Stress in its many guises is unavoidable. The body has numerous ways
of dealing with the effects of stress, ranging from upgraded release of
so-called stress hormones to changes in brain chemistry that modulate
excess stress and prevent potentially negative effects on brain
function. Perhaps the body’s first line of defense against stress,
however, is the production of heat shock proteins, a.k.a. HSPs.
Heat shock proteins are molecular chaperones that ensure proper
protein folding. Newly synthesized proteins must attain a certain
configuration, or shape, to properly function. Heat shock proteins
guide, or help fold, them into their proper shape for optimal function.
Proteins not properly folded tend to aggregate, or stick together.
Improperly folded proteins not only don’t function correctly but also
figure in degenerative diseases. One example: The accumulation of
beta-amyloid protein in the brain is the underlying cause of Alzheimer’s
disease. Brain cells tend to lose the capacity to produce heat shock
proteins with age, explaining the degenerative brain disease that can
accompany advanced age.
Recent studies also show that SIRT1, a protein stimulated by resveratrol
stimulates what’s called heat shock factor, the precursor of heat shock
proteins. That helps explain research findings that resveratrol has
antiaging properties. Even more fascinating is research showing that
heat shock protein 70 blocks muscle atrophy under disuse conditions in
both young and old animals. That suggests that heat shock proteins may
help preserve muscle. They also remove damaged proteins, thus making
room for the production of new, more efficient ones.
While I discussed the general function of heat shock proteins in a recent
IRON MAN
feature [“Shocking Muscle Growth,” September ’09], I didn’t detail
practical ways to boost HSP release in the body. You may have seen ads
for sports supplements that are said to boost HSP release. The salient questions about such
supplements are whether they work, the best way to use them, and what
you can expected if you use them. To answer those questions, I
interviewed Joe Evans, Ph.D.
Evans is head of a consulting firm that advises the pharmaceutical
and nutracuetical industries. He’s also logged more than 20 years in
research. He has specialized in natural product development for treating
type 2 diabetes and obesity. Evans earned a doctorate in biochemistry from Drexel
University and received postdoctoral training in molecular biology,
biochemistry, cell biology and physiology at Dartmouth Medical School
and the University of Copenhagen. He’s published numerous papers in
professional science journals and is eminently qualified to discuss the
practical use and effectiveness of HSP supplements.
JB: What exactly are heat shock proteins?
JE: HSPs are very important proteins that exist in all organisms,
from bacteria to man. They protect your organs and tissues from all
kinds of stress. Specifically, they protect other proteins in the body
under stressful conditions—exercise, chemical stress, exposure to toxic
chemicals and drugs and other forms of stress. They can be viewed as a
defense mechanism of the body against stress.
While HSPs operate both outside and inside the cell, it’s the
intracellular function that interests us most. HSPs protect
intracellular protein structures, including enzymes, receptor proteins,
transcription proteins and so on. Those proteins are all subject
to damage under stress conditions. You can compare HSPs to an ambulance
responding to an emergency in the cell, but HSPs aid cellular function
under normal conditions too. They ensure the normal synthesis of vital
cellular protein structures, ensuring the production of perfect
proteins.
JB: So would it be accurate to say that people deficient in HSPs would be more subject to stress-related diseases?
JE: While malfunction of HSP response has been well characterized in
animal studies, the human studies of this aspect are not yet complete.
On the other hand, based on the established functions of HSPs, we
believe they would protect humans against such conditions as oxidative
stress and inflammatory-related diseases.
JB: Various supplement companies are now offering products aimed at
bodybuilders and athletes that are supposed to boost HSPs. Are there
any legitimate products that accomplish that task?
JE: The ingredient that I’m most familiar with is called TEX-OE,
which is an extract of the prickly pear cactus. That plant has a long
record of safe use by Native Americans. More recently, several patents have been
awarded for use of prickly pear extract to trigger HSP responses. While
other natural HSP triggers likely exist, I’ve examined the data related
to TEX-OE, and I’m convinced that it’s effective in boosting HSP response in the human body. Data on the effectiveness of TEX-OE are thus
far unpublished in any professional science journals, but I’m presently
negotiating to get the material published.
JB: Do you feel that claims for commercial sports supplements should have solid scientific support?
JE: I believe that supplement consumers should demand scientific
proof of product effectiveness, but I can assure you that the pilot
studies done with human subjects on oral doses of TEX-OE are all
consistent in that they demonstrate a substantial increase in HSP
response. The studies have involved various forms of stress, such as
deep-sea diving,hyperbaric chambers
, thermal stress involving a sauna and several exercise experiments.
Eight of the initial studies have been completed. They all have
involved preconditioning the subjects through an oral dose of TEX-OE
about two hours prior to stress exposure. Regular blood samples were
taken to determine the heat-shock response. While no definitive placebo
was used, half of the participants got TEX-OE, and the other half
received no extract. In all studies researchers measured a 200 percent
increase in HSP response in subjects who took the TEX-OE extract,
particularly in HSP 27 and HSP 70.
More important was the time shift in the production of HSPs. In those
who didn’t take the extract, the HSPs took more than two hours to
appear, and by that time proteins were already showing signs of damage.
In those who took the TEX-OE, the HSPs appeared in a matter of minutes.
That has significant implications for those involved in exercise. It
likely translates into increased muscle recovery after a workout, along
with decreased muscle soreness. Some of the studies involved highly
trained cyclists, making it harder to see a significant response, yet
they did respond after taking TEX-OE.
JB: I’ve read that using TEX-OE will result in a sustained elevation
of HSPs for two to three days after the initial dose. How does that
work?
JE: We don’t know the precise mechanism, but we suspect that it
involves a stimulation of heat shock factor, the precursor substance the
body produces for HSPs. It’s a plausible mechanism, and as long as you
have a priming of heat shock factor, you’ll get a sustained rise of HSP
response. That explains why you don’t need to take TEX-OE every day. The
effect lasts for a few days
following initial dosing.
JB: One confusing issue related to HSP is caffeine intake. Many
bodybuilders load caffeine as coffee prior to training. Some studies
show that caffeine may interfere with HSP response, while others show
that it boosts HSP response. Can you clear that up?
JE: The usual suggestion is not to take in more than 200 milligrams
of caffeine prior to exercise—about two cups of coffee. The problem with
taking in more is that it elevates cortisol and brings on
vasoconstriction, or a tightening of blood vessels. In addition, the
studies that showed caffeine boosting HSP during exercise involved
extracellular production of HSP—quite different from intracellular
production. Most HSP-induced cellular protection occurs inside the cell.
Extracellular HSP production is mainly involved in immune response.
JB: You mentioned cortisol, the body’s primary catabolic hormone. Is there any interaction between cortisol and HSPs?
JE: Extended cortisol release is associated with a high rate of
inflammation, which signals HSP release. The HSPs reduce the negative
effects of excess inflammation, including what cortisol induces. So in
that respect HSP can counter some of cortisol’s catabolic effects.
JB: Are any other supplements or nutrients synergistic with TEX-OE in boosting HSP response?
JE: Several nutrients can be considered complementary. One example:
high-quality protein. Protein supplies the amino acids your body needs
for protein synthesis. HSPs ensure that the conformation and structure
of synthesized proteins is optimal. Carbohydrates also help because they
spur insulin release; insulin helps with amino acid uptake into muscle.
Some animal data show that
alpha lipoic acid also induces HSP response.
JB: What about medical contraindications to using a supplement like TEX-OE?
JE: There are no known side effects of TEX-OE, nor are there any established
drug interactions.
The plant that TEX-OE is extracted from has a long record of safety.
Still, we don’t recommend the product for those under age 18 or for
nursing or pregnant women.
JB: What can the typical bodybuilder expect from using an HSP-boosting supplement?
JE: The effects of an HSP supplement aren’t immediately apparent, but
right from the start a boost in HSPs improves cell protection and
rescues vital proteins from damage. The increased cellular protein
repair induced by HSPs results in significantly improved exercise
recovery. In addition, you’ll be able to use more of the proteins that
you generate during exercise.
Some amino acids are watery, while others are more fatty. When the
amino acids stick together, a process called aggregation occurs, which
results in malformed proteins. HSPs act as protein chaperones,
maintaining orderly protein conformation and stability. The production
of “perfect” protein structures, supported by HSPs, will add to muscle
hypertrophy. I’d estimate that results like those will be evident within
three weeks to a month after you start using HSP supplements. More
muscle also means more calorie use at rest and translates into less
bodyfat.
JB: Should HSP supplements be used in cyclical fashion—that is, getting off them for a certain amount of time?
JE: With some supplements it’s a good idea to cycle on and off. Take
creatine. After you use it for an extended period, the creatine
transport protein in muscle downgrades, limiting uptake into muscle. So
you stop using it, letting the creatine transport protein to
activate
again. Since you don’t need to take HSP supplements every day, however,
you’re already cycling. In addition, there is no evidence that you need
to totally stop using the supplement. In testing the TEX-OE product for
extended times, we didn’t notice any decrease in effectiveness.
JB: Various dosing schemes are suggested for TEX-OE, such as taking
it two hours prior to training on an empty stomach, avoiding fiber
intake within two hours of dosing or taking it right before bed on an
empty stomach. What would you say is the best way to use this product?
JE: The natural fiber content of TEX-OE has been removed so the
supplement can be more effectively absorbed. I think it’s best to take
it away from a meal—at least two hours after eating—for best results.
One possible benefit of taking it at night is that it will interact with
the increased protein synthesis that occurs at that time, fostering the
chaperone effect, and produce more efficient protein folding. Still, I
feel that taking it prior to training is best.
JB: Is it possible to produce excess HSPs with the supplement?
JE: A supplement such as TEX-OE isn’t directly pushing out HSPs but
is instead facilitating the release of heat shock factor, the precursor
substance. Your body ultimately determines the amount of HSP produced,
so there is a built-in safety factor.
JB: In the studies done thus far on TEX-OE, were any significant side effects noted?
JE: The researchers who conducted the studies reported that the
supplement was well tolerated, and no significant side effects were
apparent. MRI, which sells a TEX-OE supplement, keeps track of reported
side effects through various retail outlets and has thus far not
received any reports of adverse effects.
JB: Do the supplements produce better effects in those under age 40?
JE: I don’t think there are any age or gender factors involved in the
use of TEX-OE. Consider that HSP 70 is one of the most highly conserved
proteins in the body. That means its function doesn’t downgrade with
age, as is the case with many other body substances, such as hormones.
The amino acid structure of HSP 70 is the same in bacteria as it is in
humans. Nature has evolved a perfect protein to do its job. On the other
hand, HSP production in general does tend to decline with age in most
people.
JB: Some studies have pointed out that the higher estrogen counts in
women tend to blunt HSP release during exercise. Does that mean HSP
supplements work better in men?
JE: Pilot studies involving human exercise did have female subjects,
and all of them showed significant increases in HSPs with the use of
TEX-OE supplements. I think TEX-OE will work well for women and men,
producing similar exercise-recovery and training-efficiency benefits.
JB: Certain supplements, such as HMB and creatine, seem to produce
better results for those engaged in intense exercise. Can the same be
said of HSP supplements?
JE: People who don’t train regularly tend to not adapt as much to
exercise, leading to recurring muscle damage. HSP supplements would
likely be an asset to recreational exercisers. In those who train harder
or more frequently, the HSPs will also improve recovery and training
efficiency.
JB: Are there any known interactions between HSP supplements and drugs?
JE: I can’t speak about all HSP supplements, but there are no known
interactions between any drugs and the TEX-OE extract. Some test
subjects have used various drugs with no apparent interactions.
JB: Would using TEX-OE aid bodyfat loss?
JE: By helping to protect and maintain muscle, increased HSPs will yield more efficient
metabolism, which tends to produce a leaner body. HSP supplements protect proteins from being degraded, but not fat tissue.
JB: Considering that there are various HSPs, does a
supplement such as TEX-OE affect the entire range of HSPs?
JE: The clinical data show an increase primarily in HSPs related to exercise, such as HSP70 and HSP27.
JB: Do HSP supplements interact with anabolic hormones, such as anabolic steroids and
growth hormone?
JE: That hasn’t been tested with the TEX-OE products, but it does
make sense that the HSP boosters would be synergistic with anabolic
drugs. Those hormones promote increased protein synthesis, and HSPs work
within the cell to ensure that the newly synthesized proteins have the
proper shape or conformation. Imagine the synthesis of newly formed cell
proteins as an assembly line. The HSPs can be viewed as quality-control
workers, ensuring that the finished product is up to par. In fact, HSPs
are better than quality-control workers, who only remove defective
products. In contrast, HSPs are capable of repairing malformed proteins.
JB: A few studies suggest that increased body temperature brings on
HSP release. Keeping that in mind, should a person taking an HSP
supplement prior to training always try to maintain a higher body
temperature during workouts?
JE: The body temperature that turns on HSP release is far higher than
would be encountered during exercise. I don’t think increasing body
heat while using the supplement will make much of a difference. If you
exercised in a sauna or hot tub, then the HSP production would probably
kick in.
JB: Other studies say that
antioxidants
interfere with HSP production during exercise because the free radicals
produced during exercise are a stress reaction that helps release HSPs.
So should one not take antioxidants prior to training?
JE: One study found that using a form of vitamin E called gamma
tocopherol lowered HSP release. This particular form of vitamin E was an
efficient quencher of peroxynitrate, a noxious free radical that also
promotes HSP release. On the other hand, the HSPs blocked by gamma
tocopherol in that study were the extracellular versions. Indeed, other
antioxidants, such as lipoic acid, have been shown to increase
intracellular HSPs. If anything, we feel that antioxidants are
complementary with HSP supplements such as TEX-OE.
JB: Thank you, Dr. Evans, for taking the time to explain HSP supplement use.
©,2015 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.
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