Table 2.
Relevant clinical trials on the effects of Rhodiola rosea L on mental and physical performance.
| Reference | Study Design | Condition | Participants | Intervention | Control | Duration | Outcome Measures | Results |
|---|---|---|---|---|---|---|---|---|
| Darbinyan (2000) | randomized, placebo-controlled, double-blind, crossover with a wash-out period | Work-related fatigue | 56 healthy male and female physicians aged 24–35 | 170 mg of R. rosea SHR-5 extract | Placebo | 42 days total duration; 14 days intervention |
Overall level of mental fatigue calculated according to the Fatigue Index, involving complex perceptive and cognitive cerebral functions | A statistically significant improvement in the Fatigue Index observed in the R. rosea treatment group compared to placebo |
| Edwards (2012) | multicentre, non-randomized, open-label, single-arm study conducted in 13 centres in UK | Life-stress symptoms | 101 ambulatory subjects between 30 and 60 years of age with life-stress symptoms | 200 mg of R. rosea dry extract WS® 1375, twice daily | None | 4 weeks | (1) Numerical Analogue Scales (NAS) of subjective stress Symptoms; (2) Perceived Stress Questionnaire (PSQ); (3) Multidimensional Fatigue Inventory 20 (MFI-20); (4) Numbers Connecting Test (NTC); (5) Sheehan Disability Scale (SDS); (6) Multidimensional Mood State Questionnaire (MDMQ); and (7) Clinical Global Impressions (CGI) |
All outcome variables showed consistent and steady improvements with regard to stress symptoms, fatigue, quality of life, mood, concentration, disability, functional impairment and overall therapeutic effect. A statistically significant improvement between baseline and week 4 based on the two-sided Wilcoxon signed-rank test was observed |
| Spasov (2000) | randomized, double-blind, placebo-controlled, 2 parallel groups study | Non-specific fatigue and stress during examination | 40 healthy medical students, 17–19 years old | 50 mg of R. rosea SHR-5 extract, twice daily | Placebo | 20 days | Physical fitness measured as: physical work capacity and an increase in pulse rate, neuro-motoric fitness, mental work capacity, self-evaluation of fatigue and general well-being | The students receiving R. rosea demonstrated significant improvements in physical fitness, neuro-motor functions, mental performance, and general well-being |
| Spasov (2000) | randomized, placebo-controlled, 3 parallel groups study | Study-related fatigue and stress | 60 healthy male students, 17–18 years old | 660 mg of R. rosea extract with no ethyl alcohol | Placebo and untreated | 20 days | Psychological fatigue, situational anxiety, motivation, precision of motor function, process of excitement, need for rest, mental work capacity and neuromotor function | An increase in physical work capacity, coordination, kinaesthetic sensitivity, and general well-being, along with a decrease in fatigue and situational anxiety observed in the R. rosea treatment group |
| Shevtsov (2003) | randomized, double-blind, placebo-controlled, parallel-group study with an extra non-treatment group | Work-related fatigue and stress | 161 healthy cadets, 19–21 years old | (1) 370 mg of R. rosea SHR-5 extract; (2) 555 mg of R. rosea SHR-5 extract |
Placebo and untreated | Single dose | Total Antifatigue Index (TAFI) calculated by two efficacy parameters: capacity for mental work, physiological parameters and safety parameters | A pronounced anti-fatigue effect reflected in the TAFI found in both R. rosea treatment groups. Statistically highly significant results for both doses. |
| Schutgens (2009) | randomized, double-blind, placebo-controlled, 3 parallel groups study | Experienced levels of stress and fatigue | 30 healthy students; mean age: 21.1 years | 144 mg of SHR-5 R. rosea extract, twice-daily | Placebo and ADAPT-232 | 7 days | (1) Ultra-weak photon emission; (2) Self-evaluated stress; (3) Self-evaluated fatigue. |
A statistically significant decrease in the experienced level of fatigue and decreased photon emission observed in the Rhodiola treatment group |
| Goyvaerts (2012) | open-label design | Burnout and fatigue syndrome | 330 female (74%) and male (26%) patients between 18 and 81 years | 288 mg of Rhodiola rosea SHR-5 extract | None | 8 weeks | Total burnout score: (1) Fatigue; (2) Exhaustion; (3) Depression; (4) Insomnia; (5) Loss of power. |
The Rhodiola extract showed an impressive, highly significant and continuous decline in the complaints of up to 63%, together with very good tolerability. |
| Olsson (2009) | randomized, double-blind, placebo-controlled, parallel group study | Fatigue syndrome | 60 patients diagnosed with fatigue syndrome; mean age: Rhodiola group—41 years, Placebo group—42.1 years | 144 mg of R. rosea SHR-5 extract, 4 capsules per day | Placebo | 28 days | (1) Fatigue (Pines’ burnout scale); (2) Depression (MADRS rating scale); (3) Quality of life (SF-36 questionnaire); (4) Saliva cortisol upon awakening; (5) Attention (CCPT II test). |
A notable anti-fatigue effect that increased mental performance, particularly the ability to concentrate and decreased cortisol response to awakening stress in burnout patients. |
| Lekomtseva (2017) | open-label, single-arm, multicentre study conducted in 5 hospitals in Ukraine | Prolonged or chronic fatigue syndrome |
100 subjects, 31 male, 69 female ones. Mean age: 37.8 ± 9.5 years |
200 mg of R. rosea dry extract WS® 1375, twice daily | None | 8 weeks | (1) Multidimensional Fatigue Inventory 20 (MFI-20); (2) NAS of chronic fatigue symptoms; (3) NTC; (4) SDS; (5) Pittsburgh Sleep Quality Index (PSQI); (6) PAQ; (7) Beck Depression Inventory II (BDI-II); (8) (CGI). |
A significant improvement in prolonged or chronic fatigue symptoms over 8 weeks. The values of nearly all outcome variables markedly improved over time, with a substantial alleviation of symptoms that could already be observed after the first week of treatment. |
| Kasper (2017) | exploratory, open-label, multicentre, single-arm trial conducted at four centres in Vienna, Austria | Burnout symptoms | 118 outpatients aged 30–60 years suffering from burnout symptoms | A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin) | None | 12 weeks | (1) Maslach Burnout Inventory; (2) Burnout Screening Scales I and II; (3) SDS; (4) PSQ; (5) NCT; (6) MDMQ; (7) NAS for different stress symptoms and impairment of sexual life; (8) Patient Sexual Function Questionnaire; (9) CGI Scales. |
The majority of the outcome measures showed clear improvements over time. A steady and substantial, statistically relevant alleviation of the majority of the assessed burnout symptoms was observed as early as 1 week after the start of treatment. |
| Bystritsky (2008) | open-label design | Generalized anxiety disorder (GAD) | 10 participants with a DSM-IV diagnosis of GAD between the ages of 34 and 55 | 340 mg of R. rosea extract (Rhodax®) | None | 10 weeks | (1) HARS; (2) Four-Dimensional Anxiety and Depression Scale; (3) CGI of Severity/Improvement Scale |
Significant improvements in GAD symptoms were found with R. rosea, with a reduction in HARS scores similar to that found in clinical trials. |
| Cropley (2015) | open-label, randomized, repeated measures design | Self-reported anxiety, stress, cognition, and other mood symptoms | 81 mildly anxious students randomized into one of two conditions: treatment = 40; control = 41 volunteers | 2 × 200 mg of a dry extract from R. rosea roots daily (Vitano®) | Untreated | 14 days | Primary outcomes: (1) Anxiety; (2) Stress. Secondary outcomes: (3) Mood; (4) Sleepiness; (5) Sleep; (6) Cognitive tests; (7) Choice reaction time; (8) Sustained Attention to Response Test (SART); (9) Symbol Digit Processing. |
The experimental group demonstrated a significant reduction in self-reported anxiety, stress, anger, confusion and depression at 14 days and a significant improvements in total mood. No relevant differences in cognitive performance were observed. |
| Darbinyan (2007) | randomized, double-blind, placebo-controlled study with 3 parallel groups | Mild to moderate depression | 89 male and female patients diagnosed with mild or moderate depression, age 18–70 years | 2 groups: (1) R. rosea SHR-5 extract 340 mg/day, (2) R. rosea SHR-5 extract 680 mg/day |
Placebo | 6 weeks | (1) Beck Depression Inventory (BDI); (2) Hamilton Rating Scale for Depression (HAM-D) questionnaires. |
Overall depression, insomnia, emotional instability and somatization significantly improved following medication. R. rosea shows anti-depressive potency. |
| Mao (2015) | randomized, double-blind, placebo-controlled study with 3 parallel groups | Mild to moderate major depressive disorder (MDD) | 57 male and female patients: R. rosea (n = 20), sertraline (n = 19), placebo (n = 18). Mean age: 45 years | (1) 340 mg of R. rosea SHR-5 extract, or (2) sertraline 50 mg HCl |
Placebo | 12 weeks | (1) Hamilton Depression Rating (HAM-D); (2) Beck Depression Inventory (BDI); (3) Clinical Global Impression Change (CGI/C). |
Patients taking R. rosea 1.4 times the odds of improvement, patients on sertraline 1.9 times the odds of improvement. R. rosea better tolerated than sertraline. |
| Gao (2020) | randomized, double-blind, placebo-controlled study with 3 parallel groups | Mild to moderate major depressive disorder (MDD) | 100 patients (33/33/34) with a DSM IV Axis I diagnosis of MDD aged 18–50 years | (A) sertraline (B) sertraline and Rhodiola (0.6 g/day) daily, (C) sertraline and Rhodiola capsule tablet (0.3 g/day). |
Placebo | 12 weeks | (1) Hamilton Depression Rating (HAM-D); (2) Beck Depression Inventory (BDI); (3) Clinical Global Impression Change (CGI/C). |
Statistically significant reductions in HAM-D, BDI, and CGI scores for all treatment conditions. The decline in HAM-D, BDI, and CGI scores was greater for group B versus group C and A. |
| Williams (2021) | placebo-controlled, double-blind, counterbalanced, crossover study | Resistance exercise performance | 10 resistance-trained males | 1500 mg/day standardized R. rosea extract for 3 days, additional 500 mg 30 min before testing | Placebo | 3 days | (1) Performance during repeated bench press exercise; (2) Blood concentrations of lactate (LA), epinephrine (EPI), and norepinephrine (NE). |
R. rosea increased mean bench press velocity. Higher LA and NE levels following exercise in the R. rosea-treated group, suggesting increased CNS and/or sympathetic activity. |
| Noreen (2013) | randomized, placebo-controlled, double-blind, crossover study | Endurance exercise performance, perceived exertion, mood and cognitive function | 18 recreationally active college women (22 ± 3.3 years, 56.6 ± 6.2 kg) | 3 mg·kg−1 of standardized R. rosea extract 1 hour before testing | Placebo | Single dose | (1) Rating of perceived exertion (RPE) (10-point Borg scale); (2) Blood lactate concentration, salivary cortisol, and salivary α-amylase; (3) Profile of Mood States (POMS) questionnaire and a Stroop Colour Test; |
R. rosea ingestion decreased heart rate during the warm-up and the mean RPE in the trial. Subjects completed the test significantly faster with R. rosea. Higher concentration of salivary alpha amylase in the R. rosea treatment group. |
| Duncan (2014) | placebo-controlled, double-blind, crossover study | Exercise performance, substrate utilisation, mood State, and rating of perceived exertion | Ten males, recreational exercisers (mean age ± S.D. = 26 ± 6 years) | 3 mg⋅kg−1 body mass of R. rosea (Indigo Herbs) | Placebo | Single dose | (1) Two 30-m cycling trials at an intensity of 70% of VO2 max; (2) Heart rate; (3) Rating of per ceived exertion (RPE); (4) mood state; (5) substrate utilisation |
Ingestion of R. rosea favourably influenced RPE and exercise affect without changes in energy expenditure or substrate utilization during 30-m submaximal cycling performance |
| Jowko (2016) | randomized, double-blind, placebo-controlled trial | Mental and physical performance, hormonal and oxidative stress biomarkers | 26 healthy, male, physical -education students (13/13) | 600 mg of standardized R. rosea extract | Placebo | 4 weeks | (1) Psychomotor tests for simple and choice reaction time—Vienna Test System; (2) VO2peak test; (3) Hormonal profile (cortisol, testosterone, and growth hormone); (4) Biomarkers of oxidative stress; (5) Muscle damage (CK). |
R. rosea ingestion improved psychomotor performance and shortened reaction time and total response time. No changes in endurance exercise capacity and hormonal profile were observed. R. rosea ingestion raised plasma total antioxidant capacity. |
| Ballman (2018) | randomized, blinded, placebo-controlled and counterbalanced study | Anaerobic exercise performance | 11 physically active female participants, aged 18 to 24 years | 1500 mg/day standardized R. rosea extract for 3 days, 500 mg 30 min before testing | Placebo | 3 days | 3 × 15 second Wingate Anaerobic Tests (WAnTs)—mean watts, anaerobic capacity, anaerobic power, mean peak watts, and mean total work | All WAnTs outcome measures were higher in the R. rosea treatment trial. R. rosea enhanced power output and total work during repeated WAnTs. |
| De Bock (2004) | randomized, placebo-controlled, double-blind, crossover study | Improvement in endurance exercise performance | 24 healthy and physically active male and female students (12/12), mean age: male—21.8 years, female—20.2 years | 2 capsules containing 100 mg of standardized R. rosea extract | Placebo | Phase I: 2 days Phase II: 4 weeks |
(1) Endurance exercise capacity; (2) Muscle strength; (3) Speed of limb movement; (4) Reaction time; (5) Ability to sustain attention. |
Time to exhaustion, O2 uptake and CO2 output significantly improved in the R. rosea group. Acute R. rosea intake can improve the endurance exercise capacity in young healthy volunteers. |
SHR-5: dry extract of root and rhizome of Rhodiola rosea L., drug-extract-ratio 2.5–5:1, first extraction solvent ethanol 70%, second extraction solvent water. Abbreviations: HAM-D—Hamilton Depression Rating; HARS—Hamilton Anxiety Rating Scale; CGI—Clinical Global Impressions, TAFI—Total Antifatigue Index; SDS—Sheehan Disability Scale; PSQ—Perceived Stress Questionnaire; NTC—Number Connection Test; MDMQ—Multidimensional Mood State Questionnaire; NAS—Numerical Analogue Scales; BDI—Beck Depression Inventory; RPE—rating of perceived exertion; WAnTs—Wingate Anaerobic Tests; POMS—Profile of Mood States.