Elicit: 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.
Methods
We analyzed 37 sources from an initial pool of 999, using 5 screening criteria. Each paper was reviewed for 5 key aspects that mattered most to the research question.
- Papers identified with Elicit search: n = 999
- Papers screened out: n = 962
- Papers included for extraction: n = 37
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 |
| Maniscalco et al., 2014 | Observational (case report), retrospective | 1 female, 68 years, recurrent depression | No mention found | Drug interaction (Rhodiola + paroxetine) | No |
| Edwards et al., 2012 | Open-label, single-arm, prospective, multicentre | 101 adults, 30–60 years, life-stress symptoms | WS® 1375, 200 mg twice daily, 4 weeks, oral | Stress symptom improvement, safety | Yes |
| Hung et al., 2011 | Systematic review/meta-analysis | 503 participants, various randomized controlled trials | 60–680 mg, 1–42 days, oral | Efficacy/safety for various indications | Yes |
Adverse Effects Profile
| Study | Adverse Effects Reported | Frequency/Incidence | Severity Assessment |
|---|---|---|---|
| Mao et al., 2015 | Nausea, sexual dysfunction, insomnia, headache | Rhodiola rosea: 30%; Sertraline: 63%; Placebo: 16.7% | No serious adverse events |
| Punja et al., 2014 | Headache, light-headedness, diarrhea | 10 events in each group | Mild to moderate; no severe adverse events |
| Bystritsky et al., 2008 | Dizziness, dry mouth | Not mentioned | Mild or moderate |
| Maniscalco et al., 2014 | Vegetative syndrome | Single case | Clinically significant |
| Edwards et al., 2012 | Dizziness, gastrointestinal | 36/101 (35.6%) | Mostly mild; no serious adverse events |
| Hung et al., 2011 | Headache, hypersalivation | 3/503 | Mild |
Drug Interactions
Several studies and reviews highlighted the potential for drug interactions with Rhodiola rosea, particularly with psychotropic medications:
- Case reports documented serotonin syndrome and other serious reactions when Rhodiola rosea was combined with selective serotonin reuptake inhibitors or other psychotropic drugs.
- Pharmacokinetic studies suggest that Rhodiola rosea may inhibit cytochrome P450 2C9 activity, affecting the metabolism of other drugs.
- Reviews recommend caution when combining Rhodiola rosea with medications metabolized by cytochrome P450 enzymes or with central nervous system-active drugs.
Dose-Response Relationships for Safety
- Across the studies reviewed, there is no clear evidence of a dose-dependent increase in adverse events within the commonly used dose range (100–680 milligrams per day).
- Reviews noted that effective and safe doses are typically 200–600 milligrams per day, with rare and mild side effects at these doses.