Extreme mountain ultramarathon induced cumulative stress reflective of muscle damage and immune response activation, while salivary miR-21 and miR-210 did not demonstrate acute alterations, suggesting they may not serve as highly responsive markers for the combined hypoxia-strenuous exercise stressor.
Key Findings
Results
Circulating reactive oxygen species (ROS) production increased following completion of the Tor des Géants ultramarathon.
Seven healthy male participants who successfully completed the 2019 Tor des Géants race were included.
Biological specimens were collected 1–2 days prior to the race and immediately post-completion.
ROS production was assessed from capillary blood samples.
Total antioxidant capacity remained stable despite the increase in ROS production.
Results
Urinary creatinine concentration increased following the race, indicative of muscle damage.
Urine samples were collected pre- and post-race from seven male finishers.
Increased urinary creatinine was interpreted as reflective of muscle damage.
The authors characterized the overall response as 'cumulative stress reflective of muscle damage and immune response activation.'
Creatinine was assessed alongside neopterin from urine samples.
Results
Urinary neopterin concentration increased following the race, indicative of immune response activation.
Neopterin is a marker associated with immune system activation.
Both creatinine and neopterin increased subsequent to race completion in the seven participants.
The increase in neopterin was interpreted as evidence of immune response activation during the extreme ultramarathon.
Urine was one of three biological matrices (blood, saliva, urine) used in this multi-matrix study.
Results
Salivary miR-21 and miR-210 expression levels showed heterogeneity among participants and did not demonstrate acute alterations post-race.
Salivary hsa-miR-210 and hsa-miR-21 were measured pre- and post-race in seven male finishers.
Expression levels for both miR-21 and miR-210 'displayed heterogeneity among participants.'
Neither miRNA showed a consistent acute alteration in response to the combined hypoxia-strenuous exercise stressor.
The authors concluded these miRNAs 'may not serve as highly responsive markers for the combined hypoxia-strenuous exercise stressor.'
Results
Changes in salivary miR-210 were significantly correlated with changes in heart rate.
This correlation was identified among the seven male finishers of the 2019 Tor des Géants.
miR-210 is known to be associated with hypoxia-related pathways.
The significant correlation with heart rate was a notable finding despite the lack of a consistent group-level acute alteration in miR-210.
Heart rate was among the physiological parameters monitored during the race.
Discussion
The authors suggest that the absence of acute miRNA alterations may indicate the existence of adaptive mechanisms in finishers that facilitate their capacity to manage extreme challenges.
The study participants were all finishers of the Tor des Géants, an extreme mountain ultramarathon.
The authors propose that the lack of acute salivary miRNA response 'may suggest the existence of adaptive mechanisms in finishers that facilitate their capacity to manage extreme challenges.'
Prior investigations of Tor des Géants finishers have demonstrated oxi-inflammatory responses, providing context for interpreting the miRNA findings.
This interpretation implies that trained ultramarathon finishers may mount different molecular-level stress responses compared to less-trained individuals.
Methods
Blood glucose (glycemia) was assessed from capillary blood as part of the multi-matrix biomarker panel.
Glycemia was measured from capillary blood alongside ROS production and total antioxidant capacity.
Biological specimens included blood, saliva, and urine collected pre-race (1–2 days before) and immediately post-completion.
The study represents a multi-matrix approach using three different biological specimen types simultaneously.
The sample size was seven healthy adult male participants.
What This Means
This research examined how finishing one of the world's most extreme ultramarathon races — the Tor des Géants, a roughly 330 km mountain race in the Italian Alps — affects the body at a biological level. Seven male finishers of the 2019 race provided blood, saliva, and urine samples before and immediately after the event. The researchers measured markers of oxidative stress, muscle damage, immune activity, blood sugar, and small molecules in saliva called microRNAs that are thought to signal cellular stress related to oxygen deprivation and inflammation.
The study found that markers of oxidative stress (free radical production) in the blood went up after the race, and urine markers linked to muscle breakdown and immune system activation also increased — consistent with the enormous physical demands of the event. However, the body's overall antioxidant defenses appeared to hold steady. Interestingly, the two salivary microRNAs studied (miR-21 and miR-210) did not show consistent changes across participants, and the responses varied considerably from person to person. Changes in one of the microRNAs (miR-210) were significantly related to changes in heart rate during the race.
This research suggests that while extreme ultramarathon racing clearly stresses the body in measurable ways, salivary microRNAs may not be reliable rapid-response indicators of the combined strain of intense exercise and high-altitude hypoxia — at least in people capable of finishing such an extreme event. The authors propose that experienced ultramarathon finishers may have developed adaptive biological mechanisms that buffer these molecular stress signals, which could explain the muted and variable microRNA responses observed. The use of multiple biological samples (blood, urine, and saliva) provides a more complete picture of the body's response to extreme endurance challenges.
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Purcaro C, Di Filippo E, Vezzoli A, Bondi D, Giardini G, Fulle S, et al.. (2026). Effects of extreme mountain ultramarathon on stress-related biomarkers from multiple biological matrices in adult male runners.. Physiological reports. https://doi.org/10.14814/phy2.70966