Exercise upregulates copeptin levels which is not regulated by interleukin-1

Abstract

Objective Studies have suggested that arginine vasopressin (AVP) and its surrogate marker copeptin increase during exercise, independently of serum sodium and/or osmolality. In extreme cases, this can lead to runners-induced hyponatremia. Interleukin-1 (IL-1) increases during exercise and induces AVP in animal models. We here therefore investigate whether copeptin (a surrogate marker for AVP) increases upon exercise in young and healthy males, and whether this increase is regulated by IL-1. Design In a randomized, placebo-controlled, double-blind, crossover trial in 17 healthy male volunteers, the effect of the IL-1 receptor antagonist anakinra on exercise-induced copeptin was compared with placebo. Methods Participants exercised for one hour at 75% of VO 2max and were not allowed to drink/eat 6 hours before and during the study. Participants received either 100 mg of anakinra or placebo 1h before exercise. Blood was drawn at certain time intervals. Results In both groups, copeptin levels were induced by 2.5-fold upon exercise (p<0.001), from 4.5–10.6 pmol/l in the placebo, and 4.3–11.3 pmol/l in the anakinra group, (p = 0.38). One hour after exercise, copeptin levels dropped to 7.7 and 7.9 pmol/l in the placebo and anakinra group, respectively (p = 0.58). The increase of copeptin levels was not explained by sodium concentrations. Conclusions Exercise induces a continuous rise of plasma copeptin levels in healthy male volunteers independently of sodium levels and fluid intake. This increase is not regulated by the IL-1 pathway.

Estrogen to Progesterone Ratio and Fluid Regulatory Responses to Varying Degrees and Methods of Dehydration

“…Since AVP acts primarily on the kidney to promote fluid retention through the kidney tubules (Jaenike and Waterhouse, 1961), with greater levels of body mass loss, less fluid is available for retention and increased fluid consumption is required to recover these losses. The level of %BM observed in this investigation following exercise heat stress would likely negatively impact cognition and athletic endurance performance based on recent meta-analyses (Goulet, 2013;Wittbrodt and The observed increase in copeptin concentration following exercise in the heat is consistent with previously reported results in men (Popovic et al, 2019), suggesting women have a similar fluid regulatory response to dehydrating exercise. The exercise copeptin response did not appear to be moderated by sex hormone concentration or E:P. While estrogen has been observed to be related to copeptin concentration at rest (Blum et al, 2014), it does not appear that the relationship is affected or apparent with integration of dehydrating stimuli.…”

“…Understanding the mechanisms that may contribute to the dehydration response is helpful when making recommendations for fluid needs (Perrier, 2017). Mechanistically, fluid regulatory responses, such as arginine vasopressin (AVP), a primary fluid regulatory hormone, and copeptin, a surrogate marker for AVP (Morgenthaler et al, 2006), are commonly increased by dehydration stimuli (Stacey et al, 2018a;Popovic et al, 2019;Giersch et al, 2020;Suh et al, 2021). Specifically, copeptin concentration is increased with fluid restriction (Giersch et al, 2020), hypertonic saline infusion (Suh et al, 2021), and exercise (Popovic et al, 2019).…”

“…Mechanistically, fluid regulatory responses, such as arginine vasopressin (AVP), a primary fluid regulatory hormone, and copeptin, a surrogate marker for AVP (Morgenthaler et al, 2006), are commonly increased by dehydration stimuli (Stacey et al, 2018a;Popovic et al, 2019;Giersch et al, 2020;Suh et al, 2021). Specifically, copeptin concentration is increased with fluid restriction (Giersch et al, 2020), hypertonic saline infusion (Suh et al, 2021), and exercise (Popovic et al, 2019). Changes in fluid regulatory hormones can alter body fluid balance, increasing fluid retention with increased AVP concentration.…”

Impact of Nutrient Intake on Hydration Biomarkers Following Exercise and Rehydration Using a Clustering-Based Approach

“…Model fits were generally weak (R 2 ≤ 0.37), suggesting that many factors (not dietary consumption alone) influence hydration biomarkers. Beyond water intake or hydration status, copeptin can also be influenced by heat exposure [25,48] and exercise [49], which limits its utility as a hydration biomarker. Similarly, heat exposure and exercise impacts P osm [50] and urinary indices [51,52], which highlights and supports lack of a gold-standard tool for hydration assessment [53].…”

Antidiuretic hormone and the activation of glucose production during high intensity aerobic exercise

“…Of note, although copeptin, a surrogate marker of ADH, is a stable molecule and easy to measure, ADH and copeptin have different decay kinetics, with ADH having a shorter half-life [ 17 ]. For this reason, copeptin level may not be an adequate marker of ADH levels when ADH levels change rapidly, such as during and after intense exercise [ 18 ].…”