Rhodiola

Rhodiola (Rhodiola rosea L.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomic and Common Names

Rhodiola rosea L. is a flowering perennial plant found in Arctic regions of Europe, Asia, and North America. Known by several other names — including roseroot, rosenroot, golden root, and arctic root — this member of the family Crassulaceae has been used for medicinal purposes for centuries, with the Greek physician Dioscorides describing medicinal application in 77 AD.

Rhodiola rosea L., mainly known within the medicinal plant industry as golden root, Arctic root, or rose root, derives its name from its economic significance, distinctive morphology, and restricted geographical distribution.

The genus Rhodiola contains more than 100 different species, and at least 20 of these are used in traditional Asian medicine. However, most animal and human studies have been conducted on R. rosea, so whether other species confer the same health benefits is unknown.

Plant Part Used and Harvesting

The most valuable parts of the plant used in therapy are R. rosea roots and rhizomes, of a golden metallic colour, harvested after at least a 5-year vegetative period.

Arctic root is the common name for the underground stem (or rhizome) and root of the plant Rhodiola rosea L. The plant is cultivated or gathered to obtain the underground organs (root and rhizome) for medicinal use.

Common Preparations and Dosage Forms

As a dietary supplement, numerous preparations of extracts are used worldwide, including teas, homeopathic preparations and tinctures, as well as standardized extract. The European Medicines Agency's monograph specifies the use of a dry extract (DER 1.5–5:1), with ethanol 67–70% V/V as the extraction solvent.

Species Adulteration and Quality Issues

The United States Herbal Medicines Compendium identifies several Rhodiola species as potentially confounding in the commercial supply of Rhodiola rosea, including R. crenulata, R. kirilowii, R. sacra, R. serrata, R. sachalinensis, and R. yunnanensis. Analysis has indicated the intentional or accidental substitution of R. rosea with R. crenulata in commercial products; a typical adulterant species is also R. sachalinensis, which has a similar chemical composition to R. rosea but contains lower amounts of rosavins and salidroside.

Rhodiola is not a regulated substance under most government and public health agency policies, which eliminates any requirements that Rhodiola products must contain adequate or standardized levels of active compounds.

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2. Traditional and Historical Use

Antiquity and Early European Use

This member of the Crassulaceae family has been used for medicinal purposes for centuries, with the Greek physician Dioscorides describing medicinal application in 77 AD. In Linné's Materia Medica (1749), the root of Rhodiola is recommended for the treatment of headaches, hysteria, hernias, and discharges, and for use as an astringent. A monograph on the root is also found in the first Swedish national pharmacopoeia.

Scandinavian and Russian Folk Medicine

The herb has been used traditionally in Iceland, Norway, Sweden, Russia, as well as Eastern Europe and Asia, as a "tonic herb" said to fight fatigue, aid convalescence from illness, prevent infections, and enhance sexual function. In traditional and popular Russian medicine, R. rosea is used to increase physical endurance, work productivity, longevity, and resistance to altitude sickness, and to treat fatigue, depression, anaemia, impotence, gastrointestinal ailments, and infections and disorders of the nervous system.

Tibetan, Chinese, and Central Asian Use

R. rosea has a long history of use as a medicinal plant, appearing in reports from Asian and European countries. The therapeutic use of Rhodiola rosea roots traces back to Tibetan Traditional Medicine (TTM), which has influenced its more recent use in Traditional Chinese Medicine (TCM), where it was employed to treat altitude sickness, fatigue, and mood disorders, as well as headaches, diarrhoea, skin conditions and swelling, typically in the form of infusions and tinctures.

In Middle Asia, tea prepared from R. rosea is used as a remedy against colds and influenza. It is recommended for the treatment of cancer and tuberculosis in Mongolia.

Soviet-Era Research and the Adaptogen Concept

The traditional use of R. rosea as a tonic in Siberian and Russian medicine stimulated extensive research leading to the identification of R. rosea as an adaptogen — a substance that nonspecifically increases the resistance of an organism and does not disturb normal biological function. In the twentieth century, Soviet physicians classified Rhodiola as an adaptogen. Rhodiola rosea has been used for a long time in Eastern Europe and Asia to enhance physical and mental performance.

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3. Key Constituents and Active Compounds

Primary Bioactive Classes

The pharmacological effects of Rhodiola rosea are linked to several active compounds, including rosavins (rosavin, rosarin, rosin), salidroside, tyrosol, and a range of flavonoids and tannins. The two major constituents — salidroside and tyrosol — exhibit adaptogenic, antifatigue, antidepressant, antioxidant, anti-inflammatory, antinociception, and anticancer bioactivities, modulate immune function, and show potential cardiovascular, neuronal, liver, and skin disorder prevention.

Eight compounds — including rosarin, rosavin, rosin, salidroside, tyrosol, rhodionin, catechin, and gallic acid — have been suggested as reference markers for distinguishing Rhodiola species from other plants. Salidroside is present in all species of the Rhodiola genus and in a wide variety of species outside this genus, while the rosavins (rosavin, rosin, rosarin) are specific components characteristic of R. rosea.

Standardization of Commercial Extracts

Most standardized extracts contain at least 3% rosavins and 1% salidroside to ensure consistency. This 3:1 ratio of rosavins to salidroside reflects the naturally occurring ratio in the root and is the ratio used in most published clinical research.

Salidroside, a phenylpropanoid glycoside, is the main bioactive component of Rhodiola rosea L. Among the 28 different compounds identified in R. rosea, p-tyrosol, salidroside, and five salidroside-like glycosides (rhodiolin, rosiridin, rosarin, rosavin, and rosin) possess strong antioxidant activities.

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4. Mechanisms of Action

Adaptogenic and HPA Axis Modulation

Rhodiola primarily exerts its effects through dose-dependent modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the serum levels of stress hormones such as cortisol. The plant's adaptogenic activity is linked to its ability to influence several neuroendocrine pathways simultaneously, including the hypothalamic-pituitary-adrenal (HPA) axis, the sympathoadrenal system, and key neurotransmitter systems including serotonin and dopamine.

Monoaminergic Neurotransmitter Effects

Several active compounds found in R. rosea extracts — including salidroside, rosavin, rosarin, triandrin, and tyrosol — stimulate the brain and increase the concentration of neurotransmitters such as norepinephrine (NE), serotonin (5-HT), acetylcholine (ACh), and dopamine (DA).

Rosavins appear to contribute to rhodiola's adaptogenic, antidepressant, and cognitive effects, likely through interactions with monoaminergic neurotransmitter systems and HPA axis modulation, though their mechanisms remain less completely characterised than those of salidroside.

Heat Shock Protein Induction

Its mechanisms include upregulation of heat shock protein 70 (HSP-70), modulation of NF-kB inflammatory signalling, stimulation of AMPK in metabolic tissues, and effects on monoamine neurotransmitter pathways.

MAO Inhibition

Several studies utilizing Rhodiola rosea, which contains a complex mixture of phytochemicals, reported some positive drug-drug interaction (DDI) findings based on in vitro CYP450 enzyme inhibition, MAO-A and MAO-B inhibition, and preclinical pharmacokinetic studies in either rats or rabbits.

Antioxidant Activity

Rhodiola rosea's antioxidant properties help neutralize free radicals, reducing oxidative stress and protecting cells from damage. Salidroside, another active compound present in Rhodiola, also contributes to the plant's antioxidant and neuroprotective effects.

Neuroplasticity and Synaptic Effects

Rosavin, salidroside, and commercially available R. rosea extract have been shown to increase long-term potentiation (LTP) in in vitro slice physiology experiments. Rosavin was more active at higher concentrations than salidroside, while salidroside was more effective at lower concentrations.

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5. Scientific Evidence by Area of Use

5.1 Fatigue and Stress

Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system and treat stress-induced fatigue and depression. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue, and burnout.

A systematic review published in BMC Complementary and Alternative Medicine (Ishaque et al., 2012) comprehensively evaluated the evidence. Of 206 articles identified in the search, 11 met inclusion criteria. Ten were described as RCTs and one as a controlled clinical trial. Two of six trials examining physical fatigue in healthy populations reported R. rosea to be effective, as did three of five RCTs evaluating R. rosea for mental fatigue. However, all of the included studies exhibit either a high risk of bias or have reporting flaws that hinder assessment of their true validity. Research regarding R. rosea efficacy is therefore contradictory.

Orally administered for 2–6 weeks, a dry SHR-5 extract prepared with 70% ethanol (v/v) and administered in daily doses of 288–680 mg (1–4 tablets) has been shown to improve mood, cognitive performance and attention, and to relieve fatigue in stress-related conditions.

One trial highlighted in a 2022 review had 101 adult subjects with life-stress symptoms take 200 mg of Rhodiola rosea extract twice daily for four weeks, resulting in significant improvements in stress symptoms, fatigue, mood, and quality of life. Additionally, a trial with 118 burnout patients taking 200 mg daily for eight weeks reported notable reductions in fatigue and burnout symptoms.

Evidence strength: Moderate preliminary evidence from multiple small RCTs. Results are generally positive for stress-induced fatigue and mental performance, but studies are heterogeneous, use different preparations and outcome measures, and meta-analysis has not been feasible. More large, high-quality replication trials are needed.

5.2 Depression

Clinical assessment of R. rosea rhizome extracts in humans with various depressive syndromes is based upon results from two randomized, double-blind, placebo-controlled trials of 146 subjects with major depressive disorder and seven open-label studies totaling 714 individuals with stress-induced mild depression. Overall, results of these studies suggest a possible antidepressant action for R. rosea extract in adult humans.

According to a study in the journal Phytomedicine led by researchers at the Perelman School of Medicine of the University of Pennsylvania, Rhodiola rosea may be a beneficial treatment option for major depressive disorder. The proof-of-concept trial was the first randomized, double-blind, placebo-controlled, comparison trial of oral R. rosea extract versus the conventional antidepressant therapy sertraline for mild to moderate major depressive disorder. Subjects with MDD were randomized to either R. rosea extract 340–1,360 mg daily, sertraline 50–200 mg daily, or placebo for 12 weeks. Although R. rosea produced less antidepressant effect versus sertraline, it also resulted in significantly fewer adverse events and was better tolerated.

A reviewed trial involving 60 participants with mild-to-moderate depression found that daily doses of 340–680 mg of Rhodiola rosea significantly improved depression symptoms and overall mental health.

Evidence-based data supporting the effectiveness of R. rosea for depression in adults is limited, and a comprehensive review of available animal and human studies is warranted.

Evidence strength: Preliminary. Two randomized controlled trials involving humans with diagnosed depression have been reported. Results are encouraging but not definitive. The University of Pennsylvania trial found R. rosea inferior to sertraline in antidepressant effect but with a superior tolerability profile. Large-scale replication is lacking.

5.3 Cognitive Performance and Mental Acuity

It belongs to the family of Crassulaceae with notoriety for stimulating physical endurance, attention span, memory, and work productivity. Rhodiola rosea is a moderately well-studied adaptogen that supports stress resilience and reduces fatigue by modulating the HPA axis, thus enhancing the activity of key neurotransmitters and conferring protection against oxidative stress. Evidence from both clinical and observational studies supports the role of Rhodiola in enhancing cognitive performance, improving mood, and increasing physical endurance, especially in individuals exposed to frequent, high-stress environments.

In a study on 80 healthy students, a 14-day regimen of 400 mg R. rosea root extract significantly reduced anxiety, stress, anger, and confusion while improving mood.

Evidence strength: Preliminary to moderate. Most cognition studies have been conducted in healthy populations under stress conditions (e.g., exam periods, night-shift work), with generally positive outcomes for attention and mental processing speed. Study quality is variable.

5.4 Physical Exercise Performance

The beneficial effects of R. rosea on enhancing physical performance have been evaluated in professional athletes and non-trained individuals.

In an endurance exercise performance test, 24 healthy volunteers treated with 100 mg of R. rosea extract (containing 3% rosavin and 1% salidroside) exhibited significant increases in time to exhaustion, VO₂, VCO₂, peak O₂ output, and peak CO₂ output.

Research by Noreen et al. examined the efficacy of a 3 mg·kg⁻¹ body mass dose of R. rosea on 6-mile cycle time trial performance in 18 active women. They reported that R. rosea significantly decreased submaximal exercise heart rate, reduced RPE (rating of perceived exertion), and improved time trial performance time.

Two of six trials examining physical fatigue in healthy populations reported R. rosea to be effective. None of the studies examining R. rosea for physical or mental fatigue measured outcomes consistently — no two studies reported the same outcomes — and as such, meta-analysis could not be performed.

Evidence strength: Weak to moderate. Some positive signals exist for endurance and time-to-exhaustion measures, but trials are small, heterogeneous in design, and results are not uniform across studies. No strong consensus exists on ergogenic benefit.

5.5 Anxiety

R. rosea exhibits antidepressant and anxiolytic properties that have been validated in randomized controlled trials. Patients suffering from mild to moderate depression reported improved mood, reduced anxiety, and enhanced quality of life following Rhodiola administration, with a favorable safety profile.

Evidence strength: Preliminary. Anxiety outcomes have largely been measured as secondary endpoints in stress or depression trials. Dedicated, adequately powered anxiety trials are limited.

5.6 Anti-aging and Longevity (Preclinical)

Rhodiola rosea extracts have demonstrated strong anti-aging effects in different model organisms, such as fruit flies, worms, and yeast. The mechanisms of Rhodiola rosea extracts' anti-aging effects remain unclear.

Evidence strength: Preclinical only. Anti-aging findings derive from model organisms. No established human clinical evidence exists for longevity effects.

5.7 Cardioprotective and Hepatoprotective Effects

The pharmacological effects of Rhodiola rosea, including its role in increasing longevity, stimulating the central nervous system, and elevating work performance, as well as its cardio-, neuro-, and hepatoprotective effects and immunotropic, antiviral, anti-inflammatory, and antibacterial activities, have been studied extensively.

Evidence strength: Largely preclinical (animal models and in vitro). Limited human evidence specifically targeting cardioprotective or hepatoprotective endpoints.

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6. Regulatory Status and Official Monographs

The European Medicines Agency (EMA) Committee on Herbal Medicinal Products (HMPC) adopted a Community Herbal Monograph on Rhodiola rosea L., rhizoma et radix (EMA/HMPC/232091/2011) on 27 March 2012. In 2011/2012, the European Medicines Agency approved its use for stress-related symptoms.

R. rosea is one of the main representatives of the group of plant adaptogens used for medicinal purposes linked to stress and age-related impairments of cognitive functions as a tonic and immunomodulating therapeutic agent, as noted by the European Food Safety Authority (EFSA, 2012).

Health Canada's Natural Health Products Directorate has also published an official monograph for Rhodiola rosea. For non-standardized ethanolic dry extracts, the monograph specifies not to exceed 400 milligrams of extract and a quantity crude equivalent (QCE) of 2 grams of dried root/root and rhizome per day, and not to exceed 200 milligrams of extract and a QCE of 1 gram of dried root/root and rhizome per single dose.

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7. Dosages Reported in Clinical Studies

The following dosage ranges appear in published human studies; they should be understood as descriptive of what was studied, not as prescriptive recommendations:

• Daily doses of 288–680 mg of dry SHR-5 extract (ethanol 70% v/v) administered orally for 2–6 weeks have been used in studies examining mood, cognitive performance, and fatigue relief.
• A trial used 200 mg twice daily (400 mg/day) for four weeks in subjects with life-stress symptoms.
• A depression study used daily doses of 340–680 mg of Rhodiola rosea.
• The University of Pennsylvania MDD trial dosed subjects at 340–1,360 mg daily of R. rosea extract for 12 weeks.
• Rhodiola rosea extract WS® 1375 was used at 200 mg twice daily for 4 weeks in subjects with life-stress symptoms. Two hundred milligrams of dry extract from R. rosea roots and rhizomes is equivalent to 300–1,000 mg of R. rosea roots and rhizomes.
• In an endurance exercise test, 100 mg of R. rosea extract (containing 3% rosavin and 1% salidroside) was administered to 24 healthy volunteers.
• A study on 80 healthy students used 400 mg of R. rosea root extract daily for 14 days.

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8. Safety Considerations and Drug Interactions

General Tolerability

In contrast to most conventional antidepressants, R. rosea extract appears to be well-tolerated in short-term studies with a favorable safety profile. Rhodiola rosea-based preparations are often noted for their good tolerability, which is a critical factor for long-term use.

No case of overdose has been reported according to the EMA community herbal monograph. Hypersensitivity to the active substance is listed as a contraindication.

Drug Interactions: CYP450 Enzymes

Rhodiola rosea-based preparations may influence the metabolism of other drugs by inhibiting cytochrome P450 enzymes, particularly CYP2C9, CYP2D6, CYP3A4, and the activity of the P-gp transporter. 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.

Studies of isolated salidroside showed no significant interactions with CYP450 enzymes. However, Rhodiola rosea extracts contain a mixture of biologically active substances, complicating precise predictions of their effects and increasing the risk of unwanted interactions.

Drug Interactions: Serotonergic Agents

Particular attention should be given to the potential interactions of Rhodiola rosea with psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, given the risk of serotonin syndrome.

Case reports have documented serotonin syndrome and other serious reactions when Rhodiola rosea was combined with selective serotonin reuptake inhibitors or other psychotropic drugs. One documented case involved a 68-year-old woman who suffered restlessness and trembling 15 days after she began taking Rhodiola at a dose of 400 mg/day in conjunction with paroxetine (an SSRI) at 20 mg/day; the symptoms disappeared 2 days after cessation of the herb. Researchers concluded the symptoms were most likely due to serotonin syndrome, due to the additive pharmacodynamic effect of the herb.

Rhodiola has been found to modulate monoaminergic transmission, as well as inhibit the activity of cytochrome P450 enzymes CYP2D6 and CYP3A4. These findings suggest that Rhodiola may increase the risk of serotonin toxicity when combined with certain psychotropic medications, and potentially increase the plasma concentrations of co-administered psychotropics.

Populations with Limited Safety Data

While many individuals report no adverse effects, comprehensive safety data is lacking, particularly for vulnerable populations such as children and pregnant women.

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9. Body Systems and Health Areas Associated with Rhodiola

• Central Nervous System: Rhodiola's adaptogenic effect increases attention and endurance in situations of decreased performance caused by fatigue and sensation of weakness, and reduces stress-induced impairments and disorders related to the function of neuroendocrine and immune systems.
• Neuroendocrine (HPA Axis): Modulation of the HPA axis, which regulates serum levels of stress hormones such as cortisol.
• Cardiovascular: Cardioprotective effects have been studied extensively, primarily in preclinical models.
• Hepatic: Hepatoprotective effects have been studied, primarily in preclinical models.
• Immune System: Salidroside and tyrosol exhibit immunomodulatory bioactivities.
• Musculoskeletal/Exercise: The beneficial effects of R. rosea on enhancing physical performance have been evaluated in professional athletes and non-trained individuals.
• Mood and Mental Health: R. rosea demonstrates multi-target effects on various levels of the regulation of cell response to stress, affecting components of the neuroendocrine, neurotransmitter receptor, and molecular networks associated with possible beneficial effects on mood.

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References

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