Eleuthero

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim.
(syn. Acanthopanax senticosus [Rupr. & Maxim.] Harms)

[Fam. Araliaceae]

Overview

Eleuthero root has been widely known in the U.S. as “Siberian ginseng.” It was first marketed in the U.S. in the late 1970s (Foster, 1991), and since become one of the top-selling herbal dietary supplements in the natural foods class of trade (Brevoort, 1998; Tyler, 1998). It has been used in Traditional Chinese Medicine (TCM) for over 2,000 years and is listed in the Shen Nong Ben Cao Jing, China’s oldest pharmacopoeia, as well as in the pharmacopeia of Li Shih-Zhen of the Ming dynasty (Halstead and Hood, 1984). However, it was modern Russian researchers who popularized this herb in the West (Foster and Chongxi, 1992; Kenner and Requena, 1996). From the 1940s through the 1960s, Soviet scientists conducted extensive clinical research on eleuthero in their search for a more abundant and economical alternative to Asian ginseng (Panax ginseng). “Adaptogen” has traditionally been defined as a substance useful for both sick and healthy individuals, which improves dysfunction without side effects (Brekhman, 1980; Davydov and Krikorian, 2000; Farnsworth, et al.. 1985). In the case of eleuthero, “adaptogen” is defined as a substance that is innocuous and relatively free of side effects, has nonspecific actions, increases resistance to a wide range of environmental or other physical stressors, and may have a normalizing action in the body, irrespective of a diseased state (Brekhman, 1980). Russian Olympic athletes, explorers, divers, sailors, and miners have used eleuthero as a preventive agent against stress-related illnesses (Brekhman, 1980; Fulder, 1980). Eleuthero is official in Russia, China, France, and Germany (see “Regulatory Status” below). Scientific comparisons of eleuthero to the more familiar Asian ginseng (“true ginseng”) underscored that they differ considerably chemically and pharmacologically, and cannot be considered interchangeable. Accordingly, the herb industry has recommended that the common name “Siberian ginseng” be replaced with the more preferred common name “eleuthero” (Foster, 1992; McGuffin, 2001). Federal regulations now require that, “the common or usual name of ingredients of dietary supplements that are botanicals…shall be consistent with the names standardized in Herbs of Commerce, 1992 edition” (US FDA, 1999). This nomenclature has been accepted by the U.S. Food and Drug Administration.

Description

Eleuthero preparations consist of the dried roots and/or rhizomes of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (syn. Acanthopanax senticosus [Rupr. & Maxim.] Harms [Fam. Araliaceae]), The dried root contains no less than 4% water-soluble extractive (BHP, 1996), and no less than 6% water- and ethanol-soluble extractive (DAB, 1999).

Primary Uses

Immunology

Decrease in severity, duration, or frequency of attacks of herpes simplex type II infections (Williams, 1995)

Decrease in the occurrence of influenza complications (Shadrin et al., 1986)

Fatigue

Tonic for invigoration and fortification in treatment of: fatigue, debility (Bradley, 1992; Blumenthal et al., 1998), declining work capacity and concentration, convalescence (Blumenthal et al., 1998); chronic fatigue syndrome and supportive therapy during radiation or chemotherapy (Brown, 2000)

Functional asthenia (Bruneton, 1999)

Memory Disturbance

Improvements in selective memory (Winther et al., 1997)

Other Potential Uses

Decrease in total cholesterol, LDL cholesterol, and triglyceride levels (Szolomicki et al., 2000); atherosclerosis (Golikov, 1963)

Insomnia and other conditions characterized by anxiety-like behavior in modern Chinese medicinal use (as a single-herb remedy) (Chang, 1986). This is consistent with eleuthero’s observed sedative activity, primarily in animal studies (Newall et al., 1996)

Chronic inflammatory conditions (Bradley, 1992)

Vision, perception

Increased color perception level and functional stability level, enhanced spectral and contrast sensitivity and range of signal light visibility and increased speed of color discrimination (Sosuova, 1986)

Dosage

Internal

Crude Preparations

Powdered root: 2–3 g daily (Bradley, 1992), 1–4 g daily (MediHerb, 1994).

Decoction: 9–27 g (PPRC, 1997).

Infusion: 150 ml of boiling water is poured over 2–3 g and steeped for 5–10 minutes (Blumenthal et al., 1998).

Fluid extract: 1:1 (g/ml), 33% ethanol, 2–4 ml, 1–3 times daily (Pizzorno and Murray, 1999; Werbach and Murray, 2000), 1:2 (g/ml): 2–8 ml per day (MediHerb, 1994), 2–3 g daily powdered or cut root aqueous alcoholic extract (Blumenthal et al., 1998).

Tincture: 1:5 (g/ml), 10–20 ml, 1–3 times daily (Pizzorno and Murray, 1999).

Native extract: 20:1 (w/w), 300–450 mg, 3 times daily; tablets containing 150 mg native extract, 2–3 tablets, twice daily (PPRC, 1997).

Standardized Preparations

Dry extract: (>1% eleutheroside E), 100–200 mg, 3 times daily (Werbach and Murray, 2000).

Note: In healthy individuals, maintenance doses should be based on the lower end of the dosage range. For treatment of illness and high-stress situations, the upper end of the dosage range should be considered (MediHerb, 1994).

Duration of Administration

Some sources recommend a course of one month (Bradley, 1992) to three months (Blumenthal et al., 1998) followed by a two month break (Bradley, 1992). A repeat course is feasible (Blumenthal et al., 1998). While the issue has not been studied specifically, it is a general practice to temporarily halt herb consumption after a reasonable period when it is not considered essential for maintaining vital functions. This provides an opportunity to reassess the case and either stop its use completely, continue at a lower dose, or re-institute its use as before. Such a recommendation is not a limitation, but advice on its reasonable use, as opposed to assuming regular, ongoing consumption is necessary or appropriate.

Chemistry

Eleuthero contains ca. 0.6–0.9% eleutherosides A-G in an approximate ratio of 8:30:10:12:4:2:1. Eleutheroside A is the sterol daucosterol; eleutheroside B is the phenylpropanoid syringin; eleutheroside C is the sugar methyl a-D-galactoside. Eleutheroside D is the lignan (-)-syringaresinol di-O-b-D-glucoside, and its diastereoisomer is eleutheroside E (Bradley, 1992; Farnsworth et al., 1985). Eleuthero also contains immunostimulant polysaccharides (Fang et al., 1985; Huang, 1999). An extensive review of the chemistry of eleuthero with 29 chemical structures has been published (Tang and Eisenbrand, 1992).

Pharmacological Actions

Human

Increases lymphocyte count (Blumenthal et al., 1998); adaptogen; tonic (BHP, 1996); anti-stress activity (Wagner et al., 1994); immunomodulatory effect on the cellular immune system (Bohn et al., 1987); tranquilizes central nervous system; reduces heart palpitations and headaches due to high-altitude hypoxia syndrome (Huang, 1999); increases phagocytic activity of neutrocytes (Szolomicki et al., 2000); increases the absolute numbers of immunocompetent cells, particularly T-cells, predominantly of the helper/inducer type, but also on cytotoxic and natural killer cells (Bohn et al, 1987); in TCM theory, reinforces and tonifies vital energy known as “qi,” invigorates the function of the “spleen” and “kidney,” and tranquilizes (Chang and But, 1986; PPRC, 1997).

Animal

Enhances endurance (Blumenthal et al. 1998); chemical-, biological-, and radioactive-protective (Collisson, 1991; Minkova and Pantev, 1987; Yonezawa et al., 1989); antioxidant, antihypertensive, hypo/hyperglycemic activity (Farnsworth et al., 1985; Hikino et al., 1986; Medon et al., 1981); sedative (Medon et al., 1984); stress reduction (Takasugi et al., 1985). Eleuthero’s isolated glucosides protect against myocardial infarction and can lower blood sugar levels in normal and hyperglycemia-induced mice (Hikino et al., 1986; Tang and Eisenbrand, 1992).

In vitro

Mutual potentiation of antiproliferative effects on leukemia cells when applied in combination with conventional antimetabolite drugs (Hacker and Medon, 1984); slight gamma radiation protection (Ben-Hur and Fulder, 1981); inhibition of hexobarbital metabolism in mice (Medon et al., 1984).

Mechanism of Action

Most studies on eleuthero were conducted to investigate its adaptogenic effects. The chemical compounds and pharmacological actions of eleuthero support the theory that the primary benefit of an adaptogen is its protective and inhibitory action against free radicals (Davydov and Krikorian, 2000). The exact mechanisms of action of eleuthero and/or the significance of its constituents are not yet fully understood (MediHerb, 1993), despite numerous pharmacological investigations in human and animal models.

According to the literature, eleuthero acts via the following mechanisms:

Increases immune system function by enhancement of T-cell activation (Wagner, 1985). Active principles responsible for its immunomodulation activities are not yet known (Wagner, et al., 1994).

Intensifies regeneration, in vivo, of subcellular structures and accelerates recovery during experimental myocardial infarction; may be related to the transformation of lipids into glycogen (Afanas’eva and Lebkova, 1987).

May support and enhance adrenal function and the optimal functioning of the hypothalamic-pituitary-adrenal cortex axis (Baranov, 1982; Brekhman and Dardymov, 1969; Filaretov et al., 1988; Kirilov, 1964). Greater energy and better reaction to stress are associated with optimal adrenal function.

Maximizes the utilization of oxygen by working muscles, which prolongs the aerobic state (Asano et al., 1986).

Increases endurance and reduces activation of the adrenal cortex in response to stress (alarm phase reaction) and also has significant prophylactic effects on stress reactions (Brekhman and Kirillov, 1969; Czygan, 1984).

In vitro, ethanolic fluid extract increases phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30–40% (Wildfeuer and Mayerhofer, 1994).

In vitro, binds to progestin, mineralocorticoid, glucocorticoid receptors, and estrogen receptors, which could explain the observed glucocorticoid-like activity of the extract (Pearce et al., 1982).

Increases cAMP levels (Wagner et al., 1994).

Contraindications

The Commission E contraindicates eleuthero for patients with high blood pressure (Blumenthal et al., 1998). This is based on a Russian study on patients with rheumatic lesions of the heart that recommended that eleuthero not be given to persons with blood pressure higher than 180/90 mm Hg (Mikunis et al., 1966; Farnsworth et al., 1985). However, there is no other literature available to support the contraindication of eleuthero in otherwise normal hypertensive patients. Based on Russian clinical experience, eleuthero should not be used during the acute phase of infections, though it is used to treat dysentery in combination with antibiotic use (MediHerb, 1994).

Pregnancy and Lactation: No known restrictions (Brown, 2000; McGuffin et al., 1997). An absence of teratogenicity with administration of eleuthero has been demonstrated in animals (Farnsworth et al., 1985).

Adverse Effects

No side effects have been documented for eleuthero in healthy individuals (Farnsworth et al., 1985; Blumenthal et al., 1998). In rare cases, mild, transient diarrhea has been reported. In rare cases, sleep disturbances have been reported (Hänsel, 1991; Brown, 2000). In patients with rheumatic heart disease, side effects such as pericardial pain, headaches, and elevated blood pressure have been reported (Werbach and Murray, 2000). Reports of neonatal/maternal androgenization (“hairy baby” syndrome) have been attributed to maternal ingestion of products labeled as “Siberian ginseng” (Koren et al., 1990), though subsequent investigations determined the implicated product did not contain eleuthero but was adulterated with Chinese silk vine (Periploca sepium) (Awang, 1991; Awang, 1996b).

Drug Interactions

There are few well-documented reports of interactions with eleuthero. Mutual potentiation of beneficial effects when eleuthero is administered with the radioprotector drug adeturone has been reported (Minkova and Pantev, 1987). Eleuthero potentiates effects of antibiotics monomycin and kanamycin in treatment of Shigella dysentery and Proteus enterocolitis (Brinker, 2001).

One case of unexplained elevated digoxin levels has been reported (McRae, 1996). It is unclear whether some unknown component of eleuthero was converted to digoxin in vivo, interfered with digoxin elimination, caused a false serum assay result, or was a result of a possible substituted herbal material, since the identity of the raw material was not confirmed and may have been another case of adulteration with Chinese silk vine (Awang, 1996a; 1996b). Possible interactions with prescription drugs warrants caution regarding the concomitant use of eleuthero and antipsychotic drugs, barbiturates, and sedatives (Medon, 1984); however, there are no actual reports to support this speculation. Eleuthero may produce an enhanced effect on insulin and antidiabetic therapy, at least theoretically (Brinker, 2001); diabetics should monitor blood glucose levels closely due to the potential hypoglycemic action.

American Herbal Products Association (AHPA) Safety Rating

Class 1: Herbs that can be safely consumed when used appropriately (McGuffin et al., 1997).

Regulatory Status

Canada: Drug Identification Number (DIN) assigned (Health Canada, 2001).

China: One eleuthero-containing multi-ingredient product has schedule OTC status with a Drug Identification Number (DIN) assigned (Health Canada, 2001).

European Union: Dried root official in the European Pharmacopoeia, 3rd ed. Supplement 2000 (Ph.Eur., 2000).

France: Traditional Herbal Medicine (THM) for specific indication (Bradley, 1992; Bruneton, 1999). Added to French Pharmacopoeia in 1996 (Bruneton, 1999; Ph.Fr., 1996).

Germany: Approved non-prescription drug of the German Commission E (Blumenthal et al., 1998). Official in the German Pharmacopoeia (DAB, 1999).

Russian Federation: Official in the State Pharmacopoeia of the Union of Soviet Socialist Republics since 1962 (Foster, 1991; Fulder, 1980; Schulz and Hänsel, 1996; USSR, 1990).

Sweden: As of January 2001, no eleuthero products are listed in the Medical Products Agency (MPA) “Authorised Natural Remedies” (MPA, 2001).

Switzerland: No licensed herbal medicines containing eleuthero. No monograph in the Swiss Pharmacopoeia.

U.K.: Not included on the General Sale List, and no product licenses granted (Bradley, 1992; Newall et al., 1996).

U.S.: Dietary supplement (USC, 1994).

Clinical Review

Nine studies are outlined in the following table, “Clinical Studies on Eleuthero,” conducted on 1,984 participants. All but one of these studies (Dowling et al., 1996) demonstrate positive effects for immune response, stress, fatigue, and cardiovascular health. The table includes four double-blind, placebo-controlled (DB, PC) studies investigating the effects of eleuthero on concentration, selective memory, cognitive function, and well-being (Winther et al., 1997); ergogenic parameters in athletes (Dowling et al., 1996); immune protection against herpes simplex type II infection (Williams, 1995); and immunomodulatory measurements (e.g., T-cells) in healthy volunteers (Bohn et al., 1987). A single-blind, placebo-controlled (SB, PC) study evaluated eleuthero’s effects on work capacity, stamina, and fatigue in male athletes (Asano et al., 1986). Clinical studies on eleuthero extracts have been extensively conducted in the former Soviet Union since the early 1960s. More than 2,100 normal and stressed human subjects were orally administered eleuthero root fluid extract, 33% ethanol. The studies examined the adaptogenic response of humans to adverse conditions such as heat, noise, motion, workload increase, and exercise. These studies also measured a significant improvement in auditory disturbances, increased mental alertness, work output, and quality of work under stress (Farnsworth et al., 1985).

Branded Products

Elagen: Eladon Ltd. / 63 High Street / Bangor, Gwynedd / LL57 1NR / U.K. / Tel: +44-01-24-83-7005-9 / www.elagen.com. Hydro-alcoholic dried extract (10:1) of Eleutherococcus senticosus root extract standardized root at 0.4% eleutheroside B and 0.4% eleutheroside E in 375 mg tablets. This product is now called Eleugetic^®.

Eleukokk^®: Pharma-Inter-Med / Am Born 19 / 22765 Hamburg / Germany. 10 g of test preparation consisted of 1.96 g eleuthero root ethanolic fluid extract 1:1 (0.20% (w/v) eleutheroside B, 1.30 g sorbitol water 70% (w/v), and 6.74 g dessert wine. This product is no longer available.

Maxim-L^®: Omega Nutripharm. No manufacturer information available. Eleuthero root fluid extract with 30–34% ethanol (eleutherosides B and E present).

Medexport: Moscow, Russia. No manufacturer information available. Eleuthero root fluid extract Ph. USSR: 42-358-72, 335 ethanol. Each ml of fluid extract contains 75 mg of soluble extractive of Eleutherococcus senticosus, including 0.53 mg of syringin (eleutheroside B) and 0.12 mg of syringaresinol di-glucoside (eleutheroside D).

Taigutan^® Eleuthero root fluid extract: Dr. Mewes Heilmittel GmbH / PF 1325 / 56194 Höhr-Grenzhausen / Germany / Tel: +49-02-62-49-4529-0 / Fax: +49-02-62-49-4529-1 / www.paesel.lorei.de. A 1:1 (w/v) extract in 35% (v/v) ethanol. Unable to confirm manufacturer.

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