Rhodiola

• How It Works

  Rhodiola may improve physical and mental performance by reducing fatigue caused by stress, but it may also interact with some prescription medications.

  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. Although drug interactions are not well documented, rhodiola may interact through some pathways the body uses to metabolize prescription medications. Therefore, 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.
• Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450 3A4: Lab studies suggest rhodiola may increase the risk of side effects of these drugs.
  • You are taking drugs that are substrates of Cytochrome P450 2C9: Rhodiola may increase the risk of side effects of these drugs including phenytoin and warfarin.
  • You are taking drugs that are substrates of P-glycoprotein: Lab studies suggest 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.
• Scientific Name

  Rhodiola rosea

• 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 researched, although studies in humans are limited.

  In vitro studies indicate that salidroside from rhodiola may have neuroprotective ^(8) (9) and anticancer effects ⁽¹⁰⁾. Animal studies suggest benefits with rhodiola on cognitive function, but most were determined to have a high risk of bias ⁽²⁴⁾.

  In humans, rhodiola supplementation improved physical endurance ⁽¹⁾ and mental performance ^(2) (3), reduced stress-induced fatigue ^(4) (5), and improved stress symptoms ^(19) (20). Preliminary data suggest it may improve symptoms of generalized anxiety disorder (GAD) ⁽⁶⁾ and mild to moderate depression ⁽⁷⁾. It was also better tolerated and had fewer side effects than sertraline, although it was also less effective ⁽²²⁾.

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

• Purported Uses
  • Depression
  • Fatigue
  • Enhanced mental and physical performance
• Mechanism of Action

  In animal models, rhodiola exhibits dose- and time-dependent Th1 and Th2 cytokine modulation effects ⁽¹⁶⁾. Salidroside in rhodiola confers neuroprotective effects via nitric oxide (NO) pathway inhibition in vitro ⁽⁹⁾ and induction of antioxidant enzymes thioredoxin, heme oxygenase-1, and peroxiredoxin-I; downregulation of proapoptotic Bax protein; and upregulation of antiapoptotic Bcl-XL proteins ⁽⁸⁾. Rhodiola constituents may 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: In preclinical studies, rhodiola inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme ^(12) (21). Clinical relevance is yet to be determined.
  • Cytochrome P450 2C9 substrates: Rhodiola modestly inhibits CYP2C9, and may affect drugs metabolized by this enzyme, particularly those with a narrow therapeutic index such as phenytoin and warfarin ⁽²³⁾.
  • P-glycoprotein substrates: In preclinical studies, rhodiola was shown to inhibit P-gp activity and can interfere with the metabolism of certain drugs ^(12) (21). Clinical relevance is yet to be determined.
  • 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⁾.
• 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.

  22. Mao JJ, Xie SX, Zee J, et al. Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial. Phytomedicine. 2015 Mar 15;22(3):394-9.

  23. Thu OK, Spigset O, Nilsen OG, et al. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. Mar 2016;72(3):295-300.

  24. Ma GP, Zheng Q, Xu MB, et al. Rhodiola rosea L. Improves Learning and Memory Function: Preclinical Evidence and Possible Mechanisms. Front Pharmacol. 2018;9:1415.