following conditions exist: appro-
priate carrier foods are available; the food industry can pro-
duce and distribute fortified carrier foods; and those subgroups
identified as at risk of MND have access to adequate amounts
of these foods (Gibson and Ferguson, 1998; Hess and Brown,
2009; Scrimgeour et al., 2011). Fortification may be considered
a more appealing option than supplementation as it does not
require the population to alter existing food beliefs and prac-
tices and therefore may result in less disruption to the health
sector. Furthermore, since food fortification costs are supported
by industry and the consumer, the cost burden to governments
are usually low. Many countries are now recommending for-
tification programs as a national policy (Figure 6). Therefore,
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1233
Figure 6 Fortification status in world till March, 2011 (FFI, 2011). (Color figure available online.)
fortification programs have become more common in lower in-
come countries (Gibson and Ferguson, 1998; Hess and Brown,
2009; Scrimgeour et al., 2011). Several zinc compounds are
approved for human consumption and may be used as food for-
tificants including the sulfate, chloride, gluconate, oxide, and
stearate salts (WHO/FAO, 2006). The preferred choices are
zinc oxide or zinc sulfate (Table 6), the two cheapest forms
of zinc that are generally recognized as safe (GRAS) for human
consumption (WHO/FAO, 2006; Hess and Brown, 2009; Scrim-
geour et al., 2011). Tracer studies of foods fortified with either
zinc oxide or sulfate showed that there was no difference in zinc
absorption by school children or adults when either compound
was used to fortify common cereal staples.
The available studies clearly show that zinc fortification can
increase total daily zinc absorption, it is reasonable to say that
individuals at risk of zinc deficiency who consume zinc fortified
foods will have enhanced zinc status. Most absorption studies
also show that adding zinc to food does not adversely affect
the absorption of other minerals, like iron. Despite the known
positive impact of zinc fortification on total zinc absorption,
studies available regarding young children have not shown a
positive effect of zinc fortified complementary foods on indica-
tors of young children’s zinc status, growth or other zinc-related
functional responses.The zinc compound used should meet the
purity requirements of the Food Chemicals Codex and, must
have a status of GRAS. It is noticed that although a number of
studies have been carried out with zinc acetate, it is not GRAS
and therefore cannot be used in food fortification in the United
States and as well as other counties. Zinc acetate is reported to
have an offensive taste when not diluted with sugar and a high
Tab le 6 Common zinc salts used for fortification in different countries
Common zinc salts and their properties used as fortificants
Zinc compound StatusaSolubility Zn (%) Cost (US$/kg) Cost (US$/kg Zn
Acetate No Water soluble 29 5.60 19.30
Chloride Yes High water solubility 48 20.74 43.20
Gluconate Yes Water soluble 14 5.00 35.70
Oxide Yes Not solubleb80 2.33 2.33
Stereate Yes Insoluble 10
Dried sulfate Yes Water soluble 36 3.74 10.40
Hydrated sulfate Yes Water soluble 23 3.15 13.70
aGenerally recognized as safe (GRAS).
bSoluble in dilute acid or alkali (adopted from Ranum, 2001).
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1234 N. KHALID ET AL.
reactivity in foods. For these reasons, zinc acetate has not been
used in commercial food fortification, and this lack of use has
prevented it from receiving GRAS status. All of the zinc sources
are white, so the color is not a problem; the potential problem
is that some of the more soluble sources cause color changes in
certain food ingredients, such as chocolate. Also, some zinc salts
may impart undesirable flavors. For example, zinc oxide has a
bitter taste, and zinc sulfate is very astringent. Zinc acetate has
a slight odor of acetic acid, whereas the other salts are odorless.
The most important difference between the zinc sources is their
solubility, because it relates to both bioavailability and effects
on food quality. Zinc oxide is not soluble in water but soluble in
dilute acid. This implies that it will be inert in dry foods but that
it should be available for absorption after exposure to stomach
acid. Zinc acetate, zinc gluconate, and zinc sulfate are soluble in
water, and zinc chloride is very soluble. Zinc oxide is the most
commonly used zinc source for the fortification of cereal-based
foods, followed by zinc sulfate and, to a very small extent, zinc
gluconate. Zinc sulfate is specified for use in the corn-soy blend
(USDA, 1998) and the wheat-soy blend produced for the US
Food for Peace Program. Zinc acetate and zinc gluconate find
use in dietary supplements and some weaning foods. Pakistan
has launched national wheat fortification program assisted by
Global Alliance for Improved Nutrition (MIH, 2011) and mi-
cronutrient initiative (MI) (MIH, 2011), it’s a three year program
executed by Nutrition Wing of the Ministry of Health, from this
program it is estimated that 48 million (32% of Pakistan’s pop-
ulation) get benefit. Total budget for the program is US $3.4
million (MIH, 2011).
Bioavailability of Different Zinc Salts
The bioavailability status reviewed by Davidsson (1999)
gives perfect idea about the nature of different salts. There have
been very few studies on zinc absorption from fortified cereals.
One study on rats by Ranhotra et al. (1977) at the American
Institute of Baking showed little difference in absorption of the
different sources when they were added to bread. Absorption
of zinc carbonate was poor, but absorption of zinc oxide was
nearly as good as that of the more soluble forms. No adverse
effects on bread quality were found by Ranhotra et al. (1977).
In a chick feeding study (Sandoval et al., 1997) with a corn and
soybean meal, the bioavailability of two commercial forms of
zinc sulfate was 99% and 81%, whereas that of two sources of
zinc oxide was 78% and 54%. A second experiment found a
bioavailability of 94% for zinc sulfate and 74% for zinc oxide.
Studies in Turkey (Saldamli et al., 1996) reported that bread
fortified with zinc acetate had an acceptable quality and was
effective in preventing zinc deficiency in children. It appears
that zinc fortification has little detrimental effect on flour and
bread quality. One study, in which levels up to 500 ppm of zinc
were added as zinc chloride, even showed a beneficial effect of
this addition on baking (Vadlamani and Seib, 1999). The dif-
ferences in the availability of zinc from different compounds as
mentioned earlier are largely a function of their solubility, which
is dependent on pH, both in the food and in the stomach. In one
study Henderson et al. (1995) compared the absorption of zinc
from zinc acetate and zinc oxide in humans with gastric pH of
low (3) and high (5). They concluded that absorption was
higher from the acetate than from the oxide in subjects with high
gastric pH (low gastric acid production), but the absorption was
similar when gastric acid production was normal. Absorption of
both forms of zinc was greater at low gastric pH than at high gas-
tric pH. These results suggest that although the oxide may have
sufficient bioavailability for a normal population, it might not be
suitable for malnourished children whose stomach pH is higher
because of reduced ability to produce stomach acid, and that
therefore it should not be used in therapeutic supplementation
programs.
Level of Zinc in Different Cereals
Zinc fortification of cereal flour is a safe and appropriate
strategy for enhancing the zinc status of population subgroups
who consume adequate amounts of fortified cereal flour (Brown
et al., 2010). The levels of micronutrients added to cereals are
based on restoring the levels in refined cereals back to the level
contained in the whole grain product. Drake et al. (1989) demon-
strated that the levels of zinc in the three main cereal staples
before and after milling. They found that after milling of rice,
zinc decreases from 20 to 11 ppm, in wheat 29 to 7 ppm, and
in maize 18 to 7 ppm. The addition of 20 ppm zinc to white
wheat flour would nearly replace the zinc lost to milling. Higher
levels of zinc might be added to obtain a greater benefit, par-
ticularly when the intake of the cereal is not high. Higher zinc
addition rates are often used in the special complementary foods
and in branded ready-to-eat cereals. For example, 40 ppm zinc
is added to the corn-soy blend and 50 ppm to the World Food
Program’s version of the corn-soy blend (Ranum, 1999). Even
at the lower levels of 20–30 ppm of added zinc, the impact on
meeting dietary requirements would be significant. At a reason-
able daily intake of 100 g of cereal enriched with 20 ppm zinc,
children would receive 20% of their daily zinc requirement.
Such fortification levels would not present a safety hazard. At
the likely upper limit of a sustained intake of 500 g of cereal
per day, which would supply over 1800 kcal/day of energy, the
maximum amount of zinc added to the diet would be 15 mg/day,
or 100% of the adult recommended daily intake, if all cereals
were fortified with 30 ppm zinc. The proper level of zinc for
mass fortification programs is that which would increase the
intake of zinc by the targeted individuals, without imposing a
risk of excessive intake on the rest of the population. Interna-
tional Zinc Nutrition Consultative Group recommends a total
zinc intake of no more than 40 mg/day by adults. To determine
the appropriate level of fortification, it is necessary to measure
or estimate the amount of the food vehicle being consumed by
different segments of the population. International Zinc Nutri-
tion Consultative Group concluded that the appropriate levels
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1235
of zinc fortification of cereal staples used for mass fortifica-
tion programs is generally between 30 and 70 mg Zn per kg of
flour depending on the range of usual flour consumption (Brown
et al., 2010). Higher levels may be desirable for foods targeted
to young children.
There are several zinc compounds that are available for for-
tification (IZiNCG, 2004). Many compounds are listed by the
USDA as GRAS, there is no consensus as to which of the GRAS
compounds is most appropriate for fortification programs. Zinc
sulfate and zinc oxide are the GRAS salts that are least expensive
and most commonly used by the food industry. Despite theoret-
ical considerations that suggest that zinc may be better absorbed
from water soluble compounds, like zinc sulfate, several studies
indicate that zinc is equally well absorbed from cereal products
fortified with either zinc sulfate or zinc oxide (Brown et al.,
2002).
Biofortification
This refers to the breeding of staple crops for higher levels
of vitamins and minerals that are essential for human nutrition
and health (Bouis, 2002); this approach contrasts with indus-
trial fortification efforts that focus on processed food items.
Biofortification involves breeding staple food crops, such as
rice, wheat, maize, and pearl millet both for higher yields and
higher nutrient content (Bouis, 2002; Welch and Graham, 2004;
Scrimgeour et al., 2011). This method has multiple advantages,
including the fact that it capitalizes on the regular daily in-
take of a consistent amount of food staple by all family mem-
bers, and, because staple foods predominate in the diets of the
poor, this strategy implicitly targets low-income households
(Nestel et al., 2006; Rosado et al., 2009; Scrimgeour et al.,
2011) specifically, zinc biofortification could provide both a
feasible means of reaching zinc-deficient populations in rela-
tively remote, or rural areas, and it could deliver fortified foods
to people with limited access to commercially marketed fortified
foods that are more readily available in urban areas (Nestel et al.,
2006; Rosado et al., 2009; Scrimgeour et al., 2011). Recently, a
zinc-biofortification study, conducted in Mexico (Rosado et al.,
2009) they reported that absorption of zinc was greater from the
zinc bio-fortified wheat than from control wheat when fed to
adult women as their primary source of energy and nutrients.
The results of their study confirmed that zinc absorption from
the same quantities of wheat flour was greater from the zinc
biofortified wheat than from wheat with a more typical zinc
concentration. Though substantial quantities of zinc were lost
with moderate extraction (80%), absorption of zinc from the
zinc biofortified wheat remained significantly higher than that
from the control wheat. Indeed, the quantity of zinc absorbed
from zinc fortified 80% extracted wheat was similar to that from
the 95%-extracted wheat because of the simultaneous reduction
in phytate. The findings are of practical interest because it indi-
cates that the benefits of the zinc-biofortified wheat are not lost
with a moderate degree of milling. Follow-up long-term feed-
ing studies are needed to verify the efficacy of zinc biofortified
wheat.
Biofortification in Pakistan Staple Food Wheat
Wheat is the staple food of Pakistan. Wheat is consumed all
over world as a major source of food. Wheat contains higher
content of phytates and these hinder with absorption of Zn and
iron, so biofortification is one of recommended method to over
comes the problem of bioavailability. Wheat flour fortification
program has been successfully implemented in Pakistan to re-
duce the prevalence of micronutrients deficiency. Bread wheat
(Triticum aestivum L.) and tetraploid or durum wheat (Triticum
durum L.) are the wheat genotypes that are grown on large
scale to feed millions of people all around the world (Saldamli
et al., 1996; Hussain et al., 2010). Wheat is a major source of
calorie intake in central and western and South Asia (Fig 7).
It is grown on very poor soils like alkaline calcareous soils
of semi arid regions. These anthropogenic and climatic factors
lead to decreased availability of soil Zn (IZA, 2009). Wheat is
highly susceptible to Zn deficiency in such conditions and pro-
duces low grain yield with low levels of grain Zn concentration.
Wheat grains contain about 25–30 μg Zn per gram dry weight,
while for a measurable impact of Zn biofortification on human
health, desired wheat grain Zn concentration should be >50 μg
per gram of dry weight (Cakmak et al., 1998). There is a pos-
sibility to fortify wheat flour for micronutrients as adopted by
Government of Pakistan for Iron and recently MI launch differ-
ent programs to fortify food with Zn salts. Genetic engineering,
breeding, and agronomic approaches are important tools of bio-
fortification (Zimmermann and Hurrell, 2002; Cakmak, 2008).
Increased grain Zn concentration is an important quality pa-
rameter of food. The biofortification approach relies on crop
management and improvement strategies for higher grain Zn.
The absorption of dietary Zn is mainly limited by high phytate in
our food. Phytate:Zinc molar ratio >15 reduces Zn absorbance
to only 15% (White and Broadley, 2005; Brown et al., 2001).
Zinc Wheat for Pakistan
Scientists are trying to develop zinc wheat for the Pakistan es-
pecially in Punjab province where per capita wheat consumption
averages about 350 g per day. The people in Pakistan especially
in villages much prefer to consume whole wheat rather wheat
flour in refined form. Farmers replicates seeds only from fewer
varieties that gives them good yield, hence only few modern
varieties are found among them, these must be replaced period-
ically with modern varieties, as they lose their resistance to new
evolving strains of disease. The main strategy of HarvestPlus is
to incorporate high zinc and iron traits into new wheat varieties
that are resistant to new strains of yellow and stem rust. Har-
vestPlus estimates, under an optimistic scenario, that high zinc
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1236 N. KHALID ET AL.
Figure 7 Daily calorie intake of wheat in different countries of world (modified from Hussian et al., 2010). (Color figure available online.)
wheat varieties would be consumed by “100 million Pakistanis”
10 years after release (HarvestPlus, 2011).
DIETARY DIVERSIFICATION/ MODIFICATION
To make food with a higher content of absorbable zinc and
better bioavailability is the main aim of dietary diversification
(Gibson and Anderson, 2009) and it is not an easy task. In terms
of dietary diversification, three main strategies are adopted all
around the world with certain modification. These strategies in-
clude complementary food enhancement or enrichment, agricul-
tural interventions, and behavioral change (Gibson and Ander-
son, 2009). All of these techniques must be applied in Pakistan
in order to elevate Zn deficiency. The main focus of agricultural
interventions is to increase productivity of local crops that are
utilized as staple food; like wheat, rice, maize, sorghum, and
millet. During agricultural intervention main attention will be
paid upon macro and micronutrient status. Many researchers
have proven that higher intake of zinc are positively correlated
with higher intakes of iron and protein (Galal et al., 1987). Agri-
cultural interventions in Pakistan include research on develop-
ment of new varieties of wheat breed with higher concentration
of Zinc. These new techniques are ongoing with cooperation
of HarvestPlus group (HarvestPlus, 2011). Intervention of new
varieties that are lower in phytate content (Khan et al., 2007)
and have higher bioavailability is also on it way and Pakistan
Agricultural Research Board has funded 27.288 million Rupees
for development of wheat varieties having higher zinc and iron
content (Baig, 2011). Similarly, by modification of agronomic
practices like utilization of Zinc fertilizers is another interven-
tion (Kanwal et al., 2010). Other interventions include increased
utilization of leafy vegetables and consuming higher vitamin A
content foods (Gibson and Anderson, 2009). It is also recom-
mended to increase utilization of animal’s foods (meat and fish)
as regular part of diet beside milk and vegetables because it
increases the intake bioavailable zinc especially for infants and
school-age children. Recent studies have proven that there are
some indigenous fish species in Cambodia and Bangladesh that
are rich sources of Iron, vitamin A and Zinc (Roos et al., 2003).
Many scientists have concluded that both short-term measures
(supplementation and fortification) and long-term solutions
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ZINC DEFICIENCY IN 185 MILLION PEOPLE IN PAKISTAN 1237
(dietary diversification or modification and biofortification) can
be used to alleviate zinc deficiency in developing countries es-
pecially Asia and Africa (Gibson, 2006).
Dietary diversification or modification includes some tech-
nological perspectives at lower level and changing diet patterns
(Gibson and Anderson, 2009). Both of these are prime im-
portant in developing countries where diet are basically from
plant-based and consumption of animal-source foods, such as
meat, poultry, and fish, is limited because of economic, cultural,
and religious constraints. As a result, the zinc content of low
income countries diets is low and the efficiency of absorption
is limited. Dietary inadequacy is probably the primary cause
of zinc deficiency (Gibson and Anderson, 2009). Promotion of
house based livestock husbandry, aquaculture, and production
of zinc-rich food besides leafy vegetables can increase zinc
content of diet. Technological perspectives include reduction of
phytates in diet at household level by simple techniques like
germination, microbial fermentation, and soaking to activate
phytase, which is present naturally in cereals and legumes (Gib-
son et al., 2006). Similarly, use of ascorbic acid containing fruits
to destroy antinutritional factors like thiaminases and disruption
of carotenoid-protein complexes is also recommended (Gibson
et al., 2006).
This combination of two dietary strategies suggested by Gib-
son and Anderson (2009) that involving increased consumption
of animal-source foods and phytate reduction is considered as
the best to enhance both the content and bioavailability of zinc in
the diets of rural households in low income countries (Gibson,
2006). Utilization of animal foods in combination of vegeta-
bles have the added advantage of simultaneously improving the
content and bioavailability of iron, zinc, calcium, and essen-
tial vitamins like B12 and A, and as well as enhancing protein
quality and better digestibility (Gibson et al., 2003).
To increase the zinc content of plant-based materials, several
strategies can be utilized. These include art of plant breeding, the
use of zinc fertilizers, and genetic modification techniques like
marker assisted technology. All of these methods are promising,
but research is needed to evaluate their economic, environmen-
tal, and health effects. Promoting programs of exclusive breast
feeding up to six months of age is also considered as zinc in-
tervention programs. Complementary feeding programs should
be implemented in a better way with diversity of nutrients and
consideration of their positive and negative impacts. These in-
terventions if properly implemented would result in increase
uptake of zinc leading towards a better society with improve nu-
trient status and positive development of a developing country.
CONCLUSION
It is common saying, “health people make a healthy and pro-
gressive country.” Pakistan isstill a developing country, and it is
mandatory for Government to provide safe and nutritious food to
185 million people, so to make Pakistan a healthy and developed
country. Zn and Iron are limiting micronutrient in all segments
of population. This is not only common for Pakistan millions of
people around world is unable to achieve target goals in terms
of nutrition. Pakistan has agriculture based economy. Fortifica-
tion and biofortification are best recommended method to solve
this hidden hunger. Zinc supplementation must be incorporated
as national vaccination program, if to achieve millennium tar-
get goals. But it remains a question mark on policy maker and
Government?
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... Zinc is mostly stored in the skeletal muscles, and the total amount of zinc in an adult human body is approximately 2 to 3 g, with a daily requirement of 12 to 16 mg/day. 2,3 Decreased intake, malabsorption or high loses of micronutrients from the gut may lead to zinc deficiency, resulting in impaired growth, neuronal abnormalities, iron deficiency anemia due to decreased iron absorption, and even cardiovascular diseases. 2 With zinc deficiency targeting more than 2 billion people worldwide, it results in more than 0.5 million deaths per year in infants and children below 5 years of age. ...
... 7 With roughly 17% of global population consuming a zinc-deficient diet, around a quarter of the pediatric population below the age of 5 suffers from stunted growth. 8 In Pakistan, as concluded by Khalid et al, 3 20.6% of the pediatric population of Pakistan had zinc levels below 60 μg/dL. ...
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Pediatric populations from lower-income countries may experience a higher incidence of zinc deficiency, which may cause physical and neurological dysfunctions. This case control study aims to assess different levels of zinc between malnourished and well-nourished children. Our study included 108 participants, all children less than 12 years of age. Out of the 108, 54 were malnourished children (cases), while 54 were well nourished (control group) and were screened for zinc deficiencies. Zinc deficiencies were 4 times more common in malnourished cases than in controls (OR: 3.89 95% CI: 1.1-14.9) with median value of zinc in cases being 91.69 and that of controls was 117.6. Our findings indicate significant deficiencies in malnourished children as compared to well-nourished children. Additionally, our findings support literature surveyed that suggest dietary changes alone would not be able to replenish zinc levels in children.
... To extend our previous findings, we modeled chronic changes in zinc homeostasis and included zinc supplementation as well as zinc deficiency in the study presented here. Zinc deficiency is frequently observed in around 30% of the world's population and poses a global health problem [47]. By cultivating A549 cells [48,49] in culture media with different zinc contents, we achieved a more physiological and long-term alteration of the intracellular labile zinc concentration than in our previous study [33]. ...
... To extend our previous findings, we modeled chronic changes in zinc homeostasis and included zinc supplementation as well as zinc deficiency in the study presented here. Zinc deficiency is frequently observed in around 30% of the world's population and poses a global health problem [47]. By cultivating A549 cells [48,49] in culture media with different zinc contents, we achieved a more physiological and longterm alteration of the intracellular labile zinc concentration than in our previous study [33]. ...
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Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.
... Published by Rynnye Lyan Resources FULL PAPER of 4% to 73%. The highest prevalence is found in Southeast and South Asia (34-73%) (Khalid et al., 2014). A total of 77.48% zinc deficiency was found in Indonesia based on the 2010 Riskesdas secondary data study (Anwar et al., 2018). ...
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One in five people in the world is at risk of zinc deficiency. In Indonesia, 77.48% of the population has zinc deficiency. Zinc deficiency causes sperm abnormalities, such as hypertrophy and hyperplasia of the fibrous sheath, axonal disorders, and abnormal midpiece. Serum zinc levels of infertile males were significantly lower than normal males. Factors causing a lack of serum zinc are inadequate dietary zinc intake and zinc absorption inhibitors. Serum zinc levels are influenced by unclear factors. The purpose of this study was to analyze the relationship between Body Mass Index (BMI), zinc, iron, protein, tannins and phytate intake with serum zinc levels of infertile male farmers in the Larangan district. This research was an observational study with a cross-sectional design. The sample selection used a total sampling technique of as many as 58 male infertile farmers. Data was collected through interviews using a food frequency semi-quantitative questionnaire, measurement of height using a microtoise, weighing using a digital stepping scale, and laboratory tests of venipuncture blood samples. Data analysis was performed using Pearson correlation and Spearman range. The average BMI of respondents was above the normal limit (26.09). The average zinc intake was 8.99 mg/ day, the average iron intake was 18.31 mg/day, the average protein intake was 85.71 g/ day, and the average tannin intake was 139.93 mg/day. The average phytate intake was 1147.73 mg/day and the average serum zinc level was 78.02 μg/dL. The bivariate analysis showed that there was no relationship between BMI (p-value = 0.29), zinc intake (p-value = 0.42), iron (p-value = 0.33), protein (p-value = 0.70), tannins (p-value = 0.19), and phytate (p-value = 0.63) with serum zinc levels. The average zinc intake of infertile male farmers was below the cut of nutritional adequacy rate. Infertile male farmers are advised to increase their consumption of animal zinc sources to make ends meet zinc intake per day.
... For the promotion of mass production and consumption of biofortified wheat, there is a need to know its acceptance level among masses along with the level of their willingness to pay for such products once they enter the market [38,39]. A study conducted on Znbiofortified wheat flour's efficacy among women, children, and non-lactating women of childbearing age in India have revealed promising outcomes by the introduction of low zinc wheat flour (LZWF) and high zinc wheat flour (HZWF) to more than 6 thousand respondents [40]. ...
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A range of nutritional needs are met through the use of fortified farm-based foods. Wheat biorfortification with zinc is such an example where biorfortification is carried out for a crucial element like Zinc. Zinc-biofortified wheat (Zn-wheat) has been officially launched in Pakistan since 2016 but its wide-scale dissemination, adoption and consumption have not taken place till to date. On the other hand, essential nutrients deficiencies have wide-ranging implications for public health especially for children and lactating mothers. This study is undertaken to know the reasons for the slow progression of scaling up of biofortified wheat varieties in Pakistan, people’s awareness about biofortified wheat and to recognize the role of information in acceptance and willingness to pay for this wheat. For this purpose, randomly selected 474 households were interviewed from four districts of Punjab province. They were categorized into four groups based on their exposure to information in real and hypothetical cheap talk (game theory context). Study findings reveal that respondents were ready to pay for fortified wheat if they are aware about nutrient aspects and Zn deficiency. Using Discrete Choice Experiment, the preferences for and factors affecting the willingness to pay for fortified wheat are evaluated. Main factors having positive impact include household head’s education and income, having pregnant women and children <5 years age. It was also found that people having valid information about nutrients of a food would be willing to pay more. The study highlights need for policy focus on educating people about nutritional aspects as well as making available biofortified foods to promote healthy living.
... The prevalence is low 4-7% in north America and Europe, and high in north Africa and eastern Mediterranean which, accounts 25-52%, south and central America 68% and in south and south east Asia (34-73%) [6]. Ethiopia is one of the five countries who together contribute 47% of the child deaths attributable to zinc deficiency in Africa [7]. ...
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Background Zinc is an essential mineral known to be important for the normal physiological functions of the immune system. It is one of the basic nutrients required during pregnancy for the normal development and growth of the fetus. However, Zinc deficiency during pregnancy causes irreversible effects on the newborn such as growth impairment, spontaneous abortion, con- genital malformations and poor birth outcomes. Even though, the effect of Zinc deficiency is devastating during pregnancy, there is scarcity of evidence on Zinc deficiency and related factors among pregnant women in the current study area. Objective To assess Zinc deficiency and associated factors among pregnant women attending ante- natal clinics in public health facilities of Konso Zone, Southern Ethiopia. Methods Institution based cross-sectional study was conducted among randomly selected 424 preg- nant mothers. Data were collected using pre tested questionnaire (for interview part), and 5 blood sample was drawn for serum zinc level determination. Data were entered to Epi-Data version 3.1 software and exported to SPSS version 25 for analysis. Binary logistic regres- sion analysis was computed and independent variables with a p-value � 0.25 were included in multivariable analysis. Serum zinc level was determined using atomic absorption spec- troscopy by applying clean and standard procedures in the laboratory. Finally adjusted odds ratio with 95% confidence level, P-value < 0.05 was used to identify significant factors for Zinc deficiency. Result The prevalence of Zinc deficiency was found to be 128 (30.26%) with the mean serum zinc level of 0.56±0.12 g/dl. Age, 25–34 years [AOR 2.14 (1.19,3.82)], and 35–49 years [AOR 2.59 (1.15, 5.85)], type of occupation, farming [AOR 6.17 (1.36, 28.06)], lack of antenatal fol- low up during pregnancy [AOR 3.57 (1.05,12.14)], lack of freedom to purchase food items from market [AOR 3.61 (1.27, 10.27)], and inadequate knowledge on nutrition [AOR 3.10 (1.58, 6.08)] were factors associated with Zinc deficiency. Conclusion Zinc deficiency is a public health problem among pregnant mothers in the current study area. Improving maternal nutritional knowledge, motivating to have frequent antenatal follow up, and empowering to have financial freedom to purchase food items from market were the modifiable factors to reduce Zinc deficiency. Nutritional intervention that focused on improv- ing nutritional knowledge and insuring access to Zinc sources food items should be deliv- ered for pregnant mothers
... In the subgroup analysis by region, we found that Zn concentration in the plasma/serum of patients with BC in Africa and Asia was significantly lower than those in non-BC participants; it was also found to be significant in hair in Asia; no significant differences between cases and non-BC participants were found in samples from Europe and South America. The reason for these differences may attribute to the dietary shortage of Zn in Africa and Asia, especially in South Asia, South East Asia, and sub-Saharan Africa (100,101). In addition, rs10822013 on the chromosome at 10q21.2 in the zinc finger protein 365 (ZNF365) gene is a genetic risk variant for all four stages of BC among East-Asian women (102). ...
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Introduction Heavy metals were classified as essential, probably essential, and potentially toxic in the general population. Until now, it has been reported inconsistently on the association between heavy metals and BC. In this meta-analysis, we aimed to assess the association between heavy metals and BC and review the potential mechanisms systematically. Methods We searched for epidemiological studies in English about the association between heavy metals and BC published before September 2020 in PubMed, Web of Science, and Embase databases. In total 36 studies, comprising 4,151 individuals from five continents around the world were identified and included. Results In all biological specimens, Cu, Cd, and Pb concentrations were higher, but Zn and Mn concentrations were lower in patients with BC than in non-BC participants [SMD (95% CIs): 0.62 (0.12, 1.12); 1.64 (0.76, 2.52); 2.03 (0.11, 3.95); −1.40 (−1.96, −0.85); −2.26 (−3.39, −1.13); p = 0.01, 0.0003, 0.04, <0.0001, <0.0001]. Specifically, higher plasma or serum Cu and Cd, as well as lower Zn and Mn, were found in cases [SMD (95% CIs): 0.98 (0.36, 1.60); 2.55 (1.16, 3.94); −1.53 (−2.28, −0.78); −2.40 (−3.69, −1.10); p = 0.002, 0.0003, <0.0001, 0.0003]; in hair, only lower Zn was observed [SMD (95% CIs): −2.12 (−3.55, −0.68); p = 0.0004]. Furthermore, the status of trace elements probably needs to be re-explored, particularly in BC. More prospective studies, randomized clinical trials, and specific pathogenic studies are needed to prevent BC. The main mechanisms underlying above-mentioned findings are comprehensively reviewed. Conclusion For BC, this review identified the current knowledge gaps which we currently have in understanding the impact of different heavy metals on BC. Systematic Review Registration www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176934 , identifier: CRD42020176934.
... Zinc is the fourth essential micronutrient controlling a number of proteins in humans (Cakmak, 2008;Shivay et al., 2015;Krezel and Maret, 2016). It plays a major role in the function of the brain, immune system, and endocrine system, and its deficiency is connected to many physiological and growth disorders, such as premature death, stunted growth, underweight children, poor appetite, delayed healing, taste abnormalities, blindness, cognitive losses, or mental lethargy (FAO, 2004(FAO, , 2021Bhutta et al., 2007;Khalid et al., 2014;Sauer et al., 2016). A direct positive correlation has been observed for serum Zn level with the development of diabetes (Anjum et al., 2012), depressive disorders, and bipolar depression (Cope and Levenson, 2010). ...
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Zinc (Zn) is a critical micronutrient that synergizes nutrient use efficiency, and improves plant growth and human health. Low Zn bioavailability in soils affects produce quality and agricultural productivity worldwide ultimately inducing deficiency in humans and animals. Zn deficiency is a leading cause of malnutrition in underdeveloped countries where a widespread population depends upon staple cereals for daily intake of calories. Modern cereal cultivars are inherently low in Zn, eventually, plants need to be enriched with soil application of ZnSO 4 , but due to higher fixation losses, it becomes an inefficient source. Rhizosphere microbiome contains Zn-solubilizing bacteria (ZSB) that improve Zn bioavailability, thus increase the root function, Zn uptake, and plant growth. Niha Corp developed a hybrid process of bioactive nutrient fortified fertilizer (BNFF), which has been used to formulate Zabardast Urea (ZU) by coating bioactive Zn (BAZ) and ZSB on urea. Data obtained for 15 wheat varieties from 119 farmer field demonstration plots and eight replicated trials on 42 locations across multi-environment conditions conclude that ZU significantly improved the plant biomass and yield by 12% over non-Zn control and produced grains with 57 μg/g Zn contents, which can meet a major part of the recommended dietary allowance (RDA) of humans. The study recommends that this microbe-mediated hybrid invention (ZU) is a feasible approach to boost Zn bioavailability and Zn use efficiency, with enhanced yield and quality that may contribute to improve human health. To the best of our knowledge, this is the first wide-scale field testing of Zn enrichment in the grains of bread wheat using an innovative BNFF Urea Z technology.
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Zinc malnutrition is one of the major concerns particularly in the developing countries as most of the population is dependent on zinc-poor cereal-based diet. Low concentration of zinc in cereals and other plants is due to various reasons such as the unavailability of micronutrients in soil which can be linked to extensive use of chemical fertilizers. Poor bioavailability of zinc is due to the presence of insoluble forms of Zn in soil, soil receiving high phosphorus application, physicochemical conditions of soil like alkaline pH, high reactivity of zinc in soil, and water logging. Surveys have revealed that large areas in the world including India are deficient in zinc. Effective, sustainable, and economic strategies are needed to enhance the zinc uptake by plants. The use of chemical fertilizers to supplement the zinc requirement is not effective as it is expensive, leads to chemical pollution, and any such zinc fertilizer added to soil again becomes immobilized in soil and hence becomes unavailable to plants. The utilization of biofertilizers is a well-known approach to overcome the menace of zinc deficiency. Biofertilizer formulations containing zinc solubilizing bacteria (ZSB) can help in the solubilization of zinc and to make it available to crops. However, a systematic and detailed study and review of literature is required for the design of an effective zinc biofertilizer. The parameter that needs to be evaluated include selection of effective ZSB, determination of better carrier material for improving shelf life of ZSB, routine checking of the biofertilizer to satisfy the proper viable count, methods of storage, and production. The success of such biofertilizers will also need wide publicity and awareness programs among farmers. This chapter, therefore, discusses some of the aspects associated with the possible design of zinc biofertilizers.
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Hunger and zinc (Zn) malnutrition are major health risk factors in the developing countries. Wheat is a major staple food in the world but it is inherently low in grain Zn concentration especially when grown on Zn deficit calcareous soils. Therefore, producing Zn enriched wheat grains at the farmers' fields is the best solution against human Zn deficiency. Biofortification approaches include selection, improvement and management of cultivated wheat genotypes to ensure optimum grain Zn concentration for human consumption. Soil and foliar application of Zn to wheat grown on Zn deficient soils enhances both the grain yield and grain Zn concentration. Genotype screening for higher grain yield and grain Zn concentration is prerequisite to ensure adoptability of poor farmers to newly developed genotypes for Zn biofortification. Conclusively, simultaneous consideration of grain yield and grain Zn concentration of wheat is the sustainable and economical approach to achieve our food targets.
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The final permanent solution to micronutrient malnutrition in developing countries is a substantial improvement in dietary quality-higher consumption of pulses, fruits, vegetables, fish and animal products that the poor already desire but cannot presently afford. Meanwhile breeding staple foods that are dense in minerals and vitamins provides a low-cost, sustainable strategy for reducing levels of micronutrient malnutrition. Getting plants to do the work of fortification, referred to as "biofortification," can reach relatively remote rural populations that conventional interventions are not now reaching and can even have benefits for increased agricultural productivity. Biofortification, thus, complements conventional interventions. The symposium articles discuss several examples of ongoing research projects to develop and disseminate nutrient-dense staple food crops and issues that remain to be resolved before successful implementation can be attained.
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OBJECTIVE: To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea. DESIGN: Cluster randomised comparison. SETTING: Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh. PARTICIPANTS: 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period. INTERVENTION: Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy. MAIN OUTCOME MEASURES: Duration of episode of diarrhoea, incidence of diarrhoea and acute lower respiratory infections, admission to hospital for diarrhoea or acute lower respiratory infections, and child mortality. RESULTS: About 40% (399/1007) of diarrhoeal episodes were treated with zinc in the first four months of the trial; the rate rose to 67% (350/526) in month 5 and to >80% (364/434) in month 7 and was sustained at that level. Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group. Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group. Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group (0.76, 0.59 to 0.98). Admission for acute lower respiratory infection was lower in the intervention group, but this was not statistically significant (0.81, 0.53 to 1.23). The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94). CONCLUSIONS: The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that can be incorporated in existing efforts to control diarrhoeal disease.
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The dietary requirement for zinc is literally the amount required in the diet to maintain optimally the various metabolic and physiological functions of life (Smith et al. 1983). The dietary zinc requirement for a population is not a single value. Instead it varies over a wide range depending on the age and physiological state of the individuals and on composition of the diet, particularly with respect to the amount and proportion of organic and inorganic components of the diet which influence zinc absorption and utilization (Hambidge et al. 1986).
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The absorption of zinc can be assumed to be determined to a large extent by the chemical environment at its site of absorption. Thus, absorptive efficiency will be influenced by the solubility of the zinc compounds present, by the presence of ligands of low molecular weight and by the competition between zinc and other minerals for carriers or uptake sites. To understand the mechanisms of zinc absorption, it is important to identify the factors promoting or inhibiting zinc uptake. Such knowledge can be used to improve zinc absorption from diets low in zinc and to develop special diets such as infant and enteral formulas intended for use at times when sensitivity to a suboptimal zinc supply may be increased. Efforts to eliminate strong antagonists of zinc absorption during food preparation and processing can also be made once these factors have been identified.
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