Review on Stress Reduction from Rhodiola

Stress, a physiological reaction to threat or pressure, is mediated by hormones, cytokines, and catecholamines. If untreated, these signals can lead to chronic stress or “burnout.” Stressors may be physical, emotional, environmental, external, or self-driven. The World Health Organization calls stress “the health epidemic of the 21st century.” Stress-related conditions include depression; anxiety; diabetes; and cardiovascular, gastrointestinal, musculoskeletal, and neurological diseases. Treatment options include lifestyle modifications (exercise, relaxation, meditation, and diet changes), herbal remedies, and pharmacological therapy. However, most treatments address only a single symptom of stress. An ideal therapy would affect all relevant symptoms and have a good safety profile. The authors reviewed the literature on several herbal and prescription treatments for stress. They found a significant amount of data on Rhodiola (Rhodiola rosea, Crassulaceae) extract (RRE*) and outlined a comprehensive approach to stress using RRE.

RRE is the main adaptogen** for stress according to the Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA). In vitro and in vivo, it was shown to normalize stress hormones, boost energy, and activate mitochondrial adenosine triphosphate (ATP) synthesis. Excess reactive oxygen species (ROS) in mitochondria damage cells. RRE’s antioxidant and anti-inflammatory effects may counter such damage and thus protect against heart and brain disorders. In rabbits under immobilization stress, stress hormones were significantly elevated in those that had received placebo but were virtually unchanged in those treated with RRE (1 mg/kg) for seven days before the stressor. Rats given RRE (50 mg/kg) swam significantly longer than untreated ones. Clinical studies of stress, burnout, and chronic fatigue syndrome (CFS) report RRE effective, safe, and well tolerated. Better mental work capacity, attention, task performance, and mood were seen with RRE, with fewer feelings of stress and anxiety. In a single-arm study, 101 adults with life-stress symptoms took open-label RRE (200 mg b.i.d.) for 28 days. Improvements in all outcomes, seen as soon as three days after treatment began, continued throughout the trial. In 81 students with mild anxiety due to stress who were randomly assigned to receive RRE or no treatment, the RRE group reported significant improvements in anxiety, stress, anger, confusion, vigor, and total mood at 14 days as compared with the untreated group. Studies with varied designs and populations report significant cognitive benefits in RRE-treated subjects over untreated or placebo groups. Effects in 56 healthy physicians on hospital night duty over two weeks of RRE use suggest relief of general fatigue in some stressful situations. In a double-blind, randomized clinical trial, 50 patients with CFS took 576 mg/d RRE or placebo for four weeks. Symptoms significantly improved in the active group over placebo. In an open-label, single-arm study of 101 patients with CFS, RRE use for up to eight weeks brought significant improvements in fatigue, mood, concentration, quality of life, and general well-being. Alleviation of burnout symptoms was reported by 330 German patients after using RRE for eight weeks. These almost universally reported improvements in stress and related conditions, coupled with RRE’s safety and tolerability—it has no known adverse effects or herb-drug or drug-drug interactions—make it a strong choice to prevent and counter effects of stress.

The study was funded by Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany. Author I-G Anghelescu has received consulting fees and/or honoraria from Schwabe, Boehringer Ingelheim, Otsuka, Janssen, Lundbeck, Lilly, Medice, Servier, and Trommsdorff. Author D. Edwards has received honoraria and support from Bayer, Besins, Pfizer, and Schwabe. Author E. Seifritz has received consulting fees and/or honoraria from Schwabe, Otsuka, Janssen, Lundbeck, Eli Lilly, Servier, Hoffmann La Roche, Vifor, Takeda, Sunovion, Pfizer, AstraZeneca, and Angelini. Author S. Kasper has received grants/research support, consulting fees, and/or honoraria from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe, and Servier.

* Rhodiola is found in many herbal products, but only those using RRE WS® 1375 (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) had, at the time of writing, met standards of the Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA) to become registered medicinal drugs.

** Herbal adaptogens normalize body functions, strengthen systems affected by stress, and boost non-specific stress resistance. 


Anghelescu I-G, Edwards D, Seifritz E, Kasper S. Stress management and the role of Rhodiola rosea: a review. Int J Psychiatry Clin Pract. January 11, 2018; [epub ahead of print]. doi: 10.1080/13651501.2017.1417442.

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