A Situation of Malnutrition with Peculiar Changes in the Immune System

Eating disorders: a situation of malnutrition with peculiar changes in the immune system

A Marcos*

Instituto de NutricioÂn, Facultad de Farmacia, Ciudad Universitaria, Madrid 28040, Spain

Eating disorders, such as anorexia nervosa and bulimia nervosa, are signi®cant public health concerns for a great deal of the population, and thus are even considered to be epidemics. These syndromes have a common aim: the pursuit of a desirable and extremely low weight, which is obviously very far from the ideal body weight. Therefore, these patients show abnormal food behavior, leading to a situation of malnutrition. Nutrients play an important role in the development and functionality of the immune system. Thus, the assessment of immunological parameters acquires great interest as a useful tool to evaluate the nutritional status of these patients. In addition, it is very well known that a depleted immune system as a consequence of malnutrition is linked to an increased susceptibility to infections. However, an extensive literature has pointed out that anorexic patients, even though severely malnourished, are relatively free from infectious diseases. As the immune system is altered by distorted food behaviors, such as in case of eating disorders, the awareness of the characteristics of other systems involved in these pathologies, and therefore altered, would be very helpful for the understanding of the mechanisms triggered in these syndromes. In fact, the interactions among the immune system and the remaining systems in eating disorders are beginning to be studied. Finally, the main goal is to limit the evolution of these illnesses through an early diagnosis and appropriate therapy to subsequently get a constant and de®nitive cure for the patients. Descriptors: anorexia nervosa; bulimia nervosa; immune system; nutritional status European Journal of Clinical Nutrition (2000) 54, Suppl 1, S61±S64

Introduction both syndromes are associated with serious morbidity and mortality. In general, the prognosis for severe and refrac- Anorexia nervosa (AN) and bulimia nervosa (BN) are tory BN is less favorable than for uncomplicated AN. psychiatric illnesses that are typi®ed by abnormal eating Serious medical complications are more likely to occur in patterns. These patients respond differently to the macro- those cases with the presence of self-induced vomiting, nutrient content of food (fat, carbohydrate and protein) than which might impair the prognosis of the evolution of the normal subjects do (Drenowski et al, 1988). illness (Comerci, 1990, Garner, 1993). These pathologies AN is a syndrome which mainly includes three features: are frequently associated with depression and anxiety a marked fear of fatness, a disturbed perception of body (DSM-III-R) (American Psychiatric Association, 1987), size (body image), and an obsessive desire to lose increas- thus they have been classi®ed as multifactorial disorders ing amounts of weight (American Psychiatric Association, (Garner, 1993; Pomeroy et al, 1994). 1987). The rest of the symptoms and characteristics are shown in Table 1. Besides, anorexia, per se, usually is not associated with AN; the appetite in AN remains normal or The immune system is increased until late in the course of the illness (Comerci, The complexity of the interactions between nutrition, 1990). immunity and infection is well recognized (Scrimshaw & Similarly to AN, patients with BN pursue thinness. SanGiovanni, 1997). Nutrients are known to play an However, in BN the distinguishing feature is binge important role in the appropriate maintenance of the eating, which is the rapid consumption of a large quantity immune mechanisms involved in the defence of the host of food in a discrete period of time, usually less than 2 h, (Chandra, 1997). invariably followed by purging. This abnormal eating Despite the fact that all the processes that occur in these behaviour could simply be an attempt to satisfy hunger syndromes may affect immune functions, few studies have without gaining weight (Chiodo & Latimer, 1983) and may focused on this ®eld, and the results are controversial represent an attempt to use food to relieve dysphoria and=or (Marcos, 1997). Nutrients are capable of modulating cyto- anxiety (Kaye et al, 1986). Table 1 summarizes the main kines, and hence cytokine participation is essential in features of patients with AN or BN (American Psychiatric triggering certain mechanisms involved in infection pro- Association, 1994). cesses (Grimble, 1994). These disorders usually occur in girls during early to late It is important to stress the fact that infection-induced adolescence. Long-term follow-up studies indicate that malnutrition, the most common form of cytokine-induced malnutrition, results from the actions of proin¯ammatory *Correspondence: A Marcos, Instituto de NutricioÂn, Faculdad de cytokines such as tumor necrosis factor, and interleukins-1 Farmacia, Ciudad Universitaria, Madrid 28040, Spain. and-6. These cytokines are known to be able to initiate an E-mail: [email protected] acute phase reaction, which is quite stereotyped, including Eating disorders and the immune system A Marcos S62 Table 1 DSM-IV diagnostic criteria for anorexia nervosa and bulimia nervosa

Anorexia nervosa Bulimia nervosa

A. Refusal to maintain body weight over a minimally normal weight for A. Recurrent episodes of binge eating. An episode of binge eating is age and height (e.g. weight loss leading to maintenance of body weight characterised by both of the following: 15% below that expected), or failure to make expected weight gain (1) eating in a discrete period of time (e.g. within any 2-hour period), during period of growth, leading to body weight below 15% of that an amount of food that is de®nitely larger than most people would eat expected. in a similar period of time in similar circumstances; and B. Intense fear of gaining weight or becoming fat, even though under- (2) a sense of lack of control over eating during the episode (e.g. a weight. feeling that one cannot stop eating or control what or how much one C. Disturbance in the way in which one's body weight or shape is is eating). experienced, undue in¯uence of body shape and weight on self- B. Recurrent inappropriate compensatory behaviour to prevent weight evaluation, or denial of the seriousness of current low body weight. gain, such as self-induced vomiting; misuse of laxatives, diuretics, or D. In postmenarchal females, amenorrhea, i.e. the absence of at least three other medications; fasting; or excessive exercise. consecutive menstrual cycles. (A woman is considered to have C. The binge eating and inappropriate compensatory behaviours both amenorrhea if her periods occur only following hormone, e.g. occur, on average, at least twice a week for 3 months. estrogen administration). D. Self evaluation is unduly in¯uenced by body shape and weight. Restricting type: during the episode of anorexia nervosa, the person does E. The disturbance does not occur exclusively during episodes of not regularly engage in binge eating or purging behaviour (i.e. self- anorexia nervosa. induced vomiting or the misuse of laxatives or diuretics). Purging type: the person regularly engage in self-induced vomiting or the Binge eating=purging type: during the episode of anorexia nervosa, the misuse of laxatives or diuretics. person regularly engage in binge eating or purging behaviour (i.e. self- Nonpurging type: the person uses other inappropriate compensatory induced vomiting or the misuse of laxatives or diuretics). behaviours, such as fasting or excessive exercise, but does not regularly engage in self-induced vomiting or the misuse of laxatives or diuretics.

leukopenia with relative lymphocytosis and a very depleted CD4=CD8 ratio, an index of nutritional status. This out- come is typical, especially in those patients who haven't been properly diagnosed and treated at the onset of the illness (Marcos et al, 1993a, b, 1997a). In a one-year follow-up study where 15 patients with AN were properly diagnosed and treated from the onset of the illness, a tendency to leukopenia was shown. In addition, a relative lymphocytosis was found, but only at the ®rst stage of the study (at admission to the hospital). Lymphocyte subsets of these patients showed some altera- Figure 1 Interrelationships among cytokines, nutrients and infection. tions compared with controls during the follow-up. Thus, at admission, all the subsets, except CD19 cells, were lower than in the control group. During this year, an improvement fever, loss of appetite, decreased food intake, cellular in CD2, CD3, CD4 and CD8 subsets was shown 2 months hypermetabolism and multiple endocrine and enzyme after admission. It is at this point precisely when patients responses, among other symptoms (Grimble, 1994; Figure had left the hospital and were at home. However, during the 1). However, in the speci®c case of eating disorders, following stages, the levels of the lymphocyte subsets patients do not show exactly this stereotyped reaction, decreased again. Regarding natural killer (NF) cells, they especially that related to fever. In our research group we remained at very low levels during the one-year follow-up. consider the presence of fever a symptom of improvement, even during hospitalization, and it is commonly a motive to congratulate the patient. These cytokines are capable of activating the hypotha- lamic ± pituitary ± adrenal axis (HPAA) and to have a direct stimulatory effect on adrenal corticosterone secretion in vitro. In turn, glucocorticoids alter the production of these cytokines, as a feedback mechanism (Beisel, 1995). Although all these cytokines are impaired in protein- energy malnutrition, they do not seem to be depleted in eating disorders. On the contrary, some authors have reported a spontaneous and elevated production, contribut- ing to weight loss, cachexia and osteoporosis in AN patients (GonzaÂlez-HernaÂndez et al, 1995). Weight changes caused in AN produce an altered cortisol secretion pattern, leading both to a T cell redis- tribution and to modi®cations of the T, B and NK cell circadian rhythm (Abo et al, 1981). Regarding white blood cells, the leukocyte pattern is modi®ed both in AN and BN. The most signi®cant ®nding is an important prevalence of Figure 2 Lymphocyte subsets in controls and AN patients.

European Journal of Clinical Nutrition Eating disorders and the immune system A Marcos S63 sate for the lower capacity of their T lymphocytes to produce IL-2 (Bessler et al, 1993). Such a mechanism provides a relatively normal immune response and could explain why these patients are not prone to infections. Although the study of the immune system can reveal very important information about the nutritional status of these patients, further research is necessary in this ®eld. However, it is necessary to take into account other related ®elds, such as the endocrine system and the central nervous system, which must also be involved, and their study could be very helpful in determining the real mechanisms acting in these disorders (Figure 3).

Conclusion According to our experience and the literature consulted, the research in this ®eld should be focused on groups of patients homogenized as much as possible. Thus, the age at the moment of the study, the age of patients at the onset of the disorder, the onset of diagnosis and of appropriate treatment, the duration of the illness at the moment of the study, and the type of AN or BN patients (restricted or purgative) should be strictly taken into account.

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