Rhodiola Rosea: Medicinal Use And The Science Behind It
Rhodiola rosea is an adaptogenic herb with potent antioxidant and neuroprotective properties that has been extensively studied in clinical and experimental research. Rhodiola regulates the neuroendocrine response to stress, reduces the adverse effects of stress, including mental and physical fatigue, promotes cognitive function, and delays cognitive decline.
Sara Adaes

Sara Adaes

Ph.D Neuroscience, Neuropharmacology.

Summary

Rhodiola Rosea, also known as Roseroot, Golden Root, or Arctic Root, is an herb with a long history of use as a health-enhancing supplement. It has been used for centuries in traditional folk medicine to improve mood, alleviate anxiety, depression, stress, and fatigue, enhance energy and alertness, and increase longevity. (1) The most studied and acknowledged property of Rhodiola rosea is its potent adaptogenic effect. (2)  Adaptogens are compounds that promote homeostasis and that are used to increase attention, endurance in fatigue, and resistance to stress. (3)

Rhodiola has many biologically active compounds. They include: (1)

  • Phenylpropanoids: rosavin, rosin, rosarin (which are specific to Rhodiola);
  • Phenylethanol derivatives: salidroside (also known as rhodioloside), tyrosol;
  • Flavanoids: rodiolin, rodionin, rodiosin, acetylrodalgin, tricin;
  • Monoterpernes: rosiridol, rosaridin;
  • Triterpenes: daucosterol, beta-sitosterol;
  • Phenolic acids: chlorogenic and hydroxycinnamic, gallic acids.

Rosavins (a term that can be used to generically refer to rosavin, rosin, and rosarian)  and salidroside are Rhodiola’s main bioactive compounds. (4) Reported pharmacological properties of Rhodiola rosea extracts and its compounds are abundant and include adaptogenic and stress-protective, anxiolytic, antidepressant, anti-fatigue, cognitive-enhancing, anti-anoxia, anti-inflammatory, antioxidant, anti-allergic, antimutagenic, immune-enhancing, hepatoprotective, cardioprotective, neuroprotective, and anti-aging effects. (1) , (3)

Effects of Rhodiola rosea in human trials

Clinical trials have supported the traditional medicinal use of Rhodiola rosea, particularly its adaptogenic effects. These have been demonstrated in several double-blind, randomized, placebo-controlled clinical trials. Rhodiola rosea root extracts have been shown to improve mood,5  decrease anxiety and stress, (5-7) combat depression, (6,8,9) decrease fatigue, (10-13) and improve cognitive performance in contexts of stress and fatigue. (10,12,13)

In a randomized, double-blind, placebo-controlled trial in subjects with stress-related fatigue (burnout), Rhodiola rosea extract administered at a dose of 576 mg/day for 4 weeks produced a marked beneficial effect, with a significant reduction in fatigue and an improvement in attention (as determined by cognitive performance ratings). (10)

Rhodiola’s beneficial effects seem to have a fast onset. Treatment with Rhodiola rosea extract in subjects with life-stress symptoms at a dose of 200 mg twice daily for 4 weeks produced clinically relevant improvements in stress symptoms as early as 3 days after starting treatment. Continued improvements were observed after 1 and 4 weeks. (7)

Rhodiola administered at a dose of 340 mg/day for 10 weeks to patients with generalized anxiety disorder showed a positive anxiolytic benefit with a significant reduction in anxiety and depression rating scores.6 Rhodiola rosea root extract also promoted significant reductions in anxiety and stress and significant improvements in mood when administered to students (average age ~21) at a dose of 200 mg twice daily for 2 weeks. No changes in cognitive processing were observed in this study. (5)

Even at low-dose regimen, Rhodiola was able to decrease mental fatigue and improve physical fitness and psychomotor and cognitive performance, as observed in healthy students during stressful examinations that received 50 mg twice daily for 20 days, (11) or young, healthy physicians during night duty who received 170 mg/day for 2 weeks. (12)

In a trial in patients with mild to moderate depression, Rhodiola extract showed an antidepressant effect when administered at doses of either 340 or 680 mg/day over a 6-week period. (9) However, in patients with a major depressive disorder, Rhodiola at escalating doses ranging from 340 mg/day to 1360 mg/day only produced a non-significant decrease in depression scores. (8)

The anti-fatigue effects of Rhodiola were not restricted to mental fatigue. Studies also showed that Rhodiola increased endurance and physical work capacity, and shortened the recovery time between periods of high-intensity exercise. (3)

Mechanisms of action

One of the main mechanisms of action of Rhodiola is the regulation of the hypothalamic–pituitary–adrenal (HPA) axis. The activation of the HPA axis is the major neuroendocrine response to stress. As a consequence of HPA activation by stress, the hypothalamus releases a number of chemical mediators (neuropeptides and hormones) that stimulate the production of stress hormones (glucocorticoids) by the adrenal gland. Stress hormones then act on the brain and other tissues to trigger metabolic and neuromodulatory changes necessary for stress adaptation. However, chronic HPA axis hyperactivity and persistently elevated levels of stress hormones can be harmful, interfering with normal brain function, and prompting the development of a number of conditions, including affective disorders, cognitive decline, and accelerated aging. (14–16) Cortisol is the main stress hormone involved in the HPA axis regulation of the stress response. (17) A decrease in stress-induced cortisol secretion is a characteristic mechanism of action of adaptogens. (18)

Rhodiola was shown to reduce cortisol levels in subjects with stress-related fatigue. (10) Likewise, Rhodiola was shown to inhibit the increase in cortisol production induced by acute stress in animal studies. (19) Rhodiola also inhibited the production of other chemical mediators of the stress response, including corticotropin-releasing factor (CRF), (20) c-Jun N-terminal protein kinase 1 (JNK1), (19) nitric oxide (NO), (19) heat-shock protein 70 (Hsp70), (18) Hsp72, (21) neuropeptide Y (NPY), (21) and the opioid β-endorphine (20)

Therefore, these results indicate that Rhodiola may effectively downregulate the HPA stress response, which is essential in decreasing the mental and physical damage caused by stress.

Given the negative influence of stress in the brain and cognitive function, the beneficial cognitive effects of Rhodiola can be partially attributed to an improvement in the resistance to stress. But Rhodiola can also exert positive cognitive effects by stimulating the central nervous system. (1,4) It has been proposed that Rhodiola promotes the release of acetylcholine, dopamine, noradrenaline, and serotonin in pathways that activate the cerebral cortex, including the frontal and prefrontal cortex. Through these actions, Rhodiola may enhance cognitive functions such as attention, memory, and learning. (1)

Rhodiola is likely to enhance mood and exert its antidepressant effects via a modulation of the levels of monoamine neurotransmitters. Rhodiola inhibits monoamine oxidase (MAO) A and B, (22) which are responsible for the catabolism of dopamine, noradrenaline, and serotonin. (23) These neurotransmitters have important roles in the regulation of mood and in the pathophysiology of depression. By blocking their degradation, Rhodiola can potentially increase their levels in the brain and thereby exert a mood-enhancing effect. Accordingly, Rhodiola appears to stimulate the release of these neurotransmitters in brain regions involved in mood and affect, such as the limbic system. (1) Rhodiola may also exert antidepressant effects by modulating the production of the endogenous opioid β-endorphin, (20) which has also been associated with the pathophysiology of depression. (24)

Neuroprotective and antioxidant effects in animal and in vitro studies

Rhodiola rosea is rich in flavonoids and phenolic compounds. These molecules are known to have potent antioxidant properties. Increased oxidative stress is usually observed as a consequence of psychological stress, contributing to its detrimental effects. Oxidative stress is associated with fatigue and can be highly damaging to neurons, contributing to neurodegeneration and to the development of cognitive impairments. (25) Antioxidants are known to be neuroprotective and to contribute to an improvement in cognitive function. (26) Accordingly, animal and in vitro studies have shown that Rhodiola exerts neuroprotective effects through an antioxidant action.

Rhodiola has been shown to decrease the levels of free radicals, such as superoxide, (27) and to protect neurons from injury associated with oxidative stress. (1) (28) Rhodiola was also shown to enhance neurogenesis impaired by oxidative stress. (29) Calcium homeostasis, which is essential for the proper functioning of the nervous system, was also shown to be stabilized by Rhodiola. (30)

In vitro studies showed that Rhodiola (through the action of salidroside) can protect neurons and from oxidation and apoptotic cell death induced by excessive glutamate, (31), (32) excessive intracellular free calcium, (31–33) hydrogen peroxide (H2O2), (34) hypoxia, (33) hypoglycemia, (33) ,(35) and amyloid beta. (36)

Standing in line with these effects, Rhodiola rosea extract has shown a protective effect against cognitive deficits induced by neuronal toxic injury and oxidative stress. (28) Rhodiola rosea extract also protected from cerebral ischemia-reperfusion injury by decreasing oxidative damage, resulting in an improvement of cognitive function following the ischemic injury. (37)

Rhodiola was also shown to protect from oxidative damage associated with fatigue caused by long-time endurance training in mice. (38) This antioxidant effect is likely also associated with the increased physical work capacity observed in humans following the intake of Rhodiola. (3)

These protective properties are likely to underlie Rhodiola’s ability to promote longevity observed in animal studies. Rhodiola rosea extract significantly increased the mean and maximum lifespan of Drosophila melanogaster (fruit fly) (27), (39) and of the nematode worm Caenorhabditis elegans. (40)

Effective doses

Doses used in clinical trials that showed adaptogenic and cognitive benefits were most often within the 300-600 mg range. A study that compared the effect of two doses (370 mg or 555 mg) of Rhodiola rosea extract in decreasing fatigue and improving the capacity for mental work found no differences between the two doses, (13) indicating that the lower dose is sufficient. Even at low-dose regimens (50 mg twice daily (11) and 170 mg/day (12) ), Rhodiola was able to decrease mental and physical fatigue and improve cognitive and physical performance.

Safety and side effects

Rhodiola rosea has a very low level of toxicity. In toxicity studies in rats, the LD50 (lethal dose at which 50% of animals die) was calculated to be around 3360 mg/kg. The Human Equivalent Dose would be around 542 mg/kg41 (roughly 38000 mg for a 70kg/150lbs adult).

Rhodiola rosea has been shown to be safe and well tolerated in multiple clinical trials. When reported, adverse effects are mostly of mild intensity. (7) No adverse effects were detected in human trials of Rhodiola extract administered at doses of 400 mg/day for 2 weeks,5 576 mg/day for 4 weeks, (10) of 660 mg/day for 3 weeks, (42) and of 680 mg/day for 6 weeks. (9) At a dose of 340 mg/day for 10 weeks, adverse events were mild to moderate, the most common being dizziness and dry mouth. (6)

In a randomized, double-blind, placebo-controlled study with Rhodiola rosea doses ranging from 340 mg/day to 1360 mg/day (dose escalation, highest dose maintained for 6 weeks in some patients), there were no treatment-related serious adverse events. The only side effects reported for Rhodiola were nervousness and dizziness. There were no clinically meaningful changes in systolic and diastolic blood pressure, pulse rate, or weight. No significant changes were observed in any laboratory values. (8)

Therefore, an intake at an effective dose (around 300-600 mg/day, based on clinical studies) is unlikely to induce any major adverse effects.

Summary and conclusion

Rhodiola rosea has been extensively studied, both in clinical trials and in animal and in vitro research. The potent adaptogenic effect of Rhodiola was repeatedly demonstrated in clinical trials. Through its ability to regulate the neuroendocrine response to stress, Rhodiola can mitigate the detrimental effects of stress, reduce stress-induced mental and physical fatigue, and promote cognitive function. Rhodiola contains potent antioxidant molecules which confer strong neuroprotective properties that contribute to an enhancement of brain function and to a delay in cognitive decline. Anti-aging effects have also been reported for Rhodiola rosea.

Rhodiola rosea root extracts have shown clinical efficacy at doses of 300 to 600 mg day. Rhodiola has a good safety profile, is unlikely to induce any major side effects at the effective doses, and seems to be suited for long-term use.

References

  1. Brown RP, Gerbarg PL, Ramazanov Z. Rhodiola rosea: A Phytomedicinal Overview. HerbalGram. 2002;(56):40-52.
  2. Kelly GS. Rhodiola rosea: A possible plant adaptogen. Altern Med Rev. 2001;6(3):293-302. http://www.ncbi.nlm.nih.gov/pubmed/11410073.
  3. Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017;1401(1):49-64. doi:10.1111/nyas.13399.
  4. Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): Traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010;17(7):481-493. doi:10.1016/j.phymed.2010.02.002.
  5. Cropley M, Banks AP, Boyle J. The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms. Phytother Res. 2015;29(12):1934-1939. doi:10.1002/ptr.5486.
  6. Bystritsky A, Kerwin L, Feusner JD. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD). J Altern Complement Med. 2008;14(2):175-180. doi:10.1089/acm.2007.7117.
  7. 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;26(8):1220-1225. doi:10.1002/ptr.3712.
  8. Mao JJ, Xie SX, Zee J, et al. Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial. Phytomedicine. 2015;22(3):394-399. doi:10.1016/j.phymed.2015.01.010.
  9. Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. 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. doi:10.1080/08039480701643290.
  10. Olsson EMG, Von Schéele 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. 2009;75(2):105-112. doi:10.1055/s-0028-1088346.
  11. Spasov AA, Wikman GK, Mandrikov VB, Mironova IA, Neumoin V V. 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. doi:10.1016/S0944-7113(00)80078-1.
  12. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. 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. 2000;7(5):365-371. doi:10.1016/S0944-7113(00)80055-0.
  13. 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. 2003;10(2-3):95-105. doi:10.1078/094471103321659780.
  14. Aguilera G. HPA axis responsiveness to stress: implications for healthy aging. Exp Gerontol. 46(2-3):90-95. doi:10.1016/j.exger.2010.08.023.
  15. Sapolsky RM. Glucocorticoids, stress, and their adverse neurological effects: relevance to aging. Exp Gerontol. 1999;34(6):721-732. http://www.ncbi.nlm.nih.gov/pubmed/10579633.
  16. Swaab DF, Bao A-M, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005;4(2):141-194. doi:10.1016/j.arr.2005.03.003.
  17. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8(4):383-395. http://www.ncbi.nlm.nih.gov/pubmed/17290797.
  18. Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity. Pharmaceuticals. 2010;3(1):188-224. doi:10.3390/ph3010188.
  19. Panossian A, Hambardzumyan M, Hovhanissyan A, Wikman G. The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug Target Insights. 2007;2:39-54. http://www.ncbi.nlm.nih.gov/pubmed/21901061.
  20. Lishmanov IB, Trifonova Z V, Tsibin AN, Maslova L V, Dement’eva LA. [Plasma beta-endorphin and stress hormones in stress and adaptation]. Biull Eksp Biol Med. 1987;103(4):422-424. http://www.ncbi.nlm.nih.gov/pubmed/2952180.
  21. Panossian A, Wikman G, Kaur P, Asea A. Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells. Front Neurosci. 2012;6:6. doi:10.3389/fnins.2012.00006.
  22. van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401. doi:10.1016/j.jep.2009.01.007.
  23. Schwartz TL. A neuroscientific update on monoamine oxidase and its inhibitors. CNS Spectr. 2013;18 Suppl 1:25-32; quiz 33. doi:10.1017/S1092852913000734.
  24. Hegadoren KM, O’Donnell T, Lanius R, Coupland NJ, Lacaze-Masmonteil N. The role of beta-endorphin in the pathophysiology of major depression. Neuropeptides. 2009;43(5):341-353. doi:10.1016/j.npep.2009.06.004.
  25. Hajjar I, Hayek SS, Goldstein FC, Martin G, Jones DP, Quyyumi A. Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J Neuroinflammation. 2018;15(1):17. doi:10.1186/s12974-017-1026-z.
  26. Lalkovičová M, Danielisová V. Neuroprotection and antioxidants. Neural Regen Res. 2016;11(6):865-874. doi:10.4103/1673-5374.184447.
  27. Schriner SE, Abrahamyan A, Avanessian A, et al. Decreased mitochondrial superoxide levels and enhanced protection against paraquat in Drosophila melanogaster supplemented with Rhodiola rosea. Free Radic Res. 2009;43(9):836-843. doi:10.1080/10715760903089724.
  28. Qu ZQ, Zhou Y, Zeng YS, Li Y, Chung P. Pretreatment with rhodiola rosea extract reduces cognitive impairment induced by intracerebroventricular streptozotocin in rats: Implication of anti-oxidative and neuroprotective effects. Biomed Environ Sci. 2009;22(4):318-326. doi:10.1016/S0895-3988(09)60062-3.
  29. qiang Qu Z, Zhou Y, shan Zeng Y, et al. Protective effects of a rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat. Casadesus G, ed. PLoS One. 2012;7(1):e29641. doi:10.1371/journal.pone.0029641.
  30. Palumbo DR, Occhiuto F, Spadaro F, Circosta C. 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. 2012;26(6):878-883. doi:10.1002/ptr.3662.
  31. Chen X, Liu J, Gu X, Ding F. Salidroside attenuates glutamate-induced apoptotic cell death in primary cultured hippocampal neurons of rats. Brain Res. 2008;1238:189-198. doi:10.1016/j.brainres.2008.07.051.
  32. Cao L-L, Du G-H, Wang M-W. The effect of salidroside on cell damage induced by glutamate and intracellular free calcium in PC12 cells. J Asian Nat Prod Res. 8(1-2):159-165. doi:10.1080/1028602042000325645.
  33. Zhang W, Zhu L, Niu F, Deng R, Ma C. [Protective effects of salidroside on injury induced by hypoxia/hypoglycemia in cultured neurons]. Zhongguo Zhong Yao Za Zhi. 2004;29(5):459-462. http://www.ncbi.nlm.nih.gov/pubmed/15706905.
  34. Cai L, Wang H, Li Q, Qian Y, Yao W. Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome c release and inactivating of caspase cascade. Acta Biochim Biophys Sin (Shanghai). 2008;40(9):796-802. http://www.ncbi.nlm.nih.gov/pubmed/18776992.
  35. Yu S, Liu M, Gu X, Ding F. Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation. Cell Mol Neurobiol. 2008;28(8):1067-1078. doi:10.1007/s10571-008-9284-z.
  36. Jang SI, Pae HO, Choi BM, et al. Salidroside from Rhodiola sachalinensis protects neuronal PC12 cells against cytotoxicity induced by amyloid-beta. Immunopharmacol Immunotoxicol. 2003;25(3):295-304. http://www.ncbi.nlm.nih.gov/pubmed/19180794.
  37. Zou Y-Q, Cai Z-Y, Mao Y-F, Li J-B, Deng X-M. [Effects of salidroside-pretreatment on neuroethology of rats after global cerebral ischemia-reperfusion]. Zhong Xi Yi Jie He Xue Bao. 2009;7(2):130-134. http://www.ncbi.nlm.nih.gov/pubmed/19216855.
  38. Ma L, Cai D, Li H, Tong B, Wang Y, Pei S. [Protective effects of salidroside on oxidative damage in fatigue mice]. Zhong Xi Yi Jie He Xue Bao. 2009;7(3):237-241. http://www.ncbi.nlm.nih.gov/pubmed/19284953.
  39. Jafari M, Felgner JS, Bussel II, et al. Rhodiola: a promising anti-aging Chinese herb. Rejuvenation Res. 2007;10(4):587-602. doi:10.1089/rej.2007.0560.
  40. Wiegant FAC, Surinova S, Ytsma E, Langelaar-Makkinje M, Wikman G, Post JA. Plant adaptogens increase lifespan and stress resistance in C. elegans. Biogerontology. 2009;10(1):27-42. doi:10.1007/s10522-008-9151-9.
  41. Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers Pharmacology and Toxicology Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials .; 2005. http://www.fda.gov/cder/guidance/index.htm.
  42. Spasov AA, Mandrikov VB, Mironova IA. [The effect of the preparation rodakson on the psychophysiological and physical adaptation of students to an academic load]. Eksp Klin Farmakol. 2000;63(1):76-78. http://www.ncbi.nlm.nih.gov/pubmed/10763116.
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