Food and Nutrition MFN 004 Unit 10
Food and Nutrition MFN 004 Unit 10
Food and Nutrition MFN 004 Unit 10
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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10.3 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.
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.
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.
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$ .
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
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.
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
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.
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.
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.
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.
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%
.....................................................................................................................
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:
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:
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
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 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.
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"
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
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.
......................................................................................................................
3) Enumerate the dietary component affecting Cu absorption.
.....................................................................................................................
4) Name the various proteins which deliver copper to:
a) Liver and Kidney
.............................................................................................................
b) Other tissues
....................................................................................................................
...............................................................................................................
..
......................................................................................................)...........
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.
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.
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.
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
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.
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.
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.
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.
, 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:
+
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)
Before we proceed to study chrorniun, let us recapitulate what we have learnt so far
by answering the check your progress exercise 4.
.....................................................................................................................
.....................................................................................................................
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.
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.
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.
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.
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:
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.
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.
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.
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
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.
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.
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.
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.
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?
.....................................................................................................................
......................................................................................................................
.....................................................................................................................
.....................................................................................................................
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;
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.
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.
L
Thyroid cell arranged in follicles mound
central luinen containing colloid
Let us next review the physiological functions and metabolic effects of thyroid honnones,
in order to understand the importance of iodine in humans.
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.
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.
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
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,
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
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.
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.
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
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.
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.
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.