As I sat on my recliner checking out the scenery in South Beach, Miami, it occurred to me just how friggin’ hot it gets in the summertime. It felt like a barbecue on the planet Mercury. But besides prompting many fine (and not so fine) ladies to strip to the near-bare essentials, there’s something to “heat” itself, which may surprise you. It makes you big? Makes you grow? Hold on, Antonio. Has your brain succumbed to lack of oxygen, heatstroke, or what?

Well, check this out. There are a few studies out there showing that heat may contribute to skeletal muscle hypertrophy. So, if you plan on doing German volume training, don’t do it in Germany, do it in Miami!

Sweat Like an Animal!
For example, one study looked at heat stress-associated muscle hypertrophy in rats. Male rats were randomly divided into four groups: 1) control (CC, N (number) =15); 2) control with the injection of cyclosporine A [CsA] (CA, N=15); 3) heat-stressed (HC, N=15); and 4) heat-stressed with the injection of CsA (HA, N=15). The heat-stress groups (HC and HA) were exposed to heat (41 degrees C for 60 minutes) in a controlled heat chamber without anesthesia. Soleus and extensor digitorum longus (EDL) muscles were dissected and weighed, one, seven and 14 days after exposure. And go figure! The weight of the slow-twitch soleus muscle increased seven days following heat exposure. How did this happen? Scientists also found that the expressions of heat shock protein 72 (HSP72) and calcineurin in both muscles were also increased within one and seven days following heat stress, respectively.

Administration of CsA, a specific inhibitor for calcineurin, depressed heat stress-associated increases in muscle weight and calcineurin expression, especially in soleus. What this means is that a calcineurin-dependent signaling pathway plays an important role in the heat stress-related skeletal muscular hypertrophy. According to the scientists, “Application of heat stress to skeletal muscles may be a useful tool to gain muscular mass and force generation not only in athletes, but also in patients during rehabilitation.”1 Other studies have shown similar results.1-3 One theory holds that heat stress promotes cell proliferation (e.g., activation of satellite cells) and induces muscular hypertrophy.3   

So here’s your workout strategy. When you go to the gym, tell the old man at the front desk to turn off the friggin’ AC. Let the room get hot. Sweat like a horse (not a pig ‘cause pigs don’t sweat) and grow like one too!

Tumor Necrosis Factor-alpha Inhibitors
Tumor necrosis factor-alpha (or TNF-alpha) is a cytokine involved in the inflammatory process. There’s evidence it plays a role in glucose metabolism and insulin sensitivity. I’m sure you’re wondering what this has to do with the price of chips in Chili? Well keep reading, there may be something to TNF-alpha; or more specifically, drugs that inhibit TNF-alpha. Anyhow, first some background.

We know regular exercise offers protection against heart disease and type 2 diabetes. Some scientists believe that diabetes in particular may be related to a chronic low-grade systemic inflammation reflected by a two- to threefold-elevated level of several cytokines (e.g., TNF-alpha). Fat or adipose tissue contributes to the production of TNF-alpha.4

Thus, scientists tested the idea that the TNF-alpha protein levels in skeletal muscle are important in regulating the improvements in glucose homeostasis associated with diet and exercise regimens.

Twenty human subjects were recruited for this study; they were overweight and insulin insensitive. All subjects completed an eight-week control period, followed by randomization to eight weeks of moderate cycling exercise (30 minutes three times per week), or to a diet with the following characteristics: low in saturated fat, high in fiber, low glycemic index and rich in complex carbohydrates. What happened? Both interventions reduced fasting plasma insulin levels by about 20 percent. Diet reduced skeletal muscle TNF-alpha protein by 54 percent. Oddly though, exercise training didn’t significantly change TNF-alpha protein expression, but GLUT4 protein expression increased by 105 percent. Therefore, the metabolic benefits of a diet aimed at cardiovascular risk reduction are associated with a decrease in skeletal muscle TNF-alpha protein.5

    So, where does that lead us? Well, think about it. If we can decrease TNF-alpha levels, theoretically we can increase insulin sensitivity and decrease various inflammatory markers in the body (and in muscle). Is it possible that by doing this, especially with regard to insulin sensitivity, we can, in turn, promote better gains in skeletal muscle mass? Mmm… sounds like science fiction. Well, think again. There’s already a drug out there used to treat rheumatoid arthritis and psoriasis that in essence is a TNF-alpha inhibitor. What is that drug? Enbrel.

Dramatic success in the treatment of chronic inflammatory diseases has been seen with this drug. In fact, it’s very effective in blocking the inflammatory response in mice. For instance, a histological (tissue) examination of transverse sections from whole muscle autografts in mice sampled at five days after transplantation demonstrates that Enbrel blocks the acute inflammatory cell response in vivo.6 Enbrel, used as a new treatment for psoriasis, may, in fact, help your muscles recover from intense exercise. Remember that there’s an inflammatory response in skeletal muscle post-exercise. Could Enbrel mediate a “better” adaptive response? Keep an eye out for new research on these TNF-alpha inhibitors.

References
1.    Kobayashi T, Goto K, Kojima A, et al. Possible role of calcineurin in heating-related increase of rat muscle mass. Biochem Biophys Res Commun, Jun 17 2005;331(4):1301-1309.
2.    Goto K, Honda M, Kobayashi T, et al. Heat stress facilitates the recovery of atrophied soleus muscle in rat. Jpn J Physiol, Jun 2004;54(3):285-293.
3.    Uehara K, Goto K, Kobayashi T, et al. Heat-stress enhances proliferative potential in rat soleus muscle. Jpn J Physiol, Jun 2004;54(3):263-271.
4.    Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol, Apr 2005;98(4):1154-1162.
5.    Ferrier KE, Nestel P, Taylor A, Drew BG, Kingwell BA. Diet but not aerobic exercise training reduces skeletal muscle TNF-alpha in overweight humans. Diabetologia, Apr 2004;47(4):630-637.
6.    Grounds MD, Davies M, Torrisi J, Shavlakadze T, White J, Hodgetts S. Silencing TNFalpha activity by using Remicade or Enbrel blocks inflammation in whole muscle grafts: an in vivo bioassay to assess the efficacy of anti-cytokine drugs in mice. Cell Tissue Res, Jun 2005;320(3):509-515.

 ALAN: SAME BIO PLEASE