Health Care Professional Information

Scientific Name
Rhodiola rosea
Common Name

Golden root, Rose root, Hong Jing Tian, Rose root extract, Rosenroot, SHR-5

Clinical Summary

Rhodiola is a plant used in traditional medicine in Eastern Europe and Asia to enhance physical and mental performance, stimulate the nervous system, and fight depression. Rhodiola rosea extract and its key constituent salidroside have been esearched, although studies in humans are limited.

In vitro studies indicate that salidroside from rhodiola may have neuroprotective (8) (9) and anticancer effects (10).
Supplementation with rhodiola has been shown to improve physical endurance (1) and mental performance (2) (3), reduce stress-induced fatigue in humans (4) (5), and improve stress symptoms (19). However, additional, well-designed studies are needed to determine the true efficacy of rhodiola (20).
Preliminary data also suggest that it may be effective against generalized anxiety disorder (GAD) (6), and in the treatment of mild to moderate depression (7).

A small study showed that salidroside may have cardioprotective effects in patients with breast cancer receiving treatment with epirubicin (11), but more data are needed to confirm this effect.

Because rhodiola inhibits cytochrome P450 enzymes, p-glycoproteins and monoamine oxidase, it may interact with certain prescription drugs.

Purported Uses
  • Depression
  • Fatigue
  • Enhanced mental and physical performance
Constituents
  • Flavonoids: proanthocyanidins
  • Monoterpene glycoside: rosiridin
  • Phenylpropanoid glycosides: rosin, rosavin, and rosarin
  • Triterpenes
  • Phenolic acids: gallic acid
  • Phenylethanol derivatives: salidroside (rhodioloside) and tyrosol
    (13) (14) (15)
Mechanism of Action

In animal models, rhodiola exhibits dose- and time-dependent Th1 and Th2 cytokine modulation effects (16). Salidroside confers neuroprotective effects via nitric oxide (NO) pathway inhibition in vitro (9) and through induction of antioxidant enzymes thioredoxin, heme oxygenase-1, and peroxiredoxin-I; downregulation of proapoptotic Bax protein; and upregulation of antiapoptotic Bcl-XL proteins (8). Another study shows the constituents of rhodiola have synergistic antioxidant activity (17). In vitro, rhodiola inhibits monoamine oxidases (MAOs) A and B suggesting that it has antidepressant effects (13).

In human breast cancer cells, salidroside induces cell-cycle arrest and apoptosis via mechanisms as yet unidentified, but independent of the estrogen receptor (10).

Contraindications
  • Patients taking prescription antidepressant medications should use rhodiola with caution as concurrent use was reported to cause tachyarrhythmia (18).
Adverse Reactions
  • Dizziness and dry mouth(6)
  • Case Report: A 26-year-old Chinese female presented to the emergency department with significant tachyarrhythmia following ingestion of rhodiola along with her antidepressant for 3 days (18).
Herb-Drug Interactions
  • Cytochrome P450 3A4 substrates: Rhodiola inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme (12) (21).
  • P-glycoprotein substrates: Rhodiola was shown to inhibit P-gp activity and can interfere with the metabolism of certain drugs (12) (21).
  • Antidepressants: Rhodiola has MAO inhibition activity and may increase the serotonergic side effects (13).
  • Antihypertensives: Rhodiola has MAO inhibition activity and may increase the hypotensive side effects (13).
  • CNS Stimulants: Rhodiola has MAO inhibition activity and may enhance the hypertensive effect (13).
Literature Summary and Critique

Zhang H, et al. Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer. Drugs R D. Jun 1 2012;12(2):101-106.
The cardioprotective effects of salidroside were evaluated in 60 patients with breast cancer randomized to receive salidroside 600 mg/day or placebo (n=30 each) starting 1 week before and throughout chemotherapy. Evaluation measures included echocardiography, strain rate (SR) imaging, and plasma concentrations of reactive oxygen species (ROS) assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2. Although no differences in SR peak were observed at an epirubicin dose of 200 mg/m2, SR significantly normalized with salidroside vs placebo at 300 mg/m2 and 400mg/m2 of epirubicin. In addition, plasma concentrations of ROS were unchanged with salidroside, but significantly increased with placebo. The investigators concluded that salidroside may be protective against epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

Darbinyan V, et al. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-348.
Rhodiola rosea rhizome standardized extract SHR-5 was evaluated in 89 patients suffering from a current episode of mild to moderate depression in this double-blind placebo-controlled trial. Men and women aged 18-70 years with Hamilton Depression (HAMD) scores between 21 and 31 were randomized to receive either two 170-mg tablets daily (Group A: 340 mg/day total, n=31), two 170-mg tablets twice daily (Group B: 680 mg/day total, n=29), or placebo (Group C: n=29) for a 6-week period. Efficacy from total and specific subgroup HAMD scores with respect to depressive complaints was assessed on days 0 and 42 of the study period. In Groups A and B, overall depression, insomnia, emotional instability, and somatization, but not self-esteem, improved significantly following treatment compared with placebo. No serious side-effects were reported in any treatment group.

Shevtsov VA, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. Mar 2003;10(2-3):95-105.
In this study 161 cadets, ages 19 to 21 years, were randomized to receive either a single dose of standardized rhodiola extract, a single dose that was 50% stronger than the standardized dose, or placebo. Researchers found that the cadets who received rhodiola extract showed significant lowering of fatigue as measured by an antifatigue index compared with those on placebo. There was no difference in the index between the two dosage groups. However, these results cannot be generalized. More well-designed studies are warranted.

Dosage (Inside MSKCC Only)
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References
  1. De Bock K, Eijnde BO, Ramaekers M, et al. Acute Rhodiola rosea intake can improve endurance exercise performance. Int J Sport Nutr Exerc Metab. Jun 2004;14(3):298-307.
  2. Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. Oct 2000;7(5):365-371.
  3. Shevtsov VA, Zholus BI, Shervarly VI, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine. Mar 2003;10(2-3):95-105.
  4. Spasov AA, Wikman GK, Mandrikov VB, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. Apr 2000;7(2):85-89.
  5. Olsson EM, von Scheele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. Feb 2009;75(2):105-112.
  6. Bystritsky A, Kerwin L, Feusner JD. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD). J Altern Complement Med. Mar 2008;14(2):175-180.
  7. Darbinyan V, Aslanyan G, Amroyan E, et al. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-348.
  8. Zhang L, Yu H, Zhao X, et al. Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochem Int. Nov 2010;57(5):547-555.
  9. Li X, Ye X, Sun X, et al. Salidroside protects against MPP(+)-induced apoptosis in PC12 cells by inhibiting the NO pathway. Brain Res. Mar 25 2011;1382:9-18.
  10. Hu X, Zhang X, Qiu S, et al. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells. Biochem Biophys Res Commun. Jul 16 2010;398(1):62-67.
  11. Zhang H, Shen WS, Gao CH, et al. Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer. Drugs R D. Jun 1 2012;12(2):101-106.
  12. Hellum BH, Tosse A, Hoybakk K, et al. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea. Planta Med. Mar 2010;76(4):331-338.
  13. van Diermen D, Marston A, Bravo J, et al. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. Mar 18 2009;122(2):397-401.
  14. Mao Y, Li Y, Yao N. Simultaneous determination of salidroside and tyrosol in extracts of Rhodiola L. by microwave assisted extraction and high-performance liquid chromatography. J Pharm Biomed Anal. Nov 5 2007;45(3):510-515.
  15. Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. Jun 2010;17(7):481-493.
  16. Lin SS, Chin LW, Chao PC, et al. In vivo Th1 and Th2 cytokine modulation effects of Rhodiola rosea standardised solution and its major constituent, salidroside. Phytother Res. Nov 2011;25(11):1604-1611.
  17. Palumbo DR, Occhiuto F, Spadaro F, et al. Rhodiola rosea Extract Protects Human Cortical Neurons against Glutamate and Hydrogen Peroxide-induced Cell Death Through Reduction in the Accumulation of Intracellular Calcium. Phytother Res. Jun 2012;26(6):878-883.
  18. McGovern E, McDonnell TJ. Herbal medicine—sets the heart racing! Ir Med J. Jul-Aug 2010;103(7):219.
  19. Edwards D, Heufelder A, Zimmermann A. Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms—results of an open-label study. Phytother Res. 2012 Aug;26(8):1220-5.
  20. Ishaque S, Shamseer L, Bukutu C, Vohra S. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complement Altern Med. 2012 May 29;12:70.
  21. Spanakis M, Vizirianakis IS, Batzias G, Niopas I. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacology. 2013;91(1-2):112-6.

Consumer Information

How It Works

Bottom Line: Rhodiola was shown to improve physical and mental performance by reducing fatigue caused by stress.

Rhodiola is used in traditional medicine in Eastern Europe and Asia as a stimulant, to improve performance, and to reduce fatigue and depression. Some pilot studies in humans do support these claims, but more studies are needed. Because it may interact through pathways the body uses to metabolize prescription medications, patients should ask their doctor before taking rhodiola supplements.

Purported Uses
  • Depression
    Human studies showed that rhodiola may improve anxiety or mild to moderate depression.  Further research is needed.
  • Fatigue
    Several studies found that rhodiola can reduce fatigue under stressful conditions.
  • Performance
    Rhodiola improved exercise capacity and mental performance in human studies. 
Research Evidence

Cardioprotection
Sixty patients with breast cancer were randomly assigned to receive salidroside 600 mg daily or placebo starting one week before and throughout chemotherapy. Echocardiography and other tests were done at baseline and 7 days after each new epirubicin dose. The investigators concluded that salidroside may be protective against epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

Depression
This study was done to determine whether rhodiola extract was effective in treating men and women with mild to moderate depression. Eight-nine patients were divided into three groups receiving either different doses of rhodiola or a placebo. The study found that depression improved in both groups receiving rhodiola compared with placebo, without any serious side-effects being reported.

Fatigue
This study was done to determine the effects of rhodiola extract on mental performance under stress and fatigue. One hundred and sixty-one cadets were divided into groups that received either different doses of rhodiola or a placebo. The study found that the groups who received rhodiola had lower fatigue and performed better compared with those on placebo.

Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450 3A4 (Rhodiola may increase the risk of side effects of these drugs).
  • You are taking drugs that are substrates of P-glycoprotein (Rhodiola may increase the risk of side effects of these drugs).
  • You are taking antidepressants (Rhodiola may increase the risk of side effects of these drugs).
  • You are taking drugs for high blood pressure (Rhodiola may increase the risk of side effects of these drugs).
  • You are taking drugs that stimulate the central nervous system (Rhodiola may increase the risk of side effects of these drugs).
Side Effects
  • Dizziness
  • Dry mouth
  • A case of fast and irregular heart beat has been reported with simultaneous use of rhodiola and an antidepressant.
E-mail your questions and comments to aboutherbs@mskcc.org.