Journal of Acupuncture Research 2022; 39(4): 275-282
Published online November 23, 2022
https://doi.org/10.13045/jar.2022.00206
© Korean Acupuncture & Moxibustion Medicine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The purpose of this study was to analyze acupuncture treatment methods and acupoints used to treat obstructive sleep apnea (OSA) or obstructive sleep apnea-hypoapnea syndrome (OSAHS). The data were retrieved from January 2010 to May 2022 from the China National Knowledge Infrastructure database. The search terms included “adult,” “obstructive sleep apnea,” “obstructive sleep apnea hypoapnea syndrome,” “acupuncture,” and “electro-acupuncture.” Clinical trials for acupuncture treatment of OSA or OSAHS were included in this review (4 non-randomized controlled studies, 1 was a case report, and 10 randomized controlled studies). For OSA and OSAHS treatment, the acupoints that were most frequently used included REN23, LU7, ST40, EX9, LI11, and DU20. Compared with the control or Western treatment group, the treatment outcome measures of participants in the acupuncture treatment group significantly improved. In some studies, participants in the acupuncture group did not have side effects and the treatment was cost-effective. The data analyzed in this review suggest that acupuncture is an effective treatment for OSA or OSAHS.
Keywords acupuncture, adult, electroacupuncture, obstructive sleep apnea hypoapnea syndrome
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder wherein frequent arousal and a decrease in arterial oxygen saturation occur repeatedly during sleep due to the obstruction of airflow through the upper respiratory tract [1]. Untreated OSA can cause various complications including increased risk of surgery, hypertension, heart failure, stroke, coronary artery disease, arrhythmia, pulmonary hypertension, diabetes, and erectile dysfunction [2]. Furthermore, OSA-induced complications can contribute to the deterioration of the quality of life (QOL) of each individual [3].
Current OSA treatments include the use of the continuous positive airway pressure (CPAP) machine, an oral appliance, surgery, and other adjuvant treatments (weight control, posture therapy). Among the treatments, CPAP is the most representative treatment for OSA [4] and involves the use of a machine that is specifically designed to maintain constant air-flow pressure in the upper airways to prevent the airway from collapsing or narrowing [1]. CPAP can improve sleep quality, cognitive function, daytime sleepiness, health-related QOL (for mild OSA), and mood as well as decrease blood pressure, however, in patients with severe or moderate OSA, no significant improvement in the QOL was observed [1].
Herbal medicine and acupuncture treatment of OSA has been reported in Korea, although this was a case report and so the nature of the report limits its relevance in treatment effectiveness of CPAP [5].
In China, OSA is classified into the “snoring” and “snoring while sleeping” categories, and the main etiologies are pulmonary, splenic, or renal dysfunction, or a condition/disease that is caused due to Three Intestine dysfunction [6]. In addition, the cause of OSA is attributed to the poor spread of qi as well as impaired pulmonary, splenic, and renal function. Moreover, when a condition/disease reaches the throat where the lung, spleen, and kidney meridian veins are situated, it leads to “clogging” of the throat and prevents smooth passage of air [6]. Based on this hypothesis of the pathology underlying OSA, various research studies evaluating either Chinese medicine alone or an integration of Chinese and Western medicine are ongoing in China. This review presents analysis of data from the latest clinical studies on OSA in China retrieved from the China National Knowledge Infrastructure (CNKI) database. This review was undertaken with an aim to provide basic data for future domestic OSA treatment and clinical research and to contribute to the evidence based for Oriental treatment of OSA.
To investigate the clinical efficacy of traditional Chinese medicine for OSA or obstructive sleep apnea-hypopnea syndrome (OSAHS), the CNKI database was searched for clinical trials published from 2010 to 2022. The following keywords in English were used: “Obstructive Sleep Apnea,” “Obstructive Sleep Apnea Hypopnea Syndrome,” “acupuncture,” and “electroacupuncture.”
A total of 26 studies were retrieved from the CNKI database (Table 1 [6–20]) . Of these, 4 studies included pediatric patients (≤ 15 years), 4 were reviews and meta-analyses, and 3 were unrelated to OSA. Therefore, 15 studies were included in the analysis (Fig. 1).
Analysis by the year of publication showed that, from January 2010 to May 2022, 5 studies were published between 2010 and 2015, 7 between 2016 and 2020, and 3 between 2021 and 2022 (Table 2).
Among the 15 studies, 4 reported findings from non-randomized controlled studies, 1 was a case report, and 10 reported outcomes from randomized controlled trials (Table 3 [6–20]).
OSA constitutes a recurrent obstruction of the upper airway during sleep, and the resultant increased resistance induces snoring, intermittent hypoxia, and hypercapnia. Moreover, sleep cycles are impaired by frequent arousal. These physiological changes during sleep induce an increase in the production of reactive oxygen species and systemic inflammation due to repeated hypoxia-reoxygenation. OSA is related to the amount of abdominal fat, and the prevalence of OSA is reported to be high not only in the West, but also in Korea where there has been an increase in the proportion of the obese individuals due to westernized eating habits and lifestyle [21]. A study of the prevalence of sleep apnea in adults aged 40 to 69 years showed that the prevalence of mild obstructive sleep apnea was 27% in men and 16% in women in Korea [22].
Polysomnography is an objective test to study sleep and is used to accurately diagnose and evaluate sleep disorders. This test includes measurement of the patients’ brain waves, eye movements, electromyography of the lower extremities and jaws, electrocardiograms, chest and abdominal breathing movements, blood oxygen saturation, and respiratory flow are recorded mainly during sleep and then analyzed. Snoring, sleep apnea, insomnia, narcolepsy, and periodic limb movements are identified in polysomnography, which is useful for diagnosing abnormal behavior during sleep as well as for diagnosing the therapeutic effect.
In the majority of studies included in this review, OSA was diagnosed using polysomnography. In particular, the apneahypopnea index (AHI), which is used as an evaluation index in most studies, is an index for evaluating the severity of OSA and represents the sum of sleep apnea and hypopnea that is divided by the total sleep time. Thus, an AHI of < 15, 15 to < 30, and ≥ 30 indicates mild, moderate, and severe sleep apnea, respectively.
In this study, to determine the effects of acupuncture on OSA and OSAHS the results of a literature review of 15 studies published from 2010 to May 2022 were assessed. The analysis showed that acupuncture or electroacupuncture had a significant effect on OSA and OSAHS. Although most of the studies described acupuncture treatment for OSA or OSAHS, conditions/diseases such as depression and stroke that may be caused by, or accompany OSA or OSAHS, were also investigated. Therefore, the acupoints used for these other conditions/diseases differ slightly, depending on the characteristics of the diagnosed condition/disease (Table 4). With regard to the improvement of OSA, common acupoints could be ascertained (Table 5 [6–20]). In particular, REN23 was used in 11 of the 15 studies and was the most frequently used acupoint (Table 5 [6–20]). REN23 is located in the larynx, which is the intersection of the yin and yin you veins, and the branches of the sublingual and glossopharyngeal nerves are located under the acupoint [7]. Thus, by directly stimulating the sublingual and glossopharyngeal nerves, the pressure on the lumen of the throat can be reduced and this would keep the pressure constant in the throat and strengthen the muscles [8].
The second most frequently used acupuncture point was LU7, which comprises the pulmonary meridian, eight extra meridians, and yin meridian, and harmonizes the pulmonary qi that reaches the throat [8]. In addition, ST40 was relevant in the context that one of the causes of OSA is wetness, and ST40 was used to remove moisture and phlegm [7].
Shen et al [6] conducted a study on patients with mild OSHAS, and the AHI, LSaO2, and LAT levels were higher in the group that was treated with electroacupuncture as compared with the control group which received noninvasive positive pressure ventilation (
Zheng et al [7] compared patients with obstructive sleep apnea hypopnea treated with simple herbal medicine, simple acupuncture, or a combination of herbal medicine and acupuncture. The authors determined that the AHI, snoring index, minimum oxygen saturation, sleep stage, and ESS score was significantly higher in the group that received acupuncture and herbal medicine compared with the other treatments (
Wang [8] observed that OSAHS showed a better improvement when acupuncture along with Western therapy was applied to patients with acute cerebral infarction accompanied by OSAHS, compared with the control group which was Western therapy such as thrombolytic drug administration. The AHI and SaO2 improved more when acupuncture was combined with other treatments compared with the control group (
Sun et al [9] reported the AHI, snoring index, longest apnea time (LAT), nocturnal hypoxic saturation (LSaO2), serum interleukin (IL-33), serum interleukin-37 (IL-37), and QOL in the treatment group compared with the control group, and determined that the AHI, snoring indices, LAT, IL-33, and IL-37 levels in the treatment group receiving acupuncture and CPAP treatment were lower than the control group (
Zhou et al [10] compared the AHI, SaO2, and the Epworth Sleepiness Scale (ESS) score. Unlike in the control group which did not receive treatment, other than health education, the treatment group received health education, acupuncture and electroacupuncture, and the AHI, SaO2, and all ESS scores were significantly better than the control group (
Zhao [11] investigated the treatment of severe OSA accompanied by anxiety and hypoventilation syndrome, and the control group received intelligent CPAP. Moreover, in the treatment group, acupuncture and Yiqi Huatan Anshen prescription were administered. The results showed that the AHI and the Hamiltonian Anxiety Scale score in the treatment group decreased from the pretreatment level, and the oxygen saturation SpO2 improved compared with the baseline (
Liang et al [12] conducted a study with a control group that received nasal continuous positive airway pressure (nCPAP) therapy and a treatment group that received acupuncture, and both groups showed improvement after 3 months of treatment (
Lulu et al [13] investigated the effect of acupuncture on the improvement of sleep apnea and reduction of blood pressure in patients with OSA accompanied by hypertension. In the control group, gingko biloba extract and CPAP were administered, whereas in the treatment group acupuncture was added to these two treatments. As a result, the respiratory index was better than the control, blood pressure was lower, and the oxidizing substances, including reactive oxygen species and malondialdehyde, were lower after treatment compared with the control (
Zhang et al [14] reported that in the treatment of OSA accompanied by essential hypertension, the AHI and ESS scores were lower than the control and the LSaO2 were higher than the control (
Zhu et al [15] conducted a study on patients suffering from poststroke OSA and dysphagia. The control group received oropharyngeal rehabilitation training and routine neurological treatment and in addition, the treatment group had acupuncture and moxibustion. The results on polysomnography and symptoms of dysphagia improved in the treatment group compared with the control group (
Li et al [16] showed that in patients with OSAHS, compared with the control group treated with nCPAP alone, the polysomnography test results were better than the control group when the Xing Nao Kai Qiao needling technique was used which employs PC6, EX11, and SP6 as the main acupoints (
A study by Cui et al [17] involved a comparison of patients with OSA with and without hypertension, and showed that the patient group with OSA and hypertension had significantly reduced ambulatory blood pressure during acupuncture treatment compared with patients with OSA (
Song et al [18] reported that the AHI, LSaO2, LAT, the pulse pressure, self-rating anxiety score, self-rating depression score, and Epworth sleepiness scale score improved more in the group treated with electroacupuncture and nCPAP compared with the control group treated with nCPAP alone (
Zhou et al [19] studied the changes in serum interferon (IFN)-γ and IL-4 between the normal group and the OSAHS group. In the case of OSAHS patients, the pretreatment level of IFN-γ increased compared with that in the normal group, and IL-4 level decreased. Moreover, the level of IFN-γ decreased and the level of IL-4 increased after receiving acupuncture and noninvasive mechanical ventilation (
A case study by Ye et al [20] reported on sleep apnea in a stroke patient. The AHI decreased from baseline, LSaO2 increased, and the ESS score significantly decreased (all
Acupuncture was reported to be effective in treating OSA and OSAHS in 15 studies. CPAP, which is currently the most commonly used OSA treatment, was used as the control alone or in a treatment combination. It was inferred that acupuncture may replace CPAP and when used together with the treatment, a synergistic effect occurred. OSA and OSAHS can be seen as a result of lifestyle-related conditions/diseases. Most of the treatment periods were less than 30 days, so judging treatment continuity is limited. Currently, oriental medical treatment approaches for OSA and OSAHS in Korea are insufficient. Based on the studies reviewed, the results are meaningful if observed over a long period of time. In addition, Zhou et al [10] and Zheng et al [7] used the Bang-REN23, which is an acupoint located 1 cun to the left and right from the REN23, and is used for the treatment of OSA and OSAHS. It is an acupoint that is not frequently used for OSA treatment in Korea. In the future, it would be good if papers using the above acupoints could be published in Korea to prove the effect.
A total of 15 studies related to OSA or obstructive sleep apnea hypopnea syndrome were analyzed to determine the research trends of treatment using acupuncture from January 2010 to May 2022.
The most commonly used acupoints in obstructive sleep apnea studies were REN23, LU7, ST40, EX9, LI11, and DU20.
The use of acupuncture in the treatment of OSA is reliable and economical. It may be a good alternative to CPAP (which is generally used) or may be a more effective method. In addition, a greater synergistic effect will be achieved when the two treatments are combined.
More effective and appropriate treatment methods can be selected by using acupuncture points suitable for OSA and its conditions/diseases.
Clinical Studies on Obstructive Sleep Apnea or Obstructive Sleep Apnea Hypopnea Syndrome.
1st Author [ref] (y) | Study title | Journal |
---|---|---|
Sun [9] (2022) | Clinical study on needle knife acupuncture and acupuncture combined with continuous positive airway pressure ventilation in the treatment of obstructive sleep apnea hypopnea syndrome | Guiding Journal of Traditional Chinese Medicine and Pharmacy |
Shen [6] (2022) | Effect of electro-acupuncture on sleep quality and inflammatory response in patients with mild obstructive sleep apnea hypopnea syndrome | Guangming Journal of Chinese Medicine |
Zhou [10] (2021) | Observations on the efficacy of acupuncture for obstructive sleep apnea-hypopnea syndrome | Shanghai Journal of Acupuncture and Moxibustion |
Zhao [11] (2020) | Clinical observation of Yiqi Huatan Anshen prescription combined with acupuncture in treating severe obstructive sleep apnea hypopnea syndrome with anxiety | China’s Naturopathy |
Liang [12] (2020) | Clinical research of function of using acupuncture adjusting obstructive sleep apnea-hypopnea syndrome patients’ sleeping respiration | Liaoning Journal of Traditional Chinese Medicine |
Lu [13] (2020) | Effect of the acupuncture on the patients with obstructive sleep apnea hypopnea syndrome combined with hypertension | Journal of Hainan Medical University |
Zhang [14] (2019) | Clinical efficacy observation on treatment of obstructive sleep apnea syndrome complicated with essential hypertension with acupuncture combined with medicine | Hebei Journal of Traditional Chinese Medicine |
Zheng [7] (2018) | Protective effect of Chinese medicine combined with acupuncture on obstructive sleep apnea hypopnea syndrome: a randomized controlled study | Modern Medicine Journal of China |
Zhu [15] (2018) | Clinical observation of acupuncture-moxibustion plus rehabilitation for post-stroke obstructive sleep apnea coupled with deglutition disorders | Shanghai Journal of Acupuncture and Moxibustion |
Li [16] (2017) | Clinical observation of obstructive sleep apnea hypopnea syndrome treated by consciousness-restoring and orifices-opening acupuncture | Henan Traditional Chinese Medicine |
Cui [17] (2015) | Effect of acupuncture therapy on ambulatory blood pressure in patients with obstructive sleep apnea syndrome | Liaoning Journal of Traditional Chinese Medicine |
Wang [8] (2015) | Therapeutic observation of acupuncture for acute cerebral infarction coupled with obstructive sleep apnea-hypopnea syndrome | Shanghai Journal of Acupuncture and Moxibustion |
Song [18] (2015) | Curative observation of the electro-acupuncture and nasal continuous positive airway pressure on patients with obstructive sleep apnea hypoventilation syndrome | Journal of Emergency in Traditional Chinese Medicine |
Zhou [19] (2012) | Effect of acupuncture and moxibustion on changes of IFN-γ and IL-4 serum levels in obstructive sleep apnea syndrome patients | Journal of Liaoning University of Traditional Chinese Medicine |
Ye [20] (2010) | Study of acupuncture on stroke combined with obstructive sleep apnea syndrome | Modern Journal of Integrated Traditional Chinese and Western Medicine |
Number of Studies by Publication Year Intervals.
Publication period | |
---|---|
2010–2015 | 5 (34) |
2016–2020 | 7 (46) |
2021–2022 | 3 (20) |
General Characteristics of the Studies Included in the Review.
First author [ref] (y) | Study type | Sample size (T:C) | General characteristics | |||
---|---|---|---|---|---|---|
Sex | Age (y), mean (SD) | Treatment period (d) | ||||
Male | Female | |||||
Sun [9] (2022) | RCT | T: 30 | 24 | 6 | 45.77 ± 7.82 | 90 |
C: 30 | 23 | 7 | 44.40 ± 1.69 | |||
Shen [6] (2022) | RCT | T: 50 | 28 | 22 | 47.46 ± 3.01 | 30 |
C: 50 | 26 | 24 | 47.03 ± 3.17 | |||
Zhou [10] (2021) | RCT | T: 34 | 27 | 7 | 47 ± 13 | 30 |
C: 35 | 26 | 9 | 46 ± 11 | |||
Zhao [11] (2020) | RCT | T: 36 | 21 | 15 | 51.5 ± 3.7 | 30 |
C: 36 | 22 | 14 | 50.5 ± 3.5 | |||
Liang [12] (2020) | RCT | T: 30 | Not reported | 51.00 ± 9.05 | 90 | |
C: 30 | 49.44 ± 9.52 | |||||
Lu [13] (2020) | nRCT | T: 32 | 17 | 15 | 68.41 ± 4.57 | 14 |
C: 34 | 18 | 16 | 67.38 ± 4.48 | |||
Zhang [14] (2019) | RCT | T: 41 | 35 | 6 | 56.3 ± 11.3 | 10 |
C: 41 | 34 | 7 | 55.0 ± 11.8 | |||
Zheng [7] (2018) | RCT | T1: 19 | 46 | 14 | 56.54 ± 14.98 | 20 |
T2: 19 | ||||||
T3: 18 | ||||||
Zhu [15] (2018) | RCT | T: 40 | 17 | 23 | 63 ±11 | 30 |
C: 40 | 21 | 19 | 64 ± 10 | |||
Li [16] (2017) | RCT | T: 50 | 29 | 21 | 50.7 ± 3.5 | 30 |
C: 50 | 27 | 23 | 51.2 ± 3.3 | |||
Cui [17] (2015) | nRCT | T: 26 | 46 | 17 | 54.8 | 30 |
C: 37 | ||||||
Wang [8] (2015) | RCT | T: 63 | 35 | 28 | 64 ± 13 | 30 |
C: 63 | 35 | 28 | 63 ± 14 | |||
Song [18] (2015) | nRCT | T: 36 | 24 | 12 | 53.17 ± 10.20 | 42 |
C: 34 | 23 | 11 | 52.71 ± 11.26 | |||
Zhou [19] (2012) | nRCT | T: 20 | 20 | Not reported | 30 | |
C: 20 | 20 | |||||
Ye [20] (2010) | CS | 21 | 17 | 4 | 60.83 ± 2.02 | 30 |
C, control group; RCT, randomized controlled trial; T, treatment group.
Top 6 Acupoints Used for Treating OSA.
Frequency | Acupoint |
---|---|
11 | REN23 |
6 | LU7 |
5 | ST40, EX9 |
4 | LI11, DU20 |
OSA, obstructive sleep apnea.
Results of the Selected Studies That Were Included in This Review.
First author [ref] (y) | Group | Evaluation of treatment |
---|---|---|
Sun [9] (2022) | A: CPAP + needle knife acupuncture + acupuncture | 1. A (93.33%), B (76.67%) |
Shen [6] (2022) | A: noninvasive positive pressure ventilation therapy + electroacupuncture | 1. A (92.00%), B (76.00%) |
Zhou [10] (2021) | A: acupuncture | 1. A (82.4%), B (22.9%) |
Zhao [11] (2020) | A: CPAP + acupuncture + HM (Yiqi Huatan Anshen prescription) | 2. A (5.22 ± 1.06), B (6.65 ± 1.13) |
Liang [12] (2020) | A: acupuncture | 1. A (96.66%), B (93.33%) |
Lu [13] (2020) | A: acupuncture + GBE + CPAP | 1. A (90.62%), B (61.76%) |
Zhang [14] (2019) | A: WM + acupuncture + HM (Huatan Tongqi decoction) | 1. A (95.12%), B (80.49%) |
Zheng [7] (2018) | A: HM | 2. A (16.32 ± 6.10), B (17.61 ± 9.76), B-1 (11.18 ± 6.53) |
Zhu [15] (2018) | A: acupuncture-moxibustion + oropharyngeal rehabilitation and routine neurological treatment | 1. A (92.5%), B (75.0%) |
Li [16] (2017) | A: acupuncture (Xing Nao Kai Qiao Needling Technique) + CPAP | 1. A (88.0%), B (70.0%) |
Cui [17] (2015) | A: hypertension | 4. DSBP (mmHg) |
Wang [8] (2015) | A: acupuncture + conventional comprehensive treatment | 1. A (93.7%), B (82.5%) |
Song [18] (2015) | A: electro-acupuncture + nCPAP | 2. A (8.65 ± 3.31), B (19.42 ± 7.06) |
Zhou [19] (2012) | A: OSAS | 4. IFN-γ (ng/L) |
Ye [20] (2010) | Acupuncture | 2. 26.87 ± 3.63 |
*A: Treatment group.
†B, B-1: Control group.
‡1. Clinical efficacy, 2. Sleep apnea-hypopnea index (AHI), 3. Saturation of partial pressure oxygen [SpO2 (%)], 4. Others.
CPAP, continuous positive airway pressure; DSBP, daytime systolic blood pressure; DDBP, daytime diastolic blood pressure; ESS, Epworth sleepiness scale; GBE, Gingko biloba extract; HAMA, Hamilton anxiety scale; HM, herbal medicine; IFN-γ, interferon gamma; IL-4, interleukin-4; NSBP, nocturnal systolic blood pressure; NDBP, nocturnal diastolic blood pressure; OSA, obstructive sleep apnea; PP, pulse pressure; REM%, rapid eye movement; SAS score, self-rating anxiety score; SDS score, self-rating depression score; Stage 3%
+ Stage 4%, deep sleep stage; WM, Western medicine.
List of Acupoints Used.
First author [ref] (y) | Acupoint |
---|---|
Sun [9] (2022) | EX-HN9 |
Shen [6] (2022) | DU20, GB20, EX11, EX3, LI20, LI4 |
Zhou [10] (2021) | EX11, LI20, Bang-REN23, EX-HN22, LU7, KD3, SP3 |
Zhao [11] (2020) | LI11, ST25, SP9, ST40, LV3 |
Liang [12] (2020) | EX-HN21, DU16, DU15, LU7, KD6, ST36, ST40 |
Lu [13] (2020) | LI11, LV3, ST9, REN23 |
Zhang [14] (2019) | REN23, ST9, REN17, REN6, SP6, ST36, LU7, KD6, LI4, DU20, DU16, DU26 |
Zheng [7] (2018) | REN23, Bang-REN23, EX-9, ST40, SP9, LI11, ST44 |
Zhu [15] (2018) | DU15, GB20, REN22, REN23, LI4 |
Li [16] (2017) | PC6, EX11, SP6, EX9, REN23, GB20, LU7, ST40, KD6 |
Cui [17] (2015) | ST9, REN23, REN22, LI11, LV3 |
Wang [8] (2015) | DU20, EX9, REN23, GB20, REN22, LU7, KD6, SP9, KD3 |
Song [18] (2015) | EX-HN22, EX9, HT7, ST36, SP6, KD6 |
Zhou [19] (2012) | EX-HN21, DU20, DU15, GB20, SJ17, EX9, LU7, HT7, ST40, KD6 |
Ye [20] (2010) | REN23 |
Journal of Acupuncture Research 2022; 39(4): 275-282
Published online November 23, 2022 https://doi.org/10.13045/jar.2022.00206
Copyright © Korean Acupuncture & Moxibustion Medicine Society.
Hye Kyung Baek1*, Young Jun Kim1, Yeon Sun Lee1, Hye Ri Jo1, Mi So Park2, Dong Guk Shin3, Hyun A Shim3
1Department of Acupuncture and Moxibustion Medicine, Bucheon Jaseng Korean Medicine Hospital, Bucheon, Korea;2Department of Oriental Internal Medicine, Bucheon Jaseng Korean Medicine Hospital, Bucheon, Korea;3Department of Oriental Neuropsychiatry Medicine, Bucheon Jaseng Korean Medicine Hospital, Bucheon, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The purpose of this study was to analyze acupuncture treatment methods and acupoints used to treat obstructive sleep apnea (OSA) or obstructive sleep apnea-hypoapnea syndrome (OSAHS). The data were retrieved from January 2010 to May 2022 from the China National Knowledge Infrastructure database. The search terms included “adult,” “obstructive sleep apnea,” “obstructive sleep apnea hypoapnea syndrome,” “acupuncture,” and “electro-acupuncture.” Clinical trials for acupuncture treatment of OSA or OSAHS were included in this review (4 non-randomized controlled studies, 1 was a case report, and 10 randomized controlled studies). For OSA and OSAHS treatment, the acupoints that were most frequently used included REN23, LU7, ST40, EX9, LI11, and DU20. Compared with the control or Western treatment group, the treatment outcome measures of participants in the acupuncture treatment group significantly improved. In some studies, participants in the acupuncture group did not have side effects and the treatment was cost-effective. The data analyzed in this review suggest that acupuncture is an effective treatment for OSA or OSAHS.
Keywords: acupuncture, adult, electroacupuncture, obstructive sleep apnea hypoapnea syndrome
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder wherein frequent arousal and a decrease in arterial oxygen saturation occur repeatedly during sleep due to the obstruction of airflow through the upper respiratory tract [1]. Untreated OSA can cause various complications including increased risk of surgery, hypertension, heart failure, stroke, coronary artery disease, arrhythmia, pulmonary hypertension, diabetes, and erectile dysfunction [2]. Furthermore, OSA-induced complications can contribute to the deterioration of the quality of life (QOL) of each individual [3].
Current OSA treatments include the use of the continuous positive airway pressure (CPAP) machine, an oral appliance, surgery, and other adjuvant treatments (weight control, posture therapy). Among the treatments, CPAP is the most representative treatment for OSA [4] and involves the use of a machine that is specifically designed to maintain constant air-flow pressure in the upper airways to prevent the airway from collapsing or narrowing [1]. CPAP can improve sleep quality, cognitive function, daytime sleepiness, health-related QOL (for mild OSA), and mood as well as decrease blood pressure, however, in patients with severe or moderate OSA, no significant improvement in the QOL was observed [1].
Herbal medicine and acupuncture treatment of OSA has been reported in Korea, although this was a case report and so the nature of the report limits its relevance in treatment effectiveness of CPAP [5].
In China, OSA is classified into the “snoring” and “snoring while sleeping” categories, and the main etiologies are pulmonary, splenic, or renal dysfunction, or a condition/disease that is caused due to Three Intestine dysfunction [6]. In addition, the cause of OSA is attributed to the poor spread of qi as well as impaired pulmonary, splenic, and renal function. Moreover, when a condition/disease reaches the throat where the lung, spleen, and kidney meridian veins are situated, it leads to “clogging” of the throat and prevents smooth passage of air [6]. Based on this hypothesis of the pathology underlying OSA, various research studies evaluating either Chinese medicine alone or an integration of Chinese and Western medicine are ongoing in China. This review presents analysis of data from the latest clinical studies on OSA in China retrieved from the China National Knowledge Infrastructure (CNKI) database. This review was undertaken with an aim to provide basic data for future domestic OSA treatment and clinical research and to contribute to the evidence based for Oriental treatment of OSA.
To investigate the clinical efficacy of traditional Chinese medicine for OSA or obstructive sleep apnea-hypopnea syndrome (OSAHS), the CNKI database was searched for clinical trials published from 2010 to 2022. The following keywords in English were used: “Obstructive Sleep Apnea,” “Obstructive Sleep Apnea Hypopnea Syndrome,” “acupuncture,” and “electroacupuncture.”
A total of 26 studies were retrieved from the CNKI database (Table 1 [6–20]) . Of these, 4 studies included pediatric patients (≤ 15 years), 4 were reviews and meta-analyses, and 3 were unrelated to OSA. Therefore, 15 studies were included in the analysis (Fig. 1).
Analysis by the year of publication showed that, from January 2010 to May 2022, 5 studies were published between 2010 and 2015, 7 between 2016 and 2020, and 3 between 2021 and 2022 (Table 2).
Among the 15 studies, 4 reported findings from non-randomized controlled studies, 1 was a case report, and 10 reported outcomes from randomized controlled trials (Table 3 [6–20]).
OSA constitutes a recurrent obstruction of the upper airway during sleep, and the resultant increased resistance induces snoring, intermittent hypoxia, and hypercapnia. Moreover, sleep cycles are impaired by frequent arousal. These physiological changes during sleep induce an increase in the production of reactive oxygen species and systemic inflammation due to repeated hypoxia-reoxygenation. OSA is related to the amount of abdominal fat, and the prevalence of OSA is reported to be high not only in the West, but also in Korea where there has been an increase in the proportion of the obese individuals due to westernized eating habits and lifestyle [21]. A study of the prevalence of sleep apnea in adults aged 40 to 69 years showed that the prevalence of mild obstructive sleep apnea was 27% in men and 16% in women in Korea [22].
Polysomnography is an objective test to study sleep and is used to accurately diagnose and evaluate sleep disorders. This test includes measurement of the patients’ brain waves, eye movements, electromyography of the lower extremities and jaws, electrocardiograms, chest and abdominal breathing movements, blood oxygen saturation, and respiratory flow are recorded mainly during sleep and then analyzed. Snoring, sleep apnea, insomnia, narcolepsy, and periodic limb movements are identified in polysomnography, which is useful for diagnosing abnormal behavior during sleep as well as for diagnosing the therapeutic effect.
In the majority of studies included in this review, OSA was diagnosed using polysomnography. In particular, the apneahypopnea index (AHI), which is used as an evaluation index in most studies, is an index for evaluating the severity of OSA and represents the sum of sleep apnea and hypopnea that is divided by the total sleep time. Thus, an AHI of < 15, 15 to < 30, and ≥ 30 indicates mild, moderate, and severe sleep apnea, respectively.
In this study, to determine the effects of acupuncture on OSA and OSAHS the results of a literature review of 15 studies published from 2010 to May 2022 were assessed. The analysis showed that acupuncture or electroacupuncture had a significant effect on OSA and OSAHS. Although most of the studies described acupuncture treatment for OSA or OSAHS, conditions/diseases such as depression and stroke that may be caused by, or accompany OSA or OSAHS, were also investigated. Therefore, the acupoints used for these other conditions/diseases differ slightly, depending on the characteristics of the diagnosed condition/disease (Table 4). With regard to the improvement of OSA, common acupoints could be ascertained (Table 5 [6–20]). In particular, REN23 was used in 11 of the 15 studies and was the most frequently used acupoint (Table 5 [6–20]). REN23 is located in the larynx, which is the intersection of the yin and yin you veins, and the branches of the sublingual and glossopharyngeal nerves are located under the acupoint [7]. Thus, by directly stimulating the sublingual and glossopharyngeal nerves, the pressure on the lumen of the throat can be reduced and this would keep the pressure constant in the throat and strengthen the muscles [8].
The second most frequently used acupuncture point was LU7, which comprises the pulmonary meridian, eight extra meridians, and yin meridian, and harmonizes the pulmonary qi that reaches the throat [8]. In addition, ST40 was relevant in the context that one of the causes of OSA is wetness, and ST40 was used to remove moisture and phlegm [7].
Shen et al [6] conducted a study on patients with mild OSHAS, and the AHI, LSaO2, and LAT levels were higher in the group that was treated with electroacupuncture as compared with the control group which received noninvasive positive pressure ventilation (
Zheng et al [7] compared patients with obstructive sleep apnea hypopnea treated with simple herbal medicine, simple acupuncture, or a combination of herbal medicine and acupuncture. The authors determined that the AHI, snoring index, minimum oxygen saturation, sleep stage, and ESS score was significantly higher in the group that received acupuncture and herbal medicine compared with the other treatments (
Wang [8] observed that OSAHS showed a better improvement when acupuncture along with Western therapy was applied to patients with acute cerebral infarction accompanied by OSAHS, compared with the control group which was Western therapy such as thrombolytic drug administration. The AHI and SaO2 improved more when acupuncture was combined with other treatments compared with the control group (
Sun et al [9] reported the AHI, snoring index, longest apnea time (LAT), nocturnal hypoxic saturation (LSaO2), serum interleukin (IL-33), serum interleukin-37 (IL-37), and QOL in the treatment group compared with the control group, and determined that the AHI, snoring indices, LAT, IL-33, and IL-37 levels in the treatment group receiving acupuncture and CPAP treatment were lower than the control group (
Zhou et al [10] compared the AHI, SaO2, and the Epworth Sleepiness Scale (ESS) score. Unlike in the control group which did not receive treatment, other than health education, the treatment group received health education, acupuncture and electroacupuncture, and the AHI, SaO2, and all ESS scores were significantly better than the control group (
Zhao [11] investigated the treatment of severe OSA accompanied by anxiety and hypoventilation syndrome, and the control group received intelligent CPAP. Moreover, in the treatment group, acupuncture and Yiqi Huatan Anshen prescription were administered. The results showed that the AHI and the Hamiltonian Anxiety Scale score in the treatment group decreased from the pretreatment level, and the oxygen saturation SpO2 improved compared with the baseline (
Liang et al [12] conducted a study with a control group that received nasal continuous positive airway pressure (nCPAP) therapy and a treatment group that received acupuncture, and both groups showed improvement after 3 months of treatment (
Lulu et al [13] investigated the effect of acupuncture on the improvement of sleep apnea and reduction of blood pressure in patients with OSA accompanied by hypertension. In the control group, gingko biloba extract and CPAP were administered, whereas in the treatment group acupuncture was added to these two treatments. As a result, the respiratory index was better than the control, blood pressure was lower, and the oxidizing substances, including reactive oxygen species and malondialdehyde, were lower after treatment compared with the control (
Zhang et al [14] reported that in the treatment of OSA accompanied by essential hypertension, the AHI and ESS scores were lower than the control and the LSaO2 were higher than the control (
Zhu et al [15] conducted a study on patients suffering from poststroke OSA and dysphagia. The control group received oropharyngeal rehabilitation training and routine neurological treatment and in addition, the treatment group had acupuncture and moxibustion. The results on polysomnography and symptoms of dysphagia improved in the treatment group compared with the control group (
Li et al [16] showed that in patients with OSAHS, compared with the control group treated with nCPAP alone, the polysomnography test results were better than the control group when the Xing Nao Kai Qiao needling technique was used which employs PC6, EX11, and SP6 as the main acupoints (
A study by Cui et al [17] involved a comparison of patients with OSA with and without hypertension, and showed that the patient group with OSA and hypertension had significantly reduced ambulatory blood pressure during acupuncture treatment compared with patients with OSA (
Song et al [18] reported that the AHI, LSaO2, LAT, the pulse pressure, self-rating anxiety score, self-rating depression score, and Epworth sleepiness scale score improved more in the group treated with electroacupuncture and nCPAP compared with the control group treated with nCPAP alone (
Zhou et al [19] studied the changes in serum interferon (IFN)-γ and IL-4 between the normal group and the OSAHS group. In the case of OSAHS patients, the pretreatment level of IFN-γ increased compared with that in the normal group, and IL-4 level decreased. Moreover, the level of IFN-γ decreased and the level of IL-4 increased after receiving acupuncture and noninvasive mechanical ventilation (
A case study by Ye et al [20] reported on sleep apnea in a stroke patient. The AHI decreased from baseline, LSaO2 increased, and the ESS score significantly decreased (all
Acupuncture was reported to be effective in treating OSA and OSAHS in 15 studies. CPAP, which is currently the most commonly used OSA treatment, was used as the control alone or in a treatment combination. It was inferred that acupuncture may replace CPAP and when used together with the treatment, a synergistic effect occurred. OSA and OSAHS can be seen as a result of lifestyle-related conditions/diseases. Most of the treatment periods were less than 30 days, so judging treatment continuity is limited. Currently, oriental medical treatment approaches for OSA and OSAHS in Korea are insufficient. Based on the studies reviewed, the results are meaningful if observed over a long period of time. In addition, Zhou et al [10] and Zheng et al [7] used the Bang-REN23, which is an acupoint located 1 cun to the left and right from the REN23, and is used for the treatment of OSA and OSAHS. It is an acupoint that is not frequently used for OSA treatment in Korea. In the future, it would be good if papers using the above acupoints could be published in Korea to prove the effect.
A total of 15 studies related to OSA or obstructive sleep apnea hypopnea syndrome were analyzed to determine the research trends of treatment using acupuncture from January 2010 to May 2022.
The most commonly used acupoints in obstructive sleep apnea studies were REN23, LU7, ST40, EX9, LI11, and DU20.
The use of acupuncture in the treatment of OSA is reliable and economical. It may be a good alternative to CPAP (which is generally used) or may be a more effective method. In addition, a greater synergistic effect will be achieved when the two treatments are combined.
More effective and appropriate treatment methods can be selected by using acupuncture points suitable for OSA and its conditions/diseases.
Flowchart of study selection in this review.
Table 1 . Clinical Studies on Obstructive Sleep Apnea or Obstructive Sleep Apnea Hypopnea Syndrome..
1st Author [ref] (y) | Study title | Journal |
---|---|---|
Sun [9] (2022) | Clinical study on needle knife acupuncture and acupuncture combined with continuous positive airway pressure ventilation in the treatment of obstructive sleep apnea hypopnea syndrome | Guiding Journal of Traditional Chinese Medicine and Pharmacy |
Shen [6] (2022) | Effect of electro-acupuncture on sleep quality and inflammatory response in patients with mild obstructive sleep apnea hypopnea syndrome | Guangming Journal of Chinese Medicine |
Zhou [10] (2021) | Observations on the efficacy of acupuncture for obstructive sleep apnea-hypopnea syndrome | Shanghai Journal of Acupuncture and Moxibustion |
Zhao [11] (2020) | Clinical observation of Yiqi Huatan Anshen prescription combined with acupuncture in treating severe obstructive sleep apnea hypopnea syndrome with anxiety | China’s Naturopathy |
Liang [12] (2020) | Clinical research of function of using acupuncture adjusting obstructive sleep apnea-hypopnea syndrome patients’ sleeping respiration | Liaoning Journal of Traditional Chinese Medicine |
Lu [13] (2020) | Effect of the acupuncture on the patients with obstructive sleep apnea hypopnea syndrome combined with hypertension | Journal of Hainan Medical University |
Zhang [14] (2019) | Clinical efficacy observation on treatment of obstructive sleep apnea syndrome complicated with essential hypertension with acupuncture combined with medicine | Hebei Journal of Traditional Chinese Medicine |
Zheng [7] (2018) | Protective effect of Chinese medicine combined with acupuncture on obstructive sleep apnea hypopnea syndrome: a randomized controlled study | Modern Medicine Journal of China |
Zhu [15] (2018) | Clinical observation of acupuncture-moxibustion plus rehabilitation for post-stroke obstructive sleep apnea coupled with deglutition disorders | Shanghai Journal of Acupuncture and Moxibustion |
Li [16] (2017) | Clinical observation of obstructive sleep apnea hypopnea syndrome treated by consciousness-restoring and orifices-opening acupuncture | Henan Traditional Chinese Medicine |
Cui [17] (2015) | Effect of acupuncture therapy on ambulatory blood pressure in patients with obstructive sleep apnea syndrome | Liaoning Journal of Traditional Chinese Medicine |
Wang [8] (2015) | Therapeutic observation of acupuncture for acute cerebral infarction coupled with obstructive sleep apnea-hypopnea syndrome | Shanghai Journal of Acupuncture and Moxibustion |
Song [18] (2015) | Curative observation of the electro-acupuncture and nasal continuous positive airway pressure on patients with obstructive sleep apnea hypoventilation syndrome | Journal of Emergency in Traditional Chinese Medicine |
Zhou [19] (2012) | Effect of acupuncture and moxibustion on changes of IFN-γ and IL-4 serum levels in obstructive sleep apnea syndrome patients | Journal of Liaoning University of Traditional Chinese Medicine |
Ye [20] (2010) | Study of acupuncture on stroke combined with obstructive sleep apnea syndrome | Modern Journal of Integrated Traditional Chinese and Western Medicine |
Table 2 . Number of Studies by Publication Year Intervals..
Publication period | |
---|---|
2010–2015 | 5 (34) |
2016–2020 | 7 (46) |
2021–2022 | 3 (20) |
Table 3 . General Characteristics of the Studies Included in the Review..
First author [ref] (y) | Study type | Sample size (T:C) | General characteristics | |||
---|---|---|---|---|---|---|
Sex | Age (y), mean (SD) | Treatment period (d) | ||||
Male | Female | |||||
Sun [9] (2022) | RCT | T: 30 | 24 | 6 | 45.77 ± 7.82 | 90 |
C: 30 | 23 | 7 | 44.40 ± 1.69 | |||
Shen [6] (2022) | RCT | T: 50 | 28 | 22 | 47.46 ± 3.01 | 30 |
C: 50 | 26 | 24 | 47.03 ± 3.17 | |||
Zhou [10] (2021) | RCT | T: 34 | 27 | 7 | 47 ± 13 | 30 |
C: 35 | 26 | 9 | 46 ± 11 | |||
Zhao [11] (2020) | RCT | T: 36 | 21 | 15 | 51.5 ± 3.7 | 30 |
C: 36 | 22 | 14 | 50.5 ± 3.5 | |||
Liang [12] (2020) | RCT | T: 30 | Not reported | 51.00 ± 9.05 | 90 | |
C: 30 | 49.44 ± 9.52 | |||||
Lu [13] (2020) | nRCT | T: 32 | 17 | 15 | 68.41 ± 4.57 | 14 |
C: 34 | 18 | 16 | 67.38 ± 4.48 | |||
Zhang [14] (2019) | RCT | T: 41 | 35 | 6 | 56.3 ± 11.3 | 10 |
C: 41 | 34 | 7 | 55.0 ± 11.8 | |||
Zheng [7] (2018) | RCT | T1: 19 | 46 | 14 | 56.54 ± 14.98 | 20 |
T2: 19 | ||||||
T3: 18 | ||||||
Zhu [15] (2018) | RCT | T: 40 | 17 | 23 | 63 ±11 | 30 |
C: 40 | 21 | 19 | 64 ± 10 | |||
Li [16] (2017) | RCT | T: 50 | 29 | 21 | 50.7 ± 3.5 | 30 |
C: 50 | 27 | 23 | 51.2 ± 3.3 | |||
Cui [17] (2015) | nRCT | T: 26 | 46 | 17 | 54.8 | 30 |
C: 37 | ||||||
Wang [8] (2015) | RCT | T: 63 | 35 | 28 | 64 ± 13 | 30 |
C: 63 | 35 | 28 | 63 ± 14 | |||
Song [18] (2015) | nRCT | T: 36 | 24 | 12 | 53.17 ± 10.20 | 42 |
C: 34 | 23 | 11 | 52.71 ± 11.26 | |||
Zhou [19] (2012) | nRCT | T: 20 | 20 | Not reported | 30 | |
C: 20 | 20 | |||||
Ye [20] (2010) | CS | 21 | 17 | 4 | 60.83 ± 2.02 | 30 |
C, control group; RCT, randomized controlled trial; T, treatment group..
Table 4 . Top 6 Acupoints Used for Treating OSA..
Frequency | Acupoint |
---|---|
11 | REN23 |
6 | LU7 |
5 | ST40, EX9 |
4 | LI11, DU20 |
OSA, obstructive sleep apnea..
Table 5 . Results of the Selected Studies That Were Included in This Review..
First author [ref] (y) | Group | Evaluation of treatment |
---|---|---|
Sun [9] (2022) | A: CPAP + needle knife acupuncture + acupuncture | 1. A (93.33%), B (76.67%) |
Shen [6] (2022) | A: noninvasive positive pressure ventilation therapy + electroacupuncture | 1. A (92.00%), B (76.00%) |
Zhou [10] (2021) | A: acupuncture | 1. A (82.4%), B (22.9%) |
Zhao [11] (2020) | A: CPAP + acupuncture + HM (Yiqi Huatan Anshen prescription) | 2. A (5.22 ± 1.06), B (6.65 ± 1.13) |
Liang [12] (2020) | A: acupuncture | 1. A (96.66%), B (93.33%) |
Lu [13] (2020) | A: acupuncture + GBE + CPAP | 1. A (90.62%), B (61.76%) |
Zhang [14] (2019) | A: WM + acupuncture + HM (Huatan Tongqi decoction) | 1. A (95.12%), B (80.49%) |
Zheng [7] (2018) | A: HM | 2. A (16.32 ± 6.10), B (17.61 ± 9.76), B-1 (11.18 ± 6.53) |
Zhu [15] (2018) | A: acupuncture-moxibustion + oropharyngeal rehabilitation and routine neurological treatment | 1. A (92.5%), B (75.0%) |
Li [16] (2017) | A: acupuncture (Xing Nao Kai Qiao Needling Technique) + CPAP | 1. A (88.0%), B (70.0%) |
Cui [17] (2015) | A: hypertension | 4. DSBP (mmHg) |
Wang [8] (2015) | A: acupuncture + conventional comprehensive treatment | 1. A (93.7%), B (82.5%) |
Song [18] (2015) | A: electro-acupuncture + nCPAP | 2. A (8.65 ± 3.31), B (19.42 ± 7.06) |
Zhou [19] (2012) | A: OSAS | 4. IFN-γ (ng/L) |
Ye [20] (2010) | Acupuncture | 2. 26.87 ± 3.63 |
*A: Treatment group.
†B, B-1: Control group.
‡1. Clinical efficacy, 2. Sleep apnea-hypopnea index (AHI), 3. Saturation of partial pressure oxygen [SpO2 (%)], 4. Others.
CPAP, continuous positive airway pressure; DSBP, daytime systolic blood pressure; DDBP, daytime diastolic blood pressure; ESS, Epworth sleepiness scale; GBE, Gingko biloba extract; HAMA, Hamilton anxiety scale; HM, herbal medicine; IFN-γ, interferon gamma; IL-4, interleukin-4; NSBP, nocturnal systolic blood pressure; NDBP, nocturnal diastolic blood pressure; OSA, obstructive sleep apnea; PP, pulse pressure; REM%, rapid eye movement; SAS score, self-rating anxiety score; SDS score, self-rating depression score; Stage 3%.
+ Stage 4%, deep sleep stage; WM, Western medicine..
Table 6 . List of Acupoints Used..
First author [ref] (y) | Acupoint |
---|---|
Sun [9] (2022) | EX-HN9 |
Shen [6] (2022) | DU20, GB20, EX11, EX3, LI20, LI4 |
Zhou [10] (2021) | EX11, LI20, Bang-REN23, EX-HN22, LU7, KD3, SP3 |
Zhao [11] (2020) | LI11, ST25, SP9, ST40, LV3 |
Liang [12] (2020) | EX-HN21, DU16, DU15, LU7, KD6, ST36, ST40 |
Lu [13] (2020) | LI11, LV3, ST9, REN23 |
Zhang [14] (2019) | REN23, ST9, REN17, REN6, SP6, ST36, LU7, KD6, LI4, DU20, DU16, DU26 |
Zheng [7] (2018) | REN23, Bang-REN23, EX-9, ST40, SP9, LI11, ST44 |
Zhu [15] (2018) | DU15, GB20, REN22, REN23, LI4 |
Li [16] (2017) | PC6, EX11, SP6, EX9, REN23, GB20, LU7, ST40, KD6 |
Cui [17] (2015) | ST9, REN23, REN22, LI11, LV3 |
Wang [8] (2015) | DU20, EX9, REN23, GB20, REN22, LU7, KD6, SP9, KD3 |
Song [18] (2015) | EX-HN22, EX9, HT7, ST36, SP6, KD6 |
Zhou [19] (2012) | EX-HN21, DU20, DU15, GB20, SJ17, EX9, LU7, HT7, ST40, KD6 |
Ye [20] (2010) | REN23 |
Yong Ho Ku, Jae Hui Kang, Hae Jin Kong, Hwa Yeon Ryu, Hyun Lee*
Journal of Acupuncture Research 2019; 36(2): 59-71Bo Hyun Kim, Tae Han Yook, Beom Yong Song, Yoo Min Choi, Jin Hyeon Shin, Sanghun Lee, Young Ju Jeon, Je Heon Noh, Jong Uk Kim*
Journal of Acupuncture Research 2018; 35(4): 214-218Sung Jin Kim, Seong Mok Jeong, Chang Hee Lee, Jin-Young Yoon, Sung Eun Shim, Jeong Hyon Kim, Bon Hyuk Goo, Yeon Cheol Park, Yong-Hyun Baek, Sang Soo Nam, Byung-Kwan Seo*
Journal of Acupuncture Research 2018; 35(4): 158-168
Flowchart of study selection in this review.