Acute effects of betahistine hydrochloride on food intake and appetite in obese women: a randomized, placebo-controlled trial

Abstract

Background: Central nervous system histaminergic tone is thought to play a role in appetite regulation. In animal models, histamine receptor 1 (HRH1) agonists and histamine receptor 3 (HRH3) antagonists decrease food intake.

Objective: The objective of this study was to examine the acute effects of betahistine hydrochloride (an HRH1 agonist and HRH3 antagonist) on food intakes and appetites.

Design: The study was a proof-of-concept, randomized, double-blinded, placebo-controlled, dose-ranging study performed to examine the effects of betahistine in women with class I or II obesity [body mass index (BMI; in kg/m²) of 30-39.99]. After a 24-h placebo run-in period, subjects received a placebo (n = 19) or 48 (n = 19), 96 (n = 17), or 144 (n = 21) mg betahistine/d for 24 h. Treatment was followed by a buffet test meal to assess energy intake. Hunger, satiety, and desire to eat were measured after consuming the meal by using visual analog scales. Data were analyzed by using regression models with the assumption that there would be an increasing effect of betahistine doses. Analyses were adjusted for age, log fat and lean mass, food preferences, and intake during a buffet test meal obtained during the placebo run-in period.

Results: Of the 79 obese women (mean ± SD age: 42 ± 11 y; BMI: 35 ± 3) enrolled in the study, 76 women completed the study. The betahistine dose did not significantly change intakes from those observed during the run-in period of the buffet test meal (P = 0.78). Hunger, fullness, and desire to eat (all P > 0.62) similarly showed no differences according to the betahistine dose.

Conclusions: Betahistine did not produce an effect on food intakes or appetites. More potent histaminergic modulators may be required to elucidate the possible role of histaminergic pathways in human obesity. This trial was registered at clinicaltrials.gov as NCT00459992.

FIGURE 1.

Flow of participants through the trial.

FIGURE 2.

Energy intake during buffet test meal. Change in caloric intake from baseline on the betahistine-treatment day (Δ kcal; A: linear regression model adjusted for age, race, log fat and lean mass, percentage of items disliked from buffet test meal, and percentage of actual relative to predicted total daily energy requirements on the run-in day, with dose as a continuous variable; P = 0.49) and actual caloric intake on the betahistine-treatment day (total buffet kcal; B: linear regression model adjusted for age, race, caloric intake during buffet test meal on the run-in day, log fat and lean mass, percentage of items disliked from buffet test meal, and percentage of actual relative to predicted total daily energy requirements on the run-in day, with dose as a continuous variable; P = 0.76). ○, placebo (n = 19); ▴, 48 mg/d (n = 19); Δ, 96 mg/d (n = 17); •, 144 mg/d (n = 21).

FIGURE 3.

Percentage macronutrient intake during buffet test meal. Percentage protein (A; P = 0.1), fat (B; P = 0.15), and carbohydrate (CHO) (C; P = 0.02) linear regression model adjusted for age, race, corresponding percentage macronutrient intake during the buffet test meal on the run-in day, log fat and lean mass, and percentage of items disliked from buffet test meal, with dose as a continuous variable. ○, placebo (n = 19); ▴, 48 mg/d (n = 19); Δ, 96 mg/d (n = 17); •, 144 mg/d (n = 21).

FIGURE 4.

Mean (±SD) values of appetite assessment during the test day. Hunger (A; P = 0.66), fullness (B; P = 0.62), and desire to eat (C; P = 0.90) were assessed during day 2 by using a visual analog scale (in mm). Repeated-measures ANCOVA adjusted for age, race, log fat and lean mass, and percentage of items disliked from the buffet test meal.