Monday, January 23, 2017

Overlooked and Hushed Up?! The 10-20% Performance Gain From Short-Term Glucocorticoid ('Dex', 'Pred' & Co) Use

Even though their efficacy is still doubted by some doping researchers, the existing evidence leaves little doubt that glucocorticoid doping is as prevalent and efficient as it is risky (Duclos. 2010).
If you have read my "all about cortisol"-article from 2013, you belong to the handpicked elite of fitness enthusiasts, who understand that the glucocorticoid and/or its natural, i.e. cortisone, or artificial, i.e. dexamethasone and prednisone, cousins are not - as many people believe - generally bad for you. Rather than that, the allegedly fat building, muscle burning hormone(s) can, if elevated at the right times and not chronically, help you boost fat loss, strength and overall exercise performance. That's bogus? Well, I know that the vendors of so-called "cortisol-blockers" want to make you believe just that. The effects of the publicly downplayed doping practices in various sports and scientific evidence speak a very different language, though.
Chronically elevated glucocorticoids can occur in the early phase of overtraining:

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In various sports synthetic Glucocorticoids (GC), which are widely prescribed and used as immunosuppressive and anti-inflammatory drugs (note: after a +30% increase in prescription rate over the last 20 years, 1% of the population is on GCs, today | Fardet. 2011), were and still are used strategically as performance enhancing drugs. That this (ab-)use of synthetic glucocorticoids is not yet another 'broscientific' practice based on hear-say, not scientific evidence has now, more than sixty years after the invention of prednisone, the most commonly prescribed oral GC (76.6 - 92%), been re-investigated by Australian researchers (Tacey. 2017). And their review, which was meant to explore the limited research into the metabolic response following exercise, subsequent to exogenous GC treatment in healthy volunteers, clearly indicates that "short-term [<7 days] GC administration is likely to improve performance" (Tacey. 2017).
Table 1: Study characteristics and results following short term GC administration; a = compared with placebo results, Shaded boxes = values not reported by article (Tacey. 2017)
Table 1 gives you an overview of the (as previously pointed out) limited research into the short-term effects of glucocorticoid administration in healthy (including athletic) populations.
Beware! Glucocorticoids don't have the candy-like side-effect profile of creatine or whey! 71% of patients who consume them chronically report side effects within the first 3 months of treatment. With treatment induced Cushing's syndrome (i.e. excess glucocorticoids) being able to trigger diabetes, osteoporosis, hypertension, increased lipid accumulation, immunosuppression, delayed wound healing, glaucoma, neuropsychiatric disorders and skeletal muscle myopathy. I am sure you want to avoid (ab-)using this drug for performance enhancing effects for more than the 7 days that were tested in the study at hand (note: it would also be stupid to do so, because, after the short period of proven benefits, your performance will go down the drain). If you have to take them for medical reasons, you should know that exercise has been shown to mitigate most if not all of the effects of chronic glucocorticoid treatment (Pinheiro. 2009).
As you can see without having to scrutinize the data, all but one study observed statistically significant beneficial effects on exercise performance ranging from increases in knee extension performance (K) over shuttle run performances (S) to general strength increases (force output | FO) and increased VO2max (that's what the studies where the table only states "increased" measured). To give you a better idea of what exactly happened in the studies I will briefly summarize the individual results of six of them for you:
  • Arletaz et al. 2007: Ten recreational male athletes who had been randomized to oral prednisolone (60mg/day for 1 wk) treatment exhibited sign. improved cycling times (at 70-75% peak O2) significantly.
  • Casuso et al. 2013: The ingestion of  2 × 2 mg of dexamethasone for five consecutive days increased the one-legged dynamic knee-extensor exercise time to exhaustion by 29% and the total running distance the 17 healthy, but probably (undisclosed) not regularly trained young men covered in the shuttle run test by 19%.
    Figure 1: Performance benefits of 2x2 mg of dexamethasone for five days (Casuso, et al. 2013).
  • Le Panse, et al. 2009: Treatment with 50mg/day prednisone significantly increased the time to exhaustion (66.4 vs. 47.9, P < 0.01 | that's +39%) in a similar 75% VO2max cycling trial as it was used by Arletaz et al., albeit this time in recreational female athletes who had been cycling and/or running two to three times per week for at least 3 years.
    Figure 2: The study by Le Panse is interesting because it was done in female gymrats and because it shows the individuality of the response to prednisone (50mg/day) treatment (Le Panse. 2009).
    The results of this study are not just interesting because the subjects were (a) women and (b) representative of the average gymrat. They are also quite revealing because they show a sign. individuality - with one of the subjects (subject 6 in Figure 2) seeing no benefits at all and another one more than doubling her performance (subject 1 in Figure 2).
  • Marquet et al. 1999: With (male) athletes (cycling, judo, volleyball, boxing, rugby, triathlon, basketball, soccer) and non-athletes as study subjects, Marquet's study unquestionably sticks out, not just because it allows us to tell whether the short-term administration, but also because the scientists tested both (a) a low dose (0.5mg/day) and (b) a high-dose (1.5mg/day) regimen.

    Each treatment, i.e. low- and high-dose, was administered for 5 days before a standardized test was conducted. A test that found quite a plethora of effects, but no consistent effects on the subjects' sleep, exhaustion during exercise, maximal O2 consumption (VO2max), ventilatory threshold, maximal blood lactate, rest and exercise blood pressures or relevant interactions with the subjects' training status (i.e. the effects were identical for athletes and non-athletes).
    Figure 3: The effects of low and high dose of dexamethasone on heart rate, blood glucose and aldosterone (the 'water retention hormone') in trained and untrained subjects (Marquet. 1999).
    What the administration of dexamethasone did do, however, was to significantly (a) decrease the subjects' heart rate at rest and during maximal exercise, (b) increase their blood glucose at rest and (c) decrease their blood glucose levels during exercise.

    In addition, sign. lower blood levels of ACTH, b-endorphin, cortisol and cortisol-binding globulin were observed in response to dexamethasone - changes that went hand in hand not with water retention, but rather with an increase in the diuretic natriuretic factor during exercise and lowered levels of the "water retention hormone" aldosterone.
  • Nordsborg, et al. 2008: In response to 2 × 2 mg dexamethasone for 5 days, the scientists observed sign. increases in Na+, K+ pump subunits expression, a non-sign. increase in thigh blood flow during low-intensity exercise and an improved exercise performance for only 7 out of 9 subjects, recreationally active male subjects aged 24 ± 4 years.
  • Zorgati, et al. (2014): In ten healthy, physically active (running/swimming or playing soccer three to five times per week for at least 3 years), male volunteers (20.6 ± 0.9 years), the administration of 60mg/day of prednisone for one week, the scientists observed an increase in absolute peak force of the dominant leg in the first 30 seconds of a hopping test designed to elicit the subject's maximal force development, as well as a decrease in basal and end-exercise plasma interleukin-6 and saliva DHEA (p < 0.01) and increases of interleukin-10 (p < 0.01).
    Figure 4: Absolute maximal force (Fmax) (means ± SD) during the first three 30-s hopping bouts (1, 2, 3), and during the fourth bout until exhaustion (4) after placebo (PLA) and prednisone (Cor) treatment (Zorgati. 2014).
    Interestingly enough, no increase in hopping endurance, or significant effect on blood lactate, TNF-alpha, or saliva testosterone was found.
If you are now asking yourselves, what happened to the sixth study by Collomp et al. (2007), don't worry. I have singled it out, because it is the only one that can tell us something about the usefulness or stupidity of glucocorticoid abuse outside of the low-to-no-training pre-contest week, for which the previously discussed study results indicate often-times game-changing endurance and - at least in some cases - relevant strength benefits.
Figure 5: Changes in cycling time to exhaustion and selected hormones (Collomp. 2007).
Unlike all other studies, Collomp's 2007 study assessed the effects of taking prednisone at 60mg/day during a regular one-week training period with 2h of standardized physical training per day in eight recreational male athletes, actively cycling and/or running 2–3 times/week for at least 3 years. Nevertheless, some of the results are "old news" and have been observed in one or several of the previously discussed studies as well:
  • a significant endurance increase after one week on prednisolone which, on average, doubled the cycling times to exhaustion compared to placebo,
  • an extreme individuality in the size of the benefits among the eight subjects
The decline in ACTH, DHEA, and free testosterone, as well as (not shown in Figur 5) prolactin, growth hormone, and TSH (based on previous studies you can expect FT4 and FT3 dropped, as well), on the other hand appears to be even more drastic in the peri-workout period during which it was measured in the study at hand. What this means or the long(er) term effects of glucocorticoid administration, on the other hand, is not 100% clear. Mostly, because the of "the complexity of the hormonal and metabolic responses to short-term glucocorticoid administration during exercise" (Collomp. 2007) and the questionable role the acute elevation of alleged markers of anabolism such as testosterone, or growth hormone will actually have on the exercise-induced adaptational response aka "your gains".
Believe it or not. Cortisone can decrease body fat levels | more.
So, what should I remember about "cortisol" or rather glucocorticoids and performance? Well, while their long-term administration has unquestionable negative side effects in both average Joes and Olympic athletes, the latter can significantly benefit from their short-term (5-7 days) low-dose (ab-)use - not just, but especially if they compete in sports where a 10-20% increase in endurance or strength endurance performance can make the difference between victory and defeat ... and let's be honest: the number of Olympic sports where this wouldn't be the case be counted on the fingers of one hand.

Furthermore, athletes who belong to the same group of hyper-responders as subject 8 or subject 1 in Le Panse (2009) would go from "zero to hero" within one week - or how else would you describe performance increases of 100% and more? Comment on Facebook!
References:
  • Arlettaz, Alexandre, et al. "Effects of short-term prednisolone intake during submaximal exercise." Medicine and science in sports and exercise 39.9 (2007): 1672.
  • Casuso, Rafael A., et al. "Glucocorticoids improve high-intensity exercise performance in humans." European journal of applied physiology 114.2 (2014): 419-424.
  • Duclos, Martine. "Glucocorticoids: a doping agent?." Endocrinology and metabolism clinics of North America 39.1 (2010): 107-126.
  • Fardet, L., I. Petersen, and I. Nazareth. "Description of oral glucocorticoid prescriptions in general population." La Revue de medecine interne/fondee... par la Societe nationale francaise de medecine interne 32.10 (2011): 594-599.
  • Le Panse, Bénédicte, et al. "Short-term glucocorticoid intake improves exercise endurance in healthy recreationally trained women." European journal of applied physiology 107.4 (2009): 437-443.
  • Marquet, P., et al. "Dexamethasone in resting and exercising men. I. Effects on bioenergetics, minerals, and related hormones." Journal of Applied Physiology 87.1 (1999): 175-182.
  • Nordsborg, Nikolai, et al. "Effect of dexamethasone on skeletal muscle Na+, K+ pump subunit specific expression and K+ homeostasis during exercise in humans." The Journal of physiology 586.5 (2008): 1447-1459.
  • Pinheiro, Carlos Hermano da Justa, et al. "Exercise prevents cardiometabolic alterations induced by chronic use of glucocorticoids." Arquivos brasileiros de cardiologia 93.4 (2009): 400-408.
  • Zorgati, Houssem, et al. "Ergogenic and metabolic effects of oral glucocorticoid intake during repeated bouts of high-intensity exercise." Steroids 86 (2014): 10-15.