A recent systematic review examined the evidence supporting oxytocin as a potential brain-targeted approach for regulating appetite and metabolic outcomes in patients with overweight or obesity. The review, led by Abdulrahman A. Alsayegh, PhD, of Jazan University, analyzed findings from 14 human studies assessing the effects of endogenous and intranasal oxytocin on eating behavior, body weight, and related metabolic measures.
Oxytocin is a hypothalamic neuropeptide best known for its role in social bonding and reproduction, but growing evidence suggests it also influences appetite regulation and energy balance. The researchers evaluated interventional and observational studies published between 2015 and 2025, including randomized controlled trials, crossover studies, and cohort analyses involving adults with overweight or obesity.
Across several short-term interventional studies, intranasal oxytocin – most commonly administered as a single 24 IU dose – was associated with reduced caloric intake and increased satiety, particularly in patients with obesity. Functional magnetic resonance imaging findings suggested that oxytocin modulates activity in brain regions involved in reward processing and cognitive control. Specifically, reduced activation of the ventral striatum and increased engagement of the prefrontal cortex were observed during exposure to food cues, a pattern consistent with diminished hedonic eating and improved behavioral regulation.
However, longer-term findings were more mixed. In an 8-week randomized controlled trial involving 61 adults with obesity, repeated intranasal oxytocin administration four times daily reduced reported energy intake but did not result in significant changes in body weight, fat mass, or resting energy expenditure compared with placebo. These results suggest that short-term appetite suppression does not necessarily translate into sustained weight loss.
Beyond appetite regulation, some studies included in the review reported potential metabolic effects. In a 12-week pilot randomized controlled trial involving 30 older adults with sarcopenic obesity, daily oxytocin administration at 24 IUwas associated with increased lean body mass by apprxoimately 5% and reduced LDL cholesterol levels by an average of 10 mg/dL. Observational studies also linked higher endogenous oxytocin levels with healthier dietary patterns and more favorable lipid and glucose profiles, although these associations do not establish causality.
The review also highlighted evidence from obstetric populations indicating that obesity is associated with altered oxytocin signaling. Lower circulating oxytocin levels and reduced pulsatility during labor were observed in women with higher body mass index, potentially contributing to prolonged labor and increased cesarean delivery risk.
The authors noted several limitations across the existing literature, including small sample sizes, short study durations, and heterogeneous populations. They emphasized the need for larger, longer-term clinical trials to clarify optimal dosing strategies, durability of effects, and long-term safety.
Overall, the review positions oxytocin as a neuromodulator with measurable effects on appetite-related brain pathways and selected metabolic parameters, while underscoring that its clinical role in obesity management remains to be defined.
Disclosures can be found in the study.
Source: Frontiers in Endocrinology