Heat-shock proteins

Don't use sauna, a supplement or a drug to raise your heat-shock proteins: there is no evidence in people that raising them improves protein quality control or health. Use the sauna for the reasons that have outcome data.

What they are

Molecular chaperones shepherd other proteins into the right shape and rescue them when heat, oxidation or crowding knocks them out of it. The best-known are the heat-shock proteins (HSP70, HSP90 and a family of small ones), named because they surge when a cell is heated. Their master switch is HSF1 (heat shock factor 1), a protein that controls which genes get switched on; it sits dormant until stress activates it and then turns on the whole chaperone programme.^[1] They are one arm of the system described in loss of proteostasis.

In animals, more is not simply better

In the worm C. elegans, extra copies of the master switch (hsf-1, the worm's version of HSF1) extend lifespan.^[2] But an engineered version of it extended lifespan without raising chaperones at all, working instead through the cell's structural scaffolding, so "more chaperones, longer life" is not established even in worms.^[3]

Mice engineered to make extra human HSF1 got a better response to a challenge, but their everyday chaperone levels barely shifted, and no aging or lifespan endpoint was measured at all.^[4] One research group gave old and middle-aged male mice a nasal spray of the human chaperone Hsp70 for the rest of their lives and reported median lifespan up by about 10–16%.^[5] The groups were small (25–34 mice each), the result has never been repeated, and the untreated mice died young, at a median of about 19–20 months, against the roughly 30 months a well-run study's control animals should reach; when controls die early, a treatment can look better than it is.^[6]

Does heat raise them in people?

Inconsistently, and only as a marker. The most-cited study is not a sauna study: 25 healthy university-age adults sat in a heat chamber at 73 °C for 30 minutes, and in the 13 who gave blood samples a circulating heat-shock protein (HSP72, from the HSP70 family) rose by 48.7%, but with a standard deviation of ±53.9%, so the variation between people exceeded the average effect.^[7] What rises in the blood is heat-shock protein outside cells, which acts as a stress and immune signal; it is not evidence that the chaperones inside your cells are folding proteins better.

Studies that took muscle samples get closer, and disagree:

• Heating one thigh with deep-tissue diathermy for 2 hours a day over 6 days raised muscle HSP70 by about 45% and HSP90 by about 38% in 20 adults.^[8]
• In 7 active young men, an hour of soaking one leg in hot water raised none of the chaperones measured.^[9]
• In 7 young adults, 3 hours of leg heating raised the genetic instructions for HSP72 without raising the protein itself.^[10]

A 2025 meta-analysis pooling blood and tissue measurements found no significant change in heat-shock proteins after either single or repeated heat sessions, though it had few studies to work with.^[11] None of the muscle studies was a sauna, and none of these studies measured whether proteins actually fold better.

Exercise gives one small hint in the other direction: in a trial of 38 older adults, muscle samples showed about 35% more HSP70 than in young adults who had not been training, and 12 weeks of strength training brought it down by roughly 30%, suggesting less cellular stress.^[12] That is a change in a marker, not proof that proteins are handled better.

A drug built to boost them failed

Arimoclomol turns up the cell's heat-shock response, so it is the closest thing to a "chaperone booster" tested in people. In 152 patients with inclusion body myositis, a muscle disease marked by clumped protein, 20 months on the drug did not slow the loss of function compared with placebo, and more people stopped because of side effects (18% vs 5%).^[13] In 239 patients with early amyotrophic lateral sclerosis (ALS), it did no better than placebo on a combined score of function and survival over 76 weeks, and more people quit because of side effects (16% vs 5%); the authors add that a higher dose would not have been tolerated.^[14] If boosting chaperones does not help in diseases defined by misfolded protein, there is little reason to expect it to help a healthy person.

The cancer caution

HSF1 is not a free lunch. Deleting it protects mice from tumours driven by mutations in RAS, one of the commonest cancer-causing genes, or by a frequent cancer mutation in p53, a gene that normally suppresses tumours, and human cancer cell lines depend on HSF1 much more than non-cancerous cells do, because malignant cells lean on the chaperone system to survive.^[15] Anything that durably turns HSF1 up in a healthy adult is turning a knob that cancers also like to see turned up.

What to do

1. Use the sauna for the reasons that have outcome data behind them, not to tune your chaperones.
2. Ignore products sold to "activate heat-shock proteins". No supplement or drug has been shown to improve protein quality control in people.

Further reading

• Hipp MS, Kasturi P, Hartl FU. The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol 2019.^[16]
• Iguchi M, et al. Heat stress and cardiovascular, hormonal, and heat shock proteins in humans. J Athl Train 2012 — heat chamber, not sauna.^[17]
• Hafen PS, et al. Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscle. J Appl Physiol (1985) 2018 — muscle biopsies.^[18]
• Price BS, et al. Heat thermotherapy to improve cardiovascular function and cardiometabolic health: A systematic review and meta-analysis. Exp Physiol 2025.^[19]
• Benatar M, et al. Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Neurol 2024.^[20]
• Dai C, et al. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 2007.^[21]