The concept behind exercising to increase muscle strength and bulk is that training must be strenuous enough to break down muscle fibers. Some trainers say if muscles aren’t sore the day after a session, then one needs to work out twice as hard. The goal is to break down muscle fibers so they can be rebuilt quickly, stronger than before. The pain relates to lactic acid buildup in the exercised muscle that creates soreness the next day. Soreness may be even worse the second day. By the third day recovery is well on its way. So-called weekend warriors often experience this phenomenon as well.

In 1962, scientists discovered the mechanism explaining the muscle breakdown and hypertrophy response to resistance training.¹ Heat shock proteins (HSPs) are responsible. These proteins exist in the cells of all living organisms. 

HSPs, like other proteins, are a family of proteins consisting of chains of amino acids whose organization allows them to perform certain functions. They support muscle protein synthesis and protect cells against protein-damaging stressors. HSPs can be called “stress proteins” because they are protective against excessive stress and support and improve muscle quality and strength. HSP 70 is the family member that is most responsive to stressors.

How Do HSP Work?
Levels of HSPs rise immediately in response to damaging external stresses, including elevated core body temperature, hypoxia, oxidative stress, ischemia, pH alterations, energy depletion, changes in calcium levels, protein damage, and abnormal protein production. All of these occur during heavy exercise or physical labor.²
HSPs play a role in muscle health and hypertrophy in several ways:

1) They eliminate damaged proteins by fixing them or destroying them.³
2) They facilitate muscle protein repair by attracting amino acids to damaged sites and encouraging them to convert into new muscle fibers.⁴
3) They “chaperone” amino acids during formation of new cellular proteins to make sure the amino acids are properly organized so that the proteins function as they should for optimal cellular homeostasis and survival.⁴ 
4) They shield against excessive muscle damage and inflammation during exercise and protect against future assaults.⁵
5) They inhibit tissue-damaging reactive oxygen species (ROS) formed during exercise that can cause protein degradation.
6) They increase glutathione levels. Glutathione is a protein that functions as a potent antioxidant, reducing tissue damage and decreasing recovery time. Because of its role in protein synthesis, it helps to build muscle strength and endurance.
7) By regulating metabolic intracellar processes, HSPs stimulate the anabolic factors, growth hormone, and insulin-growth factor 1 (IGF-1).

A Role for Dietary Supplements?
In 2009, a blog titillated its reader with this intriguing comment: “HSPs are arguably one of the most revolutionary discoveries in the nutrition industry today and it’s safe to say that any nutritional supplement that can incorporate the incredible ability of HSPs could possibly transform the sports nutrition industry forever.”⁶ 

The writer neglected to name any promising dietary supplements. Since 2009, however, research has identified some dietary supplements supported by clinical data.

Vitamin C complexed with sodium bicarbonate creates a compound where vitamin C scavenges excess ROS, and sodium bicarbonate maintains acid-base and electrolyte balance, and alleviates respiratory alkalosis. An in vitro study compared the complex to vitamin C alone. Both vitamin C and the vitamin C-sodium bicarbonate complex upregulated HSPs in cells exposed to heat stress.⁷

Researchers studied the effects of whey protein hydrolysate, whey protein, and casein on HSPs in an animal study. The group of exercised rats that had consumed whey protein hydrolysate had a statistically significant higher expression of HSP 70 compared to the whey protein or casein groups.⁸

Another study in exercised rats evaluated the effects of a dipeptide of glutamine and alanine, L-alanyl-L-glutamine, or alanine and glutamine in free form. Both compounds increased muscle HSP 70 expression, and improved defense against ROS muscle damage. These results suggested that either compound can enhance the beneficial effects of high-intensity exercise training.⁹

Other compounds are of interest as well. But, to this point, our search of the literature has not revealed any human studies specifically showing a beneficial effect on HSP 70 in humans. We heartily agree with the aforementioned blogger’s statement, “nutritional supplements that can incorporate the incredible ability of HSPs could possibly transform the sports nutrition industry forever.” We’re still waiting to see studies. Today’s informed consumer will require data.  

References

1. Ritossa, F. A new puffing pattern induced by temperature shock and DNP in Drosophila Experientia. 1962;18: 571-573. https://doi.org/10.1007/BF02172188
2. Kültz D. 2003. Evolution of the cellular stress proteome: from monophyletic origin to ubiquitous function. J Exp Biol 2006:3119–3124.
3. Dimauro I, Mercatelli N, Caporossi D. Exercise-induced ROS in heat shock proteins response.  Free Radical Biol Med 2016;98:46-55.
4. Hancock PA, Ross JM, Szalma JL. A meta-analysis of performance response under thermal stressors. Hum Factors. 2007:49;851-877.
5. Beere, HM. ‘The stress of dying’: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci. 2004 117: 2641-2651.
6. Heat Shock Proteins: Scientific Discovery Shocks Nutrition Industry! May 5, 2009. http://blog.bodybuilding.com/StudiesAndResearch.
7. Yin B, et al. Vitamin C and sodium bicarbonate enhance the antioxidant ability of H9C2 cells and induce HSPs to relieve heat stress. Cell Stress Chaperones. 2018 Jul;23(4):735-748. doi: 10.1007/s12192-018-0885-2.
8. Soaresde Moura C, et al. Whey protein hydrolysate enhances the exercise-induced heat shock protein (HSP70) response in rats. Food Chemistry. 2009:136;1350-1357.
9. Petry ER, et al. Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: involvement of heat shock protein pathways. Life Sci. 2014 Jan 17;94(2):130-6. doi: 10.1016/j.lfs.2013.11.009.

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Gregory Stephens
Windrose Partners

Greg Stephens, RD, is president of Windrose Partners, a company serving clients in the the dietary supplement, functional food and natural product industries. Formerly vice president of strategic consulting with The Natural Marketing Institute (NMI) and Vice President of Sales and Marketing for Nurture, Inc (OatVantage), he has 25 years of specialized expertise in the nutritional and pharmaceutical industries. His prior experience includes a progressive series of senior management positions with Abbott Nutrition (Ross Products Division of Abbott Laboratories), including development of global nutrition strategies for disease-specific growth platforms and business development for Abbott’s medical foods portfolio. He can be reached at 267-432-2696; E-mail: gregstephens@windrosepartners.com.


Sheila Campbell

Sheila Campbell, PhD, RD, has practiced in the field of clinical nutrition for more than 30 years, including 17 years with Ross Products Division of Abbott Laboratories. She has authored more than 70 publications on scientific, clinical and medical topics and has presented 60 domestic and international lectures on health-related topics. She can be reached at smcampbellphdrd@gmail.com.