The physical, physiological, and biological effects of qigong therapy

Qigong is a Chinese traditional practice that has been developed for thousands of years. One of its purposes is to improve and sustain health. Research has also shown that Qigong is effective in improving many health outcomes. Many research gaps exist, especially concerning study design and investigations into the physiological and biological effects of Qigong practice. To fill in the knowledge void, this review focuses on the state of qigong research regarding its physical, physiological, and biological effects. Our findings suggest that far-infrared, bio magnetic, and neurological applications are common measurements in understanding the physical effects of Qigong. Heart rate variations, pulse, and blood pressure changes are also commonly used in measuring physiological effects of Qigong. Last, biological effects of Qigong may include biochemical parameters, glucose, and immune parameters, among others. More methodological rigorous research exploring the particular physiological and biological pathway of Qigong practice and health outcomes is needed. Future research should also closely examine the feasibility and adaptability of Qigong therapy while evaluating the effects of Qigong versus other forms of mind-body exercise. Last, researchers, health providers and community leaders should investigate and improve the physical and psychosocial health and health behaviors of minority populations through culturally appropriate and adaptable exercises like Qigong.


Background
Qigong is an increasingly popular modality of traditional Chinese medicine (TCM) believed to be over 4,000 years old [1]. Written records referring to Qi (vital energy) and its effects are thought to be as old as 3,300 years. Qigong exercise is based on the traditional Chinese belief and Taoist philosophy that human body contains a network of energy pathways through which vital energy circulate. As a mind-body practice in Energy Medicine, Qigong aims to achieve a harmonious flow of vital energy in the body and regulate the functional activities of the body through regulated breathing, mindful meditation, and gentle movements [2].
Qigong is a mind-body practice that uses breathing adjustment, body postures and/or mindful meditation to harmonize the body, mind, and spirit. Its main theory is that discomfort, pain, and sickness are a result of energy; that is, if there is a free flow of energy (Qi) and a balance of energy (Qi) in the energy channel, health can be improved, maintained and disease prevented. Blocked Qi was considered to be the original of many illnesses and diseases [3].
In the past decade, a growing number of studies globally have critically evaluated the effectiveness of qigong exercise in physical, mental and cognitive health improvement. Existing systematic reviews and meta-analyses examined the clinical evidence of the beneficial effects of qigong on different medical conditions, including cancer [4][5][6][7], cardiopulmonary diseases [8,9], hypertension [10][11][12], infectious deceases [13]; movement disorder [14,15] and fibromyalgia [16]. Other reviews also examined the overall effectiveness of qigong on chronic condition management including diabetes [17] and pain management [18]. Several recently published systematic reviews further provided evidence on the effectiveness of Qigong exercises on reducing psychological distress including depressive symptoms, anxiety symptoms [19,20].
Whereas health effects of Qigong practice have been addressed in the current medical and public health literature, few reviews have systematically evaluated the key components of Qigong biofields that are closely associated with its healing effects, except two review articles published about ten years ago [21,22] . Researchers in complementary and alternative medicine (CAM) continue to have different conceptualization in ways to measure Qi. Chen et al proposed that if there was bioenergy, then it should be detectable and measurable by physical instruments or biomarkers [23]. Others argued that bioenergy also exists in the forms of electrical, magnetic, and/or electromagnetic substance in nature and that it's transmission and reception would interact at the cellular and molecular levels [24]. However, to date, the concept of Qi bioenergy has not been well-articulated. This research gap points to the ongoing methodological challenges in Qigong therapy research; mainly, knowing what is to be measured, what could be measured, and finding appropriate technologies and measurements to properly develop the approaches and instrumentation associated with the practice of Qigong [25,26].

Results
Our search yielded 59 English-language results and 13 Chineselanguage results; the major methods for measuring or evaluating Qigong effects can be classified into the following three categories of detector: 1) physical signal detectors; 2) physiological dynamics methods; 3) biological materials as detectors.

Physical signal detectors
Physical detectors are the primary methods that most researchers have used as they fit into the traditional energy assessment model ( Table 1) [22]. Such studies typically assess heat, magnetism, electricity, or radiation. Many other exploratory studies of external Qigong effects have used various physical detectors, including Gamma ray, microwave, and high-frequency X-ray. Body temperature changes before, during, and after the practice of Qigong have been documented by many empirical studies [27][28][29], in which far-infrared measurement was amongst the most commonly used physical detectors of Qi [21]. A few studies tested with far-infrared thermography demonstrated the significant temperature change on the body surface with infrared detectors during both self-qigong practices or with a qigong healer. Working with Spanish children aged between 10-12, Matos et al. [30] showed that there were statistically significant changes in temperature measured by thermography occurred during the exercises and at the beginning and at the endpoint of the observation interval (p<0.001), and effects remain stable after weeks of training. Through direct observation, Lo et al. [27] reported significant changes in the maximum temperature measured by infrared images in body surface temperature including front, back and face regions. However, current far and infrared findings are predominantly limited in Chinese literature, and most focused on directly observing the external Qi dissipated from Qigong masters rather than recording the flow of Qi per se [21].
Biomagnetic is another commonly used application to measure healing effects. The application of magnetic field is a widely used ancient healing technique around the world. Previous studies in therapeutic touch suggested that the 8-to 10-Hz frequency band may be associated with emission from the human biofield during therapeutic interventions [31,32]. Similarly, in an observational Qigong study conducted in Japan, Hisamitsu [33] found that the 8-12 Hz frequency band was emitted when participants performed breathing techniques. This study finding suggested that Qigong breathing appeared to stimulate a large biomagnetic field emission similar to other alternative therapies.
Brain change associated with Qigong has been central in scholarly inquires. Due to its high costs, few studies have thus far investigated functional-MRI changes in large-scale studies. Current available f-MRI studies with Qigong masters suggested that the response amplitude of the SII-insula region under the state of Qigong (3.5%) was greater than that before Qigong (1.2%) [34]. Another observation study in China reported significant frontal lobe and left temporal lobe changes (p<0.05) under Qigong stimulation state [35]. After a short-term meditation training, MRI images showed increased brain connectivity in the anterior cingulated, suggesting that Qigong meditation might have the potential to rewire neurons in the brain and rebuild connections among neurotransmitters. However, limited study to date has included f-MRI scans before and after Qi practice with a large sample of layman practitioners.
In addition to neuroimaging techniques such as f-MRI, EEG and   EMG are also commonly used to measure the electrical activity of the brain surrounding Qigong [36]. Effects were shown across practitioners of various experiences, ranging from Qigong masters to those with no prior experiences. The effects appear to be most pronounced in the studies conducted among Qigong masters of at least 20-25 years of practice [37,38]. However, a recent review study in the physiological effects of biofield-based therapies suggested that EEG changes were inconsistent and may not specific to biofield therapies [39]. Evoked potentials, another electrophysiological recording method, have also been applied to Qigong research. Although signals can be recorded cerebral cortex, visual cortex [40], auditory evokes potential [41], or spinal cord, studies using evoked potentials are limited to measuring the effects of qigong meditation. There is limited pre, during or post data on the physical exercise component of Qigong. Table 2 presents physiological methods in assessing therapeutic effects of Qigong. Clinical research studies consistently use heart rate variability as a marker of autonomic tone. The majority of the studies included in this review presented HRV either as a primary or secondary outcome or interests. Although most researcher concluded significant changes in heart rate before, during, and after Qigong exercise, there are other observational studies that showed no heart rate changes before or after QG practice [34]. Regarding heart rate variability, a quasi-experimental design study among wheelchair-bound older adults observed no differences between experimental groups and control groups regarding all HRV parameters after 12 weeks of Qigong [42]. Another cross-sectional analysis reported, however, that all HRV parameters were significantly higher in practitioners than those of non-practitioners. The number of years of Tai Chi experience did not correlate with the value of heart rate variability parameters [43]. It is important to note that these study discrepancies may be explained by various Qigong training styles, length of each program, and exercise frequency and intensities [44].  TC, TG, HDL-C and LDL-C were tested at the beginning the intervention and after the intervention.

Physiological dynamics methods
To explore the effect of QG exercise on blood lipid metabolism of elder intellectuals After 8 weeks of intervention, there appeared a trend of improvement of blood lipid metabolism for both men and women. There seem to be a gender difference for the outcome in this study that women, in general, improved more significantly than men. For middle age female participants, HDL-C and LDL-C improved significantly, for senior female participants, TC, TG, HDL-C and LDL-C improved significantly; for middle age male participants, HDL-C and LDL-C improved significantly; for senior male participants, TG, HDL-C and LDL-C improved significantly. The majority of the empirical studies aiming to quantify Qi started with measuring changes in blood pressure and pulse. A growing number of direct observational studies have consistently shown the decrease of blood pressure and pulse after practicing Qigong [45][46][47]. Researchers utilized a mix of vital measures including heart rate, respiration rate, systolic blood pressure, diastolic blood pressure to demonstrate the health and clinical effects of Qigong in community-dwelling persons as well as patients with diabetes [1], hypertension [47], or cancer [48]. The recent randomized control trials (RCT) on Qigong exercises show that intervention groups (Qigong) reported a significant reduction of Systolic blood pressure, but not diastolic BP [49]. In addition, most RCT design is only up to 6 months post intervention. Further studies need to be clear about design mechanism as well as length in potential follow-up time.
Other physiological studies which measure blood lipids change in Qigong exercise generally found an improvement of blood lipids metabolism after Qigong. Interestingly, Li et al. [50] observed a gender difference in the change; compared to 24 male participants enrolled in the trial, female participants (n=24) reported greater and more significant improvement. Similarly, another quasi-trial designed study reported the improvement in blood lipids metabolism was more significant in the older adults groups compared to a younger age group [51]. While both studies show that Qigong practice can improve blood lipids metabolism under well-designed conditions, studies with blood lipids metabolism as the primary outcome of interests were limited to only projects conducted in China. Its generalizability to other racial/ ethnic groups remains to be tested.

Biological materials as detectors
Given the biological material, such as individual cells and biological molecules such as proteins and antibiotics are assumed to possess Qi (vital energy), and that they may be particularly sensitive to the internal qi or external qi emitted by qigong practitioners; the concept of a biological detector has long been documented in the field of CAM. Table 3 presents biological detectors commonly used in Qigong research.
Measuring indicators of metabolic syndrome including BMI, HDL cholesterol, triglycerides) and glucose control have been linked with understanding the medical effects of Qigong [52]. A recent randomized control trial in diabetic patients in the U.S found that compared to control group, participants in Qigong intervention group reported significant reduction in plasma glucose levels (p<0.01), and significantly improved fasting glucose (p<0.01) [53].Using glucose detectors will contribute in understanding the unique presence of Qigong efforts and dynamics.
Biomarkers are generally considered to be proteins or enzymes -measured in serum, plasma, or blood -that provide independent diagnostic and prognostic value by reflecting an underlying disease state. Recent studies on examining the medical effects of Qigong practice have begun to incorporate biomarker assessments mainly in immune parameters including IL6, TNF-a, or ACTH. A direct observational study in Hong Kong reported an increase of IL6 at seven weeks of Qigong practice and that TNF-a increased in un-stimulated cultures at three and seven weeks [45]. In a double-blinded RCT of Qigong vs sham-Qigong study in Korea, Lee et al. [47] reported that there were significant effects of group and time, and group x time interaction for ACTH levels (p<0.05). Another RCT study of Qigong conducted in Spain reported that the levels of TNF significantly changed after intervention; Cytokines TNF-α〈 (pg/ml) for the control group was 1.89 and IFN-γ (pg/ml) was 10.40 [54]. However, with the exceptions of studies on Qigong meditations, other biomarker studies assessing endorphin or stress hormones remain scarce [55].
Growth hormone is known to undergo large changes in circulating concentrations in response to stimuli such as exercise, sleep and fasting. Growth hormone stimulates the liver and other organs, including the skeleton, to synthesize and secrete insulin-like growth factors (IGF) [56]. In addition, the modulation of immune cells by Qigong therapy may be related to the activity of the sympathetic nervous system (SNS) as well as the neurohormonal axis. Using an observational study design with 10 Korean older adults, Lee et al. [57] argued that that mild movement of Qigong changed somatic growth and enhanced neurohormone concentration and immune functions. Corroborate with this finding, Ryu et al. [58] reported strong correlations between growth hormones and insulin-like growth factor after Qigong practice. These results showed how Qigong training impacted the secretion of growth factors in practitioners, while additional research is now required to determine which aspects of Qigong training contributed to these changes in growth factors, and to ascertain whether exercise in general would result in similar alterations, or if they were augmented by the traditional meditative aspects of Qigong. Observational studies and clinical trials have thus far concluded that Qigong therapy may induce psychological, neurohormonal and immunological changes [59][60][61].

Discussion
In summary, our review shows that there has been an increased body of literature on Qigong-related effects concerning physiological processes and variables. Most of these studies suggested that Qigong practice brings significant changes on parameters such as the blood pressure, heart rate variability, decrease of plasma triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol, an increase of HDL cholesterol, skin temperature, as well as immunological and neurohormonal enhancements.
These findings show that the bio-physiological effects of Qigong may apply to persons of all age groups, ranging from primary school children, college students to mid-age adults or older adults. Our finding also demonstrates that most of the studies on Qigong-related effects concerning physiological, biological, or CVD-related processes were applied in various chronic disease preventions or intervention studies. We still have the most rudimentary understanding on how these processes may manifest itself in chronic stress reduction or stress management. Overall, many authors only examined stress as secondary outcomes [62]. Trial research has found that Qigong practice may improve certain conditions, especially those that are chronic like musculoskeletal disorders and psychological distress. Type of Qigong and length of practice may influence results. However, many limitations exist, especially concerning study design. More methodological rigorous research exploring the particular pathway of Qigong practice and stress reduction is needed.
Another important methodological issue to consider in understanding physiological effects of qigong pertains to the standardized issues of Qigong practice. From the available data, it appears that there are differences in the bio and physiological outcomes depending on the type of Qigong practiced, making it difficult to draw a concrete conclusion. However, our review was unable to find sufficient evidence that one form of Qigong is more effective than another for any specific condition. Even in studies where results are not significant, it is unclear if it might be a study design limitation or   >0.6 year of experience CDSB 10 ml blood was drawn at pre (10-min before training), mid (before meditating), post-training To observe the response of plasma growth hormone (GH), insulin-like growth factor-I (IGF-I) and testosterone (T) to an acute period of ChunDoSunBup (CDSB) Qitraining.
Although the basal level of GH was not different between the two groups, after the portion of the training in which the subjects were physically active (the mid-training point), plasma GH levels increased by 7.26 fold (p < 0.05) in the elderly trainees and by 1.66 fold (p < 0.05) in the young. In response to CDSB Qi-training, IGF-I levels in the young increased significantly at mid-training point, but there were no increase in the elderly. Significant correlations existed between GH and IGF-I levels in the young subjects, but not in the elderly. The T level at the mid-training point increased significantly in elderly subjects but not in the younger age.  [63]. Future studies should examine the effectiveness of one form of Qigong to another, and further research is needed to more rigorously examine the better form of Qigong for specific quantifiable bio-physical effects.
While some subset of biofield devises, including those based on EEG heart rate variabilities that are widely used and employed in clinical settings, other devise modalities still have unclear clinical relevance. The interactions of biofield, defined as "an organizing principle for the dynamic information flow that regulates biological function and homeostasis', can affect and be affected by various biological, biochemical, cellular, and neurological across multiple levels of biology. As this review shows, given TCM posits that the disruption of energy flow is the cause of diseases, the harmonization of the flow of vital energy, or Qi, is posed as the solution to such ailments; in other words such interactions mainly focuses on the mechanical interactions. While current technological advances help us better assess the efficacy of devices, further research on Qi energy could benefit from the application of novel modalities with particular emphasis in mechanical or physical interactions [64].
Last, whereas many studies in this review have consistently suggested the significant physiological and biological effects of Qigong therapies, the broader question remains: what is the mechanical pathway behind such healing effects? Currently, biomedical researchers have stated that energy field therapies are effective because they project 'information' into tissues [65]. While researchers consider this an interesting hypothesis, it leaves many unanswered questions of why tissue repairs are not activated naturally. Why would it be necessary to trigger healing process with an external signal and not something that occurs from within? And what is the mechanism behind the signal triggering healing process? Although the answers posed here are beyond what this paper aimed to address, next steps of scientific inquiry is necessary to better understand the bio-physical and chemical pathways of Qigong healing process.

Limitations
Despite these significant findings, there are some limitations to the current state of methodological issues pertaining to Qigong research. First, small sample size makes it difficult to interpret results and raises questions in generalizability. For example, current publication on external qi on physical and biological systems frequently involves a single, or few qigong masters. Such situations may also introduce conflict of interests; participants should not be involved in the design of the study and should be blinded during the measurement. Second, there is a lack of sophisticated research design and compatible control groups undermine the results of many methods studies. Third, most Qigong practices may lack a facilitation program or manual to be successfully replicated. Given there is no generic form of Qigong, which calls to question how closely the type of Qigong used in these research trials resembles traditional forms, whether the cultural component of Qigong influences researchers and participants, and whether Qigong is treated just as a low-intensity exercise.
Furthermore, due to the lack of investigation in current literature, the role of culture or belief in Qigong practice remains central. In areas of biomedicine, cultural belief has been shown to impact compliance which could also influence health outcomes [66]. When investigating a practice or treatment such as Qigong which often explicitly incorporates non-biomedical beliefs about "energy," considering the influence of beliefs is necessary to examine which components may influence the outcome. Further, evidence shows that the concept of Qi, which does not have a biomedical analog, could very important among Qigong practitioners [67]. While their findings are impressive, most of these studies have methodological weaknesses. Moreover, it is not clear how much Chinese culture contributes to these outcomes or whether the benefits of qigong can be realized in an American population [68]. It is necessary to thoroughly examine how culturally relevant practices like Qigong may specifically relate to their health. Future studies should consider improving the conceptual framework on cultural believes in biomedical studies, and measures to better operationalize the potential impact of cultural beliefs in health outcomes.

Future research directions
In order to further understand the Qi measurement issues; there are multiple areas of research which should be addressed concerning study design, the complexities of Qigong, and the role of culture. It should be noted that CAM researchers have proposed a variety of directions for research pertaining to older adults which apply to Qigong research as well, including: understanding motivations for use or practice, safety concerns, longitudinal study design, larger sample size, including qualitative or ethnographic study design, and challenging the common health research approach of a biomedical framework [69]. Longitudinal, population-based studies should be conducted in community-dwelling settings to understand the current practice of and sociodemographic and health associations with Qigong. Although traditional doubleblind clinical trials may be difficult to apply to qigong study due to a lack of a compatible sham qigong, in reality, a reasonably large sample size with a compatible control may be crucial for examining such an alternative therapy. The next step should also include information about culturally relevant exercise behaviors with additional qualitative interviews to understand their practice of Qigong.
Furthermore, future studies in this area should not only focus on physical or chemical detectors, but also use more biological or life detectors to increase our understanding of the bio-information contained within qigong. Furthermore, future research needs to evaluate the effectiveness of different forms of Qigong and another mind-body exercise, particularly Tai Chi, a similar and less meditative exercise to Qigong, in order to ascertain the appropriateness of these exercises for persons with different functional abilities.

Practice and policy implications
Last, this review has implications for health providers and policymakers. As one of the five treatment principles in traditional Chinese medicine, Qigong exercise postulates balance and harmonization as the principle aim of a treatment [70]. Recent CAM research of older adults has called for further integration of nonbiomedical biomedical options for addressing certain health concerns [69]. Health providers should provide information to older adults about Qigong as exercise, especially since there is some evidence that Qigong practice lowers medical costs and visits [71]. Integrating Qigong classes into community exercise offerings may be able to address these issues of maintaining exercise in advancing age, especially for minority adults who desire culturally-specific group exercise activities [72].

Conclusion
In conclusion, the existing body of measurement research regarding Qi indicates that Qigong may be an effective way of improving health outcomes, including overall quality of life, psychological distress, and pain. Research methodology should rigorously evaluate Qigong versus other forms of mind-body exercise and whether cultural specificity and CAM beliefs affect health outcomes. Research scientists, health providers, and community leaders should work in concert to investigate and improve the physical and psychosocial health and health behaviors of minority populations through culturally appropriate and adaptable exercise like Qigong.