ArticlePDF AvailableLiterature Review

Whole-Body Cryotherapy in Athletes: From Therapy to Stimulation. An Updated Review of the Literature

May 2017
Frontiers in Physiology 8

DOI:10.3389/fphys.2017.00258

Authors:

Giovanni Lombardi

Istituto Ortopedico Galeazzi

Ewa Ziemann

Poznan University of Physical Education

Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are the main purposes for application. However, the most recent studies confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting the underlying physiological responses. In addition to its therapeutic effects, whole-body cryotherapy has been demonstrated to be a preventive strategy against the deleterious effects of exercise-induced inflammation and soreness. Novel findings have stressed the importance of fat mass on cooling effectiveness and of the starting fitness level on the final result. Exposure to the cryotherapy somehow mimics exercise, since it affects myokines expression in an exercise-like fashion, thus opening another possible window on the therapeutic strategies for metabolic diseases such as obesity and type 2 diabetes. From a biochemical point of view, whole-body cryotherapy not always induces appreciable modifications, but the final clinical output (in terms of pain, soreness, stress, and post-exercise recovery) is very often improved compared to either the starting condition or the untreated matched group. Also, the number and the frequency of sessions that should be applied in order to obtain the best therapeutic results have been deeply investigated in the last years. In this article, we reviewed the most recent literature, from 2010 until present, in order to give the most updated insight into this therapeutic strategy, whose rapidly increasing use is not always based on scientific assumptions and safety standards.

| Effects of WBC on circulating levels of cytokines and inflammatory markers.

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REVIEW

published: 02 May 2017

doi: 10.3389/fphys.2017.00258

Frontiers in Physiology | www.frontiersin.org 1May 2017 | Volume 8 | Article 258

Edited by:

Duane C. Button,

Memorial University, Canada

Reviewed by:

Vincent Martin,

Blaise Pascal University, France

Sandro Remo Freitas,

Universidade de Lisboa, Portugal

*Correspondence:

Giovanni Lombardi

giovanni.lombardi

@grupposandonato.it

Specialty section:

This article was submitted to

Exercise Physiology,

a section of the journal

Frontiers in Physiology

Received: 01 February 2017

Accepted: 10 April 2017

Published: 02 May 2017

Citation:

Lombardi G, Ziemann E and Banﬁ G

(2017) Whole-Body Cryotherapy in

Athletes: From Therapy to Stimulation.

An Updated Review of the Literature.

Front. Physiol. 8:258.

doi: 10.3389/fphys.2017.00258

Whole-Body Cryotherapy in Athletes:

From Therapy to Stimulation. An

Updated Review of the Literature

Giovanni Lombardi 1*, Ewa Ziemann 2and Giuseppe Banﬁ 1, 3

1Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy,

2Department of Physiology and Pharmacology, Gdansk University of Physical Education and Sport, Gdansk, Poland,

3Vita-Salute San Raffaele University, Milan, Italy

Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports

medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are

the main purposes for application. However, the most recent studies conﬁrmed the

anti-inﬂammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting

the underlying physiological responses. In addition to its therapeutic effects, whole-body

cryotherapy has been demonstrated to be a preventive strategy against the deleterious

effects of exercise-induced inﬂammation and soreness. Novel ﬁndings have stressed

the importance of fat mass on cooling effectiveness and of the starting ﬁtness level

on the ﬁnal result. Exposure to the cryotherapy somehow mimics exercise, since it

affects myokines expression in an exercise-like fashion, thus opening another possible

window on the therapeutic strategies for metabolic diseases such as obesity and type 2

diabetes. From a biochemical point of view, whole-body cryotherapy not always induces

appreciable modiﬁcations, but the ﬁnal clinical output (in terms of pain, soreness, stress,

and post-exercise recovery) is very often improved compared to either the starting

condition or the untreated matched group. Also, the number and the frequency of

sessions that should be applied in order to obtain the best therapeutic results have been

deeply investigated in the last years. In this article, we reviewed the most recent literature,

from 2010 until present, in order to give the most updated insight into this therapeutic

strategy, whose rapidly increasing use is not always based on scientiﬁc assumptions and

safety standards.

Keywords: whole-body cryotherapy, cryochamber, recovery, inﬂammation, metabolic effects, irisin

INTRODUCTION

Local and systemic cold therapies (cryotherapies) are widely used to relieve symptoms of

various diseases including inﬂammation, pain, muscle spasms, and swelling, especially chronic

inﬂammatory ones, injuries, and overuse symptoms (Bettoni et al., 2013; Jastrzabek et al., 2013).

The beneﬁcial eﬀects of cold as a therapeutic agent have been known for a long time, with ancient

population aware about the reinvigorating eﬀects of cold water either taken orally or used for baths.

The use of cold, mainly locally, still remains in our daily common activities. A still up-to-date survey

of a sample of Irish emergency physicians highlighted the fact that 73% of consultants frequently

“prescribe” cold, 7% never suggest to use cryotherapy, and 30% is unsure about the beneﬁts of

using cold. Experience (47%) and common sense (27%) were the most frequently declared reasons

for using ice, while only 17% referred to scientiﬁc reasoning (Collins, 2008).

Lombardi et al. Updates for Whole-Body Cryotherapy

Forty years ago, following personal observations of Prof.

Toshiro Yamauchi (who recognized that the combination of

cold and physical exercise was beneﬁcial for clinical outcomes

of treatments received by his patients’, aﬀected by rheumatoid

arthritis, coming back from mountain localities after winter

holidays), whole-body cryotherapy was introduced into clinical

practice (Yamauchi et al., 1981a,b).

At present, the use of very cold air in special, controlled

chambers may be proposed for treating symptoms of various

diseases (Bouzigon et al., 2016). Beside its clinical applications,

a brief full body exposure to dry air at cryogenic temperatures

lower than −110◦C has become widely popular in sports

medicine, often used to enhance recovery after injuries and to

counteract inﬂammatory symptoms resulting from overuse or

pathology (Furmanek et al., 2014). The number of studies about

the use of whole-body cryotherapy (WBC) in sports medicine

is growing, however, it is still lower than the topic’s potential if

the wide range of application of this methodology is considered.

Studies published on athletes had mainly focused on post-

training or competitive season recovery. Only a limited number

of papers had investigated the eﬀects of WBC used in preparation

phase for competitive season to enhance form and performance,

or during periods of high intensity of training to limit overuse

and overreaching. Studies should be acknowledged to deﬁne

safety, eﬀectiveness, and eﬃcacy of the treatment in athletes and

to discover underlying molecular mechanisms supporting the

claimed beneﬁcial eﬀects.

This review article collects the most recent literature (since

2010, Banﬁ et al., 2010b) on whole-body cryotherapy with the

purpose of delivering a complete and updated overview of the

newest ﬁndings and the directions taken in research in this ﬁeld.

In particular, given the high number of new scientiﬁc ﬁndings

mostly associated with great technological developments of this

therapeutic method, this review discusses both technical aspects

(i.e., therapeutic protocols, contraindications, thermoregulatory

responses) and eﬀects on a wide range of physiological (i.e.,

hematological, metabolic, energetic, endocrinological, skeletal,

muscular, inﬂammatory) and functional parameters (post-

exercise and post-traumatic recovery, pain, performance). We

are aware of the limitations of this literature review. Almost

all published research included in this review discuss results of

using whole-body cryotherapy without providing any insight

into molecular mechanisms involved in observed responses to

the treatment. Also, although the review takes a non-systematic

approach, an alternative meta-analysis would only oﬀer a limited

article coverage due to the type and, sometimes, the quality

of available papers. Furthermore, we only reviewed reports on

the WBC procedures performed in cryochambers (regardless of

the cooling system, but considering the operating temperature);

we do not consider treatments performed in cryosauna (also

named cryocabins). Exposure to cold in a cryosauna cannot

be deemed whole-body since during the treatment the head

remains outside of the cabin. The two settings were concluded

to, activate diﬀerent molecular pathways and, possibly, exert

diﬀerent outcomes. Indeed, in a cryosauna, cooling is delivered

through direct insuﬄation of liquid nitrogen vapors into the box.

Free vapors are heavy and tend to remain within the cabin, below

the chin; contrarily, in a nitrogen-cooled cryochamber liquid

nitrogen ﬂuxes through pipes inside the chamber’s wall, and thus,

there is no free nitrogen within the chamber. These diﬀerences

also account for diﬀerent safety standards of these treatments:

free nitrogen vapor in a cryosauna could be potentially hazardous

due to the risk of asphyxia.

In the present paper we refer to “whole-body cryotherapy,”

which is the most commonly used term to deﬁne the

methodology, but also to “whole-body cryostimulation,” which

better describes eﬀects of WBC in improving the metabolic

and inﬂammatory responses as well as in enhancing recovery

from exercise and injuries. In contrast, the term “cryotherapy”

refers to a real therapy aimed at treating painful symptoms of

inﬂammatory or traumatic conditions.

TECHNICAL ASPECTS

Standardized Protocol for WBC

WBC is performed in special chambers, with the temperature and

humidity strictly controlled. A subject, minimally dressed (for

e.g., bathing suit, socks, clogs, headband, and surgical mask to

avoid direct exhalation of humid air), enters a vestibule chamber

at −60◦C, where he stays for about 30 s of body adaptation and

then passes to a cryochamber at −110◦to −140◦C, depending on

the cooling system (electrical or nitrogen), where he remains for

no more than 3 min. It is mandatory to remove any sweat before

entry to avoid the risk of skin burning and necrosis. Access to the

chamber is allowed only in the presence of a skilled personnel,

controlling the procedures. A patients is free to leave the chamber

at any time.

Contraindications

Being a medical therapy, WBC should follow strict guidelines

and indications. Currently accepted contraindications for WBC

include: cryoglobulinaemia, cold intolerance, Raynaud disease,

hypothyroidism, acute respiratory system disorders, cardio-

vascular system diseases (unstable angina pectoris, cardiac failure

in III and IV stage according to NYHA), purulent-gangrenous

cutaneous lesions, sympathetic nervous system neuropathies,

local blood ﬂow disorders, cachexia, and hypothermia, as well

as claustrophobia and mental disorders hindering cooperation

with patients during the treatment. When performed in the

appropriate and controlled conditions, WBC is a safe procedure,

which was demonstrated to be deleterious neither for lung

(Smolander et al., 2006) nor heart function (Banﬁ et al.,

2009a); however, recorded observation of a very slight, clinically

irrelevant increase in the systolic blood pressure (Lubkowska and

Szygula, 2010) justiﬁes precautions indicated for patients aﬀected

by cardiovascular conditions.

Temperature Changes

Studying body temperature modiﬁcations following WBC,

in comparison to changes observed in response to other

cooling techniques, represents a hot topic. This is thought

to be important since cooling eﬀectiveness is the function of

temperature decrease within a certain range.

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Lombardi et al. Updates for Whole-Body Cryotherapy

Shifts in skin temperature (Tsk) of chosen body regions

monitored by thermography and contact thermometry, before

and immediately after a single WBC session (30 s at −60◦C,

3 min at −120◦C) showed, for the ﬁrst time, the inﬂuence

of body mass index (BMI) on the range of alternations. The

highest magnitude of temperature changes was observed within

lower extremities (tibias: −8.7◦C; feet: −5.2◦C), the mean

total body temperature decreased by 5.8◦C, while the internal

body temperature dropped only by 0.8◦C. The mean changes

of temperatures at diﬀerent sites correlated with BMI (r=

−0.46); for example, explicative images show that temperature

decreased down to 8.1◦and 7.9◦C in a thin volunteer (BMI <

25 kg/m2) and down to 4.8◦and 5.5◦C in an obese participant

(BMI >30 kg/m2), in the chest and back regions, respectively

(Cholewka et al., 2012). Even more precisely than BMI, the

fat-free mass index (FFMI: fat-free mass/height2) and body fat

percentage in males were both found to correlate with changes

in skin temperature following WBC, (Hammond et al., 2014).

Body composition was, thus, observed to be one of the main

determinants of potential temperature changes and, possibly, of

therapy’s eﬀectiveness. Cooling eﬃcacy, indeed, diﬀers between

males and females as demonstrated by Hammond et al.; however,

despite females having higher levels of adiposity than males,

they experience greater mean temperature changes compared

to males (12.07 ±1.55◦C vs. 10.12 ±1.86◦C). Compared to

males, females have 20% smaller body mass, 14% more fat,

33% smaller lean body mass, and 18% smaller surface area, a

higher subcutaneous to visceral fat ratio and a smaller ratio

of fat mass index (FMI) to FFMI. Furthermore, females’ BSA-

to-mass ratio is higher than males, and the heat loss increases

proportionally to this ratio. Under cold stress, females have a

more extensively vasoconstricted periphery, with greater surface

heat losses and show a signiﬁcantly reduced sensitivity of the

shivering response. Taken together these evidences could explain

the discrepancy in cooling eﬃciency between sexes (Hammond

et al., 2014).

Costello analyzed reduction in skin, muscle (vastus lateralis,

at 1, 2, and 3 cm) and rectal temperatures following a single

exposure to either WBC (−110◦C) or cold-water immersion

(CWI, at 8◦C). Immediately after these procedures, the

maximum drop in Tsk was observed with WBC (−12.1 ±1.0◦C),

marking a bigger drop compared to CWI (−8.8 ±2.0◦C). On the

contrary, core (−0.3◦to −0.4◦C) and muscle (−1.2◦to −2.0◦C)

temperatures shifted slightly with no diﬀerences between the

two treatments and the maximum decrease occurring after

60 min (Costello et al., 2012b). Similar results were obtained

on changes in Tsk at the patellar region; a greater drop was

observed with WBC immediately after the procedure, while 10–

60 min after the treatment a lower temperature was reached

with CWI (Costello et al., 2014). Interestingly, the authors had

set the question whether or not either WBC or CWI were

capable of achieving the Tsk (<13◦C) believed to be required

for analgesic purposes (Bleakley and Hopkins, 2010), yet they

concluded that this temperature was reached by neither of the

two procedures (Costello et al., 2014). Zalewski et al. conﬁrmed

that the maximum drop in core temperature occurred 50–60 min

post-WBC (Zalewski et al., 2014).

In a systematic review, comparing 10 controlled trials,

considering either a 10 min-long ice pack application, 5 min

CWI, or 2.5–3 min WBC (−110◦to −195◦C), the authors

illustrated that the largest reduction in Tsk was obtained by the

ice pack application due to the higher heat transfer constant

(k=2.18) compared to water (k=0.58) and air (k=0.024). The

obtained results conﬁrmed negligible intramuscular temperature

variation regardless of the cooling modality as well as importance

of adiposity in determining cooling eﬃciency (k=0.23 vs. k=

0.46 of muscles; Bleakley et al., 2014).

In summary, the following reports have been made about the

WBC treatment:

- WBC is a medical practice that must be performed in

specialized facilities under supervision of a well-trained

personnel.

- WBC has contraindications that must be considered before

prescription.

- Cooling eﬃciency and, possibly, treatment eﬀectiveness can be

inﬂuenced by body composition.

- Due to diﬀerences in body composition, cooling eﬃciency is

potentially greater in females than in males.

- WBC eﬀectiveness in lowering Tsk exceeds that of CWI; muscle

and core temperatures seem to decrease in a similar way in

response to both treatments.

- The maximum decrease in core temperature has been noted

50–60 min post-WBC.

HEMATOLOGY

The study of hematological response to WBC allows to deﬁne

a wide range of eﬀects covering modiﬁcation of oxygen supply

potential, inﬂammatory response, and coagulation function.

Erythrocytes and Hemoglobin

We studied hematological parameters, including iron

metabolism ones, in 27 athletes belonging to National Italian

Rugby Team, during a summer camp (Lombardi et al., 2013a).

Two daily sessions of WBC (3 min, −140◦C) were performed

for seven consecutive days, one in the morning before the ﬁrst

training session, the second in the evening after the second

training session. Athletes were strictly controlled for diet,

especially the correct iron uptake. A typical plasma volume

shift due to a prolonged training session of aerobic exercises

was taken into account when interpreting the results. Among

hematological parameters, erythrocytes (RBC), hematocrit

(Ht), and hemoglobin (Hb) decreased noticeably; particularly,

Hb decreased from 15.06 ±0.84 to 14.70 ±0.62 g/dL.

Red cell distribution width (RDW) increased, indicating

a rise of anisocytosis of RBC, although reticulocytes were

stable, but the immature fraction of reticulocytes (IRF) was

signiﬁcantly decreased (Lombardi et al., 2013a). A decrease

of hemoglobinization could be a speciﬁc feature of the WBC

treatment. Indeed, a similar decrease of Hb (about 0.3 g/dL) and

IRF had been previously reported in rugby players, however, in

that case, RBC and Ht had not been aﬀected (Banﬁ et al., 2008).

This diﬀerence could be attributable to a milder WBC protocol,

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Lombardi et al. Updates for Whole-Body Cryotherapy

with only ﬁve WBC (one per day, at −110◦C). The decrease

in the levels of Hb as well as RBC and Ht, is transitory and it

recovered during continuative treatments as demonstrated by

Szygula and colleagues in a study performed on students of

the Polish National Military Academy, who can be considered

physically active subjects, continuously performing exercises and

controlled for variables as diet and lifestyle (Szygula et al., 2014).

Recruited cadets were divided into two groups of 15 subjects;

one group was treated with WBC, the other did not receive the

treatment. Hematological parameters were measured after 10, 20,

and 30 sessions, which were performed daily in a cryochamber

at −130◦C, for 3 min. After 10 sessions, Hb decreased from a

mean of 15.1 ±0.74–14.4 ±0.94 g/dL and remained at this

concentration after 20 sessions (14.5 ±0.71 g/dL). It then rose to

15.1 ±1.1 g/dL after 30 sessions. Similar changes were observed

for Ht and RBC. The decrease of Hb, RBC and Ht lasted through

20 sessions of the WBC treatment; then the bone marrow reacted

by releasing new RBCs (Szygula et al., 2014). A decrease in

Hb and RBC was already described in elite Polish ﬁeld hockey

players after 18 sessions of WBC (Straburzy´

nska-Lupa et al.,

2007). Hb also showed a decreasing though not statistically

signiﬁcant trend, dropping from 15.0 ±1.0 to 14.4 ±0.8 g/dL,

in nine collegiate physically active subjects, who had completed

30 min step up/down exercise, aimed at inducing delayed-onset

muscle soreness (DOMS), and had been treated with two daily

WBC sessions for 5 consecutive days. In opposite, the control

group, which had undergone the same DOMS-inducing training

without the WBC or any other recovery treatment, experienced

stable levels of Hb (Ziemann et al., 2014). Nevertheless, some

data revealed that Hb and RBC were stable in 12 professional

tennis players, following 10 sessions of WBC applied twice a day,

at –120◦C for 3 min, over 5 days, during a controlled training

camp (Ziemann et al., 2012) as well as in 16 kayakers treated

twice a day for the ﬁrst 10 days of a 19 day physical training

cycle (Sutkowy et al., 2014). It is thus, possible that shifts in

Hb and RBC induced by WBC are dependent on the discipline

and baseline hematological proﬁle. This issue, however, still

has not been investigated. Mean curpuscular volume (MCV)

grew following the WBC treatment applied in rugby players

and in ﬁeld hockey players (Straburzy´

nska-Lupa et al., 2007;

Lombardi et al., 2013a); in the latter group values of MCV,

mean curpuscular hemoglobin (MCH), and of mean curpuscular

hemoglobin concentration (MCHC) remained elevated up to a

week after the end of the treatment (Straburzy´

nska-Lupa et al.,

2007).

A slight dehemoglobinazion has two direct consequences.

Firstly, since the OFF-score, a parameter used to calculate

the probability of blood doping in athletes, depends on Hb

concentration and Ret count (Sottas et al., 2010; Robinson et al.,

2011; which remained stable), WBC may reduce the result of this

score and, thus, cannot be considered a performance enhancing

practice. On the other hand, the use of WBC to mask illicit

practices is unjustiﬁed because the potential decrease in Hb is

too small and the change itself is short-lasting and/or temporary

(Lombardi et al., 2013a). Secondly, the decrease in Hb and RBC

should be considered when the timeline of recovery strategies,

within a competitive season, is drawn.

Iron Metabolism

Martial status was not modiﬁed after the treatment in 27 rugby

players submitted to two daily WBC sessions for 7 consecutive

days (Lombardi et al., 2013a). Only soluble transferring receptor

(sTfR) increased signiﬁcantly, but not pathologically, possibly

demonstrating initial high functional iron demand (Lombardi

et al., 2013b). Similar results were obtained in a more recent

paper by Dulian and colleagues. Regardless of the ﬁtness level,

in a cohort of obese subjects (BMI >30 kg/m2), serum iron

and ferritin remained unchanged after the 1st and 10th WBC

session. Only hepcidin, a hepatocyte-derive peptide hormone

mediating iron depletion in inﬂammation (Lombardi et al.,

2013b), decreased moderately (Dulian et al., 2015).

Hemolysis

WBC enhances hemolysis, which could explain the Hb decrease

during initial phase of the treatment. A decrease of haptoglobin,

scavenger protein for free Hb released from broken RBC was

described in the above-mentioned paper by Szygula and co-

workers, after 10 and 20 WBC sessions, but a recovery appeared

after 30 sessions, following the changes in Hb and RBC.

Contemporarily, bilirubin increased, reﬂecting Hb catabolism.

Hemolysis stimulated release of erythropoietin (EPO), which

increased by 4.5% compared to baseline after 10 sessions, and

further by 10.8 and 10.1% after 20 and 30 sessions, respectively,

possibly supporting the recovery of RBC number after the initial

decrease. Even in the case of EPO, the shifts in concentrations

remained within physiological ranges (Szygula et al., 2014).

Leukocytes

Levels of leukocytes did not show any changes after 14 sessions of

WBC (twice a day, over 7 days) in the group of 27 rugby players,

belonging to National Italian Rugby Team, studied during a

summer camp (Lombardi et al., 2013a). The same was found for

the group of 16 kayakers treated twice a day for the ﬁrst 10 days

of a 19 day physical training cycle (Sutkowy et al., 2014).

At the same time, leukocytes increased in the students of

the Polish Military Academy after 10 and 20 sessions, but

returned to baseline values after 30 sessions. The increase trend

covered both granulocytes and lymphocytes (Szygula et al., 2014).

Similar increase was also reported in tennis players, but not for

subcategories of granulocytes and lymphocytes (Ziemann et al.,

2012). Despite the increase, leukocytes always remained within

the physiological range. Mobilization of leukocytes from the bone

marrow and organs of residence has been hypothesized as a

possible cause of these increases although an explanation of this

phenomenon is still lacking.

In endurance trained runners, a simulated 45 min trail run,

designed speciﬁcally to trigger exercise-induced muscle damage

(EIMD), followed by four sessions of WBC applied once a day,

resulted in an increase in neutrophil count of 114% compared

to baseline, with the maximum peak recorded 1 h after the

exercise. The correspondent increase in neutrophils, following

passive recovery, accounted for 101% shift against baseline. The

authors hypothesized that the increase of circulating neutrophils

stimulated angiogenesis (via vascular endothelial growth factor—

VEGF expression) and the consequent improved perfusion was

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Lombardi et al. Updates for Whole-Body Cryotherapy

associated with a reduced delayed onset of muscle soreness

(DOMS) and, hence, an improved recovery (Pournot et al., 2011).

Platelets

Platelets did not shift in response to WBC sessions applied in

groups of rugby and tennis players (Lombardi et al., 2013a;

Ziemann et al., 2014) nor students of the Polish Military Academy

(Szygula et al., 2014).

In summary, the following reports have been made about the

WBC treatment:

- WBC causes a decrease in Hb, Ht, and RBC after 5, 10, and 20

sessions. A recovery of hemoglobinization is reached after 30

sessions. Ret counts remains unaﬀected by WBC.

- The eﬀect of WBC on RBC and Hb can be inﬂuenced by the

type and intensity of physical training since in some groups of

athletes these changes did not occur.

- Hemolysis may be the cause behind the drop in RBC, Hb, and

Ht following the WBC treatment of 10–20 sessions.

- EPO is induced in the course of WBC with the aim to recover

to baseline levels of RBC and Hb.

- WBC should not have a boosting eﬀect on bone marrow and

is not inﬂuencing athletes’ hematological parameters usually

controlled to test for illicit bone marrow stimulation.

- The level of leukocytes either does not change or only slightly

increases in response to WBC. Cryotherapy possibly mobilizes

leukocytes, especially neutrophils, with a positive eﬀect on

DOMS.

- Platelets are not aﬀected by WBC.

LIPIDS CONCENTRATIONS AND ENERGY

METABOLISM

Lipids are the main source of energy as well as the main

thermogenic substrate. It is thus, possible that an intense cold

stimulus of WBC aﬀects lipid metabolism.

Sixty-nine physically active male subjects (10 professional

rugby players and 39 healthy individuals including policemen

and soldiers) were divided into three groups based on the

number of WBC sessions (−130◦C, 3 min): (i) 5, (ii) 10,

and (iii) 20. Five sessions of WBC did not modify the lipid

proﬁle. Ten sessions induced a 34% decrease in triglycerides

and much more after 20 sessions (from 108 ±50 mg/dL,

before the start of the treatment, to 69.4 ±27.2 mg/dL, after

20 sessions). After 20 sessions, high density lipoprotein (HDL)

cholesterol signiﬁcantly increased (from 53.2 ±16.5 to 63.1 ±

27.4 mg/dL), whilst low density lipoprotein (LDL) cholesterol

decreased noticeably (from 97.7 ±48.3 to 72.8 ±52.0 mg/dL;

Lubkowska et al., 2010a). Concentrations of total cholesterol and

LDL also decreased in physically active males, who underwent a

30 min step up/down exercise supplemented with WBC applied

twice a day over 5 consecutive days; compared to the control

group, total cholesterol and LDL dropped by 43 and 52%,

respectively (Ziemann et al., 2014).

Adipose tissues, both white (WAT) and brown (BAT), become

activated during cold exposure. BAT is particularly consumed

during exposure to cold, contributing to energy metabolism.

However, 6 months of moderate aerobic activity combined

with WBC did not change body mass, fat, or lean body

mass percentages. Circulating adiponectin, leptin, and resistin

concentrations were also not modiﬁed while, again, LDL and

triglycerides decreased and HDL increased. The experiment was

performed on 45 overweight and obese men, asked to complete a

test on a bicycle ergometer, beginning with a workload of 1 W/Kg

of fat-free mass, then increased by 0.5 W/Kg half until exhaustion.

Participants exercised three times a week under researchers’

supervision; once a week they completed a 45 min-long walking

session and, twice a week, attended a 45 min gym session. After 1

month from the start of the ﬁtness program and 1 month before

its end, 20 daily WBC treatments at −130◦C for 3 min were done

(Lubkowska et al., 2015).

Ten WBC sessions (−120◦C, 3 min), applied twice day over

5 days, in 12 professional tennis players, during a controlled

training camp, aﬀected neither the resting metabolic rate nor the

percentage of fat used as a metabolic substrate; this was also the

case with healthy, physically active men treated with two daily

WBC sessions, for 5 consecutive days between step up/down 30

min-long exercises (Ziemann et al., 2012, 2014).

Recently, a diﬀerential eﬀectiveness of WBC has been implied

to depend on the starting ﬁtness status of the subject. Middle-

aged obese men (BMI >30 kg/m2) were grouped based on their

ﬁtness level (low and high cardiorespiratory ﬁtness level) and

exposed to 10 consecutive sessions of WBC over 2 weeks. Irisin,

a myokine induced by exercise stimulating WAT browning,

linked to enhanced thermogenic capacity (Boström et al., 2012;

Lombardi et al., 2016), increased slightly in both groups over the

course of 24 h after the ﬁrst session of WBC. More interestingly,

irisin plasma concentrations increased by 20% in subjects with

a low ﬁtness level, but decreased slightly in subjects with a high

ﬁtness level (Dulian et al., 2015). The observed increase in irisin

corresponds with data of Lee and co-workers, who investigated

changes of myokine—irisin and adipokine—ﬁbroblast growth

factor 21 (FGF21) in response to cold water immersion. In

contrast to trends in irisin, they observed a greater reduction in

FGF21, interpreted as a pronounced eﬀect of the non-shivering

thermogenesis (Lee et al., 2014). There are no data about changes

in FGF21 in response to WBC.

In summary, the following reports have been made about the

WBC treatment:

- WBC has a dose-dependent improving eﬀect on the lipid

proﬁle.

- WBC does not aﬀect the rest metabolic rate and energy

expenditure during exercise.

- WBC has a stimulatory eﬀect on irisin expression, which

should act at the adipose tissue level by enhancing

thermogenesis.

BONE METABOLISM AND SKELETAL

HEALTH

Bone health is essential not only in whole-body health, but also

in determining and sustaining athletes’ performance (Lombardi

et al., 2016; Sansoni et al., 2017). Due to high energy expenses

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associated with high-level physical activity (Lombardi et al.,

2012), the risk of osteopenia and stress fractures (the inability

of the skeleton to modify its own microarchitecture depending

on applied loads) is always present. Based on these ﬁndings, the

availability of medical tools favoring recovery of the bone tissue

is highly desirable (Banﬁ et al., 2010a; Lombardi et al., 2011).

Ten professional rugby players, belonging to Italian National

Team, submitted to single daily sessions of WBC for 5

consecutive days (−110◦C, 2 min), were compared to 10 players,

who completed the same training protocol without WBC

(Galliera et al., 2012). Bone metabolism was studied through

biochemical parameters. The soluble ligand of the receptor

activator of nuclear factor κB (RANKL) and its decoy receptor

osteoprotegerin (OPG) constitute a fundamental cytokine system

connecting the immune system and bone metabolism in

order to link pro- and anti-inﬂammatory balance to calcium

stores. RANKL is released from osteoblasts and lymphocytes

and activates osteoclasts, inducing bone resorption. Osteoclasts

express RANK, speciﬁc receptor of RANKL, which induces an

intracellular signal to reabsorb bone. The eﬀect of RANKL on

RANK is blocked by OPG (Banﬁ et al., 2010a). WBC did not

aﬀect plasma RANK and RANKL concentrations in athletes, but

increased OPG, thus, causing the OPG/RANKL ratio, an index of

resorption-to-formation balance, to grow as well. The increased

osteogenic potential may have a role in the post-fracture recovery,

but also in prevention of more insidious stress fractures (Galliera

et al., 2012).

In summary, the following reports have been made about the

WBC treatment:

- WBC could counteract the inﬂammation-induced bone

resorption.

INFLAMMATORY MARKERS

The anti-inﬂammatory and analgesic eﬀects of cryotherapy are

the most searched for by athletes and patients. The eﬀectiveness

of the treatment in this speciﬁc ambit has been demonstrated by

a number of studies although the available data is contrasting and

still debated. Indeed, along with studies reporting direct eﬀect

of WBC on inﬂammatory markers, there are several reports that

did not link any changes with the treatment at all. Nevertheless,

almost all of these studies agree on general beneﬁts induced by

the treatment including improved pain, mood, and quality of

life (QoL). A prototypic example was found in patients aﬀected

by ﬁbromyalgia, an auto-inﬂammatory disease of unknown

pathogenesis and highly variable clinical presentation, always

characterized by chronic systemic inﬂammation, generalized

pain, and severe fatigue, which invariably and considerably

deteriorates the QoL; regardless of the conventional analgesic

therapy, compared to subjects not treated with WBC (n=

50), patients receiving the WBC treatment (n=50) exhibited

large clinical improvements in all the investigated parameters

depicting the QoL and the ability to perform daily activities

[pain by visual analog scale (VAS), global health status (GH),

fatigue severity scale (FSS), and short form (SH)-36; Bettoni et al.,

2013].

Tumor necrosis factor (TNFα), interleukin 6 (IL-6), and

IL-10 did not change in 11 runners, who underwent a 48-

min pro-EIMD training protocol and were treated four times

with either WBC at −110◦C or passive recovery. On the

contrary, the increase in the pro-inﬂammatory marker IL-

1β24 h post treatment and C-reactive protein (CRP) 96 h

post-WBC, were strongly attenuated compared to passive

recovery. In parallel, WBC had a greater inducing eﬀect on the

anti-inﬂammatory IL-1 receptor antagonist (IL-1ra) 1 h post-

treatment. The authors concluded that a unique session of

WBC (3 min at −110◦C), performed immediately after exercise,

enhanced muscular recovery by restricting the inﬂammatory

process (Pournot et al., 2011). Five days of WBC applied

twice a day (−120◦C, 3 min), combined with moderate-intensity

training, in six professional tennis players, during a controlled

training camp, decreased TNFαserum concentrations by 60%

as opposed to 35% decrease observed in the untreated group.

IL-6, instead, increased slightly, but signiﬁcantly due to WBC

(Ziemann et al., 2012). The pro-inﬂammatory role of IL-

6 has been recently revised (Peake et al., 2015). Indeed, it

has a dual eﬀect depending on the production site and its

basal concentration. Chronically high, even if moderately, IL-

6, characterizing chronic inﬂammatory conditions (e.g., obesity,

sedentariness) stimulating the hepatic synthesis of this cytokine,

cause pro-inﬂammatory, and potentially deleterious eﬀect. On

the contrary, even very high, pulsatile spikes of IL-6, originating

from low basal concentrations, derived from contracting muscles,

act as a powerful anti-inﬂammatory mediator (Lombardi et al.,

2016). In 18 professional male volleyball players, a session of

submaximal exercise increased IL-1βand IL-6 by 60%. The

WBC treatment (−130◦C, 3 min), however, performed before the

exercise, prevented these increases. This study, thus, highlighted

a possible preventive eﬀect of WBC on exercise-induced

inﬂammation (Mila-Kierzenkowska et al., 2013). However, in

rugby players, a single session of WBC (−130◦C) did not

aﬀect IL-6 values, regardless of the treatment‘s duration (1,

2, or 3 min; Selfe et al., 2014). The protective eﬀect of WBC

was also demonstrated in 18 physically active college-aged

men, who underwent eccentric workout inducing DOMS. A

single session of WBC (−110◦C, 3 min) performed after the

exercise had the same eﬀect of a passive recovery (increased

IL-6, IL-1β, and IL-10). After 5 days, the repeated performed

exercise induced the similar biochemical modiﬁcations in

the untreated group, while in the WBC-treated group (5

days, twice daily) IL-6 and IL-1βwere unchanged compared

to baseline with IL-10 strongly elevated (Ziemann et al.,

2014).

In healthy young men, the extent of IL-6 increase, 30 min and

24 h after a single session of WBC, was much greater than the

corresponding increases observed after 10 days of the treatment

(Lubkowska et al., 2010b). Interestingly, the same authors also

demonstrated that in 45 healthy men, a diﬀerent number

of sessions had a diﬀerent eﬀect on particular inﬂammatory

parameters. Five sessions of WBC increased IL-10 by 30%,

but this change was dissipated 2 weeks after the end of the

treatment. After 10 sessions IL-1αdecreased by 17%, while IL-

6 and IL-10 increased by 10% and 14% respectively, yet even

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in this case, these modiﬁcations were lost after 2 weeks. After

20 sessions of WBC the cytokine balance was conﬁrmed just

like after 10 sessions, but in this case, the decrease in IL-1α

was sustained 2 weeks after the end of the treatment. IL-1β,

TNFα, and IL-12 remained unchanged over the observation

period. Consequently, the authors suggested to use 20 sessions

in order to induce adaptation (Lubkowska et al., 2011). In

professional rugby players, a slight, yet not signiﬁcant decrease

in ferritin and transferrin concentrations was observed that,

together with an increase in the sTfR concentration, further

supported the anti-inﬂammatory eﬀect of WBC. Indeed, these

parameters generally have a contrary behavior, when a chronic

inﬂammatory process is ongoing (Lombardi et al., 2013b).

Interestingly, as for hematological parameters and martial status,

a shift in the cytokine proﬁle depends upon ﬁtness capacity. Pro-

inﬂammatory cytokines (IL-6, TNFα) and adipokines (resistin,

visfatin) were higher in obese LCF subjects compared to the

obese HCF ones. IL-10 increased equally in both groups,

with adiponectin and leptin unaﬀected (Ziemann et al., 2013).

Even the drop in CRP, observed regardless of the number

of sessions (either 1 or 10), was much greater in obese LFL

than in obese HFL (Dulian et al., 2015). The anti-inﬂammatory

eﬀect of WBC is in line with previous reports (Banﬁ et al.,

2009b).

Table 1 presents the ﬁndings about the eﬀects of WBC on

circulating levels of cytokines and inﬂammatory markers.

It is worth noting that cooling therapies are often applied

interchangeably in athletes’ recovery treatment. Reducing

inﬂammation may have another interesting aspect when

achieved in athletes. The latest paper published by Roberts

and co-workers revealed that a cooling therapy (cold water

immersion-CWI: 10 min using a circulatory cooling unit,

temperature at 10.1 ±0.3◦C) used after resistance training

as a recovery strategy attenuates both acute changes in

satellite cell numbers and kinase activity that regulates muscle

hypertrophy, which may translate into smaller, but longer-

term training gains in muscle strength and hypertrophy.

Consequently, reduced inﬂammation in response to WBC may

have a negative eﬀect on muscle hypertrophy (Roberts et al.,

2015).

In summary, the following reports have been made about the

WBC treatment:

- WBC induces anti-inﬂammatory eﬀects.

- Findings about the eﬀect of WBC on IL-6 are not always

concordant, probably due to diﬀerences in exercise protocols

applied. In general terms, a single session of WBC increases IL-

6 concentration, while multiple sessions recover it to baseline.

In this sense, WBC seems to mimic exercise-induced impacts.

- More consistently, WBC stimulates the anti-inﬂammatory

response (reduced IL-1βand increased IL-10, IL-1Ra).

- Fitness capacity aﬀects the inﬂammatory response to WBC in

non-athletes.

- Further, investigations should focus on establishing, whether

reduced inﬂammation has a beneﬁcial eﬀect on athletes’

performance if they combine training and cold therapy.

ENDOCRINE FUNCTION AND HORMONE

PROFILE

Monitoring hormones is essential to assess health status

especially in athletes, who experience chronic intense workloads

associated with psychophysically stressful situations. WBC is

used to relieve stress conditions owing to the activation

of neuroendocrine and metabolic axes regulating thermal

homeostasis. However, only a few of reports published so far had

considered this aspect.

Salivary steroid hormones were monitored in 25 professional

top level rugby players, during a summer training camp.

The athletes were submitted to the WBC treatment (−140◦C,

3 min) twice a day for 7 consecutive days, the ﬁrst before

the morning training session, the second after the evening

workout. Saliva was collected before the start of the camp,

after the evening WBC session on the ﬁrst day, and after

the last WBC session on the last day. Compared to baseline,

at the end of the ﬁrst day (2 WBC sessions completed)

cortisol and dehydroepiandrosterone (DHEA) decreased. After 7

days, cortisol, DHEA, and estradiol decreased, yet testosterone

increased. Importantly, in the majority of subjects variations

exceeded the critical diﬀerence (CD). CD is the minimal value,

calculated between two consecutive measurements of the same

parameter, using the same method, on the same individual

and including analytical and biological variabilities, which when

exceeded, testiﬁes that an external factor is really modifying

the investigated parameter. Notably, the testosterone-to-cortisol

ratio, widely accepted as an index of the potential athletic

performance status, increased as a result of the observed changes

(Grasso et al., 2014).

Cortisol increased in six professional tennis players treated

with WBC twice a day for 5 days (−120◦C, 3 min) after

moderate-intensity training, during a controlled training camp

(Ziemann et al., 2012), while testosterone remained stable.

Cortisol and testosterone were both stable in 16 kayakers from

Polish National Team, who combined exercise with two daily

WBC sessions during the ﬁrst 10 days of a training cycle in

preparation for the World Championships (Sutkowy et al., 2014).

Six elite rowers were subject to a 6 day training cycle combined

with training sessions scheduled twice daily, each preceded by

WBC (−125/−150◦C, 3 min). During a control training session

without WBC, subjects experienced an increase in cortisol on the

3rd day of training; WBC delayed and reduced this increase on

the 6th day (Wozniak et al., 2013). After a normal training week,

10 elite synchronized swimmers performed two 2 week sessions

of an intensiﬁed training, randomly combined either with or

without daily WBC. The two sessions were separated by a 9 day

light training period. Although salivary cortisol was unchanged,

WBC mitigated signs of functional overreaching observed during

the control period such as reduced sleep quantity, increased

fatigue and impaired exercise capacity (Schaal et al., 2015).

A randomized, counterbalanced and crossover study on 14

habituated English Premier League academy soccer players, a

single WBC session (−135◦C, 2 min), performed within 20 min

after a repeated sprint exercise (15 ×30 m), increased salivary

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TABLE 1 | Effects of WBC on circulating levels of cytokines and inﬂammatory markers.

Subjects WBC mode WBC sessions Effects References

IL-6

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 5 sessions Increased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

5 consecutive days No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 10 sessions Increased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 20 sessions Increased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

4 weeks* No difference 2 weeks after the end of

treatment compared to baseline

12 tennis players

(6 treated, age: 23.0 ±3.0 years,

BMI 23.2 ±1.8; 6 Kg/m2untreated,

20.0 ±2.0 years, BMI 24.4 ±

1.9 kg/m2)

3 min, −120◦C 10 sessions Increased at the end of the treatment

compared to baseline

Ziemann et al., 2012

2 per day

5 consecutive days Signiﬁcant difference vs. controls

12 men, obese

(age: 38.4 ±8.2 years, BMI >

30 kg/m2, divided in HFL group and

in LFL group, visceral fat area

>100 cm2)

3 min, −110◦C 10 sessions (morning

after light breakfast)

No effect on HFL group Dulian et al., 2015

No effect on LFL group

No difference between the groups

11 runners

(age: 31.8 ±2.0 years, simulated

trail with WBC treatment or passive

recovery, blood drawings before

and after the trail, and after 1, 24,

48, 72, and 96 h during recovery)

3 min, −110◦C 4 sessions No effect Pournot et al., 2011

14 obese men

(age: 40.0 ±4.0 years, divided in

HFL group and in LFL group)

3 min, −110◦C 10 sessions (morning

after light breakfast)

Decreased in LFL group compared to

baseline

Ziemann et al., 2013

18 volleyball players

(age: 28.3 ±4.0 years)

2 min, −130◦C 1 session Decreased at the end of the treatment

compared to baseline

Mila-Kierzenkowska et al.,

2013

14 rugby players

(Mean age: 24 years)

1, 2, 3 min,

−135◦C

1 session No effect Selfe et al., 2014

18 men

(9 treated, age: 21.7 ±0.9 years; 9

untreated, age: 22.0 ±2.0 years)

3 min, −110◦C 10 sessions No effect Ziemann et al., 2014

2 per day

5 consecutive days

IL-10

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 5 sessions Increased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

5 consecutive days Increase 2 weeks after the end of treatment

compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 10 sessions Increased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

(Continued)

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TABLE 1 | Continued

Subjects WBC mode WBC sessions Effects References

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 20 sessions Increased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

4 weeks* Increased 2 weeks after the end of treatment

compared to baseline

11 runners

(age: 31.8 ±2.0 years, simulated

trail with WBC treatment or passive

recovery, blood drawings before

and after the trail, and after 1, 24,

48, 72, and 96 h during recovery)

3 min, −130◦C 4 sessions No effect Pournot et al., 2011

14 obese men

(age: 40.0 ±4.0 years, divided in

HFL group and in LFL group)

3 min, −110◦C 10 sessions (morning

after light breakfast)

Increased in both groups compared to

baseline

Ziemann et al., 2013

18 men

(9 treated, age: 21.7 ±0.9 years; 9

untreated, age: 22.0 ±2.0 years)

3 min, −110◦C 10 sessions Increased compared to baseline Ziemann et al., 2014

2 per day

5 consecutive days

IL-12

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 5 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

5 consecutive days No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 10 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 20 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

4 weeks* No difference 2 weeks after the end of

treatment compared to baseline

IL-1α

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 5 sessions Decreased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

5 consecutive days No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 10 sessions Decreased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 20 sessions Decreased at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

4 weeks* No difference 2 weeks after the end of

treatment compared to baseline

IL-1β

15 healthy men (age: 22.0 ±0.8

years, BMI 23.2 ±1.4 kg/m2)

3 min, −130◦C 5 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

5 consecutive days No difference 2 weeks after the end of

treatment compared to baseline

(Continued)

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TABLE 1 | Continued

Subjects WBC mode WBC sessions Effects References

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 10 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 20 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

4 weeks* No difference 2 weeks after the end of

treatment compared to baseline

11 runners

(age: 31.8 ±2.0 years, simulated

trail with WBC treatment or passive

recovery, blood drawings before

and after the trail, and after 1, 24,

48, 72, and 96 h during recovery)

3 min, −110◦C 4 sessions Signiﬁcantly lower in WBC vs. passive

recovery after 1 and 24 h

Pournot et al., 2011

18 volleyball players

(age: 28.3 ±4.0 years)

2 min, −130◦C 1 session Decreased compared to baseline Mila-Kierzenkowska et al.,

2013

18 men

(9 treated, age: 21.7 ±0.9 years; 9

untreated, age: 22.0 ±2.0 years)

3 min, −110◦C 10 sessions Decreased in treated subjects compared to

untreated subjects

Ziemann et al., 2014

2 per day

5 consecutive days

IL-1ra

11 runners

(age: 31.8 ±2.0 years, simulated

trail with WBC treatment or passive

recovery, blood drawings before

and after the trail, and after 1, 24,

48, 72, and 96 h during recovery)

3 min, −110◦C 4 sessions Decreased Pournot et al., 2011

Signiﬁcantly lower in

WBC vs. passive

recovery after 1 h

URIC ACID

46 subjects

(24 M, 22 F; age: 37.5 ±3.1 years;

BMI: 26.9 ±4.2 kg/m2)

3 min, −130◦C 10 sessions Increased in both males and females

compared to baseline

Miller et al., 2012

1 per day

2 weeks*

30 men

(age: 27.8 ±6.1 years; BMI:

22.1–33.2 kg/m2)

3 min, −130◦C 20 sessions No effect after 1 session Lubkowska et al., 2012

1 per day (morning)

20 consecutive days Increased after 10 and 20 sessions

IL-3

45 men from Military Academy (age:

23.5 ±0.8 years; BMI: 25.0 ±2.1

kg/m2); 30 treated vs. 15 untreated

3 min, −130◦C 30 sessions Decreased after 10, 20, and 30 sessions Szygula et al., 2014

1 per day (morning)

5 consecutive days Signiﬁcant differences between groups at

each time-point

TNFα

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 5 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

5 consecutive days No difference 2 weeks after the end of

treatment compared to baseline

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 10 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

(Continued)

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TABLE 1 | Continued

Subjects WBC mode WBC sessions Effects References

15 healthy men

(age: 22.0 ±0.8 years, BMI 23.2 ±

1.4 kg/m2)

3 min, −130◦C 20 sessions No effect at the end of the treatment

compared to baseline

Lubkowska et al., 2011

1 per day (morning)

2 weeks* No difference 2 weeks after the end of

treatment compared to baseline

12 tennis players

(6 treated, age: 23.0 ±3.0 years,

BMI 23.2 ±1.8 Kg/m2; 6 untreated,

20.0 ±2.0 years, BMI 24.4 ±

1.9 kg/m2)

3 min, −120◦C 10 sessions Decreased compared to baseline Ziemann et al., 2012

2 per day

5 consecutive days Signiﬁcant difference vs. controls

11 runners

(age: 31.8 ±2.0 years, simulated

trail with WBC treatment or passive

recovery, blood drawings before

and after the trail, and after 1, 24,

48, 72, and 96 h during recovery)

3 min, −110◦C 4 sessions No effect Pournot et al., 2011

14 obese men

(age: 40.0 ±4.0 years, divided in

HFL and LFL)

3 min, −110◦C 10 sessions (morning

after light breakfast)

Decreased in LFL group compared to

baseline

Ziemann et al., 2013

18 volleyball players

(age: 28.3 ±4.0 years)

2 min, −130◦C 1 session No effect Mila-Kierzenkowska et al.,

2013

hsCRP

12 men, obese

(age: 38.4 ±8.2 years, BMI >30

kg/m2, divided in HFL and LFL,

visceral fat area >100 cm2)

3 min, −110◦C 10 sessions, in the

morning, preceded by

light breakfast

Decreased 30 min and 24 h after 1 session in

both groups

Dulian et al., 2015

Decreased 30 min and

24 h after 10 sessions in

both groups

RESISTIN

14 obese men

(Age: 40.0 ±4.0 years, divided in

HFL and LFL)

3 min, −110◦C 10 sessions (morning

after light breakfast)

Increased in HFL group compared to baseline Ziemann et al., 2013

Decreased in LFL group

compared to baseline

VISFATIN

14 obese men

(age: 40.0 ±4.0 years, divided in

HFL and LFL)

3 min, −110◦C 10 sessions (morning

after light breakfast)

Increased in HFL group compared to baseline Ziemann et al., 2013

Decreased in LFL group

compared to baseline

*Excluding Saturday and Sunday; HFL, high ﬁtness level; LFL, low ﬁtness level.

testosterone up to 24 h post-exercise. Still, the treatment had

no eﬀect on cortisol, blood lactate, and CK (Russell et al.,

2017).

In summary, the following reports have been made about the

WBC treatment:

- WBC aﬀects the hormonal asset, decreasing hormones typically

associated with psychophysical stress, such as cortisol, and

increasing testosterone, a typical anabolic hormone.

- Cortisol modiﬁcations during WBC treatment cycles are not

consistent in the current literature, possibly owing to diﬀerent

stressors applied.

REDOX BALANCE

Oxidative stress is the main factor aﬀecting athletes’ performance.

Muscle activity generates oxidants released in the intercellular

space following membrane leakage or breaking. Oxidants activate

chain reactions, amplifying production of reactive oxygen species

(ROS), which damage membranes, cellular structures and DNA.

Inﬂammation activates innate immunity, which produces ROS

and, through a vicious cycle, ROS-sustained inﬂammation

(Slattery et al., 2015). WBC has been advocated to possibly

enhance antioxidant capacities and, thus, counteract the exercise-

induced ROS production.

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Lombardi et al. Updates for Whole-Body Cryotherapy

The study on WBC eﬀects on an oxidant-antioxidant balance

was performed in 16 kayakers belonging to Polish National

Team submitted to a 19 day physical training cycle. During

the ﬁrst 10 days of the training cycle, the kayakers combined

exercise with two daily WBC sessions: the ﬁrst in the morning

before exercise, the second session in the afternoon after exercise.

Day by day, the temperature was decreased from −120 to

−145◦C. Blood drawings were performed at the beginning

of the training period as well as after 5, 11, and 19 days.

Lipid peroxidation products malondialdehyde (MDA), conjugate

dienes, and thiobarbituric acid reactive substances (TBARS) did

not show any changes. Glutathione peroxidase (GPx) activity

decreased after 5 days, yet later it increased again to baseline

following WBC (11th day). On the last day of training, 9

days after the end of the WBC treatment, TBARS decreased

compared to baseline and the level on day 5, whilst GPx increased

compared to day 5. WBC may improve the eﬃciency of TBARS

elimination that positively impacts strenuous exercise (Sutkowy

et al., 2014).

Eighteen professional volleyball players performed the ﬁrst 40

min submaximal exercise bout on an ergometer 2 weeks after the

end of season, and the second bout 2 weeks after the ﬁrst one. A

single WBC treatment (−130◦C) was conducted before the ﬁrst

exercise bout. The activity of RBC catalase after WBC +exercise

was two times lower compared to that recorded after control

exercise, without WBC, as was the activity of RBC superoxide

dismutase (SOD; −8%; Mila-Kierzenkowska et al., 2013).

SOD and GPx activities were lower (by 44 and 42%,

respectively) after 3 days of training combined with WBC than

without the treatment in six elite rowers, subject to a 6 day

training cycle. Lower levels of TBARS and conjugated dienes

in erythrocytes were also found in the WBC-treated group

(Wozniak et al., 2013).

In healthy subjects, 24 males and 22 females, after 10 daily

WBC sessions, plasma uric acid, SOD, and total antioxidants all

increased compared to both baseline and the control group not

submitted to WBC. TBARS, although unchanged compared to

baseline, were also higher than in the control group (Miller et al.,

2012). During a 6 month long physical exercise program with two

daily WBC exposures over 20 sessions, a signiﬁcant decrease in

SOD, catalase and glutathione reductase activities was observed

(13, 8, and 70%, respectively). SOD activity increased after

successive WBC sessions, while catalase activity progressively

decreased (Lubkowska et al., 2015).

Although a general beneﬁcial antioxidant eﬀect already after a

limited number of WBC sessions is described in these studies, a

dose-dependency was observed in healthy men, with 20 sessions

being the optimal number (Lubkowska et al., 2012).

In summary, the following reports have been made about the

WBC treatment:

- WBC has a dose-dependent improving eﬀect on the redox

balance after exercise.

- WBC is able to decrease the activity of RBC enzymes probably

as a reaction to a decrease in total oxidants and an increase in

antioxidants.

MUSCLE DAMAGE PARAMETERS,

FATIGUE RECOVERY, AND PAIN

From athletes’ and sports physicians’ point of view the eﬀect of

WBC on muscle damage and recovery is the most important

one. Indeed, muscle recovery has been the most claimed and,

possibly, the most debated eﬀect of WBC. In this speciﬁc ﬁeld,

the stimulatory eﬀect of WBC is particularly claimed.

EIMD was studied in nine endurance runners, comparing

three diﬀerent recovery modalities: WBC, far-infrared (FIR), and

passive. The runners performed three identical repetitions of

a simulated trail run on a motorized treadmill. Recovery was

evaluated 1, 24, and 48 h post-exercise. The eventual decrease

in maximal isometric force, after three isometric voluntary

contractions of knee extensor muscles, was used for judging

muscle damage due to strenuous exercise. The best results were

observed after WBC at 1, 24, and 48 h post-exercise. WBC-

enhanced psychological recovery within days after the exercise

including decreased perception of muscular tiredness and pain,

already after the ﬁrst session of WBC. At the same time the pain

sensation was lowered by FIR only 48 h after the exercise and it

did not change at all as a result of passive recovery. Well-being,

evaluated through a standardized questionnaire for tiredness and

pain, was improved after 24 h due to WBC and after 48 h due to

FIR. Still, an increase in serum activity of creatine kinase (CK),

typical of strenuous exercise, was not improved by three WBC

sessions (Hausswirth et al., 2011).

A 40% decrease in CK activity was reported in rugby players

after ﬁve consecutive daily sessions of WBC (Banﬁ et al., 2009b);

it also decreased by 34% after 10 sessions in kayakers (Wozniak

et al., 2007). The same decreasing trend of CK was also conﬁrmed

in 12 professional tennis players (CK dropped from 305.0 to 241.4

U/L in six treated subjects, while remained unchanged in the

control group ones: 286.7 and 295.5 U/L), during a controlled

training camp, during which players were treated with WBC

twice a day for 5 days (−120◦C, 3 min; Ziemann et al., 2012).

The same was also noted in six elite rowers, subject to two 6

day training cycles with training sessions twice a day, all either

preceded by WBC or not (Wozniak et al., 2013) as well as in

physically active males treated with two daily WBC sessions

for 5 consecutive days between step up/down 30 min exercises;

in the latter case, the changes were also accompanied by a

signiﬁcantly improved pain perception (Ziemann et al., 2014). In

professional rugby players, after a 7 day training camp with two

daily WBC sessions, lactate dehydrogenase (LDH), and aspartate

aminotransferase (AST) activities increased as a consequence of

high workload, whilst CK decreased slightly, but signiﬁcantly.

Moreover, kidney function (estimated glomerular ﬁltration rate,

eGFR), which could be impaired following muscle damages, was

unaﬀected by the treatment (Lombardi et al., 2014).

The WBC-induced attenuation in serum soluble intercellular

adhesion molecule (sICAM)-1 immediately after EIMD may be

responsible for reduced acute inﬂammatory response muscle

damage (Ferreira-Junior et al., 2014). The level of sICAM-1

together with CK and LDH activities decreased in rugby players

after 5 consecutive days of daily WBC sessions (Banﬁ et al.,

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Lombardi et al. Updates for Whole-Body Cryotherapy

2009b). After muscle damage is induced by exercise, leukocytes

are mobilized to injured tissues by sICAM-1 intervention, where

pro-inﬂammatory cytokines and ROS are released. WBC causes

vasoconstriction and reduces the number of leukocytes reaching

the muscles by inhibiting sICAM-1 (Ferreira-Junior et al., 2014).

However, it was also hypothesized that cold could induce an

extra-release of sICAM1 and, therefore, cause a decrease of

muscle inﬂammation; the ﬁnal net eﬀect is the same (Dugué,

2015).

Beneﬁcial eﬀects of WBC on psychological recovery within

days after exercise included a decreased perception of muscular

tiredness and pain- an greater-improvement compared to the

eﬀect of other recovery modes, namely FIR and passive (Pournot

et al., 2011). Daily WBC in 10 top level female synchronized

swimmers (−110◦C, 3 min), applied following training sessions,

improved athletes’ tolerance to training load by preserving sleep

quantity during the period of intensive training before the

Olympic Games (Schaal et al., 2015). The eﬀect was evaluated

after the athletes had been randomly assigned either WBC or

non-WBC supported recovery. WBC use had a beneﬁcial eﬀect

on sleep duration, limiting sleep latency possibly conditioned by

post-exercise parasympathetic reactivation (Schaal et al., 2015).

On the contrary, in a randomized, counterbalanced and

crossover design, 14 habituated English Premier League academy

soccer players, Russell and colleagues found that a single

WBC session (−135◦C, 2 min), performed within 20 min after

a repeated sprint exercise (15 ×30 m), increased salivary

testosterone, yet had no eﬀect on cortisol, blood lactate, and CK

nor on performance (peak power output), recovery, and soreness

perceptions (Russell et al., 2017).

It is worth noting that, most of the data reviewed had been

obtained from athletes oﬀ season or during preparation training

phase. It mostly come from endurance athletes or from athletes

with a dominating aerobic metabolism. Limited data exist on the

conjunction of resistance training and WBC.

In summary, the following reports have been made about the

WBC treatment:

- WBC could limit the release of intracellular enzymes, but only

after a prolonged cycle of consecutive sessions.

- WBC-associated improvements in muscular tiredness, pain,

and well-being after strenuous exercise have been reported in

the majority, but not all, of the reviewed studies.

- WBC-mediated enhancement of muscular recovery depends

on the limitation of the exercise-induced inﬂammatory

response.

PERFORMANCE RECOVERY

Performance recovery using diﬀerent cooling methods,

especially CWI and contrast water immersion, has been

extensively studied so far. Their average eﬀect on recovery

of trained athletes is rather limited, as reported in a recent

review, but under appropriate conditions (whole-body cooling,

recovery from sprint exercise) post-exercise cooling has

positive eﬀects even for elite athletes (Poppendieck et al.,

2013).

Positive eﬀects induced by WBC after 96 h were reported in

18 physically active subjects, who performed a single maximal

eccentric contractions of the left knee extensors, through two

WBC sessions (−110◦C) 24 and 48 h after exercise. The eﬀects

were negative at 24 and 48 h post-exercise (Costello et al.,

2012a). Positive eﬀects were also reported 24 and 48 h after the

treatment in nine runners completing a simulated 48-min trail

run, submitted to three WBC sessions, immediately after the

exercise as well as 1 and 2 days after (Hausswirth et al., 2011).

Eleven endurance athletes were tested twice in a randomized

crossover design with 5 ×5 min of high intensity running

followed by 1 h of passive recovery, including either WBC

(−110◦C, 3 min) or a 3 min walk. Time-to-exhaustion diﬀerence

between a ramp-test protocol before running and 1 h post-

recovery was lower in WBC-treated subjects. WBC improves

acute recovery during high-intensity intermittent exercise in

thermoneutral conditions. This could be induced by enhanced

oxygenation of the working muscles as well as by reduction

of cardiovascular strain and increased work economy at

submaximal intensities (Krüger et al., 2015). In addition to

beneﬁcial eﬀects on inﬂammation and muscle damage, WBC

induces peripheral vasoconstriction, which improves muscle

oxygenation (Hornery et al., 2005), lowers submaximal heart

rate and increases stroke volume (Zalewski et al., 2014),

stimulates autonomic nervous parasympathetic activity and

increases norepinephrine (Hausswirth et al., 2013). These eﬀects

favor post-exercise recovery and induce analgesia (Krüger et al.,

2015).

Although these evidences, a recent meta-analysis by Bleakley

et al., based on a small number of randomized studies,

highlighted that WBC sustains improvements in subjective

recovery and muscle soreness following metabolic or mechanical

overload, but little beneﬁt toward functional recovery (Bleakley

et al., 2014). The authors concluded that, until further researches

will be available, less expensive cooling modality (local ice-pack,

cold water immersion) would be used in order to gain the same

physiological and clinical eﬀects to WBC.

EXPOSURE

Time

Three-minute WBC exposure signiﬁcantly diﬀer from a 1–2-min

exposure. Blood volume decreased within vastus lateralis and

gastrocnemius occurred 0–5 min after WBC in 14 professional

rugby players. Oxyhemoglobin and deoxyhemoglobin increased

in 15 min post-WBC, reaching baseline values indicative

of venous pooling. Extreme cold induces vasodilation after

constriction in very short time. Gastrocnemius is more

susceptible to pooling at all exposure times than vastus lateralis.

Two-minute WBC exposure causes changes in core and Tsk,

tissue oxygenation in vastus lateralis, and gastrocnemius and

thermal sensation. The optimum exposure time is 30 s at −60◦C

followed by 2 min WBC at −135◦C (Selfe et al., 2014).

It is also crucial to keep a constant temperature between two

consecutive treatments. Door opening and subject permanence

within a chamber increase temperature and reduce therapeutic

eﬀectiveness, particularly for electrical cryochambers, but also

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Lombardi et al. Updates for Whole-Body Cryotherapy

for liquid nitrogen-cooled chambers. A 2 min wait between

two consecutive treatments would allow temperature recovery to

therapeutic levels.

Sessions

The number of sessions is crucial for WBC eﬀectiveness, as

previously discussed. A recent Cochrane review, reporting on

the absence of beneﬁcial eﬀects of WBC on prevention and

treatment of muscle soreness in athletes, involves on only four

papers. One out of these four papers talked about six treatments

in cryocabin, the other two investigated the eﬀects of a single

treatment in a cryochamber and the ﬁnal one reported the

eﬀects of only three treatments in a cryochamber (Costello

et al., 2015). A single session is probably not suﬃcient to exert

any signiﬁcant eﬀect. Twenty consecutive sessions should be a

minimum for eﬀectiveness evaluation; 30 sessions should be the

optimum, because a complete hematological and immunological

recovery after the initial response is possible (Szygula et al.,

2014). Studies evaluating long-term WBC treatment are not

easily performable in professional athletes during competitive

seasons, but they could be proposed during training and summer

camps. Although oﬀseason injuries are rarer than contusions

incurred during competitions, it is important to note that

standardization of exercise and training oﬀseason is more easily

achievable.

Furthermore, randomization is very diﬃcult, if not

impossible, to be proposed to elite athletes, and professional

teams: the treatment is proposed to improve recovery or to

prevent injuries, thus, it should not be limited to a subgroup of

athletes. On the other hand, when WBC is used for accelerating

recovery from trauma/injury, only injured athletes are treated.

Crossover studies could be more easily performed during

training camps (but not during competitive season), but they

would be only devoted to physiological modiﬁcations and not to

recovery.

Diﬀerent, and sometime discrepant results presented in

current literature could be attributable to diﬀerent levels

of subjects ranging from “physically active” to “elite” to

“national/international selection.” A stratiﬁcation of WBC eﬀects

should be evoked for diﬀerent subjects, because of diﬀerent

adaptation to eﬀort, recovery capacity/velocity, and energy

metabolism.

CONCLUSIONS

Based on the ﬁndings here collected, the majority of evidence

supports eﬀectiveness of WBC in relieving symptomatology

of the whole set of inﬂammatory conditions that could

aﬀect an athlete. A small number of studies that did not

report any positive eﬀects should, however, not be neglected.

The same applies to improvement of post-exercise recovery,

and noteworthy, to limiting or even preventing EIMD. The

perception of WBC is changing from a conventionally intended

symptomatic therapy to a stimulating treatment able to enhance

the anti-inﬂammatory and -oxidant barriers and to counteract

harmful stimuli. Importantly, cooling eﬀectiveness depends

on the percentage of fat mass of a subject and the starting

ﬁtness level. These results, combined with evidence that WBC

somehow mimics exercise, at least in its ability to induce a

pulsatile expression of myokines (IL-6, irisin), open another

window of possible therapeutic strategies for obesity and type 2

diabetes.

As above highlighted, some of the applied WBC protocols

have been ineﬀective in inducing appreciable modiﬁcations

of certain biochemical parameters. However, in these

cases, the ﬁnal clinical output (in a subjective assessment:

in terms of pain, soreness, stress, and recovery) was

signiﬁcantly improved even when compared to other recovery

strategies.

WBC, used either as a therapy or stimulation, is a medical

treatment and as such it has contraindications and standard

safety procedures. The undeniable risks for the users can be

rendered negligible if all the procedures are conducted following

precise rules under supervision of highly-skilled personnel. If

these procedures are carefully followed, WBC is absolutely

safe.

The scientiﬁc debate on WBC, often shaded by non-scientiﬁc

discussions hold in newspapers and web dictated by curiosity or

accidents (recent incident in a non-controlled cryocabin), needs

consensus and international cooperation for building up wide

and controlled studies.

AUTHOR CONTRIBUTIONS

GL and EZ: conception and design, data acquisition; drafting

paper; ﬁnal approval; agreement for all the aspects of the work.

GB: conception and design, data acquisition; critical revision;

ﬁnal approval; agreement for all the aspects of the work.

FUNDING

This work has been funded by an unrestricted grant from the

Italian Ministry of Health and grant from the Polish Ministry of

Science and Higher Education No. 0026/RS3/2015/53.

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Conﬂict of Interest Statement: The authors declare that the research was

conducted in the absence of any commercial or ﬁnancial relationships that could

be construed as a potential conﬂict of interest.

distributed under the terms of the Creative Commons Attribution License (CC BY).

The use, distribution or reproduction in other forums is permitted, provided the

original author(s) or licensor are credited and that the original publication in this

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Frontiers in Physiology | www.frontiersin.org 16 May 2017 | Volume 8 | Article 258

Whole-body cryostimulation in obesity. A scoping review

Article

May 2022
J THERM BIOL

Currently available treatments for the management of obesity struggle to provide clinically significant weight loss and reduction of the chronic low-grade inflammatory state in order to reduce obesity-related complications. This scoping review aims to provide an up-to-date picture of the therapeutic effects of Whole-Body Cryostimulation (WBC) in patients with obesity and evidence-based indications for its complementary use in the treatment of obesity. We searched the literature until the end of August 2021, retrieving 8 eligible studies out of 856, all evaluated for their methodological quality using the Downs and Black checklist. Overall, the limited data presented in this review article seem to support the efficacy of WBC as an adjuvant treatment in obesity. The cryogenic stimulus has important anti-inflammatory/antioxidant effects and its effectiveness is directly related to the individual percentage of fat mass and initial fitness capacity, mimicking an exercise-induced effect. Based on the limited results gathered, WBC emerges as a promising adjuvant therapy to reduce systemic inflammation, oxidative stress, abdominal obesity, and body mass. However, the data presented in this review article fail to reach definitive conclusions with regards to the efficacy of WBC in the treatment of obesity. Application of WBC protocols yields the potential to widen the therapeutic armor for the treatment of obesity and obesity-related disorders but larger, high-quality studies are still needed.

Combination of whole body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome

Article

Full-text available

Jun 2022
J TRANSL MED

Background The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population. Methods Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total. Results A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function. Conclusions Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms.

The Comparative Effect of Different Timings of Whole Body Cryotherapy Treatment With Cold Water Immersion for Post-Exercise Recovery

Article

Full-text available

Jul 2022

Despite several established benefits of Whole Body Cryotherapy (WBC) for post-exercise recovery, there is a scarcity of research which has identified the optimum WBC protocol for this purpose. This study investigated the influence of WBC treatment timing on physiological and functional responses following a downhill running bout. An additional purpose was to compare such responses with those following cold water immersion (CWI), since there is no clear consensus as to which cold modality is more effective for supporting athletic recovery. Thirty-three male participants (mean ± SD age 37.0 ± 13.3 years, height 1.76 ± 0.07 m, body mass 79.5 ± 13.7 kg) completed a 30 min downhill run (15% gradient) at 60% VO 2 max and were then allocated into one of four recovery groups: WBC1 (n = 9) and WBC4 (n = 8) underwent cryotherapy (3 min, −120 • C) 1 and 4 h post-run, respectively; CWI (n = 8) participants were immersed in cold water (10 min, 15 • C) up to the waist 1 h post-run and control (CON, n = 8) participants passively recovered in a controlled environment (20 • C). Maximal isometric leg muscle torque was assessed pre and 24 h post-run. Blood creatine kinase (CK), muscle soreness, femoral artery blood flow, plasma IL-6 and sleep were also assessed pre and post-treatment. There were significant decreases in muscle torque for WBC4 (10.9%, p = 0.04) and CON (11.3% p = 0.00) and no significant decreases for WBC1 (5.6%, p = 0.06) and CWI (5.1%, p = 0.15). There were no significant differences between groups in muscle soreness, CK, IL-6 or sleep. Femoral artery blood flow significantly decreased in CWI (p = 0.02), but did not differ in other groups. WBC treatments within an hour may be preferable for muscle strength recovery compared to delayed treatments; however WBC appears to be no more effective than CWI. Neither cold intervention had an impact on inflammation or sleep.

Nielaboratoryjna adaptacja badania przestrzennego sumowania bólu w dobie pandemii COVID-19

Article

Full-text available

Jun 2022

ABSTRACT: During COVID-19 pandemic associated with multiple restrictions research performance is significantly hampered. This experiment aimed to verify, whether it is possible to adapt the experimental pain induction technique and observe the spatial summation of pain (SSp) within the field-like environment (so that it is possible to conduct the experiment outside of the laboratory and obtain similar results). Two variants of the Cold Pressor Task (CPT) were chosen to induce the SSp effect: i) using a professional apparatus available in the laboratory and ii) with the use of a commercially available plastic box filled with ice and water and a thermometer to measure the temperature of the water. Volunteers' (n = 9) hands were divided into 5 segments, which were then subsequently immersed in the cold water (5°C) for 60 seconds (5-minute intertrial interval). Each participant took part in two sessions, i.e., using laboratory equipment and its non-laboratory equivalent. Preliminary observations confirmed that it is possible to induce SSp using both laboratory devices and methods adapted to non-laboratory conditions. SSp effect size was found to be similar in both methods. Small differences in the level of reported pain were observed, but these differences did not affect the SSp effect. The study showed that it is possible to adapt the procedure to induce pain and SSp within non-laboratory environment.

Cardiovascular Effects of Whole-Body Cryotherapy in Non-professional Athletes

Article

Full-text available

Jun 2022

Objectives The study aimed to investigate changes in heart rate, blood pressure, respiratory rate, oxygen saturation, and body temperature in non-professional trained runners during whole body cryotherapy (WBC). Methods Ten middle-distance runners received 3 once-a-day sessions of WBC. Subjects underwent BP measurements and ECG recorded before and immediately after the daily WBC session. During WBC we recorded a single lead trace (D1) for heart rhythm control. In addition, the 5 vital signs Blood pressure, heart rate, respiratory rate, oxygen saturation, and body temperature were monitored before, during, and after all WBC session. Results We did not report significant changes in ECG main intervals (PR, QT, and QTc). Mean heart rate changed from 50.98 ± 4.43 bpm (before) to 56.83 ± 4.26 bpm after WBC session ( p < 0.05). The mean systolic blood pressure did not change significantly during and after WBC [b baseline: 118 ± 5 mmHg, changed to 120 ± 3 mmHg during WBC, and to 121 ± 2 mmHg after session ( p < 0.05 vs. baseline)]. Mean respiratory rate did not change during WBC as well as oxygen saturations (98 vs. 99%). Body temperature was slightly increased after WBC, however it remains within physiological values Conclusion In non-professional athletes WBC did not affect cardiovascular response and can be safely used. However, further studies are required to confirm these promising results of safety in elderly non-athlete subjects.

The Acute Influence of Whole-Body Cryotherapy on Electromyographic Signals and Jumping Tasks

Article

Full-text available

May 2022

Whole-body cryotherapy (WBC) is a popular treatment in prevention as well as post-injury therapy. The parameter used to assess the risk of injury is the ability of the human body to absorb and recover energy (elasticity). Therefore, this study aimed to assess the impact of whole-body cryotherapy (WBC) at 1 and 3 min intervals on the bioelectric activity of lower-limb muscles and countermovement jumps (CMJs) using trained subjects. A total of 24 individuals participated in the study. The mean age of the study group was 27.9 ± 7.9 years, mean body weight was 77.9 ± 8.8 kg, and mean body height was equal to 181 ± 6 cm. The training routine included 2–4 training sessions per week that lasted for at least 2 h at a time (mainly football). Along with the surface electromyography (sEMG) test of the rectus femoris, the BTS G-Sensor inertia measurement device was applied. After three minutes of WBC, a 6% difference in take-off force was noted, with a 7% (p < 0.04) decrease in elasticity. In the bioelectrical activity of the rectus femoris after MVC normalization, differences (p < 0.05) were noted 3 min after WBC. In this conducted study, a reduction in flexibility of the lower-limb muscle groups in the CMJ task was noted after 3 min of WBC.

Whole-Body Cryostimulation in Fibromyalgia: A Scoping Review

Article

Full-text available

May 2022

Currently, all available therapies for the control and management of fibromyalgia (FM) are mostly focused on relieving patients’ symptoms and improving their quality of life. The purpose of this review is to provide an up-to-date overview of the evidence supporting the beneficial effects of whole-body cryostimulation (WBC) in patients with FM and evidence-based guidance on the possible adjuvant use of WBC in the treatment of FM. We searched the most recent literature by retrieving 10 eligible studies, 4 of which were abstracts only, from a total of 263 records. Thermal stress caused by cryostimulation induces an analgesic effect, improving pain, redox balance, and inflammatory symptoms in an exercise-mimicking fashion. In addition, it reduces the feeling of fatigue, improves mood, and reduces mental health deterioration with positive consequences on depressive states and improved sleep quality. Although the studies included in this review are not of sufficient quality and quantity to draw definitive conclusions about the effectiveness of WBC in FM, initial evidence indicates WBC as a promising add-on option in the multidisciplinary treatment of FM, due to its rapid action and high patients’ compliance. The application of WBC protocols has the potential to expand therapeutic options for the treatment of FM and related disorders; however, larger, high-quality primary studies are still needed.

Whole-body cryostimulation does not disturb the homeostasis of the system in physically active men - Pilot study

Article

Apr 2022
CRYOBIOLOGY

Whole-body cryostimulation (W-BC) is commonly used following exercise to accelerate recovery or as a form of therapy to prevent and cure sports injuries. This study aimed to investigate the effect of a series of 24 W-BC sessions on morphological and rheological blood indicators in physically active men. Eighteen physically active men participated in the study (mean age 22.1 ± 0.07). They were divided into two groups depending on their self-reported levels of physical activity: moderate or high physical activity. The participants completed a total of 24 W-BC sessions every second day, over a span of two months. Blood was collected at baseline, immediately after and 24 h after the first treatment, before and after the 12th treatment, before, immediately after, and 24 h after the 24th treatment, and one, two, three, and four weeks after the 24th treatment. Rheological and morphological indicators of blood were examined. The number of leukocytes was decreased in the moderate activity group (p < 0.05) but not in the high intensity group, following the first W-BC session. There were no significant changes in elongation index (EI) at a shear stress of 2.19–31.04 (Pa) in both groups as well as at the following values: aggregation index (AI), the half time (T½) and the amplitude of aggregation (AMP) in both studied groups. Differences between the first and the 12th or the 24th session became apparent in some morphological indices in one or both groups. Changes in the morphological properties were not observed after the first exposure but became evident following repeated W-BC sessions.

The Effect of Repetitive Whole Body Cryotherapy Treatment on Adaptations to a Strength and Endurance Training Programme in Physically Active Males

Article

Full-text available

Mar 2022

Despite its potential merit in sport and exercise recovery, the implications of repetitive Whole Body Cryotherapy (WBC) during training programmes require further review due to the possibility of repetitive cold interfering with long term adaptations. This study investigated the impact of two weekly 3 min WBC sessions (30 s at −60 • C, 150 s at −120 • C) on adaptations to a 6 week strength and endurance training programme. Sixteen male participants (mean ± SD age 33.4 ± 9.8 years, body mass 82.3 ± 9.8 kg) randomly allocated into WBC (n = 7) and non-cryotherapy control (CON, n=9) groups completed the programme consisting of two weekly strength and plyometric training sessions and two weekly 30 min runs (70% VO 2 max). Participants were assessed for body fat, VO2 max, muscle torque, three repetition maximum barbell squat and countermovement jump height before and after the programme. Resistance and running intensities were progressed after 3 weeks. Participants in both groups significantly improved muscle torque (WBC: 277.1 ± 63.2 Nm vs. 318.1 ± 83.4 Nm, p < 0.01, d = 0.56; CON: 244.6 ± 50.6 Nm vs. 268.0 ± 71.8 Nm, p = 0.05, d = 0.38) and barbell squat (WBC: 86.4 ± 19.5 kg vs. 98.9 ± 15.2 kg, p = 0.03, d = 0.69; CON: 91.1 ± 28.7 kg vs. 106.1 ± 30.0 kg, p<0.01, d=0.51) following the 6 week programme. For the CON group, there was also a significant reduction in body fat percentage (p = 0.01) and significant increase in jump height (p = 0.01). There was no significant increase in VO2 max for either group (both p > 0.2). There was no difference between WBC and CON for responses in muscle torque, 3RM barbell squat and body fat, however WBC participants did not increase their jump height (p = 0.23). Repetitive WBC does not appear to blunt adaptations to a concurrent training programme, although there may be an interference effect in the development of explosive power. Sports practitioners can cautiously apply repetitive WBC to support recovery post-exercise without undue concern on athletes' fitness gains or long term performance, particularly throughout training phases focused more on general strength development than explosive power.

Acute cold stress induces transient MuRF1 upregulation in the skeletal muscle of zebrafish

Article

Mar 2022
BIOCHEM BIOPH RES CO

Cryotherapy is one of the most common treatments for trauma or fatigue in the field of sports medicine. However, the molecular biological effects of acute cold exposure on skeletal muscle remain unclear. Therefore, we used zebrafish, which have recently been utilized as an animal model for skeletal muscle, to comprehensively investigate and selectively clarify the time-course changes induced by cryotherapy. Zebrafish were exposed intermittently to cold stimulation three times for 15 min each. Thereafter, skeletal muscle samples were collected after 15 min and 1, 2, 4, and 6 h. mRNA sequencing revealed the involvement of trim63a, fbxo32, fbxo30a, and klhl38b in “protein ubiquitination” from the top 10 most upregulated genes. Subsequently, we examined the time-course changes of the four genes by quantitative PCR, and their expression peaked 2 h after cryotherapy and returned to baseline after 6 h. Moreover, the proteins encoded by trim63a and fbxo32 (muscle-specific RING finger protein 1 [MuRF1] and muscle atrophy F-box, respectively), which are known to be major genes encoding E3 ubiquitin ligases, were examined by western blotting, and MuRF1 expression displayed similar temporal changes as trim63a expression. These findings suggest that acute cold exposure transiently upregulates E3 ubiquitin ligases, especially MuRF1; thus, cryotherapy may contribute to the treatment of trauma or fatigue by promoting protein processing.

Bone turnover response is linked to both acute and established metabolic changes in ultra-marathon runners

Article

Full-text available

Apr 2017
ENDOCRINE

Bone and energy metabolisms regulation depends on a two-way street aimed at regulating energy utilization. Mountain ultra-marathons are highly demanding aerobic performances that deeply affect the whole body homeostasis. In this study we aimed to investigate and characterize the metabolic profile (in terms of hormones involved in energy metabolism), the inflammatory adipokines, and the bone turnover; in particular the osteocalcin-mediated response has been compared in experienced mountain ultra-marathons runners versus control subjects. Serum concentrations of specific markers of bone turnover (pro-collagen type I N-terminal propeptide, carboxylated/undercarboxylated osteocalcin), measured by enzyme-linked immunosorbent assay, and metabolic hormones (C-peptide, insulin, glucagon, glucagon-like peptide, gastric-inhibitory peptide, ghrelin, leptin, resistin, and visfatin), measured by fluorescent-based multiplex assay, were compared before and after a 65 km mountain ultra-marathons in 17 trained runners and 12 age-matched controls characterized by a low physical activity profile. After the mountain ultra-marathons, runners experienced a reduction in pro-collagen type I N-terminal propeptide, though it remained higher than in controls; while carboxylated osteocalcin remained unchanged. Among the metabolic hormones, only glucagon and leptin were different between runners and controls at rest. C-peptide and leptin decreased after the mountain ultra-marathons in runners; while glucagon, glucagon-like peptide 1, resistin, and visfatin were all increased. Uncarboxylated osteocalcin (and uncarboxylated/carboxylated osteocalcin ratio) was decreased and this highly correlated with insulin and C-peptide levels. In conditions of high energy expenditure, homeostasis is maintained at expenses of bone metabolism. Changes in the uncarboxylated osteocalcin clearly mark the global energy needs of the body.

The effects of a single whole body cryotherapy exposure on physiological, performance and perceptual responses of professional academy soccer players following repeated sprint exercise

Article

Full-text available

May 2016

In professional youth soccer players, the physiological, performance and perceptual effects of a single whole body cryotherapy (WBC) session performed shortly after repeated sprint exercise were investigated. In a randomized, counter-balanced and crossover design, 14 habituated English Premier League academy soccer players performed 15 x 30 m sprints (each followed by a 10 m forced deceleration) on two occasions. Within 20 min of exercise cessation, players entered a WBC chamber (Cryo: 30 s at -60°C, 120 s at -135°C) or remained seated (Con) indoors in temperate conditions (∼25°C). Blood and saliva samples, peak power output (countermovement jump) and perceptual indices of recovery and soreness were assessed pre-exercise and immediately, 2 h and 24 h post-exercise. When compared to Con, a greater testosterone response was observed at 2 h (+32.5 ± 32.3 pg[BULLET OPERATOR]ml, +21%) and 24 h (+50.4 ± 48.9 pg[BULLET OPERATOR]ml, +28%) post-exercise (both P=0.002) in Cryo (trial x treatment interaction: P=0.001). No between trial differences were observed for other salivary (cortisol and testosterone/cortisol ratio), blood (lactate and Creatine Kinase), performance (peak power output) or perceptual (recovery or soreness) markers (all trial x treatment interactions: P>0.05); all of which were influenced by exercise (time effects: all P<0.05). A single session of WBC performed within 20 min of repeated sprint exercise elevated testosterone concentrations for 24 h but did not affect any other performance, physiological or perceptual measurements taken. While unclear, WBC may be efficacious for professional soccer players during congested fixture periods.

Effect of hole-body cryotherapy on selected blood chemistry parameters in professional field hockey players

Article

Full-text available

Jan 2007

Background. Whole-body cryotheraphy has been used by sports professionals as a training adjunct for many years. As bibliographic data presenting empirical research concerning this subject are limited, we carried out a study to evaluate the effect of whole-body cryotherapy on selected blood chemistry markers, including interieukin-1β (IL-1β), in professional athletes. Material and methods. The study enrolled 11 Polish men's national field hockey team members aged 25.8 ± 2.9 years (min. 21, max 31 yrs). Whole-body cryotherapy was administered twice a day (at temperatures from -120°C to -130°C) for 2.5-3 minutes, for a total of 18 procedures. In addition, all participants attended a general fitness training session in a gymnasium after each cryotherapy procedure. Blood chemistry determinations (erythrocyte sedimentation rate - ESR, leukocyte count - WBC, erythrocyte count - RBC, platelets, haemoglobin - HGB, haematocrit - HCT, MCV, MCH, MCHC, percentage of lymphocytes, monocytes and neutrophils, and interieukin-1β levels) were performed at baseline and on completion of the series of 18 cryotherapy procedures as well as one week later. Results and Conclusions. Whole-body cryotherapy significantly decreased the RBC, HGB and HCT parameters in peripheral blood. The decrease was, however, not permanent and after one week the parameters returned to baseline values (RBC, HCT) or were increased in comparison to baseline values (HGB). Whole-body cryotherapy was not found to have an immunomodulatory effect in the study group (WBC, percentage of lymphocytes, monocytes or neutrophils, IL-1β levels), except for its effect on the erythrocyte sedimentation rate (ESR), which did not change immediately after the treatment but was significantly lower one week later.

Implications of exercise-induced adipo-myokines in bone metabolism

Article

Full-text available

Nov 2016
ENDOCRINE

Physical inactivity has been recognized, by the World Health Organization as the fourth cause of death (5.5 % worldwide). On the contrary, physical activity (PA) has been associated with improved quality of life and decreased risk of several diseases (i.e., stroke, hypertension, myocardial infarction, obesity, malignancies). Bone turnover is profoundly affected from PA both directly (load degree is the key determinant for BMD) and indirectly through the activation of several endocrine axes. Several molecules, secreted by muscle (myokines) and adipose tissues (adipokines) in response to exercise, are involved in the fine regulation of bone metabolism in response to the energy availability. Furthermore, bone regulates energy metabolism by communicating its energetic needs thanks to osteocalcin which acts on pancreatic β-cells and adipocytes. The beneficial effects of exercise on bone metabolism depends on the intermittent exposure to myokines (i.e., irisin, IL-6, LIF, IGF-I) which, instead, act as inflammatory/pro-resorptive mediators when chronically elevated; on the other hand, the reduction in the circulating levels of adipokines (i.e., leptin, visfatin, adiponectin, resistin) sustains these effects as well as improves the whole-body metabolic status. The aim of this review is to highlight the newest findings about the exercise-dependent regulation of these molecules and their role in the fine regulation of bone metabolism.

The whole body cryostimulation modifies irisin concentration and reduces inflammation in middle aged, obese men

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Oct 2015
CRYOBIOLOGY

The anti-inflammatory effect induced by exposure to low temperature might trigger the endocrine function of muscle and fat tissue. Thus, the aim of this study was to investigate the influence of the whole body cryostimulation (CRY) on irisin, a myokine which activates oxygen consumption in fat cells as well as thermogenesis. In addition, the relationship between hepcidin (Hpc) - hormone regulating iron metabolism, and inflammation was studied. A group of middle aged men (n=12, 38±9 years old, BMI > 30 kg·m(-2)) participated in the study. Subjects were exposed to a series of 10 sessions in a cryogenic chamber (once a day at 9:30am, for 3 min, at temperature -110°C). Blood samples were collected before the first cryostimulation and after completing the last one. Prior to treatment body composition and fitness level were determined. The applied protocol of cryostimulation lead to rise the blood irisin in obese non-active men (338.8±42.2 vs 407.6 ±118.5 ng·mL(-1)), whereas has no effect in obese active men (371.5±30.0 vs 343.3±47.6 ng·mL(-1)). Values recorded 24h after the last cryo-session correlated significantly with the fat tissue, yet inversely with the skeletal muscle mass. Therefore, we concluded the subcutaneous fat tissue to be the main source of irisin in response to cold exposures. The applied cold treatment reduced the high sensitivity C-reactive protein (hsCRP) and Hpc concentration confirming its anti-inflammatory effect.

Body Composition, Lipid Profile, Adipokine Concentration, and Antioxidant Capacity Changes during Interventions to Treat Overweight with Exercise Programme and Whole-Body Cryostimulation

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Jun 2015
OXID MED CELL LONGEV

The aim of this study was to determine the effect of six-month-long physical exercise programme with a two-time exposure to whole-body cryostimulation (WBC) in 20 sessions on antioxidant enzyme activities, lipid profile, and body composition changes in obese people (30 adult subjects; BMI = 30.39 ± 4.31 kg/m(2)). Blood samples were taken before the programme, one month following the exercise programme, before and after the first WBC treatment, six months following the exercise programme, after the second WBC treatment, and finally one month after the intervention. Six months of moderate aerobic activity combined with WBC did not change body mass or fat and lean body mass percentages, or circulating adiponectin, leptin, and resistin concentrations. In response to intervention a significant decrease in the level of low-density lipoprotein and triglycerides was observed, with a slight increase in high-density lipoprotein concentration. The nature of changes in the activity of respective antioxidant enzymes was not identical. After one month of increased physical activity, a significant decrease in superoxide dismutase, catalase, and glutathione reductase activities was observed (13%, 8%, and 70%, resp.). The SOD activity increased significantly after successive whole-body cryostimulation sessions. As regards catalase, a significant progressive decrease in its activity was observed.

Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects

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Apr 2015
EXERC IMMUNOL REV

Cytokines are important mediators of various aspects of health and disease, including appetite, glucose and lipid metabolism, insulin sensitivity, skeletal muscle hypertrophy and atrophy. Over the past decade or so, considerable attention has focused on the potential for regular exercise to counteract a range of disease states by modulating cytokine production. Exercise stimulates moderate to large increases in the circulating concentrations of interleukin (IL)-6, IL-8, IL- 10, IL-1 receptor antagonist, granulocyte-colony stimulating factor, and smaller increases in tumor necrosis factor-α, monocyte chemotactic protein-1, IL-1β, brain-derived neurotrophic factor, IL-12p35/p40 and IL-15. Although many of these cytokines are also expressed in skeletal muscle, not all are released from skeletal muscle into the circulation during exercise. Conversely, some cytokines that are present in the circulation are not expressed in skeletal muscle after exercise. The reasons for these discrepant cytokine responses to exercise are unclear. In this review, we address these uncertainties by summarizing the capacity of skeletal muscle cells to produce cytokines, analyzing other potential cellular sources of circulating cytokines during exercise, and discussing the soluble factors and intracellular signaling pathways that regulate cytokine synthesis (e.g., RNA-binding proteins, microRNAs, suppressor of cytokine signaling proteins, soluble receptors). Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

Whole- and partial-body cryostimulation/cryotherapy: Current technologies and practical applications

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