Chapter 5 Minerals

• Macroelements: Calcium, Phosphorus,

Sodium, Potassium,Chlorium, Magnesium,

• Microelements(Trace elements):
Iron,Zinc,Copper,Selenium,
Fluoride,Manganese, Chromium,Iodine and
other trace elements.
 Calcium
• Calcium is responsible for structural
functions involving the skeleton and soft
tissues and regulatory functions such as
neuromuscular transmission of chemical and
electrical stimuli, cellular secretion, and
blood clotting. More than 99% of body
calcium is in the skeleton.
• Calcium is the most abundant divalent cation in the
human body, making up 1.5-2.0% of its total weight. All
living things possess powerful mechanisms to conserve
calcium and to maintain constant cellular and
extracellular fluid (ECF) calcium concentrations.''3 The
physiological functions of calcium are so vital to
survival that in the face of severe dietary deficiency or
abnormal losses, the same mechanisms can demineralize
bone to prevent even minor hypocalcemia. Bone
provides a vital and readily available source of calcium
for the maintenance of normal ECF calcium
concentrations, ≈ 50% of which is ionized (Ca2+) and
physiologically active.
• The endocrine system that helps
maintain calcium homeostasis in
vertebrates is integrated and complex. It
involves the interaction of two
polypeptide hormones, parathyroid
hormone (PTH) and calcitonin (CT),
and a sterol hormone, 1,25-
dihydroxycholecalciferol (calci-triol).
• Biosynthesis and secretion of the polypeptide
hormones are regulated by a negative
feedback mechanism involving ECF Ca2+ The
biosynthesis of calcitriol from the major
circulating metabolite of vitamin D, 25-
hydroxycholecalciferol (calcidiol), takes
place in the kidney and is regulated by PTH
and CT as well as by concentrations of
calcium and phosphate in the ECF.
• Other hormones, such as insulin, cortisol,
growth hormone, thyroxine, epinephrine,
estrogen, and testosterone, together with
several growth factors (e.g., the insulin-like
growth factors IGF1 and 2) and some
compounds not yet identified, as well as
certain physical phenomena, have roles in
modifying and regulating organ responses
to PTH, CT, and calcitriol.
 Plasma Calcium
• Plasma calcium is distributed in three
major fractions:ionized, protein-bound, and
complexed. The ionized form (Ca2+ ), the
only biologically active species, constitutes
46-50% of total calcium. The protein-
bound fraction, roughly equivalent to the
ionized fraction in amount, is biologically
inert.
• The normal range for total serum calcium is
narrow (2.2-2.5 mmol/L) and the same is true for
the ionized fraction. Thus, values for total calcium
<2.2 mmol/L, assuming that plasma protein
concentrations are normal, reflect clinically
significant hypocalcemia, and values >2.5 mmol/L
reflect hypercalcemia. Hypocalcemia produces a
myriad of symptoms and, when severe, can result
in tetany and possibly convulsions. Hypercalcemia
can produce functional changes in most organ
systems, which may lead to a confusing variety of
symptoms and objective findings.
 Calcium Economy
• The amounts of dietary calcium required to
maintain metabolic balance (dietary intake
equal to urinary and fecal excretion) vary with
physiological need, intestinal absorption, and
kidney retention. Dietary deprivation of
calcium induces adaptive changes in the
production and secretion of the calciotropic
hormones that minimize the development of
negative balance of these two ions
• only 30-50% of ingested calcium is
normally absorbed (fractional
absorption). With decreased intake,
serum calcium decreases slightly, and
the sequence of events depicted in the
left limbs of the feedback loops in the
figure is activated.
• In severe chronic dietary deficiency of
calcium in normal subjects, increased PTH
secretion stimulates increased plasma calcitriol
production, which increases fractional
intestinal calcium absorption. It also reduces
renal calcium excretion, but this response is
less important because of the relatively small
percentage of filtered calcium that is excreted.
Such changes reduce the consequences of this
perturbation on overall body calcium
economy.
• The tradeoff for this adaptive response is
chronic hyper-parathyroidism, a condition
that can induce progressive demineralization
of bones. Thus, as is the case for most
adaptive mechanisms, they are beneficial
when applied over a relatively short period of
time, but when applied chronically, can have
destructive effects of considerable
consequence. The intestine plays the major
adaptive role in dietary calcium deficiency,
 Main functions of calcium
• Functions examples
• Structure role bone and teeth
• calcium is present as calcium
• phosphate (hydroxyapatite)crystals
• Muscle contraction calcium binds to troponin C
• Nerve impulse transmission calcium is realsed in response
• to hormones and neurotransmitters
• Blood clotting co-enzyme for coagulation
• Ion transport and cell signalling intracellular second messenger
 Deficiency and excess of calcium
• Deficiency Eexcess
1.In children leads to hypercalcaemia
rickets Ca2+ is deposited in many
2.In adults leads to organs, particularly arteries,
osteomalacia,that is defective liver,heart, and kidney,
mineralization of bone leading to tissue calcification

3.In postmenopausal women this may interferee with organ

it may contribute to osteoporosis, function and in the kidney,
i.e.loss of bone mass results in the formation of renal
stone
 Table 1. Recommended dietary allowances for
calcium
Category and age RDA(mg/day)
Infants
0-0.5 year 400
0.5-1.0 year 600
Children,1-10 years 800
Adolescents and adults
11-24 years 1200
25 to ≥50 years 800
 Iron
• Iron deficiency is the most common
nutritional deficit worldwide and yet it can
be successfully prevented on a population
basis.
• Total body iron averages ≈ 3.8 g in men and
≈ 2.3 g in women. The iron-containing
compounds in the body are grouped into two
categories, functional (known to serve a
metabolic or enzymatic function) and storage
(used for storage and transport of iron).
• Approximately two-thirds of total body iron
is functional iron, and most of this is in the
form of hemoglobin within circulating
erythrocytes. Other iron-containing
enzymes and myoglobin make up about
15% of functional iron. About one-third of
total body iron in men is in the form of iron
stores, whereas in women storage iron
accounts for only about one-eighth.
• Nutritional iron deficiency is commonly
regarded as an insufficient iron supply to meet
the need for functional iron after storage iron
has been depleted. At the cellular level, iron
deficiency can also result from insufficient
release of storage iron despite ample iron
intake and stores---e.g., anemia of chronic
disease. Under circumstances of iron overload,
iron stores become disproportionately large,
and in severe cases can be more than 10× the
functional iron component.
 Physiology
• Among iron compounds serving major
biological functions, the best known
are heme-containing: hemoglobin for
oxygen transport, myoglobin for
muscle storage of oxygen, and
cytochromes for oxidative production
of cellular energy in the form of ATP.
 Hemoglobin
• Hemoglobin plays a critical role in transferring
oxygen from lung to tissues. Its structure of four
hemes and four globin chains provides an
efficient mechanism to combine with oxygen
without being oxidized. A remarkable feature of
hemoglobin is its ability to become almost fully
oxygenated during the short erythrocyte transit
time in pulmonary circulation, and then to
become largely deoxygenated as erythrocytes
traverse tissue capillaries.
• A number of factors affect the oxygen affinity of
hemoglobin as measured by the oxygen dissociation
curve: partial pressure of oxygen, pH, temperature, and
organic phosphate content. With moderate anemia,
biochemical changes to improve oxygen unloading to
tissues compensate for the reduced oxygen carrying
capacity of blood. With severe anemia, however, the
markedly reduced hemoglobin content decreases oxygen
delivery and can lead to chronic tissue hypoxia. Even
though a lack of iron is the most common reason for
anemia, many other pathological conditions can affect
hemoglobin or erythrocyte production, leading to anemia
and a reduced oxygen carrying capacity of blood.
 Myoglobin
• Myoglobin consists of a single heme with a single
globin chain. Myoglobin is present only in
muscles, where it accounts for ≈ 5 mg/g of tissue.
The primary function of myoglobin is to transport
and store oxygen within muscle and to release it to
meet increased metabolic needs during muscle
contraction. Myoglobin makes up ≈ 10% of total
body iron. In rats, skeletal muscle myoglobin
decreases with iron deficiency.
 Cytochromes
• Cytochromes are heme-containing compounds critical
to respiration and energy metabolism through their
role in mitochondrial electron transport. Cytochromes
a, b, and c are essential to the production of cellular
energy by oxidative phosphorylation: they serve as
electron carriers in transforming adenosine
diphosphate (ADP) to adenosine triphosphate (ATP),
the primary energy-storage compound. Animals with
significant iron deficiency show depleted levels of
cytochromes b and c and limited rates of oxidation by
the electron transport chain.
• Cytochrome c is a pink protein and is the
most easily isolated and best characterized of
the cytochromes. Like myoglobin,
cytochrome c is made up of one globin chain
and one heme group containing one iron
atom. The cytochrome c concentration in man
ranges from 5 to 100 µ g/g of tissue, and is
highest in tissues such as heart muscle that
have a high rate of oxygen utilization.
• Cytochrome P450 is located in
microsomal membranes of liver cells
and intestinal mucosal cells. The
primary function of this cytochrome is
the breakdown of various endogenous
compounds and chemicals or toxins
from external sources by oxidative
degradation.
 Other iron-containing enzymes
• Nonheme iron-containing enzymes such as the iron-
sulfur complexes of NADH dehydrogenase and
succinate dehydrogenase are also involved in energy
metabolism. These enzymes are required for the first
reaction in the electron transport chain, and account
for more iron in mitochondria than do cytochromes. In
iron-deficient rats, these dehydro-genases are severely
depleted.
• Another group of iron-containing enzymes known as
hydrogen peroxidases act on reactive molecules that
are by-products of oxygen metabolism.
• Other enzymes that require iron for their
function include aconitase, an enzyme of
the tricarboxylic acid cycle;
phosphoenolpyruvate carboxykinase, a
rate-limiting enzyme in the
gluconeogenic pathway; and ribo-
nucleotide reductase, an enzyme required
for DNA synthesis.
 Iron Deficiency
• Iron deficiency is the most common nutritional
deficiency in the United States and worldwide,
affecting mainly older infants, young children, and
women of childbearing age. In developing
countries it is estimated that 30-40% of young
children and premenopausal women are affected
by iron deficiency. Young children are most
susceptible to iron deficiency because they require
relatively high amounts of iron for rapid growth
during the first 2 years of life, and their usual diet
is low in iron unless added as a nutritional
supplement.
 Stages of iron deficiency
• A number of hematological and biochemical tests
reflecting different aspects of iron metabolism are
used to characterize the iron nutritional status.
• Serum ferritin is the test of choice for assessing iron
stores.
• Stainable iron of a bone marrow aspirate can be used
for the same purpose but involves a more elabo-rate
and somewhat painful procedure.
• Serum iron concentration (Fe), total iron binding
capacity (TIBC), andtransfer-Tin saturation
(Fe/TIBC) reflect iron supply to tissues.
• Protoporphyrin, the precursor of heme, is elevated in
erythrocytes when the supply of iron for heme synthesis is
insufficient.
• Transferrin receptors respond to an insufficient iron supply to
cells and be-come elevated on cell surfaces and in plasma.
• Erythrocyte size--measured as mean corpuscular volume
(MCV)and hemoglobin concentration are reduced as a
consequence of significant iron deficiency.
• Another measure reflects the variability of erythrocyte size
and is called red cell distribution width (RDW). This value is
elevated in iron deficiency, when red cell size becomes
increasingly variable.
• Anemia occurs when hemoglobin production is
sufficiently depressed to result in a hemoglobin
concentration or hematocrit below the central
90% or 95% of range for healthy persons of the
same age and sex.
• A diagnosis of iron-deficiency anemia is made
when anemia is accompanied by laboratory
evidence of iron deficiency, such as low serum
ferritin, or when there is a rise in hemoglobin in
response to iron treatment.
• Iron status is expressed as one of five stages
ranging from iron overload to severe iron
deficiency.
• Overload
• Normal
• Depleted stores:
• Iron deficiency
• Iron deficiency anemia
 The dignosis of iron deficiency
• 1 、 Iron deficiency,ID ： SF<30µ g/L;
• 2 、 Iron deficiency erythropoiesis,IDE ） :
SF<30µ g/L, FEP>0.9µ mol/L or
FEP/Hb(× 102 ） >0.81
• 3 、 Iron deficiency anemia, IDA ） :
SF<30µ g/L,FEP>0.94µ mol/L or
FEP/Hb(× 102 ） >0.81;Hb<120g/L
•4、 subclinical ID+IDE
• Iron depletion can be categorized into three stages
ranging from mild to severe.
• The first stage involves only decreased iron stores
as measured by decreased serum ferritin. This
stage is not associated with adverse physiological
consequences, but does represent increased
vulnerability from long-term marginal iron
balance that might progress to a more severe
deficiency with functional consequences. With
low iron stores, there is a compensatory increase
in iron absorption that often helps prevent
progression to more severe stages.
• The second stage of iron depletion is characterized
by biochemical changes that reflect a lack of
sufficient iron for normal production of
hemoglobin and other essential iron compounds,
but as yet there is no frank anemia.
• Typically there is decreased transferrin saturation
or increased erythrocyte protoporphyrin, serum
transferrin receptor, or RDW. Because the
hemoglobin concentration does not yet fall below
levels considered indicative of anemia, this stage is
often described as iron deficiency without anemia.
• The third stage of iron depletion is frank iron-
deficiency anemia, which varies in severity
according to how low the hemoglobin
concentration is.
• In the United States, most cases of iron-deficiency
anemia among children and women are mild,
characterized by a hemoglobin within 10 g/L of the
lower limit of normal for that group. Iron
deficiency, however, can result in severe anemia,
defined as hemoglobin <70g/L by the World
Health Organization. In certain developing
countries, severe iron deficiency anemia is
common.
 Consequences of Iron Deficiency
• Anemia
• Work performance
• Behavior and intellectual performance
• Body temperature regulation
• Immunity and resistance to infections
• Lead poisoning
• Adverse pregnancy outcomes
 Prevention of Iron Deficiency
• Iron deficiency can be prevented by increasing the
content and bioavailability of iron in the diet. Iron
absorption is improved by including meat, fish,
poultry, and ascorbic acid-rich foods in meals, and by
decreasing consumption of tea and milk with meals.
• Iron-fortified cereal products augment the iron content
of the diet; those with added ascorbic acid also
enhance iron absorption.
• Increased use of iron supplements, increased iron
fortification of foods, increased use of birth-control
pills which decrease menstrual blood loss, and
increased intake of ascorbic acid.
• Iron fortification:Ferrous sulfate is commonly
used to fortify infant formula and other
products sold in cans and jars, as well as bread
and other bakery products that have a short
shelf-life.
• Iron supplementation: The absorption of iron
from tablets or liquid supplements is influenced
by dose, iron stores of the recipient, whether it
is taken with or between meals, and whether it
is taken alone or as part of a vitamin-mineral
supplement.
 Treatment for Iron Deficiency
• Ferrous sulfate is the least expensive and most
widely used form of oral iron. A total dose
equivalent to 60 mg of elemental iron (300 mg
ferrous sulfate) per day is ample for an adult if
given between meals, first thing in the morning,
or at bedtime. For infants ≈ 1 year of age, 30
mg/day (2-3 mg/kg) of elemental iron first thing
in the morning rarely causes side effects; this
dose is also appropriate and adequate for older
children and adolescents.
• A response to treatment should be evident
after 1 month, when the deficit in hemoglobin
is partially corrected, usually with a rise >10
g/L. Even after a significant hemoglobin
response, iron treatment should be continued
for another 2-3 months. If there is no
correction of anemia after 1 month of iron
treatment, further laboratory evaluation (e.g.,
with serum ferritin) is indicated to either
confirm the presence of iron deficiency or
determine other causes of anemia.
Iron Requirement and Recommended
Daily Allowances

• Estimates of average requirements for

absorbed iron in adults are based on careful
experimental measurements of iron losses. The
amount of additional iron that is needed by
growing infants and children is calculated from
average weight gain and estimates of iron
necessary to supply that gain, with iron as
hemoglobin, myoglobin, and iron enzymes.
• The current RDA for iron is based on average
iron stores of 300 mg and average daily iron
losses of 1 mg for men and 1.5 mg for women.110
With a factor of variation of 1.25, the estimated
requirement for absorbed iron is 1.3 mg/day for
men and 1.8 mg/day for women. Assuming 10-
15% absorption of dietary iron in the United
States, the estimated RDA is 10 mg/day for men
and 15 mg/day for women. Pregnant women
face increased iron demand for fetal and
maternal tissue growth, and their RDA is 30
mg/day.
• For nursing mothers, the iron needed to produce
breast milk is approximately 0.15-0.3 mg/day,
which is equivalent to the iron saved by cessation
of menstrual blood loss during lactation, and
therefore their iron requirement is the baseline 15
mg/day.
• For infants and children 6 months-3 years of age,
the iron RDA of 10 mg/day is calculated on the
need for 1 mg absorbed iron/kg/day.
• For preterm or low-birth-weight infants, the
requirement is 2 mg/kg/day because of lower iron
stores at birth and greater rate of growth than
term or normal-weight infants.
 Dietary Sources of Iron
• Breast milk is a better source of iron than
nonfortified formula or cow's milk.
• Meat is a good source of iron because much of
it is in the form of heme iron, which is absorbed
2-3 × more completely than nonheme iron. In
addition, factors in meat promote nonheme iron
absorption from the entire meal.
• Nonheme iron absorption can be enhanced by
ascorbic acid ingested with the meal.
 Iron Excess and Toxicity
• Acute iron toxicity or poisoning
• Hemolytic anemia of preterm infants
• Chronic iron toxicity and iron overload
• Hereditary hemochromatosis
• Iron overload from excessive oral intake
• Iron overload from repeated transfusions for
severe anemia
Relationship between iron status
and risk of disease
• Iron status and risk of cancer
• Iron status and risk of
coronary heart disease
 ZINC
• The zinc content of the human body (1.5-
2.5 g) approaches that of iron. This level is
maintained with absorption of about 5
mg/day.
• Zinc is absorbed from the small intestine,
primarily the duodenum and jejunum but
also the ileum.
• Absorption of zinc also occurs from rat
colon.
• Homeostatic control of zinc metabolism involves a
balance between absorption of dietary zinc and
endogenous secretions through adaptive regulation
programmed by the dietary zinc supply.
• The intestine is the key organ in maintaining that
balance. When isolated from systemic influences
and pancreatic secretions, the intestine retains
evidence of adaptation to absorption programmed
by previous dietary intake
 Physiological (Biochemical)
Function
• The biochemical functions of zinc
that determine physiological effects
have received extensive study.
• Three different functions--catalytic,
structural, and regulatory---define
the role of zinc in biology.
 Catalytic roles
• Catalytic roles are found in enzymes from all
six classes of enzymes.92 Examples are the
RNA nucleotide transferases (RNA
polymerases I, II, and III), alkaline
phosphatase, and the carbonic anhydrases
 The structural function
• The structural function of zinc is a rapidly
expanding area of biological investigation.
Structural roles for zinc in metalloenzymes
exist. The cytosolic enzyme CuZn superoxide
dismutase (Cu/Zn SOD) is an example; cop-
per functions at the catalytic site whereas zinc
has a role in structure.10 The zinc finger motif
in proteins repre-sents an extremely
important structural role.
 Regulatory function
• A third generalized biochemical role for zinc is
as a stimulator of transacting factors responsible
for regulating gene expression. The only well-
studied example of this role is in the expression
of MT or MT-like proteins.
• The basic components are a metal-binding
transcription factor (MTF) and an MRE in the
promoter of the regulated gene. The MTF
acquires zinc in the cell cytosol or nucleus and
then is able to interact with the MRE to stimulate
transcription.
• Beneficial effects of zinc in protection against
various noxious agents (including organic
compounds), χ and γ radiation, and infectious
agents (endotoxins, etc.) have been well
documented.
• Zinc may act as a regulator of apoptotic cell
death. The biochemical role has not been
defined. At high zinc levels (>500µ mol/L), in
vitro evidence suggests that zinc inhibits
apoptosis induced by glucocorticoids."' Zinc
may act by endonuclease inactivation,
poly(ADP-ribose) synthetase inhibition, or
stimulation of protein kinase C activity.
 Role of zinc in the body
• Functions deficiency
• Co-factors of over 100 Causes growth retardation,
• Enzymes,e.g. Hypogonadism, and delayed
• Dehydrogenase,e.g.LDH wound healing
• Peptidases
• Carbonic anhydrase
• Enzymes of DNA and protein synthesis these effects are
• Superoxide dismutase mainly a result of

• Transcription factors are thought to contain ‘ decreased activity of

zinc finger’ that enable them to bind DNA the enzymes of
DNA synthesis
 Deficiency
• The reduction in growth with reduced zinc in the diet
is coincident with a reduction in endogenous losses.
• Reduced zinc intake clearly results in thymic atrophy
in pigs and cattle and reduced T-helper cell function
in mice. Total parenteral nutrition (TPN) without
adequate zinc leads to decreased natural killer cell
activity.
• Reduced plasma zinc concentrations are common in
inflammatory bowel disease, which may indicate
reduced zinc absorption or increased zinc losses, and
may respond to zinc therapy.
 Requirement and Status Assessment
• The World Health Organization estimates
lactating women need to absorb 5.5 mg Zn/day.
• Physiological factors undoubtedly influence the
zinc requirement to some extent. RDAs are
determined on the basis of age, sex, pregnancy,
and lactation.
• The RDA for zinc is 5 mg/day for infants, 10
mg/day for children under 10 years, 15 mg/day
for males over 10 years, 12 mg/day for females
over 10 years, 15 mg/day during pregnancy, and
19 and 16 mg/day for lactation during the first and
second 6 months, respectively.
 Food and other resources
• Foods vary greatly in their inherent zinc
content, with red meat and shellfish
constituting the best sources of zinc. Foods of
vegetable origin tend to be low in zinc except
for the embryo portion of grains, such as
wheat germ.
• The presence of phytic acid in plant products
is a major factor that limits zinc
bioavailability from these sources.
• Zinc bioavailability is greater from human
milk than cow's milk or soy protein.
• Zinc supplements, either zinc alone or
combined mineral or vitamin-mineral
preparations, are widely used. Reasons for
using zinc supplements include concern that
dietary intake may not provide sufficient
zinc (as in a vegetarian diet) or belief that
zinc has health-promoting properties.
 Excess and toxixity
• Acute zinc toxicity results in gastric dis-tress,
dizziness, and nausea.
• Death has occurred with large TPN doses of
zinc.
• Gastric problems are observed in chronic
toxicity.
• Among other chronic effects are reductions in
immune function (decrease in lymphocyte
stimulation to phytohemagglutinin) and high-
density lipoprotein (HDL) cholesterol reported
with very high supplements (300 mg zinc/day).
• A depression in lymphocyte stimulation was
not observed at 100 mg zinc/ day. In
contrast, supplementation at 150 mg
zinc/day in females decreased low-density
lipoprotein and lowered serum
ceruloplasmin ferroxidase activity. No
significant changes in HDL were found.
• Hypocupremia observed when sickle cell
anemia patients were treated with 150 mg
zinc/day resulted from a zinc-induced
copper deficiency.
 Role of zinc in the body
• Functions deficiency
• Co-factors of over 100 Causes growth retardation,
• Enzymes,e.g. Hypogonadism, and delayed
• Dehydrogenase,e.g.LDH wound healing
• Peptidases
• Carbonic anhydrase
• Enzymes of DNA and protein synthesis these effects are
• Superoxide dismutase mainly a result of

• Transcription factors are thought to contain ‘ decreased activity of

zinc finger’ that enable them to bind DNA the enzymes of
DNA synthesis