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The Influence of Menthol Gel During Exercise With Heat

The Influence of Topical Menthol Gel on Thermoregulatory and Perceptual Outcomes During Exercise Within the Heat

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05302804
Enrollment
12
Registered
2022-03-31
Start date
2022-05-01
Completion date
2022-10-01
Last updated
2024-04-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Exercise, Heat Exposure

Keywords

heat exposure, menthol, exercise

Brief summary

The purpose of this study is to examine the human thermoregulatory impact of applying a commercially available menthol gel (BioFreeze) to the skin prior to moderate intensity walking under heated conditions. Experimental Visits will consist of 30 min of treadmill walking at a moderate pace (3.5 mph, 5% grade) under hot conditions (38°C, 60%RH) and will be randomized and counterbalanced for BioFreeze or a hypoallergenic gel (control) application. Gels will be applied to areas commonly exposed during outdoor activity in warm conditions (shoulder to wrist, mid thigh to ankle). Accordingly, participants will wear shorts and a tank top shirt during exercise. Core temperature, skin temperature, galvanic skin response, laser doppler blood flow, and heart rate will be continuously recorded throughout the exercise bout via an integrated analog to digital converter. Sweat will be collected during exercise using commercially available absorbent patches. Thermal sensation will be assessed throughout exercise via the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) thermal sensation likert scale (cold to hot). Lastly, nude body weight will be recorded pre and post exercise for sweat rate determination. The BioFreeze and control trials will be separated by a 7-14 day washout period.

Detailed description

3 experimental visits to the laboratory will be conducted. All visits will take place at the University of Nebraska at Omaha, Exercise Physiology Laboratory. Visit 1 will consist of the physical activity readiness questionnaire (PARQ), adverse reaction to BioFreeze, and body composition (hydrostatic weigh, bioelectrical impedance). Visits 2 and 3 will be separated by 7-14 days, randomized, and counterbalanced for experimental (BioFreeze) and control (hypoallergenic cream) trials. Both the experimental and control visits will follow the same protocol. Participants will arrive following an overnight fast state while also refraining from strenuous activity, alcohol consumption, tobacco use, and recreational drugs for the previous 24 hour period. During these visit researchers will apply BioFreeze using a gloved hand from shoulder to wrist and mid thigh to ankle (areas outside of the clothing). A hypoallergenic cream will be applied during the control visit. Exercise will consist of 30 min of moderate intensity treadmill walking (3.5 mph at 5% grade) within a heated temperature/humidity controlled chamber (38°C, 60% relative humidity). Participants will be weighed before, and after completion of the exercise calculate sweat rate. Prior to the exercise session, participants will sit for 5 min in an ambient room temperature environment as a baseline. During baseline and during the exercise core temperature, skin temperature, laser doppler blood flow, galvanic skin response, and heart rate will be collected continuously. Sweat patches will be adhered to the forehead during exercise at minute 10 for collection of sweat composition over the next 10-20 minutes. Thermal perception using the ASHRAE scale (cold to hot) will be assessed pre and during exercise. VISIT 1 Visit 1 will take approximately 1 hour. Informed consent will be given. Participants will then complete the physical activity readiness questionnaire (PARQ) to be cleared for physical activity. Participants will have a small amount of the BioFreeze cream applied to a small area of the forearm (\ 2 x 2 in) to test for any adverse reaction over a period of 15 minutes. This initial skin reaction test is not a part of the research protocol. Those without a reaction will have height, weight, and body fat composition measured. Height and weight will be measured using a medical scale and stadiometer, respectively. Body fat will be assessed with hydrostatic weighing using an electronic load cell based system (Exertech, Dresbach, MN) correcting for residual lung volume or via a bio-electrical impedance analyzer (InBodyUSA, Cerritos, CA). VISITS 2 AND 3 Visits 2 and 3 will take approximately 2 hours each. Upon arrival at the lab, a nude body weight will be collected with the subject in a private room. While still in the room, subjects will self-insert a rectal thermistor 12-15 cm beyond the anal sphincter and don a chest strap heart rate monitor. After dressing in their exercise clothing, subjects will exit the private room so that chest, forearm, and calf thermistors can be adhered to the skin with tape. Laser doppler flow (forearm and or/finger) will be adhered with tape and galvanic skin response (fingers) will be adhered using Velcro straps to the skin. Measuring instruments will be recorded using an integrated digital to analog converter (ADInstruments, Colorado Springs, CO). Following instrumentation, subjects will sit for 5 minutes as a baseline in a temperate environment. Immediately after, a researcher with gloved hands will topically apply BioFreeze or the control hypoallergenic cream from the shoulder to wrist and mid-thigh to ankle. Subjects will then enter the heat chamber (38°C, 60% relative humidity) and immediately begin a 30-minute walk on a treadmill (3.5 mph, 5% grade). Subjects will be intermittently asked to hold their arm steady for laser doppler flow collection (10, 20, 30 minutes). Subjects will also briefly pause at minute 10 in order to adhere an absorbent patch to their forehead for sweat collection over the following 10-20 minutes. Thermal perception using the ASHRAE scale (cold to hot) will be assessed pre and during exercise. After 30 minutes of walking, subjects will exit the chamber for removal of all skin and finger sensors. Subjects will then re-enter the private room, remove their own rectal thermistor with gloved hands, and then a final nude body weight will be recorded after toweling off. The rectal thermistor will measure core temperature. The heart rate monitor will measure the beats of the heart. Skin thermistors will measure the temperature of the skin surfaces. Laser doppler flow measure the relative units of blood flow velocity. Galvanic skin response measures skin conductivity changes as individuals begin to sweat. Sweat is collected for assessment of sweat composition. Thermal perception is assessed for individual perception surrounding the temperature of the ambient environment. Nude body weight is measured to calculate sweat rate.

Interventions

5% menthol gel applied from shoulder to wrist and mid thigh to ankle, 30 minute treadmill walk (3.5 mph at 5% grade at 38°C, 60% relative humidity)

Hypoallergenic gel applied from shoulder to wrist and mid thigh to ankle, 30 minute treadmill walk (3.5 mph at 5% grade at 38°C, 60% relative humidity)

Sponsors

University of Nebraska
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

Each Subject acts as their own control in a repeated measures design

Eligibility

Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes

Inclusion criteria

* 19-45 years of age * cleared for physical activity via the 2022 physical activity readiness questionnaire (PARQ) * no self-reported adverse reactions to menthol based gels

Exclusion criteria

* outside 19-45 years of age * not cleared for physical activity via the 2022 physical activity readiness questionnaire (PARQ) * self-report or signs of sensitivity to menthol gels * pregnant * breast feeding

Design outcomes

Primary

MeasureTime frameDescription
Sweat Potassium Concentrationfinal 10 minutes of the exercise boutthis is a measure of the amount of potassium in the sweat
Average Skin Temperatureafter 30 minutes of exerciseaverage measurements from chest, forearm, and calf thermistors
Core Temperatureafter 30min exercisemeasured with rectal thermistor
Skin Blood Flow10 minutes into exercise boutLaser Doppler measurement of skin blood flow
Galvanic Skin ResponseTime to 40 micro-siemensmeasurement of skin conductance
Sweat Compositionfinal 10 minutes of exercise boutSodium concentrations in collected sweat
Sweat Ratepre to post exercise, approximately 30 minutesDifference in Nude body weight from pre to post exercise is assumed to be the amount of weight lost via sweat. This value is then expressed as liters of sweat lost per hour if the intervention was to last 1 hr.
Thermal Perceptionthroughout the 30 minute exercise boutscale of thermal comfort developed by the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE). The ASHRAE is a 7-point scale to asses thermal sensation, which consists of seven verbal anchors: cold (-3), cool (-2), slightly cool (-1), neutral (0), slightly warm (1), warm (2), and hot (3). The score is reported as the value in ()

Secondary

MeasureTime frameDescription
Skin Surface Areapreliminary testing completed prior to the study proceduresthis is a descriptive measure of the amount of total body weight that is fat. expressed as a percentage. Since this is a repeated measures study (each subject completed all conditions) this test was only done once before the experimental trials.
% Body Fatpreliminary testing before beginning the studythis is a descriptive measure of the amount of total body weight that is fat. expressed as a percentage. Since this is a repeated measures study (each subject completed all conditions) this test was only done once before the experimental trials.

Countries

United States

Participant flow

Participants by arm

ArmCount
All Study Participants
Menthol gel will be applied to the skin or a A hypoallergenic gel will be applied to the skin prior to exercise in the heat. All subjects complete both menthol gel and hypoallergenic gel conditions in a randomized cross-over study design. At least 7 days were allowed between conditions (washout). Menthol Gel: application of 5% menthol gel from shoulder to wrist and mid thigh to ankle Control Gel: application of hypoallergenic gel from shoulder to wrist and mid thigh to ankle Exercise: treadmill walking 3.5 mph at 5% grade A hypoallergenic gel will be applied to the skin prior to exercise in the heat
12
Total12

Baseline characteristics

CharacteristicAll Study Participants
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
12 Participants
Age, Continuous28 years
STANDARD_DEVIATION 8
Body Composition20.1 percent body fat
STANDARD_DEVIATION 6.3
Race and Ethnicity Not Collected— Participants
Region of Enrollment
United States
12 participants
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
10 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 120 / 12
other
Total, other adverse events
0 / 120 / 12
serious
Total, serious adverse events
0 / 120 / 12

Outcome results

Primary

Average Skin Temperature

average measurements from chest, forearm, and calf thermistors

Time frame: after 30 minutes of exercise

ArmMeasureValue (MEAN)Dispersion
Menthol GelAverage Skin Temperature37.6 degrees CStandard Deviation 0.3
Control GelAverage Skin Temperature37.2 degrees CStandard Deviation 0.5
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: 0.026ANOVA
Primary

Core Temperature

measured with rectal thermistor

Time frame: after 30min exercise

ArmMeasureValue (MEAN)Dispersion
Menthol GelCore Temperature38.1 degrees CStandard Deviation 0.3
Control GelCore Temperature37.7 degrees CStandard Deviation 0.3
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: 0.001ANOVA
Primary

Galvanic Skin Response

measurement of skin conductance

Time frame: Time to 40 micro-siemens

ArmMeasureValue (MEAN)Dispersion
Menthol GelGalvanic Skin Response1299 secondsStandard Deviation 335
Control GelGalvanic Skin Response1148 secondsStandard Deviation 298
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: 0.048ANOVA
Primary

Skin Blood Flow

Laser Doppler measurement of skin blood flow

Time frame: 30 minutes into exercise bout

ArmMeasureValue (MEAN)Dispersion
Menthol GelSkin Blood Flow196.1 arbitrary unitsStandard Deviation 69.4
Control GelSkin Blood Flow194.8 arbitrary unitsStandard Deviation 73.3
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: 0.742ANOVA
Primary

Skin Blood Flow

Laser Doppler measurement of skin blood flow

Time frame: 10 minutes into exercise bout

ArmMeasureValue (MEAN)Dispersion
Menthol GelSkin Blood Flow131.6 arbitrary unitsStandard Deviation 71.6
Control GelSkin Blood Flow119.2 arbitrary unitsStandard Deviation 43.2
Comparison: Null hypothesis was there was no difference between menthol gel and control gel~time x trial ANOVA statistical analysisp-value: 0.742ANOVA
Primary

Sweat Composition

Sodium concentrations in collected sweat

Time frame: final 10 minutes of exercise bout

ArmMeasureValue (MEAN)Dispersion
Menthol GelSweat Composition38.9 mmol/LStandard Deviation 13.8
Control GelSweat Composition43.9 mmol/LStandard Deviation 6.9
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: 0.104t-test, 2 sided
Primary

Sweat Potassium Concentration

this is a measure of the amount of potassium in the sweat

Time frame: final 10 minutes of the exercise bout

ArmMeasureValue (MEAN)Dispersion
Menthol GelSweat Potassium Concentration7.1 mmol/LStandard Deviation 1.2
Control GelSweat Potassium Concentration6.9 mmol/LStandard Deviation 1.7
p-value: >0.05t-test, 2 sided
Primary

Sweat Rate

Difference in Nude body weight from pre to post exercise is assumed to be the amount of weight lost via sweat. This value is then expressed as liters of sweat lost per hour if the intervention was to last 1 hr.

Time frame: pre to post exercise, approximately 30 minutes

ArmMeasureValue (MEAN)Dispersion
Menthol GelSweat Rate1.1 Liters per hourStandard Deviation 0.4
Control GelSweat Rate1.3 Liters per hourStandard Deviation 0.4
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: 0.051t-test, 2 sided
Primary

Thermal Perception

scale of thermal comfort developed by the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE). The ASHRAE is a 7-point scale to asses thermal sensation, which consists of seven verbal anchors: cold (-3), cool (-2), slightly cool (-1), neutral (0), slightly warm (1), warm (2), and hot (3). The score is reported as the value in ()

Time frame: throughout the 30 minute exercise bout

ArmMeasureValue (MEAN)Dispersion
Menthol GelThermal Perception0.7 units on a scaleStandard Deviation 1.6
Control GelThermal Perception1.8 units on a scaleStandard Deviation 1.3
Comparison: The null hypothesis is that there is no difference between menthol and control trialsp-value: <0.001ANOVA
Secondary

% Body Fat

this is a descriptive measure of the amount of total body weight that is fat. expressed as a percentage. Since this is a repeated measures study (each subject completed all conditions) this test was only done once before the experimental trials.

Time frame: preliminary testing before beginning the study

Population: There is only 1 arm for this variable since it is descriptive of the total subjects that subsequently participate in each condition (repeated-measures).

ArmMeasureValue (MEAN)Dispersion
Menthol Gel% Body Fat20.1 percent body fatStandard Deviation 6.3
Secondary

Skin Surface Area

this is a descriptive measure of the amount of total body weight that is fat. expressed as a percentage. Since this is a repeated measures study (each subject completed all conditions) this test was only done once before the experimental trials.

Time frame: preliminary testing completed prior to the study procedures

Population: There is only 1 arm for this variable since it is descriptive of the total subjects that subsequently participate in each condition (repeated-measures).

ArmMeasureValue (MEAN)Dispersion
Menthol GelSkin Surface Area1.98 meters squaredStandard Deviation 0.31

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026