THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 00, Number 00, 2017, pp. 1–8

ª Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2016.0250

ORIGINAL ARTICLE

Efficacy of Combined Treatment with Acupuncture

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and Bee Venom Acupuncture As an Adjunctive

Treatment for Parkinson’s Disease
Seung-Yeon Cho, KMD, PhD,1,2,* Young-Eun Lee, KMD, MS,1,2,* Kyeong-Hee Doo, KMD, MS,1,2
Ji-Hyun Lee, KMD, MS,1,2 Woo-Sang Jung, KMD, PhD,1 Sang-Kwan Moon, KMD, PhD,1
Jung-Mi Park, KMD, PhD,1,2 Chang-Nam Ko, KMD, PhD,1,2 Ho Kim,3 Hak Young Rhee, MD, PhD,4
Hi-Joon Park, KMD, PhD,5 and Seong-Uk Park, KMD, PhD1,2

Abstract
Objective: The aim of this study was to evaluate the efficacy of acupuncture and bee venom acupuncture
(BVA) for idiopathic Parkinson’s disease (IPD) through a sham-controlled trial. We also investigated whether
there is a sustained therapeutic effect by completing follow-up assessments after treatment completion.
Design: A single center, double-blind, three-armed randomized controlled trial.
Settings/Location: This study was performed at a university hospital in Seoul, Republic of Korea.
Subjects: Seventy-three (73) patients with IPD were the subjects. They were randomly assigned to the active
treatment group, sham treatment group, or conventional treatment group.
Interventions: The active treatment group received acupuncture and BVA and the sham group received sham
acupuncture and normal saline injections, twice a week for 12 weeks. The conventional treatment group
maintained anti-parkinsonian drugs without additional intervention.
Outcome measures: The Unified Parkinson’s Disease Rating Scale (UPDRS) part II and part III score,
postural instability and gait disturbance (PIGD) score, gait speed and number, Parkinson’s Disease Quality of
Life Questionnaire, Beck Depression Inventory, and postural stability at baseline and at 12, 16, and 20 weeks.
Results: Sixty-three (63) patients provided a complete data of assessments, including a final follow-up. After
12 weeks of treatment, a significant difference was observed between the active treatment group and the
conventional treatment group. After the end of the treatment, the treatment effects were maintained significantly
in the active treatment group only.
Conclusions: It is suggested that the combined treatment of acupuncture and BVA might be safe and useful
adjunctive treatment for patients with IPD.

Keywords: Parkinson’s disease, acupuncture, bee venom acupuncture

1
Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
2
Stroke and Neurological Disorders Center, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
3
Department of Epidemiology and Biostatistics, Graduate School of Public Health and Institute of Health and Environment,
Seoul University, Seoul, Republic of Korea.
4
Department of Neurology, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University,
Seoul, Republic of Korea.
5
Integrative Parkinson’s Disease Research Group, Acupuncture and Meridian Science Research Center, Kyung Hee
University, Seoul, Republic of Korea.
*These two authors contributed equally to this work.

1
 2 CHO ET AL.
Introduction
P arkinson’s disease (PD) is the second most common
progressive neurodegenerative disorder worldwide and
is characterized by resting tremors, rigidity, bradykinesia,
and postural instability.1 Currently, the standard treatment
for PD is dopamine replacement with drugs such as l-3,4-
dihydroxyphenylalanine (l-DOPA) to relieve motor symp-
toms.2 However, this treatment does not definitively delay the
progression of PD; therefore, due to l-DOPA-induced motor
complications, a large number of patients worldwide have
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started using complementary and alternative medicines (CAM)
in addition to the standard treatment. It is reported that 25.7%–
76% of patients with PD use one or more forms of CAM, and
acupuncture is the most commonly used therapy.3–7
Various acupuncture techniques, such as manual acupunc-
ture, electroacupuncture, or scalp acupuncture, have been used
to treat patients with PD. Several clinical studies have been
conducted to assess the effectiveness; however, the effective-
ness of acupuncture for PD is still debatable because of some
limitations of the study, including small sample size or un-
controlled design.3,8–11 Therefore, rigorous trials are warranted.
Recently, bee venom has begun to draw increasing atten-
tion for the treatment of PD. Bee venom has been found to
have anti-inflammatory effects and exerts protective effects
on dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine toxicity.12,13 In our previous study, both
acupuncture and bee venom acupuncture (BVA) showed
promising results as adjunctive therapies for idiopathic Par-
kinson’s disease (IPD).14 Patients with IPD were randomly
assigned to the acupuncture group, BVA group, or the control
group. After treatment for 8 weeks, the BVA group showed
significant improvement on the Unified Parkinson’s Disease
Rating Scale (UPDRS, total score, as well as part II and part
III individually), the Berg Balance Scale, and the 30-m
walking time. In the acupuncture group, UPDRS (part III and
total scores) and the Beck Depression Inventory (BDI) showed
significant improvement. In contrast, the control group showed
no significant difference in any outcome.
Another previous study was conducted to examine the ef-
fectiveness and safety of combined treatment with acupuncture
and BVA.15 Patients with IPD were treated with conventional
treatment for 12 weeks and then they received additional treat-
ment using acupuncture and BVA for 12 weeks along with the
conventional treatment. As a result, the combined treatment with
acupuncture and BVA resulted in significant improvements in
gait speed, Parkinson’s Disease Quality of Life Questionnaire
(PDQL), UPDRS part II (activities of daily living), UPDRS part
III (motor), and combined UPDRS part II + III scores compared
to their postconventional treatment assessments.
Based on these pilot studies, the authors aimed to identify
the efficacy and safety of a combined treatment using acu-
puncture and BVA for IPD through a double-blinded ran-
domized controlled trial in this study. In addition, the
authors investigated the duration of the effects by com-
pleting follow-up assessments at the end of the treatment.
Materials and Methods
Subjects
The study was performed in accordance with the ethical
standards of the Helsinki Declaration. The protocol was
approved by the Institutional Review Board of the university
hospital (KHNMC-OH-IRB-2012-01-013). This study was
conducted between October 2012 and November 2014 at
Kyung Hee University Hospital at Gangdong (Seoul, Kor-
ea). Subjects were recruited through the website and bulletin
boards. Interested subjects contacted the study coordinator,
and informed consent was obtained from all participants
after a full description of the study.
Inclusion criteria
 Patients with IPD who have been on a stable dose of
antiparkinsonian medication for at least 1 month
 Hoehn and Yahr scale I–IV

More than one point in two or more items (tremor,
rigidity, postural instability, and bradykinesia) in the
UPDRS part III
 Mini-Mental State Examination-Korean version score
greater than 24 points (out of 30)
 Consent to the study after full description.
Exclusion criteria
 Severe psychiatric or organic brain disorders other than
PD, previous or current
 Secondary parkinsonism due to medication, cerebro-
vascular disease, tumor, infection, etc.
 Atypical Parkinsonism or Parkinson plus syndrome
 Somatic disease
 Alcohol or narcotic abuse
 Expecting a baby
 Determined to be inappropriate for participation by the
investigator.
Dropout criteria

Skipped more than 8 of the total 24 treatment sessions
in the study or control group
 Not able to continue the study because of serious ad-
verse events or aggravation of the condition
 Withdrawal of the consent
 Impossible to complete the scheduled study as planned
by the judgment of the principal investigator.
Randomization and masking
This study was a double-blind (subject and assessor),
three-armed randomized controlled clinical trial. After
consent was obtained, participants were randomly assigned
to one of three groups: the active treatment group, the sham
treatment group, or the conventional treatment group in a
ratio of 2:2:1 using a sealed envelope method by a re-
searcher not involved in the assessments and interventions.
All assessments and statistical analyses were completed by
researchers who were masked to the allocation. Participants
were masked, but the physician could not be masked.
Preparation of bee venom
One milligram of dried bee venom powder (Yumil Farm,
Hwasun, Korea) was diluted in 20 mL of normal saline and
filtered through a 0.22-mm filter at the Traditional Korean
Medical Pharmacy in Kyung Hee University Hospital at
Gangdong.
 ACUPUNCTURE AND BEE VENOM ACUPUNCTURE FOR PD
Procedures
After randomization, all participants completed baseline
clinical assessments. After baseline assessments were com-
pleted, the active and the sham treatment groups received
each intervention twice a week for 12 weeks, and the con-
ventional treatment group maintained antiparkinsonian drugs
without additional intervention. All interventions were per-
formed by one doctor of Korean Medicine with more than 15
years of experience.
In the active treatment group, subjects received acu-
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puncture and BVA twice a week for 12 weeks at 10 acu-
puncture points (bilateral GB20, LI11, GB34, ST36, and
LR3), which were selected based on previous studies.14,15
For skin testing for venom allergy, an injection of 0.1 mL of
bee venom diluted in normal saline was injected into the
LI11 point before the first session. Production of a wheal
larger than 5 mm, a rash greater than 11 mm in diameter, or
severe itching at the site within 15–20 min was considered a
venom allergy. After skin testing, 0.1 mL of diluted bee ve-
nom was injected into the points listed above using a short
needle syringe (30 G · 8 mm; Becton, Dickinson and Com-
pany, Franklin Lakes, NJ). Then, sterile, disposable stainless
steel acupuncture needles (diameter = 0.25 mm, length =
30 mm, DB106 Spring Handle; Dongbang Acupuncture,
Inc., Boryeong, Chungnam, Korea) were inserted in the same
points at a depth of 1.0–1.5 cm and rotated at 2 Hz for 10 sec
to achieve de qi, the sensation felt by the subject when the
acupuncture needle is at the appropriate position for clinical
efficacy. The position was maintained for 15 min.
In the sham treatment group, subjects received a normal
saline injection and sham acupuncture twice a week for 12
weeks at 10 sham acupoints (inferior from GB20 5 cm, lateral
from LI10 2 cm, inferior from GB34 5 cm, posterior from SP9
2 cm, and superior from LR2 1 cm on both sides). For the skin
test to remain a blind test, 0.1 mL of normal saline was in-
jected at LI11. After skin testing, 0.1 mL of normal saline was
injected into the 10 sham acupuncture points using the same
syringes, and then shallow minimal acupuncture stimulation
was performed at the same points using the same acupuncture
needles for 15 min without de qi.
The initial assessments were repeated after 12 weeks in
all groups. In the active and sham treatment groups, follow-
up assessments were performed at 16 and 20 weeks. All
assessments were performed in the medication ‘‘on’’ state at
each visit by the same researcher.
Outcome measures
The primary outcome measure was the UPDRS part II +
III score. The secondary outcome measures were the
UPDRS part II and part III scores, separately, postural in-
stability and gait disturbance (PIGD) score, PDQL, BDI,
postural stability, 20-m walking time, and number of steps
to walk 20 m. PIGD score was defined as sum of walking,
freezing, and falling scores of UPDRS part II and gait and
postural stability scores of UPDRS part III (UPDRS score
No. 13 + 14 + 15 + 29 + 30). Postural stability, maximum
excursion, and directional control were assessed with com-
puterized dynamic posturography using the Balance Mas-
ter System (NeuroCom, San Carlos, CA). Each assessment
was done by the same researcher.
3
Safety evaluation
The subjects were encouraged to report all adverse events
every time they visited the study center during the study
period. In addition, changes in any prescriptions during the
study period were recorded.
Statistical analyses
The trial aimed to detect a difference in UPDRS part II +
III score among three groups. Statistical significance of
baseline demographics and clinical characteristics was cal-
culated by one-way analysis of variance for continuous
variables and by a Chi-square test for categorical variables.
Differences of the outcomes from baseline to 12, 16, and 20
weeks in each group were estimated using the paired t test,
which can take repeated measures into consideration.16 The
three groups were compared using the adjusted mean dif-
ference (least square mean difference) derived from gener-
alized linear model17 with confounders (age, sex, duration
of disease, initial diagnosis, age, Hoehn and Yahr stage, and
baseline outcome), and the authors assumed that the distri-
bution of response variables is normal because their out-
come is continuous and unbounded.18
Furthermore, the authors also longitudinally assessed the
differences between the active treatment group and the sham
treatment group in this approach on the basis of the com-
plete data using generalized estimating equation (GEE)
model.19 The authors compared information criteria of the
GEE model quasi-likelihood under the independence model
criterion (QIC) to select an appropriate correlation struc-
ture20 and used the autoregressive correlation with one de-
gree of freedom, which had the lowest QIC statistics. Based
on them, the authors estimated the adjusted mean (least
square mean) and adjusted mean differences of the two
treatments with confounders (age, sex, duration of disease,
initial diagnosis age, Hoehn and Yahr stage, and baseline
outcome) and meaningful interactions ( p-value <0.10) be-
tween confounder and treatment of each model of outcomes.
Paired t test was performed using R software version 3.0.2,
and all other statistical analyses were performed with SAS
9.1.4 for Windows and SPSS 18 for Windows.
Results
Between October 2012 and November 2014, a total of
319 patients were screened for eligibility; 73 eligible pa-
tients were randomly assigned to the active treatment group
(n = 29), the sham treatment group (n = 29), or the conven-
tional treatment group (n = 15). Four patients in the active
treatment group and five in the sham treatment group
dropped out of the study during the first 12 weeks due to a
withdrawal of consent. At week 16, one patient in the active
treatment group did not visit the hospital and was removed
from the study. A total of 63 patients provided completed
data on the outcome measures, including a final follow-up
(Fig. 1). There were no significant differences between the
baseline characteristics among three groups (Table 1).
After 12 weeks of treatment, the active treatment group
and the sham treatment group showed significant improve-
ment from baseline. The UPDRS part II + III, part II, and
part III scores separately, number of steps to walk 20 m, and
PDQL significantly improved in both the active and the
 4 CHO ET AL.
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FIG. 1. Flowchart of the
study subjects. Randomized,
double-blind, three-armed
placebo-controlled study.
Participants were randomly
assigned to the active treat-
ment group, sham treatment
group, or conventional treat-
ment group.
sham treatment groups, and the active treatment group
showed significant change in the PIGD score. There was no
significant change from baseline in the conventional treat-
ment group in all outcomes. Comparing between the groups
at 12 weeks, the active treatment group showed significant
differences in the UPDRS part II + III, part II, and part III
scores and PIGD score after adjustment for covariates
compared with the conventional treatment group, but there
were no significant differences compared with the sham
treatment group (Table 2).
After the end of the treatment, the active treatment group
showed significant lasting effects in the UPDRS part II + III,
part II, and part III scores, PIGD score, number of steps to
walk 20 m, PDQL, and BDI. The sham treatment group
showed significant lasting effects in the UPDRS part II
scores, 20-m walking time, and number of steps to walk
20 m. In the between-group analyses at 20 weeks post-
treatment, the UPDRS part II + III, part II, and part III
scores and 20-m walking time showed significant differ-
ences between both groups (Table 3; Fig. 2).
Any adverse events at any visit during the 24 sessions
were monitored. No serious adverse events were noted
during the study period. Some patients reported mild pain or
slight bleeding after acupuncture treatments and mild itch-
iness or mild swelling after BVA.
Discussion
The authors found that a combined treatment of acu-
puncture and BVA for 12 weeks was more effective in
improving activities of daily living, motor symptoms, and
PIGD score compared to a conventional treatment. The
combined treatment also significantly improved gait number
and PDQL compared to the baseline assessment. In addition,
these improvements were maintained for 8 weeks after the
end of the treatment. There were no serious adverse events
due to the treatment. These results indicate the safety and
usefulness of the combined treatment of acupuncture and
BVA for patients with IPD as an adjunctive treatment.
After 12 weeks of treatment, the sham treatment group
also showed significant changes compared to baseline, and
there were no significant differences between the active and
sham treatment groups. It is well known that neural path-
ways related to positive anticipation involve dopaminergic
pathways, and a prominent placebo effect in PD has been
confirmed through extensive clinical studies.21,22 It is reported
that up to 50% of patients with PD experience placebo effects.
Several studies have investigated the mechanism of the pla-
cebo effect in PD, and it is known to be mediated through the
activation of the damaged nigrostriatal dopamine system,
which leads to the release of dopamine in the striatum.23 The
 ACUPUNCTURE AND BEE VENOM ACUPUNCTURE FOR PD 5

Table 1. Baseline Demographics and Clinical Characteristics

Active (n = 24) Sham (n = 24) Convention (n = 15) p-Value
Age (years) 64.42 (8.24) 61.33 (8.20) 64.07 (6.33) 0.351
Sex (male) 14 (58%) 8 (33%) 10 (67%) 0.083
Duration of disease (years) 5.08 (3.68) 5.92 (4.18) 4.53 (3.25) 0.519
Initial diagnosis age (years) 59.33 (8.76) 55.38 (8.85) 59.40 (7.51) 0.206
Hoehn and Yahr stage 0.711
1 5 (21%) 8 (34%) 4 (27%)
1.5 5 (21%) 3 (12%) 5 (33%)
2 5 (21%) 3 (12%) 2 (13%)
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2.5 1 (4%) 4 (17%) 1 (7%)

3 5 (42%) 4 (33%) 3 (25%)
4 3 (12%) 2 (8%) 0 (0%)
UPDRS subscore
Part II 13.50 (6.21) 15.75 (5.69) 13.73 (4.13) 0.333
Part III 15.79 (5.51) 16.75 (5.10) 16.27 (3.92) 0.804
Part II + III 29.29 (11.00) 32.42 (9.86) 29.93 (5.51) 0.501
PIGD 5.67 (2.68) 6.33 (3.28) 5.80 (2.37) 0.704
Gait speed (sec) 22.92 (11.52) 21.75 (5.30) 20.73 (3.75) 0.705
Gait number (steps) 39.79 (5.67) 43.50 (10.68) 39.80 (8.41) 0.253
PDQL 133.92 (25.38) 130.08 (16.98) 123.67 (23.30) 0.373
BDI 15.04 (8.41) 16.79 (6.83) 16.07 (12.15) 0.793
MXE 61.87 (17.54) 62.60 (13.86) 61.66 (15.90) 0.980
DCL 76.32 (12.23) 74.47 (11.52) 77.85 (15.81) 0.720
Data are mean (SD) or number (%).
UPDRS, Unified Parkinson’s Disease Rating Scale; Part II, activities of daily living; Part III, motor examination; PIGD, postural
instability and gait disturbance. UPDRS score No. 13 + 14 + 15 + 29 + 30 (walking, freezing, and falling scores of UPDRS part II + gait and
postural stability scores of UPDRS part III); gait speed, 20-meter walking time (sec); gait number, number of steps to walk 20 m; PDQL,
Parkinson’s Disease Quality of Life Questionnaire; BDI, Beck Depression Inventory; MXE, maximum excursion; DCL, directional control;
SD, standard deviation.

dopaminergic projection to the nucleus accumbens is also
considered susceptible to the placebo effect in PD through the
reward circuitry.22 In addition, physical placebo is considered
to be even more powerful than oral placebo.22,24 Based on
this, it is possible that the sham treatment (sham acupuncture
and normal saline injection) showed powerful placebo effect
in this study.
However, the authors did find significant differences
between the groups concerning the maintenance of the
therapeutic effect. In the active treatment group, the im-
provement of the UPDRS part II + III, part II, and part III
scores, PIGD score, number of steps to walk 20 m, PDQL,
and BDI lasted for 8 weeks after the end of intervention.
While the treatment effect was prolonged in participants
within the active treatment group, the symptoms of the sham
treatment group returned toward the state of baseline. There
were significant differences in the UPDRS part II + III, part
II, and part III scores and 20-m walking time between the
groups at the 20-week postintervention follow-up. These
differences in the long-term effect suggest that the combined

Table 2. Changes of Clinical Outcomes in Each Group and Group Differences

of the Outcomes from Baseline to Twelve Weeks
Convention Active— Active—
Active (n = 24) Sham (n = 24) (n = 15) shama p-Value conventiona p-Value
UPDRS II + III 4.52 (4.98)* 3.83 (6.55)* -0.40 (3.83) -1.161 0.444 -5.350 0.001
UPDRS II 2.84 (3.17)* 2.17 (3.60)* 0.07 (2.05) -0.953 0.257 -2.914 0.001
UPDRS III 1.68 (2.48)* 1.67 (3.17)* -0.40 (2.85) -0.213 0.793 -2.349 0.008
PIGD 0.96 (1.74)* 0.63 (1.53) -0.20 (1.70) -0.481 0.244 -1.621 0.001
Gait speed 2.72 (8.53) 1.13 (2.97) -0.53 (2.95) -0.828 0.305 -1.776 0.051
Gait number 1.40 (3.39)* 2.67 (5.21)* 0.13 (3.76) -0.286 0.769 -1.737 0.115
PDQL -12.24 (11.22)* -10.04 (18.32)* -15.27 (13.48) 2.670 0.446 2.506 0.968
BDI 0.60 (7.82) 2.71 (8.57) 2.47 (5.69) 2.417 0.250 1.179 0.613
MXE -0.68 (10.22) -0.12 (12.37) -4.03 (9.00) 0.622 0.823 -1.823 0.553
DCL -1.56 (6.18) 1.79 (11.84) 1.32 (9.04) 4.133 0.095 3.934 0.150
Data are mean (SD) or number.
*p < 0.05 versus baseline by paired t test.
a
The adjusted difference (least square mean) between two groups derived by generalized linear model (GLM).
 6 CHO ET AL.

Table 3. Adjusted Difference of Clinical Outcomes in the Active Treatment Group

and the Sham Treatment Group from Twelve to Twenty Weeks
Active treatment Sham treatment Between-group Difference
group group in mean Change from baseline p-Value
UPDRS II + III
12 weeks 25.720* 27.088* -1.368 0.324
16 weeks 24.684* 27.254* -2.570 0.090
20 weeks 23.443* 28.338 -4.895 0.010
UPDRS II
12 weeks 11.336* 12.371* -1.035 0.183
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16 weeks 10.803* 12.413* -1.610 0.038

20 weeks 9.989* 12.496* -2.507 0.012
UPDRS III
12 weeks 14.369* 14.739* -0.370 0.632
16 weeks 13.867* 14.781 -0.913 0.360
20 weeks 13.437* 15.697 -2.260 0.037
PIGD
12 weeks 4.829* 5.423 -0.595 0.133
16 weeks 4.439* 5.423* -0.984 0.003a
20 weeks 4.429* 5.215 -0.785 0.112
Gait speed
12 weeks 20.055 21.129 -1.074 0.090
16 weeks 19.865 20.837* -0.972 0.144
20 weeks 19.403 21.129* -1.726 0.020
Gait number
12 weeks 39.726* 39.571* 0.154 0.870
16 weeks 38.852* 39.030* -0.178 0.842
20 weeks 38.868* 39.530* -0.662 0.449
PDQL
12 weeks 145.080* 143.450* 1.630 0.662
16 weeks 148.630* 141.660 6.968 0.095
20 weeks 148.750* 141.700 7.048 0.135
BDI
12 weeks 15.344 12.668 2.676 0.193
16 weeks 12.282* 11.543* 0.739 0.689
20 weeks 11.697* 13.252 -1.554 0.465
MXE
12 weeks 63.650 62.351 1.299 0.627
16 weeks 65.725 65.109 0.616 0.768
20 weeks 68.651* 67.066* 1.585 0.494
DCL
12 weeks 77.890 72.881 5.009 0.012
16 weeks 77.821 75.063 2.757 0.151
20 weeks 77.755 75.764 1.992 0.229
Data are mean (SD) or number.
*p < 0.05 versus baseline by paired t test.
a
Indicates a statistical difference between the two groups ( p < 0.05). To estimate adjusted difference (least square mean) of the two
groups, generalized estimating equation (GEE) which controls the correlation among observation repeated for three times (12, 16, 20 weeks
each) was used. The between-group difference is difference of adjusted means of the two treatments.

treatment of acupuncture and BVA seems to have actual
therapeutic effects rather than a simple placebo effect. PD is
a progressive neurodegenerative disease and it may be dif-
ficult for patients with moderate-to-severe disease to visit a
clinic to receive acupuncture regularly for a long period of
time. Thus, the lasting effects may be helpful to patients
with regard to long-term management.
Postural instability is one of the most disabling symptoms
in the advanced stages of PD, for it is associated with a loss
of independence and increasing number of falls, and it
contributes to the risk of hip fractures.25 Postural instability
is known to be less responsive to l-DOPA than all other
cardinal features of PD, so alternative approaches are required
to improve impairments in balance and to reduce the risk of
falls. In our previous study, 8 weeks of BVA treatment im-
proved the walking speed and the Berg Balance Scale scores
of participants.14 In this study, gait number and PIGD score
were significantly improved and the effects lasted after the
end of the treatment. Therefore, acupuncture and BVA might
be worth considering as a treatment for postural instability.
How acupuncture improves the symptoms of patients
with PD who are receiving medication is not yet clear.
 ACUPUNCTURE AND BEE VENOM ACUPUNCTURE FOR PD
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Several studies have been carried out to test whether acu-
puncture could increase striatal dopamine levels; however,
there is no evidence that acupuncture has such an effect.26,27
In contrast, a recent experimental study reported that acu-
puncture may improve the motor function of patients
with PD by increasing the dopamine efflux and the turn-
over ratio of dopamine. This suggests that acupuncture-
induced enhancement of synaptic dopamine availability
may play a critical role in motor function improvement.28
An additional study showed that acupuncture and l-DOPA
in a combination can enhance the benefits of l-DOPA
and alleviate the adverse effects, thereby suggesting a
synergic effect between acupuncture and l-DOPA.29 It is
unclear if these mechanisms are associated with our results.
However, if acupuncture and BVA affects PD through a
different mechanism from that of l-DOPA, it could be ex-
pected to show a synergic effect with l-DOPA as an adju-
vant therapy.
In this study, no serious adverse events were observed
and no patients dropped out due to side effects. Therefore,
acupuncture and BVA treatments are considered to be safe
treatment modalities if performed by a skilled physician
using the bee venom allergy test.
In summary, our results suggest that the combined treat-
ment of acupuncture and BVA might be a safe and useful
adjunctive treatment for patients with IPD.
Acknowledgments
This research was supported by Basic Science Research
Program through the National Research Foundation of
Korea (NRF) funded by the Ministry of Education, Science
and Technology (NRF-2011-0021389).
Clinicaltrials.gov, number NCT01970813.
7
FIG. 2. Changes of Unified Par-
kinson’s Disease Rating Scale
part II + III score in each group.
*p < 0.05 versus baseline by paired
t test. {The between-group differ-
ence is difference of adjusted
means of the two treatments. To
estimate adjusted difference (least
square mean) of the two groups,
generalized estimating equation
which controls the correlation
among observation repeated for
three times (12, 16, 20 weeks each)
was used.
Authors’ Contributions
S.-Y.C., drafting of article; Y.-E.L., analysis and writing;
K.-H.D., data collection; J.-H.L., data collection; W.-S.J.,
data analysis; S.-K.M., critical revision; J.-M.P., critical
revision; C.-N.K., critical revision; H.K., data analysis;
H.Y.R., diagnosis of IPD; H.-J.P., conception, design, and
final approval of version to be published; and S.-U.P.,
conception, design, interpretation of data, and final approval
of the version to be published.
Author Disclosure Statement
No competing financial interests exist.
References
1. Jankovic J. Parkinson’s disease: Clinical features and di-
agnosis. J Neurol Neurosurg Psychiatry 2008;79:368–376.
2. Ramaker C, Marinus J, Stiggelbout AM, van Hilten BJ.
Systematic evaluation of rating scales for impairment and
disability in Parkinson’s disease. Mov Disord 2002;17:867–
876.
3. Chen FP, Chang CM, Shiu JH, et al. A clinical study of
integrating acupuncture and Western medicine in treating
patients with Parkinson’s disease. Am J Chin Med 2015;43:
407–423.
4. Ghaffari BD, Kluger B. Mechanisms for alternative treat-
ments in Parkinson’s disease: Acupuncture, tai chi, and
other treatments. Curr Neurol Neurosci Rep 2014;14:451.
5. Rajendran PR, Thompson RE, Reich SG. The use of al-
ternative therapies by patients with Parkinson’s disease.
Neurology 2001;57:790–794.
6. Wang Y, Xie C, Wang WW, et al. Epidemiology of com-
plementary and alternative medicine use in patients with
Parkinson’s disease. J Clin Neurosci 2013;20:1062–1067.
 8 CHO ET AL.
7. Zeng BY, Zhao K. Effect of acupuncture on the motor and
nonmotor symptoms in Parkinson’s disease-a review of
clinical studies. CNS Neurosci Ther 2016;22:333–341.
8. Xiao D. Acupuncture for Parkinson’s disease: A review of
clinical, animal, and functional magnetic resonance imag-
ing studies. J Tradit Chin Med 2015;35:709–717.
9. Lam YC, Kum WF, Durairajan SSK, et al. Efficacy and
safety of acupuncture for idiopathic Parkinson’s disease: A
systematic review. J Altern Complement Med 2008;14:
663–671.
10. Lee MS, Shin BC, Kong JC, Ernst E. Effectiveness of
Downloaded by Tufts University package NERL from online.liebertpub.com at 07/29/17. For personal use only.
acupuncture for Parkinson’s disease: A systematic review.
Mov Disord 2008;23:1505–1515.
11. Kluger BM, Rakowski D, Christian M, et al. Randomized,
controlled trial of acupuncture for fatigue in Parkinson’s
disease. Mov Disord 2016;31:1027–1032.
12. Doo AR, Kim ST, Kim SN, et al. Neuroprotective effects of
bee venom pharmaceutical acupuncture in acute 1-methyl-
4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model
of Parkinson’s disease. Neurol Res 2010;32 Suppl 1:88–91.
13. Kim JI, Yang EJ, Lee MS, et al. Bee venom reduces neu-
roinflammation in the MPTP-induced model of Parkinson’s
disease. Int J Neurosci 2011;121:209–217.
14. Cho SY, Shim SR, Rhee HY, et al. Effectiveness of acu-
puncture and bee venom acupuncture in idiopathic Parkin-
son’s disease. Parkinsonism Relat Disord 2012;18:948–952.
15. Doo KH, Lee JH, Cho SY, et al. A prospective open-label
study of combined treatment for idiopathic Parkinson’s
disease using acupuncture and bee venom acupuncture as
an adjunctive treatment. J Altern Complement Med 2015;
21:598–603.
16. David HA, Gunnink JL. The paired t test under artificial
pairing. Am Stat 1997;51:9–12.
17. McCullagh P. Generalized linear models. Eur J Oper Res
1984;16:285–292.
18. Casella G, Berger RL. Statistical Inference, 2nd Ed.
San Francisco, CA: Cengage Learning, 2002.
19. Zeger SL, Liang KY, Albert PS. Models for longitudinal
data: A generalized estimating equation approach. Bio-
metrics 1988;44:1049–1060.
20. Diggle PJ, Kung Yee L, Heagerty, et al. Analysis of
Longitudinal Data. Oxford: Oxford University Press, 2002.
21. Schultz W. Predictive reward signal of dopamine neurons. J
Neurophysiol 1998;80:1–27.
22. de la Fuente-Fernández R, Schulzer M, Stoessl AJ. The
placebo effect in neurological disorders. Lancet Neurol
2002;1:85–91.
23. de la Fuente-Fernández R, Ruth TJ, Sossi V, et al. Ex-
pectation and dopamine release: Mechanism of the placebo
effect in Parkinson’s disease. Science 2001;293:1164–
1166.
24. Kaptchuk TJ, Goldman P, Stone DA, Stason WB. Do
medical devices have enhanced placebo effects? J Clin
Epidemiol 2000;53:786–792.
25. Kim SD, Allen NE, Canning CG, Fung VSC. Postural in-
stability in patients with Parkinson’s disease. Epidemiol-
ogy, pathophysiology and management. CNS Drugs 2013;
27:97–112.
26. Huang Y, Jiang X, Zhuo Y, Wik G. Complementary acu-
puncture in Parkinson’s disease: A spect study. Int J Neu-
rosci 2010;120:150–154.
27. Jia J, Li B, Sun ZL, et al. Electro-acupuncture stimulation
acts on the basal ganglia output pathway to ameliorate
motor impairment in Parkinsonian model rats. Behav
Neurosci 2010;124:305–310.
28. Kim SN, Doo AR, Park JY, et al. Acupuncture enhances the
synaptic dopamine availability to improve motor function
in a mouse model of Parkinson’s disease. PLoS One 2011;
6:e27566.
29. Kim SN, Doo AR, Park JY, et al. Combined treatment with
acupuncture reduces effective dose and alleviates adverse
effect of L-dopa by normalizing Parkinson’s disease-
induced neurochemical imbalance. Brain Res 2014;1544:
33–44.
Address correspondence to:
Seong-Uk Park, KMD, PhD
Stroke and Neurological Disorders Center
Kyung Hee University Hospital at Gangdong
892 Dongnam-ro, Gangdong-gu
Seoul 05278
Republic of Korea
E-mail: seonguk.kr@gmail.com
Hi-Joon Park, KMD, PhD
Integrative Parkinson’s Disease Research Group
Acupuncture and Meridian Science Research Center
Kyung Hee University
26 Kyungheedae-ro, Dongdaemun-gu
Seoul 02447
Republic of Korea
E-mail: acufind@khu.ac.kr