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By Susan T. Marcolina, MD, FACP, and Claudia Petaccio, MD
In daily life, everyone deals with stress, the mental and physical imbalance that occurs when life’s demands exceeds the ability to meet them. Physiologically, stress causes predictable systemic effects in immune function, hormone levels, and gastrointestinal and intellectual functioning.1 A wide range of events including sleep deprivation, surgery, extremes of cold and heat exposure, and anguished mental states can induce a surge of cortisol and catecholamines. Such stressors, if intense and long-lasting enough, eventually result in a decline in performance and, indeed, are risk factors for significant medical illness such as coronary artery disease and myocardial infarction.2
Stress management programs help individuals increase their adaptation response. One component of a comprehensive program could be the use of adaptogenic herbs. The term adaptogen, coined in 1947 by the Russian scientist Nicolai Lazarov and still in use today, refers to a substance that allows the body to adapt to a broad range of physical, chemical, and biological stresses and returns it to a balanced or homeostatic state. One such herb extensively studied for this purpose in Nordic countries and the countries comprising the former Soviet Union is Rhodiola rosea, also known as "golden root" and "rose root."
Taxonomy and Growth Characteristics
Rhodiola rosea L., is a member of the Crassulaceae family of plants native to circumpolar arctic alpine regions, particularly in Asia and Europe. Optimum growing conditions occur in dry sandy soils at altitudes of 5,000-18,000 feet above sea level. It is a perennial plant that grows to approximately 12-30 inches in height and bears yellow flower blossoms.3 Its thick rhizome (a root-like, horizontal stem growing just below the surface of the soil) is the portion of the plant utilized for medicinal purposes. A minimum of five to six years of growth is required before the medicinal roots are ready for harvesting. Such harvesting should occur in autumn when the plant stops its vegetative growth and the dry-matter content of the root is greatest.4
The use of R. rosea root extract (RRRE) dates back to the ancient Greek physician Dioscorides, who recorded the first medicinal applications of rodia riza in 77 C.E. in De Materia Medica. It was renamed Rhodiola rosea by Linnaeus due to the fragrance of roses emitted from the freshly cut rootstock.3,5
Traditional Russian folk medicine used RRRE to increase physical endurance and work productivity, and to treat a variety of symptoms including fatigue, depression, anemia, and infertility. In Middle Asia, RRRE tea was utilized as a treatment for colds and flu during the severe winters. In the Nordic countries, Vikings used this herb to enhance their physical strength and endurance. Today R. rosea remains a popular plant in traditional Eastern European and Asian medical systems and is used primarily to mitigate stress-related declines in work performance and to improve depression, sleep, and fatigue.1
Although Hegi, in 1963, identified more than 50 species of rhodiola plants with morphological similarities, the pharmacologic and medicinal properties of R. rosea represent a species-dependent phenomenon. Biochemical investigations of the R. rosea root in countries of the former Soviet Union over the past 40 years have revealed the presence of six distinct groups of chemical compounds (see Table).
Postulated Mechanisms for Adaptogenic Effect
Russian studies conducted primarily in animals show that RRRE stimulates norepinephrine (NE), dopamine (DA), serotonin (5-HT), and nicotinic cholinergic effects in the central nervous system (CNS). It also enhances the effects of these neurotransmitters on the brain by increasing blood-brain barrier permeability to DA and 5-HT precursors. In the brain stem, RRRE promotes the release of NE, 5-HT, and DA in ascending pathways that activate the cerebral cortex and the limbic system. This is the proposed mechanism whereby rhodiola enhances cognitive functions of the cerebral cortex and the attention, memory, and learning functions of the prefrontal and frontal cortices. The cholinergic system and the acetylcholine (Ach) neurotransmitter also contribute to memory retrieval via pathways ascending from the memory storage systems of the limbic system to various areas of the cerebral cortex. Agents that block Ach suppress the activity of these ascending pathways and interfere with memory. RRRE reverses this blockade.6,7
RRRE also modulates the release of opioid peptides that occurs as part of the pituitary adrenal axis response to stress. RRRE alters the secretion of corticotrophin-releasing factor from the hypothalamus under stress. These actions prevent sudden increases in opioid, catecholamine (NE and DA), and glucocorticoid levels, and increases stress tolerance without damage to the CNS or cardiovascular system.
In addition to its effect on neurotransmitters, RRRE contains antioxidant compounds that help protect the nervous system from free radical oxidative damage.8
Shevtsov et al conducted a randomized, double-blind, parallel-group study with two verum groups (treated with SHR-5, a standardized extract of R. rosea root called Swedish Herbal Rhodiola manufactured by the Swedish Herbal Institute), one placebo group, and one control (non-treatment) group to study the antistress effects of a single dose of SHR-5 against a background of fatigue and stress.9 The subjects were physically fit, healthy, young (age range 19-21 years) male cadets of the Russian Defense Ministry who were not heavy smokers. One treatment group took two 185 mg SHR-5 capsules and the other took three 185 mg SHR-5 capsules. Cognitive tests were used to assess mental work capacity before and after completion of night watch duty in each of the four groups.
The verum groups performed significantly better on the individual cognitive tests. A calculated total Antifatigue Index that combined measurements of work/unit time and quality of work (number of errors) showed the two rhodiola groups to perform significantly better than either the placebo or non-treatment groups (P < 0.0001).
Spasov et al performed a randomized, double-blind, placebo-controlled pilot study of a repeated, low-dose regimen of SHR-5 on a group of healthy, non-smoking 17- to 19-year-old east Indian male students during their first year medical school examination period.10 Outcome measures included physical fitness, mental capacity, and well-being. The students were randomly divided into two parallel groups receiving either SHR-5 in a dose of 50 mg or placebo twice daily for 20 days.
All students completed the test protocol and no adverse effects were observed. Despite the low dosage, investigators found significant reductions in mental fatigue, improvements in general well-being and physical fitness, and in many but not all of the cognitive tests in students taking the R. rosea extract compared to students on the placebo.
Forty-two competitive skiers (20-25 years of age) took 100 mg of RRRE or placebo 30 minutes before 30 km training races and a biathlon (20 km race carrying a rifle while skiing and shooting targets at stops).3 The athletes taking the R. rosea extract had statistically significantly increased shooting accuracy with less arm tremor and better coordination than those on placebo. Thirty minutes after the races, the heart rate in the R. rosea group was 104-106% of baseline vs. 128.7% in the placebo group (P < 0.02).
Darbinyan et al conducted a placebo-controlled, double-blind, crossover study of the effectiveness of a repeated low-dose regimen of SHR-5 (170 mg) for treating 56 healthy volunteer physicians experiencing work-related fatigue.11 Mental fatigue following night duty was evaluated using five tests addressing complex cognitive functions. A fatigue index was calculated based on these measured parameters to compare the results in both groups.
Although significant improvement was seen in the fatigue index scores of the group who took the RRRE tablets during the first two-week period, this effect was not seen in the group who took the RRRE during the third two-week period. A possible reason for this difference may have been the cumulative fatigue incurred by the second group. Since the authors did not specify the frequency of night call performed during the study, it was difficult to determine the effect on these physicians.
RRRE has demonstrated few side effects in clinical studies. RRRE should be taken early in the day as it may interfere with sleep or cause vivid dreams during initiation of therapy. It is contraindicated for people in excited states and in individuals with bipolar spectrum disorders, as it may precipitate manic episodes. Since blood pressure elevations have been observed with the use of RRRE, it should not be used in hypertensive individuals.5,12 Because it has blood-thinning properties, RRRE should not be used prior to surgery or in those using anticoagulant medication.13
Since there are no data on RRRE’s use in pregnant and nursing women, such patients should not be given this preparation.1
R. rosea has a low level of toxicity. The LD50 (lethal dose at which 50% of animals die) was calculated to be 28.6 mL/kg, which is approximately 3,360 mg. An equivalent dose in a 70 kg man would be 235,000 mg. Since usual clinical doses range between 200 mg/d and 600 mg/d for chronic supplementation, there is a huge safety margin. When using RRRE as a single dose for acute purposes (exam or athletic competition), the suggested dose is three times that used for chronic supplementation.3,6 It is best absorbed when taken on an empty stomach approximately 30 minutes prior to the morning or early afternoon meal.3
The RRRE used in human clinical studies was standardized to a minimum of 3% rosavins and 0.8-1% salidroside, since this is the ratio of these compounds that occurs naturally in the plant root (i.e., about 3:1, respectively). For this reason, whole extracts of RRRE used for medicinal purposes are standardized to these concentrations and ratios. This new standard has been adopted by the Russian Pharmacopoeia Committee.3,6,14 Table 2 summarizes some commercially available, standardized RRRE products.15
Clinical studies suggest that RRRE is effective for enhancement of physical and mental performance during periods of stress for healthy individuals. Thus far, side effects appear to be negligible. RRRE should not be used in pregnant/nursing women.
More clinical research in the form of placebo-controlled, double-blind trials is necessary to confirm the beneficial effects of RRRE. RRRE may be useful as a component of a comprehensive program for stress management that includes a healthy diet, regular exercise, smoking and substance abuse cessation, weight management, relaxation therapies, and improvement in communication and relationship-building skills.
Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA; Dr. Petaccio is a board-certified internist in Haddonfield, NJ.
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2. Kartage J, et al. Improvement in medical risk factors and quality of life in women and men with coronary artery disease in the Multicenter Lifestyle Demonstration Project. Am J Cardiol 2003;91:353-360.
3. Brown RP, et al. Rhodiola rosea: A Phytomedicinal Overview. HerbalGram 2002;56:40-65.
4. Rhodiola rosea: Russian rhodiola—Anti-aging medicine of the 21st Century. Available at www.anti-aging-guide.com/RhodiolaRosea.html. Accessed on Jan. 21, 2004.
5. Linnaeus C. Materia Medica. Liber I De Plantis. Stockholm, Sweden: Lars Salvius; 1749:168.
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7. Marina TF. Effect of Rhodiola rosea extract in the bioelectrical activity of the cerebral cortex isolated to a different extent from the brain. In: Saratikov AS, ed. Stimulants of the Central Nervous System. Tomsk, Russia: Tomsk State University Press; 1968:27-31.
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9. Shevtsov VA, 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;10:95-105.
10. Spasov AA, et al. 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;7:85-89.
11. Darbinyan, et al. Rhodiola rosea in stress induced fatigue—A double-blind, crossover 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;7:365-71.
12. Mashkovskiy MD. Doctor’s Manual: Medical Drugs. 11th ed. Volume 1. Moscow: Meditsina; 1992:140.
13. Keville K. Roseroot (Rhodiola rosea). American Herbal Association. Quarterly Newsletter; Spring 2001.
14. Dubichev AG, et al. Study of Rhodiola rosea root chemical composition using HPLC. Cemico-Pharmaceutical J 1991;2:188-193.