Hyperthermic Conditioning’s Role In Increasing Endurance, Muscle Mass, and

Neurogenesis

By Rhonda Perciavalle Patrick, Ph.D.

NOTE: The contents of this report were published on Tim Ferriss’s Four Hour Blog.
No part of this report may be reproduced, scanned, or distributed in any printed or
electronic form without permission.

For the most part, people don’t like to get hot.

The massive indoor climate control systems and pleasantly chilled water fountains
found in most gyms speak to this fact. There are some exceptions — Bikram yoga,
for example — but they’re few and far between.

But here’s the surprise: increasing your core temperature for short bursts is not
only healthful, it can also dramatically improve performance.

This is true whether it’s done in conjunction with your existing workout or as an
entirely separate activity. I’m going to explain how heat acclimation through sauna
use (and likely any other non-aerobic activity that increases core body temperature)
can promote physiological adaptations that result in increased endurance, easier
acquisition of muscle mass, and a general increased capacity for stress tolerance. I
will refer to this concept of deliberately acclimating yourself to heat, independent of
working out, as “hyperthermic conditioning.”

I'm also going to explain the positive effects of heat acclimation on the brain,
including the growth of new brain cells, improvement in focus, learning, and
memory, and ameliorating depression and anxiety. In addition, you’ll learn how
modulation of core temperature is even responsible for or plays a major role in
what has been termed the "runner's high" via an interaction between the
dynorphin/beta-endorphin opioid systems.

The Effects of Heat Acclimation on Endurance

If you’ve ever run long distances or exercised for endurance, it’s intuitive that
increased body temperature will ultimately induce strain, attenuate your endurance
performance, and accelerating exhaustion. What might not be as intuitive is this:
acclimating yourself to heat independent of aerobic physical activity through sauna
use induces adaptations that reduce the later strain of your primary aerobic activity.

Hyperthermic conditioning improves your performance during endurance training

activities by causing adaptations, such as improved cardiovascular and
thermoregulatory mechanisms (I will explain what these mean) that reduce the
negative effects associated with elevations in core body temperature. This helps
optimize your body for subsequent exposures to heat (from metabolic activities)
during your next big race or even your next workout.

Just a few of the physiological adaptations that occur subsequent to acclimation to

heat include:

● Improved cardiovascular mechanisms and lower heart rate.1

● Lower core body temperature during workload (surprise!)
● Higher sweat rate and sweat sensitivity as a function of increased
thermoregulatory control.2
● Increased blood flow to skeletal muscle (known as muscle perfusion) and
other tissues.2
● Reduced rate of glycogen depletion due to improved muscle perfusion.3
● Increased red blood cell count (likely via erythropoietin).4
● Increased efficiency of oxygen transport to muscles.4
Watch Youtube Video Here.

Hyperthermic conditioning optimizes blood flow to the heart, skeletal muscles, skin,
and other tissues because it increases the plasma volume. This causes endurance
enhancements during your next workout or race when your core body temperature
is elevated again, and here is why:

Being heat acclimated enhances endurance by the following mechanisms:

1. t increases plasma volume and blood flow to the heart (stroke volume).2,5
This results in reduced cardiovascular strain and lowers the heart rate for
the same given workload.2 These cardiovascular improvements have been
shown to enhance endurance in highly trained as well as untrained
athletes.2,5,6

2. It increases blood flow to the skeletal muscles, keeping them fueled with
glucose, esterified fatty acids, and oxygen. The increased delivery of nutrients
to muscles reduces their dependence on glycogen stores. Endurance athletes
often hit a “wall” when they have depleted their muscle glycogen stores.
Hyperthermic conditioning has been shown to reduce muscle glycogen use
by 40%-50% compared to before heat acclimation.3,7 This is presumably due
to the increased blood flow to the muscles.3 In addition, lactate accumulation
in blood and muscle during exercise is reduced after heat acclimation.5

3. It improves thermoregulatory control, which operates by activating the

sympathetic nervous system and increasing the blood flow to the skin and,
thus the sweat rate. This dissipates some of the core body heat. After
acclimation, sweating occurs at a lower core temperature and the sweat rate
is maintained for a longer period.2
Okay, up until this point we've talked about general mechanisms by which
performance gains occur as a consequence of heat acclimation. Equally important,
however, is the sort of real world difference that might be expected. So what sort of
gains can you anticipate?

One study demonstrated that a 30-minute sauna session two times a week for
three weeks post-workout increased the time that it took for study
participants to run until exhaustion by 32% compared to baseline.4

The 32% increase in running endurance in the aforementioned study was

accompanied by a 7.1% increase in plasma volume and 3.5% increase in red blood
cell (RBC) count.4 This increased red blood cell count accompanying these
performance gains feed right back into those more general mechanisms we talked
about earlier, the most obvious of which being: more red blood cells increase
oxygen delivery to muscles. It is thought that heat acclimation boosts the RBC count
through erythropoietin (EPO) because the body is trying to compensate for the
corresponding rise in plasma volume.4

In other words, hyperthermic conditioning through sauna use doesn’t just make you
better at dealing with heat; it makes you better, period. I do want to mention that
while these gains were made with a small sample size (N=6) some of the later
studies that I will point out reinforce this conclusion.

The Effects of Hyperthermic Conditioning on Muscle Growth (Hypertrophy)

Exercise induces muscle hypertrophy. Heat induces muscle hypertrophy. Both of
these together synergize to induce hyper-hypertrophy.

Okay, but seriously… Here are a few of the basics of how muscle hypertrophy
works: muscle hypertrophy involves both the increase in the size of muscle cells
and, perhaps unsurprisingly, an accompanying increase in strength. Skeletal muscle
cells do contain stem cells that are able to increase the number of muscle cells but
hypertrophy instead generally involves an increase in size rather than number.

So what determines whether your muscle cells are growing or shrinking

(atrophying)?
A shift in the protein synthesis to degradation ratio…and an applied workload on
the muscle tissue (of course). That’s it.

At any given time your muscles are performing a balancing act between NEW
protein synthesis and degradation of existing proteins. The important thing is your
net protein synthesis, and not strictly the amount of new protein synthesis
occurring. Protein degradation occurs both during muscle use and disuse. This is
where hyperthermic conditioning shines: heat acclimation reduces the amount of
protein degradation occurring and as a result it increases net protein synthesis
and, thus muscle hypertrophy (as is the case during muscle use). Hyperthermic
conditioning is known to increase muscle hypertrophy by increasing net protein
synthesis through three important mechanisms:

● Induction of heat shock proteins.8,9

● Robust induction of growth hormone.1
● Improved insulin sensitivity.10

Exercise induces both protein synthesis and degradation in skeletal muscles but,
again, it is the net protein synthesis that causes the actual hypertrophy. When you
exercise, you are increasing the workload on the skeletal muscle and, thus, the
energetic needs of your muscle cells. The mitochondria found in each of these cells
kick into gear in order to help meet this demand and start sucking in the oxygen
found in your blood in order to produce new energy in the form of ATP. This process
is called oxidative phosphorylation. A by-product of this process, however, is the
generation of oxygen free radicals like superoxide and hydrogen peroxide, which is
more generally referred to simply as “oxidative stress”.

Heat Stress Triggers Heat Shock Proteins That Prevent Protein Degradation
Oxidative stress is a major source of protein degradation. For this reason, any means
of preventing exercise-induced oxidative protein damage and/or repairing damaged
proteins, while keeping the exercise induced protein synthesis, will ultimately cause
a net increase of protein synthesis and therefore will be anabolic.

Heat shock proteins (or HSPs), as the name implies, are induced by heat and are a
prime example of hormesis. Intermittent exposure to heat induces a hormetic
response (a protective stress response), which promotes the expression of a gene
called heat shock factor 1 and subsequently HSPs involved in stress resistance.

● HSPs can prevent damage by directly scavenging free radicals and also by
supporting cellular antioxidant capacity through its effects on maintaining
glutathione.8,9
● HSPs can repair misfolded, damaged proteins thereby ensuring proteins have
their proper structure and function.8,9

Okay, let’s take a step back from the underlying mechanisms and look at the big
picture of heat acclimation in the context of increasing muscle hypertrophy:

It has been shown that a 30-minute intermittent hyperthermic treatment at 41°C

(105.8°F) in rats induced a robust expression of heat shock proteins (including
HSP32, HSP25, and HSP72) in muscle and, importantly, this correlated with 30%
more muscle regrowth than a control group during the seven days subsequent
to a week of immobilization.8 This HSP induction from a 30-minute whole body
hyperthermic exposure can persist for up to 48 hours after heat shock.8,9 Heat
acclimation actually causes a higher basal (such as when not exercising) expression
of HSPs and a more robust induction upon elevation in core body temperature (such
as during exercise).11-13 This is a great example of how a person can theoretically use
hyperthermic conditioning to increase their own heat shock proteins and thereby
reap the rewards.

Heat Stress Triggers A Massive Release of Growth Hormone

Another way in which hyperthermic conditioning can be used to increase anabolism
is through a massive induction of growth hormone.1,14,15 Many of the anabolic effects
of growth hormone are thought to be mediated by IGF-1, which is synthesized
(mainly in liver but also in skeletal muscle) in response to growth hormone. There
are two important mechanisms by which IGF-1 promotes the growth of skeletal
muscle:
1. Activation of the mTOR pathway, which is responsible for protein
synthesis.16
2. Inhibition of FOXO activation, which inhibits protein degradation. 16

Mice that have been engineered to express high levels of IGF-1 in their muscle
develop skeletal muscle hypertrophy, can combat age-related muscle atrophy, and
retained the same regenerative capacity as young muscle. 17,18 In humans, it has
been shown that the major anabolic effects of growth hormone in skeletal muscle
may be due to inhibition of muscle protein degradation (anti-catabolic) and thereby
increasing net protein synthesis.16 In fact, growth hormone administration to
endurance athletes for four weeks has been shown to decrease muscle protein
oxidation (a biomarker for protein degradation) and degradation by 50%.19

My point is good news. You don’t need to take exogenous growth hormone. Sauna
use can cause a robust release in growth hormone, which varies according to time,
temperature, and frequency.1,15

For example, two 20-minute sauna sessions at 80°C (176°F) separated by a

30-minute cooling period elevated growth hormone levels two-fold over baseline.1,15
Whereas, two 15-minute sauna sessions at 100°C (212°F) dry heat separated by a
30-minute cooling period resulted in a five-fold increase in growth hormone.1,15
However, what’s perhaps more amazing is that repeated exposure to whole-body
hyperthermia through sauna use has an even more profound effect on boosting
growth hormone immediately afterward: two one-hour sauna sessions a day at
80°C (176°F) dry heat (okay, this is a bit extreme) for 7 days was shown to
increase growth hormone by 16-fold on the third day.14 The growth hormone
effects generally persist for a couple of hours post-sauna.1 It is also noteworthy,
however, is that sauna use and exercise can synergize to significantly elevate growth
hormone when used in conjunction with each other.20

Increased Insulin Sensitivity

Insulin is an endocrine hormone that primarily regulates glucose homeostasis,
particularly by promoting the uptake of glucose into muscle and adipose tissue. In
addition, insulin also plays a role in protein metabolism, albeit to a lesser degree
than IGF-1. Insulin regulates protein metabolism in skeletal muscle by the two
following mechanisms:

1. It increases protein synthesis by stimulating the uptake of amino acids

(particularly BCAAs) into skeletal muscle.21
2. It decreases protein degradation through inhibition of the proteasome, which
is a protein complex inside cells that is largely responsible for the
degradation of most cellular proteins.22

In humans, there is more evidence indicating that the major anabolic effects of
insulin on skeletal muscle are due to its inhibitory action on protein degradation.

For example, insulin infusion in healthy humans, which increased insulin to normal
physiological postprandial (after a meal) levels, suppressed muscle protein
breakdown without significant affecting muscle protein synthesis. 21,23 In contrast,
insulin deficiency (such as in type 1 diabetes mellitus) and insulin resistance (to a
lesser extent) are both associated with increased skeletal muscle breakdown. 22,24

For this reason, hyperthermic conditioning may also lend itself to promoting muscle
growth by improving insulin sensitivity and decreasing muscle protein catabolism.
Intermittent hyperthermia has been demonstrated to reduce insulin resistance in an
obese diabetic mouse model. Insulin resistant diabetic mice were subjected to 30
minutes of hyperthermic treatment, three times a week for twelve weeks. This
resulted in a 31% decrease in insulin levels and a significant reduction in
blood glucose levels, suggesting re-sensitization to insulin.10 The hyperthermic
treatment specifically targeted the skeletal muscle by increasing the expression of a
type of transporter known as GLUT 4, which is responsible for the transporting of
glucose into skeletal muscle from the bloodstream. Decreased glucose uptake by
skeletal muscle is one of the mechanisms that leads to insulin resistance.

Relevance for Muscle Injury

Muscle atrophy primarily occurs as a consequence of tipping the balance towards
protein degradation and away from protein synthesis in the muscles. This is
particularly important after muscle injury, which causes immobilization and disuse
of muscles for some time. Of course, this does result in some muscle atrophy. Animal
studies using rats have shown that whole body hyperthermia at 41°C (105.8°F) for
30 minutes and 60 minutes attenuates hindlimb muscle atrophy during disuse by
20% and 32%, respectively.9,25 In order to return to a hypertrophic state after
injury, muscle regrowth (“reloading”) must occur. Muscle reloading, while
important for hypertrophy, induces oxidative stress particularly after periods of
disuse, which slows the rate of muscle regrowth. A 30-minute hyperthermic
treatment at 41°C (105.8°F) increased soleus muscle regrowth by 30% after
reloading as compared to non-hyperthermic treatment in rats.8 The effects of whole
body hyperthermia on preventing muscle atrophy and increasing muscle regrowth
after immobilization were shown to occur as a consequence of elevated HSP
levels.8,9,25

During injury you may be immobilized but you don’t have to be very mobile to sit in
the sauna a few times a week to boost your HSPs! This is a clear win in the injury
and recovery department. Remember, hyperthermic conditioning (from sauna use)
results in an elevation in HSP levels under normal conditions and an even greater
boost during exercise (or when core body temperature is elevated).11-13

Relevance for Rhabdomyolysis

Hyperthermic conditioning may also be able to protect against rhabdomyolysis
(muscle breakdown due to severe muscle overuse) through the induction of HSP32
also known as heme oxygenase 1.26,27 Rhabdomyolysis releases myoglobin, a
byproduct from broken down muscle tissue, into the bloodstream causing kidney
failure. Since myoglobin is a heme-containing protein, HSP32 (heme oxygenase 1)
can rapidly degrade myoglobin before it has toxic effects on the kidney.26,27 In fact,
induction of HSP32 in rats has been shown to protect against rhabdomyolysis in
rats.26 Again, heat acclimation causes a higher basal expression of HSPs and a more
robust expression upon heat stress. 11-13 The more heat acclimated your body is (the
pre-conditioning is key here), the higher your HSP32 expression will be during
physical activity and this will protect your kidneys from the toxic myoglobin
breakdown product.

That’s a sweet deal.

Longevity
In flies and worms, a brief exposure to heat treatment has been shown to increase
their lifespan by up to 15% and it’s been shown that this effect is specifically
mediated by HSPs.28-30 One possible explanation for the increased lifespan is heat
stress is known to induce hormesis. This boosts the expression of heat shock
proteins, which are known to improve longevity.

While studying the effects of something like hyperthermic conditioning on longevity

is inherently hard in humans (obviously), there have been some preliminary
positive associations with variations in the HSP70 gene associated with increased
expression and longevity.31

Effects of Heat Stress and Acclimation on The Brain

One of the ways that the brain actually responds to injury on the cellular level is
increased HSP production. This includes ischemic injury (stroke), traumatic injury,
and excitotoxicity (epileptic).32 What complicates things, however, in the context of
"hyperthermic conditioning" (or deliberate heat acclimation) is that while on the
one hand hyperthermia has been shown to reduce the frequency of seizures and the
damage they cause post-conditioning, hyperthermia can actually increase the
damage caused by seizures if they occur during a period of heat stress. In other
words, the stress and its damaging effects are additive.33,34

That (and it’s implicit warning) being said, sauna-induced hyperthermia has been
shown to induce a robust activation of the sympathetic nervous system and the
hypothalamic-pituitary-adrenal (HPA) axis. One study demonstrated that men that
stayed in the sauna that was heated to 80°C (176°F) until subjective exhaustion
increased norepinephrine by 310%, had a 10-fold increase in prolactin, and actually
modestly decreased cortisol.1,15 Similarly, in another study, women that spent
20-minute sessions in a dry sauna twice a week had a 86% increase in
norepinephrine and a 510% increase in prolactin after the session.35

Norepinephrine helps with focus and attention while prolactin promotes myelin
growth, which makes your brain function faster, which is key in repairing nerve cell
damage.36,37 In addition to increasing norepinephrine, heat acclimation has actually
been shown to increase biological capacity to store norepinephrine for later
release.38 In light of the fact that the norepinephrine response to exercise has been
demonstrated to be blunted in children with ADHD and that norepinephrine
reuptake inhibitors (NRI) are frequently prescribed to treat ADHD (among other
things), use of heat stress and subsequent acclimation should be tested for it’s
effectiveness as an interesting alternative therapeutic approach.39

Neurogenesis
Heat stress has been shown to increase the expression of brain-derived
neurotrophic factor (BDNF) more than exercise alone when used in conjunction
with exercise.

This is important because BDNF increases the growth of new brain cells as well as
the survival of existing neurons. An increase in neurogenesis is thought to be
responsible for enhancing learning. 40 BDNF’s role in the brain is also to modulate
neuronal plasticity and long-term memory, while also having been shown to
ameliorate anxiety and depression from early-life stressful events.41 In addition to
the function BDNF plays in the brain when it’s released as a consequence of exercise,
BDNF is also secreted by muscle where it plays a role in muscle repair and the
growth of new muscle cells.42

While BDNF has specifically been shown to play some role in ameliorating
depression from early-life stressful events, whole-body hyperthermia has also been
demonstrated to improve depression in cancer patients.43 In this particular study,
however, it was speculated that beta-endorphin (which is also induced by
hyperthermia), not BDNF, may have been the agent responsible for this effect. As an
aside, one of the reasons whole-body hyperthermia is sometimes used with cancer
patients is because it can enhance the effects of chemotherapeutic agents.44

The Runner’s High and The Role of Dynorphin

Ever wonder what is responsible for the “runner’s high” or the post-exercise high, in
general? You may think it is due to endorphins but that’s not the whole story.
Beta-endorphins are endogenous (natural) opioids that are a part of the body’s
natural painkiller system, known as the mu opioid system, which block pain
messages from spreading from the body to the brain in a process called
antinociception. You are probably familiar with this concept, but what is less well
known is that the body also produces a peptide known as dynorphin (a “kappa
opioid”), which is generally responsible for the sensation of dysphoria. The
discomfort experienced during intense exercise, exposure to extreme heat (such as
in a sauna), or eating spicy food (capsaicin) is due to the release of dynorphin. The
release of dynorphin causes an upregulation and sensitization of mu opioid
receptors, which interact with beta-endorphin.45 This process is what underlies the
“runner’s high” and is directly precipitated by the discomfort of physical exercise.
Translation: the greater the discomfort experienced during your workout or sauna,
the better the endorphin high will be afterward. Now you understand the
underlying biological mechanism that explains this.

Why is this relevant to hyperthermic conditioning and sauna use?

Heat stress from heat exposure in a dry sauna has been demonstrated to cause a
potent increase in beta-endorphin levels, even more than exercise alone.1,15

A study in rats explains this somewhat: dynorphin delivered directly into a part of
the hypothalamus in the brains of rats triggers a drop in their body temperature,
while blocking dynorphin with an antagonist was shown to prevent this same
response. Similarly, mu receptor agonists have been shown to induce increases in
body temperature in rats.46 What this seems to imply is that perhaps, by deliberately
manipulating your body temperature you are actually directly engaging the mu
(endorphin) and kappa opioid (dynorphin) systems since they clearly play a role in
temperature regulation in general.

In Conclusion
To recap and drive the point home: acclimating your body to heat stress by
intermittent whole-body hyperthermia through sauna use (“hyperthermic
conditioning”) has been shown to:

Enhance endurance by:

● Increasing nutrient delivery to muscles thereby reducing the
depletion of glycogen stores.
● Reducing heart rate and reducing core temperature during workload.
Increase muscle hypertrophy by preventing protein degradation through
the following three means:
● Induction of heat shock proteins and a hormetic response (which has
also been shown to increase longevity in lower organisms).
● Cause a massive release of growth hormone.
● Improving insulin sensitivity.
 ***NOTE*** It also accomplishes this arguably without the same risk that
might otherwise be associated with exogenous or supraphysiological
levels of other hormones, like growth hormone.

Hyperthermic conditioning also has robust positive effects on the brain:

● Increases the storage and release of norepinephrine, which improves
attention and focus.
● Increases prolactin, which causes your brain to function faster by
enhancing myelination and helps to repair damaged neurons.
● Increases BDNF, which causes the growth of new brain cells, improves
the ability for you to learn new information and retain it, and
ameliorates certain types of depression and anxiety.
● Causes a robust increase in dynorphin, which results in your body
becoming more sensitive to the ensuing endorphins.

Life is stressful. When you exercise you are essentially forcing your body to become
more resilient to stress (somewhat paradoxically) through stress itself.

Hyperthermic conditioning is a novel and possibly effective tool that can improve
your resistance to the sort of stress associated with fitness pursuits as well as some
that are not traditionally associated with fitness such as the protective effects of
HSPs on various types of stress. That being said, deliberately applied physical
stress, whether heat stress or ordinary exercise, is something that requires
caution.

You shouldn’t avoid it altogether, but you should use good common sense, not
overwhelm yourself, and make sure to know your limits. (NOTE: you should not
drink alcohol before or during sauna use as it increases the risk of death).47
Personal variation probably comes into play when finding your own sweet spot for
building thermal tolerance while avoiding over-extending yourself.

I believe that hyperthermic conditioning in general may be worth a closer look as a

tool in the toolbox of athletes. Perhaps it can be used for much more than just
relaxation?

But no matter how enthusiastic you might be, remember:

Heat responsibly and with someone else, never alone.

Never heat yourself while drunk, and friends don’t let friends sauna drunk.
If you are pregnant or have any medical condition, saunas are not for you. Speak
with your doctor before starting this or any regimen involving physical stressors.

Be careful, ladies and gents.

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