Disappointing Results in 28-Day Creatine + β-Alanine Study: No Performance Benefits, No Muscle Gain, No Fat Loss, No Increase in Phosphocreatine & Carnosine in 32 Women

Let's take a closer look at the study and find how it was possible that two proven ergogenics "failed".

Creatine and beta-alanine belong to the few "proven ergogenics", but according to the latest study from the University of Pittsburg, the Texas Christian University, the University of Wisconsin – La Crosse and the Texas A&M University they are not as effective as some of us may think. Specifically the effects of beta-alanine which was tested in what you may call its "comfort zone", i.e. a graded exercise test on the cycle ergometer for VO2peak with lactate threshold determination, and multiple Wingate anaerobic capacity tests. And still, the overall results of the study is that there a "no consistent additive benefits of BA [beta alanine] and CRE [creatine] supplementation in recreationally active women.

If you are using creatine already try adding bicarbonate as extra-cellular pH-buffer

The Hazards of Acidosis

Build Bigger Legs W/ Bicarbonate

HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

Bicarb Buffers Creatine

Beta Alanine Fails to HIIT Back

In today's SuppVersity article, we are going to have a closer look at the study design, its outcomes and potential explanations for the absence of the highly desirable performance enhancing effects of these two (alleged) ergogenic powerhouses.

As you may know I am not a fan of beta alanine, anyway. Yet despite my alleged bias, I have to admit that the wingate tests the scientists used to determine the effects of the supplementation protocol may have been too short for BA to work. In the most comprehensive meta-analysis of the research to-date, Hobson et al. (2012) found that there are no ergogenic effects to beta alanine on exercises lasting less than 60s or more than 240s; and in the "ergogenic" 60-240s zone, the performance benefit is only 2.85%.

Figure 1: In view of the short study duration it's no wonder that there were no significant effects on body fat and lean mass, but the fact that the beta alanine only group actually gained fat after an initial high loss of body fat is still awkward - still, statistically significant was only the time effect, which tells you that exercise works (Kresta. 2014).

And as far as the absence of benefits of creatine are concerned. The results of the study are in line with previous experimental evidence like that presented by Green et al. who report in their 2001 article in the The Journal of Strength & Conditioning Research that...

"[...] short-term Cr supplementation does not enhance MP and PP during repeated upper-and lower-body Wingate tests when not accompanied by an increase in body weight." (Kresta. 2001)

Similarly, Hoffman et al. (2008) could not find perfomance benefits of short-duration beta alanine supplementation in college football players, what the scientists from the College of New Jersey did find, though was an increases training volume and reduces subjective feelings of fatigue in their highly trained subjects in response to the ingestion of 4.5g/day of beta alanine (Hoffman. 2008).

All in all, the results are thus less surprising than they appear to be...

... at least for those of you who don't believe in the unsustainable promises of the supplement industry, but rely on experimental evidence, only. For creatine, the scientists tested the wrong type of exercise. For beta alanine the exercise duration (60s) on the wingate tests was not long enough to show significant performance increases.

Figure 2: Non-significant (!) changes in carnosine (should increase with BA supplementation) and phosphocreatine (should increase with creatine supplementation) in the BA, BAC, CRE and placebo group (Kresta. 2014).

What the previous brief review of selected experimental evidence does not explain, though, are (a) neither the beta alanine, nor the creatine or combined supplementation lead to statistically significant increases in carnosine (via beta alanine) or phosphocreatine (via creatine), (b) the levels of phosphocreatine the high energy resource, that is believed to be responsible for most of the beneficial effects of creatine actually dropped after 2 weeks on maintenance dose of 0.1g/kg creatine, when it was administered after a 0.3g/kg creatine pre-load. These results stand in contrast to previous studies, like...

• Harris and colleagues (2001) who reported that β-ALA supplementation (3.2 g/day) resulted in a 42% increase in muscle carnosine levels after four weeks of supplementation not due to the fact that the carnosine levels didn't increase, but rather due to the fact that the scientists did not find statistically significant interactions among groups in muscle carnosine levels.
  
  As Kresta et al. (2014) point out, "the lack of statistical significance was apparently due to the large variability in muscle carnosine levels observed in response to β-ALA supplementation, assay variability, and/or inadequate sample size", so that "[m]ore research is needed to determine the effects of β-ALA supplementation on muscle carnosine levels in recreationally-active women" (Kresta. 2014).
• Greenhaff et al. (1994) or Harris et al. (1992) who found significant increases in phosphocreatine with similar preloading + maintenance creatine supplementation schemes as the one used in the study at hand, but yielded significantly higher and above all consistent increases in creatine of up to 40% . Results from the present study found non-significant increases in muscle PCr of up to 40%
  
  Again, Kresta et al. suspect that "the lack of significance may have simply been a result of the small sample size", but add that "it is also known that there is individual variability in response to creatine supplementation" (Kresta. 2014) - a fact that is imho unlikely to be a likely cause of the lack of effect in all subjects, though.

Overall it is thus difficult to determine the lack of consistence improvements in carnosine and phosphocreatine levels in the study at hand, it may yet, as Kresta et al. suggest also be possible...

A study by Everaert, et al. indicates that women have naturally lower carnosine levels (Evaerart. 2011 | see figure abvove). Previous studies, e.g. Tallon (2006), however, found no such difference which is interpreted by Harris et al. in their 2012 review as evidence that "that the apparent gender difference reported by Everaert et al. (2011) may have been simply due to a higher type I:II ratio in females in the voxel sampled." (Harris. 2012)

"[...]that sex may have played a role in response to creatine and/or β-ALA supplementation. In this regard, most studies on creatine and β-ALA supplementation have been conducted on males and there is some evidence that females may respond differently to creatine and/or β-ALA supplementation. For example, Fosberg and colleagues (Forsberg. 1991) reported that females had greater total creatine amounts relative to tissue weight; however, other studies show there is no difference between males and females (Forsberg. 1991; Stegen. 2014).

There are also some data suggesting that men may have greater muscle carnosine levels than women (Derave. 2002; Harris. 2012); however, a recent study showed sex did not have an effect on increasing carnosine levels with supplementation (Stegen. 2014). Additionally, Bex and coworkers (2014) reported that carnosine loading is more pronounced in trained versus untrained individuals" (Kresta. 2014).

It is thus possible, but imho again not very likely that the fact that the subjects in the study at hand were women and or their individual training status may have had and impact on the hardly existing response to creatine and/or β-ALA supplementation.

Creatine + bicarbonate appears to offer a superior synergism | learn why

In the end, it's yet not the increase in carnosine or phosphocreatine that's important for us. What we are looking for are performance increases, which were probably absent due to the selected tests, on which previous studies have already shown that creatine and beta alanine have failed before to produce significant performance increases (see previous elaborations on the non-existent effects of BA on 60s and >240s exercise and the issue with creatine and wingate tests), plus changes in body composition for which the four-week study period may simply have been too short.

Against that background I would like to point out that the study at hand does not indicate that either beta alanine or creatine are useful. What it does, thought, is to remind us of the fact that (a) you won't see results over night and (b) even beta alanine and creatine are exercise-specific ergogenics and won't boost your performance an each and every type of exercise to the same extent. Or what do you think are the implications? Comment on Facebook!

References:

• Bex, Tine, et al. "Muscle carnosine loading by beta-alanine supplementation is more pronounced in trained vs. untrained muscles." Journal of Applied Physiology 116.2 (2014): 204-209.
• Derave, Wim, et al. "Muscle carnosine metabolism and β-alanine supplementation in relation to exercise and training." Sports medicine 40.3 (2010): 247-263.
• Everaert, Inge, et al. "Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans." Amino acids 40.4 (2011): 1221-1229.
• Green, J. Matt, et al. "The effects of creatine supplementation on repeated upper-and lower-body Wingate performance." The Journal of Strength & Conditioning Research 15.1 (2001): 36-41.
• Harris, Roger C., et al. "The absorption of orally supplied β-alanine and its effect on muscle carnosine synthesis in human vastus lateralis." Amino acids 30.3 (2006): 279-289. 
• Harris, R. C., et al. "Determinants of muscle carnosine content." Amino acids 43.1 (2012): 5-12.
• Hobson, Ruth M., et al. "Effects of β-alanine supplementation on exercise performance: a meta-analysis." Amino acids 43.1 (2012): 25-37.
• Hoffman, Jay R., et al. "Short-duration< i> β</i>-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players." Nutrition Research 28.1 (2008): 31-35. 
• Kresta, Julie Y., et al. "Effects of 28 days of beta-alanine and creatine monohydrate supplementation on muscle carnosine, body composition and exercise performance in recreationally active females." Journal of the International Society of Sports Nutrition 9.Suppl 1 (2012): P17.
• Stegen, Sanne, et al. "The Beta-Alanine Dose for Maintaining Moderately Elevated Muscle Carnosine Levels." Medicine and science in sports and exercise (2014).
• Tallon, Mark J., et al. "Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects." Biogerontology 8.2 (2007): 129-137.

More Than 3x Higher EPOC Induced Energy Expenditure With HIIT vs. LISS! But Does That Really Matter? Plus: Why Headlines Like This May Compromise Your Progress

If you are sprinting because of the increase in EPOC, you are a fool.

Those of you have been following the SuppVersity for quite some time, now, will be familiar with the term "EPOC", which refers to the amount of oxygen that is consumed in excess in the post-exercise - or, in order not to overcomplicate things, the excess post-exercise oxygen consumption, or, even simpler the amount of energy your burn after a workout because your mitochondria are "still on fire".

Assuming that you have read those of the >1250 hitherto published SuppVersity Articles that were dealing with this issue you may remember that I have repeatedly pointed out that...

... the contribution of the actual energy consumption that is caused by the "EPOC effect" would be absolutely irrelevant, if the calories in vs. calories out equation was as simple as mainstream dietitians and lifestyle magazine authors still like to present it to their clients and readers.

Now you know better than that so that I don't have to tell you why I do even care about the results of a recent study from the Universities of Central & West Florida (Townsend. 2013). After all, the EPOC is by far not the only metabolic effect that's missing from the "standard equation of exercise-induced weight loss", i.e. [calorie intake - (resting metabolic rate + calories burnt during exercise)] / [3,500 kcal/lbs] = amount of fat lost (in lbs).

Let's get to the study first!

HIIT does not work because it burns more energy! As Williams et al. (2013) observed recently the benefits of HIIT don't come from...,

• an increase in EPOC (excess post-exercise oxygen consumption)
• an increase in resting energy expenditure (RER), which actually drops in the 60min after exercise, and
• a larger amount of fat being burned during the workout

So if it's none of these, does HIIT work at all? Well if you asked Williams et al. they would probably say that based on their results it works because of its appetite suppressive effects, which have by the way been demonstrated by in another recent study that is about to be published in the scientific journal Obesity (Sim. 2013).

What is yet of much greater importance is that HIIT is intense enough to actually enforce adaptation and mitochondrial biogenesis. It helps you to build a bigger engine and the latter will help you in your efforts to lose weight and build muscle.

Before we get into the discussion, whether or not the 200% increase in EPOC Jeremy R. Townsend and his colleagues observed in 6 recreationally-trained males (age: 23.3±1.4 yrs; body mass: 81.8±9.9 kg;  height:180.8±6.3 cm), let's first take a look at the different exercise protocols the participants were exposed to on the two testing trials that were scheduled to take place at the same time of the day to minimize the effect of the circadian rhythm.

• a moderate aerobic exercise protocol consisting of a 30-minute submaximal cycling bout at 60% of heart rate reserve on an electronically braked cycle ergometer (HRR), and 
• three repeated 30-second Wingate cycling tests separated by four minutes each on a Monark 894E cycle ergometer (SIE).

Three hours before each of the trials, the subjects consumed a standardized meal replacement bar (43 g carbohydrate, 10 g protein, 6 g protein, 1004.6 kJ total). Water was consumed ad libitum and each testing trial was separated by 48 hours and was implemented in the random counterbalanced design.

"Recorded data in SIE consisted of peak power output, mean power, and fatigue index. [...] Following testing trials, supine VO 2 was measured for 30 minutes or until baseline measures were reached. A participant was considered to have reached baseline when the average of two consecutive minutes was equal to baseline values.

EPOC was determined by subtracting baseline VO2 from post-exercise recovery VO 2 measurements. [...] Energy expenditure (kJ) was determined by multiplying kcals per liter of oxygen (20.93 kJ∙L O2) by the average VO 2 during recovery." (Townsend. 2013)

As the data in figure1 goes to show you, both the VO2 and EPOC values were significantly higher during the 30 minutes of post-workout recovery in the SPIE group.

Figure 1: EPOC and corresponding additional energy expenditure in the high intensity 3x Wingate group (SPIE) and the 30min continuous exercise group (HIE) during the 30 min right after the workout (Townsend. 2013)

In fact, the average EPOC value was 316% higher in the SPIE group. This value is, however, deceiving as it does not reflect the actual difference in post-workout energy expenditure which was 39.75kcal vs. 10.25kcal and thus "only" 287% higher in the SPIEE group.

---

"Hold on, you mean 397.5kcal, right" NO, I don't! It is, in fact, nothing but a fifth of an apple and you don't want to tell me that this will make a difference, right?

If you are training like Haile you better are a marathon runner. If you do that to lose weight or have reached the point, where you need to do it not to gain weight, it's time to make a change, because in that case, the cardio is already hampering your gains and progress towards the physique you are aspiring (learn more). Train to build a bigger engine and eat to support your muscle gain or fat loss goals, not vice versa!

Thus we are back to the initial question whether EPOC matters... now if you look at the figures, you will have to admit: It does not matter. But guess what, the same is true for the 600kcal you may be spending doing LISS everyday.

If you are still heading to the gym to "burn calories" you really don't deserve the physique you're torturing yourself for. Train to get healthy, train to stay healthy, and train to build a bigger engine (which requires progressive, intense training on the track and in the gym) and have your diet take care of the rest.

Does this mean there is no role for cardio exercise in your regimen? No, it does not, but once you have achieved a point, where you are just performing it to "allow yourself that additional sweet potato", it's about time to make a switch... unless the physique you are aspiring is that of Haile Gebrselassie.

So what can you do? Lift weights, improve your conditioning and diet, if you feel you have got to lose weight, but don't train to lose weight. Train to maintain weight: Muscle weight! Train to get faster, train to get stronger and train to build your endurance. Record your progress set short-term goals for the gym, the track, and the kitchen, be patient and cherish every success and you will shed that belly, not despite, but because you are not "burning enough calories".

References:

• Sim AY, Wallman KE, Fairchild TJ, Guelfi KJ. High-intensity intermittent exercise attenuates ad-libitum energy intake. International Journal of Obesity advances online publication 9 July 2013. [epub ahead of print]
• Townsend JR, Stout JR, Morton AB, Jajtner AR, Gonzalez AM, Wells AJ, Mangine GT, McCormack, WP Emerson NS, Robinson EH, Hoffman JR, Fragala MS Cosio-Lima L. Excess Post-Exercise Oxygen Consumption (EPOC) Following Multiple Effort Sprint And Moderate Aerobic Exercise. Kinesiology. 2013; 45(1):16-21
• Williams CB, Zelt JGE, Castellani LN, Little JP, Jung ME, Wright DC, Tschakovsky ME, Gurd BJ. Changes in mechanisms proposed to mediate fat loss following an acute bout of high intensity interval and endurance exercise. Applied Physiology, Nutrition, and Metabolism. 11 June 2013 [epub ahead of print]

Are Elevated Iron and Uric Acid Levels Too Much of a Price to Pay for a Creatine-Induced 11% Performance Increase?

Video 1 (GSSI): Notre Dame's Michael Floyd goes all out on the Wingate test (click to watch)

I guess you could say that these are the "classic days", here at the SuppVersity, contrary to my previous post on choline, which is - judged by the few people who still use it today, an "old school supplement" (cf. "Choline: Stronger, Faster, Leaner & More Muscular, or Just Another Dumb-and-Barbell Story?") - yesterday's post on caffeine highlighted the efficacy of a potent ergogenic aid and metabolic activator, with the effects of which most of us are so familiar that we are alway tempted to turn to useless crap like raspberry ketones, when what we are already doing is not only tried and proven, but based on respectable scientific data even more effective than the latest "innovation" from the snake oil industry. And let's be honest, haven't we all been tempted by one or another "new creatine", as well?

+11% peak performance in one week, solely from 5x4g of creatine per day!

A a matter of fact, creatine monhydrate does in fact share the same fate of being proven, but "boring" staple supplement and although that alone should be incentive enough to address the unquestionably outstanding +11% in anaerobic peak performance, +5% in continuous anaerobic performance and a +6% increase in total workload in a classic wingate anaerobic performance test speak, Barros et al. observed in a group of trained male subjects in response to a 7-day creatine loading protocol (20g creatine monohydrate, in 5 doses spread across the day, not glucose / sugar added; cf. Barros. 2012) After all, my gut tells me that the contemporary changes in the concentration of iron in the blood of the subjects in the the creatine arm of the study could revoke the mainstream-media fearmongerish hoopla over the purported dangers of the #1 natural ergogenic.

Figure 1: Basal iron, FRAP, malondialdehyde (MDA) and uric acid levels before and after 7-day supplementation with 5x4g of creatine monohydrate per day (based on Barros. 2012)

I mean, there is no debating, the level of iron in the blood of the creatine supplemented undergraduate students (age, 23.1 ± 5.8 years; height, 175.4 ± 2.3 cm; weight, 81.1 ± 9.3 kg) all of whom had been avid trainees for at least 6 months did increase by no less than 94.3%, while the subjects in the placebo group experienced a -21% reduction of these highly reactive molecules (Just as an aside, the decline in serum iron in the placebo group and the significant difference in baseline levels between the random groups, alone, render any implications at least questionable; I mean, wouldn't you expect the serum parameters to stay the same, when you do nothing extraordinary, aside from popping some sugar pills?).

Figure 2: Changes in wingate anaerobic performance (left) and exercise induced changes iron, FRAP, malondialdehyde (MDA) levels during the wingate test at the end of the supplementation period (based on Barros. 2012)

In conjunction with the likewise highly significant increase in uric acid levels, conventional (blogosphere-)wisdom, which constantly ignores the antioxidative nature of uric acid, which acts as efficient antioxidant and chelating agent for iron ions (Karlsson. 1997), limits the oxidation of polyunsaturated fatty acid in the erythrocyte membrane and prevents hemolysis (= the rupture of red blood cells) in vitro (Einsele. 1987), would suggest that taking creatine takes a close second to fructose on the list of the villains of the bad, bad "neolithic" century.

How dangerous is the creatine induced increase in iron?

Image 1 (Paramount Pictures): I guess, it must have been creatine monohydrate, then, that turned Robert Downey Jr. into Ironman ;-)

Now, despite the as of late publicly propagated concerns about increased iron levels and their potential causative role in the etiology of insulin resistance and diabesity (obesity + diabetes), recent scientific evidence suggests that "high iron", such as all previous scapegoats people like to hold liable, just to make sure not to admit that it is the sickening combination of laziness, convenience and unsound dietary advice that is at the heart of the current obesity epidemic.

Huang et al., for example, did observe a direct effect of iron overload on diabetes risk - the latter was however a result of hereditary hemochromatosis (a genetic defect in iron metabolism) in their 2011 rodent trial (Huang. 2011). Results from two more recent studies by Silva et al. also indicate that the metabolic disturbances lead to differential expressions of the proteins involved in the metabolism of iron and thus substantiate the associative (and not causative) nature of the relation between high iron / ferritin and the metabolic syndrome (Silva. 2011; Silva. 2012).

Iron not causative? So why does phlebotomy help, then? If you read my post on the recently published data from the first controlled human trial that investigated the effects of phlebotomy on markers of blood glucose management, you will be aware that the measures they took, e.g. the HOMA-IR, are not really appropriate to assess the effects of this particular treatment (cf. "Phlebotomy: Can You Bleed Yourself Healthy and Lean?"). Furthermore, it is only logical that the removal of some of this "highly inflammable stuff" from an inflamed body will provide health benefits, even if the latter was totally benign for someone who has a lot less inflammation going on.

What is even more important, though, is that the difference between exercise-induced increases in serum iron and diet and diabesity-related increases in the storage form of iron, ferritin, in the liver. This is particularly true in view of the fact that our understanding of the former, i.e. the exercise induced release of iron into the blood stream is more than limited (Roberts. 1989; Smith. 1994). What we do see in the Barros study, however, is that the overall effect of creatine is rather anti- than pro-oxidative, since the increase in overall antioxidative capacity (as indicated by the changes in the iron-specific FRAP essay; cf. figure 1) did not just...

• negate the potential negative effects of increased basal iron levels (see lowered baseline MDA levels post supplementation in figure 1), it also 
• countered the exercise-induced lipid oxidation during the 2nd wingate test (as indicated by lower MDA levels; cf. figure 2). 

Eventually, the scientists say, the increase in antioxidant activity that is brought about by the ingestion of 20g/day creatine irrespective of whether you exercise or not could actually yield "general health benefits" (Barrios. 2012); and I would like to add that evidence for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, recovery from ischemia and, guess what, diabetes already exists (Tarnopolsky. 2000;"Creatine Ameliorates Type II Diabetes")! Certainly not bad for one of those bodybuilding supplements, "anabolics" or "gateway drugs", as creatine is often mislabeled , when a 100% clueless "journalist" tries to get the attention of his editor-in-chief, wouldn't you agree?

Suggested readings (some also mentioned in the text):

• The Pharmacology of Creatine (Part 1 and Part 2) 
• Supercharging Creatine With Baking Soda (click here to read)
• 5g/day Creatine for Type II Diabetics? (click here to read)
• All posts tagged with "creatine" (click here to read)
• Phlebotomy: Can You Bleed Yourself Healthy and Lean? (click here to read)

References:

1. Barros MP, Ganini D, Lorenço-Lima L, Soares CO, Pereira B, Bechara EJ, Silveira LR, Curi R, Souza-Junior TP. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. J Int Soc Sports Nutr. 2012 Jun 12;9(1):25. 
2. Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel ED, Cooksey RC, McClain DA. Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes. 2011 Jan;60(1):80-7.
3. Orozco MN, Solomons NW, Schümann K, Friel JK. Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men. Food Nutr Bull. 2012 Mar;33(1):53-62. 
4. Roberts D, Smith DJ. Effects of high-intensity exercise on serum iron and α1-antitrypsin in trained and untrained men. Clin Sports Med 1989, 1:63–71.
5. Silva M, Bonomo Lde F, Oliveira Rde P, Geraldo de Lima W, Silva ME, Pedrosa ML. Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator-activated receptor-α expression. J Clin Biochem Nutr. 2011 Sep;49(2):102-8.
6. Silva M, de Brito Magalhães CL, de Paula Oliveira R, Silva ME, Pedrosa ML. Differential expression of iron metabolism proteins in diabetic and diabetic iron-supplemented rat liver. J Biochem Mol Toxicol. 2012 Mar;26(3):123-9. 
7. Smith DJ, Roberts D. Effects of high volume and/or intense exercise on selected blood chemistry parameters. Clin Biochem 1994, 27:435–440.
8. Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):497-502.

The Anabolic Effects of HIIT: 3x30s High Intensity Intervals Increase mTOR & Ramp Up Marker of Protein Synthesis by +43% in Men and +222% in Women - Even in a Fasted State!

Image 1: While the study at hand clearly shows that HIIT, even done on an empty stomach, is anabolic, not catabolic, it appears as if women respond better to sprint exercises than men. And this assumption is not based on gene-assays but dates back to the results of a 1999 study by Esbjörnsson which showed a more pronounced CSA increase in the leg muscles of female subjects.

Not all too long ago, the general accepted consensus was that anyone whose main interest is in building muscle must abstain from any strenuous cardiovascular exercise... running on a treadmill? God-forbid! You could lose muscle. Over the last two years or so, this paradigm has began to totter, though. And now, at the beginning of 2012 I would estimate that the number of (recognized) trainers and trainees who recommend doing high intensity interval training (HIIT), if not for general conditioning, then at least as a means to shed fat, initially surpasses the number of the conventionalists who maintain that "classic cardio" training in the "fat-burning zone" was the way to go. Now, if this is not your first visit here at the SuppVersity, you should be aware that the latest scientific research supports the arguments of the advocates of HIIT. And not so much to my, as to the surprise of some researchers, this holds true not only for already well-conditioned gymrats and athletes, who want to finally pass beyond the 10% body-fat barrier, but also for the obese and metabolically deranged diabetic, who is trying to get his blood sugar under control (cf. "Hitting Diabetes With A Hammer").

The advantages of HIIT reach well beyond fat loss, but...


Moreover, a 2011 study by Naito et al., the results of which I have discussed in November 2011, shortly after it was published in Acta Physiologica (cf. "HIT Your Satellite Cells to Increase Your Gains"), already hinted at the fact that the advantages of HIIT reach well beyond its fat-burning effects. Yet although the increase in both satellite cell count and incorporation into the muscle Naito et al. observed speak for themselves, there's still rumors going round that this training style could be catabolic. In that the argument usually revolves around the notion that muscle damage is a major driving force of satellite cell recruitement and that if the latter is a necessary consequence of HIIT it would counter your efforts to build muscle. Now, aside from the fact that this argument is intrinsically flawed (I mean, what to you do in the gym, when you weight train? You break down muscle tissue!), a recently published study from the famous Karolinska Institute in Stockholm, Sweden, attests to the fact that the exact opposite is the case.

... it appears as if women could derive even greater benefit from all-out sprinting than men

Image 2: The exercise stimulus in the study was a Wingate test, one of standard procedures in exercise science.

In an earlier study from 1999 Esbjörnsson and his / her colleagues had observed that the cross-sectional area of the leg muscles of women exhibited a more pronounced hypertrophy response to sprint training than those of their male peers (Esbjörnsson. 1999). With the advent of our advanced understanding of the underlying principles of skeletal muscle hypertrophy and the central, but as those of you who read the Hypertrophy 101 know, in the current discussion possibly overemphasized position of the mammalian target of rapamycin (mTOR), Esbjörnsson et al. did now set out to examine, whether a sex-specific response of mTOR and its downstream targets could explain their previous results (Esbjörnsson. 2012).

To this ends, the scientists recruited nine men and eight women who despite participating in leasure time sports were only "in good shape" and not considered to be athletes. For the experiment the subjects reported to the lab fasted and, after a brief 1min warm-up, performed the well-known Wingate-test, which consists of three consecutive 30s all-out sprints with 20min breaks between the intervals on a braked cycle ergometer (average peak power was ~645W and ~935W for women and men, respectively, on a per-lean body-mass base, the peak and mean power was yet identical)

Figure 1: Illustration of the experimental protocol used in the study.

Before the warm-up and 140min after the 3rd sprint, Esbjörnsson et al. took muscle biopsies from the quadriceps muscles of the subjects to assess the local expression of mTOR and its downstream targets.

Figure 2: Phosphorylated AKT, mTOR, p70S6K and rpS6 (a.u.) in male and female study participants before the first and 140min after the third sprint of the Wingate test (data adapted from Esbjörnsson. 2012)

If you are not well-versed in the the intricacies of the mTOR-cascade, it appears as if the data in figure 2 would disprove the scientists' research hypothesis that "mTOR signalling is more pronounced in women than in men". After all, the increase in phosphorylated mTOR (p-mTOR) and AKT (p-AKT) in response to the three 30s seconds sprints was obviously more pronounced in the male, than in the female participants (mTOR +26% and AKT +17% greater increases; a difference which did not reach statistical significance, though).

Do women just make better use of the same stimulus?

As far as the phosphorylation of p70S6K, of which the current scientific evidence suggests that is a more appropriate measure of the "real-world" protein synthetic effect of mTOR, a completely different picture emerges. While the +43% increase in the male subjects is just about statistically significant (p = 0.04), the +222% increase in p-p70S6K in the female subjects appears to confirm what Esbjörnsson et al. already  had suspected.

Figure 3: Serum leucine and growth hormone levels at rest and after the sprints (data adapted from Esbjörnsson. 2012)

The slightly greater disappearance of leucine from the skeletal muscle of the male subjects (cf. figure 3) is yet only one of three possible explanations (and one you could counter by ingesting BCAAs, for example) Esbjörnsson et al. come up with based on the results of previous studies:

Image 3: If you look at the leg muscles
of some of the female speed skaters,
it is quite obvious that the leg muscles
of women respond pretty well to short,
intense bouts of all-out sprinting.
(the image shows Claudia Pechstein)

1. Lower accumulation of lactate and ammonia and a faster recovery of ATP levels in type II fibers of women than men
    
2. Lower levels of plasma catecholamins (=stress hormones) in response to sprint exercises in women than in men
    
3. Slower disappearance of leucine and thusly more sustained elevation of protein synthesis in women than in men

Whether it is any of these, or a combination of all three factors which is responsible for the differential response to statistically (!) not significantly different activations of mTOR and p-AKT, cannot be decided based on the available data.

An alternative explanation, which would, by the way, have real-world implications for the training practice, is (and I prefer to cite this, to avoid being accused of sexism) that...

women do not exhaust themselves as much as men during each bout of exercise and thereby elicit a smaller activation of AMPK, resulting in less inhibition of mTOR.

In view of the fact that previous studies by Esbjörnsson et al. refute this hypothesis, it appears unlike that an "over-expression" of AMPK, of which I have discussed in one of the previous installments of the Intermittent Thoughts that its locally expressed alpha-2 isoform does not inhibit the exercise induced increase in protein synthesis, anyway, could explain why similar exercise stimuli (peak and mean power per fat-free mass were virtually identical for men and women) and within the statistical margin identical mTOR responses induce a more pronounced protein synthetic response in women than in men. And whether the early(-ier) rise in serum growth hormone, which is the last possible explanation the scientists mention, has anything to do with it appears questionably, as well. After all, the data in figure 3 shows quite clearly that the overall GH response was much more pronounced in the male than the female participants.

We don't know about aliens, but for earthlings HIIT is anabolic - regardless of their sex

In essence, it does not even really matter, what the underlying cause of the sex-specific response to sprint training is. As far as I am concerned, the most significant result of the study is not the gender-difference, but the simple, yet as the scientists point out "novel" finding that "repeated 30-s all-out bouts of sprint exercise, separated by 20 min of rest, increased Akt- mTOR signalling in skeletal muscle." And this effect was observed in both men and women. Now, this is allegedly not exactly your "usual" HIIT protocol, if you do yet take into consideration that it was performed after an overnight fast and went without BCAAs, protein shakes all the other "obligatory" anti-catabolics, the average gymrat uses to avoid the purported catabolic effects of high intensity conditioning work, I would dare to say that it HIITs another (if not a final) nail into the lid of the casket of the "HIIT = catabolic" myth.

Electrical Stimulation Improves Clearance of Lactic Acid After Anaerobic Activity in Collegiate Athletes. EMS Turns Out to Be as Effective as 'Traditional' Massage Therapy.

Image 1: The EU-940 EMS device the
scientists used in their study to activate
the vastus medialis and lateralis (high-
lighted in the image) of their subjects, is
very different from the average EMS based
"abdominal toner" advertised on TV.

Even here, at the SuppVersity, news on ergogenics, i.e. things that improve (athletic) performance, are usually about a pill, a fancy plant extract or another 'superfood'. Today's news, however is about a much more "physical" means to improve anaerobic exercise performance, decrease lactate accumulation and improve regeneration: Electrical Muscle Stimulation (EMS).

EMS? Now, many of you will probably remember those TV spots, where you were told that "Abmaster" & Co would transform your pot-belly into a "six-packed" attractant for the opposite sex, if you did not miss this "unique" opportunity and bought one of those electro-shockers no sane fitness professionals would voluntarily substitute his/her good old sit-ups and leg raises for. Yet, while these battery-powered torture instruments did, or I should say, were intended to electrically stimulate muscles (in fact in many of the obese buyers of these products, the abs were probably covered by a layer of fat that was way too thick for actually "stimulation" of the abdominal muscles to occur), both the devices, as well as the EMS protocol Seo et al. (Seo. 2011) employed in their double-blind randomized controlled trial at the Sports Science Research Laboratory of Kyungwoon University in Korea were a little more sophisticated.

Did you know? The fatigue index is a concept used in the study of fatigue during anaerobic activities. It is the ratio of power decline to the length of the time interval in seconds between peak power and minimum power. This means lower fatigue indexes equate lower declines of exercise intensity per time unit. When looking at the data in figure 1, you may want to keep in mind that higher starting values / greater overall workloads will entail greater declines in anaerobic power per time unit and thus present with higher fatigue indexes

During and after 3 all out intervals on an ergometer (resistance: 0.8 x body weight Nm; active rest between intervals: 10 seconds) verbal feedback on perceived fatigue, fatigue indexes in W/s, mean power/weight, total work and lactic acid values (from serum drawn before, after and at 15 min and 25 min post exercise) were recorded in a group of 24 randomly selected collegiate Taekwando athletes (age: 19.8yrs, height; 177cm; weight: 66kg, training experience: 5yrs; mean values with non-significant differences between groups).

Figure 1: Fatigue index, mean power (primary axis) and total workload (secondary axis) during Wingate ergometer test
(data adapted from Seo. 2011)

Immediately after the exercise bout, eight athletes, each, received one of the following treatments:

Table 1: Outline of the massage
protocol the  athletes in the massage
group received after having performed
an exhaustive anaerobic Wingate
ergometer test (according to Lee. 1998)

• The control group received no regenerative treatment at all. 
• The massage group was subjected to a massage protocol which had been shown to effectively improve exercise recovery in a previous study by the same authors (Lee. 1998).
• The EMS group was attached to an interferential current unit (EU-940, ITO CO., LTD, Tokyo, Japan), which applied an interferential current with a carrier frequency of 4kHz and a pulse duration of 125µs via four vacuum electrodes (vacuum pressure: 60ppm) to the vastus medialis and the vastus lateralis of the subjects.*
  * "The current  intensity was set within the range of the minimum visible contraction of the quadriceps femoris muscle", so that the muscle of the quadriceps were maximally stimulated, while the current was not so intense that cross-over effects to neighboring muscle groups would occur.

Seo and his colleagues found "significant differences in the lactic acid concentrations in the blood among the three groups [...] at 15 min and 25 min after exercise".

Figure 2: Relative reduction in lactic acid concentration after a wingate performance test followed by massage or EMS therapy compared to untreated control (data adapted from Seo. 2011)

As the data in figure 1 shows, massage and EMS promote the clearance of lactic acid to a similar degree (+17-18% vs. control). So, if you are a professional athlete you should either make good use of your already existing six pack and attract a significant other who is a massage therapist or save some bucks and get yourself a reasonably professional EMS device, in case you intend to be a gold medalist at the 2012 Olympics in London ;-)

Edit (26 July): The lactate & Lactic acid confusion

After I posted this piece of information an interesting discussion around the physiological role of lactic acid broke lose on Facebook and I do not want to deny you the great information my buddy Sean Casey from CasePerformance brought to the table. So, here is what he had to say:

Lactic Acid is an interesting thing....During the 1970-1980’s various studies found lactic acid impaired strength and contraction velocity in samples of isolated muscle tissue (1). Based off these early findings, many researchers evaluated ...post workout recovery modalities on their ability to remove lactate from muscle tissue post workout. Similarly, coaches and athletes started employing post workout techniques aimed at removing lactate from muscular tissue. For instance, our high school track coach used to have us lie on our backs and rest our legs on an elevated surface w/ respect to our body. Usually we'd lie on the floor next to a wall & place legs on wall. The theory was that acid would “drain” out of our muscle tissue, allowing our legs to be fresher for the following day’s workout. (I know, a very bro-science approach; , but mentally felt good and you'd always get a cool tingly sensation when you set your legs down and the blood rushed back into them!)

Interestingly, it turns out that lactic acid may not be the best form of measurement with respect to evaluating the effectiveness of a PWRM [post workout recovery measures]. As pointed out by Cairns SP, it may have a much smaller effect on muscle fatigue than was previously hypothesized(1). Thanks to advances in technology, scientists are now able to study muscle tissue closer to physiological temperatures (old studies were completed at muscle tissue held at cooler temperatures, 50-68ºF). As shown by Westerblad et al., acid had little effect on contraction velocity when completed on muscle tissue held at 89ºF (2). On the other hand, a 2006 study by Knuth et al. did indicate that lactic acid decreased muscle contractile power even at warmer temperatures(3). 

Although the lactate question is still being debated amongst scientist, athletes must ask themselves if the research is even applicable to their post training recovery protocol. Although lactate may induce muscular fatigue, its quickly metabolized within the body (1/2 life: muscle- 9.5 minutes; blood- 15 minutes), and eliminated from our system 90 minutes after an exercise session has been completed (4)(5). Thus, exercise induced lactic acid from one workout is likely not even present during a subsequent workout depending on when you complete it.

All this being said, don't misinterpret my comments and think that I'm trying to put down the role of EMS. I've had to use one a fair amount due to various issues and have found it to be effective. Anything that can get a muscle contracting and increase blood flow is always a good thing ;-) 

References

1 Cairns SP. Lactic acid and exercise performance: culprit or friend? Sports Med. 2006;36(4):279-91.

2 Westerblad H, Bruton JD, Lännergren J. The effect of intracellular pH on contractile function of intact, single fibres of mouse muscle declines with increasing temperature. J Physiol. 1997 Apr 1;500 ( Pt 1):193-204.

3 Knuth ST, Dave H, Peters JR, Fitts RH. Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue. J Physiol. 2006 Sep 15;575(Pt 3):887-99. Epub 2006 Jun 29.

4 Karlsson J, Saltin B. Oxygen deficit and muscle metabolites in intermittent exercise. Acta Physiol Scand 1971; 82: 115-22.

5 Barnett A. Using recovery modalities between training sessions in elite athletes: does it help? Sports Med. 2006;36(9):781-96.

The only thing I would like to add to Sean's insightful dissertation is a criticism of the indiscriminate use of lactate, which is sort of 'recycled' muscle fuel, and lactic acid, which is its ugly 'degraded' relative. With the ever increasing H+ levels as they can be observed in the course of a long distance race, for example, more and more lactate gets degraded into lactic acid and thus works like a buffer similar to the beta-alanine derived intramuscular H+ buffer carnosine. Now it is no wonder that with H+ release being a measure of muscular exertion and lactic acid being a measure of H+ buffering, Faude et al. (Faude. 2009) found in what is one of the most recent reviews on the role of lactate in exercise metabolism that

[t]hirty-two studies evaluated the relationship of LTs with performance in (partly simulated) endurance events. The overwhelming majority of those studies reported strong linear correlations, particularly for running events, suggesting a high percentage of common variance between LT and endurance performance.

And, after all, it does not really matter in how far the established performance increases from massages and EMG therapy are related to their ability to accelerate lactate clearance, or more generally to their ability to increase blood flow and thus nutrient delivery and waste clearance in the respective tissue - does it?