Chronic Passive Heating in Healthy Older Adults

The Effects of Chronic Passive Heating on Vascular Function, Cognitive Function, Muscle Function and Heat Shock Protein Responses in Middle-aged to Older Adults: A Randomised, Controlled Crossover Trial

Aging is associated with a decline in cardiovascular health, cognitive function and losses in muscle strength, with half or more of those over age 65 suffering from two or more comorbidities (e.g., heart disease, type 2 diabetes). The worldwide population of older adults is growing rapidly, with one in six people expected to be over age 65 by 2050. This will place further financial burden from chronic diseases on already stressed healthcare systems. While studies show that frequent exercise is an effective way for older adults to maintain or improve cardiovascular and metabolic health, older individuals are less physically active and do not adhere well to exercise programs, often due to physical or medical limitations. Therefore, alternative methods for older adults to get the same health benefits as exercise require further exploration. Recent work has shown that passive heat therapy may be one such alternative solution.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Other: Passive heating

Detailed Description

Aging is associated with declines in cardiovascular health and cognitive function as well as chronic inflammation and the development of neurodegenerative conditions such as Alzheimer's and Parkinson's disease. Additionally, ageing results in a loss of muscle size and strength, commonly referred to as sarcopenia, leading to increased risk of falls or adverse exercise-related events. It is well understood that frequent exercise improves cardiovascular and metabolic health whilst lowering the risk of disease and all-cause mortality, acting as a treatment for many different health conditions. Despite the evidence of its efficacy, many individuals struggle with adherence to exercise programmes, particularly older adults and clinical populations, with many individuals within these populations unable to perform exercise due to physical limitations or medical contraindications. With one in six people expected to be over the age of 65 years by 2050 and corresponding increases in non-communicable diseases (e.g., cancer, diabetes, cardiovascular disease) anticipated from this aging population, the development of adjunct treatments or alternatives to exercise to improve general health in older populations is needed.

Recent work has shown that a potential solution could be the use of passive heat therapy (PHT) (e.g., hot water immersion, sauna), which can achieve health benefits comparable to exercise. Previous work by Brunt and colleagues using eight weeks of chronic heat therapy has demonstrated systemic macro- and microvascular adaptations in young, healthy individuals including improved endothelial function, reduced arterial stiffness and cutaneous vascular conductance. Chronic passive heat acclimation in young, healthy adults has also been shown to improve working memory. Additional studies have shown that ten weeks of passive heating improved muscle strength in middle-aged men and ten days of daily pulsed shortwave diathermy attenuated immobilization-induced muscle atrophy in young, healthy adults.

One potential mechanism for the physiological benefits obtained from PHT is the increase of cytoprotective heat shock proteins (HSP) (specifically HSP27, HSP60, HSP70 and HSP90) intracellularly (i) and extracellularly (e) in response to increases in deep body temperature. Increases in the expression of these HSPs have been shown to play a role in reducing inflammation and protecting the vasculature via increases in endothelial nitric oxide synthase activity. Increased HSP concentrations may also prevent the accumulation of harmful biomarkers in the brain that play a role in cognitive decline and development of neurodegenerative diseases. Aging, however, is associated with a reduction in HSP transcription activity in various tissues, resulting in an impaired heat shock response and development of a pro-inflammatory state. Previous work using acute hot water immersion has shown increases in eHSP70. The only study to test the effects of chronic hot water immersion on resting iHSP70 showed no effect, however, the magnitude of stimulus (39°C water) applied by Hoekstra and colleagues and the resultant changes in core temperature were likely too low to induce any changes in HSPs.

These studies provide promising evidence that health benefits from PHT similar to those from exercise could translate to older adults. However, most studies testing the effects of PHT on humans have been performed in young, healthy adults, whereas older individuals are likely to derive the greatest benefit from any positive effects of PHT. To date, no study has examined the longer-term effects of PHT on macrovascular, microvascular, cognitive or muscle function, or HSPs in older adults. Therefore, further research is needed to confirm that heat therapy confers the same beneficial health adaptations in older adults.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO4 0SU
      • Spinnaker Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female age ≥ 55
• Free from cardiometabolic disease
• Body mass index of 18-35 kg/m2
• Receipt of a normal 12-lead ECG approved by the School Independent Medical Officer
• Capacity to understand and provide their written, informed consent to participate in the study protocol

Exclusion Criteria:

• Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise
• Any current, or past medical (last five years), history of any cardiovascular, respiratory, cancer, renal, hepatic, gastrointestinal, haematological, lymphatic, neurological, psychiatric, or any other disease or diseases.
• Any regular medication for the last five years (not including acute courses of treatment of less than one month for discrete, resolved conditions).
• Medications that may influence physiological responses to the passive heating intervention Uncontrolled hypertension (≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic)
• Body mass index of > 35 kg/m2
• Recent long-term exposure to a hot climate (within the previous three months)
• Current smoker (or have stopped smoking within the previous three months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Passive heating intervention; ~3x per week of 1 h hot water immersion (to the clavicle, @40°C, rectal temperature ~38.5°C and <39°C) sessions over a period of 6 weeks.	Other: Passive heating; ~3x per week of 1 h hot water immersion (to the clavicle, @40°C, rectal temperature ~38.5°C and <39°C) sessions over a period of 6 weeks.
No Intervention: Control; 6 weeks of no hot water immersion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial artery flow-mediated dilation	Percentage change from baseline in brachial artery diameter assessed by ultrasound.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular function	Change from baseline in microvascular function as assessed via iontophoresis on the forearm with acetylcholine (ACh) and Insulin, Area under the curve is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Stroke volume	Change from baseline in stroke volume measured noninvasively via thoracic impedance. mL/m^2 is the unit	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Total peripheral resistance	Change from baseline in total peripheral resistance measured noninvasively via thoracic impedance.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Cardiac output	Change from baseline in cardiac output measured noninvasively via thoracic impedance. L/min is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Mean arterial pressure	Change from baseline in resting mean arterial pressure. mmHg is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Systolic blood pressure	Change from baseline in resting systolic blood pressure. mmHg is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Diastolic blood pressure	Change from baseline in resting diastolic blood pressure. mmHg is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Intracellular HSP27 concentration	Change from baseline in resting iHSP27 concentrations? Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Intracellular HSP60 concentration	Change from baseline in resting iHSP60 concentrations? Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Intracellular HSP70 concentration	Change from baseline in resting iHSP70 concentrations? Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Intracellular HSP90 concentration	Change from baseline in resting iHSP90 concentrations? Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Plasma eHSP27 concentration	Change from baseline in resting plasma eHSP27 concentrations? Measured via ELISA	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Plasma eHSP60 concentration	Change from baseline in resting plasma eHSP60 concentrations? Measured via ELISA.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Plasma eHSP70 concentration	Change from baseline in resting plasma eHSP70 concentrations? Measured via ELISA.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Plasma eHSP90 concentration	Change from baseline in resting plasma eHSP90 concentrations? Measured via ELISA.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Reaction time	Change in reaction time in response to a heating challenge. Assessed using ANAM: Automated Neurophysiological Assessment Metrics.	Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion
Logical reasoning	Change in logical reasoning in response to a heating challenge. Assessed using ANAM: Automated Neurophysiological Assessment Metrics.	Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion
Memory	Change in memory in response to a heating challenge. Assessed using ANAM: Automated Neurophysiological Assessment Metrics.	Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion
Cerebral oxygenation	Change in cerebral oxygenation in response to a heating challenge. Assessed using Near-infrared spectroscopy (NIRS) attached to the forehead.	Pre and post 6 weeks of the passive heating intervention during the first and final heating visits at time points of pre-hot water immersion, 0 hours post and 3 hours post hot water immersion
Maximum quadriceps strength	Change from baseline in quadriceps strength. Assessed using an isokinetic dynamometer.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Maximum grip strength	Change from baseline in grip strength. Assessed using a hand grip dynamometer.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Lower extremity function	Change from baseline in lower extremity function. Assessed using the Short Physical Performance Battery (balance, walking speed and sit to stand) .	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Quadriceps muscle electrical activity	Change from baseline in quadriceps muscle electrical activity. Assessed using electromyography (EMG) on the vastus lateralis of the dominant leg.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Balance capacity	Does chronic passive heating improve balance? Assessed using motion capture and force plates.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Gait characteristics	Change from baseline in gait characteristics. Assessed using motion capture and force plates.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Total minutes of physical activity (light, moderate, moderate to vigorous physical activity).	Change from baseline in physical activity levels. Assessed using wrist-worn accelerometry.	Pre and during the final week of 6 weeks of passive heating and pre and during the final week of 6 weeks no intervention with 6 weeks washout between arms
Sleep efficiency (time in bed + time asleep)	Change from baseline in sleep efficiency. Assessed using wrist-worn accelerometry.	Pre and during the final week of 6 weeks of passive heating and pre and during the final week of 6 weeks no intervention with 6 weeks washout between arms
Brachial and carotid artery blood flow velocity	Change from baseline in blood flow velocity of the brachial artery and right common carotid artery as assessed via ultrasound. cm/s is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Carotid vessel diameter	Change from baseline in vessel diameter of the right common carotid artery as assessed via ultrasound. mm is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Carotid intima-media thickness	Change from baseline in intima-media thickness of the right common carotid artery as assessed via ultrasound. mm is the unit	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Carotid compliance	Change in compliance of the right common carotid artery and return to baseline as assessed via ultrasound. µm^2 per kilopascal is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Carotid distensibility	Change in distensibility of the right common carotid artery and return to baseline as assessed via ultrasound. 10^-3/kPa is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms
Carotid stiffness	Change in stiffness of the right common carotid artery and return to baseline as assessed via ultrasound. Meters per second is the unit.	Pre and post 6 weeks of passive heating and pre and post 6 weeks no intervention with 6 weeks washout between arms

Collaborators and Investigators

• Sponsor: University of Portsmouth
• Investigators: Study Director: Zoe Saynor, PhD, University of Portsmouth

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Actual): June 6, 2025
• Study Completion (Actual): June 6, 2025

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Endothelial function; Cognitive function; Muscle strength; Passive heating; Heat shock proteins
• Other Study ID Numbers: UoPCPHHOA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No