LDH/CPK Ratio After Heat Illness is Associated with Short-Term Heat Intolerance

Background: Heat intolerance (HI) is the inability to adequately thermoregulate and withstand exercise-heat stress. Individuals who suffered exertional heat illness (EHI) are believed to be at a higher risk of developing a temporary HI. The mechanism behind it remains unclear. One theory suggests that end organ damage particularly to the central nervous system (CNS), alters heat tolerance. Creatinine phosphokinase (CPK) is a biomarker of muscle degradation and lactate dehydrogenase (LDH) is a non-specific biomarker of tissue damage; both are often elevated in EHI. Hypothesis: A higher LDH/CPK ratio indicates a more severe end-organ damage, especially to the CNS, and might be a predictive measure of short-term HI. Methods: Using the Israel Defense Force heat tolerance test (HTT) database, we identified individuals who were treated in the emergency room for EHI and their lab tests upon arrival included both LDH and CPK. Only patients who performed an HTT within 6 months of the EHI event were included. If an individual had performed multiple HTTs, within this period, the results of the last test were used. A logistic regression model assessed the association between LDH/CPK ratio and HI, accounting for possible confounders: BMI, age, smoking status and any acute illness within 10 days prior to the EHI event. Additionally, to test the hypothesis regarding CNS damage, we compared LDH/CPK ratio levels among individuals with and without neurological changes upon collapse (loss of consciousness, seizures, delirium, affective changes, aggressiveness and amnesia). Results: 73 individuals (age: 17-38 yrs.) met our inclusion criteria, of whom 19 were HI. HI individuals compared to heat tolerant (HT) individuals had higher median BMI (26.7 [IQR 24.6-29.9] vs. 24.1 [IQR 22.0-27.1], p=0.01), higher rate of smokers (21.1% vs. 11.1%, p=0.51), and were more likely to be acutely ill (31.6% and 22.2%, P=0.64). Age was similar between the two groups. Median LDH/CPK ratio was higher among HI compared to HT individuals (1.14 [IQR 0.74-2.3] vs. 0.74 [IQR 0.34-1.11], p=0.01). After accounting for the confounders, a 1-unit increase in LDH/CPK ratio was associated with higher odds of HI (odds ratio = 3.9 [95% CI 1.9-10.8]). Among the 36 individuals with neurological changes, median LDH/CPK ratio was higher compared to the individuals without neurological symptoms, regardless of HI status (1.01 [IQR 0.53-1.80] vs. 0.72 [IQR 0.36-0.89], p=0.03). Conclusion: A higher LDH/CPK ratio is associated with an increased risk of HI following EHI and might also reflect the severity of CNS damage during EHI. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.