Rhodiola Rosea for Mental and Physical
Fatigue in Nursing Students
Reviewer:
Corey Schuler, MS, DC, LN, CNS
Author:
Punja S, Shamseer L, Olson K, Vohra S
Reference:
Rhodiola rosea for mental and physical fatigue in nursing students: a randomized controlled trial.
PLoS One. 2014 Sep 30;9(9).
Design:
Parallel-group randomized, double-blinded, placebo-controlled trial.
Participants:
A total of 48 students from the Faculty of Nursing from the University of Alberta (aged 18-55 yeas) were randomized to R. rosea (n = 24) or placebo (n = 24) for 42 days.
Study Medication and Dosage:
Participants received either two capsules of
R. rosea (182 mg/capsule) or placebo at the start of their wakeful period each day for 42 days. Participants self-determined their need for one additional capsule (a half dose), to be taken within four hours of the initial dose.
Primary Outcome Measure:
Vitality-subscale of the generic health-related quality of life instrument, RAND-36, was completed at baseline, on days 7, 14, 21, 28, 35, 42 and four weeks (day 70) following the study. The vitality-subscale is comprised of 4 items collectively aimed at measuring fatigue/energy. A 10-point Visual Analogue Scale was also used to measure fatigue (VAS-F). The VAS-F was completed concurrent with the RAND-36.
Key Findings:
Participants in the R. rosea group experienced worsened symptoms of fatigue compared to placebo. The mean change in scores on the RAND-36 Vitality-subscale was significantly different between the study groups (-17.3 (95% CI -30.6, -3.9), p = 0.011), in favor of placebo. Fatigue measured using the VAS-F also significantly improved in favor of placebo (1.9 (95% CI 0.4, 3.5), p = 0.015).
Practice Implications:
Rhodiola rosea of the family of Crassulaceae, and often referred to as simply "rhodiola," has been a part of traditional medicine systems in parts of Europe, Asia and Russia for centuries. It has a reputation for improving depression, enhancing work performance, and reducing symptoms of physical and psychological stress.[1] More recently, rhodiola has received attention from the scientific community for its potential therapeutic capacity as an adaptogen. Adaptogens are natural herbal products which have a normalizing physiologic influence and help adapt to various stressors on the body.[2]
Rhodiola appears to also have an effect on learning and memory in animal studies. In subjects with experimentally-impaired memory, rhodiola improved several parameters leading researchers to conclude that improvement of learning and memory by a short rhodiola treatment is probably due to its anti-oxidative and neuroprotective effects.[3] Scopolamine-induced amnesia is thought to be a representative model for the aging human brain as it blocks cholinergic neurotransmission. This mechanism may also be responsible for its therapeutic potential for mental and physical fatigue. In fact, there is a hypothesis regarding a cholinergic deficit in chronic fatigue syndrome and an acetylcholinesterase inhibitor has been studied to test this hypothesis.[4]
One study of 101 adult subjects with life-stress symptoms were given 200 mg of rhodiola twice daily and reported reduced symptoms in as early as three days. Generally, improvements continued and resulted in statistically significant improvement between baseline and week four.[5]
A number of clinical trials have demonstrated rhodiola exerts an anti-fatigue effect, but many have methodological flaws such as a lack of randomization, blinding, inappropriate outcome measurements, inappropriate analytic approaches, and a lack of transparency in reporting.[6] This study attempts to overcome these limitations.
Rhodiola has demonstrated a very low occurrence of side effects and a lack of interaction with other drugs which make it potentially attractive for use as a safe supplement with low toxicity.[7,8] The dose used in this study ranged from 364-546 mg per day, with most participants taking 364 mg per day. This is not considered a high dose. Other research assessed significant improvement in mental fatigue in participants who received about 575 mg per day of rhodiola versus placebo.[9] Therefore, the dose may not have been consistently high enough to produce anti-fatigue results.
The design of this trial was rather strange, providing subjects significant latitude in regards to their dosing. It appears the dosing pattern was potentially the target of investigation but investigators spent little time on this aspect of their published paper. The subjects were rather unique in that they were fourth year nursing students beginning their first swing shift or overnight rotation. This may result in significant confounding as rhodiola may suppress cortisol as well as stress-activated protein kinases.[10] In the cases where subjects are experiencing hypercortisolism, the reduction of, or rather normalization of cortisol production from the adrenal cortex as mediated via ACTH secretion from the posterior pituitary, may result in a subjective experience of fatigue. However, this return to more appropriate homeostatic responses would normally be seen as healthful. This study failed to measure objective markers of the neuroendocrine stress response which rhodiola is thought to modulate. Because cortisol production is based on diurnal patterns, timing of the dose is hypothesized to be an important consideration. Most clinicians suggest early morning and early afternoon dosing of rhodiola but when considering swing shift workers, the duration of the shift work (i.e. how long the subject has been on that schedule) plays a role in timing of diurnal-based therapeutics.[11]
Patient selection criteria for the use of rhodiola may require more complexity rather than a single symptom of mental or physical fatigue. And monitoring of therapeutic success should also be more comprehensive. For example, perhaps these symptoms due to excess life-stress or poor stress response or even aging may be worthwhile secondary characteristics. Due to rhodiola's safety and low cost it may be beneficial to add to an anti-fatigue protocol; however, integrative practitioners should be mindful of a potential additive effect with other substances. Using rhodiola is typically used with additional nutritional and lifestyle interventions when used for reducing physical and mental fatigue.
[1] Perfumi M., Mahioli L., Adaptogenic and CNS effects on single dose of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice.
Phytother Res. 2007, 21, 37-43
[2] Ishague 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.
[3] Huang SC, Lee FT, Kuo TY, Yang JH, Chien CT. Attenuation of long-term Rhodiola rosea supplementation on exhaustive swimming-evoked oxidative stress in the rat. Chin J Physiol. 2009 Oct 31;52(5):316-24.
[4] Turan T, Izgi HB, Ozsoy S, et al. The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome. Psychiatry Investig. 2009 Sep;6(3):204-10.
[5] 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.
[6] Panossian A, Wikman G, Sarris J. Rosenroot (
Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010 Jun;17(7):481-93.
[7] Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010 Jun;17(7):481-93.
[8] Ishague 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.
[9] Olsson EM, von Schéele B, Panossian AG. A randomized, double-blind, placebo-controlled, parallel-group study of the standardized extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. 2009 Feb;75(2):105-12.
[10] 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.
[11] Sadeghniiat-Haghighi K, Aminian O, Pouryaghoub G, Yazdi Z. Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial. J Circadian Rhythms. 2008 Oct 29;6:10.
