Melatonin Lowers Ghrelin in a Pilot Trial, but Hedonic Appetite Stays Unchanged
A small randomized trial in women with overweight or obesity found that melatonin lowered plasma ghrelin after 8 weeks, yet the hormone change did not translate into measurable shifts in hedonic appetite, 2-arachidonoylglycerol, dietary intake, or body weight. The finding is biologically interesting because ghrelin sits near the center of appetite signaling, but the result also shows how difficult it is to move from a circulating biomarker to a true behavioral or weight outcome.
Forty-one participants completed the study. All had high hedonic appetite, defined by a Power of Food Scale score above 2.5, and they were assigned to 5 mg/day melatonin or placebo for 8 weeks. The mean age was 35.68 ± 7.51 years and the mean BMI was 30.36 ± 2.40 kg/m2. The trial was designed around a clinically relevant question: can a sleep-related hormone influence the reward-driven desire to eat palatable foods, not just fasting physiology?
A Biomarker Shift Without a Behavioral Readout
By the end of the intervention, plasma ghrelin was significantly lower in the melatonin group than in the placebo group, 4.35 ± 0.90 pg/mL versus 4.78 ± 0.75 pg/mL, with p = 0.013. The rest of the signal was flat. No significant between-group differences emerged for 2-AG, hedonic appetite intensity, dietary intake, or body weight.
That split matters because ghrelin is often framed as an orexigenic hormone that can amplify hunger and reinforce food-seeking behavior, especially when reward circuitry is already primed. A reduction in ghrelin can therefore look encouraging on paper. Yet appetite is not a single pathway. Hedonic eating draws on reward processing, sensory anticipation, and learned behavior, while 2-AG belongs to the endocannabinoid system, another appetite-related network that can intensify the appeal of palatable foods. One hormone can move while the larger eating pattern remains unmoved.
The trial therefore suggests a narrower biological effect than a behavioral one. Melatonin appears capable of influencing a hormonal marker linked to appetite regulation, but the dose and duration used here did not produce a clear clinical signal on craving-related eating or body weight.
Why Melatonin Was a Plausible Candidate
The choice of melatonin was not arbitrary. Beyond its circadian role, melatonin has been explored in metabolic research because sleep timing, circadian rhythm, and energy balance are tightly connected. Disrupted sleep and misaligned circadian signals can push appetite regulation in an unfavorable direction, and those disturbances often travel with overweight and obesity. A supplement that reinforces circadian biology could, in theory, influence endocrine signals such as ghrelin and alter eating behavior indirectly.
This study tested that hypothesis in a focused way by selecting women with already elevated hedonic appetite. That design increased the chance of detecting an effect if one existed. Still, the trial’s negative behavioral findings show how difficult it is to disrupt reward-driven eating with a single supplement. Appetite is influenced by habit, environment, palatability, stress, sleep quality, and metabolic state; a modest change in one hormone may be insufficient to overcome those pressures.
The lack of change in 2-AG is also instructive. Endocannabinoid signaling has a strong mechanistic relationship to food reward and the motivational pull of palatable foods. If melatonin had meaningfully altered the broader reward system, a shift in 2-AG might have been one place to see it. Instead, the cannabinoid-related marker remained unchanged, reinforcing the idea that the intervention’s reach was limited.
What the Pilot Design Can and Cannot Tell Clinicians
This was a pilot randomized, placebo-controlled study, and its scale naturally limits how far the findings can travel. Forty-one completed participants can identify a signal, but not settle a treatment question. The trial also measured outcomes at baseline and week 8 for 2-AG, ghrelin, and hedonic appetite, while dietary intake and weight were assessed at baseline, week 4, and week 8. ANCOVA or Quade’s ANCOVA was used to compare groups, which is appropriate for small samples, but the statistical architecture cannot compensate for a modest cohort size or short exposure period.
Clinically, the result should not be read as evidence that melatonin treats obesity, curbs cravings, or suppresses overeating. It does not. What it does show is a possible endocrine effect that may deserve a larger trial with longer follow-up, a broader metabolic panel, and measures that capture sleep quality alongside appetite behavior. Without those additions, the mechanism remains incomplete.
The intervention may still be biologically relevant, just not yet at the bedside. A lower ghrelin level can be a meaningful clue, especially in a population where appetite regulation is already strained, but the absence of changes in eating behavior and body weight prevents any therapeutic claim. For now, melatonin looks more like a probe into appetite biology than a usable obesity treatment.
Trial Registration and Research Context
The study was prospectively registered with the Iranian Registry of Clinical Trials on 21 June 2023 under ID IRCT20080904001197N22. It was conducted as the second phase of a Ph.D. dissertation at Tabriz University of Medical Sciences in Tabriz, Iran, with support from the same institution. Tehran Darou Company supplied the melatonin and placebo, while the funder had no role in the study’s design, analysis, interpretation, or publication decisions.
The authors reported no competing interests. In practical terms, the work adds a small but specific piece to the literature: melatonin can shift ghrelin in women with overweight or obesity, yet that endocrine change did not propagate into a measurable appetite or weight effect over 8 weeks. The unanswered question is whether a longer intervention, a different dose, or a population with different sleep and metabolic characteristics would produce a stronger downstream response.