D-Limonene
Summary
D-limonene is the major terpene in orange and lemon peel oil. It is absorbed and concentrates in fatty tissue, but human studies are small, uncontrolled and measure tissue levels or biomarkers (grade D). No controlled trial in PubMed supports its popular use for heartburn. High doses cause nausea, vomiting and diarrhoea.
Key facts
- Listed as generally recognised as safe (GRAS) as a flavouring in US federal regulations[4]
- Maximum tolerated dose 8 g/m² per day; nausea, vomiting and diarrhoea were dose-limiting[2]
- 2 g/day for 2–6 weeks reached a mean 41.3 μg/g in breast tissue[1]
- Described in a 2007 review; no controlled trial indexed in PubMed[4]
- 2 graded human outcomes on this page
- October 13, 2026
How it works
ProposedLimonene is fat-soluble, is absorbed after oral intake and is metabolised to perillic acid and other compounds; it accumulated in fat and breast tissue at levels far above plasma. A 2007 review attributes heartburn use to proposed acid-neutralising and peristalsis effects, which have not been tested in controlled trials. Oxidised limonene on the skin forms hydroperoxides that can cause contact allergy.[2][3][1][4][5]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Tissue biomarkers | Grade D | Mixed | Open-label · n = 43 · 2013 | 1 row |
| Absorption | Grade D | Mixed | PK study · n = 7 · 2010 | 1 row |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Breast tissue limonene levels and tumour markers (cyclin D1, Ki67) | Mixed | Grade D | Open-label trial · n = 43 · 2013 Women with newly diagnosed operable early-stage breast cancer awaiting surgery Form: D-limonene capsules · Dose: 2 g/day · Duration: 2–6 weeks before surgery Limonene concentrated in breast tissue (mean 41.3 μg/g) and tumour cyclin D1 fell 22%, with little change in Ki67 or cleaved caspase-3. Serum IGF-1 rose slightly; other blood markers did not change. | 23554130 (opens PubMed)Source [1] |
| Fat-tissue and plasma limonene levels | Mixed | Grade D | PK study · n = 7 · 2010 Healthy adults Form: D-limonene-rich homemade lemonade · Dose: 40 oz (about 1.2 L) lemonade providing 500–600 mg d-limonene daily · Duration: 4 weeks Limonene in buttock fat rose from undetectable–7.8 to 54–294 μmol/kg and was 51–195 times plasma levels, showing it accumulates in fat tissue. | 20661827 (opens PubMed)Source [3] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| D-limonene softgels (orange peel oil) | Varies[6][7] | Absorbed after oral dosing; circulating metabolites peaked well above limonene itself, and limonene concentrated in tumour and breast tissue.[2][1] | Nausea, vomiting and diarrhoea were dose-limiting in cancer patients at high doses; labels advise stopping if persistent stomach upset occurs.[2][6] | Tissue uptake and tolerability in cancer patients |
| Citrus peel in foods and drinks | Varies[3] | 500–600 mg/day from peel-rich lemonade raised fat-tissue limonene within 4 weeks.[3] | Not reported as a problem in the 4-week lemonade study.[3] | Pharmacokinetics |
Studied doses
Doses studied in human trials ranged from 500–600 mg a day from lemonade for 4 weeks and 2 g a day in capsules for 2–6 weeks, to 0.5–12 g/m² a day in 21-day cycles in an advanced-cancer dose-finding trial.[1][2][3]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
None found in our sources.
Who should be careful
- Gastritis or peptic ulcer disease
- One d-limonene label warns against use in gastritis or peptic ulcer disease, and high doses caused nausea, vomiting and diarrhoea in trials.[7][2]
- Fragrance or limonene contact allergy
- Oxidised limonene forms hydroperoxides that frequently cause positive patch tests in people with dermatitis.[5]
- Pregnancy and breastfeeding
- Labels advise against use or medical advice first; no human study cited here enrolled pregnant or breastfeeding women.[6][7]
- Ongoing heartburn
- Persistent heartburn deserves medical assessment; d-limonene has no controlled trial evidence for it.[4]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
How to read the label
- Per serving, not per softgelOne label lists 1,000 mg d-limonene per 2-softgel serving, which is 500 mg per softgel.[6]
- Heartburn-style regimensAnother label directs 1 g every other day for 20 days, then as needed; this schedule has not been tested in a published controlled trial.[7][4]
- Label dose vs studied doseA 1 g serving is half the 2 g/day used in the breast-tissue study and far below the dose-limiting levels in cancer trials.[6][1][2]
Cost per studied dose, without the sales pitch
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Cost per studied dose
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Frequently asked questions
Does d-limonene help heartburn?
It is marketed for heartburn and a 2007 review describes that use, but no controlled trial indexed in PubMed has tested it.[4]
Is d-limonene safe?
It is GRAS as a food flavouring. In cancer patients, very high doses caused nausea, vomiting and diarrhoea; the maximum tolerated dose was 8 g/m² per day.[4][2]
Does d-limonene fight cancer?
Human evidence is limited to small uncontrolled studies measuring tissue levels and biomarkers; no trial has shown a clinical benefit.[1][2]
How much d-limonene is in a softgel?
Check the serving size: one label lists 1,000 mg per 2 softgels, or 500 mg each.[6]
Can limonene cause skin allergy?
Yes. When limonene oxidises it forms hydroperoxides that commonly cause allergic contact dermatitis on patch testing.[5]
Sources
- [1]Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer.. Cancer Prev Res (Phila), 2013. open-label
- [2]Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee.. Cancer Chemother Pharmacol, 1998. open-label
- [3]Adipose tissue accumulation of d-limonene with the consumption of a lemonade preparation rich in d-limonene content.. Nutr Cancer, 2010. PK-study
- [4]D-Limonene: safety and clinical applications.. Altern Med Rev, 2007. review
- [5]Limonene and linalool hydroperoxides review: Pros and cons for routine patch testing.. Contact Dermatitis, 2022. review
- [6]D-Limonene 500 mg (Jarrow Formulas), DSLD label 201213: 1,000 mg d-limonene per 2-softgel serving (500 mg per softgel), once daily; stop if persistent stomach upset. NIH Office of Dietary Supplements, Dietary Supplement Label Database, 2019. label
- [7]D-Limonene (Integrative Therapeutics), DSLD label 305284: 1 g orange peel extract per softgel, every other day for 20 days then as needed; not for people with gastritis or peptic ulcer disease. NIH Office of Dietary Supplements, Dietary Supplement Label Database, 2024. label
What changed
- Strict adversarial pass: PMIDs re-checked; no controlled heartburn trial found in PubMed and the page says so. Biomarker studies graded D; DSLD labels verified per serving (1,000 mg per 2 softgels).
- First draft rebuilt from scratch after the earlier draft files were lost. Every PMID checked against NCBI esummary and abstracts read for each row. Label amounts re-read from the DSLD API as per-serving amounts: 1,000 mg per 2-softgel serving (label 201213) and 1 g orange peel extract per softgel (label 305284).