An extract of hops (Humulus lupulus L.) modulates gut peptide hormone secretion and reduces energy intake in healthy-weight men: a randomized, crossover clinical trial

Walker EG, Lo KR, Pahl MC, Shin HS, Lang C, Wohlers MW, et al. Am J Clin Nutr. 2022 Mar;115(3):925-940. 

Control of energy intake is key to the success of interventions designed to support weight management. Impaired gut-brain axis signalling is thought to contribute to obesity, poor weight loss outcomes, overeating, and poor adherence to dietary restriction. Approaches that restore or enhance gut-brain axis signalling may address this underlying feedback dysregulation.

Targeting bitter taste receptors (TAS2Rs) with agonists that modulate the release of peptide hormones from gut enteroendocrine cells is thought to influence the regulation of appetite, energy intake, gut function, hedonic food perceptions, and energy metabolism. Humulus lupulus (Hops) contains a range of bitter compounds, including alpha-acids (humulone, adhumulone and cohumulone) and beta-acids (lupulone, adlupulone and colupulone) that are known ligands for TAS2Rs. Hops has previously demonstrated an ability to reduce body weight and fat mass, and improve glucose homeostasis in both animal and human studies.

Study Design

A randomised, double-blind, three-treatment crossover study in 19 healthy-weight men (mean age 28.9 years; mean BMI 23.5 kg/m²) was conducted in New Zealand. It sought to investigate the efficacy and gastrointestinal (GI) site of action of a bitter supercritical CO₂ Hops cone extract to modify acute energy intake; and related hormonal, glycaemic and subjective responses. Treatments were each separated by a one-week washout. On each of the three one-day visits, participants arrived fasted at 07:30 and ate a 2000 kJ breakfast at 09:00 before taking either placebo or 500 mg of Hops extract administered in delayed-release capsules (duodenal) at 11:00 or quick-release capsules (gastric) at 11:30. Ad libitum energy intake was recorded at lunch (12:00) and afternoon snack (14:00), with participants directed to eat until comfortably full. Blood samples were taken and subjective ratings of appetite, GI discomfort, vitality, meal palatability, and mood were assessed throughout the day.

Key Findings

Total ad libitum energy intake was reduced following both the gastric (4473 kJ; p=0.006) and duodenal (4439 kJ; p=0.004) Hops treatments compared to placebo (5383 kJ).

Figure 1. Significant reduction in ad libitum energy intake after Hops extract, compared to placebo.

Gastric and duodenal treatments significantly stimulated pre-lunch ghrelin secretion and postprandial glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY) responses compared to placebo. In contrast, postprandial insulin, glucose dependent insulinotropic peptide (GIP) and pancreatic polypeptide (PP) responses were significantly reduced in gastric and duodenal treatments without affecting glycaemia. This pattern may indicate a metabolic shift toward greater insulin sensitivity.

Gastric and duodenal Hops treatments produced small but significant increases in subjective measures of GI discomfort (e.g. nausea, bloating and abdominal discomfort) with some mild to severe adverse GI symptoms reported in the gastric treatment only. Although these GI discomfort responses are expected to decrease energy intake and may be confounders, no correlation between energy intake and any measure of GI discomfort was reported.

Significant treatment effects were not found for any subjective measures of appetite or meal palatability.

Conclusion

Both gastric and duodenal delivery of Hops extract can modify the release of hormones involved in appetite and glycaemic regulation, providing a potential “bitter brake” on energy intake in healthy-weight men. The effects of chronic Hops extract administration on appetite regulation and weight management warrant further investigation in long-term studies.