Rhodiola is a genus of alpine plants containing over 200 different species that grow throughout Europe, Asia, and Alaska [1, 2], with over 70 of these in China [3]. At least 20 of these species have been used in Asian traditional medical systems, including R. alterna, R. brevipetiolata, R. crenulata, R. kirilowii, R. quadrifida, R. sachalinensis, R. sacra, and R. rosea [1]. A common Tibetan folk medicine, Rhodiola Radix, is a preparation of several Rhodiola plants that is used as a hemostatic, tonic and contusion [3-5].

One species, Rhodiola rosea (also known as "golden root" and "Arctic root"), is of particular interest. This species is widely distributed at high altitudes in Arctic and mountain regions throughout Europe and Asia, and has been a popular plant in traditional medicine in various areas of both Eastern Europe and Asia [1]. In Chinese medicine, it is used to enhance resistance against fatigue and extend life [2]. This species has been studied intensively in Russia and Scandinavia for over 35 years, and literature from these areas indicate that it has antidepressant, anticancer, cardioprotective, and central nervous system enhancing properties, while suggesting benefits in diverse conditions such as schizophrenia, seasonal affective disorder, fibromyalgia, chronic fatigue syndrome, and others [1]. The clearest benefit is adaptogenic and anti-stress activities, with improved learning and memory and anti-hypoxia effects also commonly reported [1-5].

A number of pharmacologically active components have been identified in Rhodiola species, including organic acids, flavanoids, tannins, and phenolic glycosides [1]. Phenylpropanoid tyrosol (p. tyrosol), its glucoside salidroside (also known as rhodioloside or rhodosin), and phenylpropenoids rosin, rosarin, and rosavin all play important antioxidant and neurostimulant roles in the activity of Rhodiola rosea [2], with rhodioniside, rhodiolin, and rosiridin also implicated in R. rosea's adaptogenic activity [1]. Numerous other antioxidant compounds have been identified in Rhodiola species, including gallic acid, (-)-epigallocatechin 3-O-gallate, kaempferol, kaempferol 7-O-alpha-L-rhamnopyranoside, herbacetin 7-O-alpha-L-rhamnopyranoside, and rhodiolinin [6].

The mechanisms of action of Rhodiola rosea are many. These include antioxidant activity, propyl endopeptidase inhibition [2, 5], facilitation of monoaminergic activity, and opioid receptor activation. The enzyme propyl endopeptidase metabolizes various proline-containing neuropeptides including vasopressin, substance P, thyrotropin-releasing hormone, and alpha-melanocyte-stimulating hormone, all of which may play roles in learning and memory processes [5, 7]. Indeed, other propyl endopeptidase inhibitors improve spatial memory in animal models [7-8]. Rhodiola rosea may also inhibit monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) and facilitate the transport of neurotransmittors in the brain [1]. Another mechanism of action is the release of endorphins. Russian research indicates that Rhodiola rosea induces opioid peptide biosynthesis by activating opioid receptors in both the central and peripheral nervous system [1].

Rhodiola is among the herbs classified as adaptogens. The term "adaptogen" originated in Russia in 1947, and is defined as a substance that allows an organism to counteract adverse physical, chemical, or biological stressors by generating non-specific resistance. In 1969, specific criteria were created which need to be fulfilled before a substance qualifies as an adaptogen. Because Rhodiola rosea prevents a variety of deleterious effects caused by physical and intellectual stress and illness, such as decline in work performance, sleep disturbances, irritability, hypertension, headaches, and fatigue, it is classified as an adaptogen [1]. Rhodiola is also unique among adaptogens, in that it may be more effective than others in periods of acute stress, while most are primarily effective only in periods of chronic stress.

Because of its adaptogenic properties and its ability to increase the efficiency of mitochondrial respiration in skeletal muscle [3], Rhodiola is particularly useful for athletes, who regularly engage in taxing, high-intensity exercise, as it may both improve recovery and increase work output. As far as clinical trials in humans, the research in this area is sparse but very promising. A study with 1.5 grams per day of a Rhodiola crenulata root (which has a similar profile of active constituents to Rhodiola rosea) extract for 75 days found that it increased run time to exhaustion and maximum oxygen consumption in athletes [9]. Studies on the effect Rhodiola has on the work output of animals have also been done. Administration of Rhodiola for 10 days significantly increased the time that rats could spend running on a treadbane, with an even more significant increase after 20 days [10], and Rhodiola also increased the swimming times of rats in a "swim to the limit" test by 135-159% [1, 10].

In addition to increasing physical work capacity, Rhodiola rosea increases mental work capacity and induces a resistance to mental fatigue. In fact, it may directly improve learning and memory even in non-stressful conditions. Three double-blind placebo-controlled trials have recently been conducted in humans in this regard. The largest tested the effect of two doses of a standardized Rhodiola rosea extract in 160 19-21 year old cadets on mental capacity during a period of fatigue and stress. It found that both doses reduced the level of fatigue as measured by the antifatigue index (AFI) by over 10% [11]. Another study assessed the effect the same extract had on 56 young physicians on measures of mental fatigue, including tests of associative thinking, short-term memory, calculation and ability to concentrate, and speed of audio-visual perception during two weeks of night duty. There was a statistically significant improvement on all five tests used in the treatment group [12]. The last study looked at the effects a Rhodiola rosea extract had on physical and intellectual working capacity and measures of well being during a 20 day exam period in 40 students. The students that recieved Rhodiola had significant improvements in physical fitness, psychomotor function, mental performance, and well being, with reductions in mental fatigue, improved sleep patterns and reduced sleep need, greater motivation to study, and greater mood stability. The treatment group also had 8.5% higher scores on the final exam [1, 13].

There have also been animal studies on the effect Rhodiola has on mental performance. In one of them, .1 mL of a Rhodiola rosea extract improved learning and memory within 24 hours and also improved long-term memory after 10 days in rats. However, two other doses of 20% as much and 10 times as much were ineffective, suggesting that there is a window of therapeutic activity [14]. Substantial neuroprotection has also been observed, with Rhodiola rosea having numerous benefits on metabolic processes in the brain and preventing brain damage during cerebral ischemia [15].

Rhodiola also has adaptogenic activity in high altitude environments. Studies in humans living in high altitudes have found that Rhodiola improves sleep architecture and quality and blood oxygen saturation, as well as increasing superoxide dismutase activity in red blood cells, along with other benefits [3, 16]. Two other species of Rhodiola have prevented hypoxia-mediated damage to rat viscera and had anti-hypoxic effects including lowering of arterial pressure, decrease in heart rate, and lengthening of the cardiac contraction phrase in high altitude environments [3].

In addition to these adaptogenic qualities, Rhodiola affords numerous other health benefits as evidenced by animal studies. Most studied are beneficial effects on the heart and liver, while some protection against cancer has also been seen. Among the beneficial effects in the heart are an anti-arrhythmic effect, prevention of the reperfusion-induced decrease in contraction amplitude and reduction of coronary blood flow, reduction in stress-induced cardiac damage mediated by catecholamines and elevated cAMP levels, and improved contractile force and stability after acute cooling [1, 3, 17-20]. Most of these effects are presumed to be due to activation of both central and peripheral opioid recepts. Rhodiola is also a potent hepatoprotective agent. R. sachalinensis reduces the development of chemically induced liver fibrosis and liver injury in rats [21-22], and R. rosea was protective in a toxic hepatitis model by normalizing the activity of various enzymes [23]. Administration of Rhodiola rosea also inhibits the development of two types of cancer in the liver, suppresses the growth of lung cancer, improves the clinical activity of other anticancer drugs, and has an antimutagenic effect in bone marrow cells [1, 24]. In a study with a small group of patients recovering from bladder cancer, Rhodiola appeared to improve recovery, but the difference was not statistically significant [25].

As stated earlier, there appears to be an ideal dosage range for Rhodiola above and below which it is ineffective. Unfortunately there is little literature in which the ideal dosage range has been explored in humans. The mental enhancement clinical trials described above used dosages of 370 and 555 mg, 170 mg, and 100 mg of Rhodiola rosea extract respectively, all standardized to 3.6% rosavin. In the first trial, there was a slight trend towards greater improvement in the lower dose. This would indicate that the ideal dosage for Rhodiola is in the range of 3.6-13.3 mg rosavin (total dosage varies based on the standardization of the extract), at least when using for 2-3 week periods. Rhodiola is also traditionally used in a cyclic fashion, with cycles ranging from a day to four months [1]. The general recommendation is for supplementation for 2-3 weeks prior and then throughout the duration of a high stress period, such as an exam, competition, or other deadline, followed by a period of abstinence. If Rhodiola is not already being regularly used, a dosage providing 10-20 mg rosavin is recommended prior to an expected stressful event. Few side effects are reported, but using over 30 mg of rosavin daily has been reported to cause insomnia and irritability [1].