Kim BJ, Jeong H, Park S, Lee S. Forest adjuvant anti-cancer therapy to enhance natural cytotoxicity in urban women with breast cancer: A preliminary prospective interventional study. Eur J Integr Med. 2015;7(5):474-478.
Design & Participants
Eleven women (ages 25-60) living in Seoul, South Korea, being treated for stage I–III breast cancer were all brought to a forested national park for a 14-day regimen of “forest therapy.” Participants stayed in log cabins in the forest, participated in a structured 3-mile forest hike every morning, and were free to engage in a variety of self-directed personal or group activities in the afternoons. All participants were otherwise healthy with no detectable physical or mental health issues.
Baseline blood samples were taken 3 times:
- before leaving Seoul for the 2-week forest therapy session (day 1),
- at conclusion of the forest therapy (day 14), and
- one week after returning to Seoul (day 21).
These samples were analyzed to detect natural killer (NK) cell count, as well as serum concentrations of perforin and granzyme B, NK’s cytotoxic ‘arsenal’ enzymes that lyse and disrupt tumor cell function.1
All blood measures showed statistically significant increases. NK cell count increased 39% (319.4/µL to 444.6/µL, P<0.01) between baseline and the conclusion of the forest therapy. One week after returning to the city, NK count had decreased, though was still elevated 13% relative to baseline (361.8/µL).
Cytotoxic proteases experienced sustained concentration increases throughout forest therapy and into the follow-up period. Perforin concentration increased 59% from baseline to conclusion of forest therapy (216.9 pg/mL to 344.9 pg/mL) and continued to increase to 114% (463.2 pg/mL) of baseline levels (P<0.02). Similarly, granzyme B concentration increased 155% from baseline to forest therapy conclusion (4.4 pg/mL to 11.2 pg/mL), and ultimately to 359% above baseline (20.2 pg/mL, P<0.02).
All participants completed the full course of forest therapy with no adverse effects reported.
Standard medical treatment for breast cancer (eg, surgery, radiation, chemotherapy) can be rigorous and immunosuppressive.2,3 Destruction or reduction of tumor mass may be achieved but comes at the cost of suppressing the patient’s natural antitumor NK cell functions. Complementary and integrative health (CIH, formerly known as complementary and alternative medicine, or CAM4) approaches are well known for supporting the health and well-being of the patient while simultaneously treating their disease. This small study of adjunctive forest therapy is a great example of the benefits of a CIH approach to breast cancer care.
Mental benefits of 'contact with nature' include improved cognition, memory, and attention, as well as increased feelings of prosociality, sense of purpose, spiritual connection, and quality of life.
This study utilizes an experience, known traditionally as “forest air bathing” (shinrin-yoku in Japanese), that has been a part of Asian cultures for centuries and has been empirically studied for more than a decade. People go into the forest to allow the pleasant scenes, sounds, and smells to wash over them. Of particular medical interest in forest therapy are the aromatherapeutic compounds known as “phytoncides,” a class of naturally occurring terpenes produced by many forest trees that have both in vitro and in vivo NK immunostimulatory properties.5,6 Many studies of shinrinyoku have shown NK-modulating effects in healthy participants7; however this current study is one of the first to measure oncotoxic cytokine levels in a clinically relevant population. While the design of the study precludes attributing causality of biomarker increase to forest exposure directly, previous studies providing evidence of similar NK cell effects suggest that such a cause-effect relationship is present.
Of course, the potential immunomodulation of phytoncide exposure isn’t the only advantage of participating in forest therapy. Reduction of allostatic load (eg, blood pressure, cortisol, HRV, IL-6, TNF-a) with resultant decrease in inflammation and autonomic nervous system dysfunction is one set of well-reported benefits.8-10 Improvements in both positive and negative mood and their associated clinical disorders is another.11,12 Other mental benefits of “contact with nature” include improved cognition, memory, and attention,9,13-15 as well as increased feelings of prosociality, sense of purpose, spiritual connection, and quality of life.16-18 All of these impacts of forest therapy make it a potentially valuable holistic approach to health promotion for everyone and anyone, including patients with cancer.
As a feasibility study, there were many issues that this small trial could not address. There was no comparison group acting as a control, so it is not possible to attribute biomarker changes to forest therapy alone. However, the authors do state in their discussion that they intend to have a wait-list control group for their next, larger trial. In addition, because this was a 2-week residential group experience, it is possible that activities other than spending time in the forest (eg, social interaction) were responsible for the measured effects. A similarly designed residential experience in a different setting would help differentiate this. Lastly, no measurement of airborne phytoncides was made, making it impossible to say if this proposed mechanism-of-action was truly responsible for NK immunomodulation.
The findings of this initial feasibility study, supported by evidence from the literature, are sufficient to say that a forest therapy program may be a beneficial method of adjunctive cancer care. Future studies will be necessary to determine if biomarker outcomes can be translated into clinical success—that is, whether increased NK count and cytotoxin concentration induced by forest therapy can reduce tumors and address cancer using a CIH approach.
- Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15(6):388-400.
- Sewell HF, Halbert CF, Robins RA, Galvin A, Chan S, Blamey RW. Chemotherapy-induced differential changes in lymphocyte subsets and natural-killer-cell function in patients with advanced breast cancer. Int J Cancer. 1993;55(5):735-738.
- Uchida A, Kolb R, Micksche M. Generation of suppressor cells for natural killer activity in cancer patients after surgery. J Natl Cancer Inst. 1982;68:735-741.
- NIH complementary and integrative health agency gets new name. National Center for Complementary and Integrative Health Web site. https://nccih.nih.gov/news/press/12172014. Updated April 17, 2015. Accessed January 26, 2016.
- Li Q, Nakadai A, Matsushima H, et al. Phytoncides (wood essential oils) induce human natural killer cell activity. Immunopharmacol Immunotoxicol. 2006;28(2):319-333.
- Li Q, Morimoto K, Kobayashi M, et al. Visiting a forest, but not a city, increases human natural killer activity and expression of anti-cancer proteins. Int J Immunopathol Pharmacol. 2008;21(1):117.
- Li Q. Effect of forest bathing trips on human immune function. Environ Health Prev Med. 2010;15(1):9-17.
- Lee J, Park B-J, Ohira T, Kagawa T, Miyazaki Y. Acute effects of exposure to a traditional rural environment on urban dwellers: a crossover field study in terraced farmland. Int J Environ Res Public Health. 2015;12:1874-1893.
- Tsunetsugu Y, Lee J, Park B-J, Tyrväinen L, Kagawa T, Miyazaki Y. Physiological and psychological effects of viewing urban forest landscapes assessed by multiple measurements. Landsc Urban Plan. 2013;113:90-93.
- Mao G-X, Lan X-G, Cao Y-B, et al. Effects of short-term forest bathing on human health in a broad-leaved evergreen forest in Zhejiang Province, China. Biomed Environ Sci. 2012;25(3):317-324.
- Berman MG, Kross E, Krpan KM, et al. Interacting with nature improves cognition and affect for individuals with depression. J Affect Disord. 2012;140(3):300-305.
- Shin WS, Yeoun PS, Yoo RW, Shin CS. Forest experience and psychological health benefits: the state of the art and future prospect in Korea. Environ Health Prev Med. 2009:1-10.
- Bratman GN, Daily GC, Levy BJ, Gross JJ. The benefits of nature experience: Improved affect and cognition. Landsc Urban Plan. 2015;138:41-50.
- Holden LJ, Mercer T. Nature in the learning environment: exploring the relationship between nature, memory, and mood. Ecopsychology. 2014;6(4):234-240.
- Kim W, Lim SK, Chung EJ, Woo JM. The effect of cognitive behavior therapy-based psychotherapy applied in a forest environment on physiological changes and remission of major depressive disorder. Psychiatry Investig. 2009;6:245-254.
- Piff PK, Dietze P, Feinberg M, Stancato DM, Keltner D. Awe, the small self, and prosocial behavior. J Pers Soc Psychol. 2015;108(6):883-899.
- Nakau M, Imanishi J, Imanishi J, et al. Spiritual care of cancer patients by integrated medicine in urban green space: a pilot study. Explor J Sci Heal. 2013;9(2):87-90.
- Sung J, Woo J-M, Kim W, Lim S-K, Chung E-J. The effect of cognitive behavior therapy-based “forest therapy” program on blood pressure, salivary cortisol level, and quality of life in elderly hypertensive patients. Clin Exp Hypertens. 2012;34(1):1-7.