Novel Ingredient for Sleep (Lime Peel Extract)

BENESOMNOTM has been approved as a Health Functional Food (HFF) ingredient by the Ministry of Food and Drug Safety (MFDS) of Korea

BENESOMNO™ is a nutraceutical and dietary ingredient for sleep developed by Nutra-it Inc., a company with world-class expertise in sleep science, to compete in the global market.

The name BENESOMNO™ combines the Latin words "BENE" (GOOD) and "SOMNO" (SLEEP), reflecting Nutra-it Inc.’s vision to fostering a healthier world through better sleep.

Introduction
  • Nutra-it's research team possesses world-class expertise in sleep-promoting ingredients and has successfully developed Ecklonia cava extract and rice bran extract, both approved as sleep-promoting nutraceuticals by the Korean FDA.
  • Focusing on the development of globally recognized sleep-promoting ingredients, Nutra-it successfully developed BENESOMNOTM, an innovative sleep-promoting ingredient derived from lime peel.
  • BENESOMNOTM is produced using a patented process that isolates only the active compounds with scientifically proven sleep-promoting effects from the peels of Mexican lime (Citrus aurantifolia).
  • Nutra-it applies a systematic and scientific quality management system throughout the entire production process, from sourcing lime peels to the final production of BENESOMNOTM.
  • BENESOMNOTM has been patented in Korea and has patent applications filed in the United States, Europe, and China.
Ingredient Features
Efficacy Excellent
Mechanism of action GABA agonist (GABAA receptor)
Adverse effects No
Dosage 300 mg/day (Lime extract 150 + Dextrin 150)
Raw material Mexican Key lime peel (Non-GMO)
Marker compound Vicenin-2 (flavonoid)
Available dosage forms Gummy, Granule, Tablet, Liquid etc.
Clinical Trials
  • This study aimed to evaluate the effects of SLPS in adults experiencing sleep disturbances. The randomized, double-blind, placebo-controlled clinical trial involved 80 subjects who received either SLPS (300 mg/day) or placebo for a 2-week period.
  • SLPS significantly improved polysomnographic outcomes, including a reduction in sleep latency, wake after sleep onset, and total wake time, and enhancement of sleep efficiency, total sleep time, and stage 2 sleep. Daytime sleepiness, assessed via the Epworth Sleepiness Scale, was also decreased by SLPS.
  • No serious adverse effects or side effects were reported among participants in the SLPS group during the intervention period. Our findings support SLPS as a potential natural sleep aid for improving sleep in adults with sleep disturbance.

Source: Kim et al., Efficacy and safety of standardized lime peel supplement in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study. Phytomedicine 139, 156510, 2025.

Animal assay results
Pentobarbital-induced sleep test
  • Test substance: SLPS (standardized lime peel supplement, BENESOMNOTM)
  • Test animal: ICR mice
  • Results: Administration of SLPS (100, 200, and 400 mg/kg) resulted in a dose-dependent decrease in sleep latency and increase in sleep duration. The effect of SLPS (400 mg/kg) was comparable to that of zolpidem (10 mg/kg).

출처: Kim, S., Kim, D., Lee, J., Han, J. K., Um, M. Y., Jung, J. H., ... & Cho, S. (2024). Novel neuropharmacological activity of citrus lime (Citrus aurantifolia): A standardized lime peel supplement enhances non-rapid eye movement sleep by activating the GABA type A receptor. Biomedicine & Pharmacotherapy, 179, 117410.

Analysis of sleep structure and profile
  • Test substance: SLPS (standardized lime peel supplement, BENESOMNOTM)
  • Test animal: C57BL/6N mice
  • Results: Administration of SLPS (100, 200, and 400 mg/kg) resulted in a dose-dependent decrease in sleep latency and increase in NREMS. Furthermore, no significant difference was observed between SLPS at 400 mg/kg and zolpidem at 10 mg/kg.

출처: Kim, S., Kim, D., Lee, J., Han, J. K., Um, M. Y., Jung, J. H., ... & Cho, S. (2024). Novel neuropharmacological activity of citrus lime (Citrus aurantifolia): A standardized lime peel supplement enhances non-rapid eye movement sleep by activating the GABA type A receptor. Biomedicine & Pharmacotherapy, 179, 117410.

Mechanism of Action
  • SLPS (standardized lime peel supplement) exerts sleep-promoting effects by modulating the GABAA​ receptors. When active compounds in SLPS binds to the GABA-binding site of the GABAA​ receptors, it enhances receptor activation, leading to a large influx of Cl- ions into the neuronal cells. This results in hyperpolarization, which inhibits neurotransmission and induces sedative and sleep-promoting effects.
in vitro
  • SLPS inhibited the binding of [3H]-muscimol, a well-known GABAA receptor agonist, in a dose-dependent manner. The IC50 value of SLPS was determined to be 0.026 mg/mL.
  • SLPS induced GABAA receptor activity. The heightened responses to the SLPS were almost blocked by the GABAA receptor antagonist bicuculline, confirming the specificity of the observed effects on GABAA receptor activity.

Source: Kim, S., Kim, D., Lee, J., Han, J. K., Um, M. Y., Jung, J. H., ... & Cho, S. (2024). Novel neuropharmacological activity of citrus lime (Citrus aurantifolia): A standardized lime peel supplement enhances non-rapid eye movement sleep by activating the GABA type A receptor. Biomedicine & Pharmacotherapy, 179, 117410.

in vivo
  • In the pentobarbital-induced sleep test and sleep structure analysis, the hypnotic effect of SLPS was fully blocked by bicuculline, similar to muscimol, a GABAA receptor agonist.

출처: Kim, S., Kim, D., Lee, J., Han, J. K., Um, M. Y., Jung, J. H., ... & Cho, S. (2024). Novel neuropharmacological activity of citrus lime (Citrus aurantifolia): A standardized lime peel supplement enhances non-rapid eye movement sleep by activating the GABA type A receptor. Biomedicine & Pharmacotherapy, 179, 117410.

Safety
Safety assessment in humans and animals

Both the toxicity studies in human and animals showed no adverse affects, confirming that long-term and medium-term consumption of the BENESOMNO™ at the daily intake dose (300 mg/day) is safe without any safety concerns.

Toxicity studies in humans

Toxicity studies in humans

  • A clinical trial was conducted on adults (80 males and females, aged 19 to 65 years) with a Pittsburgh Sleep Quality Index (PSQI) score of 5 or higher, and after two weeks of consuming the test ingredient, no serious adverse reactions were observed.
  • No statistically significant differences were found between groups in vital signs (body temperature, blood pressure, and pulse) or in the results of hematological and blood biochemical analyses.
Toxicity studies in animals

Toxicity studies in animals

  • Acute toxicity study: No deaths or abnormal symptoms were observed, and all animals exhibited normal weight gain (LD50 > 2,000 mg/kg)
  • 90-day repeated-dose toxicity study: No observed adverse effect level (NOAEL) > 2,000 mg/kg

    - During the 90-day observation period and the subsequent 29-day recovery period, no abnormalities were detected in body weight, food consumption, hematological and blood biochemical parameters, histopathological and ophthalmological examination, or organ weight. Additionally, there were no statistically significant differences between groups.

    - The NOAEL was determined to be ≥2,000 mg/kg body weight per day. Applying a safety factor of 10 for an adult weighing 60 kg, the estimated safe intake is ≥12 g/day. The daily intake of BENESOMNO™ is 300 mg, which is 40 times lower than this threshold.

  • Genotoxicity (Ames, chromosomal aberration, and micronucleus test): No genotoxicity was observed.