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1
Effect of forest bathing integrated with mindfulness-based stress reduction on immune cell
populations and quality of life in breast cancer patients: a controlled pilot study
Oh Sook Kwon1, Keong Sub Shin2, Do Bong Kim2, He Young Ahn3, Su Jin Park4, Chan Woo Park4,
Beom Seok Yang5, Sung Jae Lee1*
1Department of Integrative Medicine, Korea University Hospital, 126-1 Anam-Dong, Sungbuk-
Gu, Seoul, 136-705, Korea, Tel: 82-2-920-6637
2Sam Medical Center, Anyang 5-Dong, Manan-Gu, Anyang, Gyeonggi-Do, Korea
3Department of Mind-Body Integration, Seoul University of Buddhism, 1038-2 Doksan-Dong,
Geumcheon-Gu, Seoul, Korea
4Korea Forest Research Institute, 57 Hoegi-Ro, Dongdaemun-Gu, Seoul, Korea
5Korea Institute of Science and Technology, 39-1 Hawolgok-Dong, Sungbuk-Gu, Seoul, Korea
*Corresponding author
Keywords: Forest bathing, MBSR, Breast cancer patients, NK cells, Quality of life
Email addresses:
OSK:[email protected], KSS: [email protected], DBK: [email protected] HYA:
[email protected], SJP: [email protected], CWP: [email protected], BSY:
2
Abstract
Background: The therapeutic effects of forest bathing on cancer patients have not yet been
evaluated despite the known beneficial effects of this practice on immune function and stress
reduction in healthy human subjects. We performed a controlled pilot study to assess the
impact of forest bathing and its effects when used in combination with mindfulness-based
stress reduction (MBSR) in breast cancer patients.
Methods: A total of 22 breast cancer patients from an urban area were randomly divided
into 2 groups: group 1 (n = 11) was exposed only to forest bathing for 6 days, and group 2 (n =
11) underwent MBSR for 2 hours daily in addition to forest bathing. Blood samples were
collected at the beginning and on the last day of treatment, and the populations of T helper
cells and natural killer (NK) cells were counted. The participants’ quality of life was analyzed
using the World Health Organization Quality of Life Assessment Instrument-Brief Form
(WHOQOL-BREF) criteria.
Results: Forest bathing significantly increased the mean number of NK cells by 20.2%, and
the scores of certain WHOQOL-BREF domains such as domain 1 (physical health) score by
15.7%, overall quality of life by 25.0%, and general health by 41.1%. The patients exposed to
forest bathing in combination with the MBSR program showed significantly enhanced values;
the mean NK cell population increased by 40.8%, WHOQOL-BREF score of domain 1 by 41.1%,
domain 2 (psychological health) by 30.3%, and overall quality of life by 52.2%, representing
2.0-, 2.6-, 2.5-, and 2.1-fold higher increases respectively, compared with forest bathing alone
with statistical significances. The score of general health was also significantly improved by
3
62.5% with the combination treatment, however, without being significantly different from
that of forest bathing alone.
Conclusion: Forest bathing improved the immune function and quality of life of the breast
cancer patients, and the beneficial effects are enhanced by the concurrent exposure to an
MBSR program. Therefore, forest bathing and its integration with an MBSR program should
be considered as one of the complementary and alternative medicine options for treating
breast cancer patients.
4
Background
Forest bathing has been increasingly drawing attention for its proposed positive
effects on human health [1]. This practice involves visiting a forest to relax while breathing in
volatile organic chemicals produced by trees called phytoncides. Phytoncides were originally
characterized as chemical agents with antimicrobial activities, and various types with different
chemical structures have been indentified [2].
The beneficial psychological and physiological effects of forest bathing on humans
have been shown in several studies. The Profile of Mood States (POMS) test was used to
evaluate the effects of forest bathing on healthy volunteers, and the results showed
significantly increased scores for vigor and decreased scores for anxiety and depression [3].
These results suggest that forest bathing may release stress or help participants manage stress
better. The physiological benefits of this practice have been shown in studies demonstrating
the enhancement of immune cell function. Healthy male and female volunteers living in
urban areas who participated in a forest bathing trip showed significantly increased natural
killer (NK) cell numbers and its relative proportions to lymphocytes, as well as enhanced
expressions of anticancer proteins, such as perforin, GrA, and GRN synthesized from NK cells
[4-6]. Phytoncides have been implicated in the effects of forest bathing on NK cells. Li et al.
[7] showed that the phytoncides α-pinene, 1,8-cineole, and d-limonene stimulate the
proliferation of NK cells and enhance their biological activities in an in vitro study. The
changes in the stress hormone levels could also explain the effect of forest bathing on the
modulation of NK cell activity. Forest bathing was reported to decrease the levels of the
stress hormone cortisol [8–10], and cortisol level was negatively correlated with NK cell
number and activity in human subjects [11]. Citrus fragrance, which is a phytoncide, was
5
shown to regulate the levels of stress hormones, such as cortisol and dopamine, and this was
associated with the induction of NK cell activity [12]. In a study in mice, physical and/or
psychological stress decreased NK cell activity and reduced the granzyme and perforin levels
[13]. Taken together, these results support the notion that stress reduction may be one of
the mechanisms mediating the beneficial effects of forest bathing, that is, increase in NK cell
population and activity. It was suggested that forest bathing trips may have a cancer
preventive effect because NK cells are involved in immune surveillance against tumor
development and they can attack tumors by releasing proteins, such as perforin, GRN, and
GrA/B [14]. In addition, the terpenoids in phytoncides, including α-humulene, β-
caryophyllene, α-pinene, and β-pinene, were shown to have anticancer activity in animal
studies [15].
Therapies based on the fact that the mind interacts with the body and can therefore
affect human physical function and health are called “mind-body interventions” [17-18], and
they comprise a distinct category of complementary medicine as delineated by the US National
Center for Complementary or Alternative Medicine at the National Institutes of Health. This
approach is increasingly being considered in medical practice, although its incidence is still low
[16]. Cancer patients, in particular, tend to express a higher interest in this method than the
general population. A variety of mind-body intervention practices and programs have been
developed. They consist of relaxation therapies; meditation; exercise programs combined
with meditation, such as yoga and taisi; and art and music therapy among others. Mind-body
intervention therapies have been applied effectively to the treatment of cancer patients for
the reduction of adverse effects, such as pain and insomnia, and for the improvement of
quality of life [18-21]. Mindfulness-based stress reduction (MBSR) is one of the most
frequently used mind-body interventions. It is a type of meditation therapy that was
6
originally established by Kabat-Zinn and colleagues at the Stress Reduction Clinic of the
University of Massachusetts Medical Center [22, 23]. Since then, many clinical applications
and well-being programs that use MBSR have been adopted in clinical centers around the
world. MBSR has a root in the Buddhist spiritual traditions. It uses mindfulness meditation
and yoga to alleviate pain and improve the physical and emotional health of patients. Its
beneficial effects in the treatment of diseases and disorders, such as cancer, chronic pain,
hypertension, and anxiety, have been proposed [24-29].
Although the beneficial effects of forest bathing have been well documented in
healthy people, the effects of this practice on cancer patients remain to be evaluated. In
addition, cooperative effects between forest bathing and a program based on mind-body
intervention are expected for cancer patients. Here, we investigated the effects of forest
bathing and its combination with MBSR on breast cancer patients by assessing the changes in
the number of immune cell population and in quality of life.
Results
Forest bathing increases NK cell population and certain WHOQOL domain scores in breast
cancer patients
To assess whether forest bathing has beneficial effects on breast cancer patients, the
patients in group 1 (n = 11), which are described in table 1, were exposed to forest bathing for
6 days. The proportions of T and NK cells (%) to lymphocytes and the domain scores of the
WHOQOL-BREF were obtained before and after the forest bathing treatment program, and the
7
mean and standard deviation values are listed in table 3. The increase rate in each
measurement from before to after the forest bathing periods was calculated and is shown in
table 3, including the calculated significance of the differences.
The mean CD 56+ NK cell population increased significantly by 20.2% (p = 0.004) after
exposure to forest bathing. Contrary to the NK cell population, the number of CD4+ T helper
cells did not change significantly, although its mean value increased by 1.2%.
The WHOQOL-BREF was used to assess the changes in the quality of life in the group 1
patients after exposure to forest bathing. As shown in table 3-1, forest bathing significantly
increased the mean WHOQOL domain 1 (physical health) score by 15.7% (p = 0.049). In
addition, forest bathing significantly increased the mean overall quality of life scores by 25.0%
(p = 0.006) and general health by 41.1% (p = 0.026). However, the WHOQOL domain 2
(psychological health), 3 (social relationships), and 4 (environment) scores did not change
significantly, although the mean score values of domains 2 and 3 showed a slight increase.
Forest bathing in combination with MBSR increases the proportion of NK cells and WHOQOL
scores to a greater degree than forest bathing alone
To examine the effect of the combination treatment of forest bathing and MBSR on
breast cancer patients, the 11 participants described as group 2 in table 1 underwent an MBSR
program concurrent with the 6 days of forest bathing. Similar to group 1, the mean values of
the T and NK cell populations (%) in lymphocytes and the WHOQOL-BREF scores were obtained
before and after the intervention program and the percent increase and p values were
calculated. The results, which are summarized in table 4, show that forest bathing combined
with MBSR resulted in a greater enhancement of NK cell population and WHOQOL domain
8
scores than forest bathing alone. The percent increase of the NK cell population by the
combined intervention was 40.8% (p < 0.001) compared with 20.2% by forest bathing alone.
However, similar to the results obtained with group 1, the CD4+ T helper population did not
change significantly with the combination treatment and only increased slightly by 3.4%. On
the other hand, the WHOQOL domain 1 and 2 scores increased significantly in response to the
combination treatment, showing an improvement of 41.1% in domain 1 (p < 0.001) and 30.0%
in domain 2 (p < 0.001). In addition, increases of 52.2% and 62.5% in the overall quality of life
(p < 0.001) and general health (p = 0.002), respectively, were also observed. The
improvements in the WHOQOL scores by the combination treatment were considerably higher
than those obtained in group 1 by forest bathing only. No significant changes in quality of life
domains 3 and 4 were observed in group 2 (table 4).
Forest bathing and MBSR show cooperative effects in the enhancement of NK cell population
and WHOQOL scores in breast cancer patients
The considerable increase in NK cell population and WHOQOL scores in the patients
exposed to forest bathing combined with MBSR compared with forest bathing alone suggests
that forest bathing and MBSR may act in a cooperative manner in breast cancer patients. In
fact, the mean increases in NK cell population showed a 2.0-fold higher value in group 2, which
was subjected to the combination of MBSR and forest bathing, than in group 1 patients, which
were treated with forest bathing alone (p = 0.033). Likewise, the WHOQOL-BREF scores
showed an improvement of 2.6-fold in domain 1 (p = 0.037), 2.5-fold in domain 2 (p = 0.045),
and 2.1-fold in the overall score (p = 0.026; Figs. 1 and 2). However, no statistically significant
differences were observed between the 2 groups in the mean increase in the CD4+ T helper cell
9
population and WHOQOL domain 3 and 4 scores or in general health, although more or less
higher increases were seen in group 2. This result indicates that forest bathing and MBSR can
act cooperatively in breast cancer patients by enhancing immune function through an increase
in NK cell population and the improvement of some aspects of quality of life.
Discussion
The present study is the first to evaluate the effects of forest bathing in breast cancer
patients, although the beneficial effects of this practice on healthy human subjects, as
reflected in the increase in the number and activity of NK cells, have been reported previously
[3-10]. Furthermore, we assessed the effect of forest bathing in combination with MBSR.
We demonstrated that breast cancer patients showed a positive response to forest bathing by
the significant increase in NK cell population. This result is consistent with that of a previous
study that showed an increase in NK cells of approximately 36.1% in healthy individuals
exposed to forest bathing for 3 days, although the induction level of 20.2% in the present
study with breast cancer patients is lower [6]. In addition, we showed that forest bathing and
MBSR act in a cooperative manner in increasing the NK cell population and improving quality
of life. NK cell population changes have been used before as biomarkers of the response of
cancer patients to various complementary and alternative medicinal practices, such as
meditation and yoga [32, 33].
NK cells, which play a crucial role in innate immunity, are cytolytic and secrete
cytokines against tumor cells and cells infected with bacteria and viruses [34, 35]. A close
correlation between a reduction of NK cell activity and the development of cancer has been
10
observed [36-40], and the preventive effect of NK cells against cancer development has been
suggested [41]. Furthermore, the use of NK cells in cancer therapy has been proposed [42].
Therefore, an increase in NK cell population caused by forest bathing is expected to be
beneficial for cancer patients.
The mechanism underlying the increase in NK cell population by forest bathing can be
explained using physiological and psychological approaches. Physiologically, there is
evidence that phytoncides can stimulate NK cell proliferation [7]. Psychologically, the effect
of forest bathing on stress reduction can induce an increase in the number of NK cells because
NK cell activity is associated with stress in cancer patients. Prior studies have shown that
stress level affects immune function by modulating NK cells in cancer patients [43, 44], and
psychosocial treatments were shown to significantly improve NK cell levels [45]. As
mentioned earlier, the stress hormone cortisol could be one of the biochemical mediators in
the inverse relationship between stress and NK cell population growth [8-11]. Therefore, it is
possible that forest bathing can suppress cortisol and consequently stimulate NK cells.
The WHOQOL-BREF was used to assess the effect of forest bathing on the quality of
life of cancer patients because of the importance of quality of life in the health care of
patients with cancer. Patients with cancer who underwent treatment for cancer are prone
to experience higher levels of psychological stress and pain than the general public owing to
the fear of dying and changes in economic and social status [46]. A diagnosis of breast
cancer was shown to alter patients’ emotional, cognitive and social functioning [47].
Therefore, the improvement of quality of life is an important issue in the clinical treatment of
cancer patients because poor quality of life can adversely affect therapeutic outcome [48, 49].
Our study showed that forest bathing increased the WHOQOL-BREF domain 1
(physical health) score significantly in breast cancer patients. It is interesting that the
11
exposure of the patients to the combination treatment of forest bathing and MBSR caused not
only an improvement in the score of domain 1 but also in that of domain 2 (psychological
health). Furthermore, the increases in these scores were significantly higher than those
obtained with forest bathing alone. These results suggest that forest bathing combined with
MBSR could potentially result in physical and psychological benefits for breast cancer patients,
which would lead to a better therapeutic outcome and enhanced immune function.
Our results showed that forest bathing and the MBSR program acted in a cooperative
manner to enhance the NK cell population and WHOQOL-BREF scores. The psychological
effects of the MBSR program likely played a key role in this cooperative effect. The
importance of psychological factors for predicting a better prognosis in cancer patients has
been reported previously [50]. A low stress level in the POMS in breast cancer patients was
associated with a longer disease-free interval, whereas a high stress condition was associated
with cancer recurrence [51]. Feelings of fear, isolation, and aloneness among breast cancer
patients have been reported in prior studies [52]. We believe that forest bathing trips can
also contribute to enhancing the quality of life of breast cancer patients because the program
provides these patients with an environment in which they can express and share their
experiences, feelings, and concerns.
Conclusions
Forest bathing had a beneficial effect on the breast cancer patients by improving
immune function and quality of life in physical and psychological aspects. Higher positive
outcomes were obtained when the cancer patients were treated with forest bathing
12
integrated with an MBSR program. Therefore, we suggest that forest bathing should be
considered an effective complementary and alternative treatment for cancer patients. In
addition, we recommend its practice in combination with an MBSR program for a better
outcome.
Methods
Design and subject
This study was designed as a controlled intervention study. The subjects included 22
Korean women living in an urban area, with a median age of 54 years. They were found to
have breast cancer and treated either at the Korea University Hospital, Seoul, South Korea, or
at Sam Hospital, Anyang, South Korea. A minimum of 3 months but no longer than 1 year had
passed since the last treatment including surgery and chemotherapy and/or radiation therapy
for all the subjects. None of the participants had a history of either forest bathing or MBSR
treatment. None of them had serious mental or physical problems in managing their daily
life, and they did not require nursing care. Their education levels were higher than secondary
school, except in 1 subject. All of them were unemployed and staying home at the time of
the study. They were randomly divided into 2 subject groups: group 1 consisted of 11
patients who participated in only the forest bathing for 6 days, and group 2, with the
remaining 11 patients, was exposed to a combination of forest bathing and an MBSR program.
The characteristics of the subjects in each group are listed in table 1.
13
Intervention procedure
All the participating patients presented at the Korea University Hospital, Seoul, South
Korea, on the day they left for the forest, and blood samples were collected. In addition, they
spent 1 hour completing the World Health Organization Quality of Life Assessment Instrument-
Brief Form (WHOQOL-BREF) questionnaire. The participants were then transported by bus in
a 2-hour ride to the Saneum National Forest, located in Kyungkido, South Korea. After arrival
at the forest, they were given a short orientation about the schedule and intervention program.
The following day, subject group 1 was treated with only forest bathing and group 2 was
subjected to forest bathing combined with the MBSR program for 6 consecutive days. All the
participants in both groups were recommended to walk through the forest for 1 to 2 hours per
day. In addition, all the patients in group 2 attended the MBSR program for 2 hours per day,
in the morning, for 6 consecutive days, whereas the group 1 patients had a free schedule while
they stayed in the forest. After the completion of the 6-day intervention program, the
patients were driven back to the Korea University Hospital, where blood samples were
collected and the WHOQOL-BREF questionnaire was completed before they returned home.
Mindfulness-Based Stress Reduction
Significant modifications to the original version of the MBSR program designed by Jon
Kabat-Zinn [22, 23] were made in this study to fit the program within the 6-day schedule of
this study. The contents of the classes for the 6 days are summarized in table 2. The classes
were held each day from 10:00 am to 12:00 noon, for 6 consecutive days. All the classes
were run within the Saneum National Forest by a qualified teacher with 6 years of experience
14
teaching MBSR. This program, which we call MBSR-informed, used methods such as body
scan, sitting, and walking meditation with an emphasis on enhancing the participants'
moment-to-moment awareness. The classes were focused on the cultivation of mindful
awareness and designed to help strengthen the participants' innate ability to be mindfully
aware in everyday life. Unlike the standard MBSR programs, no CD-based homework was
assigned. Instead, to help the participants maintain mindfulness outside of the class, they
were encouraged to practice mindfulness while eating, taking a shower, exercising, walking,
and even while talking. The participants were strongly encouraged to pay attention to
whatever arises during their waking hours and to remind themselves of questions such as
“What am I doing in this moment?” or "What is the current state of my body?” to maintain
mindfulness.
Estimation of the populations of CD4+ T helper cells and CD56
+ NK cells in lymphocytes
The blood samples that were collected from the participants, using collection tubes
with an anticoagulant, were used for the flow cytometric analysis to estimate the percentage
of CD4+ T helper cells and NK cells in lymphocytes within 4 hours after the sampling. The flow
cytometric analysis was performed using the Cytomics FC500 flow cytometer (Beckman Coulter,
USA) according to the manufacturer’s protocol as described briefly as follows. All the
fluorochrome-conjugated antibody reagents and cell fixing and lysing solutions (Versal Lyse
Lysing solution) were purchased from Beckmann Coulter. For the analysis of the CD4+ T
helper cells, 100 μL of whole blood treated with heparin was mixed with 10 μL of CD45+-ECD
monoclonal antibody and 20 μL of CD3-FITC/CD4-PE monoclonal antibody. To analyze the
CD56+ NK cell population, 100 μL of the blood sample was mixed with 10 μL of CD45+-ECD
15
monoclonal antibody and 20 μL of CD3-FITC/CD56-PC5 monoclonal antibody. To eliminate
nonspecific staining, 100 μL of the blood sample was mixed with 10 μL of CD45+-ECD
monoclonal antibody and 20 μL of IgG1-FITC/IgG1-PE/IgG1-PC5 monoclonal antibody solution.
The 3 mixed blood samples were briefly vortexed and incubated in the dark for 15 minutes at
room temperature. Then, 1 mL of Versal Lyse lysing solution (Beckmann Coulter) was added
to each sample. The samples were further incubated for 10 minutes at room temperature in
the dark before being applied to the flow cytometer. The CD45+-ECD monoclonal antibody
was used to gate the lymphocyte cells in the flow cytometric analysis.
Assessment with the WHOQOL-BREF
Quality of life was assessed using the Korean version of the WHOQOL-BREF [30].
WHOQOL-BREF is a concise version of the WHOQOL-100 [31]. The instrument contains a
total of 26 questions consisting of 4 domains (24 questions in total): domain 1, physical health
(7 questions); domain 2, psychological health (6 questions); domain 3, social relationships (3
questions); and domain 4, environment (8 questions), and 2 separate questions to assess
overall quality of life and general health. The questionnaire is self-administered, and the
score of each domain stands for the individual’s perception of the quality of life in the domain.
The scores for each question were graded from 1 to 5, and these scores were converted to a
scale from 0 to 100 by setting score 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100. The mean
score of the questions in each domain was used to calculate the domain score for each
individual.
Statistical analysis
16
All the data are expressed as mean ± SD. The SPSS for Windows version 12.0 was
used for the statistical analysis. Comparisons within each group were performed using the
paired Student t test. The comparisons between groups 1 and 2 were done by the unpaired
Student t test. Statistical significance was set at P < 0.05.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
SJL was the principal investigator who participated in the design of the study, data
analysis and writing of the manuscript. OSK participated in the overall conduction of
experiments, data analysis and writing of the manuscript. KSS and DBK participated in the
conduction of experiments and data analysis. HYA participated in the conduction of the
MRSA program, data analysis and writing of the manuscript. SJP and CWP participated in
coordinating the study. BSY participated in data analysis and writing of the manuscript. All
authors have read and approved the final manuscript.
Acknowledgement
17
This work was supported by a grant from Korea Forest Research Institute (02-01-01-
540104).
18
References
1. Li Q: Effect of forest bathing trips on human immune function. Environ Health Prev
Med 2010, 15:9-17.
2. Abe T, Hisama M, Tanimoto S, Shibayama H, Mihara Y, Nomura M: Antioxidant
effects and antimicrobial activites of phytoncide. Biocontrol Sci 2008, 13:23-27.
3. Kasetani T, Takayama N, Park BJ, Furuya K, Kagawa T, Miyazaki Y: Relation between
light/thermal environment in the forest walking road and subjective estimations for
taking in the atmosphere of the forest. J Jpn Inst Lands Archit 2008, 71:713–716.
4. Li Q, Morimoto K, Nakadai A, Inagaki H, Katsumata M, Shimizu T, Hirata Y, Hirata K,
Suzuki H, Miyazaki Y, Kagawa T, Koyama Y, Ohira T, Takayama N, Krensky AM, Kawada T:
Forest bathing enhances human natural killer activity and expression of anti-cancer
proteins. Int J Immunopathol Pharmacol 2007, 20:3–8.
5. Li Q, Morimoto K, Kobayashi M, Inagaki H, Katsumata M, Hirata Y, Hirata K, Suzuki H,
Li YJ, Wakayama Y, Kawada T, Park BJ, Ohira T, Matsui N, Kagawa T, Miyazaki Y,
Krensky AM: Visiting a forest, but not a city, increases human natural killer activity
and expression of anti-cancer proteins. Int J Immunopathol Pharmacol 2008, 21:117–
128.
6. Li Q, Morimoto K, Kobayashi M, Inagaki H, Katsumata M, Hirata Y, Hirata K, Shimizu T,
Li YJ, Wakayama Y, Kawada T, Ohira T, Takayama N, Kagawa T, Miyazaki Y: A forest
bathing trip increases human natural killer activity and expression of anti-cancer
proteins in female subjects. J Biol Regul Homeost Agents 2008, 22:45–55.
7. Li Q, Nakadai A, Matsushima H, Miyazaki Y, Krensky AM, Kawada T, Morimoto K:
Phytoncides (wood essential oils) induce human natural killer cell activity.
19
Immunopharmacol Immunotoxicol 2006, 28:319–333.
8. Park BJ, Tsunetsugu Y, Kasetani T, Hirano H, Kagawa T, Sato M, Miyazaki Y:
Physiological effects of Shinrin-yoku (taking in the atmosphere of the forest)–using
salivary cortisol and cerebral activity as indicators. J Physiol Anthropol 2007, 26:123–
128.
9. Park BJ, Tsunetsugu Y, Kasetani T, Kagawa T, Miyazaki Y: The physiological effects of
Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field
experiments in 24 forests across Japan. Environ Health Prev Med 2010, 15:18-26.
10. Tsunetsugu Y, Park BJ, Ishii H, Hirano H, Kagawa T, Miyazaki Y: Physiological effects of
Shinrin-yoku (taking in the atmosphere of the forest) in an old-growth broadleaf
forest in Yamagata Prefecture, Japan. J Physiol Anthropol 2007, 26:135–42.
11. Garland M, Doherty D, Golden-Mason L, Fitzpatrick P, Walsh N, O’Farrelly C: Stress-
related hormonal suppression of natural killer activity does not show menstrual
cycle variations: implications for timing of surgery for breast cancer. Anticancer Res
2003, 23:2531–2535.
12. Komori T, Fujiwara R, Tanida M, Nomura J, Yokoyama MM: Effects of citrus fragrance
on immune function and depressive states. Neuroimmunomodulation 1995, 2:174–
180.
13. Li Q, Liang Z, Nakadai A, Kawada T: Effect of electric foot shock and psychological
stress on activities of murine splenic natural killer and lymphokine-activated killer
cells, cytotoxic T lymphocytes, natural killer receptors and mRNA transcripts for
granzymes and perforin. Stress 2005, 8:107–116.
14. Li Q: Effect of forest bathing trips on human immune function. Environ Health Prev
Med 2010, 15:9–17.
20
15. da Silva SL, Figueiredo PM, Yano T: Chemotherapeutic potential of the volatile oils
from Zanthoxylum rhoifolium Lam leaves. Eur J Pharmacol 2007, 576:180–188.
16. Carlson LE, Bultz BD: Mind-body interventions in oncology. Curr Treat Options Oncol
2008, 9:127–134.
17. Praissman S: Mindfulness-based stress reduction: a literature review and clinician's
guide. J Am Acad Nurse Pract 2008, 20:212-216.
18. Kang Y: Mind-body approach in the area of preventive medicine: focusing on
relaxation and meditation for stress management. J Prev Med Public Health 2010,
43:445-450.
19. Kwekkeboom KL, Cherwin CH, Lee JW, Wanta B: Mind-body treatments for the pain-
fatigue-sleep disturbance symptom cluster in persons with cancer. J Pain Symptom
Manage 2010, 39:126-138.
20. Bardia A, Barton DL, Prokop LJ, Bauer BA, Moynihan TJ: Efficacy of complementary
and alternative medicine therapies in relieving cancer pain: a systematic review. J
Clin Oncol 2006, 24:5457-5464.
21. Targ EF, Levine EG: The efficacy of a mind-body-spirit group for women with breast
cancer: a randomized controlled trial. Gen Hosp Psychiatry 2002, 24:238-248.
22. Kabat-Zinn J: Full catastrophe living: using the wisdom of your body and mind to face
stress, pain, and illness. New York: Delacourt; 1990.
23. Kabat-Zinn J: An outpatient program in behavioral medicine for chronic pain
patients based on the practice of mindfulness meditation: theoretical
considerations and preliminary results. Gen Hosp Psychiatry 1982, 4:33–42.
24. Carlson LE, Speca M, Patel KD, Goodey E: Mindfulness-based stress reduction in
relation to quality of life, mood, symptoms of stress and levels of cortisol,
21
dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate
cancer outpatients. Psychoneuroendocrinology 2004, 29:448-474.
25. Kabat-Zinn J: An outpatient program in behavioral medicine for chronic pain
patients based on the practice of mindfulness meditation: theoretical
considerations and preliminary results. Gen Hosp Psychiatry 1982, 4:33–42.
26. Kabat-Zinn J, Lipworth L, Burney R, Sellers W: Four-year follow-up of a meditation
based program for the self-regulation of chronic pain: treatment outcomes and
compliance. Clin J Pain 1986, 2:159 –173.
27. Kabat-Zinn J, Massion AO, Kristeller J, Peterson LG, Fletcher DE, Pbert L, Lenderking
WR, Santorelli SF: Effectiveness of a meditation-based stress reduction program in
the treatment of anxiety disorders. Am J Psychiatry 1992, 149:936–943.
28. Miller JJ, Fletcher K, Kabat-Zinn J: Three-year follow-up and clinical implications of a
mindfulness meditation-based stress reduction intervention in the treatment of
anxiety disorders. Gen Hosp Psychiatry 1995, 17:192–200.
29. Schneider RH, Staggers F, Alxander CN, Sheppard W, Rainforth M, Kondwani K, Smith
S, King CG: A randomised controlled trial of stress reduction for hypertension in
older African Americans. Hypertension 1995, 26:820 –827.
30. WHOQOL Group: The World Health Organization Quality of Life assessment
(WHOQOL): Development and general psychometric properties. Soc Sci Med 1998a,
46:1569–1585.
31. WHOQOL Group: Development of the World Health Organization WHOQOL-BREF
quality of life assessment. Psychol Med 1998b, 28:551–558.
32. Witek-Janusek L, Albuquerque K, Chroniak KR, Chroniak C, Durazo-Arvizu R, Mathews
HL: Effect of mindfulness based stress reduction on immune function, quality of life
22
and coping in women newly diagnosed with early stage breast cancer. Brain Behav
Immun 2008, 22:969-981.
33. Rao RM, Nagendra HR, Raghuram N, Vinay C, Chandrashekara S, Gopinath KS, Srinath
BS: Influence of yoga on mood states, distress, quality of life and immune outcomes
in early stage breast cancer patients undergoing surgery. Int J Yoga 2008, 1:11-20.
34. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM,
Ugolini S: Innate or adaptive immunity? The example of natural killer cells. Science
2011, 331:44-49.
35. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S: Functions of natural killer cells.
Nat Immunol 2008, 9:503-510.
36. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K: Natural cytotoxic activity of
peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a
general population. The Lancet 2000, 356:1795–1799.
37. Kawano T, Nakayama T, Kamada N, Kaneko Y, Harada M, Ogura N, Akutsu Y, Motohashi
S, Iizasa T, Endo H, Fujisawa T, Shinkai H, Taniguchi M: Antitumor cytotoxicity
mediated by ligand activated human V alpha24 NKT cells. Cancer Res 1999, 59:5102–
5105.
38. Tahir SM, Cheng O, Shaulov A, Koezuka Y, Bubley GJ, Wilson SB, Balk SP, Exley MA:
Loss of IFN-gamma production by invariant NK T cells in advanced cancer. J Immunol
2001, 167:4046–4050.
39. Motohashi S, Kobayashi S, Ito T, Magara KK, Mikuni O, Kamada N, Iizasa T, Nakayama
T, Fujisawa T, Taniguchi M: Preserved IFN-alpha production of circulating V alpha 24
NKT cells in primary lung cancer patients. Int J Cancer 2002, 102:159–165.
40. K. Yanagisawa, K. Seino, Y. Ishikawa, M. Nozue, T. Todoroki, K. Fukao: Impaired
23
proliferative response of V alpha 24 NKT cells from cancer patients against alpha-
galactosylceramide. J Immunol 2002, 168:6494–6499.
41. Levy EM, Roberti MP, Mordoh JV: Natural Killer Cells in Human Cancer:From
Biological Functions to Clinical Applications. J Biomed Biotechnol 2011, 2011:676198
42. Ruggeri L, Mancusi A, Burchielli E, Aversa F, Martelli MF, Velardi A: Natural killer cell
alloreactivity in allogeneic hematopoietic transplantation. Curr Opin Oncol 2007,
19:142–147.
43. Levy SM, Herberman RB, Lippman M, D’Angelo T, Lee J: Immunological and
psychosocial predictors of disease recurrence in patients with early-stage breast
cancer. Behav Med 1991, 17:67–75.
44. Andersen BL, Farrar WB, Golden-Kreutz D, Kutz LA, MacCallum R, Courtney ME, Glaser
R: Stress and immune responses after surgical treatment for regional breast cancer.
J Natl Cancer Inst 1998, 90:30–36.
45. Fawzy FI, Kemeny ME, Fawzy NW, Elashoff R, Morton D, Cousins N, Fahey JL: A
structured psychiatric intervention for cancer patients. II. Changes over time in
immunological measures. Arch Gen Psychiatry 1990, 47:729 –735.
46. Moschén R, Kemmler G, Schweigkofler H, Holzner B, Dunser M, Richter R,
Fleischhacker WW, Sperner-Unterweger B: Use of alternative/complementary
therapy in breast cancer patients – a psychological perspective. Support Care Cancer
2001, 9: 267–274.
47. Thewes B, Butow P, Girgis A, Pendlebury S: Assessment of unmet needs among
survivors of breast cancer. J Psycho Oncology 2004, 22: 51–73.
48. Hakamies-Blomqvist L, Louma ML, Sjöström J, Pluzanska A, Sjödin M, Mouridsen H,
Östenstad B, Mjaaland I, Ottosson S, Bergh J, Malmström PO, Blomqvist C: Timing of
24
quality of life (QoL) assessments as a source of error in oncological trials. J Adv
Nursing 2011, 35: 709–716.
49. Shimozuma K: Quality of life assessment. Breast Cancer 2002, 9:100–106.
50. Andersen BL, Kiecolt-Glaser JK, Glaser R: A biobehavioral model of cancer stress and
disease course. Am Psychol 1994, 49:389–404.
51. Levy SM, Herberman RB, Lippman M, D’Angelo T, Lee J: Immunological and
psychosocial predictors of disease recurrence in patients with early-stage breast
cancer. Behav Med 1991, 17:67–75.
52. Adamsen L, Rasmusen JM: Exploring and encouraging through social interaction.
Cancer Nursing 2003, 26:28–36.
25
Table 1. Summary of the subject characteristics
Group 1 (n = 11) Group 2 (n =
11)
n % n %
Age, mean ± SD
(range)
54.00 ± 9.24
(39–76)
53.00 ± 6.92
(42-69)
Marital status
Married 11 100 10 90.9
Single 0 0 1 9.1
Education
9 or less years 1 9.1 0 0
More than 9 years 10 90.9 11 100
Religion
Yes 9 81.8 9 81.8
No 2 18.2 2 18.2
Type of surgery
MRM 9 81.8 9 81.8
Partial mastectomy 2 18.2 2 18.2
Treatment after surgery
None 3 27.3 3 27.3
Chemotherapy 7 63.6 8 72.7
Radiotherapy 1 9.1 0 0
Stage of breast cancer
Stage II 2 18.2 3 27.3
Stage III 7 63.6 6 54.5
Stage IV 2 18.2 2 18.2
26
Table 2. Content of the 6-day MBSR program used in this study
Sequence Theme Content
Class day 1 Introduction and preparation Introduction to mindfulness
Class day 2
Opening the 5 senses
Raisin-eating meditation and
walking meditation
Class day 3
Familiarization with one's own
body
Body scan and mindfulness of
breathing
Class day 4
Stress reactivity versus stress response
Understanding of stress and
mindful communication
Class day 5
Awareness of nature
Mountain meditation and
mindfulness of thoughts
Class day 6
Integration of mindfulness
into daily life
Review and plan for using
mindfulness in one's daily life
27
Table 3. Effects of forest bathing on the immune cell populations and WHOQOL-BREF domain
scores of the breast cancer patients
Pre Post % Increase p
T cell population 36.50 ± 6.88 36.93 ± 8.12 1.2 0.742
NK cell population 17.08 ± 3.88 20.53 ± 5.39 20.2 0.004
QOL domain 1 51.63 ± 13.19 59.74 ± 9.46 15.7 0.049
QOL domain 2 54.17 ± 15.37 60.61 ± 9.01 11.9 0.112
QOL domain 3 55.97 ± 7.84 59.09 ± 6.62 5.6 0.279
QOL domain 4 61.36 ± 10.05 58.33 ± 10.54 −4.9 0.221
QOL overall 54.55 ± 21.85 68.18 ± 11.68 25.0 0.006
QOL general health 38.64 ± 25.89 54.55 ± 18.77 41.2 0.026
The mean and standard deviation values in group 1 (n = 11) are shown before (pre) and after
(post) forest bathing. The percent increase was calculated according to the following
formula: [(post – pre) / pre] x 100, and the p values were obtained from the difference
between the pre and post values by a paired t test. QOL stands for WHOQOL-BREF
28
Table 4. Effect of forest bathing integrated with the MBSR program on the immune cell
populations and WHOQOL-BREF domain scores of the breast cancer patients
Pre Post % Increase p
T cell population 38.01 ± 5.51 39.31 ± 6.32 3.4 0.425
NK cell population 16.19 ± 4.85 22.80 ± 6.78 40.8 <0.001
QOL domain 1 49.02 ± 18.36 69.15 ± 18.71 41.1 <0.001
QOL domain 2 56.82 ± 19.74 73.86 ± 15.38 30.0 <0.001
QOL domain 3 59.09 ± 11.39 65.63 ± 12.58 11.1 0.105
QOL domain 4 62.12 ± 16.40 66.67 ± 18.26 7.3 0.140
QOL overall 52.27 ± 23.60 79.55 ± 15.08 52.2 <0.001
QOL general health 36.36 ± 17.19 59.09 ± 23.11 62.5 0.002
The mean values, standard deviations, percent increase, and p values for the patients in group
2 (n = 11) were obtained as described in table 3.
29
Figure legends
Figure 1. Forest bathing and MBSR act in a cooperative manner to induce an increase in NK
cell population in breast cancer patients. Black bar: percent increase in the population of
each immune cell (NK and T-helper cells) in lymphocytes for the group 1 patients (n = 11) who
participated in forest bathing exclusively; white bar: increase for the group 2 patients (n = 11)
who were subjected to forest bathing integrated with the MBSR program. The mean increase
value for the patients in each group is shown as a bar graph with a standard deviation. *p =
0.033
Figure 2. Forest bathing and MBSR act in a cooperative manner to enhance the WHOQOL-
BREF domain scores in the breast cancer patients. Black bar: increase of each WHOQOL-BREF
domain score for the group 1 patients (n = 11) exposed to forest bathing alone; white bar:
increase in the scores of the group 2 patients (n = 11) who underwent forest bathing
integrated with the MBSR program. The mean increase values for the patients in each group
are shown as a bar graph with standard deviations. *p = 0.037, **p = 0.045, ***p = 0.026
12
10
8
6
4
2
0In
cre
ase in
% im
mu
ne
cell p
op
ula
tion
NK cells T helper cells
*
Figure 1
Figure 1
50
40
30
20
10
0In
cre
ase in
WH
OQ
OL
-BR
EF
d
om
ain
sco
re
Overa
ll
Genera
l health
Domain
1
Domain
2
Domain
3
Domain
4
**
Figure 2
***
*
Figure 2