Research Article: Acupuncture For Functional Dyspepsia: A Single Blinded, Randomized, Controlled Trial
Research Article: Acupuncture For Functional Dyspepsia: A Single Blinded, Randomized, Controlled Trial
Research Article
Acupuncture for Functional Dyspepsia: A Single Blinded,
Randomized, Controlled Trial
Yulian Jin,1,2 Qing Zhao,2 Kehua Zhou,3 Xianghong Jing,4 Xiaochun Yu,4 Jiliang Fang,2
Zhishun Liu,1 and Bing Zhu4
1
Department of Acupuncture and Moxibustion, Guang An Men Hospital, China Academy of Chinese Medical Sciences,
No. 5 Beixiange Street, Xicheng District, Beijing 100053, China
2
Department of Radiology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
3
Department of Health Care Studies, Daemen College, Amherst, NY 14226, USA
4
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China
Correspondence should be addressed to Jiliang Fang; [email protected] and Zhishun Liu; [email protected]
Received 11 August 2014; Revised 18 September 2014; Accepted 3 October 2014
Academic Editor: Jian Kong
Copyright 2015 Yulian Jin et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
In order to investigate the therapeutic potential of acupuncture on patients with functional dyspepsia (FD), patients were
randomized to receive acupuncture at classic acupoints with manipulations (treatment group) versus acupuncture at nonacupoints
without manipulation (control group) once every other day, three times a week, for one month and were followed up for three
months. The primary outcomes included dyspeptic symptoms, quality of life, and mental status. The secondary outcomes included
the fasting serum gastrin concentration, and frequency and propagation velocity of gastric slow waves. Sixty patients with FD
were included, among whom, four dropped out. After one months treatment, patients with FD showed significant improvements
in primary (in both groups) and secondary (in the eight patients of the treatment group) outcomes as compared with baseline
( = 0.0078 to <0.0001); treatment group has better outcomes in all primary outcome measures ( < 0.0001 except for SDS
( = 0.0005)). Improvements on dyspeptic symptoms persist during follow-up (better in the treatment group). Acupuncture with
manual manipulation had better effects on improving dyspeptic symptoms, mental status, and quality of life in patients with FD.
These effects may be related to the increased frequency and propagation speed of gastric slow waves and serum gastrin secretion.
1. Introduction
Functional dyspepsia (FD) is dyspepsia without evidence
of an organic disease that is likely to explain the cause
[1]. Based on the Rome III criteria, symptoms of FD may
include bloating, belching, early satiety, abdominal distension, nausea, or indigestion during the last three months
with symptom onset at least six month ago. These symptoms
are categorized into epigastric pain syndrome and postprandial distress syndrome [2]. Pathophysiological factors which
may cause FD include genetic predispositions, early family
environment, psychosocial factors, abnormal gastric motility,
visceral hypersensitivity, inflammation, and bacterial flora
[3]. Particularly, gastrointestinal motor abnormalities, altered
2
treatment options, treatment for FD often remains unsatisfactory [9]. The management of FD is challenging especially
when initial drug therapy fails, which is not uncommon [10].
Furthermore, besides side effects, traditional drug therapy
has been strikingly shown to have little to no efficacy [11].
For example, benefits from H. Pylori treatment were found
to be minimal [12]; acid suppression therapy was found to
be suboptimal with no apparent effects on dysmotility-like
dyspepsia [13].
From a traditional Chinese medicine (TCM) perspective, FD is characterized by disrupted qi flow inside the
middle energizer due to external pathogenic factors [14].
The middle energizer refers to spleen and stomach which
are responsible for food transformation and transportation.
Kidney is responsible for bone health and the generation
of bone marrow; excessive physical work consumes kidney
energy. Meanwhile, excessive mental work consumes blood
and causes imbalance of emotion. Blood is controlled by
heart and emotion is regulated by liver. Thus, treatment in
TCM including acupuncture should aim to facilitate qi and
blood circulation in meridians related to these organs and
thus normalizes patients status of health. With the guidance
of these diagnostic and therapeutic principles, therapeutic
effectiveness of acupuncture for abdominal pain, abdominal
distension, bloating, nausea, and others was well documented
in various TCM classics and has been reported in research
studies [1520].
Besides normalization of qi and blood in the affected
meridians, modern understandings of these results also lie
in pathophysiological research studies, in which researchers
found that acupuncture in patients with FD could accelerate
solid gastric emptying [17], increase plasma level of neuropeptide Y but not motilin [18], and induce deactivation
of the brainstem, anterior cingulate cortex (ACC), insula,
thalamus, and hypothalamus in the human body [21]. In
addition, acupuncture was also found to enhance normal
gastric myoelectrical regularity in both healthy people and
patients with diabetic gastric dysrhythmia [22, 23], alters the
frequency of gastric slow waves in healthy volunteers [24],
and accelerates solid gastric emptying in diabetic gastroparesis [25].
Acupuncture seems to be a promising treatment for FD;
however, the aforementioned clinical trials did not investigate
the effects of acupuncture on emotional symptoms [15
25], the prevalence of which has been found to be high
in patients with FD [26]; placebo effect which is common
in both patients with FD and acupuncture procedures will
likely add more uncertainties in the therapeutic effectiveness
of acupuncture [27, 28], and, finally, not all of the studies
performed acupuncture procedures based on TCM principles
including the meridian theories, such as an emphasis on Deqi
sensations.
In the present study, we aimed to determine (i) the effect
of acupuncture on dyspeptic symptoms, quality of life, and
mental status in patients with FD; (ii) the effect difference
between classic acupuncture based on TCM principles and
acupuncture on nonacupoints; and (iii) effects of classic
acupuncture on serum gastrin concentration and frequency
and propagation velocity of gastric slow waves.
3
Quality of life was measured by the short-form 36
(SF-36) questionnaires [33]. Mental statuses of patients were
evaluated via Zung Self-Rating Depression Scale (SDS) [34]
and Self-Rating Anxiety Scale (SAS) [35]. Scoring of these
standardized assessments followed guidelines published in
the Manual of Standardized Assessment Tools in Behavioral
Medicine [36]. SF-36 measures Quality of Life (QoL) across
eight domains; score of each domain = [(actual raw score
lowest possible raw score)/raw score range] 100. For the
SDS score, the following equation was used: SDS Index =
Raw Score 1.25. Grading of SDS is as the following: SDS
Index less than 53 points is considered normal, 53 to 62 as
mild depression, 63 to 72 as moderate depression, and 73 and
higher as severe depression [36]. For the grading of SAS, the
following categories were used: normal range (less than 50),
mild anxiety (50 to 59), moderate anxiety (60 to 69), and
severe anxiety (70 and higher) [36].
The secondary outcomes include fasting serum gastrin
concentration and frequency and propagation velocity of
gastric slow waves. These measurements were performed in
the eight patients with FD in the treatment group before
and after treatment, but only once in healthy volunteers. A
fasting venous blood sample was drawn from the basilic vein
prior to breakfast early in the morning. About three milliliters
of the blood sample was sent to Peking Union Medical
College Hospital for measurement of serum gastrin levels.
Meanwhile, the participant was given 120 mL 80% (w/v)
barium sulfate suspension (Qingdao Dongfeng Chemical Co.
Ltd., Shandong, China). Participants were then placed in
a supine position. Using Prestige digital X ray (GE, USA),
gastric mucosa was observed; then, a Chinese coin of fifty
cents was placed on top of the skin over the stomach of the
participant, and gastric motions around the gastric antrum
were video recorded for one minute while the participant
was in a standing position. Frequency of gastric slow waves
was directly counted as the number of waves that passed
through the gastric antrum in one minute. Propagation
velocity of gastric slow waves was assessed by the time interval
between two consecutive waves that passed through the
gastric antrum.
Safety evaluation includes possible hematoma, local
infection, fainting, and severe pain during and after acupuncture. In addition, other conditions which warrant cessation of
acupuncture treatment or withdrawal from the study if any
were also documented and analyzed.
2.5. Statistical Analysis. The statistical analysis was performed by two independent statisticians. Results were compared between the two statisticians. Differences, if any, were
discussed and the statistic test was reperformed until a
consensus was reached between the two statisticians. The
statisticians were blinded to treatments and study protocol.
All results including baseline characteristics were based on
per-protocol (PP) analyses. Statistical Analysis System (SAS),
version 6.12, was used and a significance level was set at <
0.05.
For comparisons of baseline values, chi square test was
used to explore gender differences; -test was used to explore
Excluded
(n = 28)
Peptic ulcer
Superficial gastritis
Atrophic gastritis
Gastroesophageal reux disease
Cholecystitis
Hashimoto thyroiditis
Diabetes mellitus
Severe coronary artery disease
Older than 70
(n
(n
(n
(n
(n
(n
(n
(n
(n
=
=
=
=
=
=
=
=
=
4)
7)
6)
3)
2)
1)
2)
2)
1)
3. Results
From July, 2010, to January, 2011, a total of 88 patients with
dyspeptic symptoms visited the Department of Acupuncture at Guang An Men Hospital in Beijing. Twenty-eight
patients were excluded from the present study due to the
following reasons: peptic ulcer (four patients), superficial
gastritis (seven patients), atrophic gastritis (six patients),
gastroesophageal reflux disease (three patients), cholecystitis
(two patients), Hashimoto thyroiditis (one patient), diabetes
mellitus (two patients), severe coronary artery disease (two
patients), and older than 70 (one patient). Sixty patients
were included and randomly assigned to either the treatment
group or the control group. Of these 60 patients, 56 patients
completed the study and four patients (two from each group)
dropped out from the study (dropout rate: 6.67%) after
the second visit. In the treatment group, one patient could
not tolerate the acupuncture Deqi sensations upon needle
manipulation, and the other patient in the treatment group
had transportation difficulties. In the control group, the
two patients directly stated to the therapist saying that the
Cases ()
28
28
Gender
Male () Female ()
11
17
10
18
0.7825
Age (year)
SF-36 score
49.29 10.32
48.25 11.40
0.7229
12.20 12.20
12.11 10.20
0.6145
24.32 8.28
24.79 7.48
0.8265
52.51 13.94
54.06 16.41
0.7043
4. Discussion
4.1. Selection of Acupoints. The use of classic acupoint of
ST36 in the present study is well-supported by former
research studies [1525], so was the use of PC6 [1519, 24].
In previous research studies, researchers mainly considered
the pathophysiological relationship between the meridians
or organs of liver and spleen, heart and spleen, or spleen
and kidney; acupoint of the kidney meridian is barely used
for FD in these research studies [1525]. In the present
study, we used KI3 based on the analysis of all the pathophysiological relationships between and among organs and
meridians related to FD symptoms. These diagnostic and
therapeutic principles would be a more realistic reflection
of individualized acupuncture treatment in clinical practice.
Items
PF
ES
EP
EBS
DSSS
SF-36
SDS
SAS
Groups
Treatment
Control
IGC
Treatment
Control
IGC
Treatment
Control
IGC
Treatment
Control
IGC
Treatment
Control
IGC
Treatment
Control
IGC
Treatment
Control
IGC
Treatment
Control
IGC
28
27
Baseline
9.00 2.09
8.89 2.39
After treatment
1.57 2.28
6.22 2.59
Difference
7.43 2.47
2.67 1.88
Improvement rate
82.56%
30.03%
19
21
9.74 1.91
8.43 2.87
0.42 1.43
6.05 2.52
9.32 1.97
2.38 1.80
95.69%
28.23%
21
22
6.81 2.23
7.41 3.02
0.48 1.03
6.32 3.41
6.33 2.31
1.09 1.82
92.95%
14.71%
16
17
6.31 2.39
6.71 2.78
0.50 1.55
6.47 3.00
5.81 2.17
0.24 0.56
92.08%
3.58%
28
28
24.32 8.28
24.79 7.48
2.50 3.28
19.40 8.23
21.80 8.24
5.36 3.29
89.72%
21.62%
28
28
52.50 13.94
54.00 16.41
70.00 12.54
56.00 13.42
17.00 14.04
2.88 8.74
33.52%
5.33%
28
28
57.96 9.55
57.60 11.84
45.60 8.75
54.00 10.80
12.30 9.89
3.50 5.92
21.33%
6.07%
28
28
52.30 10.48
52.36 9.67
42.30 6.22
52.20 7.98
10.00 10.22
0.11 4.89
19.11%
0.21%
value
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.0078
<0.0001
<0.0001
0.25
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.0099
<0.0001
<0.0001
0.0002
0.0005
<0.0001
0.8533
<0.0001
PF: postprandial discomfort; ES: early satiety; EP: epigastric pain; EBS: epigastric burning sensation; DSSS: dyspeptic symptom sum score; SF-36: short-form
36 questionnaire; SDS: Self-Rating Depression Scale; SAS: Self-Rating Anxiety Scale; IGC: intergroup comparison.
Groups
Treatment
Control
IGC
28
28
Baseline
24.32 8.28
24.79 7.48
Follow-up
1.68 2.36
16.43 7.41
Difference
22.60 8.68
8.36 6.58
Improvement
93.09%
33.92%
value
<0.0001
<0.0001
<0.0001
Quality of life is a heavy emphasis of the clinical management of all kinds of disorders. In the present study, the use
of modified NDI is well-supported by its high reliability and
validity in patients with dyspeptic symptoms [31, 32]. NDI
measures dyspepsia symptoms and dyspepsia-specific healthrelated QOL (H-QOL). Outcome measurements utilizing
NDI, SAS, and SDS will likely better capture the characteristics of acupuncture effects on FD. The improvement of
NDI in the present study concurs with results from other
acupuncture researchers regarding acupuncture treatment
for FD [1521]. Interestingly, the control group in which
acupuncture was used in nonclassic acupoints also induced
significant changes in dyspeptic symptoms except for epigastric burning sensations and SAS score. These results partially
concur with the results reported by Ma et al. [20] and
Zeng et al. [21]; however, the results differ from the results
Table 4: Serum gastrin concentration and frequency and propagation velocity of gastric slow waves in patients with functional dyspepsia
and healthy adults.
Items
Gastrin (pg/mL)
FGSW (n/min)
PVGSW (s)
Baseline ( = 8)
25.93 5.90
2.49 0.64
24.25 4.95
After treatment ( = 8)
44.40 6.26
3.11 0.14
19.75 2.05
FGSW: frequency of gastric slow waves; PVGSW: propagation velocity of gastric slow waves.
Note: propagation velocity of gastric slow waves was assessed by the time interval between two consecutive waves that passed through the gastric antrum.
Table 5: Comparisons of serum gastrin concentration and frequency and propagation velocity of gastric slow waves before and after treatment
as well as between patients with functional dyspepsia and healthy adults.
Items
Gastrin
FGSW
PVGSW
0.0081
0.0008
0.0279
0.0002
0.0078
0.0180
0.6401
1.0000
0.6713
FGSW: frequency of gastric slow waves; PVGSW: propagation velocity of gastric slow waves.
Note: propagation velocity of gastric slow waves was assessed by the time interval between two consecutive waves that passed through the gastric antrum.
Baseline versus after treatment refers to patients with functional dyspepsia only.
An accepted mechanism of acupuncture on the functions of the gastric system is related to its effects on
the autonomic nervous systems, which Takahashi [15]
summarized as follows: acupuncture at the lower limbs
(ST36) causes gastric muscle contraction via stimulating
the somatoparasympathetic pathway whereas acupuncture
at the upper abdomen causes gastric muscle relaxation via
stimulating the somatosympathetic pathway. As both main
acupoints KI3 and ST36 used in the present study are
located in the lower extremities, the result of enhanced
gastric motility is likely to be caused by activation of the
somatoparasympathetic pathway increasing the secretion of
gastrin and other hormones.
Furthermore, acupuncture has also been found to induce
changes in cerebral cortex activities of patients with FD [21].
Consequently, we hypothesize that effect of acupuncture on
the gastrointestinal system is related to its effects on the
peripheral nervous system, central nervous system, and the
endocrine systems related to the GI tract. However, to prove
the specific causal relationship among these systems, further
research studies are needed.
5. Limitations
As blinding is difficult in acupuncture studies, the establishment of a blank control group seems impossible. Although
nonclassic acupoint acupuncture procedures were used as
control in the present study, they are still acupuncture
procedures; thus we could not rule out the cofounding
factor of needling and placebo effects in the present study.
This study is performed at one clinical center with one
acupuncturist on a relatively small sample; the results of
the present study may not well characterize the response of
patients with FD to acupuncture treatments. In addition, the
analysis of the results did not include patients who dropped
out; data processing based on per protocol population may
8
decrease the credence of the results. To better capture the
response of patients with FD to acupuncture, further large
scale, multicenter, randomized placebo controlled trials are
warranted.
6. Conclusion
Classic acupuncture with manual manipulation could
improve dyspeptic symptoms, mental status, and quality of
life in patients with FD and is superior to nonclassic acupoint
acupuncture without manipulations. These effects may be
related to the increased frequency and propagation speed
of gastric slow waves as well as increased serum gastrin
secretion.
[10]
[11]
[12]
[13]
Conflict of Interests
[14]
[15]
Authors Contribution
[16]
Acknowledgments
[17]
This study was funded by the State Key Development Program for Basic Research of China (973, Grant code no.
2011CB505202) and the National Natural Science Foundation
of China (Grant code no. 30870668, 81273674).
[18]
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