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Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

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Journal of Traditional Chinese Medical Sciences


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Key elements that determine the efficacy of cupping therapy: A


bibliometric analysis and review of clinical studies
Jiayin Tao a, Pei Zhao a, Tingting Mo a, Ruiming Zhao b, Nan Yang a, Myeong Soo Lee c, d,
Jianping Liu e, Huijuan Cao e, *
a
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
b
Department of Respiration, China-Japan Friendship Hospital, Beijing, 100029, China
c
Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, South Korea
d
Korean Convergence Medicine, University of Science & Technology, Daejeon, 34113, South Korea
e
Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China

a r t i c l e i n f o a b s t r a c t

Article history: Objective: The aim of this review was to identify the possible mechanisms behind cupping therapy by
Received 13 March 2020 employing an evidence-based approach, and to explore its possible regional and systemic effects in the
Received in revised form human body.
3 November 2020
Methods: We searched six electronic databases and four online trial registries for articles published up to
Accepted 3 November 2020
January 1, 2020. Clinical studies on the mechanisms of retained cupping, flashing cupping, moving
Available online 9 November 2020
cupping, and vacuum cupping were considered for this review. The methodological qualities of
controlled studies were assessed using the National Institute for Clinical Excellence methodology
Keywords:
Cupping therapy
checklist, the Newcastle-Ottawa Scale, and the Cochrane risk of bias tool. Characteristic statistical
Negative pressure description and qualitative summary of results were used for data analysis.
Immunomodulation Results: Thirty-eight studies (37 full texts and one abstract) were included in this study. Due to the
Temperature clinical heterogeneity among the studies, we could not conduct a meta-analysis. The results showed that
Hemodynamics the key factors that contribute to the efficacy of cupping therapy are negative pressure and temperature.
Bibliometrics Cupping therapy mainly causes local and systemic changes in hemodynamics, immune regulation,
metabolism, and pain relief.
Conclusion: We identified negative pressure as the key element behind cupping therapy. Cupping
therapy may cause redistribution of oxygen at the cupping site and in neighboring tissues, thereby
inducing a therapeutic effect by increasing regional blood flow. It may also induce metabolic change,
immunomodulation, and neuromodulation. However, additional rigorous clinical research needs to be
conducted to further clarify the mechanism behind cupping therapy.
© 2020 Beijing University of Chinese Medicine. Production and hosting by Elsevier B.V. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction periarthritis, facial paralysis, lumbar intervertebral disc herniation,


dyspnea, and cervical spondylosis.2
Cupping therapy is a traditional therapeutic technique that is It is widely believed that it is the temperature and the contin-
used as a complementary and alternative treatment worldwide. uous vacuum generated during cupping therapy that make an
The categories of cupping therapy are becoming more diverse; impact on local skin. This continuous vacuum may stretch the skin
however, it can generally be classified into wet cupping, retained and underlying tissue, induce vascular recruitment, and cause the
cupping, flashing cupping, moving cupping, medicinal cupping, and capillaries to dilate and break. Regional stimulation causes a
needling cupping.1 According to the results of our previous studies, microenvironmental change in vivo and leads to secretion of
cupping therapy may have a significant benefit in the treatment of chemical signals. Furthermore, these regional chemical signals
pain-related conditions, herpes zoster, scapulohumeral interact with each other, eventually resulting in a systemic effect.3

* Corresponding author.
E-mail address: huijuancao@bucm.edu.cn (H. Cao).
Peer review under responsibility of Beijing University of Chinese Medicine.

https://doi.org/10.1016/j.jtcms.2020.11.001
2095-7548/© 2020 Beijing University of Chinese Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

Dr. Lowe indicated in his review that cupping therapy may have administration of drugs, medicinal injection, wet cupping, medic-
antioxidant, anti-inflammatory, metabolic regulative, and immu- inal cupping, and needling cupping) as intervention were not
nomodulatory effects in animal and human systems.4 included in this review because of the complexity of the mecha-
Investigating the mechanism and impact of cupping therapy nisms of the different treatments administered.
may help elucidate its local and systemic effects. However, high- Regarding the key elements of cupping therapy (e.g. vacuum
quality clinical evidence that can explain the key elements and and temperature), the primary outcomes of this review were
mechanism of cupping therapy is still lacking. Prof. Lee assessed changes in the indicators that reflect therapeutic effects in the
five systematic reviews and came to a conclusion that reduction of human body; the indicators were defined based on the involved
pain may be the only therapeutic effect of cupping.5 However, this disease/condition. Regarding the possible mechanism of cupping in
indication is not well proven as well. Given the variation in the the human body, the primary outcomes were any changes in
findings of previous studies, it is necessary to critically evaluate and physiological or biochemical indicators, such as hemodynamics,
summarize the existing clinical evidence for obtaining a clearer inflammatory mediators, neuroendocrine regulation, and
picture of the mechanism and therapeutic effect of cupping ther- immunomodulation.
apy. In this review, the key elements that determine the efficacy of
cupping therapy were summarized and evaluated based on evi- Data extraction and quality assessment
dence in the currently available literature. The results of this review
would provide practitioners with a clearer direction regarding the Five authors (JYT, PZ, TTM, RMZ, and NY) independently
use of cupping therapy in clinical practice. The aim of this review extracted data on participant characteristics, details of cupping
was to identify the possible mechanisms behind cupping therapy therapy and control, outcomes, and quality-related information.
by utilizing an evidence-based approach, and to explore its possible Microsoft Office Access 2016 (Office 365 MSO 18.2005.1191.0,
regional and systemic effects in the human body. Microsoft, Redmond, Washington D.C.) was used for data
extraction.
Methods Two authors (JYT and PZ) independently evaluated the meth-
odological quality of the included controlled clinical studies. The
Search strategy Newcastle-Ottawa Scale was used to assess the methodological
quality of the included analytical studies (cohort studies and case-
Literature concerning the mechanism of cupping therapy was control studies).6 Eight elements, including “comparability” be-
retrieved with no restriction on publication status. Due to language tween groups, “representative” selection samples, and “integrity”
barriers, we only included articles that were published in English and “validity” records, were assessed. The methodological qualities
and Chinese. We searched the Cochrane Central Register of of RCTs and non-randomized controlled clinical studies were
Controlled Trials, PubMed, EMBASE, China National Knowledge assessed using the risk of bias tools reported in the Cochrane
Infrastructure, Chinese Scientific Journals Database (Chongqing Handbook for Systematic Reviews of Interventions.7 The seven el-
VIP), and the Wanfang Data. Online trial registries, including the ements of the risk of bias tool are: random sequence generation,
Chinese Clinical Registry, International Clinical Trials Registry blindness of participants included, allocation concealment, blind-
Platform, ClinicalTrials.gov, and the Australian New Zealand Clinical ness of outcome assessors, selective reporting, incomplete outcome
Trials Registry were searched as well. The reference lists of the data, and other biases. The methodological qualities of case series
identified studies were also searched to identify other potentially were assessed according to the standards formulated by the Na-
relevant studies. tional Institute for Clinical Excellence.8 Scores were assigned to
The search terms we used included “cup,” “cupping,” or multi-center studies based on whether they had “clearly described”
“baguan” combined with “suction,” “negative pressure,” “temper- hypothesis/aim/objective, “clearly reported” inclusion and exclu-
ature,” “blood flow,” “nerve system,” “neurohormone,” “circula- sion criteria, “clearly defined” outcomes, prospectively collected
tory,” “blood,” “serum,” “plasma,” “immune systems,” or data, “consecutively recruited” patients, “clearly described” find-
“mechanism”. We adjusted the retrieval strategy for the different ings, and “stratified” outcomes.
databases.
Data analysis
Inclusion criteria
Microsoft Excel 2016 (Microsoft) was used to calculate fre-
All kinds of clinical studies such as randomized controlled trials quency. For binary outcomes, we used relative risk (RR) with 95%
(RCTs), cohort studies, case-controlled studies, cross-sectional confidence intervals (CI) to summarize the outcome data; for
studies, case series, and case reports were included. Animal continuous outcomes, mean difference (MD) and 95% CI were re-
studies were not included because our objective was to investigate ported (Table 1). Review Manager 5.3 software was used for data
the impact of cupping therapy on the human body. There were no calculation. However, we did not conduct a meta-analysis because
restrictions regarding the sex, age, race, nationality, or the educa- of the obvious clinical heterogeneity among the studies; only sta-
tion level of participants as long as they received cupping therapy tistical description and qualitative summary of the results were
for the management of any diseases or conditions. Retained used for data analysis.
cupping, flashing cupping, moving cupping, and vacuum cupping
were considered as interventions for this review. The controls were Results
cupping therapy performed at different temperatures and pres-
sures to find out the key elements that determine the efficacy of Search results
cupping. Placebo or sham cupping were also included if they were
compared with vacuum cupping. If the control group received We searched relevant databases and trial registries up to
placebo treatment or other treatment, such as western medicine or January 1, 2020. Out of 7539 citations retrieved after the search,
complementary and alternative medicine, the study outcome was 7432 were screened out after their titles and abstracts were eval-
considered mechanism-related. Studies that involved a combina- uated. We assessed the full texts of the remaining 107 citations; 94
tion of cupping therapy and other treatments (such as oral articles remained after duplicates were removed. Subsequently, we
346
J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

screened out 56 citations for a variety of reasons (Fig. 1). Thirty- nausea (MD ¼ 1.87; 95% CI, 2.49 to 1.25; P < .0001) or vomiting
eight studies9‒46 including 37 full texts and one abstract (a total (MD ¼ 1.01; 95% CI, 1.29 to 0.73; P < .0001) 2 h after treatment
of 1569 participants) were eligible for review. than those in the sham cupping group. However, the results of the
other trial10 showed that there was no difference between the two
Basic characteristics of the included studies groups regarding the reduction of pain intensity (141 participants;
MD ¼ 3.0 mm; 95% CI, 9.9 to 3.9; P ¼ .396).
The number of articles published over time is shown in Fig. 2. In the trial by Li,11 three groups that underwent treatment with
Thirty-one of the included studies were conducted in China; 26 different degrees of negative pressure were compared, and the
were publications in Chinese Journals, and five were published in results indicated that there were differences in the relief of urticaria
English. For the remaining seven studies, which were published in symptoms among the groups (90 participants; RR ¼ 1.27; 95% CI,
English, one was conducted in Korea,42 one in Iran,9 one in 1.01 to 1.61; P ¼ .045). However, although the researchers utilized
Singapore,29 two in Ukraine,31,32 and two in Germany.10,45 cups of different calibers to ensure that varied degrees of pressure
Ten of the 38 studies were RCTs,9,10,13,27,28,34‒38 one was a non- were applied, they did not measure the specific values of the
RCT,39 one was a cohort study,33 and the remaining were case se- pressure applied.
ries. Among the 10 included RCTs, two were three-arm trials,10,33
whereas eight trials had a parallel two-arm design. Temperature
The basic characteristics of the included studies are shown in In two trials,12,13 vacuum cupping was compared with retained
Table 1. cupping to explore the potential effect of temperature during
treatment. In one of the trials,12 adjustments were made to ensure
Assessment of risks of bias in the included trials the pressure in two types of cups were equal; results showed that
compared with fire cupping, the elevation of local blood perfusion
Eleven trials, including 10 RCTs9,10,13,27,28,34‒38 and one non- with dry cupping was significant 21 min after removing the cups (13
RCT,39 were assessed using the risk of bias tool. The methods of participants; MD ¼ 0.31 PU; 95% CI, 0.14 to 0.48, P ¼ .0015). However,
random sequence generation were reported in five trials;9‒11,28,36; the instant efficacy of the elevation of local blood perfusion with dry
the random number table was used to generate the allocation in all cupping was nearly the same as that of fire cupping (MD ¼ 0.00 PU;
of them. The methods of allocation concealment were reported in 95% CI, 0.28 to 0.28; P > .05). The other trial13 showed that there
only three trials.10,27,28 In these trials, the random number was kept was no significant difference between two groups in terms of
in a sealed opaque envelope. Due to the manipulation and the reduction of limb pain and improvement of limb activity (40 par-
particularity associated with cupping therapy, it is difficult to ticipants; RR ¼ 1.23; 95% CI, 0.83 to 1.82; P > .05). However, in this
perform a double-blind study that involves cupping therapy. Only trial, the researchers did not take steps to ensure that the negative
reports of two trials9,10 had sufficient information that permitted pressure of cupping in the two groups was the same.
the determination of the presence of a low risk of performance bias.
In one trial,9 blinding was likely broken since the patients in the Mechanism of cupping therapy in the human body
sham cupping group may not have had any feeling of negative
pressure during the treatment. In another trial10 blinding was Hemodynamic changes
highly likely to be broken based on the information from the post- Six case series,14‒19 which included a total of 75 participants,
test investigation. Since all of the studies except two9,10 were not reported blood flow data during cupping treatment. Significant
registered, it was difficult to determine whether they were pre- differences could be found with regard to increase of regional blood
designed, and whether the methods used for sample size calcula- flow in moving cupping (instant change; 20 participants;
tion were reasonable; therefore, we considered them as having an MD ¼ 58.66 PU; 95% CI, 46.53 to 70.79; P < .001), retained cupping
unclear risk of selective reporting and other bias (Fig. 3). (5 min after cupping; 15 participants; MD ¼ 37.97 PU; 95% CI, 28.75
Twenty-six case series were assessed using the National Insti- to 47.18; P < .001), and vacuum cupping (0.04 MPa cupping for
tute for Clinical Excellence guideline. The average score from that 5 min; 10 participants; MD ¼ 0.59 PU; 95% CI, 0.31 to 0.86;
evaluation was 4.5 (range 3e6). The major defect was that all 26 P ¼ .0006 and instant change; 30 participants; MD ¼ 78.54 PU; 95%
researches were single-center trials, and their outcomes were not CI, 66.26 to 90.82; P < .001).
stratified by disease stage, abnormal test results, or patient char- Another case series20 reported that peak systolic velocity (PSV)
acteristics. In addition, most reports did not include explicit state- and end-diastolic velocity (EDV) levels increased significantly (32
ments on whether patients were recruited consecutively or not spots on 22 lumbago patients; PSV: MD ¼ 8.30 cm/s; 95% CI, 7.60 to
(Fig. 4). 9.00; P < .001 and EDV: MD ¼ 3.60 cm/s; 95% CI, 3.34 to 3.86;
The only cohort study33 was assessed using the Newcastle- P < .001), whereas resistance index decreased (32 spots on 22
Ottawa Scale. Owing to the limitations on representativeness of lumbago patients; MD ¼ 0.07 cm/s; 95% CI, 0.10 to 0.04;
samples and comparability between groups, only four stars were P < .001) after cupping treatment. The results of one trial21 indi-
given, which indicated that the methodological quality of this study cated that whole blood viscosity at a sheer rate of 200 s1 and
was not very good. plasma viscosity decreased significantly (12 sub-healthy adults;
MD ¼ 0.22 mpa. s; 95% CI not clear; P < .05 and MD ¼ 0.09 mpa.
Key contributing factors behind the mechanism of cupping s; 95% CI, not clear; P < .05), whereas no significant difference was
found in whole blood viscosity at a sheer rate of 1 s1, 2 s1, and 3
Negative pressure s1. In one study,22 the yuan-acupoint was tested on the same
In two trials,9,10 vacuum cupping was compared with sham meridian as that of the cupping site. The bias ratio of blood
cupping; the presence of negative pressure was the only difference perfusion significantly decreased and was approaching normal
between the study groups. One trial9 demonstrated that individuals values as a result of cupping therapy (44 spots on 31 healthy adults;
treated with vacuum cupping had significantly less severe post- MD ¼ 20.95%; 95% CI, not clear; P < .01); this indicates a hemo-
operative nausea and vomiting after surgery than those treated dynamic change caused by cupping treatment.
with sham cupping (206 participants, P < .001). The results showed Hemodynamic changes may also cause changes in skin tem-
that patients in the vacuum cupping group were less likely to have perature. Six trials,23‒28 which involved a total of 240 participants,
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J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

Table 1
Basic characteristics of including studies.

Study ID Intervention/Comparisons Cupping site Test site Sample Conditions Main findings OR/MD (95%CI)
size (M/
F)

Negative pressure
Farhadi K. Vacuum vs. sham cupping P6 on the dominant None T: 0/ PONV Nausea: MD -1.87 (2.49, 1.25);
20169 hand 107 Vomiting: MD -1.01 (1.29, 0.73)
C: 0/99
Lauche R. Vacuum vs. sham cupping for 10 No limit on the upper None T:1/46 Fibromyalgia VAS: MD -3.0 (9.9, 3.9) mm
201610 e15 min and lower back C:1/47 syndrome
Li C. 201811 Retained cupping for 15 min with RN8, DU14, BL13, BL20, None T: 30 Urticaria Symptoms of urticaria: RR 1.27 (1.01, 1.61)
3 cm vs. 5 cm diameter cups BL23 C: 30
Temperature
Huang T Vacuum vs. retained cupping Two central points in T 7 Cupping site T: 3/10 None Blood flow: MD 0.31 (0.14, 0.48) PU
201012 e8 to L 2-3 C: 3/10
Hu YP Vacuum vs. retained cupping No limit None T: 20 Arthralgia Reducing limb pain and improving limb activity:
201813 C: 20 RR 1.23 (0.83, 1.82)
Hemodynamic change
Tian YY Retained cupping Inside of the forearm Cupping site 5/5 None Blood flow: MD 0.55 (0.31, 0.78) PU
200714
Tian YY Moving cupping Bilateral bladder Cupping site 5/9 None Blood flow: MD 0.28 (0.20, 0.36) PU
201215 meridians
Zhao YJ Moving cupping with different Governor vessel GV14 10/10 Sub-healthy Blood flow: MD 58.66 (46.53, 70.79) PU
201316 parameters (negative pressure 0.01 GV12 Blood flow: MD 58.20 (47.09, 69.31) PU
e0.02 MPa, 0.02e0.03 MPa, with the midpoint Blood flow: MD 52.27 (41.12, 63.42) PU
moving cup for 5 min or 3 min) between GV14 and
GV12
Liu W Vacuum cupping for 10 min with a GV14,GV12,GV11 GV14 15/15 None Blood flow: MD 78.54 (66.26, 90.82) PU
201317 constant negative pressure at and bilateral BL13 and GV12 Blood flow: MD 3.71 (7.85, 0.43) PU
0.04 MPa BL15 GV11 Blood flow: MD 0.36 (3.41, 4.13) PU
Left BL13 Blood flow: MD 11.87 (6.72, 17.02) PU
Right BL13 Blood flow: MD 15.17 (8.62, 21.72) PU
Left BL15 Blood flow: MD 1.53 (1.86, 4.92) PU
Right BL15 Blood flow: MD 1.65 (2.08, 5.38) PU
Jin L 201018 Retained cupping for 10 min Right BL18 Right BL18 6/9 None Blood flow: MD 37.97 (28.75, 47.18) PU
Li CQ Vacuum cupping for 5 min GV14 Left BL13 5/5 Sub-healthy Blood flow: MD -0.81 (7.98, 6.35) PU
201219 GV12 Blood flow: MD -0.41 (7.06, 6.24) PU
Tang X Retained cupping for 10 min Ashi acupoint in lower Cupping site 14/18 Lumbago PSV: MD 8.30 (7.60, 9.00) cm/s; EDV: MD 3.60
201220 back (3.34, 3.86) cm/s; RI: MD -0.07 (0.10, 0.04)
cm/s
Zhao YJ Moving cupping Bilateral bladder Venous blood 3/9 Sub-healthy Venous blood viscosity at a sheer rate of 200 s1:
201521 meridians and the MD -0.22 (CI not cleara) mpa.s; plasma viscosity:
Governor vessel MD -0.09 (CI not cleara) mpa.s
Zhao PN Vacuum cupping for 10 min Bilateral he-Sea acupoint Bilateral yuan- 14/17 None BRBP: MD -20.95 (CI not cleara) %
201822 of Jueyin and Shaoyang acupoint of Jueyin
meridians and Shaoyang
meridians
Skin surface temperature ( C)
Xin Y Vacuum cupping for 10 min Bilateral BL23, BL25, Cupping site 55 Lower back MD 1.01 (0.37, 1.65)
199423 BL31, BL40, KI1 pain
Li CQ Vacuum cupping GV14 Left BL13 20/0 None MD 0.74 (0.20, 1.68)
201124 Right BL13 MD 0.83 (0.05, 1.61)
Left BL18 MD 0.79 (0.00, 1.58)
Right BL18 MD 0.79 (0.12, 1.46)
Left BL23 MD 0.33 (0.46, 1.12)
Right BL23 MD 0.65 (0.08, 1.38)
Li CQ Vacuum cupping Governor vessel DU3 20/0 None MD 0.39 (0.17, 0.95)
201025 DU9 MD 0.64 (0.15, 1.13)
DU13 MD 0.37 (0.04, 0.78)
Zhang L Retained cupping for 15 min BL20 BL20 9/12 None MD 0.29
201126
Xu PC Vacuum cupping for 10 min BL15, BL23 Cupping site as 29/14 Low back MD 0.10 (0.37, 0.57)
201427 well as the other pain
side of cupping site
as control site
Chi LM Retained cupping vs. no treatment for SI15, GB21, LI15 SI 15 T: 3/27 Chronic neck MD 0.61 (0.35, 0.87)
201628 20 min GB21 C: 2/28 and shoulder MD 0.52 (0.24, 0.80)
LI15 pain MD 0.22 (0.01, 0.43)
Tang YH Retained cupping vs. no treatment for Bilateral bladder Upper abdomen T: 16/ Sub-healthy MD 1.08 (0.83, 1.34)
201429 10 min meridians back 15 MD 0.87 (0.15, 1.59)
C: 15/
18
Immunomodulation
Zhong L Moving cupping Bilateral bladder Venous blood 34/23 None C3b R: MD 5.83 (4.29, 7.37)  109/L (27b); MD
199930 meridians 4.15 (2.45, 5.84)  109/L (30b); immune complex

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J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

Table 1 (continued )

Study ID Intervention/Comparisons Cupping site Test site Sample Conditions Main findings OR/MD (95%CI)
size (M/
F)

rosette: MD 2.51 (1.47, 3.56)  109/L (27); MD


1.96 (0.85, 3.07)  109/L (30)
Boris V. Retained cupping No limit Venous blood 0/23 None NKc: MD -3.30 (5.56, 1.04) %
201631
Boris V. Retained cupping No limit Venous blood 0/22 None HLA-DR: RR 11.00 (0.68, 177.72)
201832
Liu ZD Retained cupping for 10min DU14, LI15, SJ14, BL11, Blisters 35 Shoulder and Compared with the scald group (control group),
201833 BL12, BL13 and Ashi back pain a total of seven proteins in the cupping group
points were increased, one protein was decreased
Gong L Retained cupping for 10 min vs. oral CV8 Venous blood T: 15/ Atopic EOS: MD -0.14 (0.21, 0.08)  109/L; IgE: MD
201634 cetirizine tablets 10 dermatitis -488.62 (694.97, 282.27) U/mL
C: 12/
13
Wang D Retained cupping for 10 min vs. oral BL12, BL13, BL20 Venous blood T: 21/ Repeated IgA: MD ¼ 0.38 (0.10, 0.66) g/L; C3: MD 0.07
201835 Yupingfeng 19 common cold (0.01, 0.13) g/L; IL-2: MD 0.47 (0.15, 0.79) U/mL
C: 18/ in deficiency
22 body
Chen C Retained cupping for 8min vs. BL13, EX-B1, GV9 Venous blood T: 24/ Children IgG: MD 3.98 (3.21, 4.75) g/L; IgA: MD 0.60 (0.47,
201736 ambroxol hydrochloride oral solution 26 cough after 0.73) g/L; SIL-2R: MD -111.14 (194.29, 27.99)
C: 27/ infection U/mL
23
Luo YH Retained cupping for 35 min vs. oral Multiple meridians Venous blood T: 22/ Ulcerative IgA: MD -0.05 (0.29, 0.19) g/L; IgG: MD -2.51
200937 Changyanning tablets 18 colitis (3.15, 1.87) g/L; IgM: MD -0.97 (1.22, 0.72)
C: 20/ g/L
16
Ye LH Retained cupping for 15 min vs. blank Bilateral CV8, CV4, ST36 Venous blood T: 27/ No limit Cupping treatment may regulate IgA, IgG, IgM,
201638 control and bilateral BL13, BL20, 28 C3, C4 level in two directions
BL23 by turns C: 25/
18
Oxygen change
Li T 201739 Vacuum cupping with a constant Infraspinatus muscle Peripheral area of 11/2 None RHb: MD -19.43 (23.26, 15.6) mmol/L; OHb:
negative pressure at cupping site MD 7.73 (5.17, 10.29) mmol/L
0.075 ± 0.005 MPa for 5 min
Gao CY Vacuum cupping with a constant Acupoint of kidney Acupoint of kidney 7/5 None RHb: MD 7.69 (5.80, 9.58) mmol/L; OHb: MD
201940 negative pressure at -4.19 (5.75, 2.63) mmol/L
0.075 ± 0.005 MPa for 8 min
Zhang L Retained cupping with negative BL20 BL20 10/11 None RHb: MD 0.3124 mmol/L; OHb: MD 1.6667 mmol/
200141 pressure 0.045 ± 0.005 MPa for L
15 min
Kim S Vacuum cupping with a constant Thoracolumbar fascia Cupping site and 10/0 None The result shows a dramatic increase of the OHb
42
2019 negative pressure at 0.045 MPa for surrounding tissue and RHb concentrations at the treatment site
5 min while the OHb and RHb levels were decreased at
the surrounding tissue
Meng XW Vacuum cupping with a constant GV14 Left BL13 10/10 None TcpO2: MD -0.80 (3.47, 1.87) kPa
201243 negative pressure at 0.075 MPa Adjacent non- TcpO2: MD -0.80 (2.95, 1.35) kPa
acupoint
Zhao YJ Moving cupping with different Governor vessel GV4 5/5 Sub-healthy TcpO2: MD 0.77 mmHg; tcpCO2: MD
201544 parameters (negative pressure 0.01 -2.77 mmHg
e0.02 MPa, 0.02e0.03 MPa, with
moving cup for 5 min or 3 min)
Exchange of substance
M. Vacuum cupping for 15 min Above the side with the Venous blood 4/8 Neck pain Cupping significantly and long-lasting increased
Emerich predominant pain, or lactate level in the subcutaneous tissue. The
45
2014 above the trapezius increasing lactate/pyruvate ratio also proved
muscle that the lactate resulted from hypoxia, indicating
an anaerobe metabolism in the surrounding
tissue.
Pain reduction
Huang J Moving cupping and retained Moving cupping on Venous blood 13/12 Non-specific b-EP: MD 125.7 (79.8, 171.60) ng/mL
201246 cupping for 15e20 min bilateral bladder low back pain
meridians and retained
cupping on bilateral
BL23

Notes: M: male; F: female; CI: confidence interval; OR: odds ratio; RR: risk ratio; MD: mean difference; T: treatment group; C: control group; PONV: postoperative nausea and
vomiting; VAS: visual analogue scale; PSV: peak systolic velocity; EDV: end-diastolic velocity; RI: resistance index; BRBP: bias ratio of blood perfusion; C3b R: Complement 3b
receptor rosette; NKc: natural killer lymphocyte cell; HLA-DR: human leukocyte antigen DR; EOS: eosinophilic granulocyte; IgE: immunoglobulin E; IgA: immunoglobulin A;
C3: complement 3; IL-2: interleukin-2; IgG: immunoglobulin G; SIL-2R: soluble interleukin-2 receptor; IgM: immunoglobulin M; C4: Complement 4; RHb: reduced hemo-
globin; OHb: oxyhemoglobin; TcpO2: transcutaneous arterial oxygen tension; tcpCO2: transcutaneous arterial carbon dioxide tension; b-EP: b-endorphin.
a
The CI was not clear because of insufficient raw data.
b
The trial was conducted twice, 27 participants for the first time and 30 participants for the second.

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J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

showed that cupping therapy can significantly increase skin surface Two case series investigated the partial pressure of oxygen
temperature (SST) at the cupping site and even at other acupoints. (tcpO2) and the partial pressure of carbon-dioxide (tcpCO2) on the
In another trial,29 SST fell and then rose during cupping, whereas skin surface. However, the results of both reports were in contrast.
the SST of the control area fell more obviously (43 lower back pain One43 reported a significant decrease in tcpO2 after cupping
patients). Therefore, all the seven trials mentioned above indicated treatment (in 20 healthy participants), whereas the other44 re-
that cupping therapy can cause a regional increase in SST. ported that after moving cupping in 10 sub-healthy adults, tcpO2
increased at first and then decreased over time; at the same time,
Immunomodulation tcpCO2 levels decreased.
One trial30 proved that cupping therapy could improve the
immune function of red blood cells by increasing the number of Changes in metabolites and protein levels. In the trial by Emerich
C3b receptors (27 participants; MD ¼ 5.83  109/L; 95% CI, 4.29 to et al45 that included 12 participants investigated the effects of
7.37; P < .001 and 30 participants; MD ¼ 4.15  109/L; 95% CI, 2.45 cupping on subcutaneous metabolic parameters. The results
to 5.84; P < .001; the trial was conducted twice) and immune showed that cupping significantly and persistently increased the
complexes (27 participants; MD ¼ 2.51  109/L; 95% CI, 1.47 to 3.56; level of lactic acid in the subcutaneous tissue. The increase in the
P < .001 and 30 participants; MD ¼ 1.96  109/L; 95% CI, 0.85 to lactic acid/pyruvate ratio also proved that the increased lactic acid
3.07; P < .001; the trial was conducted twice). In two trials31,32 that level was caused by hypoxia, indicating anaerobic metabolism in
included a total of 55 healthy females, the results showed a sig- the surrounding tissues.
nificant decrease in the number of natural killer lymphocyte cells Besides, another trial33 demonstrated that compared with the
(23 participants; MD ¼ 3.30%; 95% CI, 5.56 to 1.04; P ¼ .03), scalded group (35 patients), the cupping group had significantly
which has been linked with reproductive problems in women. The increased levels of metabolism-related proteins (hemoglobin sub-
results of one trial33 showed that levels of immune-related proteins unit beta, succinyl-CoA ligase) and antioxidant stress-related pro-
(e.g. Ig lambda-2 chain C regions and Ig gamma-1 chain C region) teins (hemopexin, prdx2). However, changes in the superficial
increased more among participants who had cupping blisters than blister fluid are only circumstantial evidence of the effectiveness of
among those in the burning group. A three-arm trial11 indicated cupping therapy.
that cupping therapy may decrease the number of CD8þ cells in
venous blood (retained cupping; diameter, 3 cm: 30 participants; Pain reduction
MD ¼ 5.52; 95% CI, 9.27 to 1.77; P ¼ .0055, diameter, 4 cm: 30 The results of a case series46 that included 25 patients who had
participants; MD ¼ 6.02; 95% CI, 9.81 to 2.23; P ¼ .0029, and non-specific low back pain showed that the b-endorphin (b-EP)
diameter, 5 cm: 30 participants; MD ¼ 5.68; 95% CI, 9.52 levels of the participants were increased (MD ¼ 125.7 ng/mL; 95%
to 1.84; P ¼ .0053). The results of another trial34 indicated a sig- CI, 79.8 to 171.60; P < .001), indicating that moving cupping therapy
nificant decrease in the eosinophilic granulocytes (25 participants; can increase the concentration of b-EP in plasma, thereby produc-
MD ¼ 0.14  109/L; 95% CI, 0.21 to 0.08; P ¼ .0001) and ing the effect of pain relief.
immunoglobulin (Ig) E levels (25 participants; MD ¼ 488.62 U/ The results of one trial33 suggested that local pain-sensing
ml; 95% CI, 694.97 to 282.27; P < .001) of participants after substances may be eliminated by blistering cupping therapy. In
cupping therapy compared with those of 50 atopic dermatitis pa- that trial, levels of pain-related proteins (calmodulin) in blisters
tients treated with oral cetirizine tablets. were elevated through cupping treatment.
The report of another trial35 indicated a significant increase in
IgA (40 participants; MD ¼ 0.38 g/L; 95% CI, 0.10 to 0.66; P ¼ .0091), Discussion
C3 (40 participants; MD ¼ 0.07 g/L; 95% CI, 0.01 to 0.13; P ¼ .0163),
and IL-2 levels (40 participants; MD ¼ 0.47 U/ml; 95% CI, 0.15 to In this review, we aimed to identify the possible mechanisms
0.79; P ¼ .0046). Another trial36 reported a significant increase in behind cupping therapy and explore its possible regional and sys-
IgG (50 participants; MD ¼ 3.98 g/L; 95% CI, 3.21 to 4.75; P<.001) temic effects. This review included 38 studies; however, because of
and IgA (50 participants; MD ¼ 0.60 g/L; 95% CI, 0.47 to 0.73; P the obvious clinical heterogeneity among the studies, we did not
<.001) levels, and a drop in interleukin-2 receptor (SIL-2R) levels conduct a meta-analysis.
(50 participants; MD ¼ 111.14 U/ml; 95% CI, 194.29 to 27.99; We divided the included studies into two categories; some trials
P ¼ .0102). Similar upward trends in the levels of IgG and IgM were explored the elements that may contribute to the efficacy of
also reported in another study.37 Dr. Ye reported that cupping cupping, whereas others showed what physical changes would
therapy may affect the immune system bidirectionally.38 However, occur after treatment. According to the results of the studies in the
the results of one trial showed that there was no significant dif- first category, negative pressure during cupping treatment may
ference in IgG, IgM, and IgA levels after cupping treatment.20 play a more critical role than temperature in the curative effect of
cupping therapy. However, it must be noted for negative pressure,
Metabolic regulation the concept of “the higher, the better” is not true. Some researchers
Oxygen in blood and tissue. Reduced hemoglobin (RHb) and believe that an appropriate amount of negative pressure could
oxyhemoglobin (OHb) changes at the cupping site were reported in induce hyperemia or stasis on local skin.47 If the negative pressure
four trials. The results of two of the trials39,40 showed that RHb is higher than 0.05 MPa, it would cause harm to local tissue,14
significantly decreased (MD ¼ 19.43 mmol/L; 95% CI, 23.26 manifesting mainly as obstruction of venous reflux. This causes
to 15.6; P < .001), whereas OHb increased (MD ¼ 7.73 mmol/L; 95% stasis of microcirculation in the blood stream, conversely leading to
CI, 5.17 to 10.29; P < .001) around the cupping site. Around the lower blood flow volume and velocity.16 The studies in second
cupping area, there was an obvious drop in OHb (MD ¼ 4.19 mmol/ category showed that changes in hemodynamics and metabolism
L; 95% CI, 5.75 to 2.63; P < .001) and a dramatic elevation in RHb were obvious after cupping therapy. Several trials suggested that
(MD ¼ 7.69 mmol/L; 95% CI, 5.80 to 9.58; P < .001). The results of the cupping therapy could significantly increase regional blood flow.
other two trials41,42 indicated that both OHb and RHb significantly Regarding blood oxygen, we believe that the disparity in the reports
increased from the baseline levels at the treatment site in 31 of regional OHb and RHb changes is caused by the different cupping
healthy participants. There were no significant changes in the levels sites utilized in the studies and the different practitioners and in-
of OHb and RHb at the peripheral area of the treatment site. dividuals involved in the studies. One opinion on the effect of
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J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

Fig. 1. Flow diagram of the review.

Fig. 2. Line chart of the number of articles published over time.

cupping therapy on blood oxygen is that cupping can induce a state cupping therapy; however, the variation of the study characteristics
of high supply and low consumption of oxygen.41 However, another and outcomes prevented us from reaching a clear conclusion in that
opinion indicates that cupping may enhance oxygen uptake39 and regard.
cause increased consumption of oxygen and accelerated energy Discussions on cupping mechanisms have gradually increased in
metabolism.43 Both opinions imply that cupping could affect recent years and several theories have been proposed. One of these
metabolism by recruiting blood volume and redistributing oxygen theories4 suggests that negative pressure on the skin is the trigger
level at the cupping site and in neighboring tissues. According to for increased blood flow, capillary rupture, and eventually ecchy-
the findings of some trials, the levels of markers related to meta- mosis (known as cupping spot in cupping treatment). Ecchymosis
bolism, immunomodulation, and pain regulation also changed after attracts macrophages to phagocytize the red blood cells,

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J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

Fig. 3. Summary of the risks of bias in the included randomized controlled trials and non-randomized controlled trials.

Fig. 4. Quality assessment for the included case series.

stimulating them to produce heme oxygenase-1 (HO-1), which can effect4,49; a finding which is partly consistent with our conclusions.
break down heme into biliverdin/bilirubin, CO, and iron. The whole Some researchers9,11 concluded that negative pressure plays the
HO-1 system directly and indirectly has significant antioxidant, key role in cupping therapy whereas some did not.10
anti-inflammatory, antiproliferative, and neuroregulatory activ- Another aspect of these studies is the determination of the
ities. Another theory suggests that cupping has a similar mecha- pathways through which cupping therapy produces its effect;
nism with acupuncture because both procedures involve body immunomodulation3,50 and neuromodulation3,48 are the two most
surface stimulation.3 During cupping therapy, changes in the commonly mentioned pathways. Some relevant clinical trials were
microenvironment caused by external stimulation lead to activa- included in our review;30‒38,46 however, the data in these studies
tion of immunomodulation. The signal is then transmitted to the were not sufficient to prove these theories.
central nervous system, thereby initiating the neuroendocrine- The entire pathway of action in proposed theories,3,4,48 such as
immunomodulatory network and generating an overall regulato- the HO-1 theory,4 are mapped at the molecular and signal trans-
ry function. Some other theories47 like the “Pain-Gate Theory,” mission levels, showing a dynamic process from the beginning of
“Diffuse Noxious Inhibitory Controls,” and “Blood detoxification treatment to its effects. In contrast, our research was based on the
theory” have also been proposed. evidence provided by clinical trials, which focus more on systemic
Despite the diversity of these theories, it seems to be generally changes, such as hemodynamic and metabolic changes, caused by
believed that negative pressure and the resulting capillary rupture cupping treatment at a certain moment or for a certain period of
lead to a series of subsequent reactions that produce a therapeutic time. Therefore, this review is a static analysis of result data and
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J. Tao, P. Zhao, T. Mo et al. Journal of Traditional Chinese Medical Sciences 7 (2020) 345e354

cannot depict the complete outline of the mechanism of action. CRediT authorship contribution statement
Many of the theories are based on logical derivations of a
combination of empirical cognition and laboratory research. They Jiayin Tao: Data curation, formal analysis, project administra-
are logically self-consistent, but whether these processes occur and tion, visualization, and writing e original draft. Huijuan Cao:
produce an effect still needs to be verified. Our research aimed to Conceptualization, methodology, supervision, and writing e review
reveal the mechanism of cupping therapy through assessment of & editing. Pei Zhao: Formal analysis, methodology, and writing e
clinical data, which can also partially support these theories. original draft. Tingting Mo: Resources, software, data curation, and
This review systematically summarized the evidence in existing validation. Ruiming Zhao: Resources, software, data curation, and
clinical research to identify the possible mechanism behind validation. Nan Yang: Resources, software, and data curation.
cupping therapy. To the best of our knowledge, this is the first re- Myeong Soo Lee: Writing e review & editing. Jianping Liu:
view of its kind. The results of this review provide an objective and Funding acquisition and writing e review & editing.
critical evaluation of the evidence in existing studies.
However, although our search strategy was thorough, we only
included articles published in English and Chinese. Information in References
relevant research reports published in other languages may be
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