Rhodiola imbricate, Rhodiola sachalinensis.
An adaptogen used to help the body adapt to physical, mental, and environmental stresses; increase energy, stamina, strength, and mental capacity; improve athletic performance and sexual function; and balance mood for depressive and anxious states.
Mechanism of Action
Rhodiola root contains phenylpropanoids and phenylethanol derivatives including salidroside (also known as rhodioloside and rhodosin), rosavin, rosin, rosarin, rhodiolin, and rosiridin. A range of antioxidant compounds have also been identified in Rhodiola rosea and related species, including flavonoids and phenolic acids such as p-tyrosol, gallic acid, caffeic acid, and chlorogenic acid; catechins; and proanthocyanidins. Salidroside is the most studied compound in Rhodiola, and along with p-tyrosol, rosin, rosavin, and rosarian, are thought to be critical for the plant’s observed adaptogenic effects.1
Many of Rhodiola’s mood, stress, and cognition-enhancing effects are credited to effects on monoamines in the CNS. Animal investigation and molecular studies suggest Rhodiola to increase
5-hydroxytryptamine2,3 and serotonin receptor expression and to act as µ-opioid receptor4,5 and κ-opiate receptor6 agonists, promoting the release of β-endorphin and exerting an anxiolytic, antiarrhythmic, and hypotensive action.7 Molecular studies demonstrate R. rosea roots to have potent antidepressant activity by inhibiting monoamine oxidase (MAO) A and may also find application in the control of senile dementia by their inhibition of MAO B.8 Rhodiola may also reduce the stress-induced release of catecholamines,9 possibly through the up-regulation of opiate pathways.10
Salidroside is credited with antioxidant and vascular protective properties and an ability to increase mitochondrial mass and up-regulate mitochondrial biogenesis factors.11 Cell culture studies have shown salidroside to protect human cortical neurons from oxidative stress. It also protects against intracellular calcium increases invoked by various free radicals and optimizes Ca2+ homeostasis.12
Research has suggested that Rhodiola is effective in asthenic conditions (decline in work performance, sleep difficulties, poor appetite, irritability, hypertension, headaches, and fatigue) developing subsequent to intense physical or intellectual strain.13
Much of the animal and human research has suggested Rhodiola to be helpful in situations of acute and chronic stress. Animal models of stress often use forced swimming to assess physical and biochemical parameters and the effects of pretreatment with medications. Several animal studies have compared pretreatment with Rhodiola salidroside to placebo on a forced swimming model of stress and reported that the serum improved some indices of free radical control and energy metabolism, increasing liver superoxide dismutase and glutathione peroxidase activity of antioxidant enzymes, stabilizing blood sugar, increasing liver glycogen and muscle glycogen reserves, and increasing the metabolism of fat. Human investigations have also shown Rhodiola to improve cardiovascular and respiratory efficiency in situations of extreme physical exertion.14
Rhodiola has shown positive effects on concentration, cognition, and mood. Rhodiola rosea may improve attention, cognitive function, and mental performance in fatigue and in chronic fatigue syndrome.15 Single acute doses of R. rosea extract exerted significant antidepressant and anxiolytic effects in mice at doses of 10, 15 and 20 mg/kg.16 Animal models of nicotine addiction show Rhodiola to increase and lessen the anxiety symptoms of nicotine withdrawal compared with control.17
A multicenter study investigated the effects of 200 mg of Rhodiola twice a day compared with placebo on stress symptoms and reported that improvements could be seen as early as 3 days, with continued improvements over each week of the study.18 One randomized controlled trial on nursing students doing shift work showed 364 mg/day of Rhodiola to reduce fatigue compared with placebo.19 A similar study showed Rhodiola to improve fatigue during night duty in young, healthy physicians compared with placebo.20 A randomized, double-blind, placebo-controlled, parallel-group clinical study investigated the effect of a single dose of standardized R. rosea extract on capacity for mental work against a background of fatigue and stress, in a population of young healthy cadets aged 19–21 years. There was a significant antifatigue effect demonstrated by Rhodiola compared with placebo.21
A phase III randomized, double-blind, placebo-controlled study with parallel groups investigated the effects of Rhodiola in the treatment of stress-related fatigue. Participants received either 576 mg of Rhodiola extract per day or placebo and were evaluated with both symptoms questionnaires and with a.m. salivary cortisol testing on days 1 and 28 of the study. Rhodiola was shown to exert an antifatigue effect, with increased mental performance and ability to concentrate and decreased waking cortisol compared with placebo in patients with fatigue syndrome.22 Researchers have proposed that Rhodiola could be an alternative medication to improve energy for thyroid cancer patients unable to use thyroid hormone medications.23
Safety in Pregnancy and Breastfeeding
There are no published studies or investigations focusing on the use of Rhodiola in pregnancy or lactation at this time.
Toxicity studies dosing rats with 100, 250 or 500 mg/kg of Rhodiola imbricata have not revealed toxicity. There were no significant changes in the organ/body weight ratio or in the histological, hematological, and biochemical variables studied, except for an increase in plasma glucose and protein levels at both the higher doses, which were restored to normal after a 2-week withdrawal of treatment.24 Toxicity investigations of R. imbricata has shown similar tolerability and safety profile.25 Meta-analyses of clinical trials have not identified significant side effects, and Rhodiola is generally well tolerated.26 Adverse events were mostly of mild intensity, and no serious adverse events were reported.
Salidroside has shown no genotoxicity under the conditions of the reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay conditions.27
Rhodiola is often dosed at 200–800 mg daily of an encapsulated root powder (standardized to 1%–2% rosavin). This herb is generally considered safe, even at doses up to 2 g/day; however, smaller doses are typical when Rhodiola is combined with other herbs in a formula or in a more concentrated extract.
Rhodiola rosea, the Arctic rose, grows at high altitudes of the Northern Hemisphere. It has been used as a remedy for altitude sickness; to treat fatigue, both mental and physical; and to improve energy and stamina. The roots are used as mild nerve stimulants in cases of depression and lethargy. Rhodiola has also been used traditionally in traditional Chinese medicine, and it continues to be used for ischemic heart disease and angina pectoris in China. In the modern era, Arctic rose has become established as an adaptogenic herb–an agent capable of increasing resistance to a variety of chemical, biological, and physical stressors.
Chin J Physiol. 2009;52(5):316–24. Attenuation of long-term Rhodiola rosea supplementation on exhaustive swimming-evoked oxidative stress in the rat. Huang SC, Lee FT, Kuo TY, Yang JH, Chien CT.
2 Phytomedicine. 2009;16(9):830–8. The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats. Chen QG, Zeng YS, Qu ZQ, Tang JY, Qin YJ, Chung P, Wong R, Hägg U.
3 Zhongguo Zhong Yao Za Zhi. 2008;33(23):2842–6. Effects of Rhodiola rosea on level of 5-hydroxytryptamine, cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress. Qin YJ, Zeng YS, Zhou CC, Li Y, Zhong ZQ.
4 Eksp Klin Farmakol. 2000;63(4):29–31. Anti-arrhythmic effect of phytoadaptogens. Maĭmeskulova LA, Maslov LN.
5 Eksp Klin Farmakol. 1997;60(3):34–6. Contribution of the opioid system to realization of inotropic effects of Rhodiola rosea extracts in ischemic and reperfusion heart damage in vitro. Lishmanov IuB, Naumova AV, Afanas’ev SA, Maslov LN.
6 Eksp Klin Farmakol. 1997;60(1):38–9. The participation of the mu-, delta- and kappa-opioid receptors in the realization of the anti-arrhythmia effect of Rhodiola rosea. Maĭmeskulova LA, Maslov LN, Lishmanov IuB, Krasnov EA.
7 Phytother Res. 2013;27(10):1543–7. Rhodiola-water extract induces β-endorphin secretion to lower blood pressure in spontaneously hypertensive rats. Lee WJ, Chung HH, Cheng YZ, Lin HJ, Cheng JT.
8 J Ethnopharmacol. 2009;122(2):397–401. Monoamine oxidase inhibition by Rhodiola rosea L. roots. van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K.
9 Eksp Klin Farmakol. 1994;57(6):61–3. The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Maslova LV, Kondrat’ev BIu, Maslov LN, Lishmanov IuB.
10 Biull Eksp Biol Med. 1993;116(8):175–6. The anti-arrhythmia effect of Rhodiola rosea and its possible mechanism. Lishmanov IuB, Maslova LV, Maslov LN, Dan’shina EN.
11 Oxid Med Cell Longev. 2014;2014:904834. Salidroside stimulates mitochondrial biogenesis and protects against H₂O₂-induced endothelial dysfunction. Xing S, Yang X, Li W, Bian F, Wu D, Chi J, Xu G, Zhang Y, Jin S.
12 Phytother Res. 2012;26(6):878–83. Rhodiola rosea extract protects human cortical neurons against glutamate and hydrogen peroxide-induced cell death through reduction in the accumulation of intracellular calcium. Palumbo DR, Occhiuto F, Spadaro F, Circosta C.
13 Altern Med Rev. 2001;6(3):293–302. Rhodiola rosea: a possible plant adaptogen. Kelly GS.
14 Aviakosm Ekolog Med. 2009;43(6):52–6. Effect of cryopowder Rhodiola rosae L. on cardiorespiratory parameters and physical performance of humans. Evdokimov VG.
15 Curr Clin Pharmacol. 2009;4(3):198–219. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Panossian A, Wikman G.
16 Phytother Res. 2007;21(1):37–43. Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Perfumi M, Mattioli L.
17 Phytomedicine. 2012;19(12):1117–24. Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats. Mannucci C, Navarra M, Calzavara E, Caputi AP, Calapai G.
18 Phytother Res. 2012;26(8):1220–5. Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms–results of an open-label study. Edwards D, Heufelder A, Zimmermann A.
19 PLoS One. 2014;9(9):e108416. Rhodiola rosea for mental and physical fatigue in nursing students: a randomized controlled trial. Punja S, Shamseer L, Olson K, Vohra S.
20 Phytomedicine. 2000;7(5):365–71. 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. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H.
21 Phytomedicine. 2003;10(2–3):95–105. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Shevtsov VA, Zholus BI, Shervarly VI, Vol’skij VB, Korovin YP, Khristich MP, Roslyakova NA, Wikman G.
22 Planta Med. 2009;75(2):105–12. 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. Olsson EM, von Schéele B, Panossian AG.
23 J Med Food. 2010;13(6):1287–92. Exploring new applications for Rhodiola rosea: can we improve the quality of life of patients with short-term hypothyroidism induced by hormone withdrawal? Zubeldia JM, Nabi HA, Jiménez del Río M, Genovese J.
24 J Appl Toxicol. 2013;33(5):350–6. Ninety days of repeated gavage administration of Rhodiola imbricata extract in rats. Tulsawani R, Meena DK, Shukla H, Sharma P, Meena RN, Gupta V, Kumar R, Divekar HM, Sawhney RC.
25 Food Chem Toxicol. 2008;46(5):1645–52. A dose dependent adaptogenic and safety evaluation of Rhodiola imbricata Edgew, a high altitude rhizome. Gupta V, Saggu S, Tulsawani RK, Sawhney RC, Kumar R.
26 Complement Ther Med. 2014;22(4):814–25. The efficacy and safety of Chinese herbal medicine, Rhodiola formulation in treating ischemic heart disease: a systematic review and meta-analysis of randomized controlled trials. Yu L, Qin Y, Wang Q, Zhang L, Liu Y, Wang T, Huang L, Wu L, Xiong H.
27 Drug Chem Toxicol. 2010;33(2):220–6. Evaluation of salidroside in vitro and in vivo genotoxicity. Zhu J, Wan X, Zhu Y, Ma X, Zheng Y, Zhang T.
28 Neuropsychiatr. 2015;29(1):36-8. The interaction of Rhodiola rosea and antidepressants. A case report. Maniscalco I, Toffol E, Giupponi G, Conca A.
29 Phytother Res. 2009;23(3):351–7. Pharmacokinetic and pharmacodynamic study of interaction of Rhodiola rosea SHR-5 extract with warfarin and theophylline in rats. Panossian A, Hovhannisyan A, Abrahamyan H, Gabrielyan E, Wikman G.