Supplement
Limonene is the fragrant compound that gives citrus peels their scent, and the body breaks it down into related molecules such as perillyl alcohol. Research has looked most at its anti-cancer activity, and animal studies found effects in breast, colon, liver and pancreatic cancer models, though the evidence is limited. Human data is thin: early trials tested perillyl alcohol rather than limonene, and small studies suggested heartburn symptoms eased.
Sources: PMID 30466983; PMID 28829378
- Updated
- How we grade
- 18 studies cited
- Best evidence
- Grade C
- Conditions studied
- 2
- Outcomes
- 8
- Graded outcomes
- 0026
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Anti-Cancer Activity D-Limonene and its metabolite perillyl alcohol demonstrate anti-cancer effects in multiple animal models (breast, colon, liver, pancreatic cancer) via inhibition of isoprenylation of growth-related proteins. Early-phase human clinical trials have been conducted with perillyl alcohol, though direct human evidence for D-limonene itself remains limited. | Changes; see studies | Moderate effect | 6 studies | |||
Studies that measured anti-cancer activity
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| Heartburn/GERD Relief Small human studies suggest D-limonene (typically 1000 mg every other day) may relieve heartburn symptoms, possibly by coating the esophageal mucosa or modulating gastric motility. Has been used as an alternative therapy for GERD symptoms. | Changes; see studies | Moderate effect | ||||
| Antimicrobial Activity In vitro studies demonstrate D-limonene has antibacterial activity against MRSA (synergistic with gentamicin), E. coli O157:H7, and antifungal properties against spoilage yeasts. Also inhibits quorum sensing in Pseudomonas aeruginosa. No human clinical evidence. | Improves (the measure goes up) | Small effect | 5 studies | |||
Studies that measured antimicrobial activity
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| Neuroprotection A 2021 review summarized neuroprotective potential of limonene from preclinical studies. In animal models, limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release. No human clinical data exists. | Improves (the measure goes up) | Small effect | 3 studies | |||
Studies that measured neuroprotection
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| Liver Protection In rodent models, D-limonene reduces diet-induced hepatic fat accumulation and shows antifibrotic effects against CCl4-induced liver toxicity in Wistar rats. Hepatoprotective mechanisms may involve enzyme induction and reduction of oxidative stress markers. | Changes; see studies | Moderate effect | 2 studies | |||
| Blood Glucose Regulation In streptozotocin-induced diabetic rats, D-limonene ameliorated hyperglycemia and diabetes-related complications. In vitro studies of Citrus medica extracts containing limonene show activities relevant to diabetes. No human clinical trials available. | Improves (the measure goes down) | Moderate effect | 2 studies | |||
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Antioxidant Activity Multiple in vitro studies demonstrate antioxidant activity of D-limonene and limonene-rich citrus peel essential oils, including DPPH radical scavenging. No human clinical trials have specifically evaluated D-limonene's antioxidant effects in vivo. | Improves (the measure goes up) | Small effect | 4 studies | |||
Studies that measured antioxidant activity
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| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cardioprotection In rodent models, D-limonene diminished CCl4-induced cardiac toxicity by alleviating oxidative stress and inflammatory markers. One small human study found that olfactory stimulation with grapefruit essential oil (rich in limonene) affected autonomic neurotransmission and blood pressure. | Changes; see studies | Small effect | 2 studies | |||
Key findings
- Anti-Cancer ActivityChanges; see studies
- Heartburn/GERD ReliefChanges; see studies
- Antimicrobial ActivityImproves (the measure goes up)
Safety notes in the studies
- In rodent models, D-limonene reduces diet-induced hepatic fat accumulation and shows antifibrotic effects against CCl4-induced liver toxicity in Wistar rats.
- In rodent models, D-limonene diminished CCl4-induced cardiac toxicity by alleviating oxidative stress and inflammatory markers.
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- Grade C
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Studies cited
18 studies from PubMed
- D-limonene diminishes CCl4-induced cardiac toxicity by alleviating oxidative stress, inflammatory and cardiac markers.
- Antibacterial Activities and Synergistic Interaction of Citrus Essential Oils and Limonene with Gentamicin against Clinically Isolated Methicillin-Resistant Staphylococcus aureus.
- Neuroprotective Potential of Limonene and Limonene Containing Natural Products.
- Insights into the chemical composition and bioactivities of citrus peel essential oils.
- Virucidal Activity of Different Mouthwashes Using a Novel Biochemical Assay.
- LUAD transcriptomic profile analysis of d-limonene and potential lncRNA chemopreventive target.
- Grapefruit essential oils inhibit quorum sensing of Pseudomonas aeruginosa.
- Citrus peels prevent cancer.
- Antifibrotic effects of D-limonene (5(1-methyl-4-[1-methylethenyl]) cyclohexane) in CCl4 induced liver toxicity in Wistar rats.
- Antioxidant and Anticancer Activities of Essential Oil from Gannan Navel Orange Peel.
- d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.
- Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release.
- Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells.
- Volatile aroma components and antioxidant activities of the flavedo peel extract of unripe Shiikuwasha (Citrus depressa Hayata).
- In vitro evaluation of the antimicrobial activity of eugenol, limonene, and citrus extract against bacteria and yeasts, representative of the spoiling microflora of fruit juices.
- Antimicrobial activity of commercial citrus-based natural extracts against Escherichia coli O157:H7 isolates and mutant strains.
- In vitro activities of Citrus medica L. cv. Diamante (Diamante citron) relevant to treatment of diabetes and Alzheimer's disease.
- Olfactory stimulation with scent of essential oil of grapefruit affects autonomic neurotransmission and blood pressure.