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Rhodiola Rosea

Scientific Name(s): Rhodiola roanensis Britton, Rhodiola rosea L., Sedum rosea
Common Name(s): Arctic root, Golden root, Rhodaxon, Roseroot, SHR-5

Clinical Overview

Use

Clinical trials supporting therapeutic claims are of limited quality and quantity. Clinical trials evaluating R. rosea for mental or physical fatigue and mild to moderate depression have reported conflicting results. Results from trials evaluating adaptogenic properties and physical endurance are equivocal.

Dosing

Clinical doses are commonly 200 to 600 mg/day. For depression, doses of 340 to 680 mg/day of R. rosea extract (as SHR-5) have been evaluated for up to 12 weeks.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and effectiveness in pregnancy and lactation is lacking.

Interactions

None well documented. Inhibition of CYP2C9 has been reported in human volunteers.

Adverse Reactions

Information is limited.

Toxicology

R. rosea was reported to be safe in toxicity studies.

Botany

R. rosea is a perennial plant with a thick rhizome and yellow, fragrant flowers. It grows in sandy soil at high altitudes in the arctic areas of Europe and Asia, including eastern Siberia. The plant reaches a height of 30 to 76 cm. Unique chemical constituents distinguish R. rosea from other Rhodiola species.1, 2

History

The Greek physician Dioscorides (AD 40-90) first recorded this plant in De Materia Medica, renaming it from Rodia riza to R. rosea, which refers to the roselike aroma of the freshly cut root. The Swedish naturalist Carl Linnaeus (1707-1778) documented use of R. rosea as an astringent to treat hernia, leucorrhea, hysteria, and headache. For centuries, the plant has been used in the Russia Federation and Scandinavia, where the majority of the research has been conducted.2, 3, 4 The plant has also been used as a hemostatic agent in Tibetan folk medicine.5 Extract of R. rosea is registered in the Russian Federation as a medicinal product for human use.4 Due to increased demand for the plant, R. rosea is listed as threatened or endangered in many areas of the world, including parts of the United States.1

Chemistry

Three cinnamyl alcohol vicianosides (rosavin, rosin, rosarin) are specific to R. rosea.4, 6 These 3 substances, along with rosiridin and salidroside, are the 5 marker compounds that must be present to reliably identify R. rosea.4, 7 R. rosea extract used in most clinical trials was standardized to a minimum of rosavins 3% and salidroside 0.8% to 1%, the naturally occurring ratio in the plant.2 The phenylethanol derivatives salidroside (rhodioloside) and tyrosol have been found in the underground part of the plants.3, 8 Flavonoids in R. rosea include rhodiolin, rodinin, rodiosin, acetylrodalgin, and tricin, as well as other catechins and proanthocyanidins.2, 9 Monoterpenes include rosiridol and rosaridin, and triterpenes include daucosterol and beta-sitosterol.2, 5 Terpenes and volatile compounds have been isolated from R. rosea and include the essential oil components of monoterpene hydrocarbons, monoterpene alcohols and straight-chain aliphatic alcohols, N-decanol, geraniol (responsible for the rose-like odor), linalool, nonanal, decanal, nerol, and cinnamyl alcohol.10 Phenolic acids, including chlorogenic, hydroxycinnamic, and gallic acids, are also present.2, 9, 11, 12

Uses and Pharmacology

Adaptogenic effects

Plant adaptogens, such as those from R. rosea, improved mental and physical performance through stimulatory effects on various physiological systems.9, 12 R. rosea's use in traditional Ayurvedic medicine for adaptogenic properties has been examined.13

Animal data

R. rosea increased the survival of freshwater snail eggs against induced stressors, including heat shock and oxidative and heavy metal stress.14 When administered to rats, injections of the plant extract prevented stress-induced elevations of beta-endorphins, adrenocorticotropic hormone, cortisol, insulin, thyroxin, and triiodothyronine.15 R. rosea given to rats increased swimming time up to 159%, with improvement continuing throughout the supplementation period.16

Clinical data

Clinical trials evaluating R. rosea for mental and physical fatigue have reported conflicting results. Positive findings were reported in a clinical trial conducted among 56 physicians experiencing fatigue during night duty17 and among students during stressful examination periods.18, 19 Improved sleep patterns and overall quality of sleep have been described with the use of R. rosea.17, 18, 19, 20 A small (N = 15), randomized, placebo-controlled, crossover study evaluated the effects of a single dose of 3 mg/kg administered 1 hour prior to an exercise bicycle session that began with a 10-minute warm-up followed by a 6-mile time trial. Results were lower with R. rosea compared with placebo for the time required to complete 6 miles, heart rate during the warm-up period but not the time trial, and patients’ rating of exertion level.21 A systematic review evaluating the efficacy of R. rosea for physical and mental fatigue reported conflicting clinical trial results for both conditions.22 Meta-analysis could not be conducted because the studies used different instruments to measure fatigue. In addition, studies had either a high risk of bias or reporting flaws that may have compromised their validity. A placebo-controlled clinical trial evaluated the effect of R. rosea on fatigue for 42 days in 48 nursing students doing shift work.23 In this study, both a visual analog scale for fatigue and the RAND-36 Vitality subscale indicated that R. rosea increased fatigue.

Other trials evaluating the effect of R. rosea on physical performance suggested a positive effect; however, most recent trials have reported no effect on time to exhaustion,24, 25, 26, 27 cardiovascular outcomes,27, 28 tissue hypoxia,26, 27, 28 exercise-induced muscle damage, delayed onset of muscle soreness, plasma cytokines,29 or rate of adenosine triphosphate turnover for R. rosea extracts.25

Cancer

In vitro and animal data

The usefulness of R. rosea as an antioxidant and anticarcinogenic agent has been suggested based on findings from in vitro studies.11, 30, 31, 32, 33 Several antioxidant compounds have been identified in the plant, including p-tyrosol, organic acids, and flavonoids. A mechanism of action has been described that includes induction of apoptosis and necrosis.34

The same researchers described experiments in animals with induced cancers. R. rosea potentiated antitumor and antimetastatic effects in mice with lung carcinoma,35 inhibited tumor dissemination,36 inhibited growth rate of Ehrlich tumors and Pliss lymphosarcoma,37 and protected tissues from cyclophosphamide toxicity.38, 39 Another in vitro experiment showed efficacy against prostate cancer cells in rats.3

Clinical data

R. rosea extract administration improved certain parameters in superficial bladder carcinoma in a small (N = 12) study.40

Depression

CNS activity of R. rosea has been reported.12 Earlier studies found that low to medium doses of the plant had stimulatory effects, while larger doses had sedative effects.2 In lower doses, R. rosea stimulated norepinephrine, dopamine, serotonin, and nicotinic cholinergic systems in the CNS. R. rosea also increased the permeability of the blood-brain barrier to precursors of dopamine and serotonin41, 42, 43 and improved cerebral circulation.44 In an in vitro study, R. rosea root extract inhibited monoamine oxidases A and B.45

Clinical data

A systematic review of 4 clinical trials of R. rosea in psychiatric disorders found sufficient positive results to warrant further research, suggesting that a stimulating adaptogenic effect is responsible for antidepressant activity.46

Clinical trials evaluating R. rosea for mild to moderate depression have reported conflicting results. A double-blind, randomized clinical trial of R. rosea (SHR-5) conducted for 6 weeks in 89 patients reported antidepressant effects as compared with use of placebo, as measured on the Hamilton Depression Rating Scale (HAM-D) as well as the Beck Depression Inventory (BDI).47 A second placebo-controlled clinical trial compared the efficacy of sertraline and R. rosea (SHR-5) in 57 patients for12 weeks.48 There was no difference between treatments for the study’s primary outcome, the change in HAM-D 17. There were also no differences between treatments for BDI or Clinical Global Impression Change scores. The odds of improvement were greater with sertraline than with R. rosea (odds ratio 1.9 vs 1.4), but R. rosea was tolerated. Earlier trials of varying methodology also produced conflicting results.49, 50

The Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder (MDD) in adults (2016) do not recommend R. rosea in the management of MDD based on insufficient evidence.51

Other uses

Antiaging

A study using the fruit fly Drosophila demonstrated increased longevity with R. rosea administration and suggested the effects were not caused by metabolic rate or male mating success.52

Cardiac

Clinical trials are lacking. Several older experiments by a small pool of researchers investigated the antiarrhythmic and inotropic effects of R. rosea extract in animal models.53, 54, 55, 56, 57, 58, 59

Dosing

Clinical doses are commonly 200 to 600 mg/day.2 Doses of 340 to 680 mg/day of R. rosea extract (as SHR-5) in depression have been evaluated for up to 12 weeks, but with conflicting results.47, 60 A daily dose of 170 mg/day for 4 weeks was evaluated in a study examining athletic performance and antioxidant effects.

Pregnancy / Lactation

Information regarding safety and effectiveness in pregnancy and lactation is lacking.9

Interactions

None well documented. In vitro studies have suggested that R. rosea may be a potent inhibitor of cytochrome P450 (CYP) 2C19, CYP 2D6, CYP 3A4, and P-glycoprotein.61, 62, 63 In a rat study, R. rosea did not affect the pharmacokinetics of theophylline or warfarin, or alter the prothrombin time with warfarin.64 In a rabbit study, R. rosea substantially increased exposure to losartan, but not losartan’s active metabolite.65 In a case report, a young woman developed supraventricular tachycardia 3 days after adding R. rosea to long-term administration of escitalopram.66 A 2-phase, randomized crossover experimental study in 13 nonsmoking healthy volunteers (20 to 26 years of age) documented a modest but statistically significant 21% reduction in CYP2C9 activity when pretreated with 2 weeks of R. rosea (equivalent to 290 mg/day R. rosea extract or 1,000 mg/day dried R. rosea). Clinical significance is unknown but may become clinically relevant when administering agents with a narrow therapeutic index, such as warfarin or phenytoin. No significant effects were observed on CYP1A2, CYP2C19, CYP2D6, or CYP3A4. Poor metabolizers with genotypes CYP2D6 *4/*4 and CYP2C9 *2/*2 were excluded from the study.68

Adverse Reactions

Information is limited.17, 23, 47, 48, 60

Toxicology

R. rosea has a very low level of toxicity in rats. The median lethal dose was calculated to be approximately 3.4 g/kg (equal to 235 g in a 70 kg person).67 R. rosea was reported to be safe in toxicity studies.13

References

1. Rhodiola rosea L. USDA, NRCS. 2008. The PLANTS Database (http://plants.usda.gov, 6 June 2015). National Plant Data Center, Greensboro, NC 27401-4901 USA.
2. Brown RP, Gerbarg PL, Ramazanov Z. Rhodiola rosea: a phytomedicinal overview. HerbalGram. 2002;56:40-52.
3. Ming DS, Hillhouse BJ, Guns ES, et al. Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res. 2005;19(9):740-743.16220564
4. Kucinskaite A, Poblocka-Olech L, Krauze-Baranowska M, Sznitowska M, Savickas A, Briedis V. Evaluation of biologically active compounds in roots and rhizomes of Rhodiola rosea L. cultivated in Lithuania. Medicina. 2007;43(6):487-494.17637521
5. Ma G, Li W, Dou D, et al. Rhodiolosides A-E, monoterpene glycosides from Rhodiola rosea. Chem Pharm Bull. 2006;54(8):1229-1233.16880679
6. Dubichev AG, Kurkin BA, Zapesochnaya GG, Vornotzov ED. Study of Rhodiola rosea root chemical composition using HPLC. Cemico-Pharmaceutical J. 1991;2:188-193.
7. Ganzera M, Yayla Y, Khan IA. Analysis of the marker compounds of Rhodiola rosea L. (golden root) by reversed phase high performance liquid chromatography. Chem Pharm Bull (Tokyo). 2001;49(4):465-467.11310675
8. Linh PT, Kim YH, Hong SP, Jian JJ, Kang JS. Quantitative determination of salidroside and tyrosol from the underground part of Rhodiola rosea by high performance liquid chromatography. Arch Pharm Res. 2000;23(4):349-352.10976582
9. Kelly GS. Rhodiola rosea: a possible plant adaptogen. Altern Med Rev. 2001;6(3):293-302.11410073
10. Rohloff J. Volatiles from rhizomes of Rhodiola rosea L. Phytochemistry. 2002;59(6):655-661.11867098
11. Lee MW, Lee YA, Park HM, et al. Antioxidative phenolic compounds from the roots of Rhodiola sachalinensis A. Bor. Pharm Res. 2000;23(5):455-458.11059822
12. Panossian A, Wagner H. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother Res. 2005;19(10):819-838.16261511
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18. Spasov AA, Wikman GK, Madrikov VB, Mironova IA, Neumoin VV. 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. 2000;7(2):85-89.10839209
19. Spasov AA, Mandrikov VB, Mironova IA. The effect of the preparation rodakson on the psychophysiological and physical adaptation of students to an academic load [in Russian]. Eksp Klin Farmakol. 2000;63(1):76-78.10763116
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24. Earnest CP, Morss GM, Wyatt FB, et al. Effects of a commercial herbal-based formula on exercise performance in cyclists. Med Sci Sports Exerc. 2004;36(3):504-509.15076794
25. Walker TB, Altobelli SA, Caprihan A, Robergs RA. Failure of Rhodiola rosea to alter skeletal muscle phosphate kinetics in trained men. Metabolism. 2007;56(8):1111-1117.17618958
26. Colson SN, Wyatt FB, Johnston DL, et al. Cordyceps sinensis- and Rhodiola rosea-based supplementation in male cyclists and its effect on muscle tissue oxygen saturation. J Strength Cond Res. 2005;19(2):358-363.15903375
27. Parisi A, Tranchita E, Duranti G, et al. Effects of chronic Rhodiola Rosea supplementation on sport performance and antioxidant capacity in trained male: preliminary results. J Sports Med Phys Fitness. 2010;50(1):57-63.20308973
28. Wing SL, Askew EW, Luetkemeier MJ, Ryujin DT, Kamimori GH, Grissom CK. Lack of effect of Rhodiola or oxygenated water supplementation on hypoxemia and oxidative stress. Wilderness Environ Med. 2003;14(1):9-16.12659243
29. Shanely RA, Nieman DC, Zwetsloot KA, et al. Evaluation of Rhodiola rosea supplementation on skeletal muscle damage and inflammation in runners following a competitive marathon. Brain Behav Immun. 2014;39:204-210.24055627
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31. Udintsev SN, Shakhov VP. The role of humoral factors of regenerating liver in the development of experimental tumors and the effect of Rhodiola rosea extract on this process. Neoplasma. 1991;38(3):323-331.1857451
32. Udintsev SN, Shakhov VP, Borovskoĭ IG. Mechanism of differential effect of low dose adaptogens on the functional activity of normal and transformed cellular elements in vitro [in Russian]. Biofizika. 1991;36(4):624-627.1793747
33. Salikhova RA, Aleksandrova IV, Mazurik VK, Mikhailov VF, Ushenkova LN, Poroshenko GG. Effect of Rhodiola rosea on the yield of mutation alterations and DNA repair in bone marrow cells [in Russian]. Patol Fiziol Eksp Ter. 1997;Oct-Dec(4):22-24.9471597
34. Majewska A, Hoser G, Grazyna H, et al. Antiproliferative and antimitotic effect, S phase accumulation and induction of apoptosis and necrosis after treatment of extract from Rhodiola rosea rhizomes on HL-60 cells. J Ethnopharmacol. 2006;103(1):43-52.16169692
35. Razina TG, Zueva EP, Amosova EN, Krylova SG. Medicinal plant preparations used as adjuvant therapeutics in experimental oncology [in Russian]. Eksp Klin Farmakol. 2000;63(5):59-61.11109531
36. Udintsev SN, Krylova SG, Fomina TI. The enhancement of the efficacy of adriamycin by using hepatoprotectors of plant origin in metastases of Ehrlich's adenocarcinoma to the liver in mice [in Russian]. Vopr Onkol. 1992;38(10):1217-1222.1343148
37. Udintsev S, Shakhov VP. Decrease in the growth rate of Ehrlich's tumor and Pliss' lymphosarcoma with partial hepatectomy [in Russian]. Vopr Onkol. 1989;35(9):1072-1075.2573197
38. Udintsev SN, Schakhov VP. Decrease of cyclophosphamide hematotoxicity by Rhodiola rosea root extract in mice with Ehrlich and Lewis transplantable tumors. Eur J Cancer. 1991;27(9):1182.1835634
39. Udintsev SN, Shakhov VP. Changes in clonogenic properties of bone marrow and transplantable mice tumor cells during combined use of cyclophosphane and biological response modifiers of adaptogenic origin [in Russian]. Eksp Onkol. 1990;12(6):55-56.2261879
40. Bocharova OA, Matveev BP, Baryshnikov AIu, Figurin KM, Serebriakova RV, Bodrova NB. The effect of a Rhodiola rosea extract on the incidence of recurrences of a superficial bladder cancer (experimental clinical research) [in Russian]. Urol Nefrol. 1995;Mar-Apr(2):46-47.7785120
41. Kurkin VA, Zapesochnaya GG. Chemical composition and pharmacological properties of Rhodiola rosea. Chem Pharm J. 1986;20(10):1231-1244.
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43. Saratikov A, Marina TF, Fisanova LL. Effect of golden root extract on processes of serotonin synthesis in CNS. J Biol Sci. 1978;6:142.
44. Pogorelyĭ VE, Makarova LM. Rhodiola rosea extract for prophylaxis of ischemic cerebral circulation disorder [in Russian]. Eksp Klin Farmakol. 2002;65(4):19-22.12449069
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