9928 B

Introduction

Rhodiola rosea L. is a medicinal plant from the Cras-

sulaceae family, with the main active substance salidro-

side, a phenylpropanoide (Steinegger-Hänsel, 1992,

Saratikov et al., 1968). Rhodiola rosea is grown in dry

and sandy ground, mainly in the Arctic and Alpine re-

gions of Europe, Asia and America. The part used in

medicine is the root-stock, while the green aerial part is

used as a food ingredient. Rhodiola has a long tradition

as a medicinal plant in several European countries, no-

tably Iceland (Hjaltalin, 1830; Hallgrímsson, 1964),

Norway (Hoeg, 1984), Sweden (Roselli, 1755; Sand-

berg and Hansen, 1998; Sandberg and Bohlin, 1993),

France (Pharmacopée Française, 1974), Greece and

Russia. Its use in the medicine was reflected already in

the first Swedish Pharmacopoeia (Pharmacopoeia Sve-

cia, 1775) and Materia Medica (Materia Medica, Lin-

naei, 1749) and appears also more recently in the

French Pharmacopoeia (1974) as well as in the Eston-

ian (Estonian Ministry of Health, 1998).

In Europe the use of Rhodiola rosea L. in medicine

dates back to the ancient Greeks (Mell, 1938).

Dioscorides referred to it in the 1st century A.D., under

Rhodiola rosea in stress induced fatigue –

A double blind cross-over study of a standardized

extract SHR-5 with a repeated low-dose regimen

on the mental performance of healthy physicians

during night duty.

V. Darbinyan

, A. Kteyan

, A. Panossian

, E. Gabrielian

, G.Wikman

and H. Wagner

Department of Neurology, Armenian State Medical University, Yerevan, Armenia

Guelbenkian Research Laboratory of Armenian Drug and Medical Technology Agency, Yerevan, Armenia

Swedish Herbal Institute, Gothenburg, Sweden

Institute of Pharmacy, Pharmaceutical Biology, Ludwig Maximilian University, Munich, Germany

Summary

The aim of this study was to investigate the effect of repeated low-dose treatment with a standardized

extract SHR/5 of rhizome Rhodiola rosea L, (RRE) on fatigue during night duty among a group of 56

young, healthy physicians. The effect was measured as total mental performance calculated as Fatigue

Index. The tests chosen reflect an overall level of mental fatigue, involving complex perceptive and cog-

nitive cerebral functions, such as associative thinking, short-term memory, calculation and ability of con-

centration, and speed of audio-visual perception. These parameters were tested before and after night

duty during three periods of two weeks each: a) a test period of one RRE/placebo tablet daily, b) a wash-

out period and c) a third period of one placebo/RRE tablet daily, in a double-blind cross-over trial. The

perceptive and cognitive cerebral functions mentioned above were investigated using 5 different tests. A

statistically significant improvement in these tests was observed in the treatment group (RRE) during the

first two weeks period. No side-effects were reported for either treatment noted. These results suggest

that RRE can reduce general fatigue under certain stressful conditions.

Key words: Rhodiola rosea L., fatigue, anti-fatigue effect, non-pathological stress, working conditions,

adaptogen, standardized extract SHR/5.

Phytomedicine, Vol. 7(5), pp. 365–371

http://www.urbanfischer.de/journals/phytomed

0944-7113/00/07/05–365 $ 15.00/0

the name of Rodia riza. In England and on the conti-

nent, the drug became known as lignum rhodium in

apothecary shops. It was Linnaeus who gave the plant

its botanical name Rhodiola and its species name,

rosea. The name alludes to the rose-like odor of the

rootstock when freshly cut. In France Rhodiola was

used as „brain tonic“ in the early 19

century (Virey,

1811) and in the alpine region of Germany against

headache (Strigl, 1928).

In Russia, Rhodiola rosea has been used traditionally

and pharmacologically for a long period of time

(Saratikov, 1966). Rhodiola rosea L. (RRE) prepara-

tions have also been used extensively in traditional Ti-

betan medicine since 300 A.D. for treating lung dis-

eases, particularly lung-heat disorders (Tsarong, 1986;

Li, 1995). Thus, among the 175 most important Ti-

betan drugs in the Handbook of Traditional Tibetan

Drugs, Rhodiola is mentioned in ten formulations, of

which nine are indicated for lung disorders (Tsarong,

1986).

It is, however, primarily in Russia and former USSR

that preparations based on Rhodiola rosea rhizome

and the glycoside salidroside (synonym: rhodioloside,

rhodosine) have gained an established position and use

within the official medicine (Muravijeva, 1978,

Mashkovskij, 1977, Turova and Sapozhnikova, 1984).

The use in medicine in the former USSR/Russia, goes

back to a number of pharmacological and clinical in-

vestigations in the early 1960, which demonstrated pri-

marily stimulant and anti-stress actions (Müller-Dietz,

1970; Saratikov, 1974). As a result of these studies,

preparations based on Rhodiola rosea became incorpo-

rated into the officinal medicine by 1969 and are de-

scribed in the last official USSR/Russian Pharma-

copoeia and in the current Russian Pharmacopoeia

(National Pharmacopoeia of the USSR, 11th Edition,

1987; National Pharmacopoeia Committee, 1996).

The stimulant and anti-stress actions of Rhodiola

rosea and its active component salidroside (synonym:

rhodioloside) have been studied extensively in the

USSR/Russia (Aksyonova, 1966, Saratikov, 1974,

Sokolov, et al., 1985). A bibliography of published sci-

entific reports on Rhodiola rosea (and salidroside)

from 1961 to 1987 contains 321 references, of which

119 are pharmacological and clinical studies (Sara-

tikov, 1988).

Pharmacologically, Rhodiola rosea and its main ac-

tive component, salidroside has pronounced and well-

documented stimulant and adaptogenic action (Wagner

et al., 1994; Brekhman and Dardymov, 1969; Sara-

tikov et al., 1968; Nörr, 1993; Petkov et al., 1986). The

stimulant effect is a part of the adaptogenic action

(Saratikov et al., 1965: Zotova, 1966: Saratikov, 1974:

Saratikov et al., 1978: Marina and Mikhaleva, 1987).

Adaptogenic action is a pharmacological effect seen in

clinical studies as an increased resistance to the harmful

effects of various stressors.

It has been shown in pharmacological investigations

that Rhodiola rosea extracts (RRE) protect laboratory

animals from the harmful effects of oxygen, cold, radi-

ation and heavy physical exercise (Saratikov et al.,

1968). The stimulant effect of Rhodiola rosea increases

working capacity, tolerance to anoxia, resistance to mi-

crowave irradiation and poisoning by toxins. It de-

creases also fatigue and regulates brain function (Azi-

zov and Seifulla, 1998, Saratikov et al., 1968). Rats

treated with Rhodiola rosea extract (RRE) showed im-

proved learning behavior in a maze model 24 hours af-

ter treatment. Significant improvement of long-term

memory has also been established using memory tests

after 10 days’ treatment (Petkov et al., 1986).

Human studies have shown that salidroside, an ac-

tive principle of Rhodiola, improved mental ability. In

correction tests, the error rates were reduced by ap-

proximately fifty persent (Wagner et al., 1994). For a

more detailed discussion see Brekhman, Dardymov and

Nörr (Brekhman and Dardymov, 1969; Nörr, 1993;

Wagner et al., 1994; Fulder, 1980).

An overview of the clinical studies of the anti-fatigue

effect of Rhodiola rosea preparations shows that a ma-

jority are based on single-dose application with a sig-

nificant effect after 1–2 h. This observation was one of

the main motivations for performing a clinical study

with repeated dose application of a low daily dose. An-

other important consideration was to make the investi-

gation in a nearly realistic work situation.

The aim of this placebo-controlled, double-blind

cross-over study was to evaluate the efficacy of a Rho-

diola rosea extract (RRE) with standardized content of

salidroside. The study was performed as treatment of

non-specific fatigue, resulting from natural physical fa-

tigue and using quantitative analysis of speed of audio-

visual perception and short-term memory as criteria for

fatigue. The study was based on a model reflecting

common work conditions.

Material and Methods

The study was performed in compliance with the re-

vised declaration of Helsinki and approved by the Ethi-

cal Review Committee of the Armenian State Medical

University of Yerevan.

Study design: The clinical investigation was carried

out as a randomized, placebo-controlled, double-blind,

cross-over study with a wash-out period. The study

was intended to investigate the efficacy of a standard-

ized extract SHR/5 from Rhodiola rosea rhizome

(RRE) in non-specific fatigue. The primary objective

was to study the anti-fatigue effect of Rhodiola rosea

Rhodiola rosea in stress induced fatigue366

preparation using repeated low-dose regimen in

healthy volunteers during work-related fatigue. The

study parameter chosen and considered relevant for as-

sessment was the degree of fatigue, based on the evalu-

ation of audial and visual short-term memory and abil-

ity for mental attention. The level of non-specific fa-

tigue after the night duties was evaluated using five

tests focused on the determination of speed of visual

and audial perception, attention capacity and short-

term memory. These tests were as follows:

Test 1: the speed of determination of words associated

by meanings, scored in seconds.

Test 2: the speed of backward spelling of a 6-letter

word, scored in seconds.

Test 3: the speed of subtraction of a given digit se-

quentially as far as possible from a number be-

tween 90 and 99 to 0, scored in seconds.

Test 4: the number of correctly recalled words, irre-

spective of sequence and with no time-limit, ten

of which were presented audially to the subject,

scored in numbers.

Test 5: the speed of rearranging digits into an order of

decreasing magnitude. The digits were ran-

domly distributed in a square, scored in sec-

onds.

For explanation of the rationale for using this test-bat-

tery in the measurement of non-pathological fatigue,

see MacKinnon and Yudofsky (1986).

A fatigue index was calculated based on these para-

meters. As a measure for fatigue, each test was given a

measure, an index, defined as the following ratio:

(score of test before night duty divided by score of test

after night duty) x 100. Five different measurements

were assessed collectively, giving a total fatigue. The to-

tal effect of taking RRE was assessed according to the

total fatigue index, FI, which directly gives the level of

performances after duty on each occasion in percent of

the performance before duty. Each subject was ran-

domly assigned the medication form two directed sets

of jars, containing Clinical A 971106 or Clinical B

971106. The volunteers were, according to the assign-

ment of test medication, divided into two groups, A

and B. During the first two weeks, the group A (26 per-

sons) each received 1 tablet from the Clinical A batch

per day, while group B (30 volunteers) each received 1

tablet from the Clinical B batch per day. During the fol-

lowing two weeks of wash-out period no participants

received any medication. After that, both groups were

again on two weeks of medication with the opposite

clinical batch.

Determination of the level of fatigue after night duty

was conducted on the basis of test results before and af-

ter duty, i.e., with a time difference of 24 hours.

Each volunteer was tested before receiving the prepa-

ration or placebo, at the end of the 2-week period of

taking the preparation, at the end of the two weeks

wash-out period and at the end of the two weeks of

cross over period. For each test occasion, all the scor-

ings for tests 1–5 were tabulated and used as ranking

data for a subsequent statistical analysis of all the tests

taken together, see Table 1.

Selection of patients. The patients were recruited ac-

cording to specified inclusion and exclusion criteria af-

ter having received written and verbal information

about the Department of Neurology, Armenian State

Medical University of Yerevan. The patients were com-

prised of young, healthy physicians on night duty, cho-

sen by Dr. V. Darbinyan and Dr. A. Kteyan during Jan-

uary 1998 – March 1999. All participants were resi-

dents of Armenia and had a similar socio-cultural

background.

Patient inclusion criteria

1. Age between 24–35, of both genders.

2. Compliance with the study specifications.

3. All patients were informed about the study and a

written consent was requested.

Patient exclusion criteria

1. Mental disease or declared psychological or major

emotional problems.

2. Somatic disease or complaint with fatigue as a symp-

tom.

3. Other medication

Study medication. The test medication (verum and

V. Darbinyan 367

Table 1

Test occasion no.

I II III IV

Group A Before receiving RRE After two weeks of After two weeks of After two weeks

receiving RRE wash-out period without of receiving placebo

any perparation

Group B Before receiving After two weeks of After two weeks of After two weeks

placebo receiving placebo wash-out period without of receiving RRE

any preparation

placebo) was manufactured according to Good Manu-

facturing Practice (GMP) by Swedish Herbal Institute

(SHI) in the form of white, sugar-coated tablets, with

the following composition: VERUM TABLETS, Extr.

sicc. Rhodiola rosea SHR/5 170 mg (containing ap-

proximately 4.5 mg salidroside), calcii phosphas diba-

sicus, solani amylum, cellulosum microcristallinum,

magnesii stearas, silica colloidalis anh.; PLACEBO

TABLETS, Lactose 170 mg, calcii phosphas dibasicus,

solani amylum, cellulosum microcristallinum, magnesii

stearas, silica colloidalis anh.; COATING FOR BOTH

VERUM/PLACEBO, Saccharose, calcium carbohy-

drate, magnesium silicate, polyvinylpyrrolidone, titan

dioxide.

Verum and placebo tablets were produced with iden-

tical organoleptic appearance, and were indistinguish-

able from each other. Each package of tablets con-

tained 60 tablets to be taken once daily for 14 days.

The medications were divided into two sets of plastic

jars which were labelled: Clinical A 971106 and Clini-

cal B 971106. An identification number was noted in a

protocol to allow a subsequent identification after the

completion of the study and statistical analysis. The in-

formation on the placebo and the active substance be-

came available to the investigators and volunteers only

after the completion of the study and after the statisti-

cal analysis was performed.

Anthropometric Data

Group A: 26 persons: 14 females, 12 males, age 25.5 ±

3.8.

Rhodiola rosea in stress induced fatigue368

Fig. 1. Mean values of Fatigue indices and total index. (Val-

ue of scoring before duty = 100).

Table 2

Group A Group B

Total fatigue index I – II III – IV I – II III – IV

Student’s T-test 0.003 0.2 0.08 0.5

P-value (n.s) (n.s.) (n.s.)

Table 3. Test scores: Mean values and standard deviations.

PERIOD

I II III IV

Group Test B/A Mean v. Std Mean v. Std Mean v. Std Mean v. Std

A 1 Before 108.98 31.7 85.5 22.0 90.5 23.2 96.2 22.4

A 1 After 135.8 48.5 86.5 26.0 111.9 40.7 110.1 32.4

A 2 Before 8.5 4.1 7.3 2.7 7.9 4.1 7.7 3.7

A 2 After 11.5 5.3 7.7 2.5 10.5 5.9 8.9 4.1

A 3 Before 34.5 12.1 33.2 12.4 35.4 12.9 43.2 22.0

A 3 After 40.8 19.8 28.9 9.3 41.8 18.3 49.1 23.3

A 4 Before 7.7 1.1 7.3 1.2 6.9 1.4 8.2 0.9

A 4 After 6.7 1.7 6.7 1.6 6.2 1.9 8.0 1.1

A 5 Before 65.4 19.4 77.5 27.9 72.3 24.5 68.4 20.7

A 5 After 72.7 20.1 80.0 35.9 83.6 30.5 72.5 28.0

B 1 Before 96.0 21.8 91.3 20.0 89.3 14.3 95.3 14.8

B 1 After 120.1 35.1 91.7 20.7 91.9 14.7 96.3 17.4

B 2 Before 8.8 2.5 8.6 2.9 8.4 3.1 8.3 2.6

B 2 After 11.2 3.6 10.3 3.7 8.8 3.3 8.9 3.4

B 3 Before 40.9 8.5 42.0 9.9 42.7 10.1 43.6 11.8

B 3 After 44.0 9.7 41.6 9.9 41.0 8.5 44.4 10.3

B 4 Before 7.4 1.3 7.9 1.6 8.1 1.4 8.0 1.2

B 4 After 7.1 2.2 7.8 1.8 8.1 1.5 7.1 1.4

B 5 Before 68.1 22.3 105.8 48.6 76.0 27.2 62.3 14.4

B 5 After 72.3 15.9 90.7 33.4 86.4 29.2 70.5 18.5

Group B: 30 persons: 19 females, 11 males, age 27.3 ±

2.9.

Statistical analysis. Statistical analysis of the total fa-

tigue indices was performed according to the Student‘s

T-test, two-tailed. Data management and calculations

were performed using PRISM Statistical Software Ver-

sion 2.01 (1996).

Results and discussion

All the patients completed the study and no adverse ef-

fects or events were observed. As presented in Figure 1

and Table 2, total fatigue index was significantly im-

proved after two weeks of taking the RRE preparation.

In different clinical trials with Rhodiola rosea prod-

ucts, psycho-stimulating, tranquilizing and antidepres-

sive effects have been demonstrated. The preparation is

also used for correction of aesthenic conditions

(Mikhailova, 1983). A few clinical studies are also

worth noting. Studies have been completed with RRE

in psychiatric practice as an adjuvant anti-depressant

(Brichenko et al, 1986) and as an anti-depressant

(Brichenko and Skarokhodova, 1987). The anti-hyp-

notic effect of the active substance was assessed by Ak-

senova (Aksenova et al., 1968). Komar studied the

stimulating effect in 254 young healthy persons,

demonstrating an increased mental work capacity after

intake of a Rhodiola rosea preparation (Komar et al.,

1981). Several other similar studies were made by a

number of investigators (Saratikov, 1974; Krasik et al.,

1970a; Krasik et al., 1970b; Lapaev, 1982; Metsch-

eryakova et al., 1975; Oleinichenko, 1966; Tuzov,

1968; Mikhailova, 1983).

The use of adaptogens against common non-patho-

logical stress under normal conditions of usual work-

ing activity could be of great practical significance. The

challenges in the experimental data in clinical practice

are the methodological difficulties in measuring such a

subjective and complex notion as fatigue. The advan-

tage of the chosen model in a common working situa-

tion causing fatigue were the similarity of the stress sit-

uation for all the participants in an actual and realistic

work situation. Regular night duty work is well known

to be stressful and to play a part in causing various

pathological conditions, such as long term disturbances

of sleep and depressions (Czeisler and Richardson,

1998).

Table 3 presents the mean values of the actual score

for each test and period. As is seen, the absolute values

of the scores vary considerably from test to test.

To be able to directly compare the tests, Table 4, pre-

sents the more relevant relative measure called Fatigue

index as defined above. The fatigue index subtracted

by 100 (FI – 100) gives directly the change in percent of

the performance before and after duty.

The difference between the tests as a measure of fa-

tigue is directly seen from this table. As an example, ap-

pears test 1 to be more sensitively dependent on the

state of fatigue than test 4, as appears directly from the

larger magnitude of a fatigue indices. To have a more

relevant and also more reliable measure of the degree

of fatigue a total fatigue index was calculated, using the

fatigue indices from each test with equal weight. The

result is displayed in Table 2 and in Figure 1. The only

significant change is seen in the verum group between

period I and period II with a change in performance of

approximately 20 % (p < 0.01). Furthermore this study

also shows that for the chosen dosage there was no ef-

ficacy in group B after six weeks of treatment. On the

second test occasion however, the subjects had been on

night duty for a considerably longer time than for the

first occasion. It should therefore be taken into consid-

eration that the low dosage used was well-adapted for

V. Darbinyan 369

Table 4. Mean values of Fatigue indices and total fatigue index. (Value of scoring before duty = 100)

PERIOD

I II III IV

Test Group Mean v. Std Mean v. Std Mean v. Std Mean v. Std

1 A 125.8 38.5 101.4 17.5 124.0 36.7 115.9 28.5

1 B 124.6 21.4 101.1 13.2 103.4 10.0 101.0 9.5

2 A 144.3 56.4 113.3 34.6 136.3 39.9 118.0 32.9

2 B 127.8 30.3 121.6 37.6 107.4 23.1 108.6 32.2

3 A 117.4 32.8 89.9 17.3 118.7 28.2 115.1 24.3

3 B 108.3 15.1 99.8 12.9 97.0 10.2 103.2 13.1

4 A 116.0 17.6 108.0 19.5 111.0 16.0 102.0 15.3

4 B 105.0 21.0 100.0 17.8 101.0 16.5 112.0 15.0

5 A 113.3 21.6 102.5 19.8 116.8 20.7 105.9 17.8

5 B 114.1 35.0 99.1 45.5 126.1 59.2 116.2 32.0

Tot. fat. ind. A 124.5 22.2 104.0 10.5 122.2 16.8 111.9 13.0

Tot. fat. ind. B 117.0 14.2 105.1 12.3 106.8 12.4 109.2 12.6

the situation on the first occasion but not sufficient on

the second occasion. It can, however, be concluded that

Rhodiola rosea SHR/5 extract possesses a clear anti-fa-

tigue effect without any reported adverse reactions or

side-effects, at the dosage used in our study in a situa-

tion of a moderate level of fatigue and stress.

To shed some more light on the asymmetry of the re-

sults between occasion I and II versus III and IV some

further questions could be asked:

A basic assumption in cross-over studies is that each

individual is in a very similar state on occasion I and af-

ter a wash-out period on occasion III. To examine if

this assumption holds, the correlation between the be-

fore-values on occasion I and on occasion III was cal-

culated. The results are presented in Table 5. The most

conspicuous feature is the difference in degree of corre-

lation between tests 1, 2 and 3 versus 4 and 5. While 1,

2 and 3 exhibit a rather good correlation, test 4 and 5

show poor correlation between occasion I and III. This

calls for a closer look at these two groups of tests.

First of all, the mean values of the test scores (before

values) on occasion I and III do not display a learning

effect to which the difference between the two groups

of tests could be attributed. Secondly, there does not

seem to be an inherent difference in the kind of test be-

tween the two groups. However, test 4 differs from all

the others in the sense that there is no time limit. On

the other hand test 5, showing the lowest correlation

does not exhibit any easily distinguishing characteris-

tic. To sum up: Judging from the mean values of the be-

fore duty scores, the important assumption of basic

similarity between occasion I and occasion III could

not be said to hold to a satisfying degree. Test 4 and 5

are responsible for the largest variation but no immedi-

ate reason for this could be seen.

The size of the study does not allow for further gen-

eral conclusions but surely suggests that in a future

study of similar design, both higher doses and a larger

number of subjects should be used. The present study

also indicates that another choice of the test battery,

could be more sensitive in assessing a general state of

fatigue.

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Rhodiola rosea in stress induced fatigue370

Table 5. Correlation between before-duty scores on occasion

I and III.

Test Group Pearson’s test P-value

1 A 0.48 0.013

1 B 0.503 0.005

1 A + B 0.481 0.0002

2 A 0.493 0.01

2 B 0.486 0.006

2 A + B 0.47 0.0003

3 A 0.588 0.002

3 B 0.685 0.0001

3 A + B 0.66 0.0001

4 A 0.125 0.54

4 B 0.54 0.003

4 A + B 0.266 0.049

5 A 0.362 0.075

5 B 0.072 0.712

5 A + B 0.193 0.16

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Address

Vahagn Darbinyan, Department of Neurology,

Institute of Surgery, Armenian Medical University,

9 Asratyan St., Kanaker Yerevan, Armenia 375000.

Tel. +0 (3742) 284 401 E-mail: [email protected]

V. Darbinyan 371

372

Loew, D. Rietbrock, N. (Eds); Phytopharmaka I-IV.

Forschung und Klinische Anwendung. Steinkopf

Verlag, Darmstadt.

Volume I: 198 pp, 1995. ISBN 3-7985-1053-9;

Volume II: 210 pp, 1996. ISBN 3-7985-1066-0;

Volume III: 215 pp, 1997. ISBN 3-7985-1094-6;

Volume IV: 186 pp, 1998. ISBN 3-7985-1131-4.

Loew, D. Blume, H. and Dingermann Th. (Eds.); Phy-

topharmaka V. Forschung und Klinische Anwen-

dung, 226 pp, Steinkopf-Verlag, Darmstadt, 1999.

ISBN 3-7985-1203-5.

Price: All volumes DM 68; öS 496,40; sFr 60.

The five volumes published up to now contain the lec-

tures presented at the annual phytomedicine symposia

of the German Society for Clinical Pharmacology. The

aim of these symposia is to review the most current

therapeutic status of rational herbal medicinal prod-

ucts (HMP). HMPs are subjected to the same scientific

requirements concerning efficacy, safety and quality as

those applied to synthetic drugs.

Today therapy with HMP is a definite component of

traditional medicine, which is subject to the rules of

controlled clinical studies according to the guidelines of

good clinical practice. It clearly needs to be differenti-

ated from the numerous methods of so called alterna-

tive medicine.

For a number of years HMPs have been placed in an

area of conflict between a tradition of several centuries

and a Evidence Based Medicine (EBM). EBM perceives

itself as a quality-orientated but not as a view-orientat-

ed implementation of scientific knowledge, and derives

concrete therapeutic recommendations from a five-lev-

el hierarchy of evidence. Though EBM seems to present

itself as a rational and pragmatic procedure for deci-

sion-making, from an optimal pharmaco-economically

orientated medical support, criticism arises from the

fact that therapeutic experience and the requirements

of daily practice are not considered in EBM.

The subjects treated in the symposia proceedings

concern the clinical-pharmacological basis of the effi-

cacy of HMP (e.g., metabolism of multi-drug-mixtures,

analysis and bioequivalence-investigations of HMP),

toxicological and safety aspects (mutagenicity and car-

cinogenicity studies), the pharmaceutical characteriza-

tion of HMP (e.g., selection of drugs and drug quality,

industrial quality control, biopharmaceutical quality

and problems of equivalence of HMP), Evidence Based

Medicine and clinical application (e.g., anxiety states,

diseases of the respiratory tract, dementia, depressive

states, gynecological diseases, cardiac insufficiency, im-

mune deficiency, cancer, benign prostatic hyperplasia,

venous diseases, application of HMP in pediatrics, and

use of HMP in self medication).

The scope of herbal drugs which have been subject to

pharmacological and clinical studies includes prepara-

tions from Aesculus hippocastanum, Anthranoid-

drugs, Cimicifuga racemosa, Crataegus spp, Cucurbita

pepo, Ginkgo biloba, Cynara scolymus, Echinacea spp,

Harpagophytum procumbens, Hypericum perforatum,

Mentha piperita, Piper methysticum, Plantago lanceo-

lata, Sabal serrulata, Senna spp, Silybum marianum,

Urtica spp., Viscum album, Vitex agnus castus as well

as ß-Aescin, volatile oils, silibinin and silymarin.

The results of pharmacological and clinical trials,

presented in the first five volumes of Phytopharmaka,

make clear that rational HMP is taking an essential

place in medicinal therapy and can meet the require-

ments of the evidence-based hierarchy from the stand-

point of quality, clinical trials and meta analyses. The

books represent an essential basis for all scientists con-

cerned with herbal medicinal products in research, clin-

ic and practice.

H. D. Reuter

Gesellschaft für Phytotherapie e.V.

Siebengebirgsallee 24

50939 Köln

Book Review