Review Article

Indian J Med Res 130, November 2009, pp 634-645

Iron content, bioavailability & factors affecting iron status of Indians

K. Madhavan Nair & Vasuprada Iyengar

Micronutrient Research Group, National Institute of Nutrition (ICMR), Hyderabad, India

Received April 24, 2009

Repeated surveys have shown that the magnitude of nutritional anaemia is of public health concern in
India. Though reduced intake of iron is a major aetiological factor, low intake or an imbalance in the
consumption of other haematopoietic nutrients, their utilization; increased nutrient loss and/or demand
also contribute to nutritional anaemia. In India, cereals and millets form the bulk of the dietaries and
are major sources of non-haeme iron. According to the current estimates, the intake of iron is less than
50 per cent of the recommended dietary allowance (RDA) and iron density is about 8.5 mg/1000 Kcal.
It is now well established that iron bioavailability from habitual Indian diets is low due to high phytate
and low ascorbic acid/iron ratios. These factors determine iron bioavailability and the RDA. There are
striking differences in the iron RDAs among the physiological groups, which need to be validated. The
other dietary factors affecting iron status are inadequate intake of folic acid and vitamins B12, A, C and
other vitamins of the B-complex group. Chronic low grade inflammation and infections, and malaria
also contribute significantly to iron malnutrition. Recent evidence of the interaction of hepcidin (iron
hormone) and inflammatory stimuli on iron metabolism has opened new avenues to target iron deficiency
anaemia. Food-based approaches to increase the intake of iron and other haematopoietic nutrients
through dietary diversification and provision of hygienic environment are important sustainable
strategies for correction of iron deficiency anaemia.
Key words Bioavailability - haemopoietic nutrients - intake - iron - iron status - RDA

Introduction

and proliferation in an iron-restricted environment.

The human body has therefore developed intricate but
exquisitely controlled mechanisms to absorb, transport
and store iron, thus ensuring a ready supply for cellular
growth and function, but limiting its participation in
reactions that produce free radicals and its availability
to invading pathogens. However, anaemia is widespread
in India in spite of diversity in food habits, particularly
in the consumption of cereals and such tight metabolic
regulation. The causality between poor dietary iron
density, bioavailability and high prevalence of anaemia
in our population has not been well established, as
anaemia has a multi-factorial aetiology. Albeit, iron

Iron is an essential micronutrient because it plays

a vital role in oxygen transport, oxidative metabolism,
cellular proliferation and many other physiological
processes. It is a redox metal and participates in most of
the reversible one-electron oxidation-reduction reactions
by switching between the two oxidation states, ferrous
and ferric. This redox activity of iron can produce free
radicals responsible for cell signalling processes and
iron mediated toxicity. Iron is also an essential mineral
for all known pathogens, because of which many have
developed complex mechanisms for iron acquisition
634

NAIR & IYENGAR: FACTORS AFFECTING IRON STATUS OF INDIANS

deficiency in a population results in consequences that

have serious implications and it is now recognized that
even mild-to-moderate anaemia, can lead to lowered
national productivity. Therefore it is important to find
and address the cause(s) so as to enforce measures to
reduce iron deficiency anaemia in India.
In this review, an attempt has been made to relate
cereal consumption pattern, iron density and anaemia
prevalence across the Indian sub-continent. Further, an
update on bioavailability of iron from Indian diets and
the factors that influence iron status of Indians are also
included. Finally an attempt has been made to answer
the question of how to meet the iron requirement.
Anaemia in India: iron deficiency alone?
Anaemia, defined as a condition where the
haemoglobin concentration is less than a defined
level resulting in decreased oxygen carrying capacity
of blood, is a serious public health problem in India
affecting all segments of the population. The vulnerable
groups are infants and young children, adolescent
boys and girls, women of child bearing age and
pregnant women1-4. Recent surveys conducted by the
National Nutrition Monitoring Bureau (NNMB)1 and
National Family Health Survey (NFHS)-32 show high
prevalence of anaemia. NFHS-3 has reported anaemia

635

prevalence of 56.2 per cent in women of 15-49 yr, 79.2

per cent among children aged 6-35 months, 57.9 per
cent in pregnant women and 24.3 per cent in men aged
15-49 yr. Data obtained from NNMB1, NFHS-25 and
NFHS -32 show neither a time trend nor an appreciable
decrease in anaemia prevalence (Fig. 1). Anaemia
prevalence seems to be the same in urban and rural
areas, but gender differences exist at the age of 15 yr,
with higher prevalence in females.
Anaemia in India is not restricted to iron deficiency
alone, although a few studies where the role of iron
nutrition has been specifically evaluated either by
biomarkers or responses to iron administration
indicate that iron deficiency is the predominant cause
of anaemia6-8. In pregnant females, sTfR (serum
transferrin receptor) used as a marker of tissue iron
deficiency suggested low iron stores and wide spread
deficiency4,9. Additionally, more than 40 - 45 per cent
of preschoolers present with iron biomarkers indicating
iron deficiency6,10. In an urban slum in India, 75 per cent
of the children who presented with anaemia responded
to iron administration, 22 per cent of anaemic children
also had biochemical vitamin B12 deficiency, 2.2 per
cent had a biochemical folate deficit and 3. 3 per cent
were suffering from infection10.

Fig. 1. Time trend of anaemia prevalence in Indian women.

Source: Ref. 2, 5.

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INDIAN J MED RES, november 2009

A recent study carried out by the National Institute

of Nutrition (NIN), Hyderabad in semi-urban school
children showed evidence for the existence of multiple
sub-clinical micronutrient deficiencies11. The link
between vitamin A deficiency and anaemia has been
recognized for many years12. These can potentially
influence the absorption and metabolism of iron. Also,
general undernutrition, haemoglobinopathies and
malaria also contribute to the observed high anaemia
rates13-15. Thus based on either the prevalence or impact
of iron supplementation studies there is no direct proof
to demonstrate inadequate intake of iron as the only
major aetiological factor of anaemia in India.
Dietary iron content in the aetiology of anaemia
Humans derive iron from their every day diet,
predominantly from plant foods and the rest from foods
of animal origin. Iron is found in food as either haem or
non-haem iron. Haem iron, which makes up 40 per cent
of the iron in meat, poultry, and fish, is well absorbed.
Sixty per cent of the iron in animal tissue (liver) and all
the iron in plants (fruits, vegetables, grains, nuts) is in the

form of non-haem iron and is relatively poorly absorbed.

Non-haem iron contributes about 90-95 per cent of total
daily iron in Indian diets. In western countries the intake
of haem iron from meat and meat products accounts for
bulk of the dietary iron and the US dietary reference
intakes (DRIs) are calculated on an assumption of 75 per
cent haem iron consumption16. On the contrary, haem iron
consumption is minimal in India with majority of Indians
obtaining non-haem iron from cereals, pulses, vegetables
and fruits17. Thus the Indian dietary is plagued by low iron
content and poor absorption.
Major sources of non-haem iron: Non-haem iron
in plant foods is chemically diverse, ranging from
simple iron oxides and salts to more complex organic
chelates such as hydroxyphosphates in phytoferritin.
The relative contribution of these chemical forms from
plant foods is not yet established.
The cereal consumption pattern in India is diverse
as rice, wheat, maize are consumed to varying quantities
B

Fig. 2. Food consumption patterns in India (A). Per cent contribution of iron from various food groups in Gujarat, Kerala, Karnataka and Tamil
Nadu as computed from NNMB database17 (B). Iron density of urban and rural diets from four Indian States. AP (Andhra Pradesh), WB (West
Bengal), MP (Madhya Pradesh) and Gj (Gujarat) (C). Values represent iron density of a days composite diet determined by chemical analyses.
Open bars represent urban diets and striated bars represents rural diets22.

NAIR & IYENGAR: FACTORS AFFECTING IRON STATUS OF INDIANS

(Fig. 2A). According to the recent diet survey in the

rural areas of 9 States, rice, wheat, and millets-ragi
(Elesine coracana) and sorghum (Sorghum vulgare)
are the widely consumed staples of various regions of
India17. The average daily intake of cereals and millets
ranged from 320 to 477 g as against a recommended
intake of 460 g, providing about 30-82 per cent of
total dietary non-haem iron. The intake of pulses in
the rural areas ranged from 18 to 37g, and contributes
to 5-10 per cent of dietary intake of iron while that
from green leafy vegetables is only 2-5 per cent. Iron
intake (Table I) and relative contribution of each food
stuff to total iron intake (Fig. 2B) varies most widely
among the States of Gujarat (23 mg), Kerala (12 mg),
Karnataka (12 mg), Andhra Pradesh (8 mg) and Tamil
Nadu (10 mg). In Gujarat the dietary intake of iron was
the highest, arising out of consumption of bajra (8 mg
Fe/100 g) as the major staple22. There are differences
also in the absolute amount of iron among regions,
Andhra Pradesh (AP) diets with rice as the staple have
lowest (7 mg/1000 Kcal) and Gujarat and Madhya
Pradesh (MP) diets with bajra as the staple have the
highest (16 mg/1000 Kcal) (Fig. 2C). Periodic diet
surveys have shown that there is an upward trend in the
iron density of Indian diets but the intake of energy has
reduced over the years, implying cereal intake does not
contribute to increased iron density (Fig. 3A, B). There
is a good agreement in the magnitude of differences in
the iron content across diets from different regions.
Iron intake and anaemia prevalence: Inter-state
differences in iron intake and anaemia prevalence
provide more insight into the complex relationship
between these two. In Orissa, cereal intake is high
with high anaemia prevalence while Kerala has the
lowest anaemia prevalence in spite of lower cereal
A

637

Table I. Iron density, intake and anaemia prevalence in rural males

and females
Region

Iron
Males
density
Iron
Anaemia
(mg/1000 intake*
prevaKcal)
(mg/d)
lence**
(%)
Kerala
7.1
13.7
8
8.2
12.1
16.5
Tamil Nadu
Karnataka
7.7
15.9
19.1
4.3
9.4
23.3
Andhra
Pradesh
Maharashtra
10.4
18.8
16.8
Gujarat
15.6
28.2
12
9.0
17.5
25.6
Madhya
Pradesh
8.5
17.4
33.9
Orissa
West Bengal
7.1
16.2
32.3
India
8.5
16.8
24.2

Females
Iron
intake*
(mg/d)
11.0
9.6
13.0
8.4

Anaemia
prevalence**
(%)
32.8
53.2
51.5
62.9

15.3
23.0
16.9

48.4
55.3
56

14.3
13.7
13.6

61.2
63.2
55.3

Iron intake among males/females 16 yr and above, **Prevalence of

anaemia in males / females of 15-49 yr
Source: Ref. 2, 17.
*

intake (Table I). The NNMB survey17 revealed that

the intake of dietary iron is grossly inadequate in most
of the States, meeting less than 50 per cent of RDA
of males (28 mg) or females (30 mg). This deficit is
highest in AP at 72 per cent and the lowest at 23 per
cent in Gujarat, in adult females. These differences in
iron intake are attributable to regional differences in
the consumption of staple foods, especially rice and
millets, as millets and wheat have relatively greater
iron content when compared to rice. Although there
is a marked regional difference in anaemia prevalence
among these States, it is surprising to note that the
extent of anaemia prevalence is not correlated with the
current intake of iron, with Gujarat showing 55 per cent
anaemia prevalence upon 23 mg/day iron intake and
B

Fig. 3. Time trends in (A) iron and (B) energy consumption.

(A) Source: Ref. 17, 58, 59; (B) Source: Ref. 60.

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INDIAN J MED RES, november 2009

Kerala showing only 33 per cent anaemia prevalence

upon 11 mg/day iron intake (Table I).
A similar scenario of no correlation emerges with
iron density. The data also suggest that the average iron
density of an Indian diet is not more than 8.5 mg/1000
Kcal, with the lowest density of 4.3 and the highest of
15.6 mg/1000 Kcal in the states of AP and Gujarat,
respectively (Table I, Fig. 2C). Despite a lower iron
density of 7.1 mg/1000Kcal only, anaemia prevalence
in Kerala is distinctly lower (8% adult males, 32.8%
adult females) compared to other States. Rice is the
major staple in south Indian States but this cannot
account for the observed differences as the other States
of AP and Tamil Nadu (TN) have anaemia prevalence
above 50 per cent, which is comparable to Gujarat
where wheat and millets are the main staples17.
Bioavailability of non-haem iron
Gastric pH and solubility: It appears that neither higher
density nor intake of iron can adequately account
for the observed inter-state differences in anaemia
prevalence, necessitating identification of other factors.
The majority of dietary non-haem iron enters the GI
tract in the ferric form, which is insoluble and thus
inaccessible. This needs to be converted to the ferrous
form for absorption at the enterocyte. It is well known
that acidic pH is essential and critical for iron to be
in the soluble ferrous form which in turn determines
its subsequent intestinal bioaccessibility. Achlorhydria
has been recognized as an associated feature of iron
deficiency anaemia for many years. It is, however, not
known whether the extent of acid secretion in Indians is
associable with the high prevalence of iron deficiency
anaemia. Evidence for enhanced iron absorption in
the presence of normal gastric acidity compared to
cases of achlorhydria presents an interesting option18.
The gastric acidity measured by different groups in
Delhi, Vellore and Mumbai was compared with that
reported from western countries (Table II)19. The basal
acid output in normal Indians is significantly lower
(~ pH 3.4) than that in western subjects (pH 2.5)19. This
difference may compromise non-haem iron solubility
and accessibility in Indians and can therefore be
considered in the aetiology of high anaemia prevalence.
It is possible that the predominantly vegetarian dietary
habit of Indians has led to such an adaptation of
decreased acid secretion, as it is known that the amino
acid composition of protein ingested plays an important
role in determining acid secretion. It would also be
important to correlate Helicobacter pylori infection in

Table II. Comparison of basal acid output in different populations

Basal acid output*
Control
Delhi
Present
2.99
Vellore
3.18
(Ganguli et al, 1962)
Bombay
3.91
(Vakil and Mulekar, 1963)
Edinburgh
2.5
(Bruce et al, 1959)
Glasgow
2.2
(Kay, 1953)
Philadelphia
(Marks and Shay, cited by
2.7
Marks, 1961)
*
Mean values expressed in mEq. HCl per hour
Source: Ref. 19.

Duodenal ulcer
5.46
7.07
8.30
6.0
6.8
5.4

Indians on gastric acid secretion and iron absorption,

as these have been shown to influence iron absorption
in Bangladeshi children20.
Food matrix: It is very well known that the food matrix
can influence iron solubility in the gastric milieu before
it reaches the absorptive surface of the intestinal mucosa
as numerous dietary factors determine the oxidation
state of iron, especially from a typical Indian diet. Thus
the possibility of food matrix effect on non-haem iron
solubility is important. In an attempt to evaluate the
impact of food matrix, in vitro non-haem iron solubility
from typical Indian composite diets of Andhra Pradesh,
West Bengal, Madhya Pradesh and Gujarat (based on
NNMB diet survey, 2001)21 was carried out. Role of
various dietary components in modulating solubility of
iron was studied and iron content, iron density, phytate
and phytate density showed significant correlation22.
Iron and phytate content and density were negatively
correlated to iron availability. In vitro solubility of iron
from these meals decreased from 7.9 to 1.52 per cent
as phytate content increased from 0.3-1.3 g/d (Fig. 4A).
Further, diets with rice (low in iron and phytates) as
staple had better availability compared to diets with Bajra
(high in iron, phytate) as staple22. Thus adequate iron
availability can be achieved principally by minimizing
inhibitors (phytates, tannins) and enhancing promoters
(ascorbic acid, meat/fish).
Though the essentiality of ascorbic acid for efficient
absorption of dietary non-haem iron is generally
accepted, the intake is very low in Indian dietaries. For
example, intake of ascorbic acid has been shown to
be about 40 mg in all the States17 which is considered

NAIR & IYENGAR: FACTORS AFFECTING IRON STATUS OF INDIANS

639

A
B

Fig. 4. Relationship between iron availability (A) and phytate density (B) of Indian diets. Phytate and iron content of a days composite diet
was determined by chemical analyses and correlated with in vitro iron availability. Source: Ref. 22.

sufficient for enhancing iron uptake. It should, however,

be borne in mind that the ascorbic content derived from
the Nutritive Value of Indian Foods23 is for uncooked
food, the content of which, upon cooking may be
negligible due to the thermal instability of ascorbic acid.
Thus, only observable difference in diet patterns among
the above mentioned four states is the increased intake
of fish, nuts and oilseeds, in Kerala (Fig. 2B), which
could have contributed to increased solubility of iron
resulting in the lower anaemia prevalence. Inadequate
consumption of above these food groups can lead to
reduced intake of other haematopoietic nutrients, vitamin
A, beta carotene (nuts and oil seeds), riboflavin and folic
acid, further accentuating anaemia.
Iron density of plant foods can be increased either by
chemical fortification or by biofortification. In animals
and plant tissues, the major iron storage protein is ferritin.
Therefore, targeting ferritin iron in staple crops through
conventional plant breeding technique(s), known as
biofortification, is an emerging strategy. However, the
bioavailability of iron content so enhanced is as yet not
known and the issue of ferritin iron bioavailability is still
very controversial. Studies have shown that ferritin iron
from plant sources are absorbed to an extent similar to
that of ferrous sulphate24-26. We tested bioavailability of
iron from pea ferritin using the Caco-2 cell line, with
ferrous sulphate as positive control24. Iron bioavailability
from pea ferritin was modulated by the concomitant
presence of dietary factors such as phytic and ascorbic
acid, and gastric pH, suggesting it was similar in
solubility and bioaccessibility to ferrous sulphate

(Fig. 5). Therefore, it is essential that all strategies be

aimed at simultaneously improving endogenous nonhaem iron absorption enhancers in plant foods, rather
than just increasing iron content or density.
Recommended dietary allowance of iron
Bioavailability of non-haem iron from commonly
consumed plant based diets in India is estimated to be
low due an abundance of phytic acid and polyphenols
coupled with lowered consumption of meat or ascorbic
acid. It is thus believed that plant-food based diet

Fig. 5. Ferritin response as a surrogate marker of pea ferritin iron

bioavailability in Caco-2 cells. Bars that do not share a common
superscript are significantly different at P<0.05. Source: Ref. 24.

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INDIAN J MED RES, november 2009

(vegan diet) might predispose to developing iron

deficiency anaemia. However, surveys in vegans have
found that iron deficiency anaemia is no more common
in them than among the general population, although
vegans tend to have lower iron stores27,28. The reason
for the adequate iron status of many vegans may be
that commonly eaten vegan foods are high in iron.
In fact, the iron density (mg/1000 Kcal) of vegan
foods is superior to animal-derived foods and vegan
diets are high in vitamin C27,28. Thus commonly eaten
combinations, such as pulses and citrus fruits result in
enhanced iron absorption and it is easy to obtain iron on
a vegan diet that would meet the RDA for iron. Studies
have shown that absorption rates can rise significantly
from less than 5 per cent to more than 15 per cent if
animal products and vitamin C are amply provided
simultaneously and that bioavailability of meals with
a similar content of iron, energy, protein, fat, etc., can
vary more than ten-fold27,28. Therefore to translate
physiological iron requirements into recommendations
for dietary iron intakes, the bioavailability of iron (i.e.,
its absorption for utilization by the body) from different
diets needs to be calculated.
Iron bioavailability of the Indian diet: Iron absorption
from various Indian diets carried out by chemical
balance studies reported iron absorption to vary from
7-20 per cent (median-10%)29. In 1983, detailed iron
absorption studies from habitual Indian diets of single
staple (wheat, rice, ragi or sorghum) were performed in
adult men by the extrinsic tag technique30. Mean iron
absorption from single meal ranged from 0.8 to 4.5 per
Table III. Current recommended dietary allowances of iron for
Indians
Age
(yr)

Iron
(mg/d)

Mean Iron mg/

Energy 1000
(Kcal/d) Kcal
Children
1-3
12 108/Kg
8.8
4-6
18 98/Kg
9.8
7-9
26
1,240
21.0
Boy
10-12
34
1,690
21.0
Girl
10-12
19
1,950
9.7
Boy
13-15
41
2,190
18.7
Girl
13-15
28
1,970
14.2
Boy
16-18
50
2,450
20.4
Girl
16-18
30
2,060
14.6
Men
>18
28
3,030
9.2
Women
>18
30
2,340
12.8
38
2,640
14.4
Pregnant women
30
2,820
10.6
Lactating women
Computed based on absorption rates of 3 per cent for males, 5 per
cent for females
Source: Ref. 34

cent depending on the type of staple used. The extent

of absorption was the lowest (0.8-0.9%) with milletbased diets, highest (4-5%) with rice-based diets and
intermediate (1.7-1.9%) with wheat-based diets. Apte
and Iyengar31 demonstrated that during pregnancy iron
absorption increased from a mean of 7 to 30 and further
to 33 per cent at gestational weeks 8-16, 27-32 and 3639, respectively, using the chemical balance method.
The absorption of iron was better among those with
low per cent transferrin saturation than in women with
high per cent transferrin saturation. As much as 58 per
cent of 30 mg of dietary iron ingested per day could
be absorbed by an iron deficient full term pregnant
woman. However, the magnitude of the difference in
iron absorption between non pregnant and pregnant
Indian women is striking even when the same balance
method is used.
It is important to have an accurate measure of iron
content as well as its bioavailability from the Indian diet
to suggest RDA. A comparison between the extrinsic
tag and the chemical balance methods indicated that
the latter overestimated iron absorption32. The iron
content of whole days diet ranged from 29-42 mg,
providing high iron/energy ratios (8.2-13 mg/1000
K cal). However, it is known that about 1/3rd of the total
iron in cereals and pulses is due to contamination, and
in vitro availability studies carried out on contaminant
iron revealed that it was essentially unabsorbable33.
A uniform absorption value of iron of 3 per cent for
Indian men and 5 per cent for indian women from a
mixed cereal-pulse vegetarian diet was considered for
deriving the iron RDA30,34. RDA of iron (Table III)34
suggested earlier now appear to be unrealistic for the
following reasons:
(i) The fact that the diets should provide an average of
14.2 mg of iron/1,000 Kcal (range 8.8-21) with lowest
iron density recommended for children 1-6 yr and adult
males and the highest for 7-18 yr boys.

Fig. 6. Comparison of Indian and United States RDA for iron in the
different physiological groups. Source: Ref. 16, 34.

NAIR & IYENGAR: FACTORS AFFECTING IRON STATUS OF INDIANS

641

Table IV. Dietary iron absorption (%) from habitual Indian diets in
different physiological groups

Table V. Recommended intakes for iron from meals with

bioavailability 5-10 per cent

Physiological
Rice based Mixed cereal Wheat/millet
groups
diet
diet
diet
Children
5
3
2
5
3
2
Adolescent male
8.3
5
3.3
Adolescent female
5
3
2
Adult male
8
5
3.3
Adult female
Pregnancy
13.3
8
5.3
5
3
2
Post menopausal
10
6
4
Anaemic male
16.7
10
6.7
Anaemic female
7.3
4.5*
3**
Adult female
Anaemic female
17.5
10.2*
7**
*
60 per cent of rice based diet; **40 per cent of rice based diet
Source: Ref. 34, 36

Age (yr)
1-6
7-9
Males 10-18

(ii) Even if an iron density of 10.8 mg/1,000 Kcal is

assumed for all socio-economic groups and age/sex
categories, very few Indians would satisfy RDAs
for iron and energy with the present patterns of food
consumption.
These current considerations make it essentially
impossible for the Indian population to meet the iron
requirements by normal diet alone.
A comparison of Indian and US iron RDA (Fig. 6)
reveals that the US recommendations are 2-3 times
lower than the Indian RDA. This difference is due to
the higher bioavailability of iron in the US diet mainly
attributable to increased ascorbic acid content and haem
iron consumption16,34. This magnitude of difference in
RDA in itself is cause for concern as physiological
requirements for the different age/sex categories do
not vary to this extent across populations. This implies
that enhancing bioavailability rather than density or
content is of paramount importance for addressing iron
deficiency anaemia in India.
Realistic estimate of Indian iron RDA: The iron density of
Indian diet is around 8.5 mg/1000 Kcal based on diet survey
records and is around 9 mg/1000 kcal based on chemical
analysis22,35 which is lower than previously estimated (14.2
mg/ 1000 Kcal). A more recent iron absorption study was
carried out using state-of-the-art stable isotopes in normal
and iron deficient women consuming a single rice-based
meal containing a total of 4.3 mg iron36. The mean
fractional absorption in iron-deficient subjects was 17.5
and 7.3 per cent in normal women, which is greater than
absorption values (5%) used earlier for calculating iron
RDA of for adult women. Considering the fact that iron
absorption is inversely related to body iron stores and that

Females 10-18
Males 19+

RDA mg/day
6**
9**
19 (10-14 yr)*
20 (15-18 yr)*
17 (10-14 yr)**
18 (15-18 yr)**
17*

19-50 Adult female

16**
Pregnancy
It is recommended that iron supplements of
100 mg iron be given to all pregnant women
during the second half of pregnancy are
adequate. In anemic women higher doses are
usually required.
Lactation
15
Iron absorption can be significantly enhanced when each meal
contains a minimum of 25 mg of vitamin C, assuming three meals
per day. This is especially true if there are iron absorption inhibitors
in the diet such as phytate or tannins; *5 per cent absorption; **10
per cent absorption
Source: Ref. 34

Indians have reduced iron stores compared to their peers

in developed world, a realistic estimate of iron absorption
would be 5 per cent for adult male and 10 per cent for
adult female (Table IV). These figures are in agreement
with the recommendations of WHO/FAO, which for
didactic reasons, lists three bio-availability levels of 5, 10,
and 15 per cent37. According to these recommendations,
for developing countries, it may be realistic to use figures
of 5 and 10 per cent and in populations consuming more
Western-type diets, two levels would be adequate - 12 and
15 per cent - mainly depending on meat intake. When the
bioavailability of iron decreases to 10 per cent, mean iron
stores are reduced to about 25 mg and about 40-50 per cent
of women consuming this diet would have no iron stores.
Those consuming diets with an iron bioavailability of
5 per cent have no iron stores and they are iron deficient.
Based on the above considerations the RDA of iron is
derived (Table V).
Lifecycle approach: Iron requirements are least in
adult men and post-menopausal women and highest
in the second and third trimesters of pregnancy and in
the rapidly growing infant between 6 and 18 months
of age (Fig. 7). Many studies have established the
relationship between maternal iron status, foetal iron
stores and birth weight. Iyengar and Apte38 showed
that foetal body weight is directly correlated to total
iron, reflecting the essentiality of iron during foetal

INDIAN J MED RES, november 2009

Absorbable iron (mg/1000 Kcal)

642

Fig. 7. Iron requirements in different physiological groups. Computed

using daily iron and net energy requirements. Source: Ref. 34.

development. The next high risk period for nutritional

iron deficiency is the adolescent growth spurt and the
onset of menstruation in girls. The needs of women of
childbearing age are much higher than those of men,
but quite variable because of the wide range in monthly
menstrual blood loss, and may need to absorb as much
as 2.5 mg each day to replenish losses. In tune with
these physiological needs, the government has recently
reviewed the NNACP (National Nutritional Anaemia
Control Programme) to include all the vulnerable groups,
known as the lifecycle approach39. This approach
covers all physiological groups except adolescent boys
and adult men. The amount of dietary iron absorbed
is predominantly determined by physiological need
which increases when body stores are depleted and
decreases as iron stores are replenished.
Other determining factors
Although it is established that the major cause of
anaemia in India is nutritional iron deficiency, it is
indeed difficult to prioritize cause(s) when there are
confounding factors such as multiple micronutrient
deficiencies and widespread low grade inflammation.
However, as explained earlier, the inter-State differences
in the anaemia prevalence cannot be explained based on
the iron intake or density or bioavailability alone. The
other factors that will have a profound influence in the
aetiology of iron deficiency include (i) simultaneous
presence of other micronutrient deficiencies, especially
that of haematopoietic nutrients (vitamin A, B12, folic
acid and riboflavin), and (ii) acute and chronic infections
such as malaria, tuberculosis, and HIV/AIDS.
Haematopoietic micronutrients: Ascorbic acid is
known to improve the absorption of non-haem iron
by reducing ferric iron to ferrous iron thus increasing

its solubility. Vitamin C status is often marginal, as

major dietary sources are seasonal vegetables and fruits.
Folate and vitamin B12 are necessary for erythropoiesis
and the synthesis of DNA. The intakes of green leafy
vegetables, which are major sources of folate, and
animal products, which are main source of vitamin B12,
are meagre in India. Inadequacy in riboflavin intake21
also reduces absorption and utilization of iron. Vitamin
B6 is required for haem synthesis and therefore for
erythropoiesis. Recent studies11,17,40 have indicated that
there are other deficiencies that are currently widespread
but not recognized. For example, dietary intake surveys
show that intake of all the key micronutrients is low21.
Sub-clinical deficiencies of riboflavin, pyridoxine and
folic acid in pregnant women and children have been
reported40. A study carried out in apparently normal
healthy children also revealed high prevalence of
sub-clinical folate, vitamins B6, B2, C, B12, D and B1
deficiencies11.
Folate nutrition in Indians: Folate, as methyl/methylene
tetrahydrafolate (MTHF), acts as a coenzyme in
several single carbon transfers required for the
biosynthesis of purine and pyrimidines in nucleic acid
synthesis. Deficiency of this vitamin decreases several
biochemical functions. There are no detailed studies on
folate nutritional status in the Indian population, but
folate deficiency in the population is known41. Poor
folate content of human foetal liver was reported with
the mean total liver folate showing an increase from 95
to 262 g depending on the age (<28 to 37-40 wk) of
the foetus42. Studies conducted in pregnant women also
suggested poor folate status based on RBC folate levels
and deficiency ranged from 40.5-53.3 per cent during
different gestational periods43,44. Supplementation of
folic acid was shown to increase the RBC folate, and
in women who did not receive folic acid supplements,
the levels decreased from 329 129 nmol/l at term to
256 118 nmol/l postpartum45. Significantly higher
levels of RBC folate were observed only with 200 and
300 g of folic acid supplementation; the increments
were 91 and 195 nmol/l respectively. A subsequent
study with 500 g folic acid given with 60 mg iron
showed a reduction in the per cent of small for date
births (<2.5 kg) from 30 to 16 per cent43 and RBC
folate levels were higher in infants born to mothers
who received 300 g of folic acid than those born to
the control group. The birth weights of infants born to
mothers who had received either 200 or 500 g folic
acid daily were higher than those born to mothers who
had not received any supplements46. These studies

NAIR & IYENGAR: FACTORS AFFECTING IRON STATUS OF INDIANS

clearly indicate folate deficiency in the population,

especially in the vulnerable groups.
Vitamin B12 nutrition in Indians: There are not many
studies that have specifically addressed vitamin B12
nutrition in Indians and there is no cut-off level for its
deficiency. The current cut-off in the western countries
is 200 pg/ml. However, the available data suggest that
prevalence of B12 deficiency in children is 44 per cent11.
Iron metabolism in inflammation
Anaemia is also a consequence of a synergy of
inflammation and insufficient bioavailable dietary
iron and other haematinic nutrients. It is now widely
recognized that infection is a much more important
cause of anaemia than previously thought. Over and
above the deficit in the intake of these haematopoietic
nutrients, disease processes also reduce appetite,
resulting in further iron deficit47. With the onset of
the inflammatory response, the plasma concentrations
of several nutrients, including serum iron, decrease
drastically. In addition serum ferritin concentration was
shown to parallel the rapid rise in C reactive protein
(CRP), both as part of the acute phase response.
Iron metabolism, infection and inflammation are
inextricably linked. Iron deficiency per se has been
shown to decrease both cell-mediated immune response
and bactericidal activity of leukocytes in children48. On
the other hand, iron status is compromised in infection.
The influence of malaria, mild and severe respiratory
infections in young children on biomarkers of iron
status has been studied and a significant decrease in
haemoglobin was seen in children with varying degree
of malaria while no significant changes were observed
during upper respiratory tract infections (URTI) and
pneumonia. Mean serum transferrin receptor levels
changed in pneumonia affected children but not in
children with URTI49,50. These results suggest that mild
infection may not cause any significant disturbance
in Hb or transferrin receptor, but this is not true for
aggressive infections. In children with meagre body iron
stores, infection tends to aggravate anaemia by blocking
iron utilization. It is hypothesised that upon infection,
iron is sequestered in the macrophages and hepatocytes
and iron absorption decreases, thus limiting iron to the
invading pathogen. This also results in decreased plasma
iron levels, which if maintained, leads to iron restricted
erythropoiesis and ultimately frank anaemia.
The anaemia of infection has recently been shown to
be the consequence of induction of hepcidin expression,

643

brought on by the action of the inflammatory cytokine

IL-6. Hepcidin is a 25 amino acid hepatocyte-derived
peptide that can be increased to up to 100-fold during
infections and inflammation causing a decrease in serum
iron levels51. Urinary or serum hepcidin concentrations
are widely altered in anaemia of chronic infection, iron
overload, iron deficiency and haemochromatosis52.
Hepcidin controls plasma iron concentration and
tissue distribution of iron by inhibiting intestinal and
macrophage iron efflux. Iron per se has also been
shown to modulate hepcidin levels51. Thus hepcidin is
now considered as the iron hormone.
Iron and oxidative stress
Multiple micronutrient deficiencies co-exist with
anaemia in India. Many of these micronutrients, in
addition to their role in the aetiology of anaemia, are
pro- or anti-oxidant. Ascorbic acid in the presence of
iron is a pro-oxidant whereas alpha tocopherol is an
antioxidant that can quench OH. Optimal concentration
of glutathione peroxidase, a key antioxidant enzyme
which also protects haemoglobin against oxidation in
erythrocyte, requires selenium. However, it is difficult to
assess the extent of deficiencies of these micronutrients,
their contribution to iron mediated oxidative stress
in the vulnerable segments of the population where
iron supplementation is practiced53. It is essential to
condition the system with these micronutrients to
achieve optimum impact of the lifecycle approach
of iron deficiency control programme. These will
not only reduce the anaemia prevalence but also
reduce the oxidative stress associated with excess
iron supplementation. In support of this, we have
shown that preconditioning of iron deficient rats with
alpha tocopherol and ascorbic acid protected against
iron mediated oxidative damage54-56. This raises the
question of whether iron deficient pregnant women
are more susceptible to oxidative stress resulting from
excess iron absorption, particularly when given daily
pharmacological doses of iron53. The other strategies
to control deleterious effects have been previously
reviewed57.
Conclusions
Anaemia in India is multifactorial and low iron
bioavailability is a major aetiological factor, given the
current iron density of 8.5 mg/1000 Kcal. Inter-state
differences in anaemia prevalence are not correlated
either with iron intake or density. Intake of fish, fruits,
nuts and oilseeds seems to have contributed to lower
anaemia prevalence in Kerala. Decreased gastric acid

644

INDIAN J MED RES, november 2009

production, food matrix interactions, lack of other

haemopoietic nutrients, low grade inflammation
and oxidative stress are factors that contribute to
iron dyshomeostasis and need to be addressed. Low
absorption reported from mixed-cereal diet is the basis
for the current high RDAs and needs to be verified.
Recent stable isotope studies have shown absorption
rate of 10 per cent in adult females, thus reducing the
RDA to 16 mg as against 30 mg. Thus the RDAs for
the other groups have to be re-established. A holistic
approach that can simultaneously address all these
issues is the lifecycle approach to anaemia correction.
A number of potential dietary sources that contain high
quantities of ascorbic acid, animal products and iron
absorption enhancers need to be urgently promoted
including many leafy vegetables and legumes. This
is possible if there is accessibility, availability and
affordability to diversify food to enhance absorbability
of iron in the general population. For the vulnerable
groups food fortification and food supplementation
are important alternatives that complement food-based
approaches to satisfy the iron needs.
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Reprint requests: Dr K. Madhavan Nair, Scientist E, Micronutrient Research Group, National Institute of Nutrition (ICMR)

Jamai Osmania, Hyderabad 500 007, India

e-mail: nairthayil@hotmail.com