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 safety in 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. IM