Journal of Ethnopharmacology 149 (2013) 597599

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep

Ethnopharmacological communication

Effects of red ginseng extract on sleeping behaviors

in human volunteers
Hyun Jeong Han a, Hye Yun Kim a, Jae Joon Choi b, Sun-Young Ahn b, Seong-Hyun Lee c,
Ki-Wan Oh b,n, Seok-Yong Kim c,n
a
College of Medicine and Myongji Hospital, Kwandong University, Gangreung 210-701, Republic of Korea
b
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea
c
College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea

art ic l e i nf o a b s t r a c t

Article history: Ethnopharmacological relevence: The ginseng root has been traditionally used as a sedative in oriental
Received 25 March 2013 countries. However, the condition ginseng abuse syndrome (GAS), dened as hypertension, nervous-
Received in revised form ness, sleeplessness, skin eruption, and morning diarrhea, was coined as a result of a study of people who
1 July 2013
had been using a variety of ginseng preparations. However, we reported that administration of RGE
Accepted 1 July 2013
Available online 16 July 2013
increased rapid eye movement (REM) and non rapid eye movement (NREM) sleep via GABAergic systems
in animals. Therefore, this study was performed to investigate how red ginseng extract (RGE) affects
Keywords: sleeping behaviors in human volunteers.
Red ginseng extract (RGE) Materials and methods: RGE (1500 mg) was orally administered to young male healthy volunteers (from
Human volunteers
15 to 37 years old ages, n 15) three times a day for 7 days. Overnight polysomnographic (PSG) studies
Polysomnographic (PSG)
were performed two times, 1 day before and 7 days after RGE administration. We investigated differences
Sleeping behaviors
Sleep architecture in sleep architecture parameters such as total sleep time (TST), sleep efcacy (SE: total sleep time/time in
bed), proportion of each sleep stage, and wakefulness after sleep onset (WASO) between baseline PSG
and PSG after RGE administration.
Results: Total wake time (TWT) was signicantly reduced (P o0.05) and SE was increased (Po 0.05),
although slow wave sleep stage 1 (N1) was reduced (P o0.01) and non-rapid eye movement (REM) sleep
was increased (Po 0.03) after administration.
Conclusion: From these results, it is presumed that RGE intake would improve the quality of sleep, thus
having benecial effects on sleep disturbed subjects.
& 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Despite the benecial effects of ginseng, the condition ginseng

The ginseng root has been traditionally used as a treatment
material for asthenia, artherosclerosis, hyperglycemia, and relief of
symptoms associated with stress, cancer, senility and aging. As
ginseng is promoted as a tonic capable of invigorating the users in
physical, mental, and sexual aspects, recent consumption of
ginseng has increased every year. According to Traditional Chinese
Medicine, American ginseng (Panax quinquefolis L) is a cool or
yin tonic used to treat hot symptoms such as insomnia, stress,
palpitation, and headache, while Asian (or Korean) ginseng (Panax
ginseng C.A. Meyer) is hot, or yang, and is used to treat cold
diseases (Awang, 1991; Zhang et al., 2004; Azike et al., 2011).
n
Corresponding authors. Tel.: +82 43 261 2851/82 43 261 2827;
fax: +82 43 268 2732.
E-mail addresses: kiwan@chungbuk.ac.kr (K.-W. Oh),
drsykim@chungbuk.ac.kr (S.-Y. Kim).
abuse syndrome (GAS), dened as hypertension, nervousness,
sleeplessness, skin eruption, and morning diarrhea, was coined as
a result of a study of people who had been using a variety of
ginseng preparations for 1 month at least (Siegel, 1979).
However, because there have been some conicting opinions about
the impact of various ginseng preparations on sleep, especially white
and red ginseng, the effects of red ginseng (heat steamed ginseng) on
sleep were studied (Lee et al., 1990, 2012; Mitra et al., 1996). From our
previous experiments, red ginseng extract (RGE) enhanced
pentobarbital-induced sleep, and repeated administration of RGE
increased rapid eye movement (REM) and non rapid eye movement
(NREM) sleep via GABAergic systems in animals (Lee et al., 1990; Cho
et al., 2010). In this study, RGE (1500 mg) was orally administered to
young male healthy volunteers three times per day for 7 days.
Overnight polysomnograms (PSG) were recorded to understand the
differences in sleep parameters after RGE administration during one
night of observation.

0378-8741/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jep.2013.07.005
598 H. Jeong Han et al. / Journal of Ethnopharmacology 149 (2013) 597599

2. Materials and methods previous animal experiment, we found that repeated administration
of RGE for 9 days reduced the number of sleep/wake cycles and
2.1. Preparation of red ginseng extract NREM sleep via GABAAergic systems in rats (Lee et al., 2012). In the
present study, similar results were obtained after a single dosage. -
RGE was kindly provided by the Korea Ginseng Cooperation Waves in REM sleep and NREM sleep were increased respectively,
(Daejeon, Republic of Korea). RGE yielded 4.37% saponins; the and -waves were increased in wakefulness (Ma et al., 2009).
main components of ginsenosides were Rb1 (12.6%), Rb2 (6.2%), Rc Regarding the effects of ginseng on sleep, somewhat contra-
(6.9%), Rd (3.4%), Re (6.4%), Rf (2.1%), Rg1 (15.8%), and Rg3 (1.4%). dictory opinions have emerged. A case study reported that GAS
The identied constituents are well standardized and qualied by symptoms appeared in some people with long term administra-
the Korea Ginseng Cooperation. Others constituents in RGE are tion of ginseng. However, GAS symptoms do not appear from all
starch, sugars, fat, ber, proteins, vitamins, minerals etc. who ginseng consumed (Siegel, 1979). This means that some
people experienced sleep disorder after intakes of ginseng. How-
2.2. Subjects ever, the traditional opinion is a little different. It has been
traditionally accepted that American ginseng can be used to treat
Fifteen healthy subjects were enrolled by the Kwandong Medical insomnia, but Asian ginseng disturbs sleep (Awang, 1991). Accord-
Sleep Center (KMSC) over a period 3 months. The participants were ing to this clinical study, sleep efcacy was signicantly increased.
healthy men aged between 15 and 37 years without sleep problems Other sleep architecture parameters such as REM sleep were
who were recruited from a community-dwelling population. We increased, and total wake time was remarkably reduced. It is
carefully interviewed all potential participants and excluded if they presumed that RGE does not interfere with sleep, but rather
or their bed partners reported any sleep complaints including sleep increases sleep efcacy, although some users may experience side
apnea, snoring or excessive daytime sleepiness. The institutional effects such as insomnia after long term administration Table 1.
review board approved the study, and written informed consent was Two commercial forms of ginseng are available. White ginseng
obtained from the participants. We prescribed RGE 1500 mg three consists of the dried root of ginseng, and red ginseng is prepared by
times a day (t.i.d) according to the approved study protocol. All steaming the fresh, unpeeled root before drying (Ha et al., 2007; Yoon
enrolled subjects were invited to our sleep center to participate in et al., 2010). White ginseng is air-dried, and red ginseng is produced
baseline overnight PSG before taking RGE. They were then instructed by steaming raw ginseng at 98100 1C for 23 h. Red ginseng is
to consecutively intake RGE for 7 days. A follow-up overnight PSG reportedly more pharmacologically active than white ginseng. Such
was conducted. different biological activities between red and white ginseng may
result from the production of different chemical constituents during
2.3. Measurement of sleep behaviors steaming treatment. Ginseng saponins, referred to as ginsenosides,
are believed to have a pharmacologically important role. Several
Overnight PSG data were collected in our sleep center using investigators have reported new ginsenosides from red ginseng that
grassfactor (Cornet, London, UK). Channels included six central are not usually found in raw ginseng (Kim et al., 2000; Lau et al.,
electroencephalograms, bilateral electrooculogram, chin electro-
myogram, thoracic and abdominal respiratory belts, airow sensor, Table 1
nger pulse oximetry, electrocardiogram, body position, and Comparison of sleep architecture indices in RGE (red ginseng extract) adminstered
bilateral piezoelectric sensors to detect leg movements. Data were volunteers (n 15).
evaluated by trained technicians, and sleep stages were assessed
Sleep architecture Control (mean7 SD) RGE (mean7 SD) P value
in 30-s epochs according to standard criteria (Smith and Karacan,
1971; Hoque et al., 2013). Sleep-disordered breathing was mea- Age (years) (1537 years) (1537 years)
sured by the apneahypopnea index (number of apnea plus BMI (kg m  2) 22.9 70.5 22.9 7 0.5 1.0
hypopnea events per hour of sleep) and by prevalent sleep TIB (min) 424 79.8 400 74.2 .06
disordered breathing coded as an apneahypopnea index of 15 TST (min) 341 716.4 369 7 6.8 .05n
N1 (% of TST) 0.09 70.01 0.067 0.01 .01n
or more events per hour (1999). Calculated variables of sleep N2 (% of TST) 0.56 70.02 0.55 7 0.02 .70
fragmentation included arousal index dened as the number of N3 (% of TST) 0.18 70.01 0.22 7 0.02 .51
arousals per hour of sleep and minutes of wake after sleep onset. REM (% of TST) 0.177 0.02 0.18 70.01 .03n
Sleep duration was measured as total sleep time after sleep onset. Total wake time (TWT, min) 85.6 722.8 30.9 7 3.9 .05n
WASO 66.47 19.5 5.4 7 3.5 .10
Latency to onset (min) 19.2 7 9.0 5.4 7 1.5 .12
2.4. Statistics Latency to REM (min) 1417 27.8 100. 7 9.1 .10
Sleep efciency (%) 0.81 70.05 0.92 7 0.01 .05n
Data are presented as means 7SEM. For statistical compari- Sleep maintenance (%) 0.85 70.04 0.94 7 0.01 .10
RERA 9.53 71.7 10.3 7 2.07 .66
sons, the results were analyzed using one-way analysis of variance
AHI 1.197 0.32 1.40 7 0.32 .48
(ANOVA). A P value o0.05 was considered statistically signicant. RDI 2.89 70.54 3.117 0.52 .59
Individual values were compared with Students t-test. Arousal index 12.2 7 1.34 11.2 7 1.22 .41
PLMS index 2.3 71.80 2.8 7 1.83 1.0
LM arousal index 0.18 70.14 0.117 0.06 .75
3. Results and discussion O2 desaturation index 1.147 0.25 1.707 0.43 .12
Epworth sleepiness scale 6.677 0.96 6.6770.96 1.0
Stanford sleepiness scale 2.677 0.13 2.6 7 0.16 1.0
Considering sleep architectures, signicant differences between BDI 4.2 71.01 4.2 7 1.01 1.0
placebo and RGE treated groups were observed in stage 1 proportion
(% of TST) of slow wave sleep (SWS, Po0.01), in REM sleep (% of TST, Abbreviations: BMI body mass index; TIB time in bed; TST total sleep time;
Po0.03), in total wake time (TWT, Po0.05) and in sleep efciency REM rapid eye movement; WASO wake after sleep; RERA respiratory event
related arousals; AHI-apnea hypopnea index; RDI respiratory disturbance index;
(Po0.049). TST was statistically signicant (Po0.05). Stage 1 propor- PLMS index periodic limbs movement during sleep isolated leg movement index;
tion (% of TST) of SWS and TWT was signicantly decreased, but REM BDI beck depression inventory.
sleep and sleep efciency were increased after RGE administration. n
P value was considered statistically signicant. Individual values were
All other sleep architecture parameters remained unchanged. In our compared with Students t-test.
 H. Jeong Han et al. / Journal of Ethnopharmacology 149 (2013) 597599
2003; Sun et al., 2011). Studies showed that red ginseng was
more potent in inducing anxiolyyic effects than white ginseng
(Bhattacharya and Mitra, 1991; Cha et al., 2005; Park et al., 2005).
As RGE rather than white ginseng increased sleep behaviors, new
ingredients should be interested about. We still do not know what
kinds of ginsenosides play on important roles in sleep behaviors. Red
ginseng would have stronger sedative effects than white ginseng from
this study. In conclusion, it is presumed that RGE does not interfere
with sleep, but rather increases sleep efcacy.
Acknowledgement
This work was supported by the 2012 grant from The Korea
Society of Ginseng funded by Korea Ginseng Corporation, and by
Priority Research Centers Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Education,
Science and Technology (2009-0094034).
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