Balneotherapy, i.e., the treatment of diseases by bathing, has been practiced since ancient times for therapeutic and medical purposes, and its therapeutic effects on cardiovascular and dermatological diseases have been documented.15–17 Our previous double-blind, placebo-controlled study of NBIW and our in vitro and in vivo studies suggested that NBIW increases body temperature, promotes blood flow via nitric oxide production, and improves mental stress and sleep quality.12 However, the placebo control contained magnesium sulfate and sodium sulfate, both of which are known to promote blood circulation; hence, warm bathing in the placebo control also showed mild effects in some analysis items, making it difficult to analyze the effectiveness of NBIW. Therefore, we conducted the present randomized, open-label, crossover trial to further investigate the effects of bathing in NBIW. The study included assessments of immune function because of the close correlation between stress, sleep, and immune function.
A number of previous studies reported on the efficacy of balneotherapy in improving mental stress and sleep disorders, and a large-scale randomized controlled trial (N = 500) conducted in 2016 in Chongqing, China, showed that balneotherapy is effective in reducing mental stress and sleep disorders and alleviating general health concerns.18 Moreover, given that balneotherapy reduces levels of cortisol, a stress biomarker, some authors have suggested that it may be beneficial in controlling mental stress.19 In the stress assessment in the present study, BJSQ category C (Social Support) was significantly improved by the use of NBIW compared with the control, suggesting that bathing in NBIW reduced stress, improved the psychological state, and altered the participants’ interpersonal cognition.
Balneotherapy over a period of 2 to 3 weeks may have beneficial effects on sleep quality.20 It is thought to improve sleep by lowering systemic blood pressure and core body temperature by dilating peripheral blood vessels throughout the body, reducing pain by inhibiting inflammation and pain-related substances, and relaxing muscles.21 The PSQI-J, the primary sleep endpoint in this study, assesses subjective sleep quality, including insomnia; the total score ranges from 0 to 21, and a score of 6 or more indicates a potential sleep problem.14,22 In the present study, the PSQI-J score confirmed that the NBIW intervention led to significantly greater improvements in subjective sleep quality than the control intervention. Furthermore, in the actigraphy sleep assessment, which was used as an objective assessment of sleep, the mean values of each item during the 3-week period showed a significant reduction in sleep latency and bed out latency and a trend towards improved sleep in many items with the NBIW intervention compared with the control intervention. These changes were observed from the first week of starting the measurements and became increasingly evident at 3 weeks, suggesting that this sleep-improving effect is sustained and may be enhanced by continued NBIW bathing.
Mental stress and sleep quality are known to interact closely, and studies have shown that sleep quality is reduced in stressful environments23,24 and that stress can be reduced by improving sleep quality.25 In this study, NBIW bathing was considered to improve the quality of sleep not only subjectively but also objectively. NBIW may have these effects by promoting blood circulation via production of nitric oxide and increasing body temperature, which together help to alleviate stress.12
A large number of studies have shown that mental stress increases the risk of a wide range of diseases and may be a risk factor for cancer and autoimmune diseases.26,27 Mental stress is also particularly strongly associated with cardiovascular disease.28 For example, several articles have reported that mental stress induces myocardial ischemia in patients with coronary artery disease29,30 and that depression is correlated with cardiovascular disease.31 In addition, the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC study), which was sponsored by the Ministry of Education, Science, Sports and Culture of Japan, identified mental stress as being associated with increased coronary artery disease and increased stroke mortality in women,32 and in the large-scale international case-control INTERHEART study, psychosocial factors were found to more than double the risk of myocardial infarction.33 One of the primary mechanisms underlying the onset of cardiovascular disease due to mental stress may be inflammation-mediated vascular endothelial dysfunction resulting from the release of inflammatory cytokines as a result of suppression of the parasympathetic nervous system.34 A previous study showed that the bicarbonate ions in NBIW act directly on vascular endothelial cells to induce nitric oxide production through phosphorylation of endothelial nitric oxide synthase.12 As such, these findings suggest that continued NBIW bathing with warm water may also reduce the risk of cardiovascular disease by improving both mental stress and vascular endothelial function.
Immune function is also thought to be closely related to stress and sleep.35,36 Several studies have shown that stress is a risk factor for cancer and autoimmune diseases, suggesting that stress affects immune tolerance and anticancer immunity.27,37 Furthermore, sleep deprivation is known to alter the secretion of inflammatory markers such as interleukins, tumor necrosis factor-α, other cytokines, chemokines, and acute phase proteins.38,39
In this study, changes in several immune factors were seen with NBIW and control bathing. The CD4+:CD8+ T-cell ratio did not change significantly with the NBIW bathing intervention, but it decreased with the control bathing intervention because of an increase in CD8+ and CD8+CD28+ T cells. CD8+ T cells are known to fluctuate in number and function in response to stress,40–42 and because this study was performed in participants who felt “regularly stressed,” the results suggest that bathing in NBIW water may have suppressed the stress-related increase in the number of CD8+ T cells.
The proportion of naive T cells, as represented by CD4+CD45RA+, decreased slightly after NBIW bathing, while the number of memory T cells showed a tendency to increase, resulting in a lower naïve to memory cell ratio. Thus, given that tissue-resident and circulating memory T cells play an essential role in anti-tumor immunity, NBIW bathing may enhance anti-tumor immune function.43
The proportion of CD16+CD56- cells, a marker of mature NK T cells, decreased significantly in the NBIW bathing intervention. CD16+CD56- mature NK T cells are increased by post-traumatic stress,44 suggesting that NBIW bathing may reduce CD16+CD56- mature NK T cells by alleviating stress.
The proportion of CD20+ B cell markers among total lymphocytes, the number of B cells, and the level of neutrophil phagocytosis and NK T cell activity increased significantly after both interventions, suggesting that warm bathing itself improves immune function; however, the significant change in neutrophil phagocytosis from before to after the intervention period was greater with NBIW than with control.
This study has some limitations. Most of the participants were middle aged, and recruiting people with self-perceptions of being stressed on a daily basis may limit the generalizability of the results.
Taken together, the results of this study suggest that NBIW bathing has a positive influence on stress, sleep, and immune function. Stress, sleep, and immune function interact with each other, so the effect of NBIW on immune function may be mediated through the improvements in stress and sleep. In addition, given that bicarbonate ions stimulate nitric oxide production in macrophage cell lines stimulated by lipopolysaccharide and interferon-gamma, which in turn promotes inflammatory responses,45,46 it is conceivable that increased bicarbonate ions in the blood due to NBIW bathing may have a direct effect on immune system cells. In the future, further studies of such mechanisms are warranted.