**1. Introduction**

Anorexia Nervosa (AN) is a severe psychiatric disorder characterised by low body weight, restrictive eating patterns, and body image disturbances. It has one of the highest standardised mortality [1,2] and relapse rates [3] of all psychiatric disorders and is frequently chronic in nature [4]. The underlying pathophysiology of AN is still poorly understood and research regarding its aetiology is ongoing. Meta-analyses have reported

**Citation:** Patsalos, O.; Dalton, B.; Kyprianou, C.; Firth, J.; Shivappa, N.; Hébert, J.R.; Schmidt, U.; Himmerich, H. Nutrient Intake and Dietary Inflammatory Potential in Current and Recovered Anorexia Nervosa. *Nutrients* **2021**, *13*, 4400. https:// doi.org/10.3390/nu13124400

Academic Editors: Fernando Fernandez-Aranda, Janet Treasure and Empar Lurbe

Received: 31 October 2021 Accepted: 7 December 2021 Published: 9 December 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

alterations in the immunological profile of AN patients, specifically increased concentrations of pro-inflammatory cytokines, which have been suggested as a potential contributing factor to the development and maintenance of the disorder [5,6].

Patients with AN lose weight through limiting their caloric intake and, for some, excessive physical exercise. Importantly, aside from the significantly reduced calorie intake, the macronutrient composition of their diets differs significantly from that of lean and healthy, or normal-weight people [7]. Research has shown that people with AN consume less fat, protein, and carbohydrates, but more fibre than their healthy peers [8,9]. Furthermore, it has been reported that even after treatment and weight restoration, recovered AN patients continue to exhibit suboptimal dietary intake of micronutrients and vitamins [10], as well as limited food variety [11].

Diet plays an important role in the regulation of inflammation [12] and associations between dietary patterns and inflammatory status have been reported [13]. For example, intake of dietary fibre has been associated with lower C-reactive protein (CRP), whereas consumption of saturated fatty acids has been associated with higher CRP concentrations [14,15]. It is widely accepted that the Mediterranean diet, which is generally plant-based and high in fibre and low in saturated fats, has anti-inflammatory effects and confers overall lower health risks as compared to a Western-style diet [16,17]. It also is recognised that poor nutrition significantly impacts immune function with many micronutrient deficiencies conveying profound alterations in the regulation of the immune system [18,19].

Given their highly disordered eating patterns and nutrition intake, AN patients often present with nutrient deficiencies [20]. For example, zinc deficiency has been consistently observed in AN patients and this deficiency has been associated with severe immune dysfunction, mainly affecting T-helper cells and delaying wound healing [21–23]. Another important nutrient is cholesterol: hypercholesterolaemia, which has been extensively studied in the context of cardiovascular disease, is frequently exhibited in people with AN and has wide ranging effects, including promoting inflammatory processes and the production of monocytes and neutrophils [24]. Crucially, sterols bind directly to several immune receptors, regulating cytokine expression [25]. It is possible, therefore, that the immunological alterations seen in AN patients could result in part from their disordered eating and patterns of nutrient intake.

In the last decade, there has been significant interest in the role of the immune system, particularly the role of cytokines in psychiatric disorders, including depression [26–31], anxiety [32–34], and post-traumatic disorder [35–37], all of which frequently co-occur with AN. Cytokines are small messenger molecules of the immune system involved in autocrine, paracrine, and endocrine signalling as well as brain functioning [38]. They are produced by a variety of cells including macrophages, as well as astrocytes and microglia [26] and have been shown to access the brain via humoral, neural, and cellular pathways [38]. In addition, they have been shown to play a role in appetite and feeding regulation via their influence on metabolic pathways and neurotransmitter signal transduction, as well as through modulating the hypothalamus-pituitary-adrenal (HPA) axis (see Himmerich et al. [29] for a review). Recent research has reported altered cytokine concentrations in AN patients compared to healthy comparison groups [39,40]. Additionally, when comparing people with current AN to those recovered from AN, significant differences in concentrations of several inflammatory markers have been reported, suggesting that some inflammatory markers could be state markers of the disorder and others trait markers of AN [41,42].

Given the evidence of cytokine alterations in AN, the reported effects of diet on inflammatory status and vice versa, and the disordered eating patterns of people with AN, we hypothesized that the documented altered inflammatory profile could result, at least partly, from their diet. Hence, primarily, we sought to compare the nutrient intakes of AN participants to people recovered from AN (recAN) and healthy controls (HC), and determine whether these groups differed in the inflammatory potential of their diet, using the Dietary Inflammatory Index (DII®) [43]. In addition, we explored the associations between DII scores and cytokine concentrations in participants with AN, recAN, and HC.
