[Objectives] The aim of this study was to evaluate the changes in serum brain-derived neurotrophic factor (BDNF) concentrations during 15 min of combined hot bath and bicycle ergometer endurance exercise in healthy young men.

  [Methods] The experiment was conducted in a parallel design. The subjects were 10 healthy men (aged 23.7±0.8 years). The experimental group performed a combination of head-out water immersion (HOI) at 40°C and bicycle ergometer exercise (40°C HOI-ex), while the control group performed only HOI at 40°C (40°C HOI). After 30 min of rest, 40°C HOI-ex or 40°C HOI was performed for 15 min, followed by a 30 min recovery period. During the experiment, heart rate, blood pressure, and core temperature (esophageal temperature) were continuously measured. Blood samples were collected at four time points: after rest, immediately after intervention, 15 min after recovery, and 30 min after recovery. Serum BDNF, P-selectin, platelet count, hemoglobin, hematocrit, plasma cortisol, and lactic acid were then measured.

  [Results] A significant increase in serum BDNF concentrations was observed immediately after intervention and 15 min after recovery in the 40°C HOI-ex group compared with the values taken after resting. No changes in serum BDNF concentrations were observed in the 40°C HOI group. Core temperatures significantly increased immediately after intervention, 15 min after recovery, and 30 min after recovery compared with resting for both 40°C HOI-ex and 40°C HOI groups, with between-group differences. Platelet counts were unchanged in both 40°C HOI and 40°C HOI-ex groups. A significant increase in P-selectin was observed immediately after intervention and 15 min after recovery in the 40°C HOI-ex group compared with when at rest. No changes in P-selectin were observed in 40°C HOI.

  [Discussion] The combination of hyperthermia and exercise can increase serum BDNF in a short time of 15 min by an additive effect, and the increase in serum BDNF in this study may be platelet-derived.

  In 2018, we reported an epidemiological study on disease-preventive effects of habitual hot spa-bathing in the elderly in Beppu city, which has the highest number of hot spring sources in the world. In this analysis, women with diabetes mellitus were observed more often as hot spa-bathers than non-spa-bathers [odds ratio (OR): 1.238, confidence interval (CI): 1.011-1.517]. To see whether there is an apparent harmful effect of spa-bathing, complicated background diseases of women with diabetes mellitus were investigated in this study. We compared background diseases of women complicated with diabetes mellitus in spa-bathers and non-spa-bathers. Compared with non-spa-bathers, female spa-bathers with diabetes mellitus revealed a higher occurrence of cancer history (OR: 2.626, CI 1.517-4.545). The occurrence of diabetes mellitus in women with no cancer history was not significantly different between habitual spa-bathers and non-spa-bathers (OR:1.041, CI 0.837-1.293). The observed odds ratios suggest that spa-bathing associated cancer surviving promotion leads to an increasing number of diabetic women with a past history of cancer and contributes to more women with diabetes mellitus in spa-bathers rather than habitual spa-bathing promoting the pathogenesis of diabetes mellitus.

  We have previously reported that high-temperature (42°C) culture inhibited the proliferation of human umbilical endothelial cells (HUVECs). We described how the proliferative capacity and telomere length (TL)-related parameters of HUVECs, one of somatic cells, change with culture temperature. It was speculated that a combination of cytostatic manipulations, such as anticancer treatments, and high-temperature conditions would more effectively suppress the growth of somatic cells. Therefore, we hypothesized that increasing the core body temperature (BT) as a pretreatment for cancer treatment enhances the effectiveness of cancer treatment. In the present study, various cells (HUVECs, Jurkat cells, and SLVL) were cultured under different temperature conditions (35°C, 37°C or 39°C) combined with anticancer manipulations (X-ray irradiation or addition of 1-β-D-Arabinofuranosylcytosine [Ara-C]), which resulted in changes in the proliferation rate and TL. The degree of cell proliferation inhibitory effect depended on the combination of cell type, anticancer procedure, and temperature condition. Therefore, the best therapeutic condition might be selected in advance by checking the proliferation rate of biopsied cancer cells being cultured under combinations of anticancer manipulations at altered temperature conditions.