**1. Introduction**

A recent publication analysing the top 100 most cited works on AN reported that only 12 of these papers dealt with treatment, leading the authors to conclude that much work is required to translate 'progress in other areas into effective therapeutic strategies' ([1], p. 13). In contrast to the dearth of literature on treatment, the category encompassing the largest number of papers, 35, addressed the mechanisms underlying the disorder, i.e. 'papers examining diverse theories on AN aetiology and/or maintenance, including family linkage analyses, genetic and heritability studies, biological theories, personality, as well as psychosocial and cultural factors' ([1], p. 10). Moreover, the enterprise of translating theory into effective therapeutic strategies appears to be more challenging than expected. For example, only about 10% of the 4500-word paper, 'Building a model of the aetiology of eating disorders by translating experimental neuroscience into clinical practice' [2], is dedicated to the implications for treatment.

As stated elsewhere [3, 4] given the astonishing contemporary panorama of an absence of psychopharmacological treatments for AN, research with animal analogous models of the human disorder may be helpful in generating new hypotheses for improving AN treatment. A recent example of treatment translation is the reported anxiolytic effect of warmth in anorexia nervosa [5]. In this study postprandial anxiety was significantly reduced in patients resting immediately after lunch for half an hour in a room at 32°C. Bearing in mind the high level of premeal anxiety characteristic of AN patients [6], the significant decrease in postprandial anxiety in warmed AN patients was considerably greater than that achieved by conventional treatments in patients with comparable levels of premeal anxiety such as exposure and response prevention [7].

Interestingly, recent research has underscored the paramount importance of ambient temperature (AT) in the development and more importantly on the reversal of exhaustive running activity, severe weight loss, and self-starvation in rats simultaneously placed on a restricted feeding schedule and given free access to an activity wheel [8–12]. Although self-starvation in rats exposed to this experimental arrangement was first described in the mid-1960s of the twentieth century [13], the term activity-based anorexia (ABA) quickly became dominant describing both the experimental procedure and its resulting behavioural outcome [14]. ABA stands as the best animal model reproducing the main signs of AN (overactivity, extreme weight loss, restricted eating, hypothermia, disturbed sleep, alterations in hypothalamic-pituitary-adrenal/gonadal axis, alterations in diverse appetite-regulating hormones, and severe reductions in grey and white brain matter volume).

Supplying rats exposed to ABA with heat (AT raised to 32°C) reversed excessive activity, improved food intake, and allowed body weight recovery in animals. This reversion was particularly noteworthy as three circumstances concurred in these animals: (a) the increase in AT was delayed until rats had lost 20% of body weight, a point where the spontaneous recovery of rats is unattainable by the animals themselves; (b) animals continued being exposed to the 1.5 h/day restricted food schedule and unrestricted access to the activity wheel; and (c) increased AT allowed for nearly 100% recovery in warmed rats, but there was no single recovery for animals maintained at room temperature (21°C), and a 100% of animals had to be removed to prevent death. This experimental effect of AT has been demonstrated in both male and female animals [10–12].

A more conclusive outcome regarding food intake and body weight was reported in a study [12] where sedentary rats housed at 21°C were food deprived (1.5 h/day) during the first phase of the study that lasted a week. During Phase 2, the animals continued to be submitted to the same restricted feeding schedule for two additional weeks, but AT was increased to 32°C for half of the animals, whereas the other half was maintained at 21°C.

During Phase 2, on average all the animals increased food intake in comparison with Phase 1, but animals maintained at 21°C ate on average 21.5% more than animals housed at 32°C. However, in terms of body weight, only the warmed animals gained a significantly greater amount of weight, and by the end of the experiment, both groups had a similar body weight.

Thus, according to the results, in terms of body weight gain, a warmer environment was more effective than overall food consumption as the buffering effect of higher AT on heat dissipation helped the body weight gain in warmed rats.

In line with this effect of AT on body weight, the same beneficial effect of warming would be expected in AN patients during weight restoration programmes. Moreover, the rate of body weight would be preserved even under a lower caloric supplementation provided that the standard AT of hospital wards was raised. Thus, we should bear in mind the difficulties patients have in gaining weight despite the

**181**

*Warming in Anorexia Nervosa: A Review DOI: http://dx.doi.org/10.5772/intechopen.90353*

(1796–1875), [21] with starved animals.

**nineteenth century**

Ticehurst' (p. 24).

environment at 32° [5].

treatment of AN.

elevated caloric intake during conventional nutritional rehabilitation programmes [15] and that roughly a third of ingested calories cannot be processed by patients and are dissipated through elevated diet-induced thermogenesis [16, 17] that further heightens the anxiety of AN patients [18]. Recent data indicate that heat is crucial for reducing anxiety following meals when patients remain in a warmer

Unfortunately, the manipulation of AT in ABA rats has been overlooked [19] which deprived us from recognizing the pivotal role of AT in the fate of rats exposed to ABA. Likewise, AN research has also been susceptible to a conspicuous neglect concerning the role of AT in the human disorder, either as a risk factor, as a modulating factor in the course of the disorder, or last but not least its potential in the

A historical review of the literature reveals that the suggestion of keeping patients warm is not new, since supplying AN patients with heat was first recommended by William Gull [20]. Undoubtedly, the practice of supplying patients with heat was justified by the evidence accrued by a Swiss physiologist, Charles Chossat

**2. First report of heat for the treatment of AN patients: back to the** 

Although applying heat to AN patients was first prescribed by William Gull (1816–1890) in 1874, this recommendation has been overlooked for over 140 years. On Friday, October 24, 1873, William Gull first reported the use of an external heat supply to AN patients in his seminal presentation on AN to the Clinical Society of London which was published the following year in the Transactions of the Clinical Society of London [20]: 'I have observed that in the extreme emaciation, when the pulse and respiration are slow, the temperature is below the normal standard. This fact together with the observation made by Chossat on the effect of starvation on animals, and their inability to digest food in the state of inanition, without the aid of external heat, has direct clinical bearings—it being often necessary to supply external heat as well as food to patients. The best means of applying heat is to place an india-rubber tube, having a diameter of 2 inches and a length of 3 or 4 feet, filled with a hot water along the spine of the patient, as suggested by Dr. Newington, of

Gull's recommendation was based on the early preclinical animal starvation studies performed by Chossat who discovered the healing effects of heat on starved animals. Charles Chossat, a physiologist, physician, and politician from Geneva [22], performed detailed observations on the consequences of starvation in different species. Chossat's main work, Recherches expérimentales sur l'inanition [21], advanced many of the findings now established by experimental physiology on the effects of starvation on the contribution to weight loss by the different organs and tissues in animals starved to death. Thus, Ancel Keys and his colleagues in the Minnesota Starvation Experiment found the quantitative experimental studies of Chossat 'were surprisingly elaborate for the time' ([23], p. 198). Furthermore, in Chapter 9, entitled 'Morphology of Some Organs and Tissues', the authors pay tribute to the work of Chossat in the section 'The History of an Error' referring to the erroneous assertion in the physiology textbooks regarding the absence of cardiac atrophy as a result of undernutrition and starvation in spite of the different findings

In the 47-page fourth chapter of Recherches expérimentales sur l'inanition,

entitled 'Du réchauffement artificiel', Chossat describes the results of 13

of Chossat [21] regarding heart atrophy in starved animals.

#### *Warming in Anorexia Nervosa: A Review DOI: http://dx.doi.org/10.5772/intechopen.90353*

*Weight Management*

as exposure and response prevention [7].

male and female animals [10–12].

both groups had a similar body weight.

was maintained at 21°C.

As stated elsewhere [3, 4] given the astonishing contemporary panorama of an absence of psychopharmacological treatments for AN, research with animal analogous models of the human disorder may be helpful in generating new hypotheses for improving AN treatment. A recent example of treatment translation is the reported anxiolytic effect of warmth in anorexia nervosa [5]. In this study postprandial anxiety was significantly reduced in patients resting immediately after lunch for half an hour in a room at 32°C. Bearing in mind the high level of premeal anxiety characteristic of AN patients [6], the significant decrease in postprandial anxiety in warmed AN patients was considerably greater than that achieved by conventional treatments in patients with comparable levels of premeal anxiety such

Interestingly, recent research has underscored the paramount importance of ambient temperature (AT) in the development and more importantly on the reversal of exhaustive running activity, severe weight loss, and self-starvation in rats simultaneously placed on a restricted feeding schedule and given free access to an activity wheel [8–12]. Although self-starvation in rats exposed to this experimental arrangement was first described in the mid-1960s of the twentieth century [13], the term activity-based anorexia (ABA) quickly became dominant describing both the experimental procedure and its resulting behavioural outcome [14]. ABA stands as the best animal model reproducing the main signs of AN (overactivity, extreme weight loss, restricted eating, hypothermia, disturbed sleep, alterations in hypothalamic-pituitary-adrenal/gonadal axis, alterations in diverse appetite-regulating

hormones, and severe reductions in grey and white brain matter volume).

Supplying rats exposed to ABA with heat (AT raised to 32°C) reversed excessive activity, improved food intake, and allowed body weight recovery in animals. This reversion was particularly noteworthy as three circumstances concurred in these animals: (a) the increase in AT was delayed until rats had lost 20% of body weight, a point where the spontaneous recovery of rats is unattainable by the animals themselves; (b) animals continued being exposed to the 1.5 h/day restricted food schedule and unrestricted access to the activity wheel; and (c) increased AT allowed for nearly 100% recovery in warmed rats, but there was no single recovery for animals maintained at room temperature (21°C), and a 100% of animals had to be removed to prevent death. This experimental effect of AT has been demonstrated in both

A more conclusive outcome regarding food intake and body weight was reported in a study [12] where sedentary rats housed at 21°C were food deprived (1.5 h/day) during the first phase of the study that lasted a week. During Phase 2, the animals continued to be submitted to the same restricted feeding schedule for two additional weeks, but AT was increased to 32°C for half of the animals, whereas the other half

During Phase 2, on average all the animals increased food intake in comparison with Phase 1, but animals maintained at 21°C ate on average 21.5% more than animals housed at 32°C. However, in terms of body weight, only the warmed animals gained a significantly greater amount of weight, and by the end of the experiment,

Thus, according to the results, in terms of body weight gain, a warmer environment was more effective than overall food consumption as the buffering effect of higher AT on heat dissipation helped the body weight gain in warmed rats. In line with this effect of AT on body weight, the same beneficial effect of warming would be expected in AN patients during weight restoration programmes. Moreover, the rate of body weight would be preserved even under a lower caloric supplementation provided that the standard AT of hospital wards was raised. Thus, we should bear in mind the difficulties patients have in gaining weight despite the

**180**

elevated caloric intake during conventional nutritional rehabilitation programmes [15] and that roughly a third of ingested calories cannot be processed by patients and are dissipated through elevated diet-induced thermogenesis [16, 17] that further heightens the anxiety of AN patients [18]. Recent data indicate that heat is crucial for reducing anxiety following meals when patients remain in a warmer environment at 32° [5].

Unfortunately, the manipulation of AT in ABA rats has been overlooked [19] which deprived us from recognizing the pivotal role of AT in the fate of rats exposed to ABA. Likewise, AN research has also been susceptible to a conspicuous neglect concerning the role of AT in the human disorder, either as a risk factor, as a modulating factor in the course of the disorder, or last but not least its potential in the treatment of AN.

A historical review of the literature reveals that the suggestion of keeping patients warm is not new, since supplying AN patients with heat was first recommended by William Gull [20]. Undoubtedly, the practice of supplying patients with heat was justified by the evidence accrued by a Swiss physiologist, Charles Chossat (1796–1875), [21] with starved animals.
