Elsevier

Medical Hypotheses

Volume 83, Issue 4, October 2014, Pages 473-476
Medical Hypotheses

Pagophagia improves neuropsychological processing speed in iron-deficiency anemia

https://doi.org/10.1016/j.mehy.2014.07.016Get rights and content

Abstract

Pagophagia (compulsive ice chewing) has long been associated with iron deficiency anemia, but prior attempts to account for this craving have been unsatisfactory. We hypothesize that chewing ice triggers vascular changes that lead to preferential or increased perfusion of the brain. This would result in increased alertness and processing speed in anemic patients, but not in healthy controls who are already at ceiling, and would explain why anemic individuals crave ice. Preliminary support for this hypothesis was found in two studies. In Study 1, non-anemic subjects reported very low rates of pagophagia (only 4%) while anemic subjects reported significantly higher rates (56%). In Study 2, chewing ice dramatically improved response time on a neuropsychological test, but only for anemic individuals. In a small randomized controlled trial, iron deficient anemic subjects and healthy controls were assigned to chew ice or drink tepid water and then took a continuous performance test that measures response time, response time variability, errors of impulsivity and errors of inattention. In the water condition, anemic subjects performed significantly worse than healthy controls. Chewing ice had no effect on the performance of healthy controls, but significantly improved the performance of anemic patients. Potential explanations 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.

Introduction

Iron-deficiency anemia is one of the most common nutritional deficiencies in children and adolescents in the United States [1]. Iron is an essential mineral utilized by hemoglobin in red blood cells to bind oxygen inhaled by the lungs, later releasing that oxygen into peripheral tissues. As a result, iron deficiency decreases the capacity to deliver oxygen throughout the body, leading to a variety of cognitive and physical ailments. Clinically, signs of moderate to severe iron-deficiency anemia include pallor of skin, nail beds and conjunctiva, fatigue, tachycardia and, most important for our purposes, difficulty concentrating. Iron-deficiency anemia can limit the optimal mental and physical performance of a patient, resulting in decreased activity and alertness [2].

Barton et al. [3] report that up to 50% of individuals with iron-deficiency anemia develop pica, or compulsive ingestion of non-food substances. Pica can be generally divided into three categories: geophagia, or consumption of dirt, rocks, and sand; pagophagia, or compulsive ice consumption; and consumption of all other non-food substances. Pica has been found in medical diagnostic records as early as 1563, with non-medical references dating to before the common era [3], [4]. Pagophagia is the most common form of pica seen in iron deficient anemic patients, and in chart review has been seen in up to 87.3% of pica cases [3], [5]. Moreover, pagophagia’s association with iron-deficiency anemia has been well documented across adult age groups, races, and geographic locations [6], [7], [8], [9]. Pagophagia resolves as the anemic condition resolves with proper iron supplementation. Indeed, pagophagia is sufficiently associated with anemia that it is considered by many physicians to be a specific indicator for iron deficiency anemia.

The reasons for pagophagia in anemia remain a medical mystery, however. There are several standing hypotheses to explain pica in iron deficient anemic individuals, but the most widely accepted theory is the micronutrient deficiency hypothesis. This hypothesis maintains that patients consume non-food items due to deficiencies in iron, zinc, calcium, or some other micronutrient. Pica consumption can therefore be classified as an attempt to increase levels of micronutrient intake. However, this hypothesis cannot explain the onset of pagophagia, as ice typically contains few trace minerals and almost no iron.

Several other explanations have been advanced to try to explain pagophagia in anemia, but none have been supported by the available data. Kettaneh et al. [8] suggested that since anemia sometimes is associated with glossitis (inflammation or infection of the tongue) anemic patients might chew ice to reduce glossal inflammation. Additionally, they also suggest ice’s analgesic properties may allow for oral pain alleviation. However, there is no empirical data to suggest that pagophagia is closely associated with glossal pain, and the vast majority of pagophagic anemic patients do not experience oral pain of any kind. Asma et al. [10] suggested that pagophagia in anemia might be associated with Helicobacter pylori bacterial infection. However, they found that there was no difference in the rate of infection in anemic patients with and without pagophagia, and eradication of the infection had no impact on ice chewing. Finally, a genetic basis for pica has been proposed. However, the alleles that are closely correlated with development of this disease do not predict onset of pagophagia [11]. Thus, while hematologists are acutely aware of the incidence of pagophagia in anemic patients, and this behavior has been described in many cases, there is no accepted explanation for the phenomenon.

Anecdotally, some anemic patients report that they feel more alert or awake when they chew ice [12]. Some liken it to a cup of coffee, saying they must begin each day with several cups of ice, and return to ice chewing throughout the day to sustain alertness. We hypothesize that chewing ice triggers vascular changes (either through the dive reflex, or through activation of the sympathetic nervous system) that lead to preferential or increased perfusion of the brain. This would result in increased alertness and processing speed in anemic patients, but not in healthy controls, who are already at ceiling, and would explain why anemic individuals crave ice. Thus, we propose that chewing ice might have demonstrable effects on attention and concentration, and should improve performance on a neurocognitive test of attention, concentration and reaction time in anemic patients, but not in non-anemic controls.

Before addressing the effects of ice chewing in the anemic population, we first wanted to establish that pagophagia is indeed far more prevalent in anemic patients than it is in healthy controls.

Section snippets

Participants

Ninety-four subjects (27 males, 67 females) participated in the prevalence study. Their mean age was 25 years (SD 10) with a range of 18–72 years. The majority of the sample was white (67%) with some Asian (7%), some African–American (3%) some Hispanic (4%) and some of mixed race (8%). Of our participants, 10 had received a prior diagnosis of iron deficiency anemia and/or had a hemoglobin level of 12.5 gm/dl or lower, while 84 were healthy control subjects. Anemic subjects were recruited

Results – study 1

As a check on the reliability of the self-reported hemoglobin data, we first ran a t-test comparing the hemoglobin levels of men and women. As expected, women reported significantly lower hemoglobin levels (M = 13.2) than men (M = 15.5) [t(73) = 7.74, p < 0.001]. Moreover, individuals who reported being anemic reported significantly lower hemoglobin levels (M = 11) than those who denied anemia (M = 14) [t(73) = 5.31, p < 0.001]. Surprisingly, anemic individuals reported only a trend towards more day time

Discussion – study 1

This is the first study that we know of to directly compare rates of pagophagia in anemic individuals to rates in healthy controls. By recruiting individuals as they exited community blood drives we were able to get accurate hemoglobin levels on a large number of healthy controls. Even if participants did not remember their hemoglobin levels (as happened in a number of cases) we knew they were not anemic if they had been allowed to donate blood. We found a very low rate of pagophagia (only

Participants

Sixty subjects (44 females, 16 males) were recruited. Of these, 13 subjects provided laboratory proof of iron-deficiency, while 47 were healthy control subjects. Mean age was 21.5 (SD 8.5) years with a range of 18–69 years. Twenty-seven subjects were assigned randomly to the ice-chewing condition and 33 subjects were assigned to the water condition. Subjects were recruited from the undergraduate subject pool of the University of Pennsylvania and the Hematology and Oncology Department of the Penn

Results – study 2

We conducted an ANCOVA predicting the TOVA summary score from anemia status, experimental condition and their interaction. There was a marginally significant interaction between anemic status and condition [F(1, 56) = 3.51, p = .06], such that chewing ice greatly improved the overall TOVA performance of anemic subjects, but had no impact at all on non-anemic individuals. See Fig. 1.

We then tested each of the four TOVA variables that make up this composite score. There was a highly significant

Discussion – study 2

The function of pagophagia, or compulsive ice chewing, has mystified hematologists for decades. Our results show that chewing ice significantly increases alertness and improves response time in anemic individuals. Clinically meaningful improvement was seen in the ice chewing condition on the TOVA summary score, and in particular on response time and response time variability. This effect was not mirrored in the control condition, where ice chewing appeared to have no observable effect on any of

Conflict of interest

The authors have no conflict of interest to report.

Acknowledgment

This project was supported in part by a grant from the TOVA Company.

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