UNIT 10 MINERALS (MICRO MINERALS):

IRON, ZINC, COPPER, SELENIUM,

CHROMIUM, MANGANESE, IODINE
AND FLUORINE
Structure
10.1 Introduction
10.2 Micro Minerals-An Overview
10.3 Iron
10.4 Zinc
10.5 Copper
10.6 Selenium
10.7 Chromium
10.8 Manganese
10.9 Iodine
10.10 Fluorine
10.11 Let Us Sum Up
10.12 Glossary
10.13 Answers So Check Your Progress Exercises
- - -- -

1 0 . INTRODUCTION
The last unit focused on the macro minerals. Now in this unit we will study about
the micro minerals, namely, iron, zinc, copper, selenium, chromium, manganese, iodine
and fluorine. We will study the food sources, functions, metabolism and methods of
assessing status of these important micro minerals.
Objectives
After studying this unit, you will be able to:
differentiate between macro and micro minerals,
list important food sources of micro minerals,
describe the absorption and metabolic fate of each mineral,
explain the nutritional and biochemical role of various micro minerals and relate
them to physiological functions and synlptoms of inadequate intakes, and
select appropriate methods for assessing status.
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10.2 MICRO MINERALS- AN OVERVIEW

Micro minerals are those minerals, which comprise less than 0.01% of the total
body weight and are required in concentrations of one part per million or less.
Initially, these minerals were also referred to as 'trace minerals' or 'trace elements'
as their concentration in tissues were not easily quantified by early analytical. methods.
A trace elemenUmineral, as you may be aware, can be defined as a chemical
element present in minute quantities; especially one used by organisms and held
essential to their physiology. A micro mineral or a micro nutrient, on the other hand,
is an organic compound essential in minute amounts for the growth and health
of an animal.
Like macro minerals, micro minerals must also be present in the body in optimal
range for normal functioning. Whenever, the concentration is too low or too high, the
Advance Nutrition body functions are impaired. The functions and routes of metabolism for some micro
elements are well established both in animals and humans while for others, the data
are available only from animal studies. They normally function as a cation (ion with
a positive charge) complexed with organic ligands or chelators. Proteins are the most
important chelators. Besides these, porphyrin (the ring structure present in haemoglobin)
and corrins (the ring structure in vitamin B I 2) are other important chelators. As
components of enzymes and proteins, these minerals frequently participate in redox
reactions (reactions which involve the transfer of electrons) with the metal often
functioning as the electron carrier. However, minerals such as zinc and manganese
along with macro elements calcium and magnesium, perform non-redox functions in
proteins and enzymes. Since many of the micro minerals share common mechanism
for absorption, they compete with each other for absorption in the small intestine.
Thus, excess of one micro element can aggravate the deficiency of another. Iron and
zinc are the best known examples.
With this basic overview, we shall get to know about micro minerals in greater detail
in the subsequent section(s). We begin our study with iron.

10.3 IRON
Iron was a familiar inetal even in the ancient civilization. In India, iron implements
made their appearance in between 1300-1000 BC and in due course, iron was used
in a variety of cookery utensils. The presence of leached iron, especially when acidic
foods were cooked in such utensils, was considered to be a significant contributor to
dietary iron. The most important clinical applcalion of iron was described in the 17ch
century, for treating "ch1orosis"- a condition that resulted from severe iron deficiency
in adolescent females in whom the dietary iron intake was oniy 4-3 mglday as against
the average iron content of 8-11 mglday in normal persons. Major aspects of iron
inetaboIism were elucidated by 1960 and today iron is one of the most investigated
minerals in nutrition. Let us read further to understand the importance of iron in
maintaining good health.

We all associate iron with its presence in blood and that its deficiency results in low
haemoglobin levels and hence anaemia. But is iron present only in blood? Of course
not. In our subsequent discussion, we will learn about the iion stores in the human
body.

Total Body Iron

In humans, the total quantity of iron in the body varies with haemoglobin concentration,
body weight, gender and the amount of iron stored in various tissues. Approximate
distribution of body iron is shown in Table 10.1.

Table 10.1: Distribution of body iron in different compartments

Compartment Iron Content (mg) Total Body Iron %
Haemoglobin Iron UX30 67
Storage Iron -
Varies from 200 1000 627
Tissue Iron: Myoglobin 130 3.5
Enzyme Iron 8 0.2
Other-transport Iron & 83 2.28
labile pool
Yource: Modem Nutritioil in Health and Disease 8" Ed., 1994.

You may have observed in Table 10.1 that maximum amount of iron is incorporated
in haemoglobin. The amount of storage iron shall depend upon the dietary iron
consumed and its bioavailability. It would be interesting to note here that iron can
exist in a number of oxidation states ranging from Fez- to FeG+.You inust also Minerals (Micro Minerals):
remember that in the human body and food, il occurs generally as fenic (Fe") and Iron, Zinc, Copper,
Selenium, Chromium,
ferrous (Fez+)iron. We have so far discussed aboul the presence of iron in the body. Manganese, Iodine and
Let us now quickly find out about the presence of iron in food i.e. learn about the Fluori~lc
food sources of iron.

Food Sources
lion is foulld in foods in one of the two forms i.e. haem or non-haern. In the l~umatl
diet, the primary sources of liaein iron are the haemoglobin and myoglobin from
consumption of meat, poultry and fish whereas non-haem iron is obtained from
cereals, pulses, legumes, fruits and vegetables. Dietary non-haem iron accounts for
about 85% of the total iron intake even among non-vegetarians. The good plant and
animal food sources of iron are shown in the Table 10.2 (a) and (b).
Table 10.2 (a): Sources of haem iron and their content (nig)
Haem Iron Sources Fe Content
Chicken liver 7.5
Chicken 1.1

Eggs 1.1
Salmon 1.O
Source: Nutritive value of Indian roods by C. Gopalan, B.V. Ramasaslri, S.C. Balasubramanium,
revised and updated by B.S. Narasinga Rao, Y..G. Deosthala and K.C. Pant, NIN, 1989.
Table 10.2(b): Sources of non-haem iron and their content (mg1100)
Non-haem Iron Sources Fe Content
Dried apricots 5.5
Almo~lds 1.3
Raisins 3.5
Soybeans, Tofu 1.9
Spinach 3.1
Wheat germ 0.9
Kidney beans 2.5
Baked beans 1.5
Broccoli 0.5
Lentils 6.0

Source: Nutritive value of Indian foods by C. Gopalan, B.V. Ramasastri, S.C. Balasubramanium,
revised and updated by B.S. Narasinga Rao, Y.G. Deosthala and KC.Pmt, NIN, 1989.
Let us read further to find out as to how dietary iron is digested, absorbed, transported,
utilized and excreted from the human system or in other words, how are. adequate
levels of iron maintained in different body compartments.
Metabolism of Iron
In this sub-section, we will study how body gets its iron supply, how iron is transported
and utilized by the various tissues and how iron balance is maintained.
Like other minerals, we obtain iron from the diet, which is absorbed from the
gastrointestinal tract. A unique feature of iron metabolism is that the body re-utilizes
quantitatively the iron released from the degradation of erythrocytes, with very little
being excreted. Hence, it is very frequently mentioned that once iron enters the body,
the body holds on to it tenaciously. We will first learn how dietary iron is absorbed
and then review how the iron is re-utilized.
Advance Nutrition Absorption o f Iron
Before it can be absorbed, iron whether it is in the form of haem or non-haem. must
be released from the foocfmatrices where it is bond with other constituents. Proteases
(the enzyme) in the stomach and small intestine hydrolyze haem iron from the globin
portion of haemoglobin or myoglobin. In the case of non-haem iron, gastric secretion
including HC1 and pepsin aid its release from food components. Most non-haem iron
is present in the ferric form which is reduced to ferrous form in the acidic environment
of the stomach. However, as the ferrous iron passes into the small intestine (akaline
pH), some Fez+may be oxidized to become ferric iron. Following its liberation from
food components, absorption' takes place. Like other minerals, iron is also absorbed
in duodenum and upper jejunum. The process of absorption is divided into three
phases:
i) Iron uptake by enterocytes (epithelial cell of the superficial layer of the small
and large intestine tissue)
ii) Intra enterocyte transport
iii) Storage and extra enterocyte transport.
The mechanism of absorption differs for non-haem and haem iron and therefore they
will be dealt separately. Let us have a look at the non-haem iron absorption first.
a) Mechanism of Non-haem Iron Absorption
We will discuss all the three phases one by one.
i) Uptake of iron by enterocytes: Ferrous iron traverses the brush border of the
intestine better than the ferric iron. The mechanism of absorption of the latter
is not clear but it is postulated that it binds to lurninal binding proteins. Mucin,
a small protein made in the intestinal cells and released into the gastrointestinal
tract, is thought to facilitate iron absorption. It binds multiple Fe3+ions at an
acidic pH and maintains its solubility even in alkaline pH and thus aids in its
absorption. After traversing the brush border, iron binds to the receptor on the
luminal surface of enterocyte and is transported inside the cell.
ii) Intra enterocyte transport: In the enterocyte, the absorbed iron can have one
of the following metabolic fates:
transported through the enterocyte into the blood, and
a stored in the enterocyte for future use or elimination.

Iron is transported through the enterocyte to the baso-lateral membrane by iron

binding protein- mobilferrin. Mobilferrin can also bind to Ca, Cu and Zn. The multiple
metal ion-binding properties of mobilferrin may be partially responsible for interactions.
between these minerals at absorptive surface.
The iron which is not transported across the cell for release is stored as ferritin in
mucosal cells. If required for the body, it is released for transport. If not needed, the
iron remains as ferritin and is excreted when mucosal cells are sloughed off in the
lumen, Thus, ferritin in the enterocyte acts as an 'iron sink', trapping excess iron and
removing it via intestinal excretion.
iii) Extra enterocyte transfer: Little 'is known about iron transport across the baso-
lateral membrane. After crossing the.baso-lateral membrane, it binds to plasma
transport protein transferrin. Iron is oxidized before it can bind to transfemn.
This is brought about by ceruloplasmin, a Cu-containing protein. The process
has been depicted in Figure 10.1.

Ceruloplasrnin Ceruloplasmin
co2+ cul+
Figure 10.1: Oxidation of iron
 Next, we shall review the mechanism of absorption of haem iron. Minerals (Micro Minerals):
Iron, Zinc, Copper,
b) Mechanism of Absorption of Haem Iron Selenium, Chromium,
Haem iron is soluble in the alkaline environment of the intestine. It binds to the Manganese, Iodine and
Fluorine
receptor on the enterocytes and is internalized. After entering the mucosal cell, haem
is degraded to iron, carbon monoxide and bilirubin 1Xa by the enzyme
haemeo.xygenase. The liberated iron is then treated in the same manner as is the
non-haem iron.
We have read in the previous units that whatever may be the quantity of a particular
nutrient that we may consume, the entire amount may not get digested and absorbed
(bioavailable) due to varied reasons. Let us see what factors affect the bioavailability
of dietary iron.
Factors affecting Absorption of Dietary Iron
Haem iron is more bioavailable than non-haem iron because it is absorbed intact as
a soluble complex by endocytosis (process whereby cells absorb material, molecules
such as proteins, from outside by engulfing it with their cell membrane). Non-haem
iron, on the other hand, forms insoluble complexes with many components concurrently
present in the diet, rendering the iron unavailable for mucosal uptake. The absorption
of iron also depends on the iron status of the individual and on the availability of an
iron-binding mucosal transport protein (transferrin) to facilitate the uptake from the
intestines.
There are mainly four factors that determine iron bioavailabilityl absorption from the
diet. These include:
i) Form of iron; whether haem or non-haem
ii) Solubility; specially of the non-haem iron compounds
iii) Other dietary factors; inhibitors and enhancers
iv) Iron status of the individual
Our subsequent discussions will elaborate upon each of these aspects.

i) Form of Iron: We have read earlier that iron in foods occurs either as haem
or non-haem iron. Haem iron compiises of iron in combination with porphyrins
and is found only in the flesh foods in the form of haemoglobin and rnyoglobin.
Muscle meats are therefore good sources of haem iron. Haem iron is absorbed
to a much greater extent than non-haem. Haem iron absorption is generally 2-
3-fold higher than non-haem iron absorption. The average absorption of haem
iron from meat-containing meals is about 25%. The absorption of haem iron can
vary from about 40% during iron deficiency to about 10%during iron repletion.
Haem iron can be degraded and converted to non-haem iron if foods are cooked
at a high temperature for too long. Iron absorption is not affected by other
dietary factors except calcium which has been shown to depress haem iron
absorption. In addition to providing higher bioavailable iron, haem iron compounds
also enhance non-haem iron absorption. Further, non-haem iron absorption in
healthy adults may vary from less than 1% to about 0% depending on the
composition of the diet,
The next factor that is being discussed is the solubility of the irontits complex with
other substances.
-
$ .
ii) Solubility: Solubility is crucial for non-haem iron absorption as the inorganic iron
I
salts have to be solubilized in the intestine for the iron to be taken up by the
muscosal cells. The acidic pH of the stomach makes iron soluble. However, as
the chyme passes into the small intestine, the rising pH tends to precipitate iron
as femc hydroxide complexes, The presence of ascorbic acid and other organic
acids in the small intestine solubilize to chelate the iron so that it can be absorbed.
Ferrous salts are more soluble than ferric salts and are therefore better absorbed. 297
Advance Nutrition iii) Inhibitors and Enhancers: Phytates and fibre from whole grain cereals, tai?r~ins
and polyphenols in tea, oxalates in green leafy vegetables like spinach and
excess calcium taken as supplements can all depress non-haem iron absorptioiz
~ignificantly,by forming insoluble components. The Indian vegetarian diet
consisting predominantly of cereals and pulses, high in phytates, has a low isoil
bioavailability. This is further compromised when tea is drunk with a meal, as
polyphenols in tea depress iron absorption. Iron absorption from wheat has been
reported to be 5%. However, when tea is taken with a breakfast ineal comprising
of wheat chapattis and potato vegetable, the reported absorption has been o ~ l l y
1.8%. Ragi balls or sorghum breakfast with potato vegetable and tea resulted
in only 0.8-0.9% absorption of iron.
On the contrary, ascorbic acid is a potent enhancer of iron absorption. Addition
of orange juice containing 40-50 mg ascorbic acid to a breakfast meal consisting of
bread, eggs and tea was found to increase iron absorption froin 3.7% to 10%. Thus,
ascorbic acid can counter the inhibitory effect of tannins or phytates, producing a 2-
3 fold increase in iron absorption.
Thus, ascorbic acid can enhance iron absorption in a number of ways. Firstly, it
reduces insoluble feiric iron to soluble ferrous iron; secondly, ascorbic acid forms l o w
molecular weight chelates with iron that remain soluble in the intestine; thirdly, ascorbic
acid-iron chelates preferentially release the iron for absorption to the brush border.
Together, these mechanisms ensure that dietary iron is well absorbed in the presence
of ascorbic acid.
Other factors known to enhance iron absorption are meat and flesh foods and some
amino acids such as cysteine.
The best way to increase bioavailability of iron in Indian vegetarian diet is to coilsulne
adequate amounts of ascorbic acid rich fruits and vegetables with the meals, reduce
phytate content by appropriate home levels processes such as gemination a n d
fermentation and avoid dl-inking tea with the meals.
Another factor which may determine the absorption of iron is the existing iron status
of the individual. This is particularly relevant with respect to iron deficiency anaemia.
iv) Iron Status of the Individual: Lastly, iron status of the individual is a floury
determinant of how much iron is absorbed. On a mixed diet with some haein
iron, the overall absorption may approximate to 10% in normal subjects while it
is about 20% in iron deficient subjects.
Table 10.3 lists the currently known dietary factors affecting iron absorption.
Table 10.3: Dietary factors affecting iron absorption
Increase Absorption Decrease Absorption
r Gastric Acidity Increased intes'tinal motility
I Ascorbic Acid I 0 Phytates and oralates I
Certain organic acids like citric, Iron-binding phenolic colnpounds such
lactic and tartaric acid as f e ~ ~ o upyrophosphate,
s ferrous citrate
Animal proteins such as meat, fish, Calcium, Pl~ospl~orus and Magnesium
poultry

I Sugars - Fructose, sorbitol

Physiological factors-pregnancy
I 0
Zinc, Manganese and Copper
Tannic acid in coffee and tea
I
and growth
I Depleted iron status I High Imn status
I
I
I II Antacids
Achlorhydria, Hypochlorhydria
I
I
I Poor fat digestion
I
So far we have discussed about the various aspects of iron absorptiot~.However, it Minerals (Micro Minerals):
was also mentioned that once iron gets absorbed, it is utilized judiciously again and Iron, Zinc, Copper,
Selenium, Chromium,
again by our body. What is the mechanism that regulates iron balance and absorption? Manganese, Iodine and
Let us understand about 'it in detail. Fluorine

Iron Balance arzd Regulation of Iron Absorption

The body has three unique mechanislns for maintaining iron balance.

The first is the continuous reutilization of iron from catabolized erythrocytes in the
body. When an erythrocyte dies after about 120 days, it is usually degraded by the
macrophages of the reticular endothelium. The iron is released and delivered to
transfenin in the plasma, which biings the iron back to red blood cell precursors in
the bone marrow or to other cells in different tissues. Uptake and distribution of iron
in the body is regulated by the synthesis of transferrin receptors on the cell surface.
This system for internal iron transpoi-t not only controls the rate of flow of iron to
different tiss'ues according to their needs, but also effectively prevents the appearance
of free iron and the formation of free radicals in the circulation.

The re-utilization of iron is a highly significant process. As mentioned earlier, the red
blood cells (erythrocytes) contain two thirds of the total body iron. If 1/120"' of this
is to be degraded daily, (note: life span of erythrocytes is 120 days) it results in the
release of about 20 ing of iron daily within the body. Almost all of this is re-utilized
for the synthesis of new haelnoglobin and erythrocytes. Only an extremely small
proportion i.e., about 1 mg is lost from the body to be replaced by dietary iron. The
amount of iron released from erythrocytes and re-utilized for new haemoglobin is
tei-med as iron turnover in the body.

The second mechanism involves access to the specific storage protein, ferritin.. This
protein stores iron in periods of relatively low need and releases it to meet excessive
iron demands. This iron reservoir is especially important in the third trimester of
pregnancy.

The third mechanism involves the regulatioil of absorption of iron from the intestines;
decreasing body iron stores trigger increased iron absorption and increasing iron
stores trigger decreased iron absoi~tion.Iron absorption decreases until equilibrium
is established between absglption and requirement,
Now we shall discuss the transport and storage of absorbed dietary iron in our body.
Trarzsport and Storage
You have seen that transferrin binds both newly absorbed iron and iron released after
degradation of haemoglobin. Transferrin is a glycoprotein and has two binding sites
for Fe3+. It acts as an iron transport protein. Normally, in plasma it is one-third
saturated with ferric ions. It distributes iron tlvoughout the body to wherever it is
needed, mostly to eiythrocyte precursors in the bone marrow. In iron deficiency,
transfenin saturation is reduced while in iron overload, tansferrin saturation gets
increased.

Any absorbed iron in excess of body needs is stored in the liver, in two forms, as
ferritin and hnemosiderin. Ferritin and haemosiderin are the two major iron storage
proteins. The ratio of these two proteins in the liver varies according to the level of
iron stored, with fenitin predominating at lower iron concentrations and haemosiderin
at higher concentrations. Iron is released from these stores in times of need more
readily from feiritin than haemosiderin.

Binding of iron by protein during storage and transport serves as a defense mechanism.
How? If iron ions are left unbound, the redox activity of iron can lead t o the
Advance Nutrition generation of h d l free radicals that can cause damage to the cells and their
membranes.

We have been reading that once iron is absorbed;our body tries to use it conservatively
and re-utilizes it again and again. What would happen then, if iron is consumed in
excess of our requirements? Further, the iron absorption need not always be complete.
Unabsorbed iron would get excreted. Let us read how iron gets excreted from the
body.

Excretion
Our body has a limited capacity to excrete iron once it has been absorbed. Daily
losses in adult man are between 0.9 to 1.05 mg. About 0.08 mg is lost via uiine,
0.2 mg via skin, and remaining in the faeces. Women in the reproductive age lose
more iron owing to menstrual cycles.

Iron is unique among the minerals, that once absorbed the body holds onto it, and
therefore, major regulation of iron balance is through absorption of iron rather than
through excretion. The percentage of iron absorbed can vary from less than 1% to
more than 50%, depending on the food eaten and the response of the regulatory
mechanisms that reflects body's physiological need for iron. However, this regulatory
mechanism is not perfect across the entire range of intakes.

Next, we shall discuss how iron is taken up by different tissues to perform various
functions in the body.

Iron Uptake by Cells and its Functions

Iron participates in a large number of biochemical reactions. However, for iron to
perform any function, it first needs to be taken up by the cells. Let us then first
review iron uptake by cells.

Cell membranes contain a protein specific'for binding transferrin called 'transferrin

receptor'. Transferrin containing two ferric ions, binds to this receptor. Thereafter,
iron-transfenin-transferrin receptor complex is internalized by endoyctosis. Within the
cell, iron is released from transferrin.

It has been shown that intracellular iron concentration more or less remains constant.
This intracellular iron homeostasis is maintained by regulating the synthesis and action
of proteins involved in the iron acquisition, utilization and storage. When intracellular
iron is scarce, cell needs to increase its iron concentration. This is achieved by
acquisition of plasma iron and mobilization of storage iron. Also, there is a need to
prioritize utilization of iron so that iron is preferentially available for the synthesis of
life sustaining iron-containing proteins. Therefore, whenever the intracellular iron
concentration is low, the number of transferrin receptors on the cell increase. Further,
it is postulated that iron concentration also regulates the synthesis of apoferritiiz and
6-aminolevulinic acid synthase. The latter is the key enzyme for haem synthesis.

Now that we have been acquainted to the mechanism involved in iron uptake by cells,
let us focus on the functions of iron.
Iron has several vital functions in the body. It serves as a carrier of oxygen to the
tissues from the lungs by red blood cell haemoglobin, as a transport medium for
electrons within cells, and as an integrated part of impoilalit enzyme systems in
various tissues. The general classification of the reactions in which iron is involved
includes:
Oxygen transport and storage
Electron transfer
Substrate oxidation-reduction
 Four major classes of iron containing proteins carry out these reactions in the Minerals (Micro Minerals):
Iron, Zinc, Copper,
mammalian system. These are illustrated in Figure 10.2. Selenium, Chromium,
Manganese, Iodine and
Fluorine

Iron sulphllr

proteins IRON proteins

CONTAINING
PROTEINS

Haemeproteins (Functional iron)

11e1nosiderill Integral part of the proteins

Figure 10.2: Classification of major mammalian iron containing proteins

Source: Beard and Dauson, 1997
Several iron-containing enzymes, the cytochromes, have one haem group and one
globin protein chain. These enzymes act as electron carriers within the cell and their
structures do not permit reversible loading and unloading of oxygen. Their role in the
oxidative metabolism is to transfer energy within the cell and specifically in the
mitochondria. Other key functions for tlle iron-containing enzymes (e.g. cytochrome
P450) include the synthesis of steroid hormones and bile acids; detoxification of
foreign substances in the liver; and signal controlling in some neurotransmitters, such
as the dopamine and serotonin systems in the brain.

As a component of cytochromes and other enzymes of electron transport chain, it is

critical for conversion of food into ATP. Iron-containing molecules ensure that
macromolecules like carbohydrates and fats are oxidized to provide the energy
necessary for all physiological processes and movements.

Iron is a component of many. other tissu,e enzymes required for immune system
functioning. Non-haem iron proteins, as we know, are responsible for a wide range
of functions such as enzymes methane mono-oxygenase (oxidizes methane to
methanol) and ribonucleotide reductase (reduces ribose to deoxyribose; DNA
biosynthesis).
I
As a part of haemoglobin, iro~iis required for the transport of oxygen, to all cells in
the body. Thus, haemoglobin is critical for cell respiration. Most of the iron in the
body is present in the erythrocytes as haemoglobin, a molecule composed of four
units, each containing one haem group and one protein chain. The structure of
haemoglobin allows it to be fully loaded with oxygen in the lungs and partially unloaded
2- in the tissues (e.g. in the muscles), The iron-containing oxygen storage protein in the
muscles, myoglobin,is similar in structure to haemoglobin but has only one haem unit
x- and one globin chain. As myoglobin, iron functions as a ready source of oxygen to
the muscles.
55. 4

Iron is thus crucial for the survival, growth and normal functioning of the human
I system. Let us now read about the consequences of deficiency and iron overload in
I
the body. ,
Advance Nutrition Deficiency and Iron Overload
In the following discussion, we shall cover both the deficiency and the consequences
of iron overload. We shall begin with iron deficiency.

Deficiency of Iron
Iroiz deficiency and iron deficiency anaemia are often incorrectly used as synonyms.
Iron deficiency is defined as a haemoglobin concentration below the optimunz
value in aiz individual, whereas iron deficiency anaemia implies that the haemoglobin
conceiztration is below the 95th percentile o f tlze distribution of haemoglobin
concentration in a populatiorz (disregarding effects of altitude, age and sex, etc.
on haemoglobin concentration). Nonllally, iron deficiency anaemia is defined in terins
of lower then normal blood haemoglobin levels and at least two of the following three:
i) reduced serum ferritin, ii) increased erythrocyte protoporphyrin, and iii) increased
transfenin receptors. Iron deficiency is one of the most prevalent nutritional deficiencies
in the world today. It is estimated that 2 billion people worldwide suffer from different
degrees of iron deficiency, about half of them, manifesting iron deficiency anaemia.
The progression froin adequate iron status to iron deficiency anaemia develops in
three overlapping stages. The first stage is depletion of storage iron with serum
fetritin levels starting to decline. However, the transferrin saturation, erythrocyte
protoporphyrin and haemoglobin are within normal limits. As iron stores get increasiilgly
depleted, iron deficiency develops which is the second stage. During this stage, in
addition to low semm fenitin levels, transfenin saturation is also reduced and e~ythrocyte
protoporphyrin is elevated. Haemoglobin may be normal. Eventually when iron
deficiency progresses to anaemia, haemoglobin levels start declining; this is the third
and final stage of iron deficiency.
The functional effects of iron deficiency anaemia result from both a reduction in
circulating haemoglobin and a reduction in iron-containing enzymes and myoglobin.
These include:
fatigue, restlessness and impaired work performance,
disturbance in thermoregulation,
impairment of certain key steps in immune response,
e adverse effects on psychomotor and mental development particularly in children,
and
increased maternal and perinatal mortality and morbidity .
Studies in animals have clearly shown a relationship between iron deficiency and
brain functions. Several structures in the brain have high iron content. The observation
that the lower iron content of the brain in iron-deficient growing rats cannot be
increased by giving iron at a later date, strongly suggests that the supply of iron to
brain cells takes place during an early phase of brain development and that, as such,
early iron deficiency may lead to irreparable damage to brain cells. In humans, about
10% of brain-iron is present at birth; at the age of 10 years, the brain has only
reached half its normal iron content, and optimal amounts are first reached between
the ages of 20 and 30 years. Several groups have demonstrated a relationship between
iron deficiency and attention, memory and learning in infants and small children. In
the most recent well-controlled studies, no effect was noted from the administration
of iron.
Iron deficiency also negatively influences the llormal defence systems against infections.
Several studies have observed a reduction in physical working capacity in human
populations with longstanding iron deficiency, and demonstrated an improvement in
working capacity in these populations after iron administration. Well-controlled studies
in adolescent girls show that iron-deficiency without anaemia is associated with
reduced physical endurance and changes in mood and ability to concentrate.
Considering the ill-effects of iron deficiency, preventing this problem is crucial. Minerals (Micro Minerals):
Populations most at-risk for iron deficiency are infants, children, adolescents and Iron, Zinc, Copper,
Selenium, Chromium,
women of childbearing age, especially pregnant women. The weaning period in Manganese, Iodine and
infants is especially critical because of the very high iron requirement needed in Fluorine
relation to energy requirement. Let us then focus our attention on prevention of iron
deficiency.

Prevention of Iron Deficiency

Iron deficiency anaemia accounts for approximately one-half or more of all the
anaemia's seen world wide. Iron deficiency without anaemia affects a large segment
of the populations, as many as with anaemia. Thus, 70% or more of the pre-school
children, 90% or more of pregnant women and adolescent girls suffer from either iron
deficiency or iron deficiency anaemia in India. The serious functional effects of iron
deficiency anaemia on learning, cognition and physical performance inchildren and
productivity in adults, as well as, increased maternal 'and pre-natal mortality in pregnant
women make it imperative to prevent and or treat iron deficiency as a priority.

There is a major National programme, the National Nutritional A~zaernia Control

Programme that aims to prevent and treat anaemia in pregnant women using a public
health approach. Iron (100 mg elemental iron) and folic acid (0.5 mg) in the form
of tablets are provided to all pregnant women for 100 days during a pregnancy
through the ICDS.

Severely anaemic womeil are given two tablets a day for 100 days as a treatment.
Medicinal iron in a suitable form proves useful in treating iron deficiency at individual
levels. Long-term prevention of iron deficiency musl: depend on iillprovillg the bio-
availability of iron and increasing the iron content of the diets. Studies have shown
that consumption of fruits rich in ascorbic acid such as guavas with major meals can
improve haenloglobin levels. Drinking tea with ineals should be avoided. At least a
gap of 95-2 hours is needed between a meal and tea for better iron absorption.

While the deficiency of iron is a comnlon health problem; it is important to consider

the causes of this problem. Nutrilional iron deficiency implies that the diet cannot
supply enough iron to coves the body's physiological requirements for this mineral.
Worldwide, this is the most colninon cause of iroh deficie~~cy. In many tropical
countries, infestations with hookworms lead to intestinal blood losses that in some
individuals can be considerable.

Besides deficiency conditions, there call be situations (though rare) when there is
excessive accumulation of iron in the body. Let us next discuss the consequences of
iron toxicity.

Iron Overload/Toxicity
We have seen that absorption of iron is veiy effectively regulated. This prevents
overload of the tissues with iron from dietjsupplements in normal healthy individuals.
Rowever, an excessive body burden of iron can be produced by greater-than-normal
absorption from the alimentary canal, by parenteral il~jectionor by a combination of
both. For instance, people with genetic defects develop iron overload as it occurs in
idiopathic hnernoclzromatosis. It is a hereditary disorder of iron metabolism
characterized by abnolnzally high iron .absorptiolz owing to a failure of tlze iron
absorption control mechanism at the intestinal level. High deposits of iron in the
liver and the heart can lead to cirrhosis, hepatocellular cancer, congestive heart
failure and eventual death.

African or Bantu siderosis, chronic liver disease, pancreatic insufficiency, shunt

l~aemochromatosisand certain types of refractory anaemia have been found to be
associated with iron overload. It has recen~lybeen shown that excess iron intake via
Advance Nutrition overuse of iron supplements could pose a possible health risk. Cellular and tissue
injury due to free radical reactions appears to be the possible mechanism. Normally
iron is bound tightly to the proteins. However, it is possible that excess iron intake
permits some iron to be in a free form. Associated complications may include increased
risk for bacterial infection, neoplasia, arthopathy, cardiomyopathy and endocrine
dysfunction.

Next, we shall learn about the indicators of iron status in the human body. These
indicators/values provide valuable information to plan the subsequent course of treatment
and ensure proper rehabilitation.

Assessment of Iron Status

In view of widespread iron deficiency, it is important to have reliable and sensitive
measures of iron status. Iron status can be assessed by a number of methods, which
are suitable for different stages of iron deficiency. These are briefly discussed below:

i) Serum Ferritin: This method is indicative of iron stores. As we know, a long

term negative iron balance first results in depletion of iron stores with a fall in
serum ferritin levels. Plasma femtin concentration of less than 30 microgram
per litre is considered indicative of iron deficiency. In normal subjects, plasma
femtin averages 100 mcg/L. Values in excess of 250 mcg/L are indicative of
iron overload.
ii) Transferrin receptors: As iron deficiency progresses into second stage, the
number of transferrin receptors on the cell surface increase. Measurement of
serum tranfemn receptors is thought to reflect transferrin receptors on immature
red cells. Values more than 8.5 mg/L reflects iron deficiency.
iii) Erythrocyte protoporphyrin: In the early stages of iron. deficiency, there is
accumulation of free protoporphyrin (precursor of haemoglobin). Zinc
protoporphyrin is usually measured. Levels more than 40 micro moVmol haem
is associated with iron deficiency.
iv) Transferrin saturation: As iron deficiency progresses, there is a decline in
transferrin saturation. With deficiency, transferrin saturation reduces to less than
15 -16%,is indicative of iron deficiency.
L

v) Haemoglobin and Haematocrit: In the final stages of iron deficiency, anaemia

occurs. Haemoglobin and haematocrit levels indicate prevalence of anaemia.
Haematocrit represents that proportion of the total blood volume that is red
blood cell and is expressed as percentage (%). Values of these two indicators,
below which anaemia is considered to exist, according to age and sex is given
in the Table 10.4.
%ble 10.4 : Haemoglobin and haematocrit levels below which anaemia is present
Age/ Gender Group Haemoglobin (gA) Haematocrit (mmoVL)
Children 6m-59 m 110 6.83
Children 5-11 years 115 7.13
Children 12-14 years 120 7.45
Non-pregnant women 120 7.45
(above 15 years of age)
Pregnant women 110 6.83
Men (above 15 years of age) 130 8.07

Source: WHO, 2001.

So, how much iron should be consumed in order to maintain an adequate iron nutriare?
Let us read and find out.
Reauirements
= ~
Minerals (Micro Minerals):
Iron, Zinc, Copper,
In Unit 1, we have already learnt about how recommended daily intakes are computed. Selenium, Chramium,
The requirements for iron, as recommended by ICMR, for various age-groups, are Manganese, Iodine and
given in Table 10.5. The recommended intakes are based on iron absorption of 3% Fluorine
in adult men, adolescent boys and children; 5% in adult women, adolescent girls,
lactating women, and 8% in pregnant women.
Table 10.5: ICMR recommendation for daily iron intake for Indians

Glrou~ Iron (mg/day) Group Iron (mg/day)

Adult man 28.0 Adolescenls:
Adult women 30.0 Boys 10 - 12 years 34
Pregnant Women 38 Girls 10 - 12 years 19
Lactation 30 Boys 13 - 15 years 41
Children: Girls 13 - 15 years 28
1 - 3 yex 12 Boys16 - 18 years 50
4 - 6 yeas 18 Girls 16 - 18 years 30
7 - 9 yeas 26
Source: Recoinmended Diet'vy Allowarices for Macronutrients and Minerals, Dietary Guidelines
for Indians, NIN, ICMR, India (1998).

The F A O M 0 2004 recomhendations for iron for different dietary iron bjoavailability
are given in Table 10.6 for your reference.
Table 10.6: The recommerided nutrient intakes (RNIs) for iron for different dietary iron
bioavailability (mglday)
G ~ P Mean Recommended Nutrient Intake
Age Age MY (mg/clay
(years) (years) Weight for a Dietary Iron Bioavailability of

--(kg) -
15 %
-
12 %
-
10 %
-
5%

Infants and 0.5-1 9 6.2" 7.7" 9.3" 18.6"

Children 1-3 13 3.9 4.8 5.8 11.6
4-6 19 4.2 5.3 6.3 12.6
7-10 28 5.9 7.4 8.9 17.8
Males 11-14 45 9.7 12.2 14.6 29.2
15-17 64 12.5 15.7 18.8 37.6
18+ 75 9.1 11.4 13.7 27.4
Females 11-14b 46 9.3 11.7 14.0 28.0
11-14 46 21.8 27.7 32.7 64.5
15-17 56 20.7 25.8 31.0 62.0
18+ 62 19.6 24.5 29.4 58.8
Postmenopausal 62 7.5 9.4 11.3 22.6
Lactating 62 10.0 12.5 15.0 30.0

aBioavailability of dietary iron during this period.varies greatly.

Pre-menarche.
Source: FA0 /WHO Vitamin and Mineral Requirements in Human Nutrition, World Health
Organization and Food and Agriculture Organization of the United Nations 2004 and
Requirements of vitamin A, iron, jolate and vitamin B12. Report of a Joint.FAO/WHO Expert
Consultation. Rome, Food and Agriculture Organization of the United Natioas, 1988 (FA0
Food and Nutrition Series, No. 23) 305
Advance Nutrition In this section we read about the food sources, metabolism, functions, deficiency,
toxicity of iron, as well as, important indicators of iron status and the reconlmended
dietary allowances for this nutrient crucial for our survival. Let us now attempt the
questions given in check your progress exercise 1 to recapitulate the concepts we
have learnt so far in this unit.
Check Your Progress Exercise 1
1) What percentage of iron is found in association with haemoglobin?
.....................................................................................................................
2) List at least five sources of haem and non-haem iron.

.....................................................................................................................
3) Enumerate a few dietary factors which affect iron absorption.

.....................................................................................................................
4) How does our body maintain iron balance?

.....................................................................................................................
5) What are the consequences of iron deficiency?

.....................................................................................................................
6) List the various methods by which one can assess iron status.

In our next section(s) we will read further about other nlicro mincl-als VIZ. zinc and
copper.
 Minerals (Micro Minerals):
10.4 ZINC Iron, Zinc, Copper,
Selenium, Chromium,
Manganese, Iodine and
Zinc deficiency in humans was reported by A.S. Prasad among people consuming Fluorine
mostly breads and very little animal protein in Middle Eastern countries. Common
manifestations of zinc deficiency were reduction in growth and appearance of skin
lesions. In 1974, a genetic human disease-acrodermatitis enteropathica was related
to an inability to absorb adequate zinc from the normal diet. The formal recognition
of zinc as an essential nutrient came in 1974, when dietary allowances for nutrients
were made.

In the biological systems, zinc is always found in the divalent (+2) state. Zinc is
present in all body tissues and fluids. The total body zinc content has been estimated
to be 30 mmol (2 g). Skeletal muscle accounts for approximately 60% of the total
body content and bone mass, with a zinc concentration of 1.5-3 p m o l / g
(100-200 pg/g), for approximately 30%. The concentration of zinc in lean body mass
is approximately 0.46 pmollg (30 pglg). Plasma zinc has a rapid turnover rate and
it represents only about 0.1% of total body zinc content. This level appears to be
under close homeostatic control. High concentrations of zinc are found in the choroid
of the eye (4.2 pmol/g or 274 yglg) and in prostatic fluids (4.6-7.7 rnrnol/l or 300 -
500 mgIL).

Let us next get to know about the food sources rich in zinc.

Food Sources
Zinc is normally associated with the protein andlor nucleic acid fraction of foods.
Thus, foods high in proteins are good sources of zinc. Lean red meat, whole-grain
cereals, pulses and legumes provide the highest concentrations of zinc: conce~ltrations
in such foods are generally in the range of 25-50 inglkg (380-760 p o l l k g ) raw
weight. Processed cereals with low extraction rates, polished rice, and chicken,
pork or meat with high fat content have moderate zinc content, typically between 10
and 25 mglkg (150-380 pmollkg). Fish, roots and tubers, green leafy' vegetables,
and fruits are only modest sources of zinc, having concentrations < l o mg/kg
( 4 5 0 p o l l k g ) Saturated fats and oils, sugar and alcohol have very low zinc contents.
Refer to Table 10.7, where sources of zinc along with content are given.
Table 10.7 : Zinc content of foods
Foods/ Food Groups Zinc (mg/100 g) Edible Portion
Sea Food
Oysters 17-91
Shrimp 1.1
Tung 0.5-0.8
Meat and Poultry
Liver 3.1-3.9
Chicken 1.0-2.0
Beef 3.94.1
Pork 1.6-2.1
Eggs and daily products
Eggs 1.1
Milk 0.4
Cheeses 2.8-3.2
Pulses and Legumes
Legumes (cooked) 0.6-1.0
Pulses/legumes (whole) 2.8-6.1
Bengal grarn/red gram dhal 0.9-1.7
Advance Nutrition I
Grc~insand Cereal
Wheat/wheat products
I
Rice and pasta
Bread (wheat)
Bread (white)
Nuts and Oilseeds
Gingelly seeds .
Almonds
Cashewnuts
Vegetables
Fruits
Source: Nutritive Valuc of Indian Foods, ICMR and iwww.nal.usda.gov/fnic/foodeomp.
From Table 10.7, you can see that zinc is present in high amounts in nuts and red
meat. Among seafood, oysters are very high in zinc. Other good animal sources
include poultry, pork and dairy products. Among the foods of plant origin, legumes,
whole grain cereals and vegetables (leafy vegetables and roots) are the good sources.
Refining of cereals reduce the content to a large extent.

The important aspects of absorption, storage, transport and excretion of zinc shall
now be dealt in detail.

Metabolism
Zinc has been found to play an important biological role in our body. Zinc ions can
be chelated and precipitated by a number of chelating agents including some natural
constituents of the diet. I11 order to take maximum benefit of this nutrient to enhance
health, it is important to undeistand about its metabolism in detail. Let us begin with
the absorption of zinc.

Absorption
Like iron, zinc also needs to be liberated from food prior to absorption. During
digestive process; proteases, nucleases and hydrochloric acid all appear to release
zinc bound to proteins and nucleic acids.

Zinc is absorbed throughout the small intestine, with absorption being most efficient
in the jejunum. Zinc given as aqueous solution to fasting subjects is absorbed to the
extent of 60-70%. However, absorption from solid diets is less efficient and varies
widely depending upon the content of the zinc in the meal and the composition of the
diet. Tentative estimates of absorption from different types of diet have been used
for estimating requirements. These are:

a) Highly bioavailable diets (low in inhibitors, high in enhancers) 50 -60%

b) Normal availability-a mixed diet 30%

c) Low availability diet (high in phytate, calcium and other inhibitors) 15%

Table 10.8 presents the criteria for categorizing diets according to the potential
bioavailability of their zinc.
 Table 10.8: Criteria of categorizing diets according to the potential bicaavailabiiity of their Minerals (Micro Minerals):
zinc Iron, Zinc, Copper,
Selenium, Chromium,
Normal Category" Principal Dietary Characteristics Manganese, Iodine and
Fluorine
High availability Refined diets low in cereal fibre, low in phytic acid content,
and with phytate-zinc molar ratio <5; adequate protein
content principally from non-vegetable sources, such as
meats and fish.
Includes semi-synthetic formula diels based on animal
protein.
Moderate bioavailability Mixed diets containing animal or fish protein.
Lacto-ovo, ovo-vegelarian, or vegan diets not based
primarily on unrefined cereal grains or high-extraction-rate
flours.
Phytate-zinc molar ratio of total diet withiti the range 5-15,
or not exceeding 10 if more than 50% of the energy intake
is accounted for by unfermented, unrefined cereal grains
and flours and the diet is fortified with inorganic calcium
salts (>1 g Ca2+/day).
Availability of zinc impi.oves when the diet includes animal
protein or milks, or other protein sources or milks.
Low availability Diets high in unrefined, unfermented, and ungerminated
cereal grainb, especially when fortified witli inol-ganiccalcium
salts and when intake of animal protein is negligible.
Phytate-zinc molar ratio of total diet exceeds 15', high
phyrate, soya-protein products constitute the primal, protein
source.
Diets in which singly or collectively, approximately 50% of
the energy intake is accounted for by the following high-
phytate foods; high-extraction-rate (<90%), heal, rice, maize,
grains and flours, and millet; chapatti flours and tai~ok;and
sorghum, cowpeas, pigeon peas, grams, kidney beans, black-
eyed beans and groundnut flours.
High intakes of inorganic calcium salts l g Ca2+/day),either
as supplements or as adventilious contaminants (e.g, from
calcareous geophagia), potentiate the inhibitory effects and
low intC&es of animal protein exacerbates these effects.

t" intakes adequate to meet the average nonnative requirements for absorbed ziiic, the
three availability levels correspond to 50%, 30% and 15% absorption. With higher z i i ~ .
intakes, the fractional absorption is lower.
Germination of cereal grains or fermentation (e.g. leaveilit- of many flours can reduce
7 )

antagonistic potency of phytates; if done, the diet should 11ieil be classified as having
moderate zinc availability.
Vegetable diets with phytate-zinc ratios exceeding 30 are not uliknown; for such diets, an
assumption of 10% availability of zinc or less may be justified, especially if tlie intake of
protein is low, that of inorganic, calcium salts is excessive (e.g. calciuin salts providing
e1.5 g Ca2+/day), or both.
Source: Adapted from Trace elements in human nutrition and healtlz. Geneva, World
Health Organization, 1996.

Like other nutrients, zinc is also first absorbed in the enterocytes and then transported
across the basolateral membrane.
Let us now see how zinc enters the enterocytes and what its fate in these cells is.

309
1
Advance Nutrition Zinc is absorbed into the enterocytes by a carrier-mediated process. Absorption by
this process is efficient at low intakes. At high intakes, zinc appears to be absorbed
by passive diffusion. Within the enterocytes, zinc has one of the following possible
fates:

a) Used or stored within the enterocytes, and

b) Bound to the proteins such as cysteine rich intestinal proteins (CRIP) or
metallothionein. Normally, initially absorbed zinc preferentially accumulates on
CRIP. However, with the increased zinc concentrations, metallothionein
concentrations rise. This is because the diets high in zinc appear to induce gene
<xpression of metallothionein.
CRIP appears to mediate intracellular zinc transport while zinc bound to metallothionein
is nonnally lost into the lumen with sloughing of these cells. These proteins can also
bind other minerals especially copper in the enterocytes.

Zinc not bound to metallothionein or used within the cells is transported across the
basolateral membrane with the help of zinc transporters (ZnTs). Many ZnTs have
been identified in different tissues. ZnTs are found in enterocytes besides many other
tissues. Look at Figure 10.3 for better clarity regarding transport of zinc. Here, as
you can see, ZnT,, binds to the unused and unbound Zn ions and transports it across
the membrane.

I Used by Cell 1

Ilitracellular Transport
LUMEN ENTEROCYTE

Figure 10.3: Enterocyte use and transport of zinc

The utilization of zinc depends on the overall composition of the diet. Experimental
studies have identified a number of dietary factors as potential promoters or antagonists
of zinc absorption. Let us learn about these factors.

Factors affecting Zn Absorption

In the last unit you have studied that absorption of various minerals (bioavailability)
is influenced by number of factors. Similarly2in case of zinc, different constituents
of the diet, commonly known as dietary ligands may bind to zinc and either inhibit
or enhance its absorption. It has been observed that citric acid, picolinic acid, glutathione,
amino acids especially histidine and cysteine and possibly lysine and glycine serve as
ligands and appear to enhance zinc absorption, especially in the presence of inhibitors.
Zinc histidine and cysteine complexes are absorbed 30-40% more efficiently than
zinc sulphate. These two amino acids appear to be also the preferred ligands for zinc.
 <
I

Isotope studies with human subjects have identified two factors that, together with Minerals (Micro Minerals): :r,;
the total zinc content of the diet, are major determinants of absorption and utilization Iron, Zinc, Copper, o

Selenium, Chromium, ;
of dietary zinc. The first is the content of inositol hexaphosphate (phytate) in the Manganese, Iodine and i'
diet and the second is the level and source of dietary protein. Fluorine ;:
Phytates are present in whole-grain cereals and legunles and in smaller amounts in
st
other vegetables. They have a strong potential for binding divalent cations and their
depressive effect on zinc absorption has been demonstrated in humans. The illolar
ratio between phytates and zinc in meals or diets is a useful indicator of the effect
of phytates in depressing zinc absorption. At molar ratios above the range of 6 -10,
zinc absorption starts to decline; at ratios above 15, absorption is typically less than
,.
15%.

It has been observed that phytates, in the presence of high i~ltralurninalcalcium, has
a greater inhibitory effect than phytates alone. Provisionally it has been suggested
that if phytate to zinc molar ratio is greater than 15, the content of available zinc in
the diet is likely to be low (less than 15%). Available evidence shows that only hexa
and penta-phosphorylated foims of phytic acid inhibit zinc absorption. The phytate
content can also be reduced by activating the phytase present in most phytate-
containing foods or through the addition of microbial or fungal phytases. Phytases
hydrolyze the phytate to lower inositol phosphates, resulting in improved zinc absorption.
The activity of phylases in tropical cereals such as maize and sorghum is lower than
that in wheat and rye. Germination of cereals and legumes increases phytase activity
and addition of some germinated flour to ungerminated maize or sorghum followed
by soaking at ambient temperature for 12-24 hours can reduce the phytate content
substantially. Additional reduction can be achieved by the fermentation of porridge for
weaning foods, or dough for bread making. Thus, fermentation which promotes
extensive degradation of dietary phytates can significantly improve the bioavailability
of zinc.

The effect of phytate is, however, modified by the source and amount of dietary
proteins consumed. Animal proteins improve zinc absorption from a phyiate-containing
diet. Zinc absorption from some legume-based diets (e.g. white beans and lupin
protein) is comparable with that from animal protein-based diets despite a higher
phytate content in the former,
As in case of iron, absorption of zinc generally is higher from foods of animal origin
as compared to that from plant foods. Also, absorption appears to be enhanced by
low zinc status, especially carrier - mediated mechanism. This indicates that the amount
of zinc absorbed is homeostatically regulated.
What happens to zinc once it has been absorbed through the small intestine. Let us
find out.
Transport and uptake by Cells
After absorption, zinc is bound to albumin and transported to the liver. In liver, it is
concentrated and then transported to different tissues by various plasma proteins.
Albumin transports 60% of the zinc, while remaining is transported by other compounds
like 01-2 macroglobulin, transferrin, immunoglobulin and two amino acids-histidine
and cysteine.

Zinc is taken up by various tissues and is incorporated in different enzymes. Since

zinc is an important component ,of various metallo-enzymes withi4 the cells, enzyme
synthesis and zinc uptake are correlated, However, mechanism of zinc uptake by
various tissues is unknown. Multiple passive bansport system including amino acid
carrier systems have been proposed.

Next, we move over to the storage of zinc in the body.

Advance Nutrition Storage
Zinc is found in most organs, concentration being higher in liver, kidney, muscle, skin
and bone. Zinc content of muscle, brain, luni and heart is relatively stable and does
not respolld to changes in dietary zinc intake. Similarly, release of zinc from bones
is very slow and does not contribute zinc'to other tissues during deprivation. When
dietay zinc intake is insufficient, liver metallothionein zinc appears to be mobilized
and redistributed. As dietary zinc intake decreases, liver and RBC metallothionein
bound zinc reduces.

Zinc which is not absorbed by our gastrointestinal tract tends to get excreted by our
body. Zinc may also get lost from our body due to damage to cellsltissues of our body
or as a result of normal physiologic processes. The major routes of zinc excretion are
highlighted in our subsequent discussions.

Excretion
Zinc is excreted primarily through the following three routes:
i) Gastrointestinal tract: Majority of zinc is lost froin the body in faeces.
Endogenous zinc in the form of enzymes or metallo-proteins is secreted into the
gastrointestinal tract by the salivary glands, intestinal mucosa, pancreas and
liver. Some of this zinc is reabsorbed while some is excreted. Sloughed enterocytes
also contribute to faecal zinc. Endogenous intestinal losses can vary from
7 pmoll day (0.5 mglday) to more than 45 pmol /day (3 rng /day), depending on
zinc intake-the higher the intake, the greater the losses.
ii) Kidney: Very small amount of zinc is excreted in the urine (0.3-0.7 mglday),
as most of the zinc filtered by the kidney is reabsorbed. Starvation and muscle
catabolism increase zinc losses in urine.
iii) Body su@ace: Loss of zinc occurs due to the exfoliation of skin and sweating
(0.7 -1.0 mglday). Another route of zinc loss is hair, which contains 0.1-0.2 mg
Z d g hair. Strenuous exercise and elevated ambient temperatures can lead to
high losses through perspiration.
Considerable scientific efforts have been carried out to improve our understanding
regarding the biological and physiological role of zinc. The important functions of this
mineral are highlighted in our subsequent discussions.

Functions
Zinc is an essential component of a large number of enzymes participating in the
synthesis and degradation of carbohydrates, lipids, proteins and nucleic acids, as well
as, in the metabolism of other micronutrients. Zinc stabilizes the molecular structure
of cellular components and membranes and in this way contributes to the maintenance
of cell and organ integrity. Furthermore, zinc has an essential role in polynucleotide
transcription and thus, in the process of genetic expression. Zinc also plays a central
role in the immune system, affecting a number of aspects of cellular and humoral
immunity. Shankar and Prasad have reviewed the role of zinc in immunity extensively.
Its involvement ill such fundamental activities probably accounts for the essentiality
of zinc for all life forms.

These divergent functions of zinc in the body can be grouped into three categories
namely, catalytic, structyral and regulato~y.Some of the important functions are
discussed below:

I) Conzponent ofmetalloenzymes: Zinc is unique among the trace elements in that '
it is a part of enzymes for all six Enzyme Commission classes about which you
may recall studying in the Nutritional Biochemistry Course (MFN-002) in
Unit 4. As a component of these enzymes, it either provides structural integrity
to the enzyme or participates directly in the reaction at the catalytic site. Zinc
 is a component of over 300 metalloenzymes and is therefore vital for many Minerals (Micro Minerals):
fundamental life processes. For example, as a component of carbonic anhydrase, Iron, Zinc, Copper,
Selenium, Chromium,
it helps in rapid disposal of carbon dioxide; as a part of alcohol dchydrogenase, Manganese, Iodine and
it is involved in the conversion of alcohol to aldehyde such as conversion of Fluorine
retinol to retinal. It is also required for protein digestion since it's a component
of carboxypeptidasc A and aminoyeptidase, the enzymes involved in the
digestion of smaller peptides released after the action of the proteolytic enzymes
pepsin, trypsin and chymotrypsin. Superoxide dismutase which catalyzes the
removal of superoxide radical requires two atoms of both zinc and copper. Zinc
has a structural role in this enzyme.
Delta amino levulinic acid dehydratase involved in haem synthesis also contains l

zinc. Similarly, DNA and RNA polymerase and deoxykinase iilvolved in nucleic
acid synthesis are zinc-dependent. Zinc also influences polysome conformation
and is thus involved in protein biosynthesis.
2) Transcription Factor: Zinc is an important structural component of DNA-
binding proteins also known as 'tmnscriptiorz factors'. These transcription
factors contain 'zinc fingers'. The term zinc finger is used mainly to denote the
configuration of the protein, which looks like fingers. It contains a series of
polypeptide loops resulting from twisting and coiling of the cysteine and histidine
residues. Zinc is ligated to these two amino acids. The series of loops give rise
to zinc fingers.
These zinc containing transcription factors bind to promoter sequelices of specific
genes and regulates transcription. Example of metallothionein mRNA is illustrated i~ i
Figure 10.4.

-
Nucleus

Z11 Protein

Gene

Promoter L j in RNA
region of gene

.c
rn RNA
1
Metallotl~ionein
Cell
&I
Figure 10.4: Interaction of transcription factor with zinc
Further, these DNA-binding proteins containing zinc fingers also bind to the hormones
such as thyroxine, retinoic acid, 1,25-dihydroxycholecaliferoland other steroid hormones
. such as oestrogen and androgens. These proteins, with the hormones attached to
them, bind to DNA and affect gene expression. More details regarding this will be
covered under Unit 19.
Next, we come over to the consequences of zinc deficiency.
Advance Nutrition Deficiency
Zinc deficiency was identified for the first time in 1940 when malilourished Chinese
patients were found to have low concentrations of zinc in blood during war time. The
clinical features of severe zinc deficiency in humans are growth retardation, delayed
sexual and bone maturation, skin lesions, diarrhoea, alopecia (loss of hair or baldness),
impaired appetite, increased susceptibility to infections mediated via defects in the
immune system, and the appearance of behavioural changes. The effects of marginal
or mild zinc deficiency are less clear. A reduced growth rate and impairments of
immune defence are so far the only clearly demonstrated signs of mild zinc deficiency
in humans. Other effects, such as impaired taste and wound healing, which have
been claimed to result from a low zinc intake, are less consistently observed.

The frequency and effects of such mild and moderate deficiency in human population
have not been adequately investigated. Growth limiting mild zinc deficiency has been
reported in otherwise healthy male American and Canadian infants and preschool
children that responded to zinc supplement. In the small areas of Egypt and the
Republic of Iran, growth failure in adolescents was found to be responsive to zinc
supplements. Severe zinc deficiency in humans is rare.

Many studies have documented that zinc supplementation reduces morbidity from
infectious diseases. Reduced activity of the zinc-dependent hormone thymulin, one
of the factors responsible for reduced cell mediated immunity may contribute to the
increased infectitious morbidity in zinc deficiency.

Diarrhoea1 diseases are at the root of an estimated 2 million child deaths in developing
countries annually. Studies have shown that an inexpensive 20 mg/day zinc supplement
for 7-10 days in combination with oral rehydration therapy can reduce severity of
diarrhoea by 40% and duration by 20% ill children. Likelihood of future occurrence
of diarrhoea1 disease is also reported to be reduced by zinc supplements, It is now
a routine clinical practice to administer zinc supplements to children suffering from
diarrhoea.

The central role of zinc in cell division, protein synthesis and growth is especially
important for infants, children, adolescents and pregnant women; these groups suffer
most from an inadequate zinc intake. Zinc-responsive stunting has also been identified
in several studies. Thus, prevention of suboptimal zinc status and zinc deficiency in
children by an increased intake and availability of zinc could consequently have a
significant effect on child health in developing countries, particularly like ours. Even
though zinc is an essential requirement for a healthy body, too much zinc can be
harmful. We shall now discuss the main features of zinc toxicity.

Toxicity
Only a few occurrences of acute zinc poisoning have been reported. The toxicity
signs are nausea, vomiting, diarrhoea, fever and lethargy and have been observed
after ingestion of 4-8 g (60-120 rnrnol) of zinc.

Gross acute zinc toxicity has been reported after consuming water stored in galvanized
containers. Symptoms include nausea, vomiting and fever. These symptoms are
observed after ingestion of 2 g or more of zinc.

Long-term zinc intakes higher than requirements could, however, interact with the
metabolism of other trace elements. Copper seems to be especially sensitive to high
zinc doses. A zinc intake of 50 mg/day (760 p o l ) affects copper status. Because
copper also has a central role in immune defence, these observations should be
studied further before large-scale zinc supplementation programmes are undertaken.
Any positive effects of zinc supplementation on growth or infectious diseases could
be offset by associated negative effects on copper-related functions.
Intakes between 25 -50 rng zinc per day have been reported to interfere with metabolism Minerals (Micro Minerals):
Iron, Zinc, Copper,
of both iron and copper. FAONHO 2004 therefore recommended the upper level of
Selenium, Chromium,
zinc intake for an adult man at 45 mglday (690 pmoVday) and extrapolated to other Manganese, Iodine and
groups in relation to basal metabolic rate. For children, this extrapolation means an Fluorine
upper limit of intake of 23-28 mglday (350-430 pnollday), which is close to what
has been used in some of the zinc supplementation studies. Except for excessive
intakes of some types of seafood, such intakes are unlikely to be attained with most
diets. Adventitio~~s
zinc in water from contaminated wells and from galvanized cooking
utensils could also lead to high zinc intakes.

Clinical indiceslparameters which can provide useful information regarding the zinc
status in the human body have been elucidated next.

Assessment of Zn Status
Sensitive indices for assessing zinc status are unknown at present. Static indices,
such as zinc concentration in plasma, blood cells and hair, and urinary zinc excretion
are decreased in severe zinc deficiency. A number of conditions that are unrelated
to zinc status can affect all these indices, especially zinc plasma levels. Food intake,
stress situations such as fever, infection and pregnancy lower plasma zinc
concentrations whereas, for example, longterm fasting increases it. However, on a
population basis, reduced plasma zinc concentrations seem to be a marker for zinc-
responsive growth reductions. A number of functional indices of zinc status have also
been suggested, for example, wound healing, taste acuity and visual adaptation to the
dark. Changes in these functions are, however, not specific to zinc and these indices
have not been proven useful for identifying marginal zinc deficiency in humans thus
far.

Let us review some of the assessment measures.

Measurement of zinc in plasma: This is the most common method. Fasting
concentrations of less than 70 pgllitre suggests deficiency. However, fasting
plasma zinc level decreases only when dietary intake is so low that homeostasis
cannot be maintained. It should be noted that while making interpretations,
plasma zinc levels can also be affected by stress infections and administration
of oral contraceptives.
a Measurement of zinc in RBCs and neutroplzils: This method is not common.
Metallothionein concentration: Serum metallothionein concentrations are less
sensitive to zinc deficiency than levels in RBCs.
Urinary zinc levels: Excretion of zinc in urine decreases with severe zinc
deficiency. It has been suggested as an alternate method of assessing oral zinc
absorption using oral dose of 10-50 mg elemental zinc.
Hair zinc level: Low zinc may be associated with chronic low intakes of dietary
zinc. However, it is important that contamination of hair with shampoo, hair
colo'ur should be eliminated.
Measurement of activity of zinc-dependent enzymes: In zinc deficiency, the
activity of alkaline phosphatase declines faster than that of carbonic anhydrase.
It must be evident to you by now that zinc is an important element for maintaining
health and performing important metabolic functions in the body. But how much
amount of zinc would be required to maintain an optimum nutritional balance in the
body i.e., prevent deficiency, as well as, toxicity. Let us focus on this aspect,

Requirement
The ICMR has not made any recommendation concerning zinc for Indians so far.
However, the recent dietary reference intakes for North America places the
Advance Nutrition requirement for adult males at I1 mglday and adult females at 8 mglday. It is
increased to 11 mg during pregnancy and 12 mg during lactation. The US Food and
Nutrition Board has also derived a tolerable upper limit of 40 mglday for adults.
Intakes in excess of 40 mg are undesirable.
/
The FAOIWHO 2004 recommended nutrient intake (RNIs) for dietary zinc to meet
the normative storage requirements from diets differing in zinc bioavailability is presented
in Table 10.9. We may perhaps use these for estimating zinc requirements for different
populations groups in our country.
r
Table 10.9: The recommended nutrient intakes (RNIs) for dietary zinc (mglday) to meet the
normative storage requirements from diets diflering in zinc bioavailability"

Gmp Assumed High Moderate Lav

Body Bioavailability Bioavailability Bioavailaility
Weight (kg)
Infants and
Children
0 - 6 months 6 l.lb 2.8" 6.6@
7 - 12 months 9 0.8b,2.5' 4.1 8.4
1 - 3 years 12 2.4 4.1 8.3
4 - 6 years 17 2.9 4.8 9.6
7 - 9 years 25 3.3 5.6 11.2
Adolescents
Females 10-18 years 47 4.3 7.2 14.4
Males 10-18 years 49 5.1 . 8.6 17.1
Adults
Females 19 - 65 years 55 3.0 4.9 9.8
Males 19 - 65 years 65 4.2 7.0 14.0
Females 65+ years 55 3.0 4.9 9.8
Males 65+ years 65 4.2 7.0 14.0
Pregnant women
first trimester - 3.4 5.5 11.0
Second trimester - 4.2 7.0 14.0
Third trimester - 6.0 10.0 20.0
Lactating
0 - 3 months - 5.8 9.5 19.0
3 - 6 months - 5.3 8.8 17.5
6 - 12 months - 4.3 72 14.4
For information on diets, see Table 10.8. Unless otherwise specified, the inter individual
variation of zinc requirements is assumed to be 25%.
Exclusively human-milk-fed infants. The bioavilability of zinc from human milk is assumed
to be 80%; assumed coefficient of variation, 12.5%.
Formula-fed infants. Applies to infants fed whey-adjusted milk formula and to infants partly
human-milk-fed or given low-phytate feeds supplemented with other liquid milks; assumed
coefficient of varitipn, 12.5%.
Formula-fed infants. Applicable to infants fed a phytate-rich vegetable protein-based formula
with or without whole-grain cereals; assumed coefficient of variation, 12.5%.
" Not applicable to infants consuming human milk only. T

Source: Vitamin and Minerd Requirements in Human Nutrition, FAOIWHO 2004

It must have been interesting lo know about the ubiquitous presence and wide
spectrum of properties of zinc. In-depth research over the past few years is unveiling
the massive scope of zinc in maintaining good health. The next nutrient that we shall
discuss is copper. However, before we proceed, answer the following questions for
a quick recapitulation.
 Minerals (Micro Minerals):
Check Your Progress Exercise 2
1) Why is zinc referred to as the most abundant intracellular trace element?
......................................................................................................................
.....................................................................................................................
.....................................................................................................................
2) Name a genetic disease which leads to an inability to absorb adequate zinc from
diet?
.....................................................................................................................
. .
.....................................................................................................................
.....................................................................................................................
3) Describe the term 'Zinc Fingers'.
.....................................................................................................................
....................................................................................................................
.....................................................................................................................
4) Brieflydiscuss function of zinc that makes it a unique trace element.
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
5) Enumerate any five techniques of assessing Zn status. .
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
6) What are the symptoms associated with prolonged intake of Zn?
.....................................................................................................................
.....................................................................................................................
......................................................................................................................
Our next topic of discussion is copper which is essential for all higher plants and
animals. Though required in very small amounts, copper is essential for conducting
important metabolic functions in the body. Critical evaluation and adequate
understanding of its functions is essential for prompt and judicious treatment of
patients with copper imbalance which is frequently critical and associated with high
rates of mortality. Let us learn about this nutrient in detail.

10.5 COPPER

I
As early as the times of Hippocrates, copper compounds were used to treat various
diseases. However, in the 20" century, it was noticed that animals fed milk diets
developed anaemia, which could not be corrected by dietary iron alone. In 1928, E.B.
Hart and co-workers demonstrated that rats which developed the milk diet anaemia
required copper along with iron to correct anaemia. It is now known that copper is 317
Advance Nutrition a constituent of several enzymes and proteins, most of which catalyze oxidation-
reduction reactions.
In the body, copper occurs in two oxidation states- Cu" (Cuprous) or Cu2+(Cupric).
The body of a healthy adult contains a little over 0.1 g of copper with concentration
being high in liver, brain, heart, bone, hair and nails. About 25 % of body copper is
present in muscle, and 42% in the skeleton.
Next, we come over to the food sources of copper.
Food Sources
Foods containing more than 1 mg copper per 1000 kilocaloiies are considered high
in copper and include green leafy vegetables, nuts, legumes, dried fruits, muscle
meats and shellfish especially oysters. Let us look at the copper coiltent of some
important foodstuffs in Table 10.10. This information would be of great help in
planning diets requiring copper restrictionlenhanced intake.
Table 10.10: Copper content of some important foods
Food Copper Content Copper Content
(mg1100g)
Dairy
Egg, whole 0.07 Potato, without peel 0.m I
Milk, whole 0.003 Potato chips . 0.35
Yoghurt, low fat, plain 0.094 1 Potato, sweet 0.18
Cheese, Cheddar 0 I Carrot 0.05
Meat, Fish, Poultry Broccoli
Liver, beef 6.09 Spinach 0.08
Chicken 0.07 Peas
Pork 0.09 Lettuce
Tuna, canned 0.05 Tomato
Shrimp, cooked 0.30 Corn
Grairts Cabbage 0.01
Macaroni, cooked 0.08 Fruits
Corn grits, cooked 0.01 Apple 0.03
Rice, white, cooked 0.08 Banana 0.14
Roll, white bread 0.14 Grapes 0.09
Whole wheat 0.25 Peach 0.06
Nuts Pear 0.09
Peanut 0.68 Pineapple 0.05
Orange 0.04
Raisins 0.32
Prunes 0.29

Copper though present in small amounts in the food needs to be absorbed, transported,
stored and excreted efficiently so as to be able to perform its host of functions some
of which are critical for other metabolic functions in our body. A brief overview
regarding the metabolism of copper is being discussed nGxt.
I
I
Metabolism il
I
In food, most copper is present as Cu2+and some as Cul+.This copper is bound to
organic compounds especially protein. pepsin and some proteol y tic
enzymes aid in the .release of copper. Released copper forms soluble complexes with Minerals (Micro Minerals):
amino acids, organic acids and other chelators which are readily absorbed mainly in Iron, Zinc, Copper,
Selenium, Chromium,
the upper intestinal tract. Some copper is also absorbed from the stomach; however, Manganese, Iodine and
gastric,copper absorption contributes relatively little to the overall absorption. Fluorine

As in the case of other minerals, copper absorption appears to occur by two

mechanisms:

i) Saturable active mechanism, which operates when the copper concentration is

low, and
ii) Passive diffusion, which occurs at a higher concentration.
Efficiency of absorption varies from 30-50% of ingested copper. Copper absorption
is influenced by copper status. Absorption is significantly higher during periods of
low dietary copper and vice-versa. Various dietary factors influence copper
absorption.

Dietary components exerting positive effect include amino acids especially histidine,
organic acids such as citric, gluconic, lactic, acetic and malic acids. Dietary components
which inhibit absorption include high intakes of several nutrients such as zinc (as you
may recall studying in the last sectioi~),iron, molybdenum, calcium, phosphorus and
excessive intake of antacids.

Once copper is within the intestinal cell, it may be used by the cell, may be stored
in the cell or may be transported across the basolateral membrane. Copper transport
across the basolateral membrane into the plasma appears to occur by a carrier-
mediated active transport, specific for copper.

Copper which is not absorbed is excreted in the faeces. So, what happens to the
copper which is absorbed?

After absorption, ionic copper is tightly bound to plasma proteins, namely albumin and
transcuprein and is transported via portal blood to the liver. Small amount of absorbed
copper is also transported to other tissues especially kidney.

In the lives, copper is iucorporated into ceruloplasmin, which is then released in the
blood. Ceruloplasmin constitutes 95% of the total plasma copper. Cenlloplasmin then
delivers copper to various tissues. Tissues can also acquire copper from albumin,
transcuprein and low molecular weight copper compounds.

Copper enters the cell directly through channels or after binding to protein transporters.
Ascorbic acid enhances copper transfer. Glutathione appears to serve as a transporter
of copper within the cell. In the cell, copper is incorporated into various copper
enzymes and proteins such as cytochrome oxidase.

Most absorbed copper is secreted by the liver into the bile to be excreted jn the
faeces. This process is the major regulator of copper elimination. Only small amount
of copper (-10-50 mcg) is excreted through kidney. Thus, the absorption and excretion
process of copper helps in maintaining optimum levels of this element in our body so
that it can help in perfomling a number of metabolic reactions in the body. Let us
then learn about the role of copper in our body.

Functions
Copper serves as a co-factor, as well as, an allosteric component of enzymes. In
many enzymes. copper furictions as an iii~ermcdiatein electroo transfer. The list of
copper -containing enzymes with their role is given in Table 10.11.
Advance Nutrition Table 10.11: Copper-containing enzymes

, Enzymes 'hction
1) Amine oxidases Found in tissues throughout body and
catabolize physiologically active amnines.
a) Monoamine oxidase Acts on serotonin, norepinephrine, tyramine and
dopamine.
b) Diamine oxidase Inactivates histamine. Also inactivates
polyamines involved in cell proliferation i.e. it
may play a role in limiting excessive growth.
High activity in intestine, kidney and inaternal
plasma.
c) Lysy loxidase Deaminates the lysine of newly formed iinmature
elastin and collagen after which crosslinks are
formed.
d) Peptidylglycine a-amidating It is a newly identified cupro-enzyme involved
monooxygenase in the synthesis of number of bioactive peptide.

2) Ferroxidases
a) Ferroxidase I Also known as ceruloplasmin. It catalyzes
oxidation of ferrous iron and plays a role in the
transfer of iron from storage to sites of
haemoglobin synthesis.
b) Ferroxidase U Catalyzes oxidation of iron.
3) Cytochrome C oxidase It is present in mitocl~ondriaof cclls tlvoughout
the body. It is involved in electroil transport
chain, reduces oxygen to water and allows
formation o i ATP. Activity is highest in heart
followed by brain, liver and kidney tissues.
4) Dopamine P-hydroxylase It catalyzes the conversion of dopatnine to
ne~~rotransmitter - norepinephri~lin the brain.
Its concentration is higher in grey matter than
white matter of the brain. It is also present in
adrenal gland.
5) Superoxide Dismutuse (SOD ) Functions as a scavenger of superoxide radical
and protects against oxidation CLI/Z~. SOD is
present in most cells and protects intracellular
components from damage. High nrnounls are
found in brain, liver, thyroid, kidi~eyand
pituitary.
Extracellular SOD is present in high anlounts in
lungs, thyroid and uterus.
6) Tyrosinase It catalyzes the conversion 01 tyrosine to
dopamine, and oxidalion of dopalnine t?
dopaquinone, steps in the synthesis o i melanin.

After going through the functions enumerated in Table 10.11, you would liave realized
that copper plays an important function in processes fundamental to huinan health.
Thus, copper plays a role in bone formation and integrity of colinective tissue in the
heart and vascular system. It is required for the normal functioning of central nervous
system and cardiovascular system. It is involved in iron metabolism. Recent evidence
suggests a role for copper in immune function. Some indices of immune function l~ave
been shown to decline with deficiency but were not reversed by increased copper
intake.

In addition to the above, copper may have other roles, which may not involve
enzymes. Copper appears to influence gene expression through binding to specific
transcription factors. In some cases, copper has been shown to influence
transcription by binding to transcription factor, which in turn binds to promoter sequence
of DNA.
Although a very small amount of copper is required for performing the functions Minerals (Micro Minerals):
discussed above, its deficiency can result in serious consequences which are being Iron, Zinc, Copper,
Selenium, Chromium,
discussed next. Manganese, Iodine and
-
Fluorine
Deficiency
Owing to the remarkable homeostatic mechanisms, copper deficiency in humans is
rare. However, copper deficiency has been reported under special circumstances.
The predisposing factors of copper deficiency are prematurity, low birth weight and
malnutrition, especially when combined wiLh feeding practices such as cow's milk or
total parenteral nutrition. The most frequent symptoms are anaemia, neutropenia
(abnormally high levels of a type of WBC's in blood) and bone fractuyes. Other less
frequent symptoms include hypo-pigmentation, impaired growth, and an increased
incidence of infections and abnormalities of glucose and cholesterol metabolism.

It has been proposed that sub-optimal copper intakes over long periods may be
involved in the precipitation of chronic diseases such as cardiovascular disease and
osteoporosis.

While on one hand, a low intake of cbpper can affect our health, a very high
intake or abnormally high levels of copper in the body's tissues can also be damaging
to several body processes. Let us read further to find out the effects of copper
toxicity.

Toxicity
Acute copper toxicity in humans is rare and occurs due to inadvertent consumption
of copper salts. Symptoms include vomiting, diarrhoea, haemolytic anaemia, renal and
liver damage. Clinical symptoms of chronic copper toxicity appear when the capacity
for protective copper binding in the liver is exceeded which include jaundice, liepatitis
and liver cirrhosis.
'
Apart from an abnormally high or low intake, copper imbalance in various tissues
may also develop as a consequence of genetic disturbances in the metabolism of
copper. The most important one's being the Menke's and the Wilson's disease. We
will learn about these diseases while studying about selenium in section 10.6.

Now that you have realized the importance of copper in our diet, let us now move
on to the understanding of various assessment parameters of copper status.

Assessment of Copper Status

A reliable index to assess marginal copper status is currently not available. However,
severe copper deficiency may'be detected by one or more of the three parameters,
low serum copper levels, low serum ceruloplasrnin both of which respond to copper
administration; and a decline in red cell super oxide dismutase activity. Reported
normal range for these parameters are as follows:
Serum copper: 64-156 mcg/dl (10-24.6 rnrnoles/L),
Ceniloplasmin: 18 -40 mg/dl,
Erythrocyte SOD: 0.47 mg/g
Seium copper and ceruloplasrnin are reduced to levels far below normal in severe
copper deficiency. Erythrocyte SOD in severe copper deficiency has not been reported.
Sa, then what is the safe level of dietary intake for copper? Let us find out.
Requirements
Safe and adequate range for copper intake is 1.5-3 mg/day.
Advance Nutrition In this section, we learnt about the salient features of copper. In our next section, we
shall discuss about yet another important nutrient viz., selenium. However, before we
proceed, you must attempt the questions mentioned below to recapitulate your
understanding of the concepts discussed so far.

Check Your Progress Exercise 3

1) List the organs which contain a high concentration of Cu.
..................................................................................................................
.....................................................................................................................
2) Which components aid in the release of Cu in the gastrointestinal tract?

......................................................................................................................
3) Enumerate the dietary component affecting Cu absorption.
.....................................................................................................................
4) Name the various proteins which deliver copper to:
a) Liver and Kidney
.............................................................................................................
b) Other tissues

5) Enlist any five copper-containing enzymes, giving their important physiological

functions.

....................................................................................................................

6) Mention the pre-disposing factors of Cu deficiency.

...............................................................................................................
..
......................................................................................................)...........
7) What is Wilson's disease?
 Minerals (Micro Minerals):
10.6 SELENIUM . Iron, Zinc, Copper,
Selenium, Chromium,
Manganese, Iodine and
The element selenium was discovered in 1817 in association with the element sulphur. Fluorine
However, selenium as an essential nutrient remained unrecognized for many years,
although selenium toxicity in horses and cattle, "blind staggers" and "alkali disease"
was known since the 1930s.

The first description of the dietary selenium deficiency in isolated populations in the
People's Republic of China, was made in 1979. The disease known as Keshan
disease, named for the country where it was first recognized, was characterized by
cardiomyopathy affecting primarily children and young women. The disease was
often fatal. The second selenium deficiency disease Kashin-Beck disease was reported
in 1980. It was prevalent in China and Sino-Soviet border. Both the diseases were
caused primarily due to selenium deficiency in the soil.

Selenium is a non metallic element and exists in several oxidation states which include
Se2+sSe4+and Se6+.The chelnistry of selenium is similar to that of sulphur. Selenium
replaces sulphur to form organic compounds such as selenocysteine and
selenomethionine. Total selenium content of the body varies from 3-15 mg depending
on the dietary intake. Approximately 30% of tissue selenium is contained in the liver,
15% in kidney, 30% in muscle and 10% in blood plasma. Much of tissue selenium
is found in proteins as selenoanalogues of sulphur amino acids; other metabolically
active forms include selenotrisulphides and other acid-labile selenium compounds.

In the body, selenium can be bound to selenium-binding proteins. It can also be

directly incorporated into selenoprotein during translation at the ribosome complex
using a RNA specific for the amiilo acid-selenocysteine. Thus selenocysteine can
be considered as the 21" amino acid in terms of ribosome-mediated protein synthesis.
At least 15 selenoproteins have now been characterized. Table 10.12 provides a list
of these selenoproteins. We will learn about them later in the function section.
Table 10.12: A selectit n of characterized selenoproteins
Tissue Distribution
All, including thyroid I
Phospholipid hydroxide GSHPx All, including thyroid I
Gastrointestinal GSHPx Gastrointestinal tract
Extracellular GSHPx Plasma, thyroid
Thioredoxin reductase All, including thyroid
I Iodothyronine-delodinase (type 1) I Liver, kidneys, and thyroid II
1 Iodothyronine-deiodinase (type 2) 1 Central nervous system and pituitary
I Iodothyronine-deiodinase (type 3) 1 Brown adipose tissue, central nervous I
system, and placenta
Selenoprotein P Plasma
1 Selenoprotein W I Muscle 1
Sperm capsule selenoprotein Sperm tail
* GSHPx, glutathione peroxidase.
Next, we shall brief ourselves regarding the presence of selenium in food,
Food Sources
Environmental conditions and agricultural practices. have a profound influence on the
selenium content of many foods. Table 10.13(a) illustrates the wide range of selenium
content of the principal food groups and the variability in the selenium content of
dietary constituents in selected counties. This variability is exceeded only by that
found in the iodine content of foods.
Advance Nutrition Table 10.13: The selenium contents of foods and diets
a) Typical ranges of selenium concentrations (ng/g fresh weight) in food, groups
Food Group India United States Internatio~~al
Compilation
Cereals and cereal products 5-95 10-370 10-550
Meat, meat products, and eggs 40.120 100-810 10-360
Fish and marine 280-1080 40(11500 1 10-970
Fish and freshwater - - 180-680
Pulses 10-138 - -

Dairy products 5-15 10-130 1-170

Fruits and vegetables 1-7 1-60 1-20

b) Typical distribution of selenium in dietary constituents (pg/day) in selected countries

China India
Food Groups Keshan Disease Low-income Low-income United
Disease Free Vegetarian Conventional Finland Ki~~gdom
Area Areas Diets Diets
Total diet 7.7 16.4 27.4 52.5 30.0 31.0
Cereals and 5.4 11.6 15.7 21.1 2.8 7.0
cereal products
Pulses - - 3.9 3.6 1.1 -

Meat and eggs - 3.7 9.2 10.0

Fish 0.6 2.2 - 18.4 9.5 4.0
Dairy products 6.9 4.8 6.5 3.0
Fruits and 1.7 2.6 0.9 0.9 0.5 6.0
vegetables
other - - - - 1.1 3.0

Source: Vitamin and Mineral Requirement in Human Nutrition, FAOtWHO (2004)

Geographic differences in the content and availability of selenium froin soils to food
crops and animal products have a marked effect on the selenium status of
entire communities. Refer to Table 10.13(b) which presents the typical distribution of
selenium in dietary constituents in selected countries. As you would notice, the
distribution of Keshan disease and Kashin-Beck disease in China reflects the
distribution of soils from which selenium is poorly available to rice, maize, wheat and
pasture grasses.

' Selenium enters the food chain through plants. The concentralion of selenium in
plants is directly related Lo the concentration of the mineral in the soil on which plants
were grown. Among the different trace elements, selenium varies greatly in its soil
concentration. It has been suggested that <lo nglg for grain selenium and <3 nglg
for water-soluble soil selenium could be used as indices to define deficient areas.

The absorption of selenium by plants is not only dependent on the conceiltration of

selenium in the soil but also on pH, microbial activity, rainfall and the chemical form
of selenium. Higher plants can absorb selenium as selenate and can synthesize
selenomethionine and to a lesser extent, selenocysteine.

Owing to all above factors, the selenium content in food varies greatly. Overall,
animal products, especially organ meats, are thought to contain more selenium than
plant sources, as you may have noticed in Table 10.13 (a). Seafoods are also considered
good sources, although availability of the mineral from fish, especially those containing
mercury, is low.
 Selenium occurs in foods in organic form, such as, selenomethionine, selenocysteine, Minerals (Micro Minerals):
selenocystine and Se-methyl selenomethionine. In general, plant foods contain greater Iron, Zinc, Copper,
Selenium, Chromium,
proportion of organic selenium compounds. Inorganic forms include selenite (H2Se03) Manganese, Iodine and
and Selenate (H2Se04).These forms are found in some vegetables. Fluorine

Next, we shall ,discuss about the absorption, transport, storage and excretion of
selenium.

Metabolism
Selenium compounds' are generally vety efficiently absorbed by humans and selenium
absorption does not appear to be' under homeostatic control. selenium is mainly
absorbed from the duodenum. Less absorption occurs in the jejunum and ileum.
Inorganic forms of selenium (mainly selenate) are passively transported whereas
organic forms are actively transported.

Almost 5040% of dietary selenium is absorbed, with efficiency being higher for
organic forms, as compared to inorganic. Among the organic fo~ins,selenomethionine
is better absorbed than selenocysteine. Among the inorganic forms, selenales are
better absorbed than selenites.For example, absorption of the selenite fornl of selenium
is greater than 80% whereas that of selenium as selenomethionine or as selenate may
be greater than 90%. In addition, some dietary factors appear to influence the
absorption of the element. Phytates and heavy metals, such as mercury through
chelation and precipitation, hinder selenium absorption. Vitamins C, A and E, as well
as, glutathione enhance the absorption.

Refer to Figure 10.5 for a better understanding of selenium absorption.

Selenocysteine
Sele~locysteit~e
Se-illetl~y
1-Sela~o~llctl~ionine

Selenite (H,SeO,) Se
[ Selenatc (H,sco,)~
b Selenoprotcins
I
a, P-globulins I
VLDL
or

1 1
Chelation LDL
Heavy ll~ctlils(I-Ig)
Phy~atcs Inorganic
Methyl sclellide
(for excretion)

E
l netmcyctl
Figure 10.5: Absorption and transport of selenium
As you may have noticed in Figure 10.5, after absorption selenium binds to sulphydryl
groups in a and P globulins of VLDL and LDL to be transported to the different
tissues. Liver and kidneys appear to be the major target organs.

Within tissues sich as liver, organic, as well as, inorganic selenium compounds have
different fates. This is briefly discussed herewith:
Advance Nutrition 1) Selenomethionine obtained from the diet may be:
o stored as such in amino acid pool,
o used for protein synthesis, and
o catabolized to selenocysteine.
P
2) Selenocysteine obtained from the diet or after catabolism of selenomethionine
is degraded to yield free elemental selenium. This elemental selenium may
be:
attached to tRNA charged with serine to be incorporated in selenium dependent
enzymes, and
converted into selenite which may be stored or excreted,
3) Selenate from the diet is converted to selenite. Selenite is further converted to
selenide. Selenide may be:
converted to selenophosphate to yield free selenium, which is incorporated into
enzymes, and
o excreted as methyl selenide.
The above discussion can be clearly understood after going through Figure 10.6,
which illustrates the metabolic fate of. selenium.

'Selenoproteins

Amino acid

(selcnocystne)

Selenocysteine
Selenate 4 Inorganic

, A
Selenocysteine
Se ---------------+ Selenite

ser-tNA

Se
\(
Selenidc H,Se)
1
Selenodiglu~athione
Methyl
---+selenide
(llun~n~~s'?)

For excretion

Glutathione peroxidase Sel'e~~ophosphae

and 5' deiodinnse

Figure 10.6: Metabolism of selenium in tissues

4) Selenium is excreted from the body almost equally in the urine (as methyl
selenium) and faeces (unabsorbed selenium, biliary, pancreatic and intestinal
secretion). Unlike copper, selenium is rapidly excreted in urine. Selenium losses
through lungs and skin also contribute to daily selenium excretion.
After having read about the presence of selenium in human body and its association
with several disease conditions, it must be evident that selenium plays an important
I
role in maintaining our health. The most salient functions of selenium have been Minerals (Micro Minerals):
Iron, Zinc, Capper,
discussed next. Selenium, Chromium, ,I
Manganese, Iodine and 1
Fluorine I

Until recently, the only known metabolic role of selenium in humans was as a
component of glutathione peroxidase which along with vitamin E and superoxide
dismutase forms a part of the an&-oxidant defense system. However, more
selenoproteins are being discovered and currently it is estimated that 50-100
selenoproteins are present in animals. Selenoproteins in animals and humans are
involved in protection from oxidative damage, maintaining adequate thyroid hormone
status and protection from injury by a heavy metal like mercury.

Three major enzyme systems in which selenium plays an important role have been
identified in humans. These include:
a) Glutathione peroxidases,
b) Iodothyronine deiodonases, and
C) Selenoproteins P and W
Let us study them in greater detail.

a) Glutathione peroxidases: The role of selenium in the cytosolic enzyme,

glutathione peroxidase (GSHPx), was first illustrated in 1973. Four selenium
dependent glutathione peroxidases have been identified and named as Glutathione
peroxidases 1-4 (GSHP,, 1-4). During stress, infection, or tissue injury,
selenoenzymes may protect against the damaging effects of hydrogen peroxide
or oxygen-rich free radicals. This family of enzymes catalyzes the destruction
of hydrogen peroxide or lipid hydroperoxides according to the following general
reactions:
H2O2 + 2GSH - - 2H20 + GSSG
ROOH + 2GSH -.-+ ROH + H20 + GSSG
where, GSH is glutathione and GSSG is its oxidized form.

Thus, from the reaction above, it is evident that the main role of glutathione peroxidases
is to reduce hydrogen .peroxide and free hydroperoxides in different cells and
tissues by using glutathione (GSH) as the hydrogen donor. Thus, the reactive species
of hydroperoxide free radicals are converted into innocuous molecules of water.
GSHP,-l is present in virtually all cells, GSHP,.2 is localized in the gastrointestinal
tract, GSHP,.3. is present in plasma while GSHPX.4is most abundant in testis but
present in other tissues also.

GSrn4plays a major role in protecting against lipid peroxidation as it is the only

intracellular enzyme that can reduce fatty acid hydro peroxide, GSHPXw3
in plasma can
also perform this role.
b) Iodothyronine Deiodinases: Another group of selenoproteins are the
iodothyronine deiodinases essential for the conversion of thyroxine or
tetraiodothyronine (T4) to its physiologically active form tri-iodothyronine (T3).
Three types of iodothyronine deiodinases have been identified, all of them being
selenoproteins. When one iodine is removed from Tq, it is converted T3. T3'is
more active than T4. Thus, one of the deiodinase enzymes is involved in activating
T+ When one or more iodine is removed from T3, the resulting molecules do
not have enzyme activity. Therefore, another selenium-dependent deiodinase
inactivates T
Advance Nutrition Type I iodothyronine deiodinase (a selenoprotein) is found in liver, kidney and
thyroid tissue. The major role of this enzyme is to provide T3 to peripheral tissues
by deiodinating T4 secreted by the thyroid gland. Selenium deficiency causes a
decline in the Q p e I deiodinase enzyme activity, but it may not result in hypothyroidism
as there 'is a compensatory increase in plasma T4 levels. Type II iodothyronine
deiodinase, also a selenoprotein, is present in the brain, pituitary and placenta. The
major function of this enzyme is to regulate Tglevels in these tissues, and control the
secretion of thyroid stimulating hormone. Type 11 enzyme activity is also reduced in
selenium deficiency. Type 111 iodothyroizine deiodinase, another seleiloprotein, is
involved mainly in degradation of the T4 and T3. How this enzyme is affected in
selenium deficiency is not fully investigated.

Thus, these selenopr.otein enzymes regulate and maintain thyroid levels. Animal studies
have shown that a combined deficiency of selenium and iodine produces much more
severe hypothyroidism compared to iodine deficiency alone. Further, maternal deficiency
of selenium and iodine is implicated in cretinism in newborn- the most severe outcome
of thyroid hormone deficiency during pregnancy.

c) Selenoproteins P and W: The third group comprises of selenoprotein P, an

extracellular constituent with multiple selenocysteine molecules. This has an
antioxidant role, deactivating free radicals. Selenoprotein W, present in the
muscle has a suggested role in muscular degeneration seen in combined selenium
and vitamin E deficiency. Selenoprotein W gets reduced during selenium deficiency.
Another group of selenium-containing enzymes is the thioredoxin reductases. The
selenoenzyme thioredoxin reductase is involved in disposal of the products of oxidative
metabolism. It contains two selenocysteine groups per molecule and is a major
component of a redox system with a multiplicity of functions, among which is the
capacity to degrade locally excessive and potentially toxic concentrations of peroxide
and hydroperoxides likely to induce cell death and tissue atrophy.

These selenoproteins catalyze the NADPH-dependent reduction of oxidized

thioredoxin. Reduced thioredoxin provides reducing equivalents for various redox-
dependent systems, such as, ribonucleotide reductase essential for DNA synthesis,
redox regulation of transcription factors. Besides, these proteins have important
functions in regulating cell growth and inhibiting apoptosis.

The above discussion clearly indicates the importance of selenium in human nutrition.
Let us now find out how selenium status can have an impact on our health. We shall
,begin with the state of deficiency and then discuss the consequences of toxic levels
of selenium.

Deficiency
Selenium deficiency has been linked to two regional human diseases: Keshan disease
and Kashin Beck's disease.

Let us understand what these diseases are and their characteristic features.

Keshan disease: It is a cardiomyopathy (disease of the myocardium, involving heart

muscle) that was identified to affect children and women of child bearing age in
China. Sudden onset of insufficient heart function is characteristic of the acute form
of this disease while in chronic Keshan disease, heart enlargement and insufficiency
exist. Intervention trials comprising more than a million subjects in China has
demonstrated the protective effect of selenium against Keshan's disease. It is important
to note that selenium supplements cannot however reverse cardiac failure if it has
occurred.
 Kashin Beck disease: Kashin Beck disease was identified to affect growing children ~ i n e r a l s(Micro
' Minerals):
Iron, Zinc, Copper,
in parts of Siberian Russia and China. It is characterized by osteoarthritis involving Selenium, Chromium,
degeneration and necrosis of the joints and epiphyseal-plate cartilages of legs and Manganese, Iodine and
arms. It is possible that apart from selenium deficiency, many other factors may be Fluorine
contributing to the development of Kashin Beck's disease.

Suboptimal selenium status may be widespread in human population. It is accompanied

by loss of immuno-competence with the impairment of both cell-mediated immunity
and @-cell function. The early preclinical stages of development of human
immunodeficilncy virus (HIV) infection are accompanied by a very marked decline
in plasma selenium. Subclinical malnutrition assumes increased significance during the
development of acquired immune deficiency syndrome (AIDS). Selenium
supplementation in subjects has been shown to mark irnmuno-stimulant effects including
increased proliferation of activated T-cells. In addition, as selenium has well recognized
anti-oxidant and anti-inflammatory roles, other oxidative stress or inflammatory
conditions such as rheumatoid arthritis, ulcerative colitis, pancreatitis may also benefit
from selenium supplementation.

, Further, enhancement of the virulence of virus due to selenium deficiency has been
reported. There is a growing evidence that suboptimal selenium status inay also
increase risk of cancer and cardiovascular disease. However, much work is still
needed in these aspects.

Toxicity
There is a narrow margin between the beneficial and harmful intakes of selenium.
The level at which selenosis occurs is not well-defined but threshold for toxicity
appears to be 850-900 yg per day. Symptoms of chronic toxicity include brittle hair
and nails, skin lesions with secondary infections and garlic odour in the breath.
Chronic selenium poisoning in people is characterized primarily by loss of hair and
changes in finger nail morphology. In some cases, skin lesions may occul:

Next, we shall learn about the parameters indicative of selenium status.

Assessment of Selenium Status

Blood glutathione (GSH) peroxidase activity is directly related to blood selenium up
to a level of 1.27 pnolesL. Beyond this point, the activity of the enzyme plateaus
and therefore cannot be used for assessing selenium status. As of now, GSH peroxidase
remains a useful index over the assessment of usual dietary intakes but is limited by
the peak level reached at 1.27 rnmol/L. Plasma selenium level is an index of short
term status, as it has been shown to respond to selenium supplementation more
rapidly in deficient individuals than whole blood selenium. Hair and nail selenium are
not as yet established as valid parameters, although they are being investigated.

So what level of intake should be maintained to ensure the maintenance of optimum

selenium levels in plasma? Let us find out.

+
The FAOIWHO 2004 recommendation for nutrient intake for selenium by groups is
given in Table 10.14. How do these recommendations compare with the US and the
UK recommendations? Let us find out. In the UK, the reference nutrient intake has
been set at 75 and 60 mcg of selenium per day for men and women, respectively.
These are based on the intakes required to saturate plasma glutathione peroxidase.
In the U.S., recommended nutrient intake is 70 mcglday for men and 55 mcglday
for women. Thus, the present FAOIWHO' 2004 report represent a significant decrease
in the suggested need for selenium. The lower requirements presented are
physiologically justifiable and will only give rise to concern if there are grounds for
serious incertainty as to the predictability of dietary selenium intake. 329
Advance Nutrition Table 10.14: Recommended nutrient intakes by selenium, by group
Group Asfumedbody RNI (uglkgIb
Weight (kg)

Infants and Children

0 - 6 months 6 6
7 - 12 months 9 10
1 - 3 years 12 17
4 6 years - 19 2
7 - 9 years 25 21
Adolescents
Females 10 - 18 years 49 26
Males 10- 18years 51 32
Adults
Females, 19 - 65 years 55 26
65+ years 54 25
Males, 19 - 65 years , 65 34
65+ years 64 33
Pregnant women - 28
Second trimester - 30
Third trimester
Lactating
0-6 montbs - 35
6 - 12 months - 42

Recommended nutrient intake (RNI) derived from the average SeRnomntive

.t 2 x assumed
standard deviation (of 12.5%).
Source: Vitamin andSMineralRequirements in Human Nutrition, FAOIWHO (2004)
No RDI's have been suggested so far for Indians. There is a need to derive
recommendations which are applicable for a proportionally lower weight range than
that utilized in most developed countries.

Before we proceed to study chrorniun, let us recapitulate what we have learnt so far
by answering the check your progress exercise 4.

Check Your progress Exercise 4

1) Name an enzyme which constitutes selenium as its integral part.
.....................................................................................................................
.....................................................................................................................
2) Of all trace elements, selenium content in food varies greatly. Why?
) . . . . . . . . . , . . . . . . . I . . . . . . . . . . . . . . . . . . . . * . . . . . . . . . . * . . . . . . . .s.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I

.....................................................................................................................
.....................................................................................................................
3) What are the factors which hinder selenium absorption?
.............................................
........,................................................(.............,
.....................................................................................................................
 Minerals (Micro Minerals):
4) Enumerate the important functions of selenoenzymes. Name a test to indicate Iron, Zinc, Copper,
short-term changes in dietary intake of selenium. Selenium, Chromium,
Manganese, Iodine and
..................................................................................................................... Fluorine

.................................................................................................................
"

.....................................................................................................................
.....................................................................................................................
....................................................................................................................
5) Write a short note on selenium deficiency.
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
Now get down to the study of chromium.

10.7 CHROMIUM
As you will go through this section, you will realize that compared to other minerals,
the essentiality of chromium was recognized very late. Let us briefly review its
history.

By the year 1948, chromium was recognized as a consistent component of plant and
animal tissue. In 1950, it was recognized as an element which potentiated insulin
action and restored normal glucose tolerance in rats.

In humans, studies were initiated between 1964-68, wherein chromium supplementation

was shown to improve impaired glucose tolerance. Despite these studies, the essentiality
of chromium in human nutrition was documented as late as in 1977, when a female
patient on total parenteral nutrition (TPN) developed diabetes - like symptoms that
were refractory to insulin. Chromium supplementation was shown to alleviate these
symptoms and insulin was no longer required. Subsequent studies confirmed these
fmdings.

Chromium also exists in several oxidation states from Cr2- to Cr6+ however Cfl+ or
the trivalent form is also the biologically important one. Cr6+, which is consumed in
small amounts, comes from industrial sources. In the acidic environment of the
stomach, CFf is converted to C9+.

Unlike other minerals, chromium is present in small amounts in human body. The
kidneys, followed by spleen, liver, lungs, heart and skeletal muscle are the tissues with
greatest chromium concentration.

Let us review the rich and poor sources of chromium.

Food Sources
Chromium occurs in trivalent form in foods. Good sources of chromium include whole
grains, spices and condiments, meats especially organ meats, mushrooms, cheese,
prunes and tea. Brewer's yeast has a high content of biologically active organically
complexed form known as the Glucose Tolerance Factor (GTF). Chromium
complexes with nicotinic acid and amino acids to form GTE 331
Advance Nutrition We shall now brief upon the absorption, transport, storage and excretion of chromium
from our body.

Metabolism
Chromium appears to be absorbed throughout the small intestine, with absorption
being higher in jejunum. The mechanism of absorption has not been well defined but
appears to involve processes other than simple diffusion. At normal dietary intakes
(10-40 mcglday), the absorption ranges from 0.4 to 3.0% with absorption being higher
at lower intakes. As you have studied for other.rninerals, even in the case of chromium,
an inverse relation between intake and absorption appears to be a basal control
mechanism to maintain the body levels of chromium.

As comp'ared to healthy individuals, insulin-dependent diabetic patients absorb 2-4

times more chromium. It appears that these patients have an impaired ability to
convert inorganic foim to usable form and therefore require higher chromium. Like
other trace minerals, absorption of chromium is also influenced by some factors.
Enhancers and inhibitors are listed in the Table 10.15.
Table 10.15: Factors influencing absorption
Enhancers Inhibitors
Ascorbic acid Antacids
Picolinate (forms stable ipophillic ligand) Phytates
Methionine and histidine (can chelate or and
make it available better).
After absorption, chromium binds to plasma proteins for transportation. Both transferrin
and albumin are capable of binding absorbed Cr. It has been suggested that transferrin
is the main binder of newly absorbed chromium and albumin assumes the role of
chromium acceptor and transporter if transferrin binding sites are unavailable.

You have studied that transferrin has two metal binding sites, one is primarily for iron
and the second is involved in chromium transport. During conditions of iron excess
or iron overload such as iron storage diseases, all the metal transport sites on transferrin
are occupied by iron. This may explain the high incidence of diabetes in
haemochromatosis patients, which may be induced by chromium deficiency.

Although transferrin and albumin play the major roles in transportation, other plasma .
proteins such as a and p globulins and lipoproteins are also involved.
7 .

As you will go through the next section on 'Functions', you will realize that only
organically complexed chromium i.e. GTF is active. It appears that absorbed inorganic .
chromium is transported to the liver, which is postulated to be the possible site for
synthesis of metabolically active molecule. This molecule is held in a body pool and
released as needed.

Most ingested chromium is excreted in faeces. Inorganic chromium is excreted

primarily by the kidney, with small amounts being excreted through hair, sweat and
bile. Organically bound chromium is excreted through bile.

The biologically active form of chromium performs several functions; the important
ones are being subsequently discussed.
C
Functions
Active chromium as GTF potentiates the action of insulin and thus influences
carbohydrate, lipid and insulin metabolism.

Let us first study the mechanism by which chromium potentiates insulin function.
t
Role in Insulin Formation Minerals (Micro Minerals):
Iron, Zinc, Copper,
You are aware that insulin receptors are present in many cells with their concentration Selenium, Chromium,
being highest in adipocytes (cells present in adipose tissue) and hepatocytes (liver Manganese, Iodine and
cells). You also know that insulin receptor has two extracellular alpha-subunits and Fluorine
two extracellular beta-subunits. It is the alpha-subunit to which insulin binds. Once
insulin binds to the alpha-subunit of the receptor, a specific phosphorylation of the
beta-subunit occurs through a cascade of phosphorylation reactions. This leads to .
increased insulin sensitivity. The enzyme partly responsible for this phosphorylation is
the 'insulin receptor tyrosine kinase'. This enzyme is activated by chromium. In
rats, removal of chromium has been shown to result in the loss of kinase-potentiating
activity. Besides activating the kinase, chromium also inhibits phosphotyrosine
phosphatase-an enzyme responsible for inactivation of insulin receptor.

The activation of 'insulin receptor tyrosine kinase' and inhibition of 'insulin receptor
tyrosine phosphatase' by cluomium would lead to an increased phosphorylation of the
insulin receptor, wlich is associated with increased insulin sensitivity.

Since chromium improves insulin function, it is suggested that chromium may play a
role in glucose and lipid metabolism. Let us now review these functions:

Role in Glucose, Lipid and Nt~cleicAcid Metabolism

Chromium leads to a decrease in blood glucose concentration in people with elevated
glucose levels and an increase in those with low blood glucose levels. It shows no
effect in the subjects with normal blood glucose levels.

Owing to its role in improving glucose tolerance, many studies having been conducted
to see the effect of chromium supplementation in patients with impaired glucose
tolerance, and Type 2 diabetes, however, results of different studies have been
varied. From the results of various studies, it appears that supplemei~tationlevel of
200 mcglday as chromium chloride (CrC13)did not have any beneficial effect: Positive
effects were observed in studies using 400 mcg Crlday as CrC13. Almost all the
studies employing more bioavailable Cr picolinate have reported favourable effects
with greater effect reported at 1000 mcglday than at 200 mcg/day. Also human
studies include subjects of diverse genetic and nutritional backgrounds living in
environments of varying degrees of stress, all of which may affect chromium
metabolism.

Similarly, improved insulin functioil is also associated with improved lipid profile.
Although number of beneficial effects of chromium on lipid profiles have been reported,
these responses are not consistent from study to study. Overall, chromium appears
to reduce levels of total cholesterol, LDL cholesterol and triglycerides in blood and
increase level of HDL cholesterol.

Another proposed role for chromium is in relation to nucleic acid metabolism. It is

postulated that Cr3+ is involved in maintaining the structural integrity of nuclear
strands and in the regulation of gene expression.

It must be evident from the discussions above that chromium is important for glucose,
fat, protein and especially nucleic acid metabolism. Thus, its low or excessive intake
over a period of time may result in the development of metabolic changes in several
nutrients. Let us read further to know as to what happens when chromium intake is
above or below our requirements.

Deficiency
Hallmark of marginal chromium deficiency is impaired glucose tolerance. Individuals
receiving TPN without chromium have been shown to develop symptoms of deficiency
Advance Nutrition such as impaired glucose tolerance with high blood glucose level and glucose excretion
in urine. Peripheral neuropathy has also been reported which was reversed with
chromium supplementation.

Chromium deficiency results in insulin resistance characterized by hyperinsulinemia.

Hyperinsulinemia is implicated as a risk factor for coronary heart disease.

Toxicity
'
Trivalent chromium, the form of chromium found in foods and supplements, is least
toxic. Oral supplements upto 800 to 1000 mcg per day appear to be safe. However,
hexavalent chromium often found in paints, welding fumes and other industrial settings
is very toxic. Inhalation of Cf" may result in respiratory disease while direct contact
results in dermatitis and skin ulceration. Liver damage can also occur.

Let us then learn how to assess the chromiuin status.

Assessment of Chromium Status

No specific tests are currently available, which could help us to determine chromium
status. Another reason being the chromium content of physiological fluids is not
indicative of its status. Also urinary chromium, hair chromium concentrations and
fasting plasma chromium tests do not show consistent and reliable ,results.

So what level of dietary intake would suffice for our body's requirement and shall
not cause any toxic effects? Let us find out this next.

Requirements of Chromium
There is no Recommended Dietary Allowance (RDA) for chromium but adequate
intakes that can be used as a goal for individual intakes has been proposed by the
Fbod Nutrition Board of the National Academy of Services, USA. These are given
in Table 10.16.
Table 10.16: Suggested and 1 or estimated safe and adequate daily dietary intakes for
chromium
Age Group Adequate Intake Age Group Adequate Intake
(Idday) bdday)
Infants Females
0-6 months 0.2 9-13 y 21
7- 12 months 5.5 14- 18 y 24
Children 19-3Oy 25
1-3 y 11 31-50y 25
4-6y 15 50 - 70y 20
Males > 70 y 20
9-13y 25 Pregnancy
14- 18 y 35 < 18 y 29
19-30 y 35 . 19-30 y 30
31-50y 35 31-5Oy 30
50 - 70y 30 Lactation
> 70 y 30 < 18 y 44
19-30y 45
31-5Oy 45

Source: Dietary Reference Intake for vitamin A, vitamin K, Arsenic, Chromium, Copper,
Iodine, Iron, Manganese, Nickel, Silicon, Vanadium and Zinc. US Food and Nutrition
Board, (2001).
 Minerals (Micro Minerals):
10.8 MANGANESE Iron, Zinc, Copper,
Selenium, Chromium,
Manganese, Iodine and
Manganese (Mn) is a transition element and can assume 11 different oxidation states, Fluorine
from - 3 to + 7. However, in living tissues, it is found in the + 2, +3 and +4 oxidation
states. An adult man weighing 70 kg is estimated to contain 10-20 mg of the metal,
with 25% of the total body stores in the skeleton. Relatively high amounts of the
minerals are also present in livel; pancreas and intestine.
P

Although not much work has been done to identify the usual dietary intake of Mn
among Indians in different age groups, the diet can be estimated to be a poor or good
source of Mn by knowing the food sources of this element. So let us recapitulate on
the same.

Food Sources
The food sources of manganese along with their content are tabulated in Table 10.17.
Here, you can see that whole cereals, nuts, leafy vegetables and tea are good
sources of Mn. Indian diets high in foods of plant oiigin supply on an average
8.3 mg of Mnlday.
Table 10.17: Manganese content of selected foods and beverages

FooddFood Group Manganese Content (mg/100 g)

Bread, whole grains 0.50 - 2.05
Flour, whole grain 3.80
Bread, white 0,05
Flour, white 0.79
Legumes 0.24 - 0.58
Nuts 0.83 - 4.7 1
Root vegetables 0.05 - 0.62
Other vegetables 0.15 - 1.94
Fruits 0.04 - 1.60
Fruits (dried) 0.09 - 0.39
Milk and cheeses <0.01
Cofee (brewed) 0.02 - 0.03
Tea (brewed) -
0.18 0.22

Let us next learn about the absorption, transport, storage and excretion of Mn i.e. the
metabolism of manganese.

Metabolism
Intestinal absorption of Mil occurs throughout the length of the small intestine although
the exact mechanism of absorption is not clearly established.
Ingested Mn is thought to be converted into Mn3+in the duodenum. Results of the
studies suggest that mucosal uptake could be a rapidly saturable process, which
appears to be mediated by a high-affinity, low-capacity active transport system.
Available evidence also suggests that mucosal transport occurs through a non-saturable
simple diffusion process, It appears that both processes might be involved in the
absorption of mineral and may operate simultaneously.
-
Absorption of Mn from the diet is very low. On the basis of Mn retention, it has been
estimated that adult humans absorb 4.8% of ingested manganese.
Let us now see which factors influence Mn absorption.
d

* Major factors which may influence the absorption of this mineral include:
Absorption decreases with increasing intake.
Advance Nutrition 0 Percent absorption is higher among women as compared to men.
0 Increased dietary iron depresses Mn absorption whereas iron deficiency increases
its absorption. This could be possibly due to the competition for similar binding
and absorption sites between non-haem iron and Mn.
0 High levels of dietary calcium, phosphorus and phytate impair the intestinal
uptake of the element but these have been shown to be of limited significance.
Let us now study the fate of Mn which is absorbed.
After absorption, Mn is complexed with albumin and transpoi-ted to the liver, which
is the key organ in its metabolism. In the liver, Mn is found in both rapid and slow
exchanging pools. The former is the precursor of biliary Mn, which is excreted in the
faeces. The latter serves as the source of Mn for the liver and extrahepatic tissues.
Mn becomes bound as Mn2+ to a-macroglobulin before traversing the liver. From the
liver, some Mn2+appears to be oxidized by ceruloplasmin to Mn3+ and complexes with
transfenin. Transferrin bound Mn3+ is taken up by the extrahepatic tissues.
Mn is found in most organs and tissues and preferentially accumulates in the
mitochondria. There is no storage form for Mn. Bone contains substantial amount of
nlineral but there is no mechanism to release it and thus bone Mn is considered as
passive storage. It is released only as a result of normal bone turnover or in situations
of accelerating bone resorption.
Mn is almost totally excreted in the faeces (92%). Excess absorbed MI is quickly
excreted by the liver into the bile to maintain homeostasis. Only trace amounts are
excreted in urine.
Let us now briefly review some important functions of Mn.
Functions
Like other microrninerals, Mn also functions in mammalian enzyme systems. It can
function both as an integral part of metalloenzymes and as an enzyme activator.
Manganese containing metalloenzymes are few, as shown in Table 10.18, whereas
enzymes activated by Mn are much larger in number. Most of these metal activations
by Mn are non-specific, as magnesium (Mg) can substitute for Mn. There are a few
exceptions where Mn be specifically needed for activation. Examples include, activation
of glycosyl transferases, phosphoenoZ/phruvate carboxykinase and glutarnine
synthetase.
Glutamine synthetase found in high concentration in the brain catalyzes the following
reaction:
NH3 + Glutarnate + ATP + Glutamhe + ADP + Pi
Thus, glutamate synthetase converts potentially toxic ammonia into glutamine and
helps in the removal of ammonia (NH3) as it is generated. It is interesting to note
that even in severe Mn deficiency in animals, brain glutamine synthetase activity is
maintained normal, suggesting that this enzyme has a high priority among the enzymes
activated by Mn or that Mg can replace Mn.

n b l e 10.18: Mn activated enzymes and Mn containing metalloenzymes

Mn Activated Enzymes Mn Containing Metalloenzymes

Hydrolases Arginase
Kinases Pyruvate carboxylase
Decarboxylases Superoxide - Dismutase
Transferases
Lyases
* Oxidoreductases
Ligases
You have seen that Mn is involved in a number of enzyme-catalyzed reactions. Minerals (Micro Minerals):
Therefore, it performs many important functions. These are briefly discussed Iron, Zinc, Copper,
Selenium, Chromium,
herewith: Manganese, Iodine and
-

Fluorine
1) Arztioxidant activity: As Mn is a component of mitochondria1 Superoxide
Dismutase (SOD), it can protect against oxidative damage. In-vitro experiments
have indicated that Mn scavenged superoxide radicals at nanomolx concentration
whereas hydroxy radicals were scavenged at macromolar concentrations. Thus,
Mn deficiency could damage mitochondria1 membrane by depressing the activity
of SOD. Although, a little work has been done in humans, depressed activity of
the enzyme has been reported in animals.
2) Carbohydrate metabolism: Mn is required for carbohydrate metabolism. Enzymes
pyruvate carboxylase and phosphoenol pyiuvate carboxy kinase involved in
gluconeogenesis require Mn for optimal function.
Further, animal studies strongly suggest a role for Mn in regulation of insulin
transcription Ad I or in insulin mRNA turnover. Mn-deficient animals have been
shown to exhibit a diabetic response to oral glucose challenges characterized
primarily by impaired insulin production.
3) Integrity of cartilage: Mn plays an ilnportant role in proteoglycan biosynthesis,
which is essential for the integrity of cartilage. Bone defects have been observed
in birds, rats and mic,e. This has been ascribed to a reduction in the activities
of several Mn-dependent glycosyl transferases.
It must be clear by now that though Mn is classified as a trace element; it is involved
in the regulation of several enzyme activities and other important functions. However,
what would happen during sub-optimal intake of Mn? Read further to find out.
f
Deficiency 1
Mn deficiency has been observed in many species of animals and symptoms include:
impaired growth, skeletal abnormalities, depressed reproductive function and defects
in lipids and carbohydrate metabolism.
With respect to humans, there is a little evidence of Mn deficiency as this mineral
is widely distributed in a variety of foods. However, limited studies have reported
symptoms of its deficiency after consuming experimental diets deficient in Mn. These
included dermatitis, depressed growth of hair and nail, hypocholesterolemia and weight
loss. Please note that sample size was very small in these limited experimental
studies.
Evidence is accumulating that Mn deficiency may be present in selected groups. It
has been reported in patients on long-term parenteral nutrition when the solutions
were low in Mn content. Modest supplementation of iron can result in lowering of
lymphocyte Mn-SOD activity in humans. In view .of high frequency of iron
supplementation by some groups, it is worthwhile to find out the incidence of Fe-
supplementation-induced reductions in Mn status.
Mn deprivation has been associated with osteoporosis, diabetes, epilepsy, atherosclerosis
and impaired wound healing.
While a low Mn level in body tissues can affect the humin health adversely, a higher
than normal intake may also influence several functions. The consequences of toxidity
are being discussed next.

Toxicity
Mqganese is considered least toxic of the trace minerals through oral intake. However, .
some people may be at a risk to develop toxicity. For exainple, individuals with
impaired biliary andlor hepatic dysfunction are more susceptible, as dietary Mil is
337
Advance Nutrition cleared by the liver. Similarly, total parenteral nutrition (TPN) bypasses the normal
homeostatic mechanisms of the liver and gut. Therefore, patients receiving long-term
parenteral nutrition are also at a dsk.

Manganese toxicity, however, occurs primarily in industrial workers exposed to

excess airborne Mn such as in case of industries manufacturing steel, alloys and iron
products. Airborne Mn is also contributed by the Mn containing antiknock
compounds in gasoline fuel. Majority of Mn 'toxicity cases have been reported from
individuals exposed to airborne Mn in industrial areas in excess of 5 mg per cubic
meter (m3). Mn toxicity is a serious health hazard; in its severe form it results in
serious psychiatric symptoms such as hyperirritability, violent acts, hallucinations and
poor coordination. Several abnormalities occur in the central nervous system, the
morphological lesions being similar to Parkinson's disease. In workers exposed to less
than 1 mg/m3, impaired motor coordination and impaired memory have been reported.
The symptoms of Mn toxicity are apparently due to excessive tissue oxidative damage
by Mn.

So which clinical indicators can help in identifying the Mn status of an individual?

Read and find out.

Assessment of Mn Status
The body Mn status has not been yet established by laboratory tests. Though the
normal range of serum Mn concentration is found out to be 0.04 to 1.4 mcg/dl, it has
been shown that Mn supplementation significantly increased lymphocyte SOD activity
and serum Mn concentrations.

You must have understood by now that an optimum intake of Mn is imperative

for maintaining good health. However, what level of dietary intake per day would
help in maintaining equilibrium between the intake and requirements? Let us find
out.

Requirements
You have studied in Unit 1 that there are no RDA for certain nutrients including Mn.
Instead there is an average intake (AI) value established by US Food and Nutrition
Board which is presented in Table 10.19.

Table 10.19: Average intake (AI) values for manganese

Age Group Requirements (mglday)
Infants (< 6 months) 0.003
Infants (7 - 12 months) 0.6
Children (1 - 3 years) 1.2
Children (4 - 8 years) 1.5
Boys (9 - 13 years) 1.9
Boys (14 - 18 years) 22
Girls (9 - 18 years) 1.6
Adult Men 23
Adult Women 1.8
Pregnant Women 2.0
Lactating Women 2.6

Source:Dietary Reference Intake for vitamin A, vitamin K, Arsenic, Chromium, Copper, Iodine,
Iron, Manganese, Nickel, Silicon, Vanadium and Zinc. US @od and ~ u i t i o nBoard, (2001).
In this section, you studied about the nutritional significance of chronlium and magnesium Minerals (Micro Minerals):
for maintaining human health. In our next section, two very important nutrients viz., Iron, Zinc, Copper,
Selenium, Chromium,
iodine and fluorine shall be dealt in detail. However, before we proceed, you must Manganese, Iodine and
perform the check your progress exercise 5. You may have to read certain aspects Fluorine
again to clear your concepts.
Check Your Progress Exercise 5
1) .Why do IDDM patients absorb 2-4 times more chromium?
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
2) What are the factors that enhance Cr absorption?
.....................................................................................................................
.....................................................................................................................
3) How does chromium deficiency induces high incidence of diabetes in
haemochromatosis patients?
.....................................................................................................................
......................................................................................................................
.....................................................................................................................
.....................................................................................................................

4) List the factors influencing Mn absorption.

.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
5) Give the important functions of Mn.
.....................................................................................................................
.....................................................................................................................
......................................................................................................................
.....................................................................................................................
6) What is the main storage form of Mn? Describe the metabolic fate of bone Mn.
.....................................................................................................................
......................................................................................................................
.....................................................................................................................
.....................................................................................................................

7) Briefly explain the phases o f MII toxicity.

, .
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
Advance Nutrition In the following sections, we shall deal with two very important nutrients i.e. iodine
and fluorine, the dietary supply of which is necessary in view of some very important
functions that they perform. We shall begin with iodine.

110.9 IODINE
Iodine derives the nutritional importance as a constituent of thyroid hormones, 3,5,3',5'
tetraiodo-thyronine (thyroxine or T4) and 3,5,3' tri iodo-thyronine (T3).The thyroid
hormones are indispensable for normal growth and development in humans and
animals. Synthesis of the iodine containing thyroid hormones occurs exclusively in the
thyroid gland. Goitre was known to the ancient Indians, Chinese, Greeks and Romans.
Iodine as an element was discovered only in 1811; however, its presence in the
thyroid gland was discovered by Bauman et, a1 in 1895. The relation between iodine
deficiency and enlargement of the thyroid gland or goitre was shown early in the 20Lh
century when it was reported by David Marine that the thyroid gland became
hyperl~lastic(increase in number of normal cells in an organ and therefore an
increase in volurnelsize of the organ) with low level of iodine in the body. Subsequently
in 1922, Marine and Kimball demonstrated that administration of small amounts of
iodine could prevent or substantially reduce endemic goitre among school children in
Ohio.

Introduction of iodized salt as a public health measure to prevent goitre was first
introduced in Switzerland and Michigan. Following this, the incidence of goitre and
cretinism fell rapidly in these countries. Another major development for the population
at-risk of severe iodine deficiency in inaccessible mountainous areas, was the iodized
oil ( 1 ml containing 480 mg iodine) which can be given once in three years. Oral
iodized oil is also effective but the effects inay last only for one year.

Iodine is a non-metallic element of the halogen group with common oxidation states
of -I-' (iodides), It5 ,KI03 (iodates), KI04 (periodates) and less common states
of + I (iodine monochloride) and +3 (iodine tl-ichloride).In humans, iodine is typically
found and functions in its ionic form, iodide ( I-').

About 15 -20 mg iodine is found in human body, of which 70 -80% is present in the
thyroid gland. The thyroid gland weighs 15-25 grams and has a remarkable ability to
concentrate iodine. In the iodine deficient individual, enlarged thyroid gland may
contain only 1 mg iodine.

So, how can we consume adequate amounts of iodine in our diet? Let us get to know
about the food sources, next:

Food Sources
Please note that unlike other minerals studied so far, like selenium, the iodine
concentration in foods is highly variable and also depends on the concentration of
iodine content of soil in that region. The iodine present in the upper crust of the earth
is leached b y glaciation and repeated flooding, and is carried to the sea. Seawater
is, therefore, a rich source of iodine. The seaweed located near coral reefs has an
inherent biological capacity to concentrate iodine from the sea. The average iodine
content of foods (fresh and dry - basis) is given in Table 10.20.
The amount of iodide in drinking water is an indicator of the iodide content of the
rocks and soils of a region and it parallels the incidence of iodine deficiency among
the inhabitants of that region. In general, iodine deficient areas have water iodine
levels below 2 mcg/L as in Nepal and Sub-Himalayan India (0.1 -1.2 mcg IL) compared
with levels of 9 m c g L in the city of Delhi, which is not iodine deficient.
 I

1
Table 10.20: Average iodine content of foods (mglkg) Minerals (Micro Minerals): 1
Iron, Zinc, Copper, i
Faod Fresh Basis Dry Basis Selenium, Chromium, I
Mean Range Mean Range Manganese, Iodine and I

Fluorine I
Fish (fresh water)
Fish (marine)
30
832
17-40
163-3 180
116
3715
68-194
471-4591
'i
i;

Shellfish 798 308-1300 3866 1292-4987 1

Meat 50 27-97
:
Milk 47 35-56 1
93
i
Eggs :
Cereal grains 47 22-12 65 34-92 I
Fruits 18 10-29 154 62-277
Legumes 30 23-36 234 223-245
Vegetables 29 12-201 385 204-1636

Source: ICoutras D A , Matovinovic J, Vought R. The ecology of iodine. In: Stanbury JB,
Hetzel BS, eds. Endemic goitre and endemic cretinism. Iodine nutrition in health
and disease. New Delhi, Wiley Eastern Limited, 1985:185-195.
In addition to water, iodine is also contributed by sea foods, as mentioned above.,
However, a large difference in the content exists between sea water fish and fresh
water fish. Sea fish contain about 300-30,000 mcg iodinelkg in contrast to only
20-40 mcg iodinekg in fresh water fish.
Also, food additives used as bread dough oxidizers or conditioners can contribute to
the iodine content of the diet.
You must be acquainted with the physiological significance of iodine by now. Let us .
find out how the dietary iodine that we consume gets absorbed, transported, stored
and if required, excreted from our body.
Metabolism
'
Now, we will very briefly study how iodine is absorbed, distributed in the body and
excreted out.
Like other nutrients, dietary iodide is either found free or bound to antino acids. It
is primarily found as iodide or iodate. The latter form is reduced to iodide by
glutathione in the gut. Iodide is rapidly 'and completely absorbed throughout the
gastrointestinal tract and very little iodine appears in faeces.

Iodine bound to amino acids is also absorbed but less efficiently. The thyroid hormones:
thyroxine (T4) and triiodothyronine (T3) are also absorbed unaltered. Therefore, Tq
medication can be administered orally.

After absorption, free iodide appears in the blood and circulates to all tissues. Thyroid
gland traps most of the ingested iodide (80%). This is achieved against an iodide
gradient (often 40 to 50 times plasma concefitration) by sodium-dependent active
transport system. This mechanism is regulated by thyroid stimulating hormone (TSN)
secreted by pituitary. Thyroid takes up almost 120 lncg of iodide per day. Other
tissues such as salivary glands, gastric mucosa, choroid plexus and mammary glands
also concentrate the element by a similar active mechanism.

Several sulphur-containing compounds such as thiocyanate, isothiocyanate and goitrill

inhibit active transport mechanism by competing for uptake with iodide. Thus, iodide
uptake by thyroid gland may be reduced. These are called goitrogens and their
goitrogenic activity can be overcome by iodine supplementation, Refer to Box 10.1
for better understanding of goitrogens.
Advance Nutrition
Box 10.1 Goitrogens
Goitrogens are substances that interfere with iodide metabolism in any way that
inhibits thyroid hormone synthesis. As a result, there is augmentation in TSH
release and subsequent thyroid gland enlargement. These active goitrogens are
released by plant enzymes from thioglucosides or cyanogenic glucosides found in
cassava, kale, cabbage, broccoli, turnips, rapeseeds and mustards. Most important
of these is cassava, which can be detoxified by soaking in water and cooking it
well. Tobacco smoke also contributes thiocynate.

Unutilized iodide is excreted via kidneys, which forms the major route of iodide
excretion (80-90 %). The urinary output of iodide correlates closely with the plasma
iodide concentration and has been used to monitor iodide status. Some iodide is also
lost in sweat, especially in the hot tropical regions.
Iodine, as we all know, performs some very important fi~nctionsin our body particularly
those pertaining to the thyroid gland. We will now discuss the functions of iodine in detail.

Iodine is an essential constituent of the thyroid hormones: thyroxine (T4) and

triiodothyronine (T3), which have a key role in growth and development. Let us first
briefly review how these hormones are synthesized and released from the thyroid
gland.

Biosynthesis and Secretion of Thyroid Hormones

Histologically, the functional cells of the thyroid gland are arranged in follicles, which
surround a central lumen containing a colloid in which the hormones are stored in the
form of thyroglobulin. Thyroglobulin (refer to Figure 10.7) is a glycoprotein and is
synthesized in the follicular cell as prothyroglobulin and the tyrosine units are iodinated
in the intact protein.
As you may have noticed in Figure 10.7, the iodide actively transported into the cells
from extracellular fluid (ECF) is released from the thyroid cells into the colloid
follicle where it is oxidized by thyroperoxiduse in the presence of hydrogen peroxide.

L
Thyroid cell arranged in follicles mound
central luinen containing colloid

Figure 10.7: Biosynthesis and secretion of thyroid hormones

The oxidized iodine is then combined with the amino acid tyrosine in thyroglobulin to Minerals (Micro Minerals):
form mono and di-iodotyrosines (MITIDIT), which are again catalyzed by Iron, Zinc, Copper,
Selenium, Chromium,
thyroperoxidase. These are then coupled to form triiodo to thyronine and tetraiodo- Manganese, Iodine and
thyroxine. The iodinated thyroglobulin is absorbed back into the cells by a process Fluorine
known as pinocytosis. The iodinated thyroglobulin is hydrolyzed within the cells by
the cellular proteolytic enzymes to release T4 and T3 into the blood circulation. Un-
utilized mono- and di-iodotyrosines are not released into the blood but axe conserved
within the gland for further incorporation into thyroglobulin.
In blood, these hormones bind to transport proteins mainly thyroxine-binding-protein
and are distributed to the target cells in the peripheral tissues. All phases of biosynthesis
and secretion of thyroid hormones are stimulated by thyroid-secretary hormone (TSH),
which is secreted by anterior pituitary gland in response to low levels of thyroid
hormones.

Let us next review the physiological functions and metabolic effects of thyroid honnones,
in order to understand the importance of iodine in humans.

Physiologic Functions of Iodine

Thyroid hormone performs multiple functions as regulator of cell activity and growth.
The hormone has crucial metabolic roles in the foetus, and in the infant post-natally.
It promotes growth and maturation of peripheral tissues in the human embryo, the
most visible effect seen in the skeletal growth. Delayed bone development has been
seen in hormone deficient human embryos. Thyroid hormone influences neuronal cell
growth and dendrite development in the embryo. A major effect of foetal iodine
deficiency is cretinism, characterized by mental deficiency and deaf mutism.

Postnatally, linear growth, i.e. stature and bone inaturation are critically dependent on
thyroid hormone. Both are retarded when there is a deficiency of the hormone due
to low iodide intakes. The hormone plays an important role in the provision of energy
to most cells in the body; the best indicator of this is the energy available for
utilization in the basal state, i.e. the basal metabolic rate. In thyroid hormone deficiency,
the BMR is lower, slowing the overall cellular activities. Iron deficiency in children
is characteristically associated with goitre.

In the endemic iodine deficient regions of Lndia, school children have been shown to
have general IQs 10 points lower than children in non-iodine deficient areas. A high
degree of apathy has also been noled in adults living in the iodine deficient areas in
India. Even domestic animals in these areas have been reported to display apathetic
behaviour. Reduced mental function is widely prevalent in thyroid hormone deficiency
in the iodine deficient endemic areas, highlighting the key role of this hormone in
neuronal and brain development and function. Iodine deficiency is a major obstacle
to human and social development and should be prevented as a priority.
I
Soine important aspects of the metabolic influences exerted by thyroid hormones are
being highlighted in the subsequent text.

Metabolic Effects of Thyroid Hormones

Although (T,) is quantitatively predominant, (T3) is the more active form. The
mechanism of action of thyroid hormones appears to involve binding to nuclear
receptors, which, in turn, alter gene expression in pituitary, liver, heart, kidney and
most crucially, the brain cells.

Overall, thyroid hormones stimulate synthesis of enzymes, oxygen consumption and

basal metabolic rate (BMR) and thereby affect heart rate; respiratory rate, mobilization
and metabolism of carbohydrates, lipogenesis and a wide variety of other physiological
activities. They are necessary for the normal nervous system development and linear
growth. Directly or indirectly, most organs are under the influence of these substances. 343
Advance Nutrition It is probable that iodine has additional roles to that of thyroid hormones activity, e.g.
in antibiotic and anticancer activity, but these are poorly understood.
The deiodination of (T4) and (T3) takes place in extrathyroidal tissues, mainly liver.
Let us now proceed to learn about the health effects of a low iodine intake which
continues to be a serious public health problem even today despite concerted efforts
being laid down by our government to alleviate this nutritional deficiency disorder.

Deficiency
Iodine deficiency affects all populations at all stages of life, from the intrauterine
stage to old age. However, pregnant women, lactating women, women of reproductive
age, and children younger than 3 years of age are considered the most important
groups in which to diagnose and treat iodine deficiency, because iodine deficiency
occurring during foetal and neonatal growth and development leads to irreversible
damage of the brain and central nervous system and, consequently, to iireversible
mental retardation. Thus, its deficiency causes a wide spectrum of disorders. These
include:
o Mild goitre, i.e., a larger thyroid gland than normal. The mildest form of goitre
ranges from those only detectable by touch (palpation) to very large goitre that
can cause breathing problems. The enlargement of glands occurs from stimulation
of thyroid cells by TSH and without ability to increase hormones production
owing to iodine deficiency.
The most severe form is endemic cretinism, which is characterized by congenital,
severe irreversible mental and growth retardation.
Hypothyroidism, which is accompanied by low BMR, apathy, slow reflex
relaxation time with slow movements, cold intolerance and myxoedelna (ski11
and subcutaneous tissues are thickened because of accumulation of mucin and
become dry and swollen).
Collectively, these manifestations of iodine deficiency are termed 'Iodine Dejiciency
Disorders' (IDD) about which you may recall studying in the Public Nutrition Course
&EN-006) in Unit 3. .

The symptoms of IDD differ depending on the life stage at which iodine deficiency
occurs. For example, iodine deficiency in foetus has most severe consequences and
results in cretinism. There is severe mental retardation, deaf-mutism (defects of
hearing and speech), squint, disorders of stance and gait and stunted growth.
However, varying degrees of intellectual or growth retafdation are apparent when
iodine deficiency occurs in infancy or childhood and adolescence.
Apart from cretinism, hypothyroidism and goitre, other features linked to IDD are the
decreased fertility rates, increased stillbirths and spontaneous abortion rates and
increased perinatal and infant mortality.
Epidemiological studies have indicated that an ingestion of 100-200 mg of iodine daily
is sufficient to prevent deficiency except among individuals suffering from a genetic
disorder. However, excessive iodine load may develop due to continued administration
of iodine doses for a long time or phannacologicaVdietat-y reasons. The effects of
iodine overload are being discussed next.
z .

Toxicity
A wide range of iodine intakes is tolerated by most individuals, owing to the ability
of the thyroid to regulate total body iodine. This tolerance to huge doses of iodine in
healthy iodine-replete adults is the reason why WHO stated in 1994 that, "Daily
iodine intakes of up to 1 mg, i.e. 1000 pg, appear to be entirely safe". This statement,
of course, does not include neonates and young infants.
 Over 2 mg iodinelday for long periods sbould be regarded as excessive or potentially Minerals (Micro Minerals):
harmful to most people. Such high intakes are unlikely to arise from natural foods, Iron, Zinc, Copper,
Selenium, Chromium,
except for diets that are very high in seafood and/or seaweed or comprising foods Manganese, Iodine and
coiltaminated with iodine. In contrast to iodine-replete individuals, those with IDD or Pluorine
previously exposed to iodine-deficient diets inay react to sudden moderate increases
in iodine intake, such as from iodized salt. Iodine-induced thyrotoxicosis
(hyperthyroidism) and toxic modular goitre may result from excess iodine exposure
in these individuals. Hyperthyrodism is largely confined to those over 4 0 years of age
and symptoms are rapid heart rate, trembling, excessive sweating, lack of sleep, and
loss of weight and strength. Individuals who are sensitive to iodine usually have mild
+
skin symptoms.

Thus, the level of iodine in the body can be a vital biochemical indicator for assessing
the impact of a sub-optimal iodine intake and for outlining an appropiiate patient care
process. Let us find out which parameters can be helpful in the field and clinical
settings.

Assessment of Iodine Status

Iodide nutritional status is generally directed at populatioil living in areas suspected
to be iodine deficient. The assessment is based on both the physical examination and
chemical testing of individuals. It includes:
Total population count, including the number of children below 15 years of
age. It is estimated that about 10 million people are exposed to the risk of IDD
in India, they live in iodine deficient endemic areas.
0 Incidence of goitre, as established by physical examination and crelinism in the
population of the 150 million at risk stated above, 55 million are reported to have
goitre and 22 million suffer from cretinism.
The quantification of urinary iodide excretion. Urinary concentration less
than 50 mcglg of creatinine are considered at-risk. Urinary iodide less than
10 incgldl is considered deficient. While above 10 incgldl is noimal.
4 The quantification of iodide in the drinking waler. Less than 2 m c g L of water
is indicative of iodine deficient endemic area.
Determination of serum ( T 4 ) levels in various age groups. Normal levels are
4-12 mcgldl.
Detemzination of serum TSH: Values less than 1 Lo 4 micro unitslml is considered
- normal. TSH is elevaled in iodine deficiency disorders.
Detemtination of T4 and TSH: Both are used in assessing the iodine status of
the newborn in endemic areas. A new born infant with T4 less than 3 mcgldl
and TSH 50 micro unitslml or higher is conside ed to have neonatal hypo
thyroidism.
Requiremertts
The minimum amount of iodide to prevent goitre is estimated between 50 and
-.. 75 mcglday or 1 mcglkg body weight. The 1989 ICMR recoinmended RDA is
150 mcglday for adults of both sexes. Although the recommendations are the same
for both males and females, iodide needs are higher during pregnancy and lactation.
Therefore, the recommended intakes during pregnancy and lactation are 175-200
-- mcg iodine per day.

Refer lo Table 10.21 which presents the daily iodine intake recommendation by the
WHO, UNICEF and the International Council for Control of Iodine Deficiency
Disorders.

r
Advance Nutrition Table 10.21: Daily iodine intake recommendations by the World Health Organization, United
Nations Children's Fund, and International Councell for Control of Iodiilc!
Deficiency Disorders
Iodine Intake
Group Oldday) (pglkdday)
Infants and children, 0 - 59 months 90 6.0 - 30.0
Children, 6 - 12 years 120 4.0
Adolescents and adults, from 13 150 2.0
years of age through adulthood
Pregnant women 200 3.5
Lactating women 200 3.5

Source: Assessment of the iodine deficiency disorders and monitoring their- eliminution.
Geneva, World Health Organization, 2001 (WHOMHDIO1.1). '

We shall finally review the key aspects of yet another important trace element of
nutritional significance i.e., fluorine, which is very often implicated with dental health.
I
You may also have read or heard about fluorine toxicity which arises due to the
presence of fluorine in high amounts (>lppm) in drinking water. Let us get b know
more about this important aspect. I

Fluorine is potentially a toxic element. Its essentiality for humans is not established
although the role of fluoride in providing protection from dental caries in human has
been demonstrated. Fluorine (F) is a gaseous chemical element, while its ion, fluoride
(F) is composed of fluorine bound to a metal, non-metal, or an organic compound.
Examples are magnesium fluoride, hydrogen fluoride, flurohenzene fluoride. Fluoride
predominates in nature and in body, it is deposited in bones and teeth. Its incorporation
into tooth enamel markedly increases the hardness and resistance to decay.
Let us next study about the food sources of fluoride. I
Food Sources
The major source of fluoride in most diets is water, with foods providing only about
25% of total intake. These include tea and marine fish, ready-to-use infant formulas
made with fluoridated water. Other foods which significantly contribute to fluoride a

in our diet are given in Table 10.22.

I
Table 10.22: Sources of fluoride
Food Group Fluoride Content @pm)
Dairy products 0.G - 0.07
Meat, fish, poultry 0.22 - 0.92
Grain, cereal products -
0.29 0.41
Potatoes 0.08 - 0.14
Green leafy vegetables 0.10 - 0.15
Legumes 0.15 - 0.39
Root vegetables 0.09 - 0.10
Other vegetables 0.06 - 0.17
Fruits 0.06 - 0.13
Fats, oils 0.13 - 0%
Sugar -
0.21 0.35
Source: Rao GS. Dietary Intake and bi~wailability of fluoride Ann Rev. Nutr. I
Let us now see how flourhe i s metabolized in our body.
 Metabolism Minerals (Micro Minerals):
Iron, Zinc, Copper,
Soluble fluorides, even at high intake levels are allnost completely absorbed from Selenium, Chromium,
gastrointestinal tract. These include aqueous solutions of fluorides, sodium fluoride Manganese, Iodine and
(NaF) used in toothpastes, and sodium fluorosilicate used in water fluoridation. Fluorine
However, its availability from solid foods is only about 50%-80% of that absorbed
from aqueous solutions. This is because in foods, it may be bound to proteins and on
hydrolysis by enzyme proteases, may still be less available for absorption, Peak
plasma concentrations occur within 30-60 minutes of ingestion. Fluoride absorption
occurs through diffusion.

Once absorbed, the fluoride passes into the blood for distribution chiefly to the
calcified tissues. Most of the ionic fluoride enters the bone and developing teeth
where the fluoride ion replaces the hdroxyl or bicarbonate in the hydroxyapatite and
forms fluoroapatite. About half of the fluoride absorbed each day is deposited in the
skeleton or teeth within 24 hours. Nearly 99% of the fluoride in the body is in the
calcified tissues. Fluoride in the bone is in a reversible pool and can exchange for
other ions such as hydroxyl ions during the process of bone remodeling. The only
positive role clearly demonstrated for fluoride, however, is in the prevention of dental
caries. Let us learn about this important function next.

The only beneficial role demonstrated for fluoride is in reducing the prevalence and
severity of dental caries in children and adults. This is enumerated next.

Fluoride and dental caries: There are three ways in which fluoride may act to
prevent tooth decay. When fluoride is incorporated into the tooth early in life at the
time of tooth eruption, the enamel containing fluoroapatite becomes more resistant to
dissolutioll by acids. Secondly, in normal course, the enamel gets demineralized by
contact with food acids and demineralization occurs to ensure that enamel structure
is maintained. Topical application of fluoride enhances demineralization and inairltains
the integrity of the enamel. Lastly, fluoride inhibits glycolysis and then reduces acid
formation from sugars on the teetl~,helping to prevent enamel demineralization and
tooth decay. For these reasons, fluoride is considered as a beneficial element for
humans, but it is not an esseillial element. Drinking water fluoride levels of 0.7 to
1.2 mg/L is considered safe. Levels above this can cause several health risks and
should be avoided.

,In this regard, let us discuss the effects on health of fluoride toxicity.
/

Toxicity
Fluoride is a cumulative toxin. Ingestion of fluoride 1.0-1.5 mg/L for several years
may produce dentaljluorosis, i.e. browning and pitting of teeth known as mottling,
as you may recall studying in the Public Nutrition Course (MFN-006). Chronic high
level of fluoride in the range of 2-5 m g L can cause skeletal fluorosis. Crippling
skeletal fluorosis can occur where drinking water containing higher than 10 mg/L is
consumed over several. years.

The severe forms of skeletal deformity in toxic fluorosis include kyphosis (abnormal
curvature of the spine), fixed spine and other joint deformities. Hyper parathyroidism
secondary to high fluoride intake has been reported, which induces calcification of
soft tissues. You may recall that PTH is a hormone involved in calcium homeostasis,
releasing calcium from the bone into the blood when blood calcium levels tend to fall.
An abnormal increase in PTH can add calcium to the soft tissues, hardening them
in the process.
Advance Nutrition A form of severe skeletal flourosis known as "Genuvalgium" (knocked knees) has
been reported from part of India, China and African countries. The condition is
characterized by severe skeletal fluorosis and osteoporosis of the limbs. Chronic
ingestion of excess fluoride coupled with low calcium and high molybdenum intakes
appear to increase fluoride retention in the bone. While hyper-parathyrodism and
increased levels of PTH result in calcium removal from the bone, explaining the
osteoporosis of the limbs.

With this, we end our study of micro minerals. Indeed that was an exhaustive study,

Check Your Progress Exercise 6

1) Which organ of the human body constitutes maximum percentage of Iodine?
Name thyroid hormones which are absorbed unaltered.
.....................................................................................................................
.....................................................................................................................
2) What are goitrogens? Where are these found?
.....................................................................................................................
.....................................................................................................................
....................................................................................
...............................

3) What are the metabolic effects of thyroid hormones?

.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
4) Give the normal values for plasma F- and urinary F-.
.....................................................................................................................
......................................................................................................................
5) What is Fluorosis?
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................
.....................................................................................................................

1.11 LET US SUM UP

In this unit, we studied about 8 physiologically important micro minerals namely, iron,
zinc, copper, selenium, chromium, manganese, iodine and fluorine. We learn1 about
their history, food sources along with content, their physiology of metabolism inside
our body. We also focused on their vital functions, the deficiency and toxicity levels.

We also got to know about the various testsfmethods used to assess their status in
our body. Also, we learnt about their recommended level of intake of requirements
which are essential to carryout various physiological roles.
 Minerals (Micro Minerals):
10.12 GLOSSARY Iron, Zinc, Copper,
Selenium, Chromium,
Acrodermatitis Enteropathica : a genetic human disease related to an inability Manganese, Iodine and
to absorb adequate zinc froin the normal diet. Fluoiine

Alopecia : an autoimmune disease in which the immune

system mistakenly attacks the hair follicle
leading to hair fall on the scalp) loss of hair or
baldness.
Arthopathy : any disease or disorder involving a joint.

Bradykinesia : slowness of movement.

Cardiac arrhythmias : an abnormal rate of muscle contractions in the

heart.
Cardiomyopath y : a disease of the heart muscle that causes it to
lose its pumping strength.
Ceruloplasmin : a Cu-containing protein.

Chelators : compounds that bind to metal ions to fonn a

complex.
Dystonia : abnoimal muscle tone of one or more muscles.
Glucose Tolerance Factor : a compound containing chromium that aids
insulin in regulating blood sugar levels.
Goitrogens : substances that interfere .withiodide metabolism
in any way that inhibits thyroid homogenesis.
Haematocrit : proportion of the total blood volume, that is,
red blood cell; expressed as a percentage.
Haem iron : iron found in foods of plant origin.
Hypoxia : insufficient oxygen, especially as applied to
cells.
Micro minerals : minerals which comprise less than 0.01% of
the total body weight and are required in
concentration of lppm or less.
Mobiilferrin : an iron-binding protein.
Neoplasia : abnormal cell growth that may be pre-
cancerous.
Neurtopenia : decreased number of WBCs, which greatly
increase the risk of infection.
Peripheral nerves : nerves carrying impulses to and from the brain
and spinal cord.
Peripheral neuropathy : a disorder of the peripheral nerves involving
feet, hands and sometimes legs, anns and face.
It causes pain numbness, or a tingling feeling.
Rheumatoid arthritis : a crippling form of arthritis cl~aracterizedby
painful and stiff joints on both sides of the
body,
Total parental nutrition : a way to provide a liquid food mixture through
a special tube in the chest.
Transcription factors : DNA-binding proteins.
Transferrin : a glycoprotein; a iron-binding protein. 349
Advance Nutrition Ulcerative colitis : a disease that causes irritation and ulcers in
the lining of the large intestine and rectum.
Zinc fingers : a protein which looks like fingers and contains
a series of polypeptide loops resulting from
twisting and coiling of the cysteine and histidine
residues.

10.13 ANSWERS TO CHECK YOUR PROGRESS

EXERCISES
Check Your Progress Exercise 1
1) 65% of 2-4 g iron is found in association with haemoglobin.
2) Haem iron are chicken, liver, meat, fish, egg, salmon
Non-haem iron are dried apricots, soybeans, almonds, spinach, kidney beans, the
sources of lentils.

3) There are certain dietary factors which either increase or decrease iron absorption,
Factors which increase iron absorption include ascorbic acid, certain organic
acids like citric, lactic and tartaric acid, animal proteins such as meat, fish,
poultry, sugars such as fructose, sorbitol; physiological factors - pregnancy and
growth, as well as, depleted iron status and optimum gastric acidity.
On the other hand, factors which decrease iron absorptioil include increased
intestinal mobility, presence of phytates, oxalates, iron-binding pllenolic compounds
such as ferrous pyrophosphate, ferrous citrate, calcium, phosphoms, magnesium,
zinc, manganese and copper, tannic acid in coffee and tea, prolonged/excessive
use of ant-acids, achlorhydria and hypochlorhydria.

4) Our body has three unique mechanisms for maintaining iron balance, l l e s e are
storage of iron, reutilization of iron and regulation of iron absorption.

5) Iron deficiency anaemia can result from both a reduction in circulating haemoglobin
and a reduction in iron containing enzymes and myoglobin. These include: fatigue,
restlessness and impaired work performance; disturbance in thermo regulation;
impairment of certain key steps in immune response; can have adverse effects
on psychomotor and mental development in children; and increased mortality
and morbidity of mother and infant during pregnancy.

6) Iron status cab be assessed by various methods. These include measurement of

plasma ferritin concentration, serum transferrin receptors, zinc protoporphysin,
transferrin saturation and haemoglobin and haematocrit levels. Mobilferrin and
Transferrin; Serum femtin, Transferrin receptors, Erythrocyte protopoi-phyrin,
Transferrin saturation, haemoglobin and haematocrit levels.

Check Your Progress Exercise 2

1) Zinc is referred to as the most abundant intracellular trace because nearly 95%
of total body zinc is present within the cells.
2) Acrodematitis enteropathica is a genetic disease which leads to an inability to
absorb adequate zinc from diet.
3) The term zinc finger is used to denote the configuration of DNA-binding proteins
of which zinc is an important component. It comprises of a series of polypeptide
loops resulting from twisting and toiling of polypeptide loops which gives it the
impact of a finger like structure.
4) Zinc is unique among the trace elements in that it is a part of enzymes from all Minerals (i?4jcro Minerals):
six enzyme commission classes. As a component of these enzymes, it either Iron, Zinc, Copper,
Selenium, Chromium,
provides structural integrity to the enzyme or participates directly-in the reaction Manganese, Iodine and
at the catalytic site. Zinc is a component of over 200 metallo-enzymes and is Fluorine
therefore vital for many fundamental life processes.
5) Techniques of assessing Zn status are any five of the following : measurement
of zinc in plasma, RBCs and neutrophils, metallothionine concentration, urinary
and hair zinc levels, measurement of activity of zinc-dependent eilzymes.
6) The symptoms assocated with the prolonged intakes of zinc (75-300 mglday)
have been associated with impaired copper utilization, impaired immune response
and a decline of high density lipoprotein. Intakes between 25 -50 mg zinc per day
have been reported to interfere with metabolism of both iron and copper.
Check Your Progress Exercise 3
1) The organs which contain a high concentration of C u are liver, brain, heart,
bone, hair and nails.
2) The components which aid in the release of Cu in the gastrointestional tract are
gastric HC1, pepsin and some proteolytic enzymes
3) Dietary components exerting positive effect on Cu absorption include amino
acids especially histidine, organic acids such as citric, gluconic, lactic, acetic and
malic acids. While which inhibit Cu absorption include high intakes of several
nutrients such as zinc, iron, molybdenum, calcium, phosphorus and excessive
intake of antacids.
4) a) albumin and transcuperin
b) ceruloplasmin

5) Refer to Table 10.11 in section 10.5 and answer the question on your own.

6) The predisposing factors of copper deficiency are prematurity, low birth weight
and malnutrition, especially when combined with feeding practices such as cow's
milk or total parenteral nutrition.

7 ) Wilson's disease: This disease affects 1 in 30,000 in most populations. It is an

a~~tosomal recessive disease of copper storage. The defect results in impaired
biliary excretion of copper and accumulatioli of copper in the liver, brain and
cornea of eye. If the disease is not treated, copper accumulation in liver and
brain results in neurologic damage and cirrhosis.
Check Your Progress Exercise 4

1) An enzyme which constitutes selenium as its integral part is Glutathione

peroxidase (GPX).

2) The selenium content of food varies because of the variations in the selenium
content of soil where the crops are grown. Further, factors such as pH of soil,
microbial activity, rainfall etc. also determine the uptake of selenium by the plant
from the soil.

3) Phytates and heavy metals, such as mercury through chelation and precipitation
hinder selenium absorption. Vitamin C, A and E enhance absorption.

4) The three selenoenzymes have been identified with the following catalytic roles:
reduction of hydrogen peroxide and organic hydroperoxides by GPXs.
activation and inactivation of thyroid hormone by Iodothyronine deiodinases.
Advance Nutrition a NADPH-dependent reduction of oxidized thioredoxin regulation of cell growth
and inhibition of apoptosis by the enzymes thioredoxin reductases.
Serum or plasma selenium level is the test to indicate short-term changes in
dietary intake of selenium.

5) Selenium deficiency has been linked to two regional human diseases: Keshan
disease and Kashin Beck's disease. Refer to sub-section on deficiency of selenium
for details.
Check Your Progress Exercise 5

I) Insulin-dependent-diabetic patients absorb 2-4 times more chromium because

they have an impaired ability to convert inorganic form to usable form and
therefore require ligher chromium.

2) The factors that enhance Cr absorption are ascorbic acid, picolinate, methionine
and histidine.

3) During conditions of iron excess or iron overload such as iron storage diseases,
all the metal transport sites on transferrin are occupied by iron. This may explain
the high incidence of diabetes in haemochromatosis patients, which may be
induced by chromium deficiency.

4) Factors which influence Mn absorption are: absorption decreases with increasing

intake, percent absorption is higher among women as compared to men, increased
dietary iron depresses Mn absorption whereas iron deficiency increases its
absorption and high levels of dietary calcium, phosphon~sand phytate impair the
intestinal uptake of the element.

5) Antioxidant activity, carbohgydrate metabolism, integrity of cartilage and brain

development.

6) Mn is found in most organs and tissues and preferentially accumulates in the

mitochondria. There is no storage form for Mn. Bone contains substantial amount
of mineral but there is no mechanisi~lto release it and tl?us bone Mn is considered
as passive storage. It is released only as a result of normal bone turnover or in
situations of accelerating bone resorption.

7) The course and degree of Mn intoxication varies greatly but Mn toxicity has
been shown to occur in the following three phases:
a The first phase is characterized by the non-specific symptoms such as
anorexia, apathy, headache, hypersomnia, irritability and spasms.
a The next phase is characterized by expressionless face, speech disturbance,
altered gait and fine tremor.
In the third stage, there is muscular rigidity, staggering gait and fine tremor.
Check Your Progress Exercise 6
1) Thyroid gland (70-80%) constitutes maximum percentage of iodine; TJ and T4
are the hormones which are absorbed unaltared.

2) Goitrogens are substances that interfere with iodide metabolism. As a result,

there is augmentation in TSH release and subsequent thyroid gland enlargement.
These active goitrogens are released by plant enzymes from thioglucosides or
cy'nogenic glucosides found in cassava, kale, cabbage, broccoli, turnips, rapeseeds
and mustards.
3) The mechanism of action of thyroid hormones appears to involve binding to Minerals ( ~ i c r oMinerals):
nuclear receptors, which, in turn, alter gene expression in pituitary, liver, heart, , ~ r o nZinc,
, Qpper,
~elenium,~~hromium,
kidney and most crucially, brain cells. Thyroid hormones stimulate synthesis of Manganese, Iodine and
. enzymes, oxygen consuinption and basal metabolic rate (BMR) and thereby Fluorine
affect heart rate, respiratory rate, mobilization and metabolism of carbohydrates,
lipogenesis and a wide variety of other physiological activities. They are necessary
for the normal nervous system development and linear growth.

4) 0.01 -0.02 mcglml is the normal value for plasma F-

0.02-1.1 mglrnl is the normal value for urinary F-

5) Fluorosis is excessive intake of F-, early signs of which are mottling and
discolouration of the teeth. It is characterized by changes in bone, kidney and
possibly nausea, vomiting, acidosis and cardiac arrllythrnias.