A pilot randomized controlled trial of melatonin supplementation on plasma 2-arachidonoylglycerol, ghrelin, and hedonic appetite intensity in females with overweight/obesity

Hedonic appetite, the motivation to consume palatable foods for pleasure rather than physiological need, may contribute to overweight and obesity, yet few interventions have targeted it. This pilot randomized, placebo-controlled trial examined the effects of melatonin supplementation on plasma 2-arachidonoylglycerol (2-AG), ghrelin, hedonic appetite intensity, dietary intake, and body weight in women with overweight or obesity. Forty-one participants with high hedonic appetite (Power of Food Scale score > 2.5) completed the trial. Participants received either 5 mg/day melatonin (n = 21) or placebo (n = 20) for 8 weeks. 2-AG, ghrelin, and hedonic appetite were assessed at baseline and week 8, whereas dietary intake and body weight were assessed at baseline, week 4, and week 8. ANCOVA or Quade’s ANCOVA was used to compare outcomes between groups. Mean age and BMI were 35.68 ± 7.51 years and 30.36 ± 2.40 kg/m 2 , respectively. At 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 vs. 4.78 ± 0.75 pg/mL; p = 0.013). No significant between-group differences were observed for the other outcomes. Melatonin’s effect on lowering ghrelin, without significant effects on 2-AG or hedonic appetite, means that any impact on hedonic appetite remains uncertain. Trial registration : The trial was prospectively registered with the Iranian Registry of Clinical Trials ( https://irct.behdasht.gov.ir/trial/70034 ) in 21/06/2023 under the ID number IRCT20080904001197N22.