Psychological stress can induce fatigue syndrome, which is characterized by long-term exhaustion, physical weakness, depression, lack of drive, poor concentration, and difficulty sleeping. Consumers often treat stress-related fatigue with stimulants. Rhodiola (Rhodiola rosea, Crassulaceae) root extract has stimulant and stress-protective (or adaptogenic) properties. The objective of this study was to determine whether daily intake of a proprietary rhodiola extract would produce any positive effects on attention, quality of life, and symptoms of fatigue and depression in subjects with stress-related fatigue.

Sixty men and women (20-55 years) living in and around Stockholm, Sweden, responded to an advertisement to participate in this randomized, double-blind, placebo-controlled study. Included subjects had “fatigue syndrome” as classified by the World Health Organization’s International Classification of Diseases. The project was approved by the Swedish Medical Product Agency and the University of Uppsala. The subjects had daily symptoms of fatigue, enduring for at least 2 weeks, related to a specific stressor that had been present for at least 6 months, and their daily functioning was negatively affected by stress. The symptoms could not be related to substance abuse or psychiatric or other primary disorders.

The diagnosis of fatigue syndrome differs from that of chronic fatigue syndrome. Fatigue syndrome requires the identification of specific stressors while chronic fatigue syndrome focuses on the immune system and symptoms of pain in the lymph nodes, joints, and muscles.

Subjects were given 120 placebo or identical-appearing tablets of a proprietary Rhodiola rosea root extract (576 mg extract/day, SHR-5, Swedish Herbal Institute, Gothenburg, Sweden). The extract was a 4:1 concentrate made by using a 70% ethanol solvent; it contained 4.0 mg/tablet of rhodioloside along with quantified but unspecified amounts of tyrosol, rosavin, and triandrin.

The primary endpoint was a reduction in fatigue symptoms assessed according to the Pines’ burnout scale. Attention was evaluated by the Conners’ computerized continuous performance test II (CCPT II) for features such as omissions, commissions, variability, and response reaction time standard error (Hit RT SE). The reduction in depressive symptoms was estimated using the Montgomery-Asberg depression rating scale (MADRS), quality of life was measured using the SF-36 questionnaire, and the cortisol (a stress hormone) response to awakening was determined from saliva samples. Saliva sampling was chosen because it is a simple, non-invasive, non-stressful method that participants could do at home. Saliva samples were collected using Salivette cotton rolls, which participants were instructed to place in the mouth for at least 1 minute or until the cotton roll was soaking wet, at 0, 15, 30 and 60 minutes after awakening.

One person dropped out of the treatment group; each group had 3 men. The placebo group had much better compliance than the rhodiola group (P = 0.07). The number of tablets remaining in the container was 0-75 tablets in the rhodiola group and 0-29 tablets in the placebo group. There was a significant improvement in fatigue symptoms, quality of life, depression, and attention in both groups. The authors state that these improvements could be due to a placebo effect, a general effect of taking the tests twice, or a regression towards the mean. However, the rhodiola group benefited more than the placebo group on assessment of fatigue symptoms (P = 0.047) and attention (omissions—not responding when a response is required [P = 0.02], variability [P=0.005], and Hit RT SE [P=0.001] that indicate a more stable work pace). The cortisol response to awakening stress (awakening is a mild stressor) was reduced significantly following 28 days of treatment with the rhodiola extract in comparison with the control group (P = 0.038). No adverse events occurred during the study, and no major side effects that could be clearly linked to the rhodiola preparation were reported by any of the subjects.

The authors conclude that repeated administration of rhodiola extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome. According to the authors, this study is the first to show that this proprietary rhodiola extract benefits patients with chronic stress-induced fatigue. Additionally, this study is the first to suggest clinically that Rhodiola rosea root benefits stress-induced disorders by modulating cortisol. There are data suggesting that the inhibitory effect of Rhodiola rosea on the increased basal level of cortisol results in an improvement in cognitive function. This proposal is consistent with other studies suggesting that optimal corticosteroid levels are a requirement for efficient cognitive function, as significant changes (up or down) in circulating levels of corticosteroids correlate with cognitive impairment.¹ Modulation of cortisol content is believed to be a key mechanism of action of phytoadaptogens.

The authors suggest that the reason a potential effect on depressive symptoms was lacking—as has been documented in a previous trial designed to measure the effect of this specific rhodiola extract on depressed patients²—may have been due to the inadequate duration and because subjects with depression as a major symptom were excluded from this trial. The authors do not hypothesize why the rhodiola group had poorer compliance or whether the findings would have been more robust if compliance were improved. It should be noted that the effects seen in this study may be specific to the proprietary rhodiola product used and the specific dose.

—Heather S. Oliff, PhD