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 using: Human Participants, Safety Outcomes, Study Design, Single Ingredient Attribution, Original Data Quality

n = 999

Papers screened out

n = 962

Papers included for extraction

n = 37

Paper search

Using your research question, we searched across over 126 million academic papers from the Semantic Scholar corpus. We retrieved the 999 papers most relevant to the query.

Screening

We screened in sources based on their abstracts that met these criteria:

Data extraction

We asked a large language model to extract each data column below from each paper.

Study Design:

Participant Characteristics:

Rhodiola Rosea Intervention Details:

Adverse Effects and Drug Interactions:

Safety Profile and Tolerability:

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 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 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 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) 1 female, 68 years, recurrent depression No mention found Drug interaction (Rhodiola + paroxetine) No
Edwards et al., 2012 Open-label, single-arm 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 60–680 mg, 1–42 days, oral Efficacy/safety for various indications Yes
Amsterdam and Panossian, 2016 Review/meta-analysis 860 (146 major depressive disorder, 714 stress-induced depression) 340–680 mg/day, up to 12 weeks, oral Antidepressant effects, safety Yes
Thu et al., 2015 Randomized controlled trial 13 healthy males, 20–26 years Arctic Root, 290 mg/day, 14 days, oral Cytochrome P450 enzyme activity, safety Yes
Darbinyan et al., 2007 Randomized controlled trial 89 adults, 18–70 years, mild-moderate depression SHR-5, 340/680 mg/day, 6 weeks, oral Depression symptom reduction, safety Yes
Lekomtseva et al., 2017 Open-label, single-arm 100 adults, 18–60 years, chronic fatigue WS® 1375, 400 mg/day, 8 weeks, oral Fatigue improvement, safety Yes

Summary of Study Characteristics:

Effects

Adverse Effects Profile

Study Adverse Effects Reported Frequency/Incidence Severity Assessment
Mao et al., 2015 Nausea, sexual dysfunction Rhodiola rosea: 30.0% No explicit detail; no serious adverse events
Punja et al., 2014 Headache, light-headedness 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
Maniscalco et al., 2014 Restlessness, trembling Single case Clinically significant
Edwards et al., 2012 Dizziness, abdominal distension 36/101 (35.6%) Mostly mild; no serious adverse events
Hung et al., 2011 Headache, hypersalivation 3/503 Mild
Amsterdam and Panossian, 2016 No explicit detail 30.0% Likely mild; no discontinuations
Thu et al., 2015 Increased energy/concentration 2/13 Mild
Darbinyan et al., 2007 None None None
Lekomtseva et al., 2017 Cardiac, gastrointestinal 41/101 (40.6%) Mild (81.8%)

Summary of Adverse Effects Findings:

Drug Interactions

Several studies highlighted the potential for drug interactions with Rhodiola rosea, particularly with psychotropic medications:

Summary of Drug Interaction Findings:

Dose-Response Relationships for Safety

Summary of Dose-Response Findings: