Eleuthero
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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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