In 1962, an Italian geneticist named Ferruccio Ritossa accidentally left his fruit flies in a heated incubator. When he examined their chromosomes, he found something unexpected: the heat had triggered a burst of gene activity, producing proteins he’d never seen before. He wrote up the findings and submitted them for publication. The paper was rejected. Reviewers said it lacked biological importance.
Six decades later, those proteins – now called heat shock proteins – sit at the centre of one of the most compelling explanations for why regular sauna use is associated with large reductions in cardiovascular mortality. A Finnish cohort study tracking over 2,300 men found that those who used a sauna four to seven times per week had a 63% lower risk of fatal cardiovascular events compared to those who went once a week. That connection is no longer a curiosity. It may be the mechanism that makes the numbers make sense.
This article explains that mechanism. It quantifies what happens inside your cells during a single sauna session, shows how the response changes with consistent use, and addresses a complication that most sauna advocates ignore: the possibility that cold water immersion suppresses the very proteins heat exposure creates.
Stress as signal: the hormesis frame
One concept organises everything that follows: hormesis. A moderate, short-lived stress reliably triggers adaptive responses that leave you more resilient than before. Exercise works this way. So does heat.
When your core temperature rises inside a sauna, your cells don’t passively endure it. They launch a coordinated molecular defence programme, and the centrepiece of that programme is the rapid production of heat shock proteins.
What heat shock proteins actually do
Heat shock proteins (HSPs) are molecular chaperones — they supervise the folding, repair, and disposal of other proteins in your cells. Proteins must fold into precise three-dimensional shapes to function, and heat, oxidative stress, or inflammation can cause them to misfold and clump together. HSPs bind to damaged or partially unfolded proteins and either refold them correctly or escort them to the cell’s disposal machinery.
Two families matter most. HSP70 is the first responder: rapidly induced by heat stress, it stabilises unfolding proteins and prevents aggregation. HSP90 is more of a specialist, supporting the maturation of signalling proteins involved in inflammation, immune function, and cell survival.
Rising intracellular temperature triggers the pathway: it releases a transcription factor called HSF1, normally kept inactive by binding to existing HSPs. Free HSF1 migrates to the cell nucleus, binds to specific DNA sequences called heat shock elements, and switches on the genes that produce new heat shock proteins. Within minutes, the process is underway.
What a single sauna session does: the acute response
Anyone asking about heat shock proteins and sauna wants to know one thing: how much? The best available data comes from a 2023 study in the International Journal of Hyperthermia that measured serum HSP70 before and after a single Finnish sauna session.
In trained individuals, regular sauna users, a single session significantly increased circulating HSP70 by 144%. In untrained individuals, the increase was 271%.
That difference is itself informative. The untrained body, encountering significant heat stress for the first time, mounts a larger emergency response. The trained body still responds, but its baseline defences are already higher, so the acute spike is smaller. Hormesis in action: the stress response recalibrates over time, raising your resting level of protection rather than producing ever-larger emergency surges.
Longitudinal data from the same study confirmed this pattern. After ten sessions, the acute HSP70 increase attenuated — the same thermal load provoked a smaller alarm because the cells had adapted. Temperature and duration shape the magnitude of response: the Finnish study used traditional conditions (around 80–100°C, sessions of 15 to 20 minutes), and lower temperatures or shorter durations produce smaller effects. There appears to be a threshold below which HSF1 activation is minimal, though the exact boundary varies with hydration, fitness, and heat acclimatisation.
What regular sauna use does: the chronic adaptation
If a single session produces a temporary spike, regular practice raises the floor.
A 12-week randomised controlled trial by Paunovic and colleagues assigned 40 participants to either twice-weekly sauna sessions (80°C, 20 minutes) or a control group. After 12 weeks, the sauna group showed a significant 38% increase in resting HSP70 levels and a 21% increase in resting HSP90 compared to controls.
These are baseline measurements, taken at rest and days after the last session. Consistent sauna use doesn’t just trigger a temporary defence — it remodels the cellular environment so that protective chaperone proteins are present in higher concentrations all the time. A separate smaller study found elevated HSP72 after just six consecutive days of exposure, suggesting the adaptation begins quickly and doesn’t require months to initiate.
One adjacent finding worth noting: a 2017 crossover study by Hoekstra and colleagues found that 60 minutes of passive heating in 40°C water produced an HSP70 response equivalent to 60 minutes of moderate cycling. Passive heat can trigger the same molecular signal as moderate aerobic exercise, which matters for people who are injured, elderly, or unable to exercise at sufficient intensity. Sauna is not a replacement for physical activity, but it activates overlapping pathways.
From molecule to mortality: why HSPs matter for health
Elevated HSP levels are not inherently meaningful unless they connect to outcomes the body can feel or a population study can measure. Dr Jari Laukkanen’s Finnish cohort becomes essential here.
Dr Jari Laukkanen, a cardiologist at the University of Eastern Finland, followed 2,315 middle-aged men for over 20 years and found a clear dose-response relationship: the more frequently men used a sauna, the lower their risk of dying. Men in the highest frequency group (4–7 sessions per week) had a 63% lower risk of sudden cardiac death and a 37% reduction in premature death from all causes, compared to once-a-week users.
This is epidemiology, not proof of causation. But HSPs provide the most plausible biological bridge between those sessions and those outcomes.
Cardiovascular protection is where the evidence is strongest. HSP70 and HSP90 consistently protect cardiomyocytes — the muscle cells of the heart — from ischaemic damage. Research into heat therapy’s cardiovascular mechanisms has shown that HSPs stabilise endothelial function, reduce arterial stiffness, and attenuate the inflammatory cascades that drive atherosclerosis. Intracellular HSPs also suppress NF-κB, one of the master regulators of chronic inflammation, which means the anti-inflammatory effect operates through the same chaperone system rather than a separate pathway. In animal models, HSP overexpression consistently reduces infarct size after simulated heart attacks. In humans, higher circulating HSP70 is associated with lower cardiovascular risk, though the causal direction remains under investigation.
Neuroprotection is earlier-stage but consistent in direction. Because HSPs prevent protein aggregation, they are directly relevant to diseases characterised by it — amyloid plaques in Alzheimer’s, alpha-synuclein in Parkinson’s. Preclinical models show higher HSP expression slowing the toxic accumulation of these misfolded proteins. Human evidence is still building. The brain health benefits tracked in Finnish studies may operate partially through this mechanism.
A comprehensive review in Experimental Gerontology, co-authored by Dr Rhonda Patrick, a biomedical researcher and founder of FoundMyFitness, concluded that repeated sauna use produces dose-dependent reductions in morbidity and mortality through hormetic activation of HSPs and related stress-response pathways.
One necessary caveat. The same chaperone function that protects healthy cells can also protect cancer cells from the stresses designed to kill them, including chemotherapy and radiation. Some tumours overexpress HSP70 and HSP90 as a survival mechanism. There is no evidence linking regular sauna use to increased cancer risk. But HSP biology is not a simple good-news story. The proteins do not distinguish between cells you want to protect and cells you don’t.
The cold complication
Cold exposure has its own molecular story. When core temperature drops, cells produce cold shock proteins, a different family of stress-response molecules. The most studied is RBM3, an RNA-binding protein that Prof Giovanna Mallucci’s lab at the University of Cambridge identified as the principal mediator of cold-induced neuroprotection in mouse models of neurodegeneration. RBM3 appears to preserve synaptic connections and promote structural plasticity in the brain, at least in animals cooled to hypothermic temperatures.
So heat produces HSPs. Cold produces CSPs. Both are stress-adaptation responses with potentially protective effects. For the growing number of people combining sauna and cold plunge — the contrast therapy protocol — the obvious hope is that you get both: the cardiovascular and cellular protection of HSPs plus the neuroprotective benefits of RBM3.
The biology may not be that cooperative.
A 2019 randomised controlled trial by Dr Jackson Fyfe, an exercise physiologist at Deakin University, and colleagues, published in the Journal of Applied Physiology, found that cold water immersion performed after resistance training attenuated the expression of HSP27 and reduced HSP72 protein content in muscle tissue. Cold didn’t merely fail to boost heat shock proteins — it actively suppressed them.
This has direct implications for contrast therapy. If cold exposure dampens the heat shock protein response, then the sequence of sauna followed by cold plunge might partially cancel one of sauna’s most important molecular effects.
Nobody knows yet. Fyfe’s study examined cold water immersion after exercise, not after sauna. No published study has measured dual HSP and CSP expression in a sauna-to-cold-plunge protocol. The interaction effects — timing, temperature differentials, duration of each exposure, which proteins are measured and when — remain genuinely uncharacterised. It is plausible that sufficient recovery time between exposures allows both pathways to activate, or that the suppression is transient and the net effect over weeks of practice is still positive. But these are hypotheses, not findings.
Treating contrast therapy as ‘all the benefits of heat plus all the benefits of cold’ is not supported by the current evidence. Anyone serious about optimising their protocol should hold that uncertainty honestly.
What the proteins tell us
Frequent sauna use correlates with reduced mortality, but causation in humans is not yet proven. The molecular mechanism is well characterised. The epidemiology is strong. The gap between them — the definitive proof that HSPs are the reason frequent sauna users live longer — has not been clinically closed. Patrick has suggested that “in the next 10 years, sauna bathing may very well become part of the standard of care for the prevention and treatment of heart disease.” Given the evidence trajectory, that is a reasonable projection, not a conclusion.
And the contrast therapy question remains open. How heat shock proteins and cold shock proteins relate — whether they compete, coexist, or interact in ways we haven’t yet mapped — is one of the most interesting unanswered questions in thermal biology. For a field that often speaks in certainties, it deserves more attention than it currently receives.
What Ritossa’s rejected paper eventually proved is that cells are listening to temperature. What we are still learning is how to speak to them clearly.
