Effect of histaminergic manipulation on weight in obese adults: a randomized placebo controlled trial

Abstract

Objective: To determine the magnitude and determinants of weight loss in humans exposed to betahistine, a centrally acting histamine-1 (H-1) agonist and partial histamine-3 (H-3) antagonist. Design: A multicenter randomized, placebo-controlled dose-ranging weight loss trial with a 12-week treatment period. Subjects: Two hundred and eighty-one obese but otherwise healthy participants. Measurements: Weight and obesity-related comorbidities at baseline and at the end of the intervention. Results: Betahistine, at the doses tested, did not induce significant weight loss. With the exception of headache, no difference in adverse effect profile was noted between placebo and treatment groups. Subgroup analysis revealed that age below 50 years, ethnicity (non-Hispanics) and gender (women) were the strongest predictors of weight loss in this population. When these three factors were combined together, the betahistine 48 mg group (n ¼ 23) lost À4.24 ± 3.87 kg, whereas the placebo group (n ¼ 25) lost À1.65±2.96 kg during this time period (P ¼ 0.005). Conclusion: Betahistine, at the doses tested, induced significant weight loss with minimal adverse events only in women below 50 years.

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

“…These clinical findings correspond with the results of animal studies, in which it was demonstrated that the co-treatment with betahistine partially reduced olanzapine-induced weight gain sideeffects [169]. It is worthy to note that histaminergic modulation may counterbalance druginduced overfeeding and weight gain, however it may be ineffective when there is no drugdependent alteration as showed in clinical trials in obese (otherwise health) subjects [172,171]. Therefore, it is not clear whether it could be useful as a weight-loss medication in obese non-medicated people.…”

“…Barak and colleagues conducted a multicentre randomized, placebo-controlled weight loss trial using betahistine (16,32,48 mg/day) in 281 obese adults for a 12-week treatment [171]. The overall results revealed that betahistine did not induce significant weight loss in obese participants at the above dosages, while the prevalence of adverse events was low.…”

“…The overall results revealed that betahistine did not induce significant weight loss in obese participants at the above dosages, while the prevalence of adverse events was low. However, further subgroup analysis revealed that the non-Hispanics women ≤ 50 years old, treated by betahistine (48 mg/day) lost ~4.24 kg body weight, compared with the placebo group (~1.65 kg) (p=0.005) [171] (Table 1). Another randomized placebo-controlled double-blind trial reported that 24 hours treatment of betahistine (48, 96, or 144 mg/day) had no effect on food intake or appetites [172], suggesting that long term administration may be the essential factor to reveal the effect of betahistine on energy intake [172] (Table 1).…”

Role of betahistine in glycemic control of obese subjects: a placebo- controlled clinical trial

“…43 In 2008, a study reported a significant weight reduction in women aged less than 50 years who received 48 mg betahistine/day rather than a placebo throughout a 12-week randomized controlled trial. 44 In 2012; a review regarded betahistine as one of the drug candidates for future role as a centrally acting anti-obesity medications. 45 In this study, administration of betahistine (along with low calorie diet and medium intensity exercise) caused a significant reduction in FPG, HbA1c%, Cpeptide, IR and functioning Beta Cell percent.…”

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“…21 While claims have been made that Betahistine is associated with weight loss, these appear to be unfounded. 22 …”