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Panax Ginseng in combination with brewers' yeast (Gerivet®) as a stimulant

for geriatric dogs: A controlled-randomized blinded study

Article in Journal of Veterinary Pharmacology and Therapeutics · September 2007

DOI: 10.1111/j.1365-2885.2007.00876.x · Source: PubMed

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J. vet. Pharmacol. Therap. 30, 295–304, doi: 10.1111/j.1365-2885.2007.00876.x.

Panax Ginseng in combination with brewers’ yeast (Gerivet) as a

stimulant for geriatric dogs: a controlled-randomized blinded study

A. HIELM-BJÖRKMAN Hielm-Björkman, A., Reunanen, V., Meri, P., Tulamo, R.-M. Panax Ginseng in
V. REUNANEN combination with brewers’ yeast (Gerivet) as a stimulant for geriatric dogs: a
controlled-randomized blinded study. J. vet. Pharmacol. Therap. 30, 295–304.
P. MERI &
R.-M. TULAMO The study was performed on two groups of dogs, one (n ¼ 41) given Ginseng
(Panax Ginseng) together with brewers’ yeast (Saccharomyces cerevisae) and the
Faculty of Veterinary Medicine, Department other (n ¼ 39) given only brewers’ yeast (control group, but not a true
of Equine and Small Animal Medicine, placebo), for 8 weeks. Using a questionnaire and three visual analogue scales,
University of Helsinki, Helsinki, Finland the blinded owners evaluated the dogs before the trial, weekly for the 8 weeks of
the trial and twice, at 12th and 16th weeks, after the trial (follow-up). At 8th,
12th and 16th weeks the owners also answered questions concerning what
treatment their dogs likely had been getting, willingness to continue medication
and the dogs’ general status. The changes from baseline to the end of the
treatment period in the variable scores were calculated for each dog and used in
statistics. Panax Ginseng plus yeast significantly improved all evaluated
variables within the group. Four of the seven primary (mentally) outcome
measures were significant when comparing the changes in the Ginseng group
with the control group, and six of the seven were significant when compared to
an external group. As the secondary (physical) outcome measures were
significantly better in both the Ginseng and the control group compared to the
external group, it indicates that brewers’ yeast is the ingredient that has impact
on physical performance. No significant changes in blood- or urine analyses
and no side effects were seen.
(Paper received 18 April 2007; accepted for publication 20 May 2007)
Dr Anna Hielm-Björkman, Faculty of Veterinary Medicine, Department of Equine
and Small Animal Medicine, PO Box 57, University of Helsinki, Helsinki FI-00014,
Finland. E-mail: anna.hielm-bjorkman@helsinki.fi

INTRODUCTION
There is a growing interest in complementary medicine also in
the field of veterinary medicine. Some veterinarians deny any
effect of these additives as there is little evidence-based informa-
tion. However, research is beginning to be prepared in this field
and the Food and Drug Administration, the National Institute of
Health and the European Commission have started to grant
money to this field of research, and universities are showing
interest to conduct research in this area. In this study we
examined the intake of Gerivet, a tablet containing Panax
Ginseng and brewers’ yeast, and compared our findings with
those collected following the intake of brewers’ yeast alone.
Panax Ginseng (also named Chinese or Korean Ginseng) has
been in the human market for thousands of years in Asia, and
for many decades in Europe and the USA. In humans, it is used
as a stimulant, often by older people or in stressful situations. It is
the most-studied herb for ameliorating human mental alertness
and physical performance. It is widely used in Asia for dietary
and medicinal purposes and can be found in many forms, such
as whole root, root powder (white Ginseng), steamed root
powder (red Ginseng) and standardized root extracts. Ginseng
root contains at least 30 positively identified Ginsenosides (1–2%
of the root), that are glycosylated steroidal saponines (Petkov
et al., 1992; Wang et al., 1995; Kennedy et al., 2004). Sapo-
nines are high molecular weight glycosides combining a sugar
element and a steroid aglycone or triterpene molecule. The
mode of action for Ginseng is not yet fully understood but
the Ginsenosides are likely to be the active ingredients. Rg1
(a panaxtriol with two sugars) and Rb1 (a panaxtriol with four
sugars) have both shown to increase neural proliferation and
differentiation of neural progenitor cells in the dentate gyrus of
the hippocampus of both normal adult mice and gerbils in a
global ischemia model (Cheng et al., 2005). Rb1 is one of the
neuroprotective molecules of Ginseng (Wen et al., 1996) and
may elicit its anti-amnesic effect by minimizing the inhibitory
effect of beta-amyloid peptides (Lee et al., 2001). Ginseng
saponines are said to play an important role in the anxiolytic

 2007 The Authors. Journal compilation  2007 Blackwell Publishing Ltd 295
296 A. Hielm-Björkman et al.
effects of Ginseng (Park et al., 2005). Also the nonsaponin
fraction of red Ginseng contains substances that improve
learning and memory in aged rats, and this effect may be
attributed partly to the long-term potentiation in the hippocam-
pal CA1 and CA3 subfields (Wen et al., 1996; Zhong et al., 2000;
Kurimoto et al., 2004; Nishijo et al., 2004). Further, adminis-
tration of long-term Ginseng has also been shown to stabilize
membranes and to protect the mitochondrial function from free
radicals in the skeletal muscle (Voces et al., 2004), and Rb1 and/
or Rg1 are essential for exerting the ergogenic effects of Ginseng
saponines in aerobic endurance (Wang & Lee, 1998).
The other main ingredient in the Gerivet tablet is brewers’
yeast. This 100% brewers’ yeast, also known as nutritional yeast
(Saccharomyces cerevisae), is rich in many basic nutrients, such as
several vitamin Bs, 18 amino acids and at least 14 different
minerals. Pelka and Leuchgens (1995) reported significant
efficacy of yeast supplementation in cases of fatigue, headache,
giddiness, depressive mood and apathy, as also better mental
alertness, sleep, emotional stability, speed of information flow
and improvement in reciting numbers and letters forwards and
backwards. In addition, the brewers’ yeast is often given for
nervousness and fatigue, eczema, heart disorder, problems of
sugar metabolism and gout.
The aim of this study was to feed the product Gerivet to older
dogs that were already showing geriatric clinical signs. As the
patients were normal dogs living at home with their owners, the
only way to evaluate change in behaviour and alertness was by
letting the owners be the evaluators. Therefore, the study was a
double blind, randomized, controlled study with nonprofessional
subjective evaluators. This study evaluated the use of Panax
Ginseng combined with the brewers’ yeast compared with only
the brewers’ yeast as the control group. It should be stressed that
both of these compounds are thought to be stimulants and,
therefore, the yeast tablet cannot be called a true placebo. Also,
we compared the results to an external group. Panax Ginseng
plus yeast was hypothesized to increase stimulation in dogs,
compared to only brewers’ yeast that is a much milder stimulant
and even more significantly, compared to the external group.
MATERIALS AND METHODS
The study was designed as a randomized controlled, double-blind
clinical trial, with dogs allocated to groups and evaluated 11
times; during the weekly treatment at 0, 1st, 2nd, 3rd, 4th, 5th,
6th, 7th and 8th weeks and thereafter twice as follow-up, at
weeks 12 and 16. A secretary prepared the first appointments,
and upon arrival at this first visit (Time ¼ 0), the dogs were
assigned into groups in order of arrival, using a computer-
generated random list. All veterinarians, other personnel and
evaluators (owners) were blinded. Owners of the dogs were told
that some of the dogs would get a stimulant and some a placebo.
As the control product could be suspected to have the same type
of stimulating effects as Ginseng, although on a smaller scale,
there was no real placebo to compare the results with. Therefore,
9-weekly questionnaires were further sent to 20 ‘external’
 2007 The Authors. Journal compilation  2007 Blackwell Publishing Ltd
geriatric dog-owners, whose dogs were not taking any product,
and, therefore, can be seen as a waiting list group, often used as
a control group in studies of invasive procedures. Twelve
returned the data, which could be used in statistics.
The owners were required to sign informed consent forms. The
study protocol was approved by the Ethics Committee of the
University of Helsinki. The authors declared that they had no
competing interests.
Dogs
The number of dogs needed in each active group was calculated
for using a two-tailed Fisher test. The sample was sufficiently
large to detect a 34% difference (Dörling & Kirchdorfer, 1989) in
treatment outcome (effective vs. noneffective) with a statistical
power of 0.8 and allowing for a 5% alpha error.
The inclusion criterion was that the dog showed clinical signs
of geriatric behaviour. Dogs with osteoarthritis, spondylosis, a
small increase in blood urea nitrogen (BUN) but normal
creatinine and with hypothyroidism under steady-state medica-
tion, were accepted if they were without clinical signs. Exclusion
criteria included confirmed diagnosis of cancer, heart insuffi-
ciency or neurological diseases. A total of 111 normal clinically
healthy dogs, showing, however, at least three of our clinical
signs typical for geriatric dogs (not willing to move, not willing to
play, interest in surroundings decreased, sleeps more, slow in
reacting, less attentive, takes less interest in other dogs or people,
talks more, is more aggressive towards other dogs, does not
always recognize places/people, incontinent) were first chosen
based on telephone interviews. 85 dogs were included in the
study. Owners were asked to keep the dogs off other stimulants
4 weeks before and during the study and the use of analgesics
(for dogs suffering from OA, spondylosis) was recorded in the
questionnaire during the study.
Test-products
The two tablets used in this study, the Ginseng and the yeast
product, looked and smelled alike and were packed in similar
white plastic tablet containers. The package had no markings,
and the dose schedule was given on a separate paper. Both
tablets were dosed by bodyweight (BW) (see Table 1). The two
active groups will hereafter be referred to as the Ginseng group
and the control group.
The verum contained 40-mg Panax Ginseng extract and
693 mg of brewers’ yeast per tablet (Gerivet, Vetcare Ltd. Salo,
Finland). The standardized Ginseng extract used in this study
came from Korean Ginseng A.C. Mayer, G115, (GPL Ginsana
Products, Lugano, Switzerland) a product containing known and
reproducible amounts of ginsenosides.
The standardized brewers’ yeast is called E10 feed grade 100%
dried brewers’ yeast (Red Star Bioproducts, Brussels, Belgium).
To establish the role of the ingredient Panax Ginseng, the control
group was given a tablet containing 693 mg of the brewers’
yeast. The components of brewers’ yeast are given in Table 2.
Palatability was never a concern.
 Ginseng for dogs: a clinical RCT 297

Table 1. Ginseng extract dose for different dog

No of tablets/day Ginseng extract mg/kg
bodyweights (BW)
Dog BW (Ginseng extract/dog/day) (ginsenosides lg/kg)/BW in trial dogs

<10 kg 1/2 · 1 (20-mg Ginseng) 2.08–4.44 mg/kg (83–178 lg/kg)

10–25 kg 1 · 1 (40-mg Ginseng) 1.70–4.00 mg/kg (68–160 lg/kg)
>25 kg 2 · 1 (80-mg Ginseng) 1.58–3.08 mg/kg (63–123 lg/kg)

Table 2. Brewers’ yeast contains chemical analysis of E10 feed grade 100% dried brewers’ yeast (Red Star Bioproducts, Belgium)

General Average Minerals Average Amino-acids g/100 g DM Vitamins mg/kg

Proteins 44% Calcium (Ca) 0.2% Alanine 2.90 B1 Thiamine 125

Fat 1.5% Chromium (Cr) 0.75 ppm Arginine 1.94 B2 Riboflavin 35
Carbohydr. 35% Copper (Cu) 10 ppm Aspartic acid 3.62 B3 Niacin 400
Ash 8% Iodium (I) 3 ppm Cystine 0.54 B5 Pantothenic acid 50
Humidity 5% Iron (Fe) 80 ppm Glutamic acid 6.51 B6 Pyridoxine 35
Crude fibre 1.1% Lead (Pb) < 5 ppm Glycine 2.00 B12 Cobalamin 0.1
Magnesium (Mg) 0.2% Histidine 1.00 Biotin 1.5
(Of total protein 12% is nucleic prot.) Manganese (Mn) 7 ppm Isoleucine* 1.63 Inositol 3800
Phosphorus (P3O) 1.5% Leucine* 2.78 Choline 4500
Potassium (K) 1.6% Lysine* 2.68 Glutathione 6000
Selenium (Se) 0.75 ppm Methionine* 0.54
Sodium (Na) 0.2% Phenylalanine* 1.68
Total sulphur (S) 0.4% Proline 2.47
Zinc (Zn) 35 ppm Serine 2.63
Threonine* 2.10
Tryptophane* 0.51
Tyrosine 1.37
Valine* 2.05

The asterisk symbols (*) are essential amino acids. DM ¼ dry material.

Owner assessment
Using a questionnaire and three visual analogue scales (VAS),
the blinded owners evaluated the dogs twice before the trial
began; once first at home to familiarize them with the
questionnaire (these were not used for statistics) and at the first
visit, to obtain baseline values. After the initiation of medication,
the owners evaluated the dogs weekly for 8 weeks with some
additional questions at the 4th and 8th week. As a follow-up the
owners evaluated the dogs at weeks 12th and 16th when they
were not taking the products anymore. The external group
evaluated the dogs nine times, weekly.
The first part of the questionnaire used a descriptive scale of
0–4 and contained questions about the dogs’ mental attitude/-
behaviour and about their physical performance. The primary
(mentally) outcome measures were: Spryness of the dog (spryness
for short): [very spry (0), spry (1), not spry, nor dull (2), quite
dull (3), very dull (4)], Alertness/interested in its surroundings
(Alertness/interested): [very much alert (0), alert (1), alert at
times (2), not so alert (3), not at all alert (4)], seems to be
mentally tired (mentally tired): [never (0), seldom (1), sometimes
(2), often (3), very often (4)], Reacting to things and situations
(Reactiveness): [very quickly (0), quickly (1), not quickly, nor
slowly (2), slowly (3), very slowly (4)] and forgets what he was
doing (forgetfulness): [never (0), seldom (1), sometimes (2), often
(3), very often (4)]. The secondary (physical) outcome measures
were: walking: [very willingly (0), willingly (1), not willingly, not
reluctantly (2), reluctantly (3), very reluctantly (4)], self
determined physical activity outside home (physical activity): [very
often (0), often (1), sometimes (2), seldom (3), very seldom (4)]
and where walking, in relation to owner (position on walks):
[always ahead of owner (0), often ahead of owner (1), level with
owner (2), often behind owner (3), nearly always/always behind
owner (4)]. In all questions, the closer the mean is to 0, the more
alert is the dog, the closer it is to 4, the more the dog has clinical
signs of ageing.
The second part contained three 10-cm VAS: Two primary
outcome measures – one for alertness, one for quality of life
and the third as a secondary outcome measure – for
locomotion. The left end of the scales (¼0) represented totally
alert, highest quality of life and no difficulties in locomotion,
and the right end (¼10), the lowest possible alertness, the
poorest quality of life and the most severe difficulties in
locomotion.
The third part consisted of questions about possible adverse
reactions to treatment, including change in appetite, vomiting,
diarrhoea, atopic skin reactions and the need for analgesics.
At 8th, 12th and 16th weeks all the owners also answered
questions concerning the desired effect, the overall alertness of
the dog, what group their dogs likely had been in and willingness
to continue the given products. All questions were posed in the
Finnish language.

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298 A. Hielm-Björkman et al.
Veterinarian and haematological examination
All dogs were examined by a veterinarian at time ¼ 0, (clinical,
neurological and orthopaedic examination), and the blood
biochemistry was analysed to determine the health status of
the animals before they were finally included in the study.
Haematological examination included BUN, creatinine, serum
alanine aminotransferase, alkaline phosphatase, glucose and
cholesterol by Spotchem and urological tests (multistix 8 SG IV
and total protein) prepared at time ¼ 0 and at time of
withdrawal of the tested products (8 weeks after start). The
veterinarian did not evaluate any mental or physical changes in
the dogs.
Statistical analysis
The changes from baseline to the end (8 weeks) of the treatment
period in the variable scores were calculated for each dog. The
Wilcoxon signed rank test and the paired sample t-test were used
to test significant changes in variables within the treatment
group. To test for the differences in variable scores between the
groups, Mann–Whitney’s test was used for the descriptive scales,
and an independent sample t-test was used for the other
variables. P-values <0.05 were considered significant. Statistical
tests were performed by using SPSS 12.0 (Chicago, IL, USA) for
Windows.
RESULTS
Five of the dogs chosen for this study (three from the treatment
and two from the control group) were eliminated from the study
at some point for the following reasons: two never finished the
study, one had a glucose over 25 mmol/L (normal 3.5–
5.5 mmol/L) that had to be medicated and the dog was changed
to another diet, one had a painful glaucoma and had to have
surgery, and one dog was killed soon after the initiation of the
Table 3. Baseline values (at start of trial) for Ginseng-, control- and waiting list groups
Possible confounding factors at start of trial
n 41
Median, dose of Ginseng Min.–Max. (mg/kg)
Median brewers’ yeast dose; Min.–Max. (mg/kg)
Sex: male/female
Median age (years); Min.–Max.
Median duration of geriatric signs (years)
Median weight (kg); Min.–Max.
Mean ± SD of continuous variables at start of trial
Owner-assessed alertness VAS (cm)
Owner-assessed quality of life VAS (cm)
Owner-assessed Locomotion VAS (cm)
Median, Min.–Max. of variable at 4 weeks prior to trial (W)4)
NSAID doses per month (none, about 1/month,
about 1/week, 3–5/week, daily)
*Shows significant bias between external group and Ginseng group (P < 0.05).
study. Those killed later were included in the study. The 80 dogs
finally included were of 38 different breeds (of which 13 were
crossbred, 10 golden retrievers, four Belgian sheepdogs and four
dachshunds, the others 1–3 per breed), different BW (range: 3–
52.8 kg) and different age (range: 8.5–17 years). Some baseline
data per group are presented in Table 3. There was baseline bias
in the primary outcome measures ‘forgetfulness’, where the dogs
were significantly worse in the Ginseng group compared to both
the control (P ¼ 0.031) and the external group (P ¼ 0.011) and
in the VAS ‘quality of life’ where the dogs were significantly
worse in the Ginseng group compared to the external group
(P ¼ 0.038). The secondary outcome measure VAS ‘locomotion’
was also significantly worse in the control group compared to
the external group already at the start of the trial. ‘Walking’ was
very close to giving a significant bias (P ¼ 0.052); here walking
was worse in the control group compared to both the Ginseng
and the waiting list groups. There was no bias concerning blood
values, examination results, concurrent disease or medications
between the two active groups at baseline.
Data of change in means in all three groups are presented in
Table 4. Within the Ginseng group, all primary and secondary
outcome measures had significantly improved after 8 weeks
compared to baseline. When comparing the change in the
Ginseng group with the change in the control group from the
start to the end of the treatment (0–8 weeks), the Ginseng group
improved significantly in the primary outcome measures (the
mental variables). Improvement of any of the four physical
variables was not statistically significant, but 10 of the 11
evaluated variables had improved more in the Ginseng group
compared to the control group. Compared to our external group,
the Ginseng group was significantly better in 10 of the 11
variables after 8 weeks. Deterioration could be seen in both
active groups after the treatment ended (Fig. 1).
There was no significant difference in any of the blood
values, urine tests, and the intake of analgesics or answers
regarding side effects between the two groups. At the end of the
treatment period three dogs were killed in the control group but
Ginseng Control Waiting list
39 12
1.58–4.44 0 0
40.8; 19.8–77 39.4; 26.2–115.5 0
15/26 8/31 5/7
12; 8.5–17 11; 8.5–16 11.8; 8.5–15
1–2 1–2 1–2
23.4; 4.5–50.6 23.2; 3–52.8 21.0; 6–36
4.75 ± 1.92 4.53 ± 1.75 3.67 ± 2.42
4.00 ± 1.71 3.60 ± 1.87 2.78 ± 1.86*
4.39 ± 2.50 4.81 ± 2.12 3.1 ± 2.52
none, none, none,
none – 3–5/week none – about 1/week none – daily
 2007 The Authors. Journal compilation  2007 Blackwell Publishing Ltd
 Ginseng for dogs: a clinical RCT 299

Table 4. Data: mean ± SD of change of evaluated variables from W0 to W8, for Ginseng-, control- and waiting list groups. (Means below zero show
deterioration in the variable during this time)

Ginseng group Control group Waiting list group

Variable Mean ± SD P* Mean ± SD P** Mean ± SD P*** P****

Primary outcome measures

Spryness 0.70 ± 0.82 <0.001 0.39 ± 0.72 0.17 ± 0.58 0.049
Alertness/interested 0.68 ± 0.73 <0.001 0.24 ± 0.82 0.008 0.25 ± 0.75
Mentally tired 0.92 ± 1.02 <0.001 0.60 ± 0.82 0.17 ± 0.83 0.015
Reactiveness 0.47 ± 0.89 0.003 0.35 ± 0.86 )0.18 ± 0.40 0.018 0.018
Forgetfulness 0.72 ± 0.99 <0.001 0.32 ± 0.77 0.027 )0.17 ± 0.72 0.003
Alertness VAS (cm) 2.11 ± 2.38 <0.001 1.18 ± 1.34 0.041 0.55 ± 1.66 0.041
Quality of life VAS (cm) 1.25 ± 1.59 <0.001 0.35 ± 1.42 0.012 )0.48 ± 0.95 0.001
Secondary outcome measures
Walking 0.72 ± 1.01 <0.001 0.66 ± 0.74 )0.50 ± 1.17 0.002 0.003
Physical activity 0.42 ± 0.87 0.005 0.45 ± 0.72 )0.25 ± 0.75 0.022 0.010
Position on walks 0.79 ± 1.19 <0.001 0.39 ± 1.00 )0.42 ± 1.08 0.003 0.017
Locomotion VAS (cm) 1.42 ± 2.19 <0.001 0.90 ± 1.99 )0.47 ± 1.63 0.008 0.036

In the Ginseng group, the P*-values are those of the change from W0 to W8 within the group. In the control and external groups the P** and P*** show
the change compared to the Ginseng group, respectively. The P**** compares the external group with the control group. Only significant (P < 0.05)
values are shown in the table.

none in the Ginseng group. During the follow-up period, four
were killed in the Ginseng group and one in the control group.
The questions concerning the desired effect gave the following
results: At 8 weeks altogether 73% of the Ginseng group and
47% of the control group owners felt that their dogs had eaten
Ginseng (P ¼ 0.023), after 1-month follow-up, the values were
83% and 46% (P ¼ 0.003) and after 2-month follow-up 85%
and 44% (P ¼ 0.002), respectively. At 1- and 2-month follow-
up, more owners in the Ginseng group now felt that their dogs
had more geriatric signs returning after the treatment period
was over (Fig. 2) than in the control group (P ¼ 0.012 and
P ¼ 0.040, respectively). After 1 and 2 months, follow-up more
of the owners in the Ginseng group would restart the
medication immediately or at least consider it (Fig. 3), than in
the control group (at 1-month follow-up the difference between
the two groups was not significant and at 2 months
P ¼ 0.040).
DISCUSSION
The aim of the present study was to see if Panax Ginseng would
have improving effects on geriatric dogs. In four out of the seven
of the mental primary outcome measures, the improvement was
significant between Ginseng and control groups. This points us
at Panax Ginseng having an influence over mental measures.
After 8 weeks, none of the physical secondary outcome measures
were significantly better in the Ginseng group compared to the
control group, but they were all better in both the Ginseng and
the control group compared to the external group and, therefore,
it seems plausible that the product ingested by both of these
groups had some impact on physical performance. This could
mean that it is the yeast component of the Gerivet tablet that is
having an impact on physical activity and that Panax Ginseng,
together with yeast, does not add to physical performance.
A review on animal and human studies on Ginseng as an
ergogenic aid to physical performance has concluded that
compelling evidence on the efficacy of Ginseng for this indication
is lacking (Bahrke & Morgan, 1994). This could be in accordance
with our study. Also, the bias at baseline can perhaps account
for some of this effect, as the dogs in the Ginseng group seemed to
be in a worse mental shape than the control and/or waiting list
group and the dogs in the control group seemed to be in a worse
physical shape than the Ginseng and/or waiting list group. Also,
our questions focussed more on locomotion than on physical
activity. In human and lab animal research, more objective
psychometric tests, reaction time analysis, mental tasks and
maze models (Petkov & Mosharrof, 1987; Sörensen & Sonne,
1996; Park et al., 2005; Reay et al., 2005) have been used as
mental tests and, for physical activity, they have primarily
looked at physical performance measures, such as ergometric
tests and the oxygen uptake, the heart rate and blood lactate
(Forgo et al., 1981; Forgo & Kirchdorfer, 1982; Wang & Lee,
1998). Our study did not use these kinds of variables; neither did
we include any objectively evaluated learning tasks nor specific
tests of memory for the dogs. It is easier to design a standardized
test setting for humans, mice or rats, than it is for clinical canine
patients coming from very variable circumstances. To minimize
the effects of canine personality on test results (variables such as
obedience, shyness, aggressiveness, stubbornness, etc.) and
unfamiliar family dynamics at the clinic, a proxy evaluation
was used.
All variables within the Ginseng group improved during the
treatment. Ten of the 11 variables improved significantly,
comparing Ginseng to the external group. This is expected due
to the effect of owner expectance (as the owners knew that they
were under no treatment), but the inclusion of an external group
enabled us to control for possible seasonal effects. As the study

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300 A. Hielm-Björkman et al.

(a) (b)
6 6

5 5

Mean of quality of life VAS (95% CI)

Mean of alertness VAS (95% CI)

4 4

3 3

2 2

1 1

0 0
0 1 2 3 4 5 6 7 8 12 16 0 1 2 3 4 5 6 7 8 12 16

Time in weeks Time in weeks

(c) 6

5
Mean of locomotion VAS (95% CI)

0
0 1 2 3 4 5 6 7 8 12 16
Time in weeks

Fig. 1. Means with 95% CI of three different variables over time; (a) visual analogue scale (VAS) on alertness, (b) VAS on quality of life and
(c) VAS on locomotion, at weeks 0–8 during treatment and at weeks 12 and 16 during follow-up. Their means are connected by different lines for the
two groups: (–u–) Ginseng group and (–Æ–) control group in all figures. Please note that the time interval changes after 8 weeks and is different for
12 and 16 weeks.

period was from January to April (winter changing into spring), that indicated a difference in behaviour in the first week already.
we might have seen a spontaneous positive effect in both mental However, we chose 8 weeks, as there are studies that show the
and physical variables due to more light or positive temperature effect within 1 day (Kennedy et al., 2001 and 2004), after
changes. However, this was not seen in the external group; on 4 days (Wang & Lee, 1998) or only after 6 weeks of treatment
the contrary, we saw a deterioration of clinical signs, as seven of (Forgo et al., 1981). In our study, we found a larger difference
the 11 variables worsened during the study period. between the Ginseng and control group during the first part of
The duration of treatment and dose are possible confounding the study (documented as a bigger difference between the two
factors. We had some pretrial anecdotal data from dog owners groups at 4 weeks) compared with findings at 8 weeks. This may

 2007 The Authors. Journal compilation  2007 Blackwell Publishing Ltd

 Ginseng for dogs: a clinical RCT 301

100 100
16 17
29 43
90 90

Percentage (%) of dogs per group

48 80 50
Percentage (%) of dogs per group

80

70
70
57 60
60
12 wk: Dogs status 50 52
50
40
much "older"
40
12 Wk: Would restart
30 33
32 some "older"
30
20 would not
20 the same
10 would maybe
some more alert
10
11 0 would instantly
much more alert Ginseng Control
0
Ginseng Control Group
Group
100
40 23
100 90
27 12
Percentage (%) of dogs per group

90 80
32 45
70
Percentage (%) of dogs per group

80

60
70 46 60
50
60

48 40
50
16 wk: Would restart
16 wk: Dogs status 30 32
40
20 would not
30 much "older"
would maybe
23 10
20 some "older"
would instantly
0
the same Ginseng Control
10
8 Group
0 some more alert
Ginseng Control Fig. 3. Follow-up: the bars represent the percentage of owners per
group at follow-up (at time 12 or 16 weeks) that would/would not
Group restart the medication again.

Fig. 2. Dogs status assessed by their owners 4 and 8 weeks after

cessation of the treatment. Follow-up: the bars represent how the owners
perceived their dogs at follow-up (time 12 and 16 weeks, 4 and 8 weeks
after cessation of the treatment); the percentage of dogs feeling older/
more alert per group, compared to when they were eating the products.
be explained with reference to a study (Pelka & Leuchgens,
1995) showing that the brewers’ yeast caused increased values
on different mental variables only starting from 6 weeks. Thus,
there was less difference between the groups towards the end of
the study as the positive effects of the brewers’ yeast on dogs in
the control group increased over time.
The dose of Ginseng, however, is undefined, as different sources
state very different amounts. There are very few actual
references on the doses of Ginseng for dogs. Wynn and Marsden
(2003) suggest 12–16 mg/kg BW daily for dogs and one of the
toxicity studies evaluating Ginseng used 1.5, 5 or 15 mg/kgÆBW/
day on beagles (Hess et al., 1982), but no mental or physical
evaluations were prepared. The human traditional Chinese use

 2007 The Authors. Journal compilation  2007 Blackwell Publishing Ltd

302 A. Hielm-Björkman et al.
of Ginseng is 3–9 g of powdered root/person/day (Bucci, 2000)
but the dose in the USA and Europe has been lower; often just
0.5–2 g of powdered root/person/day (Ernst, 2002). The root/
extract ratio is between 3–7 (usually calculated as 5) parts root
to one part extract, depending on the concentration of ginseno-
sides in the root. The extract we used is standardized to contain
4% ginsenosides. Each Gerivet tablet contains 40 mg of
Ginseng extract. The dose used in this trial was the one the
manufacturer recommended (Table 1) i.e. 1.58–4.44 mg ex-
tract/kg BW for the dogs in our study. There are very few canine
studies on Ginseng but in some previous human or lab animal
studies, the dose has been found to be important, while in others
not (Forgo & Kirchdorfer, 1982; Petkov & Mosharrof, 1987;
Nitta et al., 1995a,b; Sörensen & Sonne, 1996; Kennedy et al.,
2001, 2004; Reay et al., 2005). In a review of 35 human Panax
Ginseng research papers, Bucci (2000) pointed out that trials (a)
with a sufficient daily dose of minimum 2 g of dried root
(meaning about 4.7–11.1 mg/kgÆBW/day of extract), (b) with a
study duration over 8 weeks and (c) for subjects over 40 years of
age, has given the best test results. Comparing this with our
setup, we used less Ginseng extract than suggested by Bucci, but
we had a sufficient administration period and were assessing
geriatric individuals. If effect is dose dependent, as has been
indicated in many of the studies, we would perhaps have seen a
greater difference between the two groups in our study if we had
used a larger dose. Therefore, more research should be done on
dogs with a higher dosage of Panax Ginseng.
The brewers’ yeast acts like a complement in the Gerivet
product but the dose of yeast is very small compared with the
effective doses recommended in feed for animals (for dogs: 1–5%
of feed). It is used here as a means of better introducing Ginseng
into the metabolism, and as the dose is so small, it will probably
take a longer time to accumulate in the body to the extent that
the beneficial effects will be seen. Very few studies on brewers’
yeast as a stimulant were found. The brewers’ yeast extract (2 g/
kgÆBW/day for 6 weeks) was used in one study to treat the
chronic fatigue syndrome in a model with mice, and a significant
difference was found between the treatment- and placebo groups
in daily activity and host immune responses (Takahashi et al.,
2006).
Concerning both Ginseng and the brewers’ yeast, we can
conclude that as dogs vary greatly by their size, the effective
doses should not be calculated by BW but preferably by
metabolic weight. Future research should therefore also look at
different doses for different sized dogs.
Side effects due to the use of Ginseng have been reported but
are very rare. The only other trial on dogs (Hess et al., 1983),
with doses up to 15 mg/kgÆBW/day, showed no negative
treatment-related effects. We saw none during our 8-week
treatment period either. Partly this can be explained by the fact
that already when choosing patients for the study, we selected
them with these criteria in mind. It has been found that
ginsenosides inhibit cyclic AMP phosphodiesterase and, thus,
perhaps augment the effects of monoamine oxidase inhibitors
(e.g. Phenelzine) and can, therefore, cause side effects, such as
irritability, insomnia and tension headaches (Jones & Runikis,
 2007 The Authors. Journal compilation  2007 Blackwell Publishing Ltd
1987). Ginseng is not advised to be used together with
immunosuppressants, such as cyclosporin, as it possesses
powerful immunostimulating properties and, can, therefore,
potentially counteract the intended medication (Harkness &
Bratman, 2003). Some case reports have linked Ginseng to
clinical signs of estrogen excess, such as swollen breasts and/or
vaginal bleeding in old women and therefore Ginseng is not
recommended in combination with estrogen medication (Palmer
et al., 1978). Also, as Ginseng appears to decrease the blood
glucose levels, patients that use insulin (or other related drugs)
together with Ginseng should be closely monitored for hypogly-
caemia (Oshima et al., 1985; Sotaniemi et al., 1995). Panax
Ginseng also might increase the effectiveness of warfarin
treatment (Ang-Lee et al., 2001). Long term use of Panax
Ginseng has been associated with hypertension; Siegel (1979)
documented a possible steroidal mechanism of action via the
adrenal cortex or pituitary. A negative effect on sleep quality due
to the Ginseng intake has also been reported (Hallström et al.,
1982).
Looking at the results in the follow-up period, many owners in
the Ginseng group found that their dogs had deteriorated already
4 weeks after finishing the treatment and even more after
8 weeks (Fig. 2), compared to when they were eating the
product. Also, more owners in the Ginseng group were sure they
had been in the ‘real stimulant’ group compared to the control
group owners, and more Ginseng group owners were ready to
restart medication compared to the control group (Fig. 3). If the
deterioration in Fig. 2 had been different between the two active
groups, this could have meant two things; either the combina-
tion product is working but has a short half-life and the owners
in the Ginseng treated group recognized a diminishing effect after
4 weeks that further diminished during the next 4 weeks.
Or, the tested product had not any real effect and the dogs in
the control group were, in fact, enjoying a longer positive effect
of the brewers’ yeast than those in the treatment group.
However, taking into account the other responses the owners
gave, it seems that the first explanation is more logical. Eight
weeks after finishing the treatment, 85% of the owners of the
Ginseng group were right in guessing whether they had been in
the treatment or control group, 100% would probably restart
treatment and 73% felt their dogs had deteriorated after finishing
the treatment. Interestingly, the respective numbers were
significantly smaller for the control group. This indicates
strongly that the owners from the Ginseng group considered
that the treatment had been effective, whereas this was not
recognized by the owners in the control group, also clearly
suggesting that the treatment with Gerivet was more effective
compared with the brewers’ yeast only. Also, it indicates that
Panax Ginseng as a treatment for geriatric clinical signs only has
a short half-life, as typical geriatric behaviour started reappear-
ing soon after the discontinuation of the treatment.
In conclusion, Ginseng plus yeast was shown to be superior to
only yeast and to the external nontreated group in improving the
quality of life of the geriatric dogs. Panax Ginseng probably has
more impact on mental issues whereas the brewers’ yeast has
more impact on the physical performance of the geriatric dog.

After cessation of Ginseng during the 2-month follow-up, the
owners could appreciate the positive effects even more clearly.
This indicates that Panax Ginseng used together with the
brewers’ yeast has shown a stimulating effect on dogs that start
to show clinical signs of old age. It is still not clear if Panax
Ginseng would have had a similar effect without being linked to
the brewers’ yeast; so it would be interesting to see the effects of
Panax Ginseng, compared with a real placebo in a randomized
trial. However, the Panax Ginseng markedly added to the mental
stimulating effect, compared to giving the brewers’ yeast only.
Also, as effect seems to taper off quite rapidly after discontinuing
the treatment, this might lead to owners wanting to go on with
feeding the product for several years and, therefore, studies
looking at long time feeding effects are needed.
ACKNOWLEDGMENTS
We thank all the veterinary students who put in time and effort
to help us with the practical management of the trial and
acquisition of the data. Further, we thank the Finnish medical
company Vetcare Ltd. that provided the products and supported
the study but had no other role in any part of the study and were
not asked permission to submit the manuscript for publication.
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