REF-1724 · Snape et al., 2026 · PLoS ONE, · Paper · PubMed

Five daily 90-min sessions of controlled-hyperthermia cycling in hot-humid air lowered resting heart rate by 8 bpm, raised plasma volume 7.3% (within the heat group; controls +3.0%, not significant, no group comparison reported) and sweat loss 500 mL in 7 endurance-trained men, against 7 who trained in temperate air, yet peak core temperature and peak heart rate in a 45-min heat test were not shown to improve more than in controls and blood markers of kidney stress did not change; adaptation markers only, no performance test

Main caveat: Seven per group; the authors note that high variability and modest sample size may have hidden real biomarker changes, and the power calculation was based on…
limited, mixed evidenceMeasured on trained to highly trained athletesRead in full

Snape and colleagues tested whether five days of controlled-hyperthermia heat acclimation changes the strain of exercise in hot-humid air and the blood markers that rise with early stress on the kidney tubules.

Fourteen endurance-trained men were randomised to five consecutive 90-min sessions at 32 °C and 70% humidity, riding first at 2.5 W/kg and then at a self-chosen intensity to hold rectal temperature at or above 38.5 °C, or to five 90-min sessions in temperate air with the same opening workload.

Before and after, each rode 45 min at 2.5 W/kg in the same hot-humid conditions with blood drawn before and straight after. In the heat group resting heart rate fell 8 bpm, plasma volume rose 7.3% and sweat loss rose 500 mL, while peak core temperature, peak heart rate and peak skin temperature in the heat test did not change differently from controls.

Copeptin, normetanephrine, NGAL and KIM-1 showed no group-by-time interaction. The authors conclude that the protocol is a time-efficient way to improve heat responses but leaves renal stress markers unchanged; they suggest longer blocks with hydration or cooling plans may be needed to protect the kidney, which this study did not test.

Participants

n = 14 healthy endurance-trained men; no exposure above 25 °C for at least 3 months; at least 5 h of aerobic exercise a week.
Heat group (HOT) n = 7: age 29 ± 10 years, VO2max 63 ± 8 mL/kg/min, maximal ramp minute power 400 ± 37 W.
Temperate group (TEMP) n = 7: age 28 ± 9 years, VO2max 55 ± 6 mL/kg/min (p = 0.051 vs HOT), maximal ramp minute power 339 ± 36 W (p = 0.011 vs HOT).
All completed both heat tests; one TEMP participant gave no venous blood.

Protocol

Heat sessions (HOT): five consecutive days, 90 min at 32.2 °C and 69.7% RH; 2.5 W/kg until rectal temperature reached 38.5 °C, then self-selected intensity to keep it there, with passive rest allowed above 39.3 °C; fluid intake weighed.
Temperate sessions (TEMP): five consecutive days, 90 min at 21.3 °C and 37.3% RH; about 30 min at 2.5 W/kg, then self-selected; drinking ad libitum.
Session duration and relative power did not differ between groups; HOT rode at a higher share of maximal heart rate (79 vs 71%, p = 0.030).
Heat stress test: 45 min at 2.5 W/kg at 32.0 °C and 70.4% RH, 48 h before the first and 48 h after the last session, 07:00-11:00, arriving euhydrated by urine checks; ingested pill for core temperature, four skin sensors, nude weighing for sweat loss, capillary haemoglobin and haematocrit for plasma volume, venous blood before and immediately after for NGAL, KIM-1, copeptin, normetanephrine and serum osmolality (not corrected for plasma volume shifts).
Conditions chosen to resemble those expected at the Tokyo 2020 Games; data collected December 2018 to June 2019.

Key Results

Heat stress test measureHOT before → after (change)TEMP before → after (change)Group × time
Resting heart rate63 ± 6 → 55 ± 9 bpm (−8 ± 5; p = 0.007, d = 1.0)61 ± 5 → 62 ± 7 (+1 ± 6)p = 0.014
Peak heart rate168 ± 9 → 163 ± 10 (−5 ± 3)176 ± 12 → 175 ± 11 (−1 ± 6)p = 0.264, not significant
Peak core temperature (pill)38.9 ± 0.6 → 38.7 ± 0.4 °C (−0.2 ± 0.3)38.6 ± 0.6 → 38.6 ± 0.6 (0 ± 0.3)p = 0.687, not significant
Resting core temperature−0.2 ± 0.3 °C−0.1 ± 0.1 °Cp = 0.586, not significant
Peak skin temperature−0.1 ± 0.4 °C+0.1 ± 0.1 °Cp = 0.065, not significant
Plasma volume+7.3 ± 5.1% (p = 0.022)+3.0 ± 6.4% (p = 0.393)interaction not reported
Sweat loss+500 ± 539 mL (p = 0.017 in the results, 0.018 in the abstract; d = 1.1)no significant changep = 0.010
Peak RPE−2 ± 2 (time effect, p = 0.007, d = 1.0)no significant changenot significant
Peak thermal comfort−1 ± 1 (time effect, p = 0.016, d = 1.3)no significant changenot significant
Blood markers after the heat test: no group × time interaction for any marker (p > 0.05). After acclimation, post-test normetanephrine −5.7% (d = 0.2), copeptin −21.5% (p = 0.314, d = 0.5), NGAL −13.9% (p = 0.716, d = 0.7) and KIM-1 +22.3% (d = 0.2), none significant.
Within each test: normetanephrine rose in both groups in both tests (p < 0.001); copeptin rose in the first test (HOT +11 ± 6, TEMP +12 ± 13 pmol/L) but not the second; NGAL rose only in TEMP in the first test (+45 ± 29 μg/L, p = 0.030); KIM-1 did not change; serum osmolality rose 10 ± 5 mOsm/kg in HOT during the second test only.
The authors describe sweat loss as up 37% and note the plasma-volume gain exceeded the +4.3% they cite from earlier short-term studies.

Practical Application

Five days of heat sessions held at a rectal temperature of 38.5 °C or more moved some adaptation markers, not all of them. Resting heart rate and sweat loss changed more than in controls and plasma volume rose within the heat group (no group comparison reported), in 7 trained men, but peak core temperature and peak heart rate at the same 2.5 W/kg in the heat did not fall significantly more than in controls (group × time p = 0.687 and 0.264), and there was no performance or heat-tolerance test, so this shows a partial adaptation, not a ready athlete.
Where it meets [SYNTH-04]: the guide says not to run a block of only five days, an inference from an occupational study whose heat-tolerance limit had not moved after 5 days. This trial measured neither that limit nor performance.It is consistent with the guide in that peak core temperature and peak heart rate in the heat test were not shown to fall more than after temperate training (7 per group, so a real difference could be missed).It sits against the guide's advice not to run a five-day block in that sweat loss rose more than in controls within five days (+500 mL, interaction p = 0.010) and resting heart rate fell more (p = 0.014), and plasma volume rose 7.3% within the heat group, close to the guide's +6.5% after 10 days (REF-001), though the controls' +3.0% was not formally compared with it.It does not show that five days makes a full block, and the guide's dose table is not tested.
Early comfort is not proof: peak RPE and thermal comfort improved within the heat group without a difference from controls, in line with the guide's warning that early comfort is not proof that heat tolerance has moved.
Kidney markers: five days of heat sessions were not shown to lower the blood markers of early tubular stress (no group × time interaction, in a sample the authors say may be too small for these markers) after exercise in hot-humid air, and kidney function itself was not measured. This is not medical advice; dark urine, very little urine, or feeling unwell after a hot session goes to a physician (practice, not from this study).
Inference, not tested here: the controlled-hyperthermia dose needed a rectal probe; at home the guide's heart-rate check at a fixed submaximal intensity stays the practical gauge, and in this trial peak heart rate at fixed work fell 5 ± 3 bpm in the heat group against 1 ± 6 bpm in controls, a difference that was not significant (p = 0.264), while resting heart rate did fall more (p = 0.014).

Limitations

Seven per group; the authors note that high variability and modest sample size may have hidden real biomarker changes, and the power calculation was based on thermoregulatory outcomes, not on the kidney markers.
The heat group was fitter at baseline (maximal ramp power 400 vs 339 W, p = 0.011; VO2max 63 vs 55 mL/kg/min, p = 0.051) and rode at a higher share of maximal heart rate during the sessions (79 vs 71%), so part of the difference may come from exercise strain rather than heat alone, a concern a reviewer raised in the published peer review.
The discussion speaks of reductions in resting and peak heart rate, but the peak heart-rate change did not differ between groups (interaction p = 0.264); no group comparison is reported for plasma volume.
Kidney markers were measured in blood only, at one time point straight after exercise, and NGAL and KIM-1 are not kidney-specific; no creatinine, filtration rate or urinary markers.
No performance, time-to-exhaustion or heat-tolerance test; outcomes are adaptation markers only. Men only.
Blinding not reported. No specific funding; the authors declare no competing interests.
How this entry was checked and changed
Why this level

a parallel trial of 7 per arm (B) taken one step down because every outcome is a physiological marker (heart rate, plasma volume, sweat loss, blood biomarkers) with no performance or heat-tolerance test