Repeated administration of ghrelin to patients with functional dyspepsia: its effects on food intake and appetite.

Abstract

Background: Ghrelin plays a major role in the regulation of food intake (FI), which makes it a strong candidate for the treatment of anorexia. Objective: We attempted to evaluate the clinical response to repeated ghrelin administration in patients with anorexia caused by functional disorders, such as functional dyspepsia (FD). Subjects and methods: Subjects included in this study were those who 1) were diagnosed with functional anorexia, including FD and other eating disorders with the exception of anorexia nervosa; 2) were lean (body mass index (BMI)!22 kg/m 2 ); and 3) exhibited decreased FI. Subjects received an i.v. infusion of ghrelin (3 mg/kg) for 30 min twice a day (before breakfast and dinner) for 2 weeks. We investigated the effects of ghrelin administration on FI, appetite, hormones, and metabolic parameters. Results: Six patients with FD were enrolled in this study. Ghrelin administration tended to increase daily FI in comparison with levels before and after completion of treatment, but this difference that was the primary endpoint of this study did not reach statistical significance (PZ0.084). Hunger sensation was significantly elevated at the end of drip infusion (P!0.0001). No severe adverse effects were observed. Conclusions: These results suggest that ghrelin administration is safe and that this treatment has stimulatory effects on appetite in patients with FD. Further studies are necessary to confirm the efficacy of ghrelin treatment for anorexia-related disorders.

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…Plasma acyl ghrelin levels correlated with "subjective symptom score" in female patients with functional dyspepsia (Shinomiya et al, 2005), whereas plasma acyl and total ghrelin levels correlated with "ingestive score" in another group of patients with functional dyspepsia (Nishizawa et al, 2006). Repeated intravenous administration of acyl ghrelin tended to increase daily food intake and significantly induced hunger sensation in patients with functional dyspepsia (Akamizu et al, 2008).…”

Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis

“…In previous studies, T 1/2 liq (half-emptying time for liquids, in minutes) decreased by 20-30% following injection of 0.7-5.9 µg/kg of ghrelin. We previously reported that ghrelin tended to increase appetite in a dose-dependent manner (i.e., more so at 5.0 than 1.0 µg/kg) in a phase I study, and that it is safe at a dose of 5.0 µg/kg [27,28,31]. Based on these findings, we adopted the present protocol.…”

“…Visual analogue scale (VAS) scores, 10 cm in length, were used to assess satiety [27][28][29]. VASs were completed pre-infusion and 15, 30, 60, and 90 min after ghrelin or saline administration.…”

The Preproghrelin 3056 TT Genotype is Associated with the Feeling of Hunger and Low Acylated Ghrelin Levels in Japanese Patients with <i>Helicobacter pylori</i>-negative Functional Dyspepsia

“…Akamizu et al reported the ability of repeated ghrelin administration to increase appetite and food intake in patients with FD (45). Recently, the acyltransferase responsible for ghrelin acylation, GOAT, was discovered (42).…”

“…Considering the present results and those of a previous study, ghrelin administration may be more useful for therapy in certain FD patients expressing the preproghrelin 3056TT genotype. The relationship between the ghrelin signaling system and eating behavior makes identifies ghrelin, growth hormone secretagogue receptor (GHSR) and GOAT as good candidate genes for hunger sensation and the risk of eating disorders (45,48).…”