A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.

Reframing anorexia nervosa as a metabo-psychiatric disorder

“…All forms of plasma ghrelin levels are elevated in acute AN [76], and resistance develops to the orexigenic hormone, which is produced by the stomach and acts on the HPA, affecting secretion of gonadotropin-releasing hormone, adrenocorticotropic hormone, and GH. The resultant lack of motivating feeding response to ghrelin, despite hunger sensation, supports an altered reward circuit, which may contribute to both onset and maintenance of AN [77].…”

Associations of Stress and Appetite Hormones with Binge Eating in Females with Anorexia Nervosa after Weight Restoration: A Longitudinal Study

“…Ghrelin secretion increased during fasting and decreased after eating a normal meal [51,52]. In a recent meta-analysis, all forms of ghrelin were found to increase in patients with acute AN during fasting compared with the healthy controls [53]. The starvation with a low body weight in AN patients at admission might trigger the increase in ghrelin to signal the hypothalamus to stimulate food intake.…”

Biased Ghrelin Receptor Signaling and the Dopaminergic System as Potential Targets for Metabolic and Psychological Symptoms of Anorexia Nervosa

“…A systematic meta-analysis showed that all subtypes of AN lead to an increase in ghrelin levels in the acute/fasting state. After receiving treatment, all AN subtypes had decreased ghrelin levels compared to before the treatment, although still increased compared to healthy controls ( 80 ). These findings make ghrelin a possible biomarker for AN.…”