||This article may present fringe theories, without giving appropriate weight to the mainstream view, and explaining the responses to the fringe theories. (December 2012)|
Adaptogens are plants that practitioners of herbal medicine claim decrease cellular sensitivity to stress. The adaptogen concept does not fit easily into the Western model of medicine, and the scientific community calls into question the validity of the concept. Most of the studies done on adaptogens were conducted in the Soviet Union (prior to its dissolution in 1991), Korea, and China during the 1980s, and they are not considered conclusive and have been criticized for having methodological flaws. Adaptogens have been claimed to treat a wide variety of medical conditions, from fatigue to cancer. However, no herbs that are considered adaptogens have ever been conclusively shown to be effective in treating any medical condition, and as a result, none of them are approved by the FDA to cure, treat, or prevent any disease.
History of the concept 
The concept adaptogen was originally created by the pharmacologist A.V. Lazarev in 1947 to describe novel effects of dibazol 12-benzyl benzimidazol, an arterial dilator developed in France. This concept was later (in the former Soviet Union) applied to describe remedies that increase the resistance of organisms to stress in experimental and clinical studies. According to the original definition, adaptogens are non-specific remedies that increase resistance to a broad spectrum of harmful factors (stressors) of different physical, chemical and biological natures.
This definition has been updated and today adaptogens are conceptualized as a "new class of metabolic regulators which increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors."
Despite an extensive amount of research in the USSR, (by 1984, more than 1,500 pharmacological and clinical published studies), the concept is not generally recognized in Western countries as it seemed to be in contrast to some of the key concepts of modern pharmacology: potency, selectivity and with efficacy balanced by an accepted level of toxicity. Adaptogens have even been described as "medicines for healthy people". In 1998, however, the term adaptogen was allowed as a functional claim for certain products by US Food and Drug Administration and it is now a generally accepted concept, also by the European Medicines Agency.
An adaptogen must have a normalizing effect, i.e., counteracting or preventing disturbances to homeostasis brought about by stressors. Moreover, it must be innocuous with a broad range of therapeutic effects without causing any major side effects. The adaptogen concept does not fit easily into the Western model of medicine, and the scientific community calls into question the validity of the concept. Most of the studies done on adaptogens were conducted in the Soviet Union (prior to its dissolution in 1991), Korea, and China during the 1980s, and they are not considered conclusive and have been criticized for having methodological flaws. Adaptogens have been claimed to treat a wide variety of medical conditions, from fatigue to cancer. However, no herbs that are considered adaptogens have ever been conclusively shown to be effective in treating any medical condition, and as a result, none of them are approved by the U.S. Food and Drug Administration (FDA) to cure, treat, or prevent any disease. In contrast, adaptogens achieved recognition in the official medicine of Russia in the early 1960s (Mashkovskij, M.D.,1978.MedicinalDrugs—Manual on Pharmacotherapy for Doctors. Part II, 8th ed. Meditsina Publishing House, Moscow, pp. 131–132; Mashkovskij, M.D. 2000. Medicinal Drugs—Manual on Pharmacotherapy for Doctors, vol. 1., 14th ed. New Wave Publishing House, Moscow, pp. 134–135). Since 1960, adaptogens have secured an established position within Russian medicine, and specific monographs for various preparations of Schisandra chinensis, Rhodiola rosea, Eleutherococcus senticosus and several other plants have appeared in several editions of the National Pharmacopoeia of the USSR (1968, 1990). Recent State lists and registers of medicines and drugs (The Ministry of Health and Medical Industry of Russian Federation, 1997, 2000) include a number of medicines based on adaptogens that are currently used in Russia. Rhodiola rosea extract, for instance, was approved in 1969 by the Pharmacological Committee of the Ministry of Health of the USSR for use as a stimulant against fatigue by patients who suffered asthenic states and by healthy people who showed astheny during periods of high mental exertion or after intensive physical work.
As a dietary supplement, numerous preparations of Rhodiola extracts are used USA and world-wide (Khanum, F., Bawa, A.S., Singh, B., 2005. Rhodiola rosea: a versatile adaptogen. Comp. Rev. Food Sci. Food Saf. 4, 55–62). The functional claim of Rhodiola dietary supplements currently mentioned in the Consolidated list of Article 13 health claims of the European Food Safety Authority (EFSA) is formulated as following – ‘‘contributes to optimal mental and cognitive activity’’ efsa_locale-1178620753812_article13.htm In Sweden Rhodiola tablets containing Rhodiola rosea SHR-5 extract have been on the market since 1985. They are currently registered as Traditional Herbal medicinal product indicated as an adaptogen in situations of decreased performance such as fatigue and sensation of weakness. Preparations of the drug now form part of the official medicine of some of European countries (Estonian Ministry of Health Affairs, 1998. Regulation no. 7, Annex 1, 21 January, Government of Estonia, Tallinn.).
Mechanism of action 
The mechanism of action has been hard to rationalize. However, by 1965 it had been demonstrated that the adaptogenic effect was dependent on cellular transcription By 1980, it was clear that the effect operated on the sympathetic nervous system.
A series of recent pharmacological studies have provided a rationale for the effects at the molecular level. The stress-protective activity of adaptogens has been found to be associated with activation of molecular chaperonin Hsp70, and other key mediators of the stress response such as cortisol, nitric oxide, stress-activated protein kinase JNK and DAF-16. Studies have demonstrated that heat-shock factor 1 (HSF1) and Neuropeptide Y might be primary upstream molecular targets of adaptogens in neuroglia cells, but the results were only suggestive, not conclusive. One recent analysis revealed that a claimed adaptogen extract, ADAPT-232, and some of its components individually, regulated the transcription of genes involved in cellular signaling pathways, most notably those of G protein-coupled receptors.
Repeated vs. single dose administration 
The repeated administration of adaptogens gives an effect analogous to that produced by repeated physical exercise by a transition from homeostasis to heterostasis. The effect is mainly related to the HPA-axis (Hypothalamic-Pituitary-Adrenal-axis). Repeat dose administration of adaptogens has been shown to be of value in sports medicine and can lead to increased endurance for long distance runners, cross-country skiers etc., or to a more rapid recovery from a stressors events. The stress protective effect by repeated intake is not the result of inhibition of the stress response, but of adaptive changes in the organism to the repeated stress-mimetic effect of the drug. Adaptogens are stress agonists and not stress-antagonists.
Administration of adaptogens in a single dose is relevant when a rapid response to stress and strain is required. This effect is associated with the sympathetic nervous system. Suitable crude drugs for this purpose are Eleutherococcus senticosus (Siberian ginseng), Rhodiola rosea and Schisandra chinensis, which also can be used for repeated administration.
Adaptogens vs. stimulants 
Despite the claims of some alternative medicine practitioners and patients, adaptogens are much less efficacious than stimulants. For example, there is no conclusive evidence that ginseng, perhaps the most famous and thoroughly tested adaptogen, is effective in treating any medical condition, and it has not been approved by the FDA for the treatment of any disease. Most studies that claim to have found benefits for ginseng and other adaptogens were conducted in China, North Korea, or the Soviet Union, and the scientific community does not find them convincing. Adaptogens are absent from mainstream medicine, but are widely used in energy drinks. In contrast, stimulants are widely used in mainstream medicine to treat conditions such as narcolepsy, obesity, and attention-deficit hyperactivity disorder.
In spite of their theoretical normalizing effect, certain dosing regimens of supposed adaptogenic plant extracts are claimed to have stimulating effects on the central nervous system. Plant adaptogens are said to stimulate the nervous system by mechanisms which are totally different from those of conventional stimulants as associated with metabolic regulation of various elements of the stress system and modulation of stimulants-response comply.[clarification needed]
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