D-Limonene Dosing Recommendations
The recommended dosing for D-Limonene as a dietary supplement is 500-1000 mg per day for adults, with 8 g/m² per day being the maximum tolerated dose based on clinical studies. 1
Dosing Guidelines Based on Evidence
Standard Adult Dosing
- Initial dose: 500-600 mg daily 2
- Maintenance dose: 500-1000 mg daily
- Maximum tolerated dose: 8 g/m² per day 1
Dosing Considerations
Safety Profile
D-Limonene has been evaluated for safety with the following parameters:
- Reference dose (RfD): 2.5 mg/kg/day
- No-observed-adverse-effect level (NOAEL): 250 mg/kg/day
- Systemic exposure dose (SED): 1.48 mg/kg/day 3
Administration
- Oral administration is the standard route
- Can be taken as a single daily dose or divided into multiple doses
- Best absorbed when taken with food to minimize gastrointestinal side effects
Side Effects and Monitoring
Common Side Effects
At therapeutic doses (500-1000 mg/day):
- Generally well-tolerated
- Minimal reported adverse effects
At higher doses (approaching MTD of 8 g/m²/day):
- Nausea
- Vomiting
- Diarrhea 1
Monitoring Recommendations
- Liver function: D-limonene may slightly increase cytochrome P-450 and aminopyrine demethylase with prolonged use 4
- Gastrointestinal symptoms: Monitor for dose-limiting GI effects, particularly at higher doses
Special Populations
Pregnancy and Lactation
- Insufficient data exists for use during pregnancy or lactation
- Caution is advised due to lack of safety data
Pediatric Use
- No established dosing guidelines for children
- Use in children should be approached with caution due to limited safety data
Clinical Considerations
Pharmacokinetics
- D-limonene accumulates significantly in adipose tissue
- Adipose tissue levels can be 51-195 times higher than plasma levels after regular consumption 2
- Primary metabolites include perillic acid, dihydroperillic acid, limonene-1,2-diol, and uroterpenol 1
Drug Interactions
- May potentially interact with medications metabolized by cytochrome P-450 enzymes due to its effect on these enzymes 4
- Caution should be exercised when using with other medications
Practical Application
For most adults using D-limonene as a dietary supplement:
- Start with 500 mg daily
- Take with food to minimize potential GI effects
- May increase to 1000 mg daily if needed and well-tolerated
- Discontinue use if significant GI side effects occur
Pitfalls and Caveats
- Commercial preparations may vary in purity and concentration
- D-limonene is a fat-soluble compound that accumulates in adipose tissue, which may lead to prolonged effects 2
- While generally recognized as safe, long-term safety data beyond 30 days is limited
- The carcinogenic effects observed in male rats are considered irrelevant for humans as they are related to α(2u)-globulin, a protein absent in humans 3