Ghrelin Increases Energy Intake in Cancer Patients with Impaired Appetite: Acute, Randomized, Placebo-Controlled Trial

Abstract

There is a pressing need for more effective appetite-stimulatory therapies for many patient groups including those with cancer. We have previously demonstrated that the gastric hormone ghrelin potently enhances appetite in healthy volunteers. Here, we performed an acute, randomized, placebo-controlled, cross-over clinical trial to determine whether ghrelin stimulates appetite in cancer patients with anorexia. Seven cancer patients who reported loss of appetite were recruited from oncology clinics at Charing Cross Hospital. The main outcome measures were energy intake from a buffet meal during ghrelin or saline infusion and meal appreciation as assessed by visual analog scale. A marked increase in energy intake (31 +/- 7%; P = 0.005) was observed with ghrelin infusion compared with saline control, and every patient ate more. The meal appreciation score was greater by 28 +/- 8% (P = 0.02) with ghrelin treatment. No side effects were observed. The stimulatory effects of ghrelin on food intake and meal appreciation seen in this preliminary study suggest that ghrelin could be an effective treatment for cancer anorexia and possibly for appetite loss in other patient groups.

Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers

“…Previous ghrelin studies have demonstrated similar increases in energy intake with a lunch-time meal. 2,7 The energy intake on the saline injection day in the current study was relatively high with the men eating more than the women. Despite these high baselines, subcutaneous ghrelin significantly stimulated energy intake.…”

“…The starting dose of ghrelin was 0.225 nmol/kg (equivalent to half ghrelin dose administered prior to the meal in our previous intravenous infusion study). 2 Doses were thereafter increased by a factor of two. No side effects were observed or reported at any dose of ghrelin administered.…”

“…We have recently reported that acute administration of intravenous ghrelin stimulates energy intake in cancer patients with loss of appetite. 2 However, intravenous administration is cumbersome and unsuited to outpatient clinical practice. A practical means of ghrelin delivery which retains bioactivity is required.…”

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

“…In one pilot study, seven cancer patients had 31% higher energy intake with i.v. ghrelin than with placebo (5 pmol kg À1 min À1 for 180 min equals 3 mg kg À1 ), with no adverse effects (Neary et al, 2004).…”

Mechanism-Based Therapeutic Approaches to Cachexia

“…More recenlty, dronabinol and other cannabinoids were proposed to stimulate appetite (Fide et al, 2005), through both a direct action on the endocannabinoid receptors, and an indirect one on anorexigenic cytokines (Klein et al, 2000;Fide et al, 2005). Finally, gastric cell-derived ghrelin was shown to improve appetite and also to interfere with insulin/IGF-1 dependent pathways (see above); of interest, only anorexic cancer patients benefit from ghrelin administration (Neary et al, 2004).…”