Pica Syndromes and Iron Deficiency Anemia Treatment: A Mini Review

Abstract

Background/Objectives: Pica, the compulsive ingestion of non-nutritive substances, has long been observed in patients with iron deficiency anemia (IDA). This behavior is particularly noted in adults, including pregnant women, and poses both diagnostic and management challenges. We conducted a review of studies from the past decade to evaluate the epidemiology and nature of pica in adult IDA patients and the outcome of various treatment strategies on anemia and pica behaviors. Methods: We searched PubMed, Scopus, and Cochrane Library for peer-reviewed articles (including observational studies, clinical trials, and reviews) published in English between 2015 and 2025. Inclusion criteria targeted studies of adult populations with IDA that reported on pica prevalence, characteristics, or treatment outcomes. We also reviewed clinical guidelines and meta-analyses on IDA treatment in adults for recommended management approaches. Results: Pica was found to be a prevalent symptom among individuals with IDA, but was readily treatable with appropriate iron deficiency treatment. Among treatment options, both oral and parenteral iron supplementation were found to be effective in resolving iron deficiency and pica. Choice of treatment depends on tolerance to oral iron, speed of resolution required, and comorbid conditions. Conclusions: Pica is closely intertwined with IDA; our review highlighted the prevalence of pica among individuals with IDA, which serves as both a clinical clue to underlying anemia and a potential source of complications. Crucially, the treatment of IDA is also effective for pica. We recommend oral iron therapy on alternate-day dosing as first-line therapy to minimize side effects, alongside dietary optimization. If IDA and pica are resistant to oral iron supplementation or oral iron cannot be tolerated, parenteral iron therapy can be considered.

1. Introduction

Anemia is a prevalent disorder that affects an estimated 24.3% of the global population, with iron deficiency anemia (IDA) accounting for 84.7% of all years lived with disability [1]. Women of reproductive age and pregnant women are among the most at-risk groups due to menstruation, pregnancy, and lactation, which increase iron requirements [2]). Iron deficiency impairs hemoglobin synthesis, leading to anemia and symptoms such as fatigue, weakness, and cognitive difficulties. Iron deficiency has also been linked to pica, an eating disorder characterized by the compulsive ingestion of non-food substances. Pica behaviors (e.g., eating ice, dirt, clay, starch, paper, etc.) have been documented since antiquity and have frequently been observed in patients with anemia across cultures. In modern diagnostic classifications, pica is recognized as an eating disorder typically defined by at least one month of persistent eating of non-nutritive items that is inappropriate to the developmental level and not culturally sanctioned. If pica occurs in the context of pregnancy or because of a nutritional deficiency, it is often considered a secondary symptom rather than a primary mental disorder. A pregnant woman or anemic adult with cravings for, and consumption of substances like ice or clay, would not necessarily be diagnosed with a pica disorder if the behavior is judged to be driven by a physiological state and resolves with its correction. This distinction underscores the importance of understanding the relationship between IDA and pica, as it has implications for both clinical recognition and management strategies.

Multiple lines of evidence over the past decades have suggested a strong association between IDA and pica. Patients with iron deficiency frequently report unusual cravings, with pagophagia (ice chewing) being the most classic. Conversely, individuals presenting with pica are often found to have an iron deficiency upon workup. In one review, pica was reported as a symptom in as many as 50% of IDA patients [3]. A large meta-analysis [4] found that across 43 studies, pica was associated with significantly increased odds of anemia (OR ≈ 2.4) and lower hemoglobin levels compared to controls. These findings strengthen the idea that the pica-IDA link is not a coincidence. It is a consistent relationship observed in diverse populations.

Pica is of particular interest in pregnant women, a population in which both iron deficiency and pica are common. Pregnancy substantially increases iron requirements, and IDA in pregnancy is associated with adverse outcomes such as preterm delivery, low birth weight, and maternal morbidity. Pica in pregnancy has been documented worldwide. A comprehensive meta-analysis of 70 studies estimated that approximately 27.8% of pregnant women exhibit pica behaviors [3]. Geophagy and pagophagia are frequently reported pregnancy pica practices. This prevalence is far higher than that in the general adult population, suggesting that pregnancy-related factors (including iron deficiency and perhaps hormonal changes or cultural norms) predispose to pica. This study [3] found that pica rates were higher in regions with greater anemia prevalence and among women with lower educational levels. This supports the theory that both nutritional deficiency and socio-cultural context influence the occurrence of pica. It is noteworthy that many pregnant women with pica are simultaneously anemic or iron-deficient; some studies report significant correlations between low hemoglobin and the presence of pica during pregnancy [2]. It has long been recognized that a pregnant woman’s craving for ice or clay should be evaluated for anemia, as pica can serve as a clinical indicator of iron status.

Furthermore, it is worth noting that pica in adolescents and early childhood differs from that in adults. It is not related to IDA and is often transient [5]. Frequencies drop sharply with age. Pica is most likely to be seen in children with developmental delays and autism, and it persists mainly within these populations [5].

Despite this knowledge, gaps remain in understanding pica’s etiology in IDA and how best to manage it. The physiological basis for cravings during iron deficiency is not fully understood. Why would someone chew ice or eat clay specifically? Several hypotheses have emerged. It is suggested that chewing ice might relieve symptoms in those with iron deficiency. For example, it was shown that pagophagia improved neuropsychological processing speed and concentration in patients with iron-deficiency anemia. Likely by enhancing sympathetic activity or cerebral blood flow, which helped reduce fatigue and cognitive slowing [6]. This could explain why anemic patients often feel driven to chew ice as a subconscious way to boost alertness. Regarding geophagia, it has been hypothesized that eating clay or soil may alleviate gastrointestinal (GI) discomfort or bind toxins and pathogens. This can indirectly help the iron-deficient individual by reducing nausea or infection. However, geophagy can also hinder the absorption of micronutrients [7]. Behavioral and cultural factors also play a role. Pica has been observed as a culturally learned behavior in some communities, such as deliberate clay eating in parts of Africa or soil ingestion at religious sites. Stress or psychiatric comorbidities such as obsessive–compulsive disorder, schizophrenia, and autism can also trigger pica in some cases. Therefore, when evaluating pica in the context of IDA, it is important to consider a complex mix of physiological, behavioral, and environmental factors.

Differentiating between IDA-mediated pica and pica caused by OCD/schizophrenia requires careful clinical evaluation, lab findings, and psychiatric history. IDA is diagnosed through a combination of clinical symptoms and lab findings. Clinical signs include fatigue, weakness, pallor, exertional dyspnea, dizziness/lightheadedness, tachycardia, glossitis, angular cheilitis, and koilonychia. Lab findings include reduced Hemoglobin (Hb), <12 g/dL in females and <13 g/dL in males, mean corpuscular volume (MCV) <80 fL, and mean corpuscular hemoglobin (MCH) < 27 pg. Ferritin, which reflects the body’s iron stores, is also measured and is often <30 ng/mL in IDA. Transferrin saturation (TSAT) measures the circulating iron supply, with values < 20% suggesting deficiency. Low reticulocyte counts, <28 pg, also support an IDA picture. Free serum iron is not typically used to assess IDA, due to its diurnal variation, making it a nonspecific finding. Hepcidin, a key regulator of iron absorption and release, is typically low in IDA but elevated in anemia of chronic disease. Chronic inflammation leads to the release of proinflammatory cytokines, such as IL-6, which increases hepcidin and contributes to decreased iron levels, with normal ferritin levels. Folic acid should also be measured to exclude megaloblastic anemia. A multiparametric approach combining Hb, reticulocytes, MCV, TSAT, and inflammation markers can help distinguish IDA from functional iron deficiency in chronic disease. A concomitant pica in the setting of these lab findings can be confidently tied to the IDA. A patient presenting with signs of pica with normal lab values and no clinical signs of anemia deserves a workup of their psychiatric history to assess for OCD/schizophrenia. There may also be pica patients who present with concomitant OCD/Schizophrenia and IDA. In which case, it may be difficult to parse what the root cause of the pica is. Careful history taking regarding the timing of pica onset and associated psychiatric symptoms such as hallucinations, delusions, or compulsions can aid in the diagnosis.

From a treatment perspective, the key to managing pica in the context of iron deficiency is to treat the iron deficiency itself. Numerous studies show that pica behaviors tend to resolve once iron deficiency is corrected [7,8,9]. Patients with pagophagia and geophagia often lose the urge to chew ice or dirt within days of starting iron therapy. Pregnant women who receive iron supplements frequently report that their non-food cravings disappear by the time they deliver. These outcomes strengthen the causal link between iron deficiency and pica. However, simply recommending iron supplementation may not be enough in all cases. Addressing pica comprehensively might require a combination of approaches, especially if the behavior has become habitual or is rooted in psychological factors. Treatment options for IDA have expanded in recent years, including various oral iron formulations and intravenous iron preparations that can quickly restore iron stores.

In this review, we synthesize current knowledge on pica syndromes in adult IDA. We review the latest data on the prevalence and types of pica in iron-deficient adults and evaluate all available treatment modalities for iron deficiency anemia, including pharmacological therapies and dietary measures concerning their efficacy in resolving anemia and pica. Through this review, we aim to inform clinical practice on how to recognize and manage pica in adults with IDA. Ultimately, understanding and addressing pica is a crucial aspect of holistic care for patients with iron deficiency, as it not only alleviates an unusual symptom but also mitigates the potential health risks associated with ingesting nonfood items.

2. Causes of IDA

2.1. Blood Loss

Blood loss is the most common cause of IDA in adult men and postmenopausal women. In cohorts of asymptomatic IDA patients, it was found that about 37% of these patients had a bleeding lesion on endoscopy [10] Adult men and postmenopausal women who present with IDA should obtain prompt endoscopic evaluations (EGD/colonoscopy) to explore a GI bleed. Another study found that around 53% of IDA patients had a bleeding-related lesion on endoscopy [11]). This demonstrates the importance of investigating possible bleeding in IDA patients before they present with prototypical signs of GI bleeding, such as abdominal pain, hematochezia, melena, and early satiety/bloating. If bleeding cannot be found on EGD or colonoscopy, and a GI bleed is still suspected, capsule endoscopy may be used to investigate a bleed in the small intestine.

In premenopausal women, heavy menstrual bleeding (HMB) can also be a cause of IDA, and is the leading cause of IDA among non-pregnant menstruating women globally [12]. It is estimated that 24–38% of reproductive-aged women experience HMB annually, and up to 60% develop anemia [13]. Cross-sectional studies have shown that menorrhagia was associated with a 2.79-fold increased risk of anemia [14] and that heavy menstrual bleeding is a major contributor to IDA in reproductive-aged women across socioeconomic settings [12].

2.2. Decreased Iron Intake/Absorption

Iron intake or absorption is the most common cause of IDA in children and premenopausal women. Decreased iron intake can be a result of vegetarian/vegan diets, which often lack elemental iron, or due to an eating disorder like anorexia nervosa. In addition to inadequate intake, another major cause of IDA is decreased absorption. Decreased absorption can be a result of Celiac disease, Irritable Bowel Disease (IBD), gastric bypass, or atrophic gastritis. Celiac disease is an autoimmune disorder triggered by gluten, which causes damage to the small intestinal mucosa and leads to malabsorption. Patients present with chronic diarrhea, steatorrhea, weight loss, and bloating. Patients with these symptoms should undergo serologic testing with tTG-IgA, which detects antibodies against tissue transglutaminase. However, confirmatory testing requires an EGD with duodenal biopsy to look for villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.

Patients suspected of IDA due to IBD will present with chronic diarrhea, abdominal pain, weight loss, fever, urgency, and tenesmus. Screening for IBD can be obtained through ESR and CRP, which are inflammatory markers associated with IBD. Stool tests can reveal increased levels of fecal calprotectin and lactoferrin. If stool and inflammatory markers suggest IBD, confirmation of diagnosis is obtained through colonoscopy and biopsies. Crohn’s disease is most likely to result in iron malabsorption due to duodenal and jejunal involvement, the primary location of iron absorption. An American IBD cohort reported a 5-year anemia prevalence of 50%, with most cases being driven by iron deficiency or functional iron deficiency [15].

Gastric bypass is another cause of malabsorptive IDA. Post Roux-en-Y patients were followed for 10 years post-surgery, and 51% of them had developed IDA [16]. This is due to the bypassing of the duodenum and jejunum, where iron is absorbed in the small intestine. Additionally, gastric acid production is greatly reduced after gastric bypass, which also affects iron absorption. Gastric acid is responsible for converting ferric iron to ferrous iron, which is the more soluble and absorbable form of iron. Gastric acid is also responsible for enhancing iron bioavailability by releasing iron from the food matrix. It is also through these mechanisms that atrophic gastritis can result in IDA. The lack of gastric acid and loss of parietal cells in the stomach lining leads to IDA. Atrophic gastritis can present with nonspecific GI issues, B12 deficiency, as well as refractory IDA. It is most often caused by autoimmune gastritis or chronic H. Pylori infection. Diagnosis is confirmed through endoscopic biopsy.

2.3. Increased Iron Demand

Increased iron demand induced by IDA is primarily due to pregnancy/lactation. In the U.S.A., 18% of pregnancies involve iron deficiency, and 5% progress to IDA [17]. Globally, anemia in pregnancy affects 36% of pregnant women, with lower-income countries facing higher rates of around 42.6%, with 40% of these anemias occurring due to iron deficiency [18]. Iron is required for the development of the placenta and fetus as well as for the expanded erythropoiesis, which occurs during pregnancy. Lactation is linked to IDA, with some regions of Ethiopia ranging from 29 to 43% of all breastfeeding mothers being anemic [19]. Similar trends were found in Myanmar [20], and much like pregnancy-related IDA, this seems to affect women from low-income countries more than high-income countries. Daily maternal iron requirements can increase to 15–18 mg during lactation, and women from developing countries may struggle to meet this requirement. Management of IDA in pregnant and lactating patients requires routine screening and early supplementation, which can be difficult in low-resource settings.

3. Pica Physiology

Iron is a critical cofactor in many enzymatic processes in the brain, including the synthesis of neurotransmitters like dopamine and serotonin [21]. Iron deficiency can lead to alterations in behavior and cravings due to these neurochemical changes. Another well-known neurological manifestation of IDA is restless leg syndrome (RLS), characterized by an uncomfortable sensation in the legs, accompanied by an urge to move them, especially at night. RLS is strongly associated with body iron status and often remits with iron therapy, indicating a neurochemical link. Pica can be compared to RLS as they are both neurological symptoms that arise in iron-deficient states and resolve with iron repletion. The same dopaminergic pathways that underlie reward and compulsion may be influenced by iron availability, leading to a craving for non-food items. Studies have also shown that IDA patients have worse odor detection, discrimination, and identification compared to controls [22], increased cravings for pungent smells [23], and a decreased sensation of taste [24]. These alterations to the gustatory and olfactory senses could also be a contributing factor towards the development of pica.

4. Forms of Pica

4.1. Pagophagia

Across adult populations, certain types of pica are especially indicative of iron deficiency. Pagophagia is the most documented form of pica associated with IDA in modern clinical reports [2]. These patients may consume dozens of ice cubes daily, sometimes to the exclusion of other cravings. Pagophagia is almost pathognomonic for iron deficiency and has been found even in non-anemic patients with low ferritin but normal iron levels [25]. This study found that approximately 9% of women with ferritin levels below 30 µg/L and normal hemoglobin exhibited pagophagia. This behavior is so closely linked to iron deficiency that it is often specifically inquired about by physicians when iron deficiency is suspected [26]. It is hypothesized that the physiology of pagophagia in IDA involves cold stimuli in the mouth, increasing blood flow velocity in the middle cerebral artery, thereby providing more oxygen to the brain and improving cognition and attention [27]. Pagophagia has been linked to tooth abrasions, enamel fractures, and dental sensitivity [2], as well as electrolyte imbalances [28], which highlight the importance of stopping the behavior. Thankfully, multiple studies [29,30] have demonstrated the efficacy of iron supplementation in eradicating pagophagia.

4.2. Geophagia

Geophagia is another prevalent form of pica, more frequently reported in certain cultural contexts and often seen in pregnancy. In a systematic review [2], which spanned decades of literature, geophagy was the single most common pica substance reported, appearing in ~45% of papers on pica, though not the most common associated with IDA. Geophagy tends to be more common in rural or resource-limited settings and may be related to cultural practices or the clay’s perceived medicinal properties, such as alleviating nausea or supplementing minerals. According to [31], prenatal geophagia was closely associated with iron and folate status, with a greater decrease in hemoglobin and folate being linked with initiation of geophagia during pregnancy. The pregnant women who ate soil had significantly lower ferritin and iron levels than those who did not. Despite its sociocultural acceptance in some locales, the risks of geophagy outweigh any perceived benefit. Geophagy has been linked to toxin exposure [32] and parasite infections [33], which can lead to potential maternal-fetal harm. These examples illustrate the detrimental effects of geophagy. A case study [34] reported a patient who presented with severe hypokalemia and hypophosphatemia due to geophagia. They determined that the clay being consumed was most likely acting as an electrolyte binder. This patient received iron supplementation therapy, which promptly resolved the pica and thus the electrolyte abnormalities. Another case report [35] and cross-sectional study [36] also reported that patients with IDA and concomitant geophagia were treated with iron supplementation, resulting in the resolution of geophagia.

4.3. Amylophagia

Amylophagia is another form of pica characterized by the consumption of starches such as uncooked rice/pasta, cornstarch, and even laundry starch. It was the third most mentioned pica syndrome in the literature, and dental caries were common oral conditions for patients with this condition [2]. A case report [37] examined two women who consumed uncooked rice, leading to abdominal discomfort and tooth damage. After treatment with iron supplementation, both women’s pica resolved.

4.4. Miscellaneous

Other, less common forms of pica have been documented in numerous case studies. There have been reports of patients consuming mothballs [38], hair [39,40], paper [41], and various other substances. However, the common factor in all these reports was the presence of IDA, as well as the resolution of the pica when the patient was treated with iron supplementation. The breakdown of the pica syndromes can be summarized in

Table 1. Pica syndromes, their side effects, and associations.

Pica	Side Effects	Associations
Pagophagia (Ice)	Dental damage (e.g., cracked teeth and enamel erosion)	Considered a specific symptom of IDA
Geophagia (Clay/Dirt)	Parasitic infection, heavy metal toxicity, GI obstruction/perforation	Practice culturally in some regions as a folk remedy or ritual
Amylophagia (Starch)	Weight gain, poor nutrition, dental damage, and blood sugar imbalances in diabetics	Often associated with pregnancy
Trichophagia (Hair)	GI obstruction, trichobezoars (hairballs)	Rapunzel syndrome (a hairball that stretches from the stomach to the small intestine)
Xylophagia (Paper)	GI obstruction, chemical exposure to ink or glue	Linked with autism and schizophrenia

.

5. Management of Iron Deficiency Anemia and Pica

Treating iron deficiency anemia is the gold standard of managing IDA-associated pica. All available evidence suggests that successful iron repletion leads to cessation of pica behaviors in most cases. Therefore, the primary goal should be to correct the iron deficiency efficiently and safely. Supportive measures can be considered to address the behavioral aspects of pica. Here we review the main treatment modalities.

5.1. Oral Iron Therapy

5.1.1. First Line Options

Oral iron supplementation is the first-line treatment for most patients with iron deficiency anemia, as it is cost-effective, widely available, and effective in raising hemoglobin in most cases. The oral iron preparations are ferrous salts (ferrous sulfate, ferrous gluconate, and ferrous fumarate), which differ in elemental iron content but have similar efficacy. Ferrous fumarate has the highest elemental iron content at 33%, followed by Ferrous sulfate with 20% and Ferrous Gluconate with 12%. A standard dose of ferrous sulfate is a 325 mg tablet, which contains 60 mg of elemental iron. A standard dose in adults is approximately 100–200 mg of elemental iron per day, divided into 2–3 doses. This has been shown to significantly improve hemoglobin and iron stores within 4–12 weeks in most individuals [42]. Findings have also shown that after Hb normalization, oral supplementation should be continued for at least 3 months to adequately replenish iron stores to an ideal target of ferritin > 100 μg/L [43].

However, oral iron has its limitations. Adherence is a major challenge; many patients do not take iron as prescribed, often because of gastrointestinal side effects or misunderstanding the regimen. Common side effects of oral iron include epigastric pain, nausea, constipation or diarrhea, a metallic taste, and black stools, which are associated with reduced compliance in 30–70% of cases [44]. These effects can be bothersome, for example, constipation from iron may be particularly problematic for pregnant women who are already prone to it. Poor adherence, often stemming from side effects, is cited as the most significant cause of treatment failure or recurrent iron deficiency with oral iron [45]. Some patients stop taking their iron once symptoms improve, or they take it erratically, leading to only partial repletion and possible return of anemia. To improve the tolerability and efficacy of oral iron, new strategies have been investigated. One evidence-based strategy is intermittent dosing. Daily dosing has long been the standard; however, results from a trial [46] demonstrated that total iron absorption is higher with alternate-day dosing compared to once-daily dosing. This finding was replicated by another trial [47], which also demonstrated that at equal iron doses, alternate-day dosing reduced iron deficiency more rapidly and triggered fewer gastrointestinal side effects. This is hypothesized to be due to oral iron supplementation acutely increasing the hormone hepcidin, which can reduce iron absorption for up to 24–48 h [48]. By spacing doses 48 h apart, hepcidin levels can normalize, potentially enhancing absorption of each dose and reducing GI side effects.

5.1.2. Second Line Options

If side effects are still a barrier, patients can take iron with food, which diminishes absorption somewhat but improves tolerance. Or they can try a different formulation of iron. There are novel formulations that have been developed, such as Ferric Maltol, Sucrosomial iron, and Ferrous Bisglycinate, which have been noted to offer efficacy comparable to traditional ferrous salts but with fewer gastrointestinal issues [42,49]. However, costs can be prohibitive in attempting to obtain Ferric Maltol and Sucrosomial Iron formulations. In the case of Sucrosomial iron, prices can be ten times as expensive. Ferric maltol is prescription-only in most regions and can cost anywhere from USD400 to USD600 per bottle. Ferric maltol was determined to be most useful in patients who were suffering IDA secondary to IBD or CKD [42]. It has also been noted that Ferric maltol does not disturb the gut microbiota and is effective in cases where conventional oral iron supplementation fails [50]. Ferrous Bisglycinate is a promising formulation that is affordable and has a favorable side effect profile. It should be considered in patients who cannot tolerate the other first-line oral formulations. Adding vitamin C to oral iron is regarded as an adjunctive strategy. Vitamin C can theoretically enhance iron absorption, and some practitioners advise taking iron with a glass of orange juice or a vitamin C tablet. However, a trial found that Vitamin C supplementation neither enhanced the hematological response to iron therapy nor mitigated any side effects [51].

5.1.3. Oral Iron and Pica

In terms of its impact on pica, oral iron is quite effective when taken in adequate amounts. It addresses the root cause gradually. However, because oral iron can take 3–4 weeks to show a significant rise in hemoglobin [42], patients with severe pica causing an immediate risk might need temporary measures. If a patient is consuming large quantities of cornstarch, they are at risk of malnutrition. In such cases, the clinician might implement behavioral interventions to curb intake during the initial weeks of iron therapy. It has been demonstrated that pica cravings decreased in patients as early as day 5–8 of therapy and completely disappeared by day 14, so that is unlikely to be a common issue [52]. Monitoring iron parameters and symptoms at follow-ups, around 4 weeks and 8 weeks, is standard. Therapy should be continued for several months, typically 3–6 months total. This is performed to replenish iron stores even after hemoglobin levels normalize, and to prevent the recurrence of anemia [42]. Oral iron supplementation can be summarized in

Table 2. Oral iron formulations, dosing, and notes.

Formulation	Dosing	Notes
Ferrous Sulfate	325 mg tablets/65 mg elemental iron	Standard first line, inexpensive, GI side effects
Ferrous Gluconate	325 mg tablet/39 mg elemental iron	Gentler GI side effects
Ferrous Fumarate	325 mg tablet/100 mg elemental iron	Higher iron content, useful for faster repletion; GI side effects
Ferric Maltol	30 mg tablet/elemental iron	Better GI tolerability; Ideal in IBD, CKD, or CHF patients; Expensive
Sucrosomial iron	30–60 mg tablet/elemental iron	Minimal GI Side effects, Expensive

.

Overall, oral iron remains the gold standard initial approach for iron deficiency anemia and pica management in adults. Its advantages are convenience and non-invasiveness. When properly managed with attention to dosing and side effect mitigation, it usually suffices to cure IDA. However, situations do arise where oral iron is inadequate or cannot be used, leading to consideration of parenteral iron.

5.2. Intravenous Iron Therapy

Intravenous (IV) iron has emerged as a crucial therapy for iron deficiency, particularly in cases where oral iron is ineffective, intolerable, or when rapid correction is desired. Modern IV iron formulations include Ferric Carboxymaltose, Iron Sucrose, low-molecular-weight iron dextran, Ferric Derisomaltose, and Iron Isomaltoside. IV iron delivers iron directly to the bloodstream, bypassing absorption issues. It can also replenish iron stores faster, often in one or two infusions totaling 1–2 g of iron.

5.2.1. Indications

Indications for IV iron in adults include iron deficiency anemia due to celiac disease, bariatric surgery, IBD; intolerance to oral iron due to severe GI side effects, need for rapid repletion such as in the third trimester of pregnancy or preoperatively before major surgery, and in chronic conditions like chronic kidney disease or heart failure where anemia coexists, and prompt treatment is beneficial. For pregnant women with IDA and pica, IV iron is an attractive option if anemia is moderate-to-severe or late in gestation because it can raise hemoglobin more quickly before delivery. Studies [53,54] have demonstrated that IV iron for anemia in late pregnancy produces faster and more sustained increases in hemoglobin compared to oral iron, and with a similar safety and side effect profile. Another recent meta-analysis found that pregnant women receiving IV iron had significantly fewer overall adverse events compared to those on oral iron; the odds of adverse effects were 61% lower with IV [55]. This is because IV iron avoids the GI issues often caused by oral iron supplementation. Many obstetricians now consider IV iron a safe and efficient option. Especially for women who cannot tolerate oral iron or who present with pica and anemia late in pregnancy, where waiting for oral iron to work might not be ideal. In non-pregnant adults, IV iron is used in specific settings (e.g., dialysis patients, cancer patients receiving erythropoiesis-stimulating agents) and increasingly, in general, IDA management when oral therapy fails.

5.2.2. IV Iron and Dosing

The IV preparations have different dosing regimens, Ferric Carboxymaltose and Ferric Derisomaltose can be given as high dosages of 1000 g; Iron Sucrose typically requires multiple smaller doses such as 200 mg daily over five doses; and Iron Dextran can be given as an off label total dose infusion of 1000 but always requires a test dose due to anaphylaxis risk. The breakdown of the IV iron therapy options can be summarized in

Table 3. I.V. Iron formulations with dosing and infusion rate.

Formulation	Dosing	Infusion Time
Ferric Carboxymaltose	750–1000 mg/dose	15 min
Low Molecular Weight Iron Dextran	25 mg initial test dose 100 mg/dose; Off label use 1000 mg/dose	2–6 h
Iron Sucrose	200–300 mg/dose	100 mg/30 min
Ferric Derisomaltose	1000 mg/dose	15–60 min

. The choice often depends on local availability and cost. From a pica resolution standpoint, IV iron’s advantage is speed. It bypasses the need for GI absorption. Particularly for patients with severe iron deficiency who are actively exhibiting dangerous pica, such as eating nails or glass, IV iron may be the fastest way to meet the body’s iron demand and hopefully stop the behavior.

Table 4. Treatment modalities and pica resolution rates.

Iron Formulation	Type	Patient Population	Pica Resolution	Side Effects	Source
Ferrous Sulfate	Oral	Adults with IDA	100% pica resolution within 4 weeks	GI Upset	Asma et al. 2009 [56]
Ferric Carboxymaltose	IV	Pregnant women with IDA	Significant geophagy reduction from 22.5% to 12.9%	Transient Hypophosphatemia	Larson et al., 2025 [9]
IV Iron (Formulation not specified)	IV	Post-Bariatric surgery adults with IDA	100% pica resolution following transfusion	None	Van Osdol et al., 2017 [57]
Iron Dextran	IV	Women with IDA	100% pica resolution within 3 weeks of infusion	N/A	Barton et al., 2010 [58]
Ferrous Sulfate	Oral	IDA in Blood Donors	100% pica resolution in 10–14 days	GI upset, constipation, metallic taste	Bryant et al., 2013 [52]

compares treatment modalities with pica resolution rates.

In summary, IV iron is an effective and rapid treatment for IDA, often resulting in a prompt resolution of pica. It should be considered in adult IDA patients with pica when oral iron is not a viable option or has failed. Other indications for IV iron include late-stage pregnancy, IBD, CKD, chronic heart failure, or malabsorption syndromes [45]. Current evidence indicates that IV iron not only works more rapidly but can be as safe as oral iron in many contexts [55]. The main drawbacks are higher costs and the need for a healthcare setting for infusions. One related treatment that should be mentioned is blood transfusions. In cases of life-threatening anemia, where hemoglobin < 7 g/dL with symptoms, red blood cell transfusions are used to stabilize the patient. Transfusions will improve the oxygen-carrying capacity immediately, but they do not address iron stores. Transfusions are generally a last resort for anemia management and are not indicated solely for pica. After stabilizing with transfusion, iron therapy must still be given to replenish stores and prevent recurrence of anemia and pica.

5.3. Dietary Interventions

Dietary management is a foundational aspect of preventing and treating iron deficiency, though as a sole therapy, it is usually insufficient for moderate to severe IDA. Nonetheless, diet plays a crucial role in maintaining iron status in the long term. A systematic review focused on dietary strategies in women found that dietary interventions using iron-enriched foods and products were effective in improving iron status [59].

Patients with IDA and those with pica from IDA should be counseled on consuming iron-rich foods. The richest sources of heme iron are found in animal products like red meat (beef, lamb), poultry (dark meat turkey, chicken), and seafood. Heme iron is more bioavailable, and its absorption is less affected by other dietary factors. Non-heme iron is found in plant-based foods, such as beans and lentils, tofu, spinach, iron-fortified cereals and breads, nuts, and seeds. Non-heme iron has lower absorption and is more susceptible to dietary inhibitors and enhancers.

For adults with iron deficiency, a dietitian or healthcare provider will typically advise increasing intake of heme iron sources if the person’s diet permits. For vegetarians or those who do not eat much meat, emphasis is placed on legumes, greens, and fortified grains. Some traditional diets have practices that improve iron intake. For example, cooking in cast-iron cookware allows small amounts of iron to leach into the food, which can be beneficial. The use of iron ingots in boiling water is an example of a simple fortification method in some communities.

6. Discussion

6.1. Future Directions

On the research front, unanswered questions include the role of other micronutrients, like zinc, in pica. It has been noted that low zinc levels occur in pica cases [4], which raises the question: should we also check zinc levels or give zinc supplements to pica patients? Can zinc supplementation also help stop pica? Other questions that remain include why some individuals with IDA develop pica while others do not. Additionally, can pica be effectively used as a screening tool in resource-poor settings? For example, asking about pica could identify women with IDA in areas where lab testing is difficult. If a community health worker in a village knows that craving clay indicates possible anemia, they could start giving iron supplements based on observation. This may be a low-cost way to target limited resources, but caution is needed, as pica is not always caused by iron deficiency; other issues can be involved in some cases. Additional research could also investigate the neurophysiological basis of pica in IDA in a more in-depth manner, as there is a notable lack of information about this topic.

6.2. Limitations of Our Review

It should be acknowledged that our review included data from a range of study designs, including many case-based studies, which inherently carry bias, such as publication bias towards unusual or positive outcomes. However, the consistency of the narrative, that pica improves with iron, across sources lends credibility. Gaps in standard diagnostic criteria for pica or IDA across studies could also lead to biases in results, affecting comparability. We also focused on the past 5–10 years for new insights, but some fundamental knowledge comes from older literature, which we referenced as needed for context.

7. Conclusions

Pica, the compulsive eating of non-food substances, is closely intertwined with iron deficiency anemia in adult populations. Our review of literature underscores that pica is prevalent among iron-deficient individuals, especially in pregnant women, and serves as both a clinical clue to underlying anemia and a source of potential health complications. Behaviorally, while cultural and psychological factors modulate pica’s expression, in the context of IDA, it predominantly represents a reversible, deficiency-driven behavior rather than a standalone mental disorder. Crucially, the treatment of iron deficiency anemia is also effective for pica. Replenishing iron stores via oral or intravenous iron leads to improvement and disappearance of pica cravings in most reported cases. Oral iron supplementation remains the first-line therapy for IDA in adults and, when taken adherently, raises hemoglobin and resolves pica. Newer dosing regimens, such as alternate-day dosing, can improve the success and tolerability of oral iron. Intravenous iron has emerged as a safe and rapid alternative for patients who cannot tolerate or adequately absorb oral iron, require rapid correction, or have comorbid conditions. Studies have demonstrated that IV iron corrects anemia more completely and quickly, often with fewer adverse effects, which may also hasten pica resolution. Dietary interventions, including increased intake of iron-rich foods, support the medical treatment and help prevent the recurrence of deficiency.

From a clinical standpoint, recognizing pica as a symptom of iron deficiency has practical importance. Healthcare providers should routinely screen for pica in patients at risk for or presenting with anemia, and conversely, investigate iron status in patients exhibiting pica. This awareness can lead to earlier diagnosis of IDA and prompt treatment, thereby averting both the consequences of anemia and the potential harms of pica behavior, such as dental damage, gastrointestinal injury, electrolyte abnormalities, or poisoning.

In conclusion, the relationship between pica and iron deficiency anemia exemplifies the impact of micronutrient status on human behavior. Pica syndromes in adults should not be viewed as isolated habits but rather as clinical signals often pointing to an underlying iron deficiency. The evidence strongly supports that by treating IDA, using oral or IV iron coupled with dietary and supportive measures, we not only correct a hematological problem but also effectively cure the associated pica behaviors. Future research may further illuminate the neurobiological basis of this connection, but current knowledge is sufficient to guide clinicians in identification and management. Ultimately, pica in an adult is much more than a curious craving; it is a call to action for iron repletion, and answering that call benefits the patient’s health in multiple dimensions.