Dallas Maverick Owner and Yahoo Partner, Mark Cuban on HGH

As a wildly successful entrepreneur and owner of the Dallas Mavericks professional basketball team, Mark Cuban did not become a billionaire by thinking conventionally.

Time and time again, he has proven to be a forward-thinking visionary and is not afraid to go down a different road from the rest of the pack.

He is genuinely a Maverick in every sense of the word.

And that's why he's championing the use of Human Growth Hormone (HGH) for therapeutic use in dealing with injuries suffered by athletes performing at the highest levels.

As the owner of a professional sports franchise, Cuban is acutely aware of the devastating consequences of injuries. Athletes may never recover the abilities they had before the injury, and their fans are cheated out of seeing their favorites in action. The monetary costs to all parties involved are also significant.

Considering his track record, it's not surprising that Cuban is not a person to sit back and mull over an adverse circumstance. He takes action, massive action, regardless of who may approve.

And that's why he has funded a clinical trial to determine if recombinant Human Growth Hormone can speed up recovery from one of the most shared and debilitating sports injuries: anterior cruciate ligament (ACL) surgery.

The two-year, $800,000 exploratory study at the University of Michigan is funded by Cuban's eponymous foundation and was approved by the U.S. Food and Drug Administration (FDA) under a special exemption.

“It’ll be a two-year study that applies HGH to injuries pre-operative to post-operative injury recovery, ” Cuban said before a recent Mavs-Los Angeles Clippers game at the Staples Center.

“So if you’re able to retain more muscle going into an operation because you’re working out and HGH helps your muscle, and you’re able to regain it faster -- then we cut the recovery time.

“And it’ll be geared around one type of injury that has hundreds of thousands of examples a year. So we’ll be able to do a placebo environment without hurting anybody, right? So here’s the way we do it now. And here’s how we do it with HGH. So hopefully it will accelerate recovery.”

To understand the controversy, let's back up and take an in-depth look at HGH, both when used solely for healing injuries, as well as when abused as a performance-enhancing drug (PED).

Most sports fans are aware that HGH has been abused as a steroid for its performance-enhancing effects, and is therefore currently banned for any use in professional basketball, baseball, football, and the Olympics.

The careers of many high-profile athletes have suffered a permanent black mark after being caught using the banned substance (i.e., Bill Romanowski, Jason Giambi, and Andy Pettitte), although Pettitte swears he used Growth Hormone only to rehab an elbow injury...but controversy remains about his adamant denials.

Although many sports-related injuries are genuine, using this drug for rehabilitation is off-label.

The Michigan study will attempt to raise awareness that Human Growth Hormone can help prevent the muscles around the knee joint from weakening past the point of no return after ACL surgery.

Their study will hopefully prove that Growth Hormone when used correctly, can assist getting players back in action, and not boost their performance unnaturally.

This will not be an easy task to unravel the benefits and effects of recombinant HGH for rehabilitation. For starters, HGH use is illegal in many countries worldwide, including the United States, for off-label purposes.

This off-label use, combined with a widespread lack of understanding of the science and potential behind the way HGH works, has deterred research into possible new therapeutic purposes.

Cuban disagrees about the narrowly approved applications of Human Growth Hormone, as do many fellow owners of major sports franchises, as well as many athletes, although the support for more clinical trials with HGH is usually voiced anonymously.

"I love to test and challenge any schools of thought that have not been thought out," he wrote in an August email to ESPN's Outside the Lines. "This partnership was a significant first step toward finding the facts about HGH."

A businessman, usually with a detailed business plan and a specific financial objective, Cuban has no method of activities in this undertaking per se.

This is all about an idea...rethinking HGH...that won't be either practical or profitable for the foreseeable future, if ever, and is sure to encounter stiff resistance along the way.

However,  Cuban's push forward is going to open up new horizons about this vital molecule that is both a protein and hormone.

All top athletes in a wide array of sports possess a freakish talent and have the ability to stop and rotate, switch direction and rapidly speed up, turn and evade (Juke or Juking -- it is what quick movement is sometimes called in athlete slang).

Consequently, their knees and lower quadriceps muscles all too often pay the price.

Athletes spend years in Spartan-like training, smashing through pain barriers to developing strength, power, and agility.

We mere mortals can only imagine their hopeless frustration when they are bed-ridden and inactive while watching in horror as their lower quadriceps muscle shrinks just before ACL surgery.

The injury causes inflammation, swelling and the release of what lead Michigan researcher Christopher Mendias calls "angry synovial fluid."

"It seems to carry a bunch of chemical signals that shrink the muscle and cause some inflammation in the tissue right around the knee joint," Mendias says. "So if you look at the entire quadriceps muscle group, the atrophy is much more pronounced toward the knee joint."

Can Athletes Ever Totally Recover from ACL Surgery?

The vexing question is this: once ACL surgery is complete, can the knee ever totally recover to its pre-injury condition?

Stem cell therapy and platelet-rich plasma (PRP) treatment are treatments appearing on the radar screen, and the promising benefits of Testosterone Replacement Therapy (TRT) is being studied.

The Michigan researchers think HGH has significant promise as well.

ACL reconstructions, using a graft from a patellar tendon or hamstring that is screwed or stapled into place, have become mechanically sound procedures that help many athletes get back in the game. Rehab protocol has also improved.

Sadly, regardless of how successful the surgery was, or how intensely the athletes attack their rehab protocol, they often are never the same.

This inability to recover is particularly the case for the two critical athletic areas of quickness and range of motion.

Even worse, numerous studies have shown their other knee is more prone to damage.

Also, they are at increased risk for early osteoarthritis. Some data shows younger athletes have a higher incidence of repeat tears in the same joint.

"I tell people the rehab is two years...you're rehabbing through the season and the off-season," says retired NFL cornerback Terrell Thomas, who had three surgeries on his right ACL, the first one in college. "It's not one of those injuries where you do your six months and move on with life."

Mendias, a Ph.D. in molecular and integrative physiology, has studied in detail why muscles and tendons grow and shrink and how they recuperate after injury.

In late 2013, he discovered a story in which Cuban called for additional research on Growth Hormone as a healing agent.

He immediately emailed the Maverick's owner.

This study is the result. In the eyes of Mendias and his partner on the project, Dr. Asheesh Bedi, the time has finally arrived for HGH to be carefully and thoughtfully explored as a possible solution to the most frustrating aspect of the roughly 250,000 ACL reconstructions performed annually in the United States.

"It's a largely successful clinical operation, but what goes unnoticed is that even though the athlete feels sturdy, and may exceed their baseline [strength] pre-injury, they often have persistent objective weakness nine months or a year out," says Bedi, an orthopedic surgeon who is a University of Michigan team physician and an associate team physician for the Detroit Lions.

"It's easy to rest on our laurels as surgeons when potentially we should be asking for more."

Bedi and Mendias hypothesize that Human Growth Hormone injections will help preserve the muscle around the joint by activating a protein called IGF-1 (Insulin-like Growth Factor-1) that stimulates strong growth while blocking another protein, Myostatin, which is triggered by injury and slows down or stops that growth.

The clinical trial is inviting men 18 to 35 years old who are about to undergo ACL reconstruction for the first time.

They cannot be athletes subject to NCAA, World Anti-Doping Agency or professional sports drug protocols.

The first patients enrolled in the spring of 2015, and the study is scheduled to end in mid-2017. Hopes are high and time will tell because HGH has been known for its rejuvenation capacity for decades, but there have been some conflicting claims in the medical community.

Though most forward-thinking physicians have been for this exogenous HGH infusion for off-label purposes, there are still many old-school doctors who see it as having a potential to be abused, dangerous and risky.

One thing is for sure that the best protocol cycles involve low doses and some doctors prescribe a dosage that is too high. This potential danger is why it is imperative for patients to closely monitor their IGF-1 levels regularly.

The study is double-blind, meaning neither the researchers nor the patients know which group is getting HGH and which is receiving a placebo.

Both teams will receive injections in the abdomen twice daily for one-week pre-surgery and five weeks after.

Patients will be monitored for six months of physical therapy, with strength in both the injured and uninjured legs tracked and general health closely watched to ensure there are no unpleasant side effects.

The short, six-week course of GH injections was designed to keep the study firmly in the realm of medical treatment as opposed to performance enhancement, Mendias says.

"No one's going back to the court or the field that quickly, so the effects of growth hormone are mostly transient," Mendias says.

"We don't think there's going to be any long-term benefits, which they're gonna go back stronger than they were before they had their injury. We're hoping to get them back as close as we can to their average strength before they had the tear."

The findings will answer many questions about Growth Hormone therapy.

The Michigan researchers plan to be "extremely transparent" about their conclusions, Mendias wrote in an email.

They will publish results regardless of whether they are helpful or not. He added they would share raw data with others in the field upon request. If follow-up studies are necessary, they will be widened to include other locations, age groups, and both genders.

With many uncertainties and hurdles along the way, Mendias estimates it may take more than a decade for the FDA to consider reclassifying Growth Hormone. If that happens, it will create an exciting challenge for elite sports.

Defining the terms for a therapeutic-use exemption for HGH (dosage, the length of treatment and the interval before an athlete could return to competition) could be a steep challenge.

Anti-doping authorities would have to devise an elaborate and detailed solution, says Thomas H. Murray, former president of the Hastings Institute, a bioethics think tank in New York State.

"Would I deny [an] athlete the possibility of a more rapid healing and a prospect of a better life long-term with less disability from that injury just because we know some people misuse this drug for sports performance?" Murray says.

"I would find that an impossible position to sustain." Murray, a scholar with extensive experience in advising sporting entities on anti-doping policy and ethics, said caution and skepticism are warranted, even though "I don't think people are going to rip ACLs to take human growth hormone," he says.

"If it's approved for ACL injuries, will people then want to use it for other, less severe injuries, and push to have it administered closer to the time of performance? Yes," Murray says. "We know all that will happen. Such policies like this come down to convenient things. Can you create a reasonable set of rules that would shut the door to the most blatant abuses but would leave it open for legitimate therapeutic uses?"

Murray has no objection to sports owners such as Cuban funding this kind of research, as long as the leagues are equally emphasizing injury prevention. But Murray refuses to take sides in the debate.

"It's important to have an appreciation for the irony in all of this," Murray says.

This paradox means it is a slippery slope, where athletes take Growth Hormone as a PED. HGH will allow them to train harder, suffer more debilitating injuries due to their increased size and speed, then be treated by a drug that may have helped cause the problem in the first place.

Dr. James Andrews, the orthopedic surgeon to the stars, has performed thousands of ACL reconstructions and says any potential policy change on Growth Hormone will be "a hard row to hoe."

But, Andrews says, a carefully controlled environment like Michigan's clinical trial is the setting to do the correct, detailed work, rather than the barely concealed, ad hoc experimentation going on in sports.

"[HGH] should be studied, it should be researched, and we may find out that the benefits are worth the risk factors," Andrews says. "My hat's off to them because that's where it needs to be evaluated."

The first NBA players who might benefit from the study are probably young teenagers now. However, Mark Cuban is not concerned by either length of time until the benefits are practical or the potential regulatory hurdles.

Cuban was asked: "Given your public profile, people may speculate that you have a commercial/profit-making interest in the study results if they are successful down the road. Please comment."

His response: "Of course I do. If this works, I will figure out an angle to make money from having sponsored a study that changed the game. And if it does turn out that it helps athletes recover faster, I of course benefit from my interests in the Mavs and the NBA.

"Feel free to make that the headline. It doesn't change anything at all. The results are the results. Either it works, or it doesn't."

Cuban first brought up the issue of HGH use for injured athletes at the NBA Board of Governor's meetings last October.

At the time, he recommended that the idea of keeping HGH on the league’s banned-substance list should be re-evaluated, with the possibility of allowing use by players recovering from injuries.

The NBA has been hit with several injuries this season, and the loss of the main players is devastating to the teams involved.

Also, the fans suffer as well, since the absence of their favorite players makes the games less attractive, and attendance drops.

In spite of the reality that a comprehensive HGH rehabilitation program may be years away, the Board of Governors has given their approval to begin the research.

Once the investigation is completed, and a possible and practical solution is available, they will then discuss the issue further.

Cuban said that once the discussion became public, several universities came forward to make proposals to him. “I just want to know what reality is,” Cuban stated. “And if we can improve recovery time, obviously that’s a plus for all of us, but there was never any basis in fact for not allowing it for use [while recovering from injuries]. It was all marketing. So let’s find out. Let’s see what’s real and not real.”

HGH has been known to be helpful in several ways and is considered a comprehensive solution to many common injuries.

NBA players, team owners, and fans are anxious to see if HGH can make a beneficial difference in the NBA.

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

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.

References

1 Hannuksela, M. L. & Ellahham, S. Benefits and risks of sauna bathing. The

American journal of medicine 110, 118-126 (2001).

2 Ricardo J. S. Costa, M. J. C., Jonathan P. Moore & Neil P. Walsh. Heat

acclimation responses of an ultra-endurance running group preparing for hot

desert-based competition. European Journal of Sport Science, 1-11 (2011).

3 King, D. S., Costill, D. L., Fink, W. J., Hargreaves, M. & Fielding, R. A. Muscle

metabolism during exercise in the heat in unacclimatized and acclimatized

humans. J Appl Physiol 59, 1350-1354 (1985).

4 Scoon, G. S., Hopkins, W. G., Mayhew, S. & Cotter, J. D. Effect of post-exercise

sauna bathing on the endurance performance of competitive male runners.

Journal of science and medicine in sport / Sports Medicine Australia 10,

259-262, doi:10.1016/j.jsams.2006.06.009 (2007).

5 Michael N. Sawka, C. B. W., Kent B. Pandolf. Thermoregulatory Responses to

Acute Exercise-Heat Stress and Heat Acclimation. Handbook of Physiology,

Environmental Physiology (2011).

6 Garrett, A. T., Creasy, R., Rehrer, N. J., Patterson, M. J. & Cotter, J. D.

Effectiveness of short-term heat acclimation for highly trained athletes.

European journal of applied physiology 112, 1827-1837,

doi:10.1007/s00421-011-2153-3 (2012).

7 Kirwan, J. P. et al. Substrate utilization in leg muscle of men after heat

acclimation. J Appl Physiol (1985) 63, 31-35 (1987).

8 Selsby, J. T. et al. Intermittent hyperthermia enhances skeletal muscle

regrowth and attenuates oxidative damage following reloading. J Appl Physiol

(1985) 102, 1702-1707, doi:10.1152/japplphysiol.00722.2006 (2007).

9 Naito, H. et al. Heat stress attenuates skeletal muscle atrophy in

hindlimb-unweighted rats. J Appl Physiol 88, 359-363 (2000).

10 Kokura, S. et al. Whole body hyperthermia improves obesity-induced insulin

resistance in diabetic mice. International journal of hyperthermia : the official

journal of European Society for Hyperthermic Oncology, North American

Hyperthermia Group 23, 259-265, doi:10.1080/02656730601176824

(2007).

11 Yamada, P. M., Amorim, F. T., Moseley, P., Robergs, R. & Schneider, S. M. Effect

of heat acclimation on heat shock protein 72 and interleukin-10 in humans. J

Appl Physiol (1985) 103, 1196-1204, doi:10.1152/japplphysiol.00242.2007

(2007).

12 Moseley, P. L. Heat shock proteins and heat adaptation of the whole

organism. J Appl Physiol (1985) 83, 1413-1417 (1997).

13 Kuennen, M. et al. Thermotolerance and heat acclimation may share a

common mechanism in humans. American journal of physiology. Regulatory,

integrative and comparative physiology 301, R524-533,

doi:10.1152/ajpregu.00039.2011 (2011).

14 Leppaluoto, J. et al. Endocrine effects of repeated sauna bathing. Acta

physiologica Scandinavica 128, 467-470,

doi:10.1111/j.1748-1716.1986.tb08000.x (1986).

15 Kukkonen-Harjula, K. et al. Haemodynamic and hormonal responses to heat

exposure in a Finnish sauna bath. European journal of applied physiology and

occupational physiology 58, 543-550 (1989).

16 Velloso, C. P. Regulation of muscle mass by growth hormone and IGF-I. British

journal of pharmacology 154, 557-568, doi:10.1038/bjp.2008.153 (2008).

17 Coleman, M. E. et al. Myogenic vector expression of insulin-like growth factor

I stimulates muscle cell differentiation and myofiber hypertrophy in

transgenic mice. The Journal of biological chemistry 270, 12109-12116

(1995).

18 Barton, E. R., Morris, L., Musaro, A., Rosenthal, N. & Sweeney, H. L.

Muscle-specific expression of insulin-like growth factor I counters muscle

decline in mdx mice. The Journal of cell biology 157, 137-148,

doi:10.1083/jcb.200108071 (2002).

19 Healy, M. L. et al. High dose growth hormone exerts an anabolic effect at rest

and during exercise in endurance-trained athletes. The Journal of clinical

endocrinology and metabolism 88, 5221-5226 (2003).

20 Ftaiti, F. et al. Effect of hyperthermia and physical activity on circulating

growth hormone. Applied physiology, nutrition, and metabolism = Physiologie

appliquee, nutrition et metabolisme 33, 880-887, doi:10.1139/H08-073

(2008).

21 Louard, R. J., Fryburg, D. A., Gelfand, R. A. & Barrett, E. J. Insulin sensitivity of

protein and glucose metabolism in human forearm skeletal muscle. The

Journal of clinical investigation 90, 2348-2354, doi:10.1172/JCI116124

(1992).

22 Lecker, S. H., Goldberg, A. L. & Mitch, W. E. Protein degradation by the

ubiquitin-proteasome pathway in normal and disease states. Journal of the

American Society of Nephrology : JASN 17, 1807-1819,

doi:10.1681/ASN.2006010083 (2006).

23 Chow, L. S. et al. Mechanism of insulin's anabolic effect on muscle:

measurements of muscle protein synthesis and breakdown using

aminoacyl-tRNA and other surrogate measures. American journal of

physiology. Endocrinology and metabolism 291, E729-736,

doi:10.1152/ajpendo.00003.2006 (2006).

24 Guillet, C., Masgrau, A., Walrand, S. & Boirie, Y. Impaired protein metabolism:

interlinks between obesity, insulin resistance and inflammation. Obesity

reviews : an official journal of the International Association for the Study of

Obesity 13 Suppl 2, 51-57, doi:10.1111/j.1467-789X.2012.01037.x (2012).

25 Selsby, J. T. & Dodd, S. L. Heat treatment reduces oxidative stress and

protects muscle mass during immobilization. American journal of physiology.

Regulatory, integrative and comparative physiology 289, R134-139,

doi:10.1152/ajpregu.00497.2004 (2005).

26 Nath, K. A. et al. Induction of heme oxygenase is a rapid, protective response

in rhabdomyolysis in the rat. The Journal of clinical investigation 90, 267-270,

doi:10.1172/JCI115847 (1992).

27 Wei, Q., Hill, W. D., Su, Y., Huang, S. & Dong, Z. Heme oxygenase-1 induction

contributes to renoprotection by G-CSF during rhabdomyolysis-associated

acute kidney injury. American journal of physiology. Renal physiology 301,

F162-170, doi:10.1152/ajprenal.00438.2010 (2011).

28 Khazaeli, A. A., Tatar, M., Pletcher, S. D. & Curtsinger, J. W. Heat-induced

longevity extension in Drosophila. I. Heat treatment, mortality, and

thermotolerance. The journals of gerontology. Series A, Biological sciences and

medical sciences 52, B48-52 (1997).

29 Lithgow, G. J., White, T. M., Melov, S. & Johnson, T. E. Thermotolerance and

extended life-span conferred by single-gene mutations and induced by

thermal stress. Proceedings of the National Academy of Sciences of the United

States of America 92, 7540-7544 (1995).

30 Tatar, M., Khazaeli, A. A. & Curtsinger, J. W. Chaperoning extended life. Nature

390, 30, doi:10.1038/36237 (1997).

31 Singh, R. et al. Anti-inflammatory heat shock protein 70 genes are positively

associated with human survival. Current pharmaceutical design 16, 796-801

(2010).

32 Yenari, M. A., Giffard, R. G., Sapolsky, R. M. & Steinberg, G. K. The

neuroprotective potential of heat shock protein 70 (HSP70). Molecular

medicine today 5, 525-531 (1999).

33 Duveau, V., Arthaud, S., Serre, H., Rougier, A. & Le Gal La Salle, G. Transient

hyperthermia protects against subsequent seizures and epilepsy-induced cell

damage in the rat. Neurobiology of disease 19, 142-149,

doi:10.1016/j.nbd.2004.11.011 (2005).

34 Lundgren, J., Smith, M. L., Blennow, G. & Siesjo, B. K. Hyperthermia aggravates

and hypothermia ameliorates epileptic brain damage. Experimental brain

research. Experimentelle Hirnforschung. Experimentation cerebrale 99, 43-55

(1994).

35 Laatikainen, T., Salminen, K., Kohvakka, A. & Pettersson, J. Response of

plasma endorphins, prolactin and catecholamines in women to intense heat

in a sauna. European journal of applied physiology and occupational

physiology 57, 98-102 (1988).

36 Salbaum, J. M. et al. Chlorotoxin-mediated disinhibition of noradrenergic

locus coeruleus neurons using a conditional transgenic approach. Brain

research 1016, 20-32, doi:10.1016/j.brainres.2004.03.078 (2004).

37 Gregg, C. et al. White matter plasticity and enhanced remyelination in the

maternal CNS. The Journal of neuroscience : the official journal of the Society

for Neuroscience 27, 1812-1823, doi:10.1523/JNEUROSCI.4441-06.2007

(2007).

38 Christman, J. V. & Gisolfi, C. V. Heat acclimation: role of norepinephrine in the

anterior hypothalamus. J Appl Physiol (1985) 58, 1923-1928 (1985).

39 Wigal, S. B. et al. Catecholamine response to exercise in children with

attention deficit hyperactivity disorder. Pediatric research 53, 756-761,

doi:10.1203/01.PDR.0000061750.71168.23 (2003).

40 van Praag, H., Christie, B. R., Sejnowski, T. J. & Gage, F. H. Running enhances

neurogenesis, learning, and long-term potentiation in mice. Proceedings of

the National Academy of Sciences of the United States of America 96,

13427-13431 (1999).

41 Maniam, J. & Morris, M. J. Voluntary exercise and palatable high-fat diet both

improve behavioural profile and stress responses in male rats exposed to

early life stress: role of hippocampus. Psychoneuroendocrinology 35,

1553-1564, doi:10.1016/j.psyneuen.2010.05.012 (2010).

42 Pedersen, B. K. Muscle as a Secretory Organ. Comprhensive Physiology (2013).

43 Koltyn, K. F., Robins, H. I., Schmitt, C. L., Cohen, J. D. & Morgan, W. P. Changes

in mood state following whole-body hyperthermia. International journal of

hyperthermia : the official journal of European Society for Hyperthermic

Oncology, North American Hyperthermia Group 8, 305-307 (1992).

44 Liu, X. L. et al. [Therapeutic effect of whole body hyperthermia combined

with chemotherapy in patients with advanced cancer]. Zhong nan da xue xue

bao. Yi xue ban = Journal of Central South University. Medical sciences 31,

350-352 (2006).

45 Narita, M. et al. Heterologous mu-opioid receptor adaptation by repeated

stimulation of kappa-opioid receptor: up-regulation of G-protein activation

and antinociception. Journal of neurochemistry 85, 1171-1179 (2003).

46 Xin, L., Geller, E. B. & Adler, M. W. Body temperature and analgesic effects of

selective mu and kappa opioid receptor agonists microdialyzed into rat brain.

The Journal of pharmacology and experimental therapeutics 281, 499-507

(1997).

47 Heckmann, J. G., Rauch, C., Seidler, S., Dutsch, M. & Kasper, B. Sauna stroke

syndrome. Journal of stroke and cerebrovascular diseases : the official journal

of National Stroke Association 14, 138-139,

doi:10.1016/j.jstrokecerebrovasdis.2005.01.006 (2005).