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Sun-Ah Lee
et al.
85
□ 원 저 □
Sleep Medicine and Psychophysiology
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
수면·정신생리 17(2): 85-90
,
2010
Effect of Korean Red Ginseng on Sleep：
A Randomized, Placebo-Controlled Trial
고려 홍삼이 수면의 질에 미치는 영향：무작위 위약-대조군 연구
Sun-Ah Lee,
1
Seung-Gul Kang,
1,2
Heon-Jeong Lee,
1,2
Ki-Young Jung,
2,3
Leen Kim
1,2
이선아
1
·강승걸
1,2
·이헌정
1,2
·정기영
2,3
·김 린
1,2
목 적
：
인삼은 한국을 비롯한 아시아 국가에서 전통적으로 불면증의 치료에 사용되어 왔으며 쥐를 이용한 동물실험에서 수면
을 촉진시키는 효과가 있다는 연구 결과가 있어왔다. 하지만 이러한 효과를 입증할 만한 임상 실험은 거의 이루어지지 않았다.
이에 본 연구에서는 고려 홍삼이 수면에 미치는 영향을 알아보고자 한다.
방 법
：
건강한 성인 남성 20명을 대상으로 하였으며 이들은 무작위로 홍삼군과 위약군에 배정되어 2주간의 실험이 진행되
었다. 홍삼군의 경우 하루 4,500 mg의 홍삼을 섭취하였다. 실험 시작시점과 2주 후인 종료시점에 수면다원검사를 시행하여 두
군간의 변수의 변화를 비교하였다.
결 과
：
총 15명의 대상자, 즉 홍삼군 8명과 위약군 7명이 수면다원검사를 시행 받았으며 홍삼군이 위약군 보다 실험 종료 시
점에서 3단계 수면이 증가한(p=0.087) 반면에 2단계 수면이 감소하는(p=0.071) 경향을 나타냈다.
결 론
：
본 연구 결과는 고려 홍삼이 깊은 잠은 증가시키고 얕은 잠은 감소시키는 경향이 있음을 보여준다. 이는 통계적으로
유의한 결과는 아니지만 홍삼이 수면의 질을 향상시키는 데 효과적임을 짐작하게 한다. 그러나, 보다 많은 대상군과 충분한 홍
삼 용량으로 보다 긴 기간 동안 진행되는 연구를 통해 고려 홍삼의 수면에 대한 효과를 확인할 필요가 있다.
중심 단어
：
고려 홍삼·수면·NRE M·수면다원검사.
INTRODUCTION
Panax ginseng, the herbal root of Panax ginseng C. A.
Meyer and also known as Asian or Korean ginseng, has been
used for thousands of years in Korea as a traditional medi-
cine to promote health and treat illness. Although there are
various forms of ginseng processed differently for use, white
ginseng and red ginseng are used most widely. White ginseng
is air-dried, while red ginseng is produced by steaming and
drying. It has been reported that red ginseng is pharmacolo-
gically more active than white ginseng(Baek et al. 1996). The
different biological activities of red and white ginsengs may
result from production of different chemical constituents dur-
ing the steaming process(Baek et al. 1996). Korean red gin-
seng is known to have broad efficacious effects against hyper-
tension, diabetes, pain and cancer, and to counteract weakness
(Baek et al. 1996).
Ginseng has a complex profile of activity including antio-
xidant, anti-inflammatory, anti-apoptotic and immune-stimu-
latory properties(Xiang et al. 2008). With these properties,
••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••
Received: April 26, 2010 / Revised: August 3, 2010
Accepted: August 12, 2010
This research was supported by a grant from The Korean So
-
ciety of Ginseng.
1
고려대학교 의과대학 정신과학교실
D
epartment of Psychiatry, Korea University College of Medicine,
Seoul, Korea
2
고려대학교 안암병원 수면-각성장애 센터
Sleep-Wake Disorders Center, Korea University Anam Hospital,
Seoul, Korea
3
고려대학교 의과대학 신경과학교실
D
epartment of Neurology, Korea University College of Medicine,
Seoul, Korea
Corresponding author: Leen Kim
,
Department of Psychiatry, Kore
a
University College of Medicine, Anam-dong, Seongbuk-gu, Seoul 136-
705, Korea
Tel: 02) 920 5355, Fax: 02) 927 2836
E-mail: leen54@chol.com
초 록
Effect of Korean Red Ginseng on Sleep
86
ginseng has effects of stabilizing and balancing the whole
physiology. Researchers have found that the active compon-
ents in ginseng include ginsenosides, polysaccharides, pepti-
des, polyacetylenic alcohols, vitamin, minor elements and en-
zymes(Xiang et al. 2008). Ginsenosides or ginseng saponins
are the major active ingredients in ginseng and more than 40
different ginsenosides have been identified(Baek et al. 1996).
The ginsenoside content of ginseng varies depending on the
Panax species, the plant age, the parts of the plant, the preser-
vation method, the season of harvest and the extraction method.
Ginsenosides are found only in Panax species, many of which
exist in very small amounts, and are believed to be responsible
for most of the actions of ginseng. Ginsenosides act through
diverse mechanisms and it is suggested that each ginsenoside
seem to have its own specific tissue-dependent effects(Murphy
and Lee, 2002).
Although many mechanisms and its components remain
unknown, ginseng has long been clinically used for treatment
of insomnia(Xiang et al. 2008). Although the efficacy in
humans is not clearly established, it has been shown in pre-
vious studies that ginseng exerts a stabilizing effect on sleep-
waking disturbances in rats. Rhee et al.(1990) showed that
ginseng can actually normalize the sleep-waking disturbances
caused by sleep deprivation in rats. In freely behaving rats
after continued 1-week intake of Panax ginseng, the amount
of wakefulness and slow wave sleep(SWS) during the 12-h
light period slightly but significantly decreased and increased,
respectively. They concluded that the health-improving ef-
fect of Panax ginseng may be, at least in part, related to its
sleep-modulatory, both sleep-enhancing and sleep-stabilizing,
activity. Lee et al.(1990) reported the amount of wakefulness
and SWS significantly fluctuated during 48h food depriva-
tion and subsequent recovery periods in freely behaving male
rats while such fluctuations were significantly less prominent in
age-matched male rats chronically treated with Panax ginseng.
The purpose of this study was to investigate the effect of
Korean red ginseng on change of sleep architecture in humans.
METHODS
1. Participants
A total of 20 healthy young male volunteers aged 19 to 25
years were studied. They were recruited through on-line and
off-line advertisement. They were selected based on review
of preliminary sleep questionnaires and sleep diaries follow-
ed by an interview with a board-certified psychiatrist. All
subjects had regular sleep and wake habits and had neither
psychiatric disorders nor cognitive problems. For assessment
of subjective sleep quality, the subjects completed Pittsburgh
Sleep Quality Index(PSQI), Athens Insomnia Scale(AIS)
and Epworth Sleepiness Scale(ESS) in addition to sleep ques-
tionnaires and sleep diaries. During 2 weeks of trial, they were
advised to maintain their usual sleep-wake habits and were
instructed to refrain from medications and excessive alcohol.
During this period, 3 of the participants wanted to be dropped
out of the trial and 2 others were excluded being suspected
of a sleep disorder after first polysomnographic recording.
As a result, only 15 participants were included. All volunteers
signed informed consent prior to entering the study.
2. Procedure
The subjects were randomly assigned to red ginseng or
placebo group and were administered red ginseng or placebo
accordingly for 2 weeks. The total daily dose of ginseng was
4,500 mg；1,500 mg were administered 3 times a day. The
polysomnographic recordings were made at baseline and at 2
weeks after. The effects of red ginseng and placebo on sleep
were assessed by comparing the changes in polysomnogra-
phic variables between the two groups. The polysomnographic
recordings were performed using an Embla S7000 and Som-
nologica 4(Medcare, Iceland) system. Electroencephalogra-
phic(EEG) leads, electrooculogram(EOG) leads and chin
electromyogram(EMG) were placed according to standardiz-
ed procedures. Airflow from nasal and oral breathing, chest
and abdominal respiratory effort, sound of breathing and oxy-
gen saturation were measured. Bilateral electromyogram leads
were placed on the anterior tibialis muscle to monitor leg
movements. Electroencephalograms(EEG) were positioned
based on the international 10-20 system. The polysomnogra-
phic recordings were interpreted according to American Aca-
demy of Sleep Medicine manual(Iber 2007).
3. Statistical Analysis
For comparison of demographic variables between the two
groups, the independent t-test was performed using SPSS for
Windows. Inter-group comparisons of changes in polysomno-
graphic variables were assessed by means of repeated measure
analysis of variance(ANOVA). All statistical analyses were
two-tailed, and the level of statistical significance was set at
p<0.05.
RESULTS
A total of 15 subjects, 8 from red ginseng group and 7 from
Sun-Ah Lee
et al.
87
placebo group, were included to undergo polysomnographic
procedures. There were no significant differences between
red ginseng and placebo groups in demographic variables(Ta-
ble 1) except for height(p=0.010), as well as subjective sleep
quality as measured by PSQI(p=1.000), AIS 8(p=0.232),
AIS 5(p=0.232) and ESS(p=0.637). The changes of total
sleep time, sleep latency and sleep efficiency between the red
ginseng and placebo group were not significantly different.
The red ginseng group showed increased stage 3 sleep(p=
0.087) and decreased stage 2 sleep(p=0.071) from the base-
line compared with the placebo group. However, this in-
crease in deep sleep was not statistically significant(Table 2).
Although not statistically significant, the total sleep time de-
creased in red ginseng group.
DISCUSSION
We have found that Korean red ginseng tends to increase
deep sleep and decrease shallow sleep. This result is in line
with the belief that ginseng is effective in sleep and prove
further that it has sleep stabilizing effect. Although efficacy in
animals does not necessarily equate with efficacy in humans,
our result is in line, at least in part, with previous findings
that Korean red ginseng increased total and NREM sleep in
rats(Ma et al. 2008).
The exact mechanism of ginseng is still unknown, but
there has been a previous report that the anxiolytic effects of
ginseng appear to be related to the GABA-benzodiazepine-
chloride channel receptor complex. Park et al.(2005) report-
ed that ginsenosides interact with the ligand-bindings of the
GABAA and GABAB receptors and induce sedative effects
at higher doses and anxiolytic-like effects at lower doses.
Active maintenance of slow wave sleep(SWS) is dependent
on increased GABA release that continuously suppresses ac-
tivity in the various wake-promoting regions of the brain.
Korean red ginseng also has an important role as a mo-
Table 1. Comparison of demo
g
raphic variables between red
g
insen
g
and placebo
g
roups
Variables Red Ginseng
Placebo t p-value
Age (yr) 023.50 (01.20)
023.43 (2.07) 0.083 0.935
Height (cm) 177.75 (04.62)
171.43 (3.26) 3.016 0.010
Weight (kg) 071.11 (10.85)
066.86 (8.28) 0.843 0.414
BMI (kg/m2) 022.46 (02.91)
023.13 (3.20) -0.426 0.677
Neck circumference (cm)
Sitting position 036.01 (01.69)
035.19 (1.66) 0.951 0.359
Supine position 035.53 (01.88)
035.47 (0.99) 0.067 0.947
Waist circumference (cm) 080.91 (06.83)
082.60 (7.00) -0.470 0.645
Data are given as mean (standard deviation). BMI：Body mass index
Table 2. Differences in chan
g
es of polysomno
g
raphy variables between red
g
insen
g
and placebo
g
roup
Red ginseng
Placebo
Variables of polysomnography Baseline 2 weeks
Baseline 2 weeks F P
Time in bed (min) 437.0 (25.3)
421.8 (57.2)
457.5 (17.0)
456.9 (14.5) 2.89 0.113
Total sleep time (min) 406.3 (33.0)
377.8 (55.3)
414.4 (34.4)
432.2 (18.4) 3.63 0.079
S1 sleep stage (%) 17.0 (06.3)
17.9 (08.4)
15.9 (04.1)
14.4 (03.5) 0.70 0.417
S2 sleep stage (%) 44.2 (04.2)
42.9 (03.9)
46.1 (06.8)
48.0 (05.4) 3.88 0.071
S3 sleep stage (%) 6.8 (02.3)
7.3 (02.6)
9.3 (03.3)
8.9 (02.5) 3.44 0.087
S4 sleep stage (%) 11.4 (05.5)
13.2 (06.3)
9.0 (05.7)
8.4 (05.5) 1.87 0.195
REM sleep stage (%) 20.6 (05.5)
19.7 (01.6)
18.8 (07.9)
20.3 (07.7) 0.02 0.886
Wake after sleep onset (min) 17.6 (12.4)
30.2 (28.7)
30.2 (28.7)
14.9 (11.3) 0.10 0.755
Sleep efficiency (%) 93.0 (06.5)
90.0 (09.5)
90.0 (09.5)
90.3 (11.7) 0.12 0.730
Sleep latency (min) 13.2 (18.3)
10.3 (11.0)
12.9 (08.9)
9.8 (03.1) 0.01 0.924
REM latency (min) 88.7 (27.9)
101.6 (42.7)
77.9 (18.3)
94.1 (60.6) 0.27 0.613
Total wake time (min) 30.8 (29.0)
44.0 (43.6)
43.1 (26.6)
24.7 (11.9) 0.09 0.775
Apnea hypopnea index (per hour) 3.9 (03.0)
4.3 (04.0)
1.7 (01.1)
4.3 (05.6) 0.44 0.518
Flow limitation arousalindex (per hour) 0.9 (01.4)
0.5 (00.4)
2.0 (02.5)
1.8 (01.7) 2.71 0.124
Periodic limb movement during sleep (per hour) 5.6 (07.6)
6.2 (09.5)
4.7 (07.7)
1.3 (02.2) 0.70 0.418
Periodic limb movement during waking (per hour) 9.5 (20.8)
9.4 (21.8)
28.9 (23.2)
27.8 (41.5) 1.92 0.189
Total arousal index (per hour) 17.5 (07.0)
17.6 (06.9)
15.8 (03.6)
15.9 (04.2) 0.40 0.539
Data are given as mean (standard deviation)
Effect of Korean Red Ginseng on Sleep
88
dulator to maintain homeostasis of autonomic-endocrine sys-
tems(Kaneko and Nakanishi 2004). Ginseng is also known
as an adaptogen, a substance which helps the body to resist
the adverse influences of physical, chemical and biological
factors, and helps the restoration of homeostasis(Ma et al.
2008). It is generally accepted that HPA axis functions to
ensure the body adaptation and is one of the most important
systems closely related to stress and there are some reports
on inhibitory effects of ginseng on stress-induced increase of
corticosterone level(Ma et al. 2007).
Another possible mechanism is through immune system.
Cytokines, especially interleukin-1β and TNF-α, are well
characterized as being involved in NREM sleep regulation
(Kryger et al. 2005). The homeostatic influence is believed
to be due to some structure or substance that accumulates
‘need to sleep’ during prolonged wakefulness. When these
substances reach a critical level, our metabolic process re-
sponds by slowing down wake-promoting neuronal activities,
thus lowering the rate of production until the substances return
to basal levels. This homeostatic process is the primary factor
necessary to initiate sleep. The substances believed to be in-
volved in sleep initiation include adenosine, gamma-amino-
butyric acid(GABA), glycine, prostaglandin D2(PGD2), in-
terleukin-1β and tumor necrosis factor(TNF)(Datta and
Maclean 2007). Non-rapid eye movement(NREM) and REM
sleep probably have separate homeostatic systems. NREM
sleep is typically replenished first and it is NREM sleep to
which above-mentioned sleep-promoting substances are spe-
cifically related. Administration of either IL-1β or TNF-α
promotes NREM sleep. The pathways in which IL-1 and TNF
promote sleep include several steps. Interleukin-1 and TNF
stimulate nuclear factor kappa B(NFκB). Nuclear factor
kappa B, in turn, induces nitric oxide synthase(NOS) to pro-
duce nitric oxide. Nitric oxide(NO) production in basal fore-
brain is needed to produce sleep. Previous research had found
that ginseng stimulates NO synthesis through promoting NOS
production and thus might have sleep-producing effect(Gillis
1997). Since the process by which IL-1 and TNF induce sleep
consists of multiple steps, the sleep-promoting effect of gin-
seng through NO stimulation might involve direct action on
NOS or indirect actions affecting IL-1 and TNF production.
As our current knowledge of the molecular steps by which
IL-1 and TNF induce sleep is still limited, the process by
which ginseng is involved in sleep regulation and immune
function is remained to be explored. Further studies examin-
ing effect of ginseng administration on changes of levels of
IL-1 and TNF might be a one way to explore this.
Some controversial reports indicated that sleep disorders
were most commonly experienced adverse events of ginseng
(Ma et al. 2008). This might be due to uncontrolled open
research designs, so the evidence from clinical trials did not
evaluate well the ginseng efficacy, and even made contradic-
tory conclusions. Besides, the actions of ginseng are less evi-
dent in non-stressed human subjects(Gillis 1997). It should
be noted that herbal medicine on pathological states are usu-
ally better, but are not obvious or can be even adverse on phys-
iological states. Further, the effect on chronic adminis-tration
might be different from that of acute one(Kitaoka et al. 2009).
The efficacy of red ginseng in human sleep is not clearly
established. Our study is of significance in that it is one of
the first clinical trials to explore the effect of ginseng on sleep.
However, there are some limitations to our study. The sample
size was too small and the trial was too short of duration. The
dosage of ginseng might have been inadequate also. The
recommended daily dose of ginseng in human beings is 1.5
to 3.0 g/day(Jin et al. 2007). However, in previous studies
with rats, the dosage of ginseng varied greatly ranging from
as low as 10 mg/kg/day to as high as 500 mg/kg/day(Ma et
al. 2008；Jin et al. 2007；Min et al. 2003；Kim et al. 2009).
In a clinical trial, Heo et al.(2008) have used ginseng up to
9.0 g/day. From this, it might be inferred that the dosage we
used in this study was too low to reach statistically signifi-
cant results but only showed a trend toward increased deep
sleep. Quite contrary to what is expected, the total sleep time
decreased in red ginseng group. This decrease might be due
to improved quality of sleep but it should be confirmed with
further studies with larger sample size.
In conclusion, the result of current study suggests that Ko-
rean red ginseng tends to increase deep sleep and decrease
shallow sleep. Further studies, well-designed clinical trials
with higher ginseng dosage, larger sample size and longer trial
duration should be conducted to confirm the sleep stabilizing
and balancing effects of Korean red ginseng.
R
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Effect of Korean Red Ginseng on Sleep
90
■
ABSTRACT
Effect of Korean Red Ginseng on Sleep：
A Randomized, Placebo-Controlled Trial
Sun-Ah Lee,
1
Seung-Gul Kang,
1,2
Heon-Jeong Lee,
1,2
Ki-Young Jung,
2,3
Leen Kim
1,2
1Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
2Sleep-Wake Disorders Center, Korea University Anam Hospital, Seoul, Korea
3Department of Neurology, Korea University College of Medicine, Seoul, Korea
Objectives: Ginseng has a long history of being used in insomnia treatment and there is some evidence from animal studies of its
sleep-enhancing property. From this, it can be assumed that ginseng has sleep-promoting effect in humans. The purpose of this
study was to investigate the effect of Korean red ginseng on change of sleep architecture in humans.
Methods: A total of 20 healthy young males with regular sleep and wake habits and without any psychiatric nor cognitive problems
were selected based on review of sleep questionnaires and sleep diaries they completed followed by an interview with a board-certified
psychiatrist. The subjects were randomly assigned to red ginseng or placebo for 2 weeks of trial. The total daily dose of ginseng was
4,500 mg. The polysomnographic recordings were made at baseline and at 2 weeks after. The effects of red ginseng and placebo
on sleep were assessed by comparing the changes in polysomnographic variables between the two groups.
Results: A total of 15 subjects, 8 from red ginseng group and 7 from placebo group, were included to undergo polysomnographic
procedures. The red ginseng group showed tendencies to increase stage 3 sleep (
p
=0.087) and to decrease stage 2 sleep (
p
=0.071)
from the baseline compared with the placebo group.
Conclusion: Korean red ginseng tends to increase deep sleep and decrease shallow sleep. Our result is in line, at least in part, with
previous findings that Korean red ginseng increased total and NREM sleep in rats. Further studies with higher ginseng dosage,
larger sample size and longer trial duration should be conducted to confirm the sleep stabilizing and balancing effects of Korean
red ginseng.
Sleep Medicine and Psychophysiology 2010；17(2)：85-90
Key words: Korean red ginseng
·
Sleep
·
NREM
·
Polysomnography.
