In order to explore the effect of forest bathing on human immune function, we investigated natural killer (NK) activity; the number of NK cells, and perforin, granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields. Twelve healthy male subjects, age 37-55 years, were selected with informed consent from three large companies in Tokyo, Japan. The subjects experienced a three-day/two-night trip in three different forest fields. On the first day, subjects walked for two hours in the afternoon in a forest field; and on the second day, they walked for two hours in the morning and afternoon, respectively, in two different forest fields. Blood was sampled on the second and third days, and NK activity; proportions of NK, T cells, granulysin, perforin, and granzymes A/B-expressing cells in PBL were measured. Similar measurements were made before the trip on a normal working day as the control. Almost all of the subjects (11/12) showed higher NK activity after the trip (about 50 percent increased) compared with before. There are significant differences both before and after the trip and between days 1 and 2 in NK activity. The forest bathing trip also significantly increased the numbers of NK, perforin, granulysin, and granzymes A/B-expressing cells. Taken together, these findings indicate that a forest bathing trip can increase NK activity, and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins.

We previously reported that a forest bathing trip enhanced human NK activity, number of NK cells, and intracellular anti-cancer proteins in lymphocytes. In the present study, we investigated how long the increased NK activity lasts and compared the effect of a forest bathing trip on NK activity with a trip to places in a city without forests. Twelve healthy male subjects, age 35-56 years, were selected with informed consent. The subjects experienced a three-day/two-night trip to forest fields and to a city, in which activity levels during both trips were matched. On day 1, subjects walked for two hours in the afternoon in a forest field; and on day 2, they walked for two hours in the morning and afternoon, respectively, in two different forest fields; and on day 3, the subjects finished the trip and returned to Tokyo after drawing blood samples and completing the questionnaire. Blood and urine were sampled on the second and third days during the trips, and on days 7 and 30 after the trip, and NK activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B-expressing lymphocytes in the blood samples, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trips on a normal working day as the control. Phytoncide concentrations in forest and city air were measured. The forest bathing trip significantly increased NK activity and the numbers of NK, perforin, granulysin, and granzyme A/B-expressing cells and significantly decreased the concentration of adrenaline in urine. The increased NK activity lasted for more than 7 days after the trip. In contrast, a city tourist visit did not increase NK activity, numbers of NK cells, nor the expression of selected intracellular anti-cancer proteins, and did not decrease the concentration of adrenaline in urine. Phytoncides, such as alpha-pinene and beta-pinene were detected in forest air, but almost not in city air. These findings indicate that a forest bathing trip increased NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone may partially contribute to the increased NK activity.

Abstract. A reduction in ankle-brachial BP index (ABPI) is associated with generalized atherosclerotic diseases and predicts cardiovascular mortality and morbidity in several patient populations. However, a large-scale analysis of ABPI is lacking for hemodialysis (HD) patients, and its use in this population is not fully validated. A cohort of 1010 Japanese patients undergoing chronic hemodialysis was studied between November 1999 and May 2002. Mean age at entry was 60.6 Ϯ 12.5 yr, and duration of follow-up was 22.3 Ϯ 5.6 mo. Patients were stratified into five groups (Ͻ 0.9, Ն 0.9 to Ͻ 1.0, Ն 1.0 to Ͻ 1.1, Ն 1.1 to Ͻ 1.3, and Ն 1.3) by ABPI measured at entry by an oscillometric method. The frequency distribution of ABPI was 16.5% of patients Ͻ 0.9, 8.6% of patients Ն 0.9 to Ͻ 1.0, 16.9% of patients 1.0 Ն to Ͻ 1.1, and 47.0% of patients Ն 1.1 to Ͻ 1.3, whereas 10.9% of patients had an abnormally high ABPI (Ն 1.3). The relative risk of a history of diabetes mellitus (DM), cardiovascular, and cerebrovascular disease was significantly higher in patients with lower ABPI than those with ABPI Ն 1.1 to Ͻ1.3. During the study period, 77 cardiovascular and 41 noncardiovascular fatal events occurred. On the basis of Cox proportional hazards regression analysis, ABPI emerged as a strong independent predictor of all-cause and cardiovascular mortality. After adjustment for confounding variables, the hazard ratio (HR) for ABPI Ͻ 0.9 was 4.04 (95% confidence interval, 2.38 to 6.95) for all-cause mortality and 5.90 (2.83 to 12.29) for cardiovascular mortality. Even those with modest reductions in the ABPI (Ն 0.9 to Ͻ1

We previously found that forest environments reduced stress hormones such as adrenaline and noradrenaline and showed the relaxing effect both in male and female subjects. In the present study, we investigated the effects of walking under forest environments on cardiovascular and metabolic parameters. Sixteen healthy male subjects (mean age 57.4 ± 11.6 years) were selected after obtaining informed consent. The subjects took day trips to a forest park in the suburbs of Tokyo and to an urban area of Tokyo as a control in September 2010. On both trips, they walked for 2 h in the morning and afternoon on a Sunday. Blood and urine were sampled on the morning before each trip and after each trip. Blood pressure was measured on the morning (0800) before each trip, at noon (1300), in the afternoon (1600) during each trip, and on the morning (0800) after each trip. The day trip to the forest park significantly reduced blood pressure and urinary noradrenaline and dopamine levels and significantly increased serum adiponectin and dehydroepiandrosterone sulfate (DHEA-S) levels. Walking exercise also reduced the levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and urinary dopamine. Taken together, habitual walking in forest environments may lower blood pressure by reducing sympathetic nerve activity and have beneficial effects on blood adiponectin and DHEA-S levels, and habitual walking exercise may have beneficial effects on blood NT-proBNP levels.

In the present study, we investigated the effects of a forest bathing on cardiovascular and metabolic parameters. Nineteen middle-aged male subjects were selected after they provided informed consent. These subjects took day trips to a forest park in Agematsu, Nagano Prefecture, and to an urban area of Nagano Prefecture as control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured during the trips. The Japanese version of the profile of mood states (POMS) test was conducted before, during, and after the trips. Ambient temperature and humidity were monitored during the trips. The forest bathing program significantly reduced pulse rate and significantly increased the score for vigor and decreased the scores for depression, fatigue, anxiety, and confusion. Urinary adrenaline after forest bathing showed a tendency toward decrease. Urinary dopamine after forest bathing was significantly lower than that after urban area walking, suggesting the relaxing effect of the forest bathing. Serum adiponectin after the forest bathing was significantly greater than that after urban area walking.

We previously reported that the forest environment enhanced human natural killer (NK) cell activity, the number of NK cells, and intracellular anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after trips to forests both in male and female subjects. To explore the factors in the forest environment that activated human NK cells, in the present study we investigate the effect of essential oils from trees on human immune function in twelve healthy male subjects, age 37-60 years, who stayed at an urban hotel for 3 nights from 7.00p.m. to 8.00a.m. Aromatic volatile substances (phytoncides) were produced by vaporizing Chamaecyparis obtusa (hinoki cypress) stem oil with a humidifier in the hotel room during the night stay. Blood samples were taken on the last day and urine samples were analysed every day during the stay. NK activity, the percentages of NK and T cells, and granulysin, perforin, granzyme AlB-expressing lymphocytes in blood, and the concentrations of adrenaline and noradrenaline in urine were measured. Similar control measurements were made before the stay on a normal working day. The concentrations of phytoncides in the hotel room air were measured. Phytoncide exposure significantly increased NK activity and the percentages of NK, perforin, granulysin, and granzyme AlB-expressing cells, and significantly decreased the percentage of T cells, and the concentrations of adrenaline and noradrenaline in urine. Phytoncides, such as a-pinene and -pinene, were detected in the hotel room air. These findings indicate that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity.The forest environment has been enjoyed by humans for a long time because of the quiet atmosphere, beautiful scenery, mild climate, and clean fresh air. We previously reported that the forest environment enhanced human natural killer (NK) cell activity, the number of NK and NKT cells, and intracellular anti-cancer proteins in lymphocytes, and that the increased NK activity lasted for more than 7 days after the trips to forests both in male and female subjects (1-5). However, it is not clear what kind of factors in the forest environment activated human NK cells. We speculate that aromatic volatile substances derived from trees, including monoterpenes and sesquiterpenes, called phytoncides, such as a-pinene and limonene (6), may play an important role. Thus, the effects of phytoncides, such as a-pinene,

Background--Hypertension is one of the main comorbidities associated with dyslipidemia. This study aimed to examine the extent to which dyslipidemia increases the risk of developing hypertension in a Japanese working-age male population.

To explore the effect of forest bathing on the human immune system, we investigated the effect of phytoncides (wood essential oils) on natural killer (NK) activity and the expression of perforin, granzyme A and granulysin in human NK cells. We used NK-92MI cell, an interleukin-2 independent human NK cell line derived from the NK-92 cell, in the present study. NK-92MI cells express the CD56 surface marker, perforin, granzyme A, and granulysin by flow cytometry and are highly cytotoxic to K562 cells in chromium release assay. Phytoncides significantly increase cytolytic activity of NK-92MI cells in a dose-dependent manner and significantly increase the expression of perforin, granzyme A, and granulysin in the NK-92MI cells. Phytoncides also partially, but significantly, restore the decreased human NK activity and the decreased perforin, granzyme A, and granulysin expression in NK-92MI cells induced by dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide. Pretreatment with phytoncides partially prevents DDVP-induced inhibition of NK activity. Taken together, these data indicate that phytoncides significantly enhance human NK activity and this effect is at least partially mediated by induction of intracellular perforin, granzyme A, and granulysin.