Elicit: Adverse Effects of Rhodiola Rosea (public)
Adverse Effects of Rhodiola Rosea (public)
What are the most common adverse effects and potential drug interactions associated with rhodiola rosea supplementation?
The most common adverse effects of rhodiola rosea are headache, nausea (up to 30%), gastrointestinal disturbances, dizziness, and insomnia, while potential drug interactions include serotonin syndrome with SSRIs and effects on drugs metabolized by cytochrome P450 2C9.
Abstract
Rhodiola rosea supplementation has most often been linked to mild, transient adverse effects. In several controlled trials using daily doses between 340 and 680 milligrams, subjects reported symptoms such as headache, nausea (up to 30% in one trial), gastrointestinal disturbances, dizziness, and insomnia. Many trials noted no adverse events at all.
Studies documenting drug interactions indicate that Rhodiola rosea can, in some instances, precipitate clinically significant events. Case reports have linked its combined use with selective serotonin reuptake inhibitors to serotonin syndrome. Pharmacokinetic investigations point to inhibition of cytochrome P450 2C9, suggesting that drugs with a narrow therapeutic index, as well as other central nervous system–active agents, might be affected when taken with Rhodiola rosea.
Results
Characteristics of Included Studies
| Study | Study Design | Population | Rhodiola Dose/Duration | Primary Outcome Focus | Full text retrieved |
|---|---|---|---|---|---|
| Mao et al., 2015 | Randomized controlled trial, multi-arm, double-blind, prospective, single-centre | 57 adults with mild-moderate major depressive disorder | SHR-5 extract, 340 mg escalating to 4 capsules/day, 12 weeks, oral | Efficacy and safety vs sertraline/placebo | Yes |
| Punja et al., 2014 | Randomized controlled trial, parallel-group, double-blind, placebo-controlled, single-centre | 48 healthy nursing students (81% female), 18–55 years | 364 mg daily, 42 days, oral | Fatigue reduction, safety | Yes |
| Bystritsky et al., 2008 | Single-arm, open-label, prospective, single-centre | 10 adults with generalized anxiety disorder, 34–55 years | 340 mg/day, 10 weeks, oral | Generalized anxiety disorder symptom reduction, safety | No |
| … | … | … | … | … | … |
Adverse Effects Profile
| Study | Adverse Effects Reported | Frequency/Incidence | Severity Assessment |
|---|---|---|---|
| Mao et al., 2015 | Nausea, sexual dysfunction, appetite change, insomnia, palpitations, gastrointestinal disturbance, yawning, dry mouth, fatigue, headache, nervousness | Rhodiola rosea: 30.0%; Sertraline: 63.2%; Placebo: 16.7% | No explicit detail; no serious adverse events |
| Punja et al., 2014 | Headache, light-headedness, diarrhea/nausea, dark stool, nosebleed, blurred vision, excess energy, heartburn, palpitations, sore throat | 10 events in each group | Mild to moderate; no severe adverse events |
| Bystritsky et al., 2008 | Dizziness, dry mouth | No mention found | Mild or moderate |
| … | … | … | … |
Drug Interactions
Several studies and reviews highlighted the potential for drug interactions with Rhodiola rosea, particularly with psychotropic medications.
- Case reports and pharmacovigilance studies document serotonin syndrome and other serious reactions when Rhodiola rosea is combined with selective serotonin reuptake inhibitors or other psychotropic drugs.
- Pharmacokinetic studies suggest that Rhodiola rosea may inhibit cytochrome P450 2C9 activity, potentially affecting drugs with a narrow therapeutic index such as warfarin or phenytoin.
- Reviews caution about possible interactions with drugs metabolized by cytochrome P450 enzymes, and recommend avoiding Rhodiola rosea in combination with certain medications without medical supervision.
Summary of Adverse Effects Findings
- No adverse effects reported: 19 studies explicitly reported no adverse effects.
- Adverse effects reported: 13 studies reported adverse effects, most commonly mild and transient such as headache and gastrointestinal disturbances.
Conclusion
Rhodiola rosea appears safe and well-tolerated across a range of doses commonly used in clinical practice and research.