Leppäluoto · Scandinavian journal of clinical and laboratory investigation 2008 · non-randomized comparative cohort study · n=20

Effects of long-term whole-body cold exposures on plasma concentrations of ACTH, beta-endorphin, cortisol, catecholamines and cytokines in healthy females.

Cited 180 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized comparative cohort study without a non-intervention control group.

PubMed 18382932 · doi:10.1080/00365510701516350 · record verified 2026-08-30

What was done

Twenty healthy females were allocated to either winter swimming in ice-cold water (0–2 °C for 20 s, n = 10) or whole-body cryotherapy (-110 °C for 2 min, n = 10) 3 times per week for 12 weeks. Venous blood samples were collected at weeks 1, 2, 4, 8, and 12 on a non-exposure day and on exposure days at 0, 5, and 35 minutes post-exposure to measure ACTH, cortisol, epinephrine, norepinephrine, IL-1-beta, IL-6, and TNF-alpha.

What was found

Plasma norepinephrine increased significantly by 2-fold to 3-fold after both types of cold exposure at every tested time point across the 12 weeks. Epinephrine concentrations showed no change. Plasma ACTH and cortisol concentrations at 35 minutes post-exposure were significantly lower in weeks 4–12 than in week 1. Cold exposure caused no changes in plasma IL-1-beta, IL-6, or TNF-alpha concentrations. Beta-endorphin data were not reported in the abstract.

Why it matters

This study shows that repeated acute whole-body cold exposures reliably stimulate sympathetic norepinephrine release without causing persistent HPA axis activation or systemic inflammatory cytokine surges, offering a potential mechanism for cold-induced pain relief.

Limits

The sample size was small (20 total, 10 per group) and limited to healthy females. The study was non-randomized, lacked a non-cold-exposed control group, and did not measure clinical pain outcomes directly.

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