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A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Standardised Extract SHR-5 of the Roots of Rhodiola rosea in the Treatment of Subjects with Stress-Related Fatigue


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The aim of the study was to assess the efficacy of the standardised extract SHR-5 of roots of Rhodiola rosea L. in the treatment of individuals suffering from stress-related fatigue. The phase III clinical trial took the form of a randomised, double-blind, placebo-controlled study with parallel groups. Participants, males and females aged between 20 and 55 years, were selected according to the Swedish National Board of Health and Welfare diagnostic criteria for fatigue syndrome. A total of 60 individuals were randomised into two groups, one (n = 30) of which received four tablets daily of SHR-5 extract (576 mg extract/day), while a second (n = 30) received four placebo tablets daily. The effects of the extract with respect to quality of life (SF-36 questionnaire), symptoms of fatigue (Pines’ burnout scale), depression (Montgomery-Asberg depression rating scale – MADRS), attention (Conners’ computerised continuous performance test II – CCPT II), and saliva cortisol response to awakening were assessed on day 1 and after 28 days of medication. Data were analysed by between-within analyses of variance. No serious side effects that could be attributed to the extract were reported. Significant post-treatment improvements were observed for both groups (placebo effect) in Pines’ burnout scale, mental health (SF-36), and MADRS and in several CCPT II indices of attention, namely, omissions, commissions, and Hit RT SE. When the two groups were compared, however, significant effects of the SHR-5 extract in comparison with the placebo were observed in Pines’ burnout scale and the CCPT II indices omissions, Hit RT SE, and variability. Pre- versus post-treatment cortisol responses to awakening stress were significantly different in the treatment group compared with the control group. It is concluded that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome. Abbreviations CCCPT II:Conners’ computerised continuous performance test II HPA:hypothalamic-pituitary-adrenal ICD:International Classification of Diseases MADRS:Montgomery-Asberg depression rating scale Qol:quality of life
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A Randomised, Double-Blind, Placebo-Controlled,
Parallel-Group Study of the Standardised Extract SHR-5
of the Roots of Rhodiola rosea in the Treatment of
Subjects with Stress-Related Fatigue
Author Erik M. G. Olsson1, 2, Bo von Schéele2, 3, Alexander G. Panossian4
Affiliation 1Department of Psychology, Uppsala University, Uppsala, Sweden
2PBM Stress Medicine AB, Stockholm, Sweden
3School of Innovation, Design and Engineering, Mälardalen University, Västerås, Sweden
4Swedish Herbal Institute Research and Development, Åskloster, Sweden
Key words
"Rhodiola rosea L.
"clinical trial
received July 8, 2008
revised September 23, 2008
accepted September 29, 2008
DOI 10.1055/s-0028-1088346
Planta Med 2009; 75: 105–112
© Georg Thieme Verlag KG
Stuttgart · New York
Published online November 18,
ISSN 0032-0943
Erik M. G. Olsson
Department of Psychology
Uppsala University
Box 1225
751 42 Uppsala
Tel.: +46 70 359 27 59
Original Paper 105
Stress-related fatigue is a widespread problem in
the Western world. Psychological stress, for ex-
ample, can often induce long-term exhaustion
and diminished interest, producing a condition
known as burnout syndrome. This disorder is
characterised by a state of continuous physical
weakness, a mood of depression, lack of drive,
poor concentration, difficulty in sleeping, tired-
ness, and listlessness [1]. In cases where efficient
and affordable treatment for the syndrome is un-
available, plants that have been traditionally
used as stimulants may offer potential applica-
In this context, Rhodiola rosea L., also known as
“roseroot” or “golden root,” has a long history as
a valuable medicinal plant and has appeared in
the Materia Medica of a number of European
countries [2], [3]. In the early 19th century, for ex-
ample, preparations of R. rosea were already be-
ing used in France as a “brain tonic” [4]. More-
The aim of the study was to assess the efficacy of
the standardised extract SHR-5 of roots of
Rhodiola rosea L. in the treatment of individuals
suffering from stress-related fatigue. The phase
III clinical trial took the form of a randomised,
double-blind, placebo-controlled study with par-
allel groups. Participants, males and females
aged between 20 and 55 years, were selected ac-
cording to the Swedish National Board of Health
and Welfare diagnostic criteria for fatigue syn-
drome. A total of 60 individuals were randomised
into two groups, one (n= 30) of which received
four tablets daily of SHR-5 extract (576 mg ex-
tract/day), while a second (n= 30) received four
placebo tablets daily. The effects of the extract
with respect to quality of life (SF-36 question-
naire), symptoms of fatigue (Pines' burnout
scale), depression (Montgomery-Asberg depres-
sion rating scale – MADRS), attention (Conners'
computerised continuous performance test II –
CCPT II), and saliva cortisol response to awaken-
ing were assessed on day 1 and after 28 days of
medication. Data were analysed by between-
within analyses of variance. No serious side ef-
fects that could be attributed to the extract were
reported. Significant post-treatment improve-
ments were observed for both groups (placebo
effect) in Pines' burnout scale, mental health
(SF-36), and MADRS and in several CCPT II indi-
ces of attention, namely, omissions, commis-
sions, and Hit RT SE. When the two groups were
compared, however, significant effects of the
SHR-5 extract in comparison with the placebo
were observed in Pines' burnout scale and the
CCPT II indices omissions, Hit RT SE, and variabil-
ity. Pre- versus post-treatment cortisol responses
to awakening stress were significantly different
in the treatment group compared with the con-
trol group. It is concluded that repeated adminis-
tration of R. rosea extract SHR-5 exerts an anti-fa-
tigue effect that increases mental performance,
particularly the ability to concentrate, and de-
creases cortisol response to awakening stress in
burnout patients with fatigue syndrome.
CCCPT II: Conners' computerised continuous
performance test II
HPA: hypothalamic-pituitary-adrenal
ICD: International Classification of Diseases
MADRS: Montgomery-Asberg depression rating
Qol: quality of life
Olsson EMG et al. A Randomised, Double-Blind … Planta Med 2009; 75: 105 –112
This document was prepared for the exclusive use of Ingemar Joelsson. Unauthorized distribution is strictly prohibited.
over, roots and rhizomes of R. rosea have been employed in tradi-
tional folk medicine to increase physical endurance, work per-
formance, longevity, and resistance to high-altitude sickness
and to treat fatigue, anaemia, cancer, impotence, and nervous
system disorders [6]. In more recent times, extensive studies of
the stimulant and stress-protective (or adaptogenic) properties
of extracts of R. rosea were conducted in the USSR [5], [6], [7],
[8], [9], [10], and preparations of the drug now form part of the
official medicine of Russia and other members of the former
USSR [11], [12], [13]. In Sweden, R. rosea was recognised as an
adaptogen and a botanical medicine in 1985, and it is classified
in the Swedish Drug and Therapy handbook (Lakemedelsboken
1997/98) as one of the most commonly used psychostimulants
in the group of officially registered herbal medicinal products
[14]. The plant has also been described as possessing stimulant
and general strengthening properties. The registered prepara-
tions Rosenrot and Arctic Root, which are based on the propriet-
ary extract SHR-5 of R. rosea, are extensively used in Sweden and
other Scandinavian countries to increase attention and endur-
ance in cases of decreased performance such as fatigue and sen-
sation of weakness.
The stimulant effect of R. rosea regulates brain function, decrea-
ses fatigue and stress- and corticotropin-releasing factor-in-
duced anorexia in rats [15], and increases working capacity, tol-
erance to anoxia, and resistance to microwave irradiation and
poisoning by toxins [5], [7]. Moreover, R. rosea has been reported
to improve the learning behaviour of rats and to induce signifi-
cant improvements in long-term memory [16]. These findings
were recently confirmed in experiments on rodents in which an
extract of R. rosea induced significant adaptogenic, stimulating,
and antidepressant- and anxiolitic-like effects [17], [18]. In addi-
tion, R. rosea may enhance emotional tone by influencing bio-
genic monoamine neurotransmission in regions of the brain in-
volved in mood and stress regulation, such as the amygdala, hip-
pocampus, hypothalamus, and midbrain. The direct stimulation
of nicotinic, cholinergic, noradrenergic, 5-hydroxytryptaminic,
and dopamine receptors in selected brain regions may contrib-
ute to the adaptogenic effects of R. rosea [7], [16]. In studies in-
volving human subjects, R. rosea and an active principle rhodio-
loside (salidroside) have been shown to improve mental per-
formance and the ability to concentrate [6], [10], [19], [20], [21].
Additionally, several investigators have suggested that R. rosea
may help individuals with mental and physical fatigue resulting
from stress conditions [19], [20], [21].
The objective of the present study was to determine whether the
daily intake of R. rosea extract SHR-5 over a 28-day period would
produce any positive effects on attention, quality of life, and
symptoms of fatigue and depression in subjects with stress-rela-
ted fatigue. Salivary cortisol levels were used to assess the anti-
stress and anti-fatigue effect of the medication, as it has been
shown that patients with chronic fatigue syndrome present a
higher cortisol response to the mild stressor of morning awaken-
ing [22].
Materials and Methods
Details of the project were submitted to and approved by the
Swedish Medical Product Agency (Läkemedelsverket, Uppsala,
Sweden) and the ethical committee of the University of Uppsala.
The study was conducted in compliance with the revised Decla-
ration of Helsinki [23].
Study population
The study population included subjects of both sexes within the
age range 20 – 55 years who were experiencing difficulties
equivalent to the criteria of “fatigue syndrome” according to
subdivision F43.8A of the International Classification of Diseases
(ICD) code F43.8 “Other reactions to severe stress” [24] as sug-
gested by the Swedish National Board of Health and Welfare
[1]. In order to fulfil these criteria, subjects must exhibit daily
symptoms of fatigue, enduring for at least 2 weeks, related to a
specific stressor that has been present for at least 6 months, and
their daily functioning must be significantly negatively affected.
Such symptoms must not be related to substance abuse or psy-
chiatric or other primary disorders. The diagnosis of “fatigue
syndrome” differs from that of “chronic fatigue syndrome” with
regard to a number of points. For example, the former requires
the identification of specific stressors whilst the latter focuses
on the immune system and symptoms of pain in the lymph
nodes, joints, and muscles.
An advertisement describing the purpose of the study and con-
taining a brief outline of the inclusion and exclusion criteria was
published, and potential participants responded with subjective
ratings and answers to questions covering the selection criteria.
All written material, including the ratings of the Pines' burnout
scale [25] and a somatic symptom evaluation, together with ad-
ditional questions concerning time and causes, was taken into
account by the licensed physician who made the diagnosis. Preg-
nant or lactating subjects; individuals presenting comorbidity of
other serious diagnoses (e. g., heart disease, stroke, insulin-de-
pendent diabetes, or cancer); those with stomach ulcers, food
or medication allergies, asthma, psychosis, or depressive epi-
sodes; and those addicted to drugs or who consumed high levels
of alcohol or nicotine were excluded.
Volunteers were provided with complete information about the
project and an informed consent form to sign before commenc-
ing the study. Subjects were recruited and tested in stress reha-
bilitation clinics belonging to the same organisation and located
in three towns in Sweden(i. e., Stockholm and two smaller towns
to the north of Stockholm). The same test leader conducted the
tests in all three locations using the same equipment in similar
rooms normally used for psychotherapy. Subjects were comfort-
ably seated in an armchair during the test period.
Study medications
All test materials were manufactured according to Good Manu-
facturing Practice by the Swedish Herbal Institute (Gothenburg,
Sweden) and presented in the form of sugar-coated white tab-
lets. The verum tablets (390 mg; batch number 8 451309) each
contained 144 mg of proprietary Rhodiola extract SHR-5 (drug
extract ratio 4:1; extraction solvent 70% ethanol). The amounts
of the active ingredients rhodioloside (4.0 mg/tablet), rosavin,
tyrosol, and triandrin were determined by analytical RP-HPLC
using an acetonitrile-water gradient system as mobile phase.
Peaks were detected by UV-PAD and analytes were quantified
at 221 nm (rhodioloside and tyrosol), 252 nm (rosavin), and
262 nm (triandrin). Analytical methods were validated for selec-
tivity, peak purity, precision (RSD < 5 %), and accuracy in the
range 50150% of the target amounts of analytes in the tablets
in accordance with ICH guidelines [26] using Effi Validation 3
software (version 1.03) for testing and calibration laboratories
subject to EN ISO/IEC 17 025 : 2001 [27]. Placebo tablets
(390 mg) were prepared using inactive ingredients that were
identical to verum tablets together with 191 mg of dicalcium
Original Paper106
Olsson EMG et al. A Randomised, Double-Blind … Planta Med 2009; 75: 105 –112
This document was prepared for the exclusive use of Ingemar Joelsson. Unauthorized distribution is strictly prohibited.
phosphate. Medications were packed in plastic jars containing
120 tablets of either verum or placebo tablets (all tablets being
identical in appearance and organoleptic properties), and these
were subsequently randomised at the factory and marked with
random numbers in a random order. Each medication pack bore
a code number (encoded in a drug list that was kept by the spon-
sor and not opened until after all data had been collected) on a
label that was designed in accordance with guidelines for Good
Clinical Practice, together with a small supplementary label with
information concerning the dosage regime.
On day 1 of the study the participants met with the test leader,
completed the subjective pre-treatment evaluations, and under-
went Conners' computerised continuous performance test II
(CPT II) [28]. Participants were supplied with an individual med-
ication pack (picked at random by the test leader, who had no
knowledge of whether it contained placebo or verum tablets), a
supply of Salivette cotton rolls (Sarstedt) for the collection of sal-
iva, and a set of instructions. Individuals were required to collect
samples of saliva (see below) at specific times after awakening
each day (starting from day 2) and were instructed to take four
of the tablets provided daily, specifically, two in the morning and
two at lunchtime, starting from day 2 for a period of 28 days. Af-
ter this time, the subjects met with the test leader, returned the
unused tablets together with the original container, completed
the post-treatment subjective evaluations, and underwent a
CPT II. Compliance with the medication regime was determined
from the number of unused tablets returned.
Test methods
The primary endpoint was a reduction in fatigue symptoms as-
sessed according to the Pines' burnout scale [25], a question-
naire with good psychometric properties. The Swedish transla-
tion has been used often and is well tested [29]. The reduction
in depressive symptoms was estimated using the Montgomery-
Asberg depression rating scale (MADRS) [30], a subjective meas-
ure of depressive symptoms that are sensitive to change, for
which good psychometric properties have been reported. Quali-
ty of life (QoL) was measured using the SF-36 questionnaire,
which represents the most commonly used instrument for esti-
mating QoL and presents good psychometric properties [31],
[32], [33]. The more general indices of physical health and men-
tal health were employed in the present study.
Cortisol response to awakening was determined from saliva
samples according to the principle employed in various studies
of burnout syndrome and chronic fatigue syndrome [22], [34],
[35]. Saliva sampling was chosen because it is a simple, non-in-
vasive, non-stressful method that participants can carry out in
their own homes, and the samples accurately reflect the levels
of the free fraction of cortisol in plasma. Saliva samples were col-
lected using Salivette cotton rolls, which participants were in-
structed to place in the mouth for at least 1 min or until the cot-
ton roll was soaking wet. Participants were asked to take the first
sample directly upon awakening while still in bed and again at
15, 30, and 60 min after awakening. The samples were main-
tained frozen (–18°C) until analysed. Levels of cortisol in saliva
were measured using Spectria [125I]-Coated Tube Radioimmuno-
assay kits (Orion Diagnostica). The within-assay coefficients of
variation have been reported to range from 0.5 to 6, whilst those
between assays never exceeded 10% [22]. The area under the re-
sponse curve was used as an index of response. The response
curve is typically higher in fatigued subjects and indicates hypo-
thalamic-pituitary-adrenal (HPA) axis functioning.
Attention was assessed using the CCPT II [28]. This method has
been used previously to evaluate treatments, and there is evi-
dence that it is sensitive to changes [36]. The five most impor-
tant indices retrieved from the test were omissions (not re-
sponding when a response is required), commissions (respond-
ing when a response is not required), response reaction time
(Hit RT), the standard error of the reaction time (Hit RT SE), and
variability of the response, all of which measure different as-
pects of attention. Attention and memory deficiency are com-
mon in a fatigued population, whilst attention span and infor-
mation-processing speed are typically lowered in patients pre-
senting chronic fatigue, although the causes of this are unclear
Statistical analyses
The results of the subjective measures and the performance tests
were analysed using two-way, between-within analyses of var-
iance (ANOVA), in which an interaction effect indicates a differ-
ent response over time between the two groups and would,
therefore, signal a treatment effect. A significant main effect on
a group in the absence of any significant interaction effects
would be interpreted as a randomisation failure. A significant
main effect of time in the absence of a significant interaction ef-
fect would indicate a change over time in both groups and could
thus be interpreted as a placebo effect or a general effect of tak-
ing the tests and ratings twice and/or a regression towards the
The levels of cortisol in saliva were evaluated by three-way
ANOVA in which main and interaction effects of group (treat-
ment× control), time (pre-treatment× post-treatment), and re-
sponse (0, 15, 30, and 60 min after awakening) were analysed.
Any interaction effect with time and group would suggest a
treatment effect. Cortisol values were logarithmised prior to
analysis owing to the excessive skewness of the distribution.
All statistical analyses were carried out using STATISTICA 8.0
software [38] installed on a PC. The alpha level was P< 0.05,
and the level for tendency was P< 0.10. No corrections were
made for mass significance.
A total of 60 individuals matching the inclusion criteria, but not
the exclusion criteria, were recruited for the study. Using a
straightforward double-blind randomisation procedure without
stratifications or blocks, 30 individuals received medication with
R. rosea and 30 received the placebo. As shown in
"Table 1, the
treatment and placebo groups included exactly the same propor-
tion of men (10 %) and women (90 %), while the differences be-
tween the two groups in terms of mean age and number of sub-
jects taking psychotropic medication were very small and not
statistically significant. Moreover, the percentage of the study
period that subjects spent on sick leave was identical in each
group. In contrast, there was a noticeable (but not significant)
difference in the level of compliance with the medication regime
between the two groups, in that the number of tablets missed by
those receiving R. rosea was greater than that of the placebo
group. The distribution (SD) of compliance differed to some ex-
tent between the two groups, with the number of tablets re-
maining in the container ranging from 0 to 75 in the treatment
Original Paper 107
Olsson EMG et al. A Randomised, Double-Blind … Planta Med 2009; 75: 105 –112
This document was prepared for the exclusive use of Ingemar Joelsson. Unauthorized distribution is strictly prohibited.
group (four subjects omitted to take 45 tablets or more), and
from 2 to 29 in the placebo group. Three tablet containers (one
in the treatment group and two in the placebo group) were not
returned at the end of the study period (
"Table 1). No adverse
events occurred during the period of study, and no major side ef-
fects that could be clearly linked to the study medication were
reported by any of the subjects.
Missing data
One subject recruited to the treatment group did not show up af-
ter the pre-treatment measurements, despite reminders by tele-
phone, e-mail, and letter,and was excluded from all further anal-
ysis. The results of the post-study CPT II test were lost for one
subject in the treatment group owing to an unidentified com-
puter problem. Three subjects in the placebo group presented
results in the post-study CPT II test that indicated an invalid pro-
tocol [28]. According to the manual associated with this test, this
outcome could have resulted from a misunderstanding of the in-
structions, a lack of motivation, distraction during the test, an
(unidentified) technical problem, or serious neurological impair-
ment (although this cause was considered unlikely, as it had not
been indicated elsewhere). The results of the post-study CPT II
test gained by these subjects were not used in the analysis of
test performance.
The collection of saliva for the determination of cortisol levels
was problematic for a number of subjects. Some of the test Saliv-
ettes were “dry” on arrival at the laboratory, probably because
subjects did not keep the cotton rolls in their mouths for a suffi-
cient length of time. Others subjects failed to send samples to
the laboratory as instructed. For these reasons, at least one of
the saliva samples was lost for eight subjects in the treatment
group (8/29) and for five in the placebo group (5/30).
Subjective measures of quality of life, symptoms, and
The subjective data obtained from Pines' burnout scale, the gen-
eral indices physical health and mental health of the QoL SF-36
questionnaire, and the MADRS are presented in
"Table 2.A
statistically significant interaction effect between time and
group was detected in the Pines' burnout scale, indicating that
the treatment group had benefited more than the placebo
group. A tendency (P< 0.1) towards a positive effect of treatment
on physical health was also noted. The significant main effects of
time with respect to Pines' burnout scale, mental health, and
MADRS all showed a positive change over time for both groups,
and this can be interpreted as a general placebo effect or a gen-
eral effect of taking the tests and ratings twice and/or a regres-
sion towards the mean. No main effects were found for group
differences (see
"Table 2).
Effects on attention
Significant interaction effects between time and group were de-
tected with respect to omissions, Hit RT SE, and variability indi-
ces derived from the CPT II, all of which indicated a more posi-
tive change in the treatment group than in the placebo group
"Table 3). A tendency (P< 0.1) towards a positive effect of
treatment on Hit RT was also noted. The significant main effects
of time with respect to omissions, commissions, and Hit RT SE
showed a positive change over time for both groups. No main ef-
fects were found for group differences (see
"Table 3).
Levels of cortisol in the saliva
A three-way ANOVA with group (treatment ×control), time (pre-
treatment×post-treatment), and response (0,15, 30, and 60min
after awakening) as independent variables was performed. The
analysis showed, as expected, a significant main effect of re-
Table 2 Results (mean and SD) of the subjective measurements of quality of life, symptoms, and functioning for the treatment and placebo groups, showing
interaction effects between time (2 levels) and group (2 levels)
Treatmentgroup (n = 29) Placebo group (n = 30) Ftime*group
Pre-treatment Post-treatment Pre-treatment Post-treatment
Mean SD Mean SD Mean SD Mean SD
Pines' burnout scale 4.27 0.54 4.01 0.58 4.33 0.56 4.26 0.51 4.13* 0.047
Physical health (SF-36) 40.94 12.56 43.63 11.74 45.58 10.65 44.83 11.44 3.80 0.056
Mental health (SF-36) 27.30 11.24 32.79 12.28 23.10 9.43 30.99 9.14 0.97* 0.33
MADRS 19.17 7.66 15.66 7.93 21.72 6.58 17.40 8.28 0.22* 0.64
* Significant main effect of t ime (P<0.05).
Table 1 Characteristics of the treatment and placebo groups at the start of the study and level of compliance with the medication regime during the study
Trea tment group
(n = 30)
Placebo group
(n = 30)
Number of women 27 (90 %) 27 (90 %) 0.00 1.00
Agea41.0 (7.9) 42.1 (8.5) 0.52 0.60
On sick leave (average percenta ge) 33.3 (42.7) 33.3 (41.7) 0.00 1.00
Number on psychotropic drugs 7 (23 %) 9 (30%) 0.34 0.56
Compliance (number of tabletsleft )a18.8 (19.8)b11.7 (6.0)b1.82 0.07
aValues shown are means(standard deviations).
bFor the treatment gro up n=29; for the placebo gro up n= 28.
Original Paper108
Olsson EMG et al. A Randomised, Double-Blind … Planta Med 2009; 75: 105 –112
This document was prepared for the exclusive use of Ingemar Joelsson. Unauthorized distribution is strictly prohibited.
sponse, representing the presence of an overall saliva cortisol re-
sponse, a finding that has been well documented in earlier stud-
ies [22], [34]. Even without taking group membership into ac-
count, an interaction effect could be detected in the study popu-
lation between time and response, indicating that the pre-treat-
ment response pattern differed from that observed post-treat-
ment. When group membership was considered, a significant in-
teraction effect between group, time, and response was noted,
signifying differential pre-treatment and post-treatment re-
sponse patterns between the two groups (see
"Table 4). As can
be observed in
"Fig. 1, the response curve displayed by the
treatment group was lower and flatter after treatment than be-
fore treatment in comparison with that of the placebo group.
This means that the cortisol response to awakening stress had
changed significantly following 28 days of treatment with R.
rosea extract in comparison with the control group.
Various studies have demonstrated the beneficial effect of R.
rosea extract on the mental performance of human volunteers
[6], [8], [19], [20], [21], [39]. The effect of a single dose of
Rhodiola on the mental performance of 85 healthy subjects was
studied by Zotova [39] using Anfimov's letter correction table,
which permits the compilation of numerically comparable data
characterising the quality and quantity of work performed. The
results indicated that, in comparison with placebo, administra-
tion of the phytoadaptogen did not affect the number of correc-
tions performed but reduced considerably the number of errors
made. In a complementary study, the effect of a single 2.5-mg
dose of rhodioloside (an active principle of R. rosea) was shown
to be highly comparable with that of the plant extract [6]. In a
further investigation involving both Anfimov's tables and the
ability to memorise paragraphs of text, 82 volunteers were trea-
ted with either R. rosea extract or tyrosol (a hydrolysis product of
rhodioloside) [40]. It was demonstrated that, whilst neither
medication affected the time taken to perform the correction
task, both improved the quality of performance, reducing the
percentage of errors by 29 – 35 % compared with the control and
increasing the volume of the short-term memory as represented
by the number of text paragraphs recalled. Using a similar proto-
col, Komar and co-workers [8] treated 254 healthy subjects with
an extract of an adaptogen (either R. rosea or Eleutherococcus
senticosus) or with a tincture of Mentha as the control. Rhodiola
was more active than Eleutherococcus in terms of its ability to
enhance working capacity (i. e., increase the number of corrected
symbols), efficiency/performance (i. e., decrease the number of
errors) and speed of information processing and perception.
More recently, a randomised, double-blind, placebo-controlled
parallel-group clinical study with an extra non-treatment con-
trol group was performed in order to measure the effect of a sin-
gle doses of a standardised extract of R. rosea (SHR-5) on the ca-
pacity for mental work (psychometric tests) against a back-
ground of fatigue and stress [21]. The study, which involved 161
healthy cadets, demonstrated that a dose of either 2 or 3 capsu-
les of the extract (equivalent to 370 or 555 mg of SHR-5 and cor-
responding to 288 or 432 mg of SHR-5 extract) produced statisti-
cally significant anti-fatigue effects in comparison with the pla-
The anti-fatigue effects of repeated doses of SHR-5 extract have
been demonstrated in two double-blind, placebo-controlled
clinical trials. Thus, Spasov et al. [20] studied the effect of admin-
istration of SHR-5 (one tablet containing 50 mg of SHR-5 taken
twice a day) over a 20-day period on healthy students during
stressful examinations; they reported that measures of physical
fitness, mental fatigue, and psychomotor performance all im-
proved in comparison with the placebo. Moreover, when healthy
Table 3 Results (mean and SD) of CCPT II for the treatment and placebo groups, showing interaction effects between time (2 levels) and group (2 levels).
Treatmentgroup (n = 28) Placebo group (n = 27) Ftime*group
Pre-treatment Post-treatment Pre-treatment Post-treatment
Mean SD Mean SD Mean SD Mean SD
Omissions 6.29 4.68 2.41 3.24 4.70 4.12 4.29 3.57 5.62* 0.02
Commissions 16.48 7.47 11.19 6.15 16.93 7.37 12.86 7.64 0.89* 0.35
Hit RT 357.00 46.44 354.61 42.45 354.43 50.03 365.54 49.95 3.67 0.06
Hit RT SE 5.83 1.91 4.87 1.30 5.22 1.05 5.44 1.71 12.33* 0.001
Variability 9.36 5.58 6.24 3.16 7.14 2.54 7.97 4.57 8.53 0.005
* Significant main effect of t ime (P<0.05).
of squares
of freedom
F-value P Tabl e 4 Main and interaction
effects indicated by three-way
Group 5.93 1 5.93 3.332 0.08
Time 0.75 1 0.75 1.075 0.30
Time × group 0.70 1 0.70 1.006 0.32
Response 8.19 3 2.73 18.537 0.000
Response × group 0.23 3 0.08 0.525 0.67
Time × response 1.07 3 0.36 4.581 0.004
Time × response × group 0.67 3 0.22 2.887 0.038
Note: The independent variables were group (treatment× placebo), time (pre-treatment ×post-treatment), and response (0, 15, 30, and 60 min after awakening); the
dependent measure was the logarithmised saliva cortisol level.
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doctors on night duty received SHR-5 (170 mg of SHR-5 corre-
sponding to 144 mg of SHR-5 extract) for 2 weeks, fatigue scores
were reduced and cognitive abilities and total mental perform-
ance were increased in comparison with placebo [19].
In the present study, daily administration of 576 mg SHR-5 ex-
tract over a 28-day period produced a pronounced beneficial ef-
fect in burnout patients, with self-rated fatigue being decreased
significantly, with a tendency towards an effect on self-rated
physical health. Additionally, a general effect was noted in which
both verum and placebo groups showed a positive development
over time with respect to several measures. Such an observation
could be due to a general placebo effect or a so-called regression
towards the mean, which is always a possibility whenever a clin-
ical group is selected.
With respect to performance testing, a significantly greater pos-
itive change in the CPT II indices omissions, Hit RT SE, and varia-
bility was detected post-treatment in the verum group than in
the placebo group. Omissions were less prevalent in both groups
after treatment, but significantly more so in the group that had
received R. rosea extract. The post-treatment standard error of
the reaction time was reduced in the treatment group but not
in the control group, indicating a more stable work pace, which
in turn implies a greater level of attention. Variability, which is
also associated with stability of work pace and better attention,
was lower in subjects treated with SHR-5 but not in those who
had received placebo. A tendency (P< 0.1) towards a more posi-
tive change in reaction time was noted in the treatment group
compared with the placebo group.
Cortisol is a known stress hormone, and it is involved in the
feedback regulation of the stress response that helps to restore
homeostasis. Subjecting animals and humans to stress produces
characteristic changes in the HPA axis, including an increase in
the level of cortisol and a reduction in the sensitivity of the HPA
to feedback downregulation. Increased levels of serum cortisol
have been observed in connection with physical exertion, clini-
cal depression, and various stressors. In chronic stress, pro-
longed cortisol secretion causes muscle wastage and hypergly-
cemia and suppresses immune/inflammatory responses [41],
The effect of plant adaptogens in the reduction or prevention of
stress-induced damage is characterised by the decrease or total
elimination of hormonal changes that are peculiar to stress, such
as increased serum cortisol [43], [44]. Free cortisol is present in
saliva, and assays of salivary cortisol have been found to be accu-
rate indicators of total plasma cortisol and plasma free cortisol
[45]. Furthermore, it is well documented that cortisol levels in-
crease rapidly by around 50 –60 % after morning awakening and
remain elevated for at least 60 min thereafter [46]. Awakening
thus acts as a mild stressor, and the measured increase in corti-
sol caused by such stress provides an indication of the responsiv-
ity of the HPA axis. Patients with burnout have been found to
present a relatively high cortisol response to awakening stress
[22]. In the present study, the post-treatment cortisol response
to awakening stress was significantly different in the group that
had received SHR-5 for 28 days than in the control group. These
results are in line with our recent demonstration that treatment
with R. rosea SHR-5 extract for 7 consecutive days prevented the
stress-induced increase of cortisol in the blood of rabbits [44].
Generally, the hypersecretion of cortisol is regarded as a marker
of a state of depression that remits with clinical improvement
[42], [47]. Thus, the inhibition by Rhodiola of the cortisol re-
sponse in stress (i.e., the anti-stress effect) might be associated
not only with increased attention and an anti-fatigue effect but
also with the recently demonstrated antidepressive effect of
SHR-5 in patients suffering from mild to moderate depression
[48]. In the present study involving patients with stress-related
fatigue, a significant change over time in depressive symptoms
was observed in both groups, but with no significant difference
between the two groups. It should be noted, however, that fati-
gue was the primary symptom in the study population selected,
and although some individuals exhibited very mild depressive
problems, subjects with depression as a major symptom were
excluded. Thus, the mean level of depressive symptoms in the
population studied was within the range of light depression
both before and after treatment for the verum group.If individu-
als presenting more evident depressive symptoms had been in-
cluded, or if the study period had been longer, it is possible that
different results may have been obtained.
Fig. 1 Cortisol response to awakening in patients with fatigue syndrome showing pre- and post-treatment logarithmised mean values of salivary cortisol
with respect to time af ter awakening for (A) placebo group (n=25) and (B) group treated with R. rosea extract SHR-5 (n= 21) over a period of 28 days. Vertical
bars denote standard deviations.
Original Paper110
Olsson EMG et al. A Randomised, Double-Blind … Planta Med 2009; 75: 105 –112
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In summary, the results of the present study show that repeated
treatment with standardised extract of R. rosea (SHR-5) seems to
have a positive effect on fatigue level, attention (as measured by
a computerised performance test), and saliva cortisol response
to awakening stress. Additionally, it is suggested that the inhibi-
tory effect of Rhodiola on the increased basal level of cortisol re-
sults in an improvement in cognitive function. This proposal is in
line with other studies demonstrating that optimal corticoste-
roid levels are a requirement for efficient cognitive function, as
significant changes (up or down) in circulating levels of cortico-
steroids result in cognitive impairment [49]. The anti-fatigue ef-
fects of Rhodiola SHR-5 extract, together with improvement in
cognitive functions in fatigue and under stressful conditions,
were reported earlier in healthy volunteers who had received
single and repeated doses of the medication [19], [20], [21].
However, the present investigation constitutes the first demon-
stration of such effects in patients with chronic stress-induced
fatigue. Additionally, this study is the first to demonstrate clini-
cally that Rhodiola exerts its beneficial health effects on stress-
induced disorders by modulation of the most important stress
marker, namely, cortisol. Modulation of cortisol content is con-
sidered to be a key mechanism of action of phytoadaptogens
[43], [44], and this is fully consistent with the results presented
here. It may be concluded that Rhodiola, acting as an adaptogen,
increases attention and endurance in situations of decreased
performance caused by fatigue and sensation of weakness and
reduces stress-induced impairments and disorders related to
the function of the neuroendocrine and immune systems.
Acknowledgements and Declaration of Interest
The authors wish to thank the volunteers for their invaluable
help with the study. The investigation was funded by project
grants from the Research and Development Division of the
Swedish Herbal Institute, a company that researches and com-
mercialises Rhodiola-derived functional products. However, the
funding sponsor played no role in any practical aspect of the
study, including the collection, management, analysis, and inter-
pretation of data and the review and approval of the manuscript.
The study protocol was formulated by AP (who is associated
with the Swedish Herbal Institute) and EO. EO enrolled the par-
ticipants, performed the study interventions, and analysed the
data. All of the authors assisted with drafting the manuscript
and were involved in its critical appraisal and final approval.
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This document was prepared for the exclusive use of Ingemar Joelsson. Unauthorized distribution is strictly prohibited.
... Despite the great interest in the R. rosea and extensive research in the field of phytochemistry, plant bio-technology remained less researched and widely used (Li et al. 2019;Olsson et al. 2009). The stages of morphogenesis of the species and the maximum age of wild populations of R. rosea are also poorly studied (Brinckmann et al. 2021). ...
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Background: Based on world experience, first, a modern assessment of the flora is needed to develop strategies for the conservation of ecosystems of rare and endangered plant species. A regional and global biodiversity strategy should focus on assessing the current state of bioresources. To preserve the biodiversity of the species and its habitat, we evaluated botanical features, ontogenetic phases, the ecological and phytocenotic structure of the rare and endangered of Rhodiola rosea L. (golden rose root) populations from the highlands of Eastern Kazakhstan. Results: R. rosea in the study region lives on damp mossy rocks, rocky slopes, overgrown moraines and along the banks of mountain rivers in the upper limit of cedar-larch forests, subalpine and alpine belts, in the altitude limit of 1700–2400 m. In the studied region, R. rosea begins to vegetate in May–June, blooms in June–July, the fruits ripen in August. The species is encountered in the high mountain ranges of the Kazakh Altai and Saur-Tarabagatai. Unfavorable habitat conditions for the species are overgrown by sedge-grass and birch-moss communities. The most common species at sites with R. rosea are: Schulzia crinita, Achillea ledebourii, Doronicum altaicum, Macropodium nivale, Hylotelephium telephium, Rhodiola algida, Carex capillaris, C. aterrima. Ontogenetic study revealed that all age-related phases were present, with the exception of the senile states. Individual life expectancy shown to be 50–55 years. The analysis of the species composition in the communities with R. rosea showed that the leading families in terms of the number of accompanying species are Poaceae, Ranunculaceae, Asteraceae, Rosaceae and Caryophyllaceae, Apiaceae, Fabaceae; while the most dominant genera are: Carex, Aconitum, Dracocephalum, Festuca, Pedicularis, Poa, Salix; the ecological groups are dominated by psychrophytes, mesophytes mesopsychrophytes; the Asian, Eurasian, and Holarctic groups are the most represented groups. Dominant life forms according to Serebyakov were rod-rooted, brush-rooted, shortrooted and long-rooted grasses, while based on Raunkiaer’s groups the overwhelming majority consisted of Hemincryptophytes (74%). Conclusions: The R. rosea populations of Kazakhstan represent an important gene stock of the species. Our study provides new insights into the species’ biology thus contributes to the conservation of biodiversity on a wide spatial scale.
... RRE is usually extracted in polar solvents, such as alcohol (Wiedenfeld et al., 2007). Since the middle of the 19th century, RRE has been studied further as an adaptogen for its antioxidant properties and effects on the central nervous system (Olsson et al., 2009;Dinel et al., 2019). Studies were then extended further for different applications, such as cardiac diseases, cancer and cerebrovascular disease (Cheng et al., 2012). ...
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Rhodiola is an ancient wild plant that grows in rock areas in high-altitude mountains with a widespread habitat in Asia, Europe, and America. From empirical belief to research studies, Rhodiola has undergone a long history of discovery, and has been used as traditional medicine in many countries and regions for treating high-altitude sickness, anoxia, resisting stress or fatigue, and for promoting longevity. Salidroside, a phenylpropanoid glycoside, is the main active component found in all species of Rhodiola. Salidroside could enhance cell survival and angiogenesis while suppressing oxidative stress and inflammation, and thereby has been considered a potential compound for treating ischemia and ischemic injury. In this article, we highlight the recent advances in salidroside in treating ischemic diseases, such as cerebral ischemia, ischemic heart disease, liver ischemia, ischemic acute kidney injury and lower limb ischemia. Furthermore, we also discuss the pharmacological functions and underlying molecular mechanisms. To our knowledge, this review is the first one that covers the protective effects of salidroside on different ischemia-related disease.
... A considerable alleviation of these complaints after the administration of R. rosea over 8 weeks was reported, along with very good tolerability [16]. Likewise, in a double-blind, placebo-controlled clinical trial, 60 participants, selected according to the diagnostic criteria for fatigue syndrome, were randomized to receive R. rosea (576 mg extract/day) or placebo for four weeks [17]. R. rosea was found to exert a notable anti-fatigue effect that increased mental performance, particularly the ability to concentrate, and decreased cortisol response to awakening stress in burnout patients. ...
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Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system, treat stress-induced fatigue and depression, enhance physical performance and work productivity and treat gastrointestinal ailments and impotence. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue and burnout. The beneficial effects of this medicinal plant on enhancing physical performance have also been evaluated in professional athletes and non-trained individuals. Moreover, even though most evidence originates from pre-clinical trials, several clinical studies have additionally demonstrated the remediating effects of R. rosea on cardiovascular and reproductive health by addressing non-specific stress damage and reversing or healing the disrupted physiologies and disfunctions. Overall, in accordance with its aim, the results presented in this review provide an encouraging basis for the clinical efficacy of R. rosea preparations in managing various aspects of stress-induced conditions.
Despite the lack of guidance available for practitioners, extensive polypharmacy has become the primary method of treating patients with severe and chronic mood, anxiety, psychotic or behavioral disorders. This ground-breaking new book provides an overview of psychopharmacology knowledge and decision-making strategies, integrating findings from evidence-based trials with real-world clinical presentations. It adopts the approach and mind-set of a clinical investigator and reveals how prescribers can practice 'bespoke psychopharmacology', tailoring care to the individualized needs of patients. Practitioners at all levels of expertise will enhance their ability to devise rationale-based treatments, targeting manifestations of dysfunctional neural circuitry and dimensions of psychopathology that cut across conventional psychiatric diagnoses. Presented in a user-friendly, practical, full-colour layout and incorporating summary tables, bullet points, and illustrative case vignettes, it is an invaluable guide for all healthcare professionals prescribing psychotropic medications, including psychiatry specialists, primary care physicians, and advanced practice registered nurses.
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Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders characterized by motor hyperactivity, attention deficit, distraction, impulsive behavior, and relationship difficulties. It affects children, and thus over the years, there has been growing attention on the use of natural product formulations and their naturally‐occurring bioactive for overcoming the problem of ADHD. Concerning this issue, this review aims to discuss the ADHD treatment potential of natural products/formulations in vitro, in vivo as well as in clinical trials. To gather the most relevant data regarding bioactive compounds with potential therapeutic effects in the management of ADHD, the following databases were searched: PubMed/MedLine, ScienceDirect, and Google Scholar for articles in English. Various medicinal plants and their isolated biomolecules have been evaluated in vitro, in vivo, and in clinical trials for their ability to treat ADHD. Most of the analyzed research results showed an improvement of ADHD signs and symptoms in in vivo models, but the molecular mechanisms of action of the bioactive compounds are unclear and incompletely elucidated. Further studies are needed to determine the bioactive compound responsible for health‐promoting effects in ADHD. In addition, clinical studies should be performed over longer periods with more participants. So far there are no concrete recommendations for their use in the treatment of attention deficit‐hyperactivity disorder. This review aims to provide updated clinical evidence on the use of natural products/formulations and their derived constituents for the treatment of attention deficit hyperactivity disorder.
Background New research supports an integrated approach to treating depression, and lifestyle modifications should be a regular component of both preventative and treatment programs. Therefore, in order to investigate the relationship between various antioxidant supplements and depressive status, we carried out a meta-analysis of randomized controlled trials (RCT). Methods We thoroughly searched PubMed, Medline, Scopus, and Web of Science databases to screen publications focusing on the effects of antioxidant supplements on depression status. The meta-analysis mainly compared depression scores between groups that received antioxidant supplements and controls. We also pooled studies reporting changes in anxiety status as a secondary outcome. Results 52 studies with 4049 participants were eventually identified. The meta-analysis found that the positive effect of antioxidant supplementation, such as magnesium (SMD = 0.16, p = 0.03), zinc (SMD = 0.59, p = 0.01), selenium (SMD = 0.33, p = 0.009), CoQ10 (SMD = 0.97, p = 0.05), tea and coffee (SMD = 1.15, p = 0.001) and crocin (MD = 6.04, p < 0.00001), on depressive status were all significant. And antioxidant supplementation also showed significant improvement in anxiety (SMD = 0.40, p < 0.00001). Subgroup analysis by scale types and countries were performed, and antioxidant supplementation's positive effects on depressive and anxiety states remained significant. Limitations This study did not limit the characteristics of the included population, and the diversity of scales also contributed to the heterogeneity. Conclusion Intake of antioxidant supplements is associated with improved depression and anxiety states, further affirms the therapeutic potential of antioxidant supplements as adjunctive therapy to conventional antidepressants.
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Background Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly. Aims To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework ( ), doi 10.17605/OSF.IO/VFDKW. Method A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation. Results Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder ( n = 9), symptom presentation and course ( n = 13), cognitive functioning ( n = 10), biological measures ( n = 24), symptom measurement scales ( n = 4) and treatment ( n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct. Conclusions More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.
Background : Adaptogens are generally referred to the substances, mostly found in plants, which non-specifically increase resilience and chances of survival by activation of signaling pathways in affected cells. Purpose : This literature review was conducted to summarize the investigation, until March 2021, on selected adaptogenic plants and plant-derived substances. Study Design : Electronic databases were searched (up to March 2021) for in vitro and animal studies, as well as clinical trials. Moreover, all modes of action connected with the adaptogenic effects of plants and phytochemicals were collected. Methods : The search of relevant studies was performed within electronic databases including Scopus, Science Direct, PubMed, and Cochrane library. The most important keywords were adaptogen, plant, phytochemical, and plant-derived. Results : The most investigated medicinal herbs for their adaptogenic activity are Eleutherococcus senticosus, Panax ginseng, Withania somnifera, Schisandra chinensis, and Rhodiola spp., salidroside, ginsenosides, andrographolide, methyl jasmonate, cucurbitacin R, dichotosin, and dichotosininare are phytochemicals that have shown a considerable adaptogenic activity. Phytochemicals that have been demonstrated adaptogenic properties mainly belong to flavonoids, terpenoids, and phenylpropanoid glycosides. Conclusion : It is concluded that the main modes of action of the selected adaptogenic plants are stress modulatory, antioxidant, anti-fatigue, and physical endurance enhancement. Other properties were nootropic, immunomodulatory, cardiovascular, and radioprotective activities.
Objective The purpose of this study was to describe the management of 2 long-term users of cannabis with nutrition and psychotherapy. Clinical Features A 28-year-old man presented with a medical history of asthma, depression, anxiety, and smoking, and was a long-term user of cannabis for 9 years (usually 3 times a week). A 39-year-old man presented with a medical history of anxiety and fatigue, and was a long-term user of cannabis for 14 years (usually twice a week). Laboratory tests showed altered blood levels of homocysteine, vitamins, and cortisol. Intervention and Outcome Both patients were given supplements of vitamins (folic acid, methylcobalamin, and pyridoxine), vitamin D, Rhodiola rosea, and L-tyrosine. Psychotherapy also was provided to both patients. After 2 months of treatment, both patients improved and reduced their cannabis consumption. Conclusion This study describes vitamin deficiencies, low cortisol levels, and hyperhomocysteinemia in 2 cannabis users who were managed with a combination of nutritional supplements and psychotherapy.
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Type 2 diabetes is the most prevalent endocrine disease in the world, and recently the gut microbiota have become a potential target for its management. Recent studies have illustrated that this disease may predispose individuals to certain microbiome compositions, and treatments like metformin have been shown to change gut microbiota and their associated metabolic pathways. However, given the limitations and side effects associated with pharmaceuticals currently being used for therapy of diabetes, there is a significant need for alternative treatments. In this study, we investigated the effects of a root extract from Rhodiola rosea in a Leptin receptor knockout (db/db) mouse model of type 2 diabetes. Our previous work showed that Rhodiola rosea had anti-inflammatory and gut microbiome-modulating properties, while extending lifespan in several animal models. In this study, treatment with Rhodiola rosea improved fasting blood glucose levels, altered the response to exogenous insulin, and decreased circulating lipopolysaccharide and hepatic C-reactive protein transcript levels. We hypothesize that these changes may in part reflect the modulation of the microbiota, resulting in improved gut barrier integrity and decreasing the translocation of inflammatory biomolecules into the bloodstream. These findings indicate that Rhodiola rosea is an attractive candidate for further research in the management of type 2 diabetes.
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Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E(2), leukotriene B(4) and thromboxane B(2) were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200-300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their antidepressant activity as well as their positive effects on mental performance under stress.
The validity of the Swedish SF-36 Health Survey was examined, replicating techniques used in the U.S. validation. Principal components analysis was used to test the internal structure of the eight SF-36 scales in relation to hypothesized associations with the two major dimensions of health—physical and mental. Hypothesized relationships between scales and external criteria were also examined by means of clinical group contrasts. Both the principal components analysis and clinical group contrasts largely replicated U.S. findings, which supported the cross-cultural stability of the SF-36 in Sweden. As expected, the Physical Functioning and Mental Health scales were most sensitive to clinical manifestations of medical and mental health, respectively. The General Health scale was associated more with physical than mental health. However, the Social Functioning scale and particularly the Vitality scale were more related to mental health in Sweden than in the corresponding U.S. study. Cultural differences and variation in study samples and selection criteria were suggested as possible explanatory factors for these differences.
We document the applicability of the SF-36 Health Survey, which was translated into Swedish using methods later adopted by the International Quality of Life Assessment (IQOLA) Project procedures. To test its appropriateness for use in Sweden, it was administered through mail-out/mail-back questionnaires in seven general population studies with an average response rate of 68%. The 8930 respondents varied by gender (48.2% men), age (range 15–93 years, mean age 42.7), marital status, education, socio-economic status, and geographical area. Psychometric methods used in the evaluation of the SF-36 in the U.S. were replicated. Over 90 % of respondents had complete items for each of the eight SF-36 scales, although more missing data were observed for subjects 75 years and over. Scale scores could be computed for the vast majority of respondents (95% and over); slightly fewer in the oldest subgroup. Item-internal consistency was consistently high across socio-demographic subgroups and the eight scales. Most reliability estimates exceeded the 0.80 level. The highest reliability was observed for the Bodily Pain Scale where all subgroups met the 0.90 level recommended for individual comparisons; coefficients at or above 0.90 were also observed in most subgroups for the Physical Functioning Scale. Tests of scaling assumptions including hypothesized item groupings, which reflect the construct validity of scales, were consistently favorable across subgroups, although lower rates were noted in the oldest age group. In conclusion, these studies have yielded empirical evidence supporting the feasibility of a non-English language reproduction of the SF-36 Health Survey. The Swedish SF-36 is ready for further evaluation.
The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inter-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
The assessment of cortisol in saliva has proven a valid and reliable reflection of the respective unbound hormone in blood. To date, assessment of cortisol in saliva is a widely accepted and frequently employed method in psychoneuroendocrinology. Due to several advantages over blood cortisol analyses (e.g., stress-free sampling, laboratory independence, lower costs) saliva cortisol assessment can be the method of choice in basic research and clinical environments. The determination of cortisol in saliva can facilitate stress studies including newborns and infants and replace blood sampling for diagnostic endocrine tests like the dexamethasone suppression test. The present paper provides an up-to-date overview of recent methodological developments, novel applications as well as a discussion of possible future applications of salivary cortisol determination.
The effect of alcohol-aqueous extract (1:1) from Rhodiola rosea L. roots on the processes of learning and memory is studied on rats. Several methods of active avoidance with negative and positive reinforcements are used, as well as of passive avoidance. Using the maze-method with negative (punitive) reinforcement, it has been found that Rhodiola extract in a single dose of 0.10 ml per rat essentially improves learning and retention after 24 hours. Significant improvement of the long-term memory is also established in memory tests after 10-day treatment with the same dose of the extract. In the other two doses tested (0.02 and 1.0 ml per rat) the extract has no substantial effect on learning and memory. In a dose of 0.10 ml per rat the Rhodiola extract had a favourable effect on the training process using the "staircase" method with positive (food) reinforcement as well. With the other methods used (active avoidance method with negative reinforcement "shuttle-box" and passive avoidance methods "step down" and "step through") Rhodiola extract in the dose used (0.10 ml per rat) had no substantial effect on learning and memory (a certain deterioration of the training process was even observed using the "shuttle-box" method, while the "step-down" method resulted in deterioration of the memory). The great significance of the method used for studying the effects of the pharmacological agents on learning and memory for the results obtained is evident.