Expert Review of Hematology

ISSN: 1747-4086 (Print) 1747-4094 (Online) Journal homepage: http://www.tandfonline.com/loi/ierr20

Pica as a manifestation of iron deficiency

Caterina Borgna-Pignatti & Sara Zanella

To cite this article: Caterina Borgna-Pignatti & Sara Zanella (2016) Pica as a manifestation of iron
deficiency, Expert Review of Hematology, 9:11, 1075-1080, DOI: 10.1080/17474086.2016.1245136

To link to this article: https://doi.org/10.1080/17474086.2016.1245136

Accepted author version posted online: 04

Oct 2016.
Published online: 19 Oct 2016.

Submit your article to this journal

Article views: 272

View Crossmark data

Citing articles: 5 View citing articles

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=ierr20
EXPERT REVIEW OF HEMATOLOGY, 2016
VOL. 9, NO. 11, 1075–1080
http://dx.doi.org/10.1080/17474086.2016.1245136

REVIEW

Pica as a manifestation of iron deficiency

Caterina Borgna-Pignatti and Sara Zanella
Department of Medical Sciences, Section of Pediatrics, University of Ferrara, Ferrara, Italy

ABSTRACT ARTICLE HISTORY

Introduction: Pica is the compulsive eating of non-nutritive substances. It is often associated with iron Received 28 July 2016
deficiency but its pathophysiology is unknown. Accepted 3 October 2016
Published online 19 October
Areas covered: We searched the literature using the keywords listed below. Our aim was to describe 2016
the phenomenon in its various aspects, to touch briefly on the historical and cultural background, and
to examine in more detail the studies that tried to analyze the relative roles of iron deficiency and pica. KEYWORDS
Expert commentary: Pica is an intriguing symptom known for centuries. Pregnant women and Geophagy; iron deficiency;
preadolescents are at the highest risk of pica. Iron absorption is reduced in the presence of non- pagophagia; pica
nutritive substances. Iron therapy usually cures the pica behavior. There are different forms of pica, one
caused directly by iron deficiency probably due to the lack of iron in some areas of the brain and one
more culturally driven and including mostly geophagy.

1. Introduction to be common in the USA, affecting 25% of iron-deficient

patients [10], geophagy is probably more common in the
The Latin word pica indicates a bird, the magpie, that is
rest of the world. Pica has been reported from many coun-
supposed to eat indiscriminately whatever it finds. In the
tries; it is an accepted habit in some cultures, especially in
medical language, the term refers to the compulsive eating
Africa, and is present also in nonhuman primates and other
of nonedible substances for more than 1 month [1]. The
animals. A literature review indicated that pregnant women
practice has been known since antiquity and Hippocrates
and preadolescents are those who consume clay most fre-
documented it more than 2000-years ago, considering it a
quently. Surprisingly enough, an entire industry has origi-
‘corruption of the blood’ [2]. It is of great historical interest
nated from geophagy, involving excavators, traders, and
that Cornelius Celsus [3] wrote in 40 AD that those who have a
vendors. Young et al. [5] published a detailed and fascinating
bad color labor under a malacia (the craving for nonfood
review of reports on geophagy written by anthropologists,
substances). Livingstone [4] mistranslated the Swahili term
geographers, nutritionists, and medical doctors creating a
for anemia with ‘disease of earth eating,’ and in American
‘pica literature database.’ In the attempt to understand the
plantations the pallor of slaves was attributed to earth eating
physiological basis for the craving, the authors formulated
(all the historical citations are taken from Young et al. [5])
two adaptive and one nonadaptive hypothesis. The adaptive
The name of the habit differs according to the substance
ones include (1) nutrient deficiency according to which cal-
eaten. There are many nonfoods that can be introduced:
cium, sodium, zinc, and iron are ingested to compensate for
geophagy is the intentional consumption of earth, pagopha-
their lack and (2) protection from enterotoxin or parasites by
gia the eating of at least a tray of ice daily for 2 months or of
reducing the permeability of the gut wall or binding directly
ice chips [6], rhizophagy the eating of uncooked rice, amy-
to toxins. According to the third, nonadaptive hypothesis,
lophagy describes eating starch and uncooked pasta. Many
there would be no benefit from geophagy which, instead,
other unusual types of pica have been reported, including
could be an epiphenomenon of neurological problems, pos-
heads of burnt matches (cautopyreiophagia), cigarettes and
sibly caused by nutrient deficiencies. Collateral effects of
cigarette ashes, paper, cardboard, mothballs, egg shells,
pica, in addition to various kinds of poisoning, include
coins, vinyl gloves, baking powder, and others. Smooth clay
abdominal problems ranging from discomfort and pain to
is the kind of earth eaten more often, while gritty pieces of
intestinal occlusion requiring surgery [11], tooth damage,
earth are usually avoided. Sponge and rubber foam, and
and electrolyte disturbances. The eating of hair can lead to
even stones (lithophagy) have been reported as nonfood
the formation of trichobezoars [12]. Infestation with hel-
substances craved by iron-deficient celiac children [7,8]. The
minths was found to be more common in geophagous
introduction of more than one substance is called polypica.
than in nongeophagous Zambian children [13]. Geophagic
A subtype of pica is food pica that consists of compulsively
pregnant women from South Africa were reported to have
eating one particular food, especially if crunchy, such as
high levels of blood lead, which can represent a risk for the
carrots, cabbage, turnips, etc. [9]. While pagophagia appears
developing fetus [14]. Lead poisoning has been common in

CONTACT Caterina Borgna-Pignatti c.borgna@unife.it Department of Medical Sciences, Section of Pediatrics, University of Ferrara, Via A.Moro 8 44124,
Ferrara, Italy
© 2016 Informa UK Limited, trading as Taylor & Francis Group
1076 C. BORGNA-PIGNATTI AND S. ZANELLA
nutritionally iron-deficient toddlers living in older houses
who ingested the flaking paint. As much as 40% lead by
weight is present in dried paint used before World War II and
is still present in millions of dwellings inhabited by under-
privileged people in the USA [15].
2. Pica and iron deficiency
There are many reports in the literature, both clinical cases
and case series, on the association between the two condi-
tions. The reported frequency in iron-deficient patients is
highly variable, reaching in a study 55% [10]. A recent research
identified pica in 11% of iron deficient, compared with 4% of
iron replete, American blood donors [16]. A metanalysis of 83
studies including 6,407 individuals with pica and 10,277 con-
trols was recently reported [17]. Pica was associated with 2.35
times greater odds of anemia, and lower Zn concentration.
More iron-deficient women than men are affected by pica.
More recently, pica has been observed also among patients
who had undergone Roux-en-Y gastric bypass who are fre-
quently affected by iron deficiency because of reduced iron
absorption and decreased iron intake. In fact, acid secretion is
nearly absent in the remaining small gastric pouch and both
heme and nonheme iron depend on the acidic environment of
the stomach for efficient absorption [18–20]. Patients do not
usually volunteer the information, either because they under-
rate its importance, or out of shame for what might be con-
sidered a weakness or a vice. On the other hand, physicians do
not often inquire about pica, despite the potential harm that it
may cause. Iron treatment stops the craving for nonnutrients
in the majority of reports, but not all. In the above-mentioned
study of blood donors [16], those given iron reported a
marked reduction in the desire to eat the nonnutritive sub-
stance (mostly ice) by days 5–8 of therapy, with disappearance
of the symptoms by days 10–14. Auerbach and Adamson [21]
have reported the near instantaneous elimination of pagopha-
gia during intravenous infusion of iron. In 16 of 17 iron-
deficient French teenagers from the island of La Réunion
who ingested large amounts of raw rice and ice cubes, treat-
ment with iron cured pica within a few weeks [22]. In a study,
47 children with iron-deficiency anemia and pica were com-
pared with iron-deficient children without pica, and with non-
anemic children. The results demonstrated significantly lower
levels of selenium and zinc and significantly higher oxidative
stress index in the iron-deficient pica group as compared with
both control groups [23].
3. Pica and pregnancy
Pica is frequent in pregnancy, and in many countries it is
considered a sign of beginning gestation. Horner et al. [24]
reviewing the pica practices of pregnant women found that
pica had declined between the 1950s and 1970s, and that
affected mainly women of lower socioeconomic status. The
authors recorded a fourfold increase in pica prevalence in
pregnant African-Americans. The risk of pica was twice as
high for women residing in rural areas. The observation is in
accordance with the data of Edwards et al. [25–27] who
noticed a decrease in the prevalence of the phenomenon
with time. A recent metanalysis including 70 studies revealed
an aggregate prevalence estimate of 28%.
Pica prevalence was higher in Africa compared with the
rest of the world, increased as the prevalence of anemia
increased, and decreased with the level of education. These
variables partially explained the heterogeneity in prevalence
reported in the literature [28].
In the past, pregnant women in the rural South of the USA
were known to travel to specific river banks to gather clay that
was then baked in the oven to the desired texture. Edwards
and coworkers [25], wanting to compare the habits of the rural
women with those of women living in a urban environment,
studied the frequency of pica, the biochemical parameters
during the course of pregnancy, and pregnancy outcomes in
553 African-American women accessing prenatal clinics in
Washington D.C. They noticed that urban pregnant women
did not report geophagy. Instead, pagophagia was present in
8% and craving for starch in 1.4% of the women. It can be
hypothesized that the widespread availability of ice could
change the habit from geophagia to pagophagia in the major-
ity of women. Gestational age, body length, and body weight
were not different, but head circumferences of infants deliv-
ered to pica women were smaller than those of non-pica
women. In conclusion, they found that in women living in an
urban environment there was a decrease in the prevalence of
pica and a shift in taste from clay and dirt to ice and freezer
frost. In the island of Pemba, Zanzibar, Tanzania, 40% of the
pregnant women interviewed suffered from some kind of pica.
By multivariate logistic regression, any pica was associated
with anemia, nausea, and abdominal pain [29]. A study of
158 American pregnant adolescents (aged ≤18 years), two-
thirds of whom were African-American and 25% were
Hispanic, revealed that 46% engaged in pica behavior. The
substances ingested included ice (37%), starch (8%), powders
(4%), and soap (3%). Serum ferritin and hepcidin concentration
were significantly lower in pica women [30]. It appears that
pica is very infrequent in privileged populations. In a cohort of
well-nourished Danish women, only 0.02% had pica [31].
4. Is pica responsible for iron deficiency?
Some authors have suggested that pica may induce iron
deficiency by replacing dietary iron sources or inhibiting the
absorption of iron [9,32,33]. Although pica is probably attribu-
table to lack of iron in the central nervous system, substances
interfering with iron absorption may exacerbate the iron defi-
ciency. Interesting reports came in the early 1970s from
Turkey, where geophagy was a common finding among chil-
dren and women. The children, in addition to severe iron-
deficiency anemia and to zinc depletion, presented with a
syndrome characterized by growth retardation, hypogonad-
ism, and hepatosplenomegaly. Some patients with this syn-
drome also had a thalassemia-like appearance with the typical
skull-bone changes. The syndrome had been known in Turkey
for several decades. Oral absorption of inorganic and radio-
active iron and zinc was reduced in the presence of clay in
some cases with prolonged geophagy. Treatment with oral
zinc for 6 months corrected impaired growth and delayed
puberty [34]. In the above-mentioned randomized controlled

trial performed in Zambian schoolchildren, 74% of whom were
geophageous, iron supplementation did not reduce the pre-
valence of geophagy or the amount of earth introduced. The
authors concluded that iron deficiency, that was slightly more
prevalent in children eating earth, could be due to impaired
iron absorption [13]. An earlier study had demonstrated that
absorption of 55Fe ascorbate was greatly decreased when
250 g of earth was eaten by five habitual geophagists [35]. A
few years later another study was carried out to determine the
effect of laundry starch on the intestinal absorption of inor-
ganic and hemoglobin iron. In vitro, laundry starch bound 19–
80% of the available 59FeSO4 and 34–68% of the available
59
Fe-hemoglobin. In vivo, laundry starch significantly inhibited
mucosal uptake of 59FeSO4 from isolated duodenal loops. The
researchers observed inhibition of iron absorption both in
anemic and non-anemic rats to whom laundry starch was
administered 1 hour before a dose of 59FeSO4. The data
obtained indicated that laundry starch in addition to decrease
the mucosal uptake or inorganic iron blunts the compensatory
increased iron absorption induced by anemia [32]. It can be
concluded that eating earth, clay, and starch interferes with
the absorption of iron and zinc. However, this hypothesis
cannot be invoked for other substances and especially for
ice. Also, this hypothesis is in contrast with the rapid disap-
pearance of pagophagia when iron deficiency is corrected
[21,36,37].
In contrast with previous in vivo and in vitro studies, recent
results reported by Seim et al. [38] suggest that geophagic
substances do not bind to bioavailable iron and are not
responsible for reduced iron absorption. These authors have
proposed a novel in vivo model for assessing the impact of
geophagic earth on iron status. They gavaged chickens with
clay commonly eaten by pregnant women in Tororo, Uganda,
at doses proportional to the quantities typically consumed by
humans. The authors checked weekly for hemoglobin, and, at
the end of the study, for liver iron, liver ferritin, and gene
expression of the iron transporters divalent metal transporter
1 (DMT1), duodenal cytochrome B, and ferroportin. Only mini-
mal impact was detected on iron status indicators and in the
transcript levels of duodenal transporters in the gavaged ani-
mals, suggesting that all birds were iron deficient. However
several methodological problems, among which the dose of
clay administered, weaken the significance of the study.
5. Is iron deficiency responsible for pica?
It is commonly felt by pediatricians and hematologists that
iron deficiency itself can induce pica. In the attempt to clarify
the matter, Young et al. [5] examined the nutrient-deficiency
hypothesis, according to which geophagy would be an
attempt to compensate for the lack of iron, zinc, or calcium.
If that were the case, people with the greatest needs would
practice geophagy more often. After careful review of the
literature and calculation of the nutritional requirements for
each substance, the authors excluded the hypothesis. In fact in
their study there was no correlation between the age when
calcium and zinc were most needed and the prevalence of
geophagy. Things are a little different for iron. Young et al. [5]
found a statistically significant correlation between geophagy
EXPERT REVIEW OF HEMATOLOGY 1077
and anemia, but geophagy did not seem to be aimed at
correcting it. In fact, they observed that clay eaters tended
to prefer white clay instead of the iron-richer red clay, and the
Ewe people of Ghana actually are known to remove iron from
red clay before consumption [39]. In addition, the fact that
pica occurs twice as often at the beginning of pregnancy than
in late pregnancy, when the need for iron is greatest, made
the authors to reject the hypothesis. Nausea of the first trime-
ster or pregnancy could well explain the craving for earth.
However, iron deficiency could be an indirect cause of pica,
mediated through complex neurological mechanisms, fitting
with the authors’ nonadaptive hypothesis.
Several reports testify to the efficacy of iron therapy in
reducing or abolishing pica. Iron therapy cured pica even
before increasing the hemoglobin level of 13 iron-deficient
pagophagic patients (16% of 81 iron-deficient patients) who
ate at least one tray of ice daily [40]. The correlation between
serum iron levels and symptoms of pagophagia was best
demonstrated by disappearance of symptoms in 22 of 23
patients with the symptom of pagophagia and iron-
deficiency anemia, when serum iron levels rose to or above
70 μg/100 ml [36]. Even the striking symptom of an individual
eating from 4 to 9 Kg of ice a day was relieved within a few
days by iron therapy [6]. Resolution of ice craving was
obtained also in a small group of iron-deficient women who
had undergone a gastric bypass [18]. Association of pica, iron
deficiency, and celiac disease has been reported, suggesting
the primary role of iron malabsorption in the genesis of pica. A
gluten-free diet was often sufficient to completely resolve the
habit [7,41]. In a study of 230 women and 32 men with iron
deficiency, 118 patients (45%) reported pica; of these, 87%
craved ice. In logistic regression analyses, young age and
severity of iron deficiency were found to predict pica [42].
The same group of researchers could not find a correlation
between common alleles of the TMPRSS6 gene that encodes
matriptase-2, a serine protease that represses hepcidin, and
pica [43].
A study aimed to determine the relationship between
pagophagia and H. pylori infection in patients with iron-
deficiency anemia found that intestinal iron absorption was
neither influenced by pagophagia nor by H. pylori infection. In
fact, ice does not affect the environment of the duodenum.
Together these results suggest that pagophagia is not a cause,
but a consequence of iron deficiency [44].
6. Psychiatric cases
Severe cases of pica have been included among the obsessive
compulsive spectrum of symptoms and disorders. In a large
French study [45], 23 adults out of 943 hospitalized patients,
but none of the 108 hospitalized children, were found to have
pica, with a prevalence estimated at 2.4%. Among psychiatric
patients, pica is often a secondary diagnosis associated with
profound mental deterioration. The ingestion of nonnutrient
substances in those cases is probably due to an incapacity of
discerning among different mouth-introduced substances.
Only two patients presented with iron-deficiency anemia but
iron therapy did not improve pica. In these cases, pica could
1078 C. BORGNA-PIGNATTI AND S. ZANELLA
therefore benefit from specific therapy [46], either behavioral
or with selective serotonin reuptake inhibitors. These cases,
however, are completely different from the form of pica asso-
ciated with iron deficiency normally seen by hematologists.
7. Neurological basis of pica
The predominant cause of pica associated with iron deficiency
could be the scarce amount of iron in the tongue, olfactory
apparatus, or other locations in the brain [47]. In the 1970s,
Mackler and coworkers demonstrated in animal models that
iron deficiency results in altered energy production, reduced
levels of iron containing enzymes, and impaired intermediary
metabolism [48]. More recently, experiments in rats have
shown that iron deficiency can modify olfactory behavior
and that DMT1 levels are significantly higher in the olfactory
bulbs of iron-deficient rats. Thus, the molecular mechanism of
olfactory iron absorption and possibly of olfactory or gustatory
function involves DMT1 and is influenced by body iron reple-
tion [49]. The gustatory function might also involve DMT1 and
might be influenced by body iron repletion. It has been sug-
gested that the iron content of the hippocampus influences
the expression of pica in humans. To investigate the role of
micronutrients in gustatory function, thresholds were esti-
mated for four basic tastes in 38 young Japanese women:
iron deficiency was found to be responsible for hypogeusia
for all tastes except salty [50]. Hunt et al. [51] demonstrated
that individuals with iron-deficient anemia, but not controls,
had a significantly improved response time on a neuropsycho-
logical test when chewing ice. These authors hypothesized
that chewing ice triggers vascular changes that lead to pre-
ferential or increased perfusion of the brain. Potential explana-
tions include activation of the dive reflex, which would lead to
peripheral vasoconstriction and preferential perfusion of the
brain or, alternatively, sympathetic nervous system activation,
which would also increase blood flow to the brain. This would
result in increased alertness and processing speed in anemic
patients and would explain why anemic individuals crave ice.
The hypothesis that ice is eaten to reduce the burning of
glossitis and stomatitis due to iron deficiency seems too sim-
plistic [52], also in view of the rapid resolution of pica follow-
ing iron infusion [21].
8. Conclusion
Pica is an overlooked phenomenon that is often associated
with iron deficiency. Pagophagia, the compulsive eating of ice
is the most common form associated with iron deficiency in
adults in the USA, while in children and in other parts of the
world geophagy (earth eating) and eating of paint or other
unusual substances is more common. Pregnant women are at
a higher risk of pica than the rest of the population. Whether
the greater availability of ice to rural women will in the future
modify the habit from geophagy to pagophagia is not known.
The causative role of iron deficiency is suggested by the
appearance of the behavior in conditions of iron malabsorp-
tion, and by the rapid response to iron therapy. In addition,
patients do not necessarily crave for iron-containing sub-
stances (e.g. for ice). The pathophysiological basis of pica is
probably to be researched in the decreased iron levels in the
central nervous system. The dangerous side effects of eating
nonnutritive substances should be kept in mind.
9. Expert commentary
Pica is a fascinating phenomenon and its association with
iron-deficiency anemia has been well known for centuries.
There appear to be at least three different kinds of pica, one
culturally driven, more frequent among certain ethnic
groups (African, Asian), one related to iron deficiency (crav-
ing for ice, or pagophagia in half of the cases), and one
present in psychiatric patients, as an expression of an obses-
sive compulsive disorder. The patients do not spontaneously
offer the information on their habit which should be actively
elicited because of its potential adverse effects. The inges-
tion of clay, stones, or fibers can cause complications requir-
ing surgery. Particular attention should be given to pregnant
women, especially African and Asian, of low socioeconomical
level. The ingestion of toxic substances such as lead is
dangerous for the fetus. Lead poisoning can cause severe
neurological problems in children eating flaking paint. Iron-
deficient individuals may be cured of pica when treated with
iron. Until recently, not many studies have been performed
in order to clarify the pathophysiology of the symptom. On
the basis of the studies reported so far, it can be said that
eating earth and starch seems to decrease iron absorption,
and therapy with iron resolves the craving only in a propor-
tion of those patients. On the contrary, pica for other sub-
stances, and in particular for ice, responds well to iron
treatment suggesting the causative role of iron depletion.
The explanation of the different behaviors could be that ice
does not interfere with iron absorption while earth does,
creating a loop between reduced absorption and lack of
response to iron. These data would fit with Young et al’s
[5] nonadaptive hypothesis.
Recently, research on iron absorption in animals has
received a new impulse, and a role for the olfactory bulb
and for the hippocampus is being discovered. Also, the finding
of pica in patients with iron malabsorption, as in celiac disease,
points to the primary role of iron deficiency. The precise
pathophysiology of pica, however, remains an enigma and is
still the source of speculation. It is clear that iron deficiency in
the presence of pica must be treated and the eating of non-
foods strongly discouraged, although pica developed on cul-
tural basis will likely continue.
10. Five-year view
The relationship between pica and micronutrient deficiencies
merit further study. The striking developments that are being
obtained in the field of iron metabolism [53] might help to
clarify this physiological enigma. Promising fields involve the
study of the molecular mechanisms of olfactory iron absorp-
tion and possibly of gustatory function. Both the olfactory and
gustatory function might involve DMT1 and other molecules
at the basis of the iron metabolism. Also, the role of the iron
content of the hippocampus could provide interesting
information.

Key issues
● Pica is defined as the compulsive eating of non-nutritive
substances. It frequently accompanies iron deficiency.
Careful inquiry is necessary to take it to light, because the
patients are sometimes ashamed of their behavior
● Its frequency is highest in pregnant women and in
preadolescents.
● Side effects span from tooth wearing to helminth infesta-
tion and lead poisoning.
● Several hypotheses have been proposed to explain pica
(and in particular geophagy) including hunger, nutrient
deficiency, protection from toxins and other pathogens,
neurological or sensory defects caused by iron and zinc
deficiency [5].
● The craving for non-food substances usually responds to
iron therapy, even earlier than does hemoglobin.
● Most studies in animals and in humans have shown a
reduction in iron absorption when earth, clay or starch,
but not ice, are administered with iron.
● Iron deficient individuals obtain better results on neuropsy-
chological tests when allowed to chew ice.
● The precise cause of the phenomenon is still unknown but
it is probably attributable to iron deficiency in the central
nervous system.
Funding
This paper was not funded.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
ORCID
Caterina Borgna-Pignatti http://orcid.org/0000-0002-2577-6871
References
Papers of special note have been highlighted as either of interest (•) or of
considerable interest (••) to readers.
1. American Psychiatric Association. Diagnostic and statistical manual
of mental disorders. 5th ed. Arlington (TX): American Psychiatric
Publishing; 2013.
2. Hippocrates, Adams F. The genuine works of hippocrates. London:
Sydenham Society; 1849.
3. Cornelius Celsus, Grieve J. De medicina. London: Wilson D. and
Durham T.; 1756.
4. Livingstone D, Waller H. The last journals of david livingstone, in
Central Africa: from eighteen hundred and sixty-five to his death.
New York (NY): Harpers and Brothers; 1875.
5. Young SL, Sherman PW, Lucks JB, et al. Why on earth?: evaluating
hypotheses about the physiological functions of human geophagy.
Q Rev Biol. 2011;86:97–120.
•• A complete review of the literature on geophagy, including
historical, anthropological, chemical annotations. Precious
source of secondary references. The authors also provide the
reader with several hypotheses for the genesis of pica.
EXPERT REVIEW OF HEMATOLOGY 1079
6. Coltman CA. Pagophagia and iron lack. JAMA [Internet].
1969;207:513–516. Available from: http://www.ncbi.nlm.nih.gov/
pubmed/4303073
7. Gupta A, Rajput S, Maduabuchi G, et al. Sponge eating: is it an
obsessive compulsive disorder or an unusual form of pica? Acta
Paediatr. 2007;96:1853–1854.
8. Trujillo Rodríguez L, Leo Carnerero E. Pica and iron-deficiency anemia
as presenting symptoms in celiac disease. Med Clin. 2002;119:759.
9. Crosby WH. Food pica and iron deficiency. Arch Intern Med
[Internet]. 1971;127:960–961. Available from: http://www.ncbi.nlm.
nih.gov/pubmed/5284066
10. Crosby WH. Pica. JAMA [Internet]. 1976;235:2765. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/946894
11. Singh A, Sharma AK, Choudhary HR, et al. Atypical jejunal perfora-
tion due to cotton threads bezoar in a postpartum woman asso-
ciated with pica. J Clin Diagn Res. 2016;10:PL01–2.
12. Kim SC, Kim SH, Kim SJ. A case report: large trichobezoar causing
rapunzel syndrome. Medicine (Baltimore). 2016;95:e3745.
13. Nchito M, Geissler PW, Mubila L, et al. Effects of iron and multi-
micronutrient supplementation on geophagy: a two-by-two factor-
ial study among Zambian schoolchildren in Lusaka. Trans R Soc
Trop Med Hyg. 2004;98:218–227.
14. Mathee A, Naicker N, Kootbodien T, et al. A cross-sectional analy-
tical study of geophagia practices and blood metal concentrations
in pregnant women in Johannesburg, South Africa. S Afr Med J.
2014;104:568–573.
15. Andrews N, Ullrich C, Fleming M. Disorders of iron metabolism and
sideroblastic anemia. In: Nathan DG, Oski FA, editors. Hematology
of infancy and childhood. 7th ed. Philadelphia (PA): Saunders
Elsevier; 2009. p. 552.
16. Bryant BJ, Yau YY, Arceo SM, et al. Ascertainment of iron deficiency
and depletion in blood donors through screening questions for
pica and restless legs syndrome. Transfusion. 2013;53:1637–1644.
17. Miao D, Young SL, Golden CD. A meta-analysis of pica and micro-
nutrient status. Am J Hum Biol. 2015;27:84–93.
18. Kushner RF, Shanta Retelny V. Emergence of pica (ingestion of
non-food substances) accompanying iron deficiency anemia after
gastric bypass surgery. Obes Surg [Internet]. 2005;15:1491–1495.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16354533
19. Beard JL, Dawson H, Piñero DJ. Iron metabolism: a comprehensive
review. Nutr Rev [Internet]. 1996;54:295–317. Available from: http://
www.ncbi.nlm.nih.gov/pubmed/9063021
20. Tabaac BJ, Tabaac V. Pica patient, status post gastric bypass,
improves with change in medication regimen. Ther Adv
Psychopharmacol. 2015;5:38–42.
21. Auerbach M, Adamson JW. How we diagnose and treat iron defi-
ciency anemia. Am J Hematol [Internet]. 2016;91:31–38. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/26408108
22. Giudicelli J, Combes JC. Pica and iron deficiency in adolescence.
Arch Fr Pédiatrie. 1992;49:779–783.
23. Bay A, Dogan M, Bulan K, et al. A study on the effects of pica and
iron-deficiency anemia on oxidative stress, antioxidant capacity
and trace elements. Hum Exp Toxicol. 2013;32:895–903.
• The first study on the effect of pica on oxidative stress and
antioxidant capacity.
24. Horner RD, Lackey CJ, Kolasa K, et al. Pica practices of pregnant
women. J Am Diet Assoc. 1991;91:34–38.
• First systematic review of the practice of pica during
pregnancy.
25. Edwards CH, Johnson AA, Knight EM, et al. Pica in an urban
environment. J Nutr. 1994;124(6 Suppl):954S–962S.
• Comparison of pica in rural and urban women, with interesting
historical annotations.
26. Edwards CH, McSwain H, Haire S. Odd dietary practices of women. J
Am Diet Assoc. 1954;30:976–981.
27. Edwards CH, McDonald S, Mitchell JR, et al. Clay-and
cornstarch-eating women. J Am Diet Assoc. 1959;35:810–815.
28. Fawcett EJ, Fawcett JM, Mazmanian D. A meta-analysis of the
worldwide prevalence of pica during pregnancy and the postpar-
tum period. Int J Gynecol Obstet. 2015;133:277–283.
1080 C. BORGNA-PIGNATTI AND S. ZANELLA
• Recent metanalysis of pica in pregnant women, including 70
articles, and examining potential variables influencing the pre-
valence of the behavior.
29. Young SL, Khalfan SS, Farag TH, et al. Association of pica with
anemia and gastrointestinal distress among pregnant women in
Zanzibar, Tanzania. Am J Trop Med Hyg. 2010;83:144–151.
30. Lumish RA, Young SL, Lee S, et al. Gestational iron deficiency is
associated with pica behaviors in adolescents. J Nutr.
2014;144:1533–1539.
31. Mikkelsen TB, Andersen AMN, Olsen SF. Pica in pregnancy in a
privileged population: myth or reality. Acta Obstet Gynecol
Scand. 2006;85:1265–1266.
32. Thomas FB, Falko JM, Zuckerman K. Inhibition of intestinal iron
absorption by laundry starch. Gastroenterology. 1976;7:1028–1032.
33. Katz ER, Kitts RL, DeMaso DR. Rumination and pica. In: Kliegman
RM, Stanton BMD, St Geme J, et al., editors. Nelson textbook of
pediatrics. Philadelphia (PA): Elsevier; 2016. p. 138–139.
34. Cavdar AO, Arcasoy A. Hematologic and biochemical studies of
Turkish children with pica. A presumptive explanation for the
syndrome of geophagia, iron deficiency anemia, hepatosplenome-
galy and hypogonadism. Clin Pediatr (Phila). 1972;11:215–227.
35. Sayers G, Lipschitz DA, Sayers M, et al. Relationship between pica
and iron nutrition in Johannesburg black adults. S Afr Med J.
1974;48:1655–1660.
36. Reynolds RD, Binder HJ, Miller MB, et al. Pagophagia and iron
deficiency anemia. Ann Intern Med. 1968;69:435–440.
• The article includes a discussion of the possible physiological
causes of iron deficiency-dependent pica.
37. Kushner R, Gleason B, Shanta-Retelny V. Reemergence of pica
following gastric bypass surgery for obesity: a new presentation
of an old problem. J Am Diet Assoc [Internet]. 2004;104:1393–1397.
Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=kush
ner+rf+pica+2004
38. Seim GL, Tako E, Ahn C, et al. A novel in vivo model for assessing the
impact of geophagic earth on iron status. Nutrients. 2016;8:1–10.
39. Vermeer DE. Geophagy among the Ewe of Ghana. Ethnology.
1971;10:56–72.
40. Uchida T, Kawati Y. Pagophagia in iron deficiency anemia. Japanese
J Clin Hematol. 2014;55:436–439.
41. Altamimi E. Lithophagia in iron-deficient patient with celiac
disease. J Pediatr Gastroenterol Nutr. 2014;59:e49.
42. Barton JC, Barton JC, Bertoli LF. Pica associated with iron deficiency
or depletion: clinical and laboratory correlates in 262 non-pregnant
adult outpatients. BMC Blood Disord. 2010;10:9.
43. Lee P, Barton J, Khaw P, et al. Common TMPRSS6 mutations and
iron, erythrocyte, and pica phenotypes in 48 women with iron
deficiency or depletion. Blood Cells Mol Dis. 2012;48:124–127.
44. Asma S, Boga C, Ozdogu H, et al. The association of pagophagia
with helicobacter pylori infection in patients with iron-deficiency
anemia. Int J Hematol. 2009;90:28–32.
45. Haoui R, Gautie L, Puisset F. Pica: a descriptive study of patients in a
speciality medical center. L’Encéphale. 2003;29:415–424.
46. Hergüner S, Özyıldırım İ, Tanıdır C. Is pica an eating disorder or an
obsessive-compulsive spectrum disorder? Prog
Neuropsychopharmacol Biol Psychiatry [Internet].
2008;32:2010–2011. Available from: http://www.ncbi.nlm.nih.gov/
pubmed/18848964
47. Barton JC, Barton JC, Bertoli LF. Pica for uncooked basmati rice in
two women with iron deficiency and a review of ryzophagia. Case
Rep Med. 2016;8159302.
48. Mackler B, Person R, Miller LR, et al. Iron deficiency in the rat:
biochemical studies of brain metabolism. Pediatr Res [Internet].
1978;12:217–220. Available from: http://www.ncbi.nlm.nih.gov/
pubmed/643392
49. Ruvin Kumara VM, Wessling-Resnick M. Olfactory ferric and ferrous
iron absorption in iron-deficient rats. Am J Physiol Lung Cell Mol
Physiol [Internet]. 2012;302:L1280–6. Available from: http://www.
ncbi.nlm.nih.gov/pubmed/22492739
50. Nagai A, Kubota M, Katayama Y, et al. Evaluation of taste acuity
by the filter-paper disc in Japanese young women: the relation-
ship with micronutrients status. Asia Pac J Clin Nutr.
2012;21:406–410.
51. Hunt MG, Belfer S, Atuahene B. Pagophagia improves neuropsy-
chological processing speed in iron-deficiency anemia. Med
Hypotheses. 2014;83:473–476.
• Research on the effects of chewing ice on the results of a
neuropsychological test. An interesting hypothesis is
presented.
52. Hadjadj ML, Martin F, Fichet D. Anemia caused by iron deficiency
and pagophagia. Apropos case Rev Med Interne. 1990;11:236–238.
53. Camaschella C. Iron-deficiency anemia. N Engl J Med.
2015;373:485–486.