Several key observations have stimulated interest in the relationship between iron deficiency and thermoregulation. Iron-deficient anemic rats were found to be unable to maintain normal body temperature when exposed to cold (39°F [4°C]) (Beard et al., 1982, 1984; Dillmann et al., 1979, 1980). Accompanying the impairment in thermoregulation were a decrease in the rate of thyroid hormone turnover and an increase in the rate of norepinephrine turnover, as compared to those observed in noniron-depleted cold-exposed (control) rats. Iron-deficient humans are unable to maintain their body temperature during exposure to cool water (82°F [28°C]) (Beard et al., 1990a; Martinez-Torres et al., 1984) or cool air (61°F [16°C]) (Lukaski et al., 1990), compared to subjects with normal iron status and equivalent body composition. Additionally, the iron-deficient subjects had lower thyroid hormone (Beard et al., 1990a) and higher catecholamine responses to cold (Lukaski et al., 1990; Martinez-Torres et al., 1984), similar to the response of iron-deficient rats. After repletion with iron supplements, the previously iron-deficient human subjects showed improved ability to maintain body temperature in the cold. These observations clearly demonstrate the link between iron deficiency and poor thermoregulation.
Iron deficiency may exert its effects on thermoregulation through two distinct, yet related, mechanisms, one involving anemia and the other involving tissue iron deficiency. Iron-deficiency anemia results in decreased oxygen transport from the lungs to tissues, and this reduction in oxygen availability inhibits physiological responses to cold, including peripheral vasoconstriction, a heat-conserving process, and increased metabolic rate, a heat-generating process. Hypoxia, created by reducing the oxygen content or the pressure of inspired air, results in hypothermia in rodents (Gautier et al., 1991). The inability to conserve and produce body heat properly accounts for hypoxia-induced hypothermia (Wood, 1991). Lack of oxygen availability for aerobic metabolism causes a decrease in metabolic rate and, subsequently, a decrease in heat production. Hypoxic rats demonstrate decreased shivering and nonshivering thermogenesis (Gautier et al., 1991) and a decrease in body temperature set-point (Gordon and Fogelson, 1991). Impaired neural control of these processes may also account for the effects of hypoxia on thermoregulation (Mayfield et al., 1987).
Tissue iron deficiency, apart from anemia, decreases the ability of muscles to utilize energy for muscular contraction, presumably via a decrease in the activity of mitochondrial iron-containing enzymes required for the oxidative production of ATP (Davies et al., 1984). This decrease in muscular function