145  Mineral Deficiencies
Anuraj H. Shankar
KEY FEATURES
• The human body requires 17 essential minerals that
must be obtained through diet or supplementation.
• Deficiencies are widespread, especially in low- and
middle-income countries, and with the greatest disease
burden among young children and pregnant women.
• From a public health perspective, the most important
mineral deficiencies are of iron, zinc, and iodine.
• Iron deficiency affects ≈18% of children under age 5
(U5) and pregnant women, causing 45 million
disability-adjusted life years (DALYs) annually from
anemia and decreased work capacity and possibly
cognition. Improved iron intake with dietary
diversification and supplements, and decreased losses
from hookworm and malaria, are effective interventions.
• Zinc deficiency affects ≈17% of people globally, causing
16 million DALYs from reduced linear growth and
infections due to reduced immunity and epithelial
integrity. The human body does not store zinc at
appreciable quantities, and sufficient daily intake is
needed. The World Health Organization (WHO)
recommends zinc as adjunct treatment for diarrhea, and
routine U5 supplementation improves linear growth and
reduces diarrheal disease. Fortification and dietary
diversification are needed along with supplementation
programs.
• Iodine deficiency affects ≈28% of people globally,
causing 4 million DALYs from infant mortality and child
brain damage and thyroid hormone–related
abnormalities. The most effective intervention at scale is
salt iodization.
• Other mineral deficiencies of significant public health
importance include selenium and its effects on chronic
inflammation with non-communicable diseases and
possible effects on HIV disease progression; calcium and
magnesium and their effects on pre-eclampsia and
eclampsia and birth outcomes; and fluorine with respect
to dental caries.
• The mineral lead (Pb) is a ubiquitous environmental
contaminant from paint, pipes, fuels, and improper
disposal of batteries and electronic hardware, causing 9.3
million DALYs due to neurologic damage, especially in
children. Decontamination and reduced exposure are a
high priority.
INTRODUCTION
Minerals are essential elements required for human life, and
typically exclude the organic elements carbon, hydrogen, nitrogen,
and oxygen.1 They cannot be made by the body and must be
obtained in adequate dietary amounts required for proper health.
Minerals are distinct from vitamins in that they are not organic
molecules composed of multiple atoms. The human body requires
17 different minerals, as indicated in Table 145.1, and these comprise
1048
4% of the total body mass.2,3 They are classified as major minerals
(daily requirement of at least 100 mg), trace minerals (daily
requirement of less than 100 mg), and ultra-trace minerals (typically
1 µg or less). Minerals are naturally present in food or may be
added through food fortification or dietary supplements.
Minerals play a variety of crucial biologic roles, including
maintenance of proper electrolyte balance and conductivity func-
tions for muscle and nerve excitation, acid–base balance, as cofactors
in enzymes required for metabolism, in forming and stabilizing
proteins, and in the crystalline structure of bones and teeth, as
well as other functions.2,3 It is important to note that many minerals
interact with each other and with vitamins; for example, healthy
bones require a balance between vitamin D, calcium, phosphorus,
magnesium, zinc, fluorine, chlorine, manganese, copper, and sulfur.
Deficiency in any of these would influence skeletal health. Interac-
tions in absorption may also be important; for example, high
intakes of iron may decrease zinc absorption, or high intake of
zinc may result in copper deficiency. A balanced diet provides all
required minerals and in the proper quantities and ratios.
Unfortunately, mineral deficiencies are widespread, particularly
for persons residing in low- and middle- income countries (LMICs),
and have a large impact on global health and tropical medicine.4–6
For some minerals, requirements are sufficiently low that even
poor diets provide the needed amounts, or reserves or nutrient
recycling may mitigate the effects of chronically low intakes. In
some cases, loss of mineral-dependent functions may be partially
compensated for by alternative biologic pathways. Under these
scenarios, clinical manifestations of deficiency may be absent or
mild and recognized only in rare cases of severe chronic deficiency.
However, for some minerals, reserves are limited and their physi-
ologic roles are such that even mild deficiencies have adverse
health effects. From a public health perspective, based on the
prevalence and impact on morbidity, mortality, and quality of life,
deficiencies of the trace minerals iron, zinc, and iodine have the
greatest burden on health and are reviewed in detail next.5,6 The
roles of other minerals are briefly discussed.
IRON
Global Burden of Iron Deficiency
Iron deficiency is widespread and affects ≈18% of all children
under 5 years of age (U5) and pregnant women, and is associated
with 45 million disability-adjusted life years (DALYs).4,6,7 Chronic
anemia associated with iron deficiency results in impaired work
capacity, reduced cognitive performance, and increased susceptibility
to infection.4,7–9
Overview of Iron Biology
Iron has multiple physiologic roles, among the most crucial being
the primary functional element of hemoglobin.10 The ferrous ion
(Fe+2) combined with the protoporphyrin IX ring structure forms
heme, the oxygen-carrying component of hemoglobin and myo-
globin. Iron deficiency leads to lower heme levels and reduced
erythropoiesis, resulting in hypochromic microcytic anemia. Iron
also has a crucial role in the electron transport chain in mito-
chondria through the family of cytochromes, with the iron–
porphyrin ring functioning to reduce ferrous to ferric iron. The
iron sulfur family of enzymes also acts as electron carriers in the
 CHAPTER 145  Mineral Deficiencies 1049

TABLE 145.1  Essential Minerals in Descending Order by Recommended Daily Intake Levels for Adult Men and Women (Non-Pregnant, Non-Lactating)
Age 19 to 50 and Key Biologic Functions and Dietary Sources 145
Dietary
Mineral RDA/AI Functional Significance Dietary Sources
Potassium 4700 mg Systemic electrolyte needed to maintain membrane action Legumes, potato skin, tomatoes, and bananas.
potentials; essential for ATP regulation.
Chlorine 2300 mg Production of hydrochloric acid in the stomach and in cellular Table salt (sodium chloride) is the main dietary source.
pump functions.
Sodium 1500 mg Systemic electrolyte needed to maintain membrane potential Table salt (sodium chloride, the main source), sea
and action potentials; essential in coregulating ATP with vegetables, milk, and spinach.
potassium.
Calcium 1200 mg Needed for muscle contractility, heart and digestive system Dairy products, canned fish with bones such as
health, builds bone, supports synthesis and function of salmon or sardines, green leafy vegetables, nuts
blood cells. and seeds.
Sulfur 850 mg Critical in tertiary protein structure, including connective tissue Mustard, egg, seafood, beans, milk, milk products,
and skin, e.g., collagen and keratin. A component of bile nuts, and meat. Sulfur in proteins is the main
acids for fat absorption and in B vitamins, thereby dietary source, followed by sulfates in water, fruits,
facilitating energy production. Needed for several enzymes and vegetables.
and antioxidant molecules, including glutathione and
coenzyme A.
Phosphorus 700 mg Key component of bones and energy processing via ATP and Meat, yeast, wheat germ, soybean flour, meat, poultry,
related molecules. cheese, milk, canned fish, nuts and cereals.
Magnesium 420 mg Required for processing ATP and for bones. Nuts, soy beans, and cocoa mass.
Zinc 11 mg Required for production of immune cells and their function, is Liver, shellfish, oysters, meat, canned fish, hard
an antioxidant, is co-factor in nearly 300 enzymes, including cheese, whole grains, nuts, eggs, and pulses.
carboxypeptidase, alcohol dehydrogenase, and carbonic Vegetables and cereals may also contain phytates
anhydrase. and oxalates that reduce zinc absorption.
Iron 8 mg Required for oxygen carrying capacity of hemoglobin and Red meat, leafy green vegetables, fish (tuna, salmon),
myoglobin, and as co-factor for several other enzymes. eggs, dried fruits, beans, whole grains, and
enriched grains.
Fluorine 3.8 mg Forms compounds with calcium and phosphorus that are Tea, meat, fish, cereals, and fruit.
stronger and less soluble than other calcium salts, leading
to stronger teeth and bones.
Manganese 2.3 mg Needed co-factor for enzymes of energy production and Cereals, spinach, whole-meal bread, nuts, pulses,
synthesis of DNA and RNA. Key component of potent fruit, dark-green leafy vegetables, root vegetables,
antioxidant enzyme superoxide dismutase. tea, and liver.
Copper 900 µg Needed for connective tissue formation and release of iron Liver, shellfish, brewer’s yeast, olives, nuts, whole
from storage sites and maturation of red blood cells. grains, beans, and chocolate.
Crucial for function of antioxidant enzyme superoxide
dismutase. Needed for T-cell function and maturation.
Chromium 200 µg Needed for normal sugar metabolism via glucose tolerance Meat and whole-grain products, as well as some
factor (GTF) that enhances glucose utilization. Roles in fat fruits, vegetables, and spices.
and protein metabolism, and maintaining healthy cholesterol
levels.
Iodine 150 µg Required for synthesis of thyroid hormones, thyroxine and Sodium or potassium iodide added to table salt,
triiodothyronine to prevent goiter, may function as an vegetables grown in iodine-rich soil, kelp, onions,
antioxidant for organs such as mammary and salivary milk, milk products, salt water fish and seafood.
glands, gastric mucosa, and the thymus.
Selenium 55 µg A cofactor essential to activity of antioxidant enzymes like Organ meats, fish and shellfish, muscle meats, whole
glutathione peroxidase. grains, cereals, dairy products and vegetables such
as broccoli, mushrooms, cabbage, and celery.
Molybdenum 45 µg Key component of oxidases, including xanthine oxidase, Milk, beans, bread, liver, and cereals.
aldehyde oxidase, and sulfite oxidase.
Cobalt 5 µg Critical component of vitamin B12, and thereby influences DNA Green leafy vegetables, some fish, liver, kidney, and
synthesis, production of red blood cells, and nerve function. milk.
AI, Adequate intake; RDA, recommended daily allowance.
Some sources further consider the trace minerals boron, nickel, silicon, strontium, tin, and vanadium to be essential, but consensus is pending.

respiratory chain involving nicotinamide adenine dinucleotide
(NADH) and oxygen. Iron is a critical component of enzymes
that produce peroxide and nitrous oxide, and microbicidal reactions
critical for immune function, and may be involved in the regulation
of cytokine production and second-messenger cascade systems.11
Fetal and infant neurologic development and brain function are
also affected by iron deficiency due to changes in neurotransmitter
regulation, myelin formation, and energy metabolism.12 Overall,
≈60% of total body iron exists within red blood cells, with the
remainder complexed with ferritin in all cells, but more so in bone
1050 PART 8  Nutritional Problems and Deficiency Diseases
marrow and spleen, and especially the liver, which is the primary
physiologic iron reserve.
Causes of Iron Deficiency
Iron deficiency occurs when loss outstrips intake to the degree
that reserves are depleted. This can occur due to chronic low
intake of iron-rich foods, or from increased demand due to blood
loss from parasitic helminth infections such as hookworm and
schistosomiasis, disrupted iron metabolism from malaria and other
infections, or impaired absorption due to gut inflammation from
infectious diseases or other conditions.4,10,11 Prevention and treat-
ment of iron deficiency and its consequences typically require
actions to both improve intake and reduce losses. Iron absorption
from the intestine and mobilization from iron stores in macrophages
and hepatocytes are tightly controlled processes regulated by
hepcidin, a small polypeptide hormone, and its receptor known
as ferroportin, an iron export protein.10
Assessment of Iron Status
Anemia is the clinical condition most commonly associated with
iron deficiency. It is assessed by measuring hemoglobin levels,
hematocrit, mean red blood cell volume, or blood reticulocyte
counts. In some cases, palm, nail bed, or conjunctival pallor have
been used. Because anemia may have other etiologies, confirmation
of iron deficiency as a cause requires an indicator of iron status;
these include serum ferritin, transferrin saturation, soluble transfer-
rin receptor, erythrocyte zinc protoporphyrin levels, serum iron,
and bone marrow biopsy iron content.10,13 Serum ferritin in conjunc-
tion with soluble transferrin receptor has been used to accurately
estimate total body iron store consistent with bone marrow iron,
considered the gold standard.
Persons Affected and Consequences
of Iron Deficiency
Women and children are most affected by iron deficiency and
related anemia as the demands of rapid growth and pregnancy
make them vulnerable.4 For women of reproductive age, menstrual
iron loss accounts for approximately 0.5 mg/day.14 During preg-
nancy the iron demands for maternal and fetal growth increase
from 0.8 mg/day in the first trimester to 7.5 mg/day in the third
trimester.14 Blood loss at delivery further depletes iron stores.
These factors are exacerbated by early onset of childbearing, greater
number of births, limited birth spacing, and poor access to antenatal
care including dietary iron supplements. Currently, for pregnant
women the World Health Organization (WHO) recommends
daily oral iron (30 mg or 60 mg where prevalence of maternal
anemia exceeds 40%) and folic acid (400 mcg) supplementation
to prevent maternal anemia, puerperal sepsis, low birth weight,
and preterm birth.
Infants are at risk for developing iron deficiency and anemia,
especially low-birth-weight and preterm infants who are born
with reduced iron stores. For all infants, delayed cord clamping
at delivery is important to optimize transfer of as much iron-rich
blood to the newborn.15 The iron content of breast milk is low
but highly bioavailable, and exclusive breastfeeding for the first
6 months of life is advocated,4,5,16 followed by use of iron-fortified
complementary foods for weaning, along with prevention and
rapid detection and treatment of infectious diseases.4,5 In addition
to anemia and associated effects, iron deficiency in young children
may compromise cognitive development.12
Control of Iron Deficiency
Current control measures other than supplementation during
pregnancy and childhood include intermittent preventive treatment
(IPT) for malaria and use of insecticide-treated bed nets (ITN),
and preventive anti-helminthics in areas endemic for soil-transmitted
helminths.4,5,17 Reduction of malaria transmission has also reduced
iron deficiency. Improved iron intake through counseling and
promotion of consumption of iron-rich foods has met with limited
success.4,5,17 However, supplementation and food fortification have
been successful in reducing iron deficiency in some areas.5 Routine
iron supplementation of infants 6 to 23 months of age reduced
the risk of anemia by 40% but without other clear benefits.18
Recently control of iron deficiency in adolescence and the peri-
conceptional period has become a priority.
Over the last 50 years some studies reported iron supplementa-
tion increased the risk of developing or reactivating malarial illness,
especially in those who are iron replete. However, a systematic
review and meta-analysis of 35 trials enrolling 31,955 children
concluded that routine oral iron supplementation in children (i.e.,
<18 years of age) did not increase the risk of clinical malaria when
regular malaria prevention or management services are provided
and that under such conditions iron can be administered without
screening for anemia or for iron deficiency.19 These findings might
extend to iron-fortified foods or food additives for improving iron
status, and co-implementation with malaria control activities would
be prudent.
Conclusion
Iron deficiency remains a serious problem, especially for pregnant
women and children. The primary impact is on hemoglobin levels
with some limited evidence indicating adverse effects on child
cognition. There is urgent need to scale up effective prevention
and treatment programs with a focus on improved implementation.
ZINC
Global Burden of Zinc Deficiency
Zinc is the second most abundant trace mineral in the body after
iron. Approximately 17% of the population is at risk for zinc
deficiency, and it is associated with 16 million DALYs.20,21 Because
zinc and iron share similar dietary sources, deficiencies tend to
co-exist. In contrast to iron, the body does not maintain zinc
reserves, and when daily intake falls below requirements, the onset
of adverse effects is relatively rapid. Deficiency affects predomi-
nantly children and pregnant women in LMICs due to their growth
needs and exposure to poor diets and diseases.4,5,20,21
Overview of Zinc Biology
Zinc is a co-factor in more than 200 enzymes with myriad roles
in basic cellular functions such as division, programmed cell death,
DNA replication, and RNA transcription; as an antioxidant; and
in stabilization of membranes.22–24 Multiple physiologic functions
are therefore affected by zinc deficiency, including linear growth,
sexual maturation, neurodevelopment, and resistance to infectious
diseases. Zinc is particularly important for tissues with rapid cell
turnover such as epithelial linings of the gut and respiratory tract
and the immune system. Zinc affects multiple aspects of immunity,
from the barrier of the skin to gene regulation within lymphocytes.
Zinc deficiency impairs the function of cells mediating non-specific
immunity such as neutrophils and macrophages, and specific
immunity mediated by T and B lymphocytes is more strongly
affected as growth and maturation of these cells are impaired,
leading to dysregulated antibody and cytokine production, especially
reduced Th1-type cytokines.
Clinically, even moderate zinc deficiency reduces linear growth
and immunity. Moderate to severe deficiency can cause hair loss,
skin lesions, diarrhea, and tissue wasting. Sensory functions may
be affected, including eyesight, taste, and smell. In severe zinc

deficiency, a wide range of disturbances occur, including severe
growth retardation and impaired bone development, along with
delayed sexual maturation, frequent dermatitis, impaired taste
acuity, and behavioral changes.23,24
Zinc supplementation during acute diarrhea reduces duration
by 10% to 50% (i.e., 12–24 hours), along with ≈30% reduction
of diarrhea of a week or more.25 The WHO recommends adjunct
zinc therapy for diarrhea in children at two times the age-specific
recommended daily allowance (RDA) per day for 10 to 14 days.
Zinc treatment together oral rehydration therapy (ORT) is sig-
nificantly more effective than ORT alone in reducing the duration
and severity of diarrheal episodes, decreasing stool output, and
lessening the need for hospitalization and may prevent future
diarrhea episodes.25 Preventive or routine zinc supplementation
of children significantly reduces diarrheal incidence by 13% and
improves linear growth.26 Neither adjunctive nor routine zinc
supplementation had consistent effects on pneumonia or malaria,
although benefits in some settings were observed.
Causes of Zinc Deficiency
Zinc deficiency is generally caused by low dietary intake. Persons
in LMICs tend to consume predominantly plant-based diets
low in both total zinc and bioavailable zinc due to high levels
of tannins and phytates that reduce absorption.27 Deficiency
can also be precipitated and/or exacerbated by infectious dis-
eases such as acute or chronic diarrhea that affect absorption
and/or loss of zinc in the feces. Viral, bacterial, and protozoan
pathogens, including rotavirus, shigella, and cryptosporidium,
have been linked to fecal zinc loss and subsequent deficiency.23,24
Non-infectious chronic diseases, including diabetes, and liver and
kidney diseases of multiple etiologies also compromise zinc status.24
Lastly, certain genetic conditions can perturb zinc metabolism
or limit absorption, such as sickle cell disease and acrodermatitis
enteropathica.
Assessment of Zinc Status
Diagnosis of zinc deficiency is not as clear as for iron.28 For
individuals, levels of plasma zinc <70 µg/dL (with age, pregnancy,
and sex-specific cutoffs), along with low intake based on dietary
assessment and/or presence of repeated bouts of infectious disease
or presence of clinical signs such as loss of taste, all contribute to
diagnosis. Because homeostatic control and infections influence
plasma zinc levels, documented changes in plasma zinc and clinical
signs of deficiency after supplementation are recommended to
confirm the diagnosis.
At the population level, determining zinc deficiency relies on
several criteria,28 including population prevalence of 25% or more
of zinc intakes below the estimated average requirement, 20% or
more with low serum zinc concentrations (based on age and
sex-specific cutoffs), or 20% or more of children U5 with WHO
height-for-age z-score < −2. Moreover, changes in the prevalence
of low plasma zinc and mean population plasma zinc levels after
intervention further confirm zinc deficiency. Because enhanced
zinc intake increases even adequate plasma zinc levels, the best
evidence for zinc deficiency is clinical improvements in population-
based health such as reduced incidence or severity of diarrhea.
Persons Affected and Consequences
of Zinc Deficiency
The increased nutritional demands of pregnancy and lactation
predispose women to zinc deficiency. Several studies indicate that
maternal zinc supplementation may reduce preterm births.4,29
Enhanced gut zinc absorption helps meet needs for pregnancy
and for breastmilk30,31 but cannot overcome generally poor-quality
diets. Mothers without zinc deficiency can satisfy a newborn’s zinc
CHAPTER 145  Mineral Deficiencies 1051
requirement through breastfeeding for the first 6 months of life.
After this age, infants must consume complementary foods contain- 145
ing sufficient absorbable zinc. In many LMICs, neither of these
requisites is satisfied.
Infants and young children are at greater risk of zinc deficiency
because of the increased requirements during linear growth.
Low-birth-weight (<2500 gm) and preterm infants have lower
zinc status as zinc from the mother is transferred mostly during
the last trimester of pregnancy, and the immature gastrointestinal
tract of preterm infants does not absorb zinc proficiently.32 Infants
in LMICs may experience sub-optimal complementary feeding
practices such as delayed introduction of foods and use of foods
with low total and absorbable zinc due to high phytate content.
In adolescence, zinc deficiency occurs due to increased physiologic
requirements at the time of the pubertal growth spurt. For the
elderly, in addition to poor zinc intake, there is some evidence
that the efficiency of zinc absorption may decrease with age.33
Control of Zinc Deficiency
The major interventions to address zinc deficiency are supplementa-
tion, fortification, and dietary diversification. Supplementation is
further divided into preventive supplementation and therapeutic
supplementation. The choice of interventions depends on the
available resources and technical feasibility.4,5,20 Although the health
benefits of zinc supplementation are well established, well-
implemented programs specifically targeted at high-risk populations
are rare and urgently needed at scale.
Dietary diversification and modification represent a sustainable
long-term approach to improving the intakes of several nutrients
simultaneously, including zinc. Homestead food production and
education interventions may be effective food-based strategies to
address zinc along with multiple micronutrients. Information on
the locally available, low-cost, culturally acceptable zinc-rich foods
is needed. Likewise, information is needed on the best ways of
implementing both large-scale and home-based food processing
interventions, such as fermentation, to enhance zinc absorption
from the usual diet.
In populations where zinc deficiency is widespread and food
distribution channels are established, food fortification is generally
the more cost-effective and sustainable strategy. Success has been
seen in fortification programs targeted to specific high-risk groups,
such as infants and young children, in the form of complementary
foods. Further research on improved agricultural practices, including
plant breeding, to enhance dietary zinc content is required.34
Conclusion
Zinc deficiency is a serious public health problem causing restricted
linear growth, increased infections and diarrhea, and mortality.
Zinc supplements are critical in treating and preventing diarrheal
disease, and possibly other infections, and to reduce mortality,
especially among children with low birth weight or stunted growth.
Increased zinc intake in pregnancy may have an impact on preterm
birth. Numerous strategies to address zinc deficiency exists;
however, assessment of the acceptability, costs, scalability, and
impact of programs is needed.
IODINE
Global Burden of Iodine Deficiency
Approximately 28% of the global population has inadequate iodine
intake, and this accounts for 4 million DALYs,4,5,35 with South
Asia and sub-Saharan Africa being most affected. However, about
50% of Europe remains mildly iodine deficient, and iodine intake
in other industrialized countries, including the United States and
Australia, has fallen in recent years. Iodine deficiency has multiple
1052 PART 8  Nutritional Problems and Deficiency Diseases
adverse effects, termed iodine deficiency disorders (IDDs), mediated
by inadequate thyroid hormone production. IDDs increase infant
mortality, miscarriage, and stillbirth, and are the main cause of
preventable mental retardation and brain damage.
Overview of Iodine Biology
Iodine is an essential component of thyroxine (T4) and triiodo-
thyronine (T3) produced by the thyroid gland. These are required
for normal neuronal migration and myelination of the brain during
fetal and early postnatal life. Hypothyroxinemia during these critical
periods causes irreversible brain damage.36 Gestational iodine
deficiency impairs fetal growth and neurodevelopment and increases
mortality. Deficiency during infancy and childhood reduces growth,
motor function, and cognitive development. Absorption of iodide,
the most readily absorbed dietary form, involves a specialized
sodium/iodine symporter (NIS) expressed on enterocytes and cells
of the thyroid. A healthy adult maintains approximately 20 mg of
iodine reserves with 70% in the thyroid.37 Adaptations to low
intake include elevated thyroid-stimulating hormone (TSH) levels
leading to an enlarged thyroid gland, or goiter, reduced T3 and
T4 production, and enhanced NIS expression for greater iodine
uptake.38 The effects of iodine deficiency on development of goiter
and other adverse effects vary considerably between populations
and individuals due to environmental, genetic, and other poorly
understood factors.
Causes of Iodine Deficiency
The iodine content of most foods is low, with typical servings
containing less than 5% of daily needs.39 Their iodine content is
strongly influenced by iodine in the soil, fertilizers, irrigation
water, and livestock feeds. Marine plants, particularly seaweed,
and animals concentrate iodine from seawater and tend to be
good dietary sources. Other primary sources include bread and
dairy products, and particularly iodized table and cooking salt.
Certain dietary substances, termed goiterogens, can interfere with
thyroid metabolism and exacerbate iodine deficiency.38 These
include cruciferous vegetables such as cabbage, cauliflower, or
broccoli and rapeseed oil, all of which contain glucosinolates, and
cassava, sorghum, and sweet potatoes, which contain cyanogenic
glucosides. Their metabolites can compete with iodine for uptake
by the thyroid. In many low-income countries, particularly in
sub-Saharan Africa, cassava is widely consumed and if not properly
prepared, can exacerbate IDD. Cigarette smoking is also associated
with higher serum levels of thiocyanate that may limit iodine
uptake by the thyroid.40 Deficiencies of selenium, iron, and vitamin
A exacerbate the effects of iodine deficiency.
Assessment of Iodine Status
Methods recommended for assessment of iodine in populations
include urinary iodine concentration (UI), goiter rate, serum TSH,
and serum thyroglobulin (Tg). These are complementary, in that
UI is a sensitive indicator of recent iodine intake (days) and Tg
shows an intermediate response (weeks to months), whereas changes
in the goiter rate reflect long-term iodine nutrition (months to
years).36 But assessment of iodine status in pregnancy is difficult,
and it remains unclear whether iodine intakes are sufficient in
this group, leading to increased interest in iodine supplementation
during pregnancy.36
Persons Affected and Consequences
of Iodine Deficiency
Globally, more than one-third of school-age children are iodine
deficient, the majority of whom live in Southeast Asia, Africa, and
the Western Pacific.35 Iodine deficiency is the greatest cause of
preventable brain damage in childhood. Iodine deficiency during
pregnancy up to the third month after birth, when much of the
brain development occurs, results in thyroid failure and irreversible
brain damage. The most serious outcomes of IDD are increased
perinatal mortality, severe mental retardation, and cretinism. In
severely endemic areas, cretinism may affect up to 5% to 15% of
the population.
Control of Iodine Deficiency
The most effective means to control deficiency is universal salt
iodization. It is among the most cost-effective interventions to
promote economic and social development in areas of iodine
deficiency and has resulted in declining prevalence of IDD
worldwide.4,35 Efforts are needed to identify alternative approaches
where conditions may limit consumption of iodized salt (e.g., risks
of hypertension) or to increase the bioavailability for high-risk
groups such as infants and pregnant women.
Conclusion
Iodine is crucial for health and brain development in children,
and deficiency during pregnancy is especially harmful for the
fetus. Salt iodization remains the most cost-effective way of
delivering iodine. Worldwide, the annual costs of salt iodization
are estimated at US$0.02 to 0.05 per child covered; the costs per
child death averted are US$1000, and per DALY gained are US$34
to 36.4,18 This intervention must be sustained, and continued
advocacy and investments must be made to continue these successes
and to reach the remaining populations with complementary
approaches.
SELENIUM
Selenium is essential for growth and reproduction. Its functions
are mediated by 25 selenoproteins, of which glutathione peroxidase
is particularly important and protects cells against oxidative
damage.41,42 Selenium intake worldwide ranges from deficient to
toxic levels, and its association with health effects is U-shaped.
Additional intake benefits those with low status but may adversely
affect those with adequate or high status. Severe deficiency is
associated with cardiomyopathy, especially in children and women
of childbearing age.41 Selenium is critical for the proper functioning
of the immune system and regulation of inflammation. Deficiency
is associated with increased mortality, decreased immune cell counts,
cognitive decline, cardiovascular disease, and higher risk of death
in the HIV/AIDS population, and high intakes are associated with
increased risk of type 2 diabetes and disorders of the nervous
system and skin.
The relationship between selenium and HIV/AIDS is of
particular interest, and several trials have indicated beneficial effects
of supplementation on disease progression, including hospitaliza-
tions, diarrheal morbidity, and improved CD4 cell counts. Labora-
tory experiments indicate selenium has an inhibitory effect on
HIV through antioxidant effects of glutathione peroxidase and
other selenoproteins.41,42 Selenium supplementation has also been
shown to reduce systemic inflammation associated with cardio-
vascular disease, although other disease markers are unaffected.43
Continued research is needed on the effects of selenium.
CALCIUM AND MAGNESIUM
Calcium and magnesium deficiencies for both adults and children
are widespread in LMICs. Calcium plays an important role in
muscle contraction and regulation of water balance in cells, and
modification of plasma calcium concentration can lead to the
alteration of blood pressure.2 Deficiency results in rickets and a
risk of osteoporosis, as well as hypertension and stroke. Magnesium

is an essential co-factor for many enzyme systems and plays an
important role in neurochemical transmission and peripheral
vasodilatation.2 Deficiency affects neurologic and neuromuscular
function, resulting in anorexia, muscular weakness, and lethargy.
For pregnant women, both calcium and magnesium play an
important role in the prevention and treatment of preeclampsia
and eclampsia during pregnancy,44,45 common causes of maternal
and fetal morbidity and mortality worldwide, with incidence rates
of 4% to 8%. Calcium supplementation reduces the risk of pre-
eclampsia by 50% and thereby reduces the risk of preterm birth.44
The WHO recommends daily calcium supplementation (1.5–2.0 g
oral elemental calcium) for pregnant women in populations with
low dietary calcium intake.17 Magnesium sulfate remains the best
means to manage preeclampsia and has been shown to reduce the
risk of preterm birth45 and risk of infant death or cerebral palsy
by 14%. Moreover, magnesium sulfate given to women with
eclampsia reduces the risk of seizures and maternal death. Continued
efforts are needed to enhance implementation and expand
coverage.46
FLUORINE
The role of fluorine, typically as sodium fluoride, in preventing
tooth decay is well established.47 However, a review of global data
indicates a marked increase in the prevalence of dental caries,
especially in LMICs.48 Focused efforts are needed to promote
water fluoridation, topical fluoride application and rinses, and a
renewed effort to include oral health within educational programs.
Tooth decay is widespread and disproportionately affects lower
socioeconomic groups and is linked to other conditions such as
cardiovascular disease. Water and salt fluoridation should be
implemented where deemed feasible, and the use of affordable
fluoride toothpastes should be encouraged.
LEAD
Lead is among the most dangerous minerals from a public health
perspective and warrants mention herein due to its toxic effects
and widespread environmental contamination in LMICs, resulting
in 9.3 million DALYs. Although formally banned from gasoline,
paint, and pipes, poor enforcement has enabled ongoing exposure,
and growing improper disposal of batteries and electronic hardware
has increased its risk. Lead affects the choline-, dopamine- and
glutamine-based systems for neurotransmission. Continuous
exposure produces neurobehavioral symptoms, brain damage, and
low IQ.49 Cognitive decline is seen at serum lead levels as low as
10 µg/dL or less. Renewed efforts to reduce lead contamination
and human exposure, especially for pregnant women and children,
are a high priority.
SUMMARY
Mineral deficiencies negatively affect billions of individuals
worldwide, imposing a heavy burden on well-being and economic
productivity. Most prominently, deficiencies in iron, zinc, and
iodine have the largest negative impact on public health; however,
other minerals, including calcium, magnesium, selenium, and
fluorine, contribute significantly to the health burden. And the
mineral lead (Pb) is an important environmental contaminant
affecting brain development. Although the causes of mineral
malnutrition are complex, the primary determinant is insufficient
dietary intake. Efforts aimed at fortifying foods or providing
supplements have had some success, but substantial efforts are
still needed for effective programming at scale. Mutually reinforcing
strategies may increase access and consumption, as most deficiencies
do not occur in isolation; measures for prevention and control
will need to rely on dietary diversification, as well as education
to promote optimum dietary intakes.
CHAPTER 145  Mineral Deficiencies 1053
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