80g Glycerol + 2L Water Decreases Body Weight in Athletes & Increases Overall Performance in Sedentary Subjects

If it does not make you as swole as the colorful ad promised it must not be working, right? The jury was not even any longer "out there" for glycerol, but a recent study makes you rethink, whether you just have to look in the right place to see the benefits.

Another of the "odd" Thursdays without an update from "Your's Truly" Adelfo Cerame. And since there is holiday today, over here, I even thought there would not be a SuppVersity Science Round Up today. But hey, you are lucky you (and Carl) got to work, so you can tune in live at 1PM EST, or even better, start listening live at 1PM in order not to miss the Strength and Hypertrophy Round Table!

As far the  topics for today's installment of the SuppVersity Science Round Up are concerned, you are actually only a couple of lines away from reading about one that's on the list:  The effects of glycerol on exercise performance. I don't have to tell you though that this is not everything. Other things I believe you may be interested in are...

• childhood obesity, physical education and attention at school
• wheat gluten hydrolysate and how they don't come up to the expectations early trials have raised
• ammonia accumulation brain-fog, toxicity, liver 'pathologies' and workout performance
• running next to a street entails 'particular downsides' ("particular" is to be taken literally, here ;-)
• homocysteine levels, mortality, cognitive impairment and more
• epigenetic programming by nicotine and different protein contents before birth

These topics alone obviously won't fit into a single episode, but by now you should be aware that the SuppVersity Science Round Up Seconds, which are always published one day after the show aired, will provide you with the things we have missed and additional information, suggested reads and graphs to the topics we covered...  apropos "won't fit in", since the above is not even everything I have up my sleeve, I thought it would be wise to take the glycerol news from the compilation and tackle it on its own, today.

Can the backbone of bad triglycerides really be good for you?

Glycerol, a 3-carbon sugar alcohol that provides the backbone of triglycerides and is naturally found in foods as a component of dietary fats (Burke. 2011), is one of those supplements that have been all the rage for some time, didn't produce the expected instant results everybody was looking for (in this particlar case mostly "skinbursting pumps" and have eventually, in the course of one or two cycles of the regular yearly reformulations of the pre-workout supplements, completely disappeared from the market. I was therefore surprised, when I hit onto a recent study by researchers from the Physical Education and Sport High School in Konya (Turkey) that was published in one of the latest issues of the Journal of Human Kinetics (Patlar. 2012).

Is glycerol save? There have not been any reported toxicity effects up to doses of 5g/kg body weight. Glycerol does accumulates in body fluids, with the exception of the brain and the eyes and increases osmotic pressure (which was the reason why people used it in "pump supplements"), as well as the total volume of water in the body. If anything was 'dangerous', or I should probably rather say 'detrimental' to it, it would probably be its energy content (it is subject to gluconeogensis in the liver), which puts you at 'danger' of adding one or another pound of body fat you would probably want to avoid. The results of the study at hand to yet suggest that this is not an issue as long as you are active.

In essence the study protocol is nothing extraordinary: Take a couple of guys, 40 in this case (age 22.82 ± 1.49 years), and feed and water them using...

• 1.2 g/kg body weight) followed by water (26 ml/kg body weight) to 10 sedentary individuals (GS) and 10 soccer players from the University team
• just plain water to the another 10 sedentary men and 10 soccer players

Conduct a baseline test in the course of which all subjects are familiarized with the exercise equipment, a cycle ergometer (Monark 814-E) and required to perform an...

• Astrand Cycle Ergometer Test and an
  
• Wingate Anaerobic Power Test
  *the videos are don't show the study participants

in a room that is kept at 30°C and a barometrical pressure of 668 mm-Hg. For the next twenty days, have half of the guys (athletic groups E and GE) perform a 20-m shuttle run test every day. And finally perform a second follow up to see and evaluate the individual and joint effects of exercise and glycerol supplementation.

What's a shuttle run? I guess those of you who play soccer or basketball will know similar drills (at least I have been tormented by my trainers with them before in both sports and could imagine they are also among the standard repertoire of football coaches - though I have never played that myself):

Video 1: The shuttle run is every trainer's darling and would actually make a nice conditioning workout to be implemented into your own routine - whatever it may you are training for (note: the video is a random pick from YouTube and has no relation to the study at hand).

"The subjects warmed up for several minutes by jogging followed by stretching. The test program was installed on the computer and  initiated. A single beep was emitted at regular intervals. The subjects had to complete a lap or shuttle (foot on or over the line) with each beep. If the subjects completed a lap early they had to wait for the beep before starting the next lap. A triple beep indicated the start of a new level with a slightly faster speed required to complete each  lap.

The subjects were encouraged to complete as many levels as possible. An observer monitored the progress of a given subject, recording each completed lap on the recorder form. The subjects were instructed to turn by pivoting and not to run in a wide arc. The test was terminated when a subject was two or more steps from the line, for two consecutive laps. The observer alerted the subject at this time." (Patlar. 2012)

The shuttle run was followed by a couple of minutes of walking to cool down and a stretching exercise. The data was collected, logged and archived for evaluation.

Now if we take a look at the results of this undertaking they are unquestionably somewhat surprising - at least at first sight (see figure 1). In absolute terms it looks as if we had an across the board, almost identical increase in performance due to the daily shuttle runs in the exercise groups and a surprisingly large beneficial effect of glycerol only in the sedentary subjects (which would by the way be in line with many of the more or less disappointing trials on the benefits of glycerol supplementation in athletes; cd. Burke. 2011):

Figure 1: Changes in anaerobic and aerobic performance - relative values on the left, absolute before (white) and after (black) on the right (Patlar. 2012)

If you take a look at the relative pre-post changes in figure 1 (left), instead of the absolute changes a more distinct picture emerges:

• the benefit the sedentary subjects derived from the supplementation looks even more pronounced,
• the aerobic performance of the soccer players in the exercise group did likewise benefit, albeit less than the performance of the sedentary group, and
• shockingly the increase in anaerobic performance which looks pretty much identical is not statistically significant, yet still reduced in the glycerol supplemented athletes in the exercise + glycerol group (note: there is an increase, it's only relatively smaller)

Now, we all know that hyperhydration goes hand in hand with an increase in body water. In figure 1 I did even plaster a huge red sticker with "hyperhydration" onto the graph to give you an idea of a possible mechanism of action. So, if we wanted to be fair, we would have to take that into account... what? Yeah and you want to know if it will make you blow up like a wale, right, ... so let's see:

Figure 2: Changes in body weight and relative power (watts per body weight) in the course of the trial (data based on Patlar. 2012)

If we assume you are a sedentary slob at 80kg you could in fact gain 1.6kg... whether that's only water or if there is some fat there, as well, I cannot tell. Notwithstanding, I mentioned in the red box on safety issues, already that you can hardly expect to down 80g of glycerol with an energetic value of 4.32kcal/g (i.e. 350kcal per day) extra everyday without gaining at least some weight (assuming all other parameters are constant; plus, this could be muscle as well - well, not if you don't work out, though ;-).

You cannot expect to lose weight, but surprisingly it may still happen that you do if you consume those 350kcal of glycerol with 2l water right before your daily shuttle run. 

At least this is what happened to the soccer players in the supplementation group: They lost 2.66lbs of body weight on average. "Weight" is the unfortunate key word here, because we have no way of telling whether that was muscle, water or fat weight, as the scientists did not measure that separately. But let's be honest, it appears more than unlikely that it is (a) water or (b) muscle. After all the relative anaerobic power increased equally in both groups and why on earth would you lose water when you hyperhydrate? Ok, it could be one of those counter-regulatory reactions our bodies love. That again should however lead to performance decrements we did not see... you see, it's like the idiomatic dog that's chasing his tail. Why don't you play ginea pig and let us know what happens ;-)

WADA Warning for competitive athletes: If you are a WADA controlled athlete, you better avoid glycerol. It may sound hilarious, but it is on the WADA list of prohibited supplements since 2012. Why? Well, the increase in blood volume could mask the use of testosterone and co. because the /dl count would be lower if the total blood volume is higher -- this is something the WADA officials consider call a "masking agent" (Wada. 2012).

How much do you need? Don't forget, for glycerol to work its hyperhydrating magic, you must consume it with similarly hilarious amounts of water as the subjects in the study at hand. According to van Rosendal et al. an effective protocol comprises 1-1.5 g/kg glycerol + 25–35 ml/kg of fluid. Assuming you weigh 80 kg you can't get way with anything below 80g of glycerol + 2l water! Obviously way more than what any of the hitherto no longer available 'pump' or pre-workout supplements contained (at least I have not come across one that has a 80g scoop and says "consume with at least 2l of water on the label" - have you?)

Bottom line: I want to be honest, I still have to make up my mind about the usefulness of this supplement. I guess what actually does the trick is the combination of hyperhydration + energy availability. I have been preaching more than enough about the importance of energy availability over the last couple weeks, so I don't think I have to go into any more details here.

What I do think, however, is that few of you will be aware of the 2008 paper by Judelson et al. in which they report that hydration status is a fundamental determinant of the endocrine response to exercise, with dehydration leading to inappropriately high cortisol and norepinephrine levels that go hand in hand with an attenuation of the testosterone response to exercise, and negative effects on carbohydrate and lipid metabolism (Judelson. 2008).

Since you should by now have gotten the notion that insufficient energy does exactly the same, glycerol could well provide a means to counter this ergolytic double whammy. Against that background it is however strange that the athletes could not derive any athletic benefit from it... and weight loss without dieting (at least they were advised to stick to their habitual diets)?

If there is one definitive message you can take home from this study, though, it would be related to the dosage advice in the blueish info-box on the top right of this last paragraph: You better know how to use a supplement correctly! And this goes for the manufacturers of supps, as well as for the consumers: While the formers should finally stop putting ingredients into their supps to have them on the label, consumers should learn to identify hilariously underdosed and thus useless 'kitchen sink supplements' that 'have it all', but in doses where 'all' does not produce 'any' effect... how you can do that? Easy: Just make sure you get your daily dose of educative SuppVersity posts every day!

References:

• Burke LM, Stear SJ, Lobb A, Ellison M, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--Part 19. Br J Sports Med. 2011 Apr;45(5):456-8. 
• Judelson DA, Maresh CM, Yamamoto LM, Farrell MJ, Armstrong LE, Kraemer WJ, Volek JS, Spiering BA, Casa DJ, Anderson JM. Effect of hydration state on resistance exercise-induced endocrine markers of anabolism, catabolism, and metabolism. J Appl Physiol. 2008 Sep;105(3):816-24
• Patlar S, Yalcin H, Boyali E. The Effect of Glycerol Supplements on Aerobic and Anaerobic Performance of Athletes and Sedentary Subjects. Journal of Human Kinetics. 2012; 34: 69-70. 
• Van Rosendal SP, Osborne MA, Fassett RG, Coombes JS. Guidelines for glycerol use in hyperhydration and rehydration associated with exercise. Sports Med. 2010 Feb 1;40(2):113-29.
• World Anti Doping Association. WADA Prohibited List 2010. < http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf > retrieved Nov. 01, 2012. 

"Inner Chest", "Upper Abs", "Biceps Peak" & Co!? Study Finds Proximal and Distal Part of the Triceps Grow Independently and According to Training Stimulus.

Image 1: Training for the peak, could it be possible, after all? (image from provitamin.in)

You probably have read my repeated notes on the issue of training individual muscles fibers in complete isolation in the 7-part SuppVersity EMG-Series. I guess in view of the results of a very recent study from the Faculty of Sports Sciences at the Waseda University in Japan (Wakahara. 2011), it might be that I will have to revise my statement. It could in fact be that you can train a specific part of a muscle fiber - if not individually, then at least predominantly.

Despite the fact that our movements are always orchestrated by the interplay of a whole host of muscle-groups and -fibers, Wakahara et al.'s results suggest that it may even be possible to target specific parts of individual fibers by selecting the correct exercises. In other words, instead of doing incline bench presses for the upper chest, you could, as many trainers recommend it for years do them with a narrower grip to target the "inner chest", i.e. the inner part of the same muscle fiber that constitutes the "outer chest" (note that this is fundamentally different from training "upper pecs" and "lower pecs", which are in fact separate muscle strands).

The muscle group for which Taku Wakahara and his colleagues were able to show this remarkable effect, was yet not the chest, but the triceps brachii. For their study, the scientists recruited 2x12 healthy young men (25.2 +/- 3.0 years, 172.8 +/- 5.0 cm, 65.3 +/- 7.8 kg; there were 7 dropouts of 19 men who started the 12-week resistance training), who had not participated in a regular resistance training program for the upper extremities for at least 6 months, for a short (single session) and long term (12 weeks) analysis of the effects of DB lying triceps extension on muscular activation and hypertrophy in the triceps brachii.

In the first experiment the scientists had one group of subjects perform 5 sets of 8 repetitions with a 2s concentric and a 2s eccentric phase at 80% of their previously established 1RM-max.

Before and immediately after the resistance exercise, T2-weighted MR images of the upper arm were obtained with an MR scanner [...] The time from completion of the exercise to initiation of the scanning was 72 +/- 21 s. In each MR image, the outline of the triceps brachii muscle was traced to determine the CSA using a software package (Image J, National Institute of Health, USA).

In view of the short timespan between the last set of the exercise and the MR scans, we may safely assume, that the CSA (cross-sectional area) increases the scientists measured in this first session were mainly a result of the increased blood-flow to the triceps aka "the pump". For me, this is particularly interesting, because if those areas of the muscles with the "greatest pump", i.e. the greatest increase in CSA immediately after training, would be identical with those areas of the muscle which exhibit the greatest hypertrophy in the course of the 12-week follow-up experiment, this would be evidence for the significance of increased blood flow and "the pump" in view of consecutive muscle growth (it would not, however tell us whether the relation between "the pump" and muscular hypertrophy is corollary or causative!).

Figure 1: Increases in cross-sectional area of the triceps brachii immediately after a single session of DB lying triceps extensions and a 12-week resistance training protocoll (data calculated based on Wakahara. 2011)

As the data I plotted in figure 1 goes to show, there is a correlation (R²=0.67) between the CSA increases after the single session and the hypertrophy response to the 3x a week (12 weeks) training regimen. The correlation is too weak to confirm Arnold Schwarzenegger's advice that "going for the pump" would be the (implying "one and only) way to grow. This, however, does not diminish the importance of Wakahara et al.'s finding that

the region-specific muscle hypertrophy after chronic resistance training is attributable to the regional difference in muscle activation during the exercise

In other words, the bros at the gym were probably right, there are inner chest, outer chest, biceps peak, upper quads etc. and you can probably train them individually.

In view of the costs of the necessary equipment, it is however not very likely that you will see a "SuppVersity Magneto-Resonance Series" with the "very best exercises for individual parts of each and every muscle fiber as determined by increases in CSA after a single training session" somewhere in the near future. But guess what, in the end you would not even need that if you rely on your own good judgement: If you exercise with heavy weights and proper form, the pump, the burn and the soreness after the workout will tell you if it was the inner chest, or the outer chest that took over the lion's share of your last workout.

No Pump + Insulin Resistant? Maybe It's Your Healthy Low Salt Diet. Low Sodium Induced Increase in Aldosterone Has Direct Negative Impact on GLUT4 Mediated Glucose Uptake

A single Triple Whopper or about six whole steaks, what do you chose to get >75% of the 2g/sodium per day the feds are telling you you should maximally consume on a daily basis?

Today I felt kind of bored with covering only the latest studies. So I dug up one from 1999 that deals with the effects of dietary salt restriction on endothelial vasodilation (increased blood flow in the arteries) and insulin sensitivity by Ross D. Feldman and Nancy D. Schmidt. Yeah, the study is 14 years old, but when you've read today's SuppVersity article you'll probably still have learned something new - at least about "common wisdom".

If you also listen to the SuppVersity Science Round-Up on the Super Human Radio Network, you should be aware that very different rules apply with respect to salt consumption for athletes and physical culturists on a whole foods diet and the average sedentary inhabitant of the Western obesity belt (check out past episodes of the Science Round-Up).

Suggested Read: On "Clean Eating" being a myth - "A Tale of Macro- & Micro-Nutrient Modifi-cations" | read more

Talking about the ScienceRound-Up: In today's installment Carl and I will be talking about the latest meta-analysis on dairy and diabetes risk and how it's possible that only low fat dairy reduces the risk of diabetes. We will discuss how this relates to the differences in the fatty acid composition of milk which in turn depend on the feed the animals receive and whether there is in fact so much estrogen in milk that it can delay menopause. From there we will segue right into a discussion of the latest study on statins showing that they make you fat and diabetic and tell you which of the statins does what. If all works well, we will close the show by addressing Sarah M. Davis' question about a recently published and heavily discussed article that's titled "Why 'Clean Eating' is a Myth" (read it). I mean, is it really? Turn in live! at 12PM EST

What some of you may yet still not have on their radar is the fat that the "common wisdom" about salt being the root cause of all evil does not even apply to the majority of those guys and girls of whom you would expect they may in fact see benefits from a reduced salt consumption.

"Salt is bad, no matter what!"

In fact, Feldman & Schmidt were able to show that the provision of either normal or salt reduced diets to subjects aged 25 to 40 year.

Figure 1: Increased aldosterone levels during salt restriction will not only make you retain salt, but also reduce glucose uptake (Luther. 2011; my edits)

"Subjects were given a standardized diet that contained 75 mmol/L sodium chloride, 60 mmol/L potassium, and 20 mmol/L calcium for 14 days. Diets contained 16% protein, 54% carbohydrate, and 35% fat. Caloric intake was 2800 kcal/day. Subjects were advised to drink approximately 2L of water/day.

To assess the effects of dietary salt restriction independent of other dietary changes, subjects were randomized on a double blind cross-over basis to a daily supplement of 16 tablets of slow release sodium (Novartis, Mississauga, Ontario; 10 mmol/L sodium chloride/tablet) or matching placebo. Each were administered for 7 days." (Feldmann. 1999)

All of the participants had normal blood glucose levels, and were free of other abnormalities on history and physical examination. They did not smoke and their blood pressures levels ranged from normotensive to high normal/borderline. So, what would happen to the poor wretches consuming the additional sodium chloride tablets? Common wisdom tells us, their blood pressure will increase and they will develop metabolic abnormalities. Truth is (I quote from the study; Feldmann. 1999, my emphases), almost the exact opposite happened:

• Did you know? Aldosterone increases are caused by falling blood pressure, increased potassium levels, a higher blood acidity and decreased sodium concentrations in the blood trigger, decreases occur when your blood pressure drops, the potassium levels get low and/or the sodium levels are high.
  Dietary sodium restriction was associated with a significant decrease in 24-h urinary sodium excretion. However, blood pressure (based on the average 24-h automatic ambulatory measurements) was not significantly decreased with dietary salt restriction.
• Moderate salt restriction was associated with a significant increase in plasma norepinephrine concentrations. Dietary salt restriction was associated with a significant decrease in the glucose-to-insulin ratio, suggesting increased systemic insulin resistance. This decrease was primarily accounted for by an increase in plasma insulin concentration.

At the same time the researchers observed a significantly reduced effect of the vasculature to the insulin-mediated increase in blood flow, of which Hornstra et al. have shown only recently that it correlates negatively with blood pressure in overweight, but insulin sensitive individuals and may be the reason why those people don't suffer from the usual obesity related increases in blood pressure as well as its cardiovascular and renal consequences (Hornstra . 2013).

---

Most of you will remember the recent post about the ability of salt to block the negative effects of high intensity exercise on the cellular integrity of your heart and kidneys don't you?

Bottom line: If you are working out and sweating, even if it's not like a pig, SALT is the last thing to fear. In fact you can even increase your heart disease risk due to the negative impact on blood lipids (+10% total +12% LDL cholesterol in salt-sensitive and unsensitive normotensive subjects; Ruppert. 1991).

Now it is important to point out that it is not clear whether these effects are transient and a response to the abrupt changes in dietary salt in take that are characteristic of these short term intervention studies.

I am certainly not recommending you copy the salt intake of the average junk-food fanatic!

But let's be realistic, here: How much salt do you actually consume on a daily basis if you follow my advice and leave as much of the processed pre-packaged junk as you can right in the supermarket!? This will leave you with actually having to put salt on your foods and there really is no good reason for the average physical culturist not to so in a way that it's tasty and supplies you with one of the most important minerals in your body.

Suggest figure: Only obese people have increased risk of CVD with increasing sodium consumption | check it out the SuppVersity Facebook Wall

Reference:

• Egan BM, Lackland DT. Biochemical and metabolic effects of very-low-salt diets. Am J Med Sci. 2000 Oct;320(4):233-9. Review.
• Hornstra JM, Serné EH, Eringa EC, Wijnker MC, de Boer MP, Yudkin JS, Smulders YM. Insulin's microvascular vasodilatory effects are inversely related to peripheral vascular resistance in overweight, but insulin-sensitive subjects. Obesity (Silver Spring). 2013 Mar 20.
• Luther JM, Brown NJ. The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol Sci. 2011 Dec;32(12):734-9.
• Ruppert M, Diehl J, Kolloch R, Overlack A, Kraft K, Göbel B, Hittel N, Stumpe KO. Short-term dietary sodium restriction increases serum lipids and insulin in salt-sensitive and salt-resistant normotensive adults. Klin Wochenschr. 1991;69 Suppl 25:51-7.

Nitrates Work! Even at Low Doses of 300-500mg. Athletes Who Take More or Confuse Nitrates With Nitrites Face Potential Health Risks. First NO2-"Victim" in the ER.

Image 1: With nitrate and nitrite, a
single letter is of literally vital importance.

You probably expected another issue of the famous "Ask Dr. Andro" segment today... ? Well, I have in fact been working on something, but firstly, the topic turned out to be so epic that I could hardly have delivered a post in the usual SuppVersity quality within the next few hours, and secondly, a previous installment of the series on creatine nitrate (cf. Ask Dr. Andro: Is Creatine Nitrate Worth It?), in which I explained why I think that the heavily marketed "revolutionary" creatine supplement probably does not provide any additional benefits beyond supplementing creatine monohydrate and nitrate, individually, urgently needed a follow up.

While the ergogenic potential of creatine monohydrate and its safety are well established (and I do not think I have to recite the whole litany about creatine causing kidney failure, again!? cf. Creatine Save - For Diabetics, As Well!), the studies which show that dietary supplementation with inorganic nitrate (NO3-) reduces whole body oxygen cost during physical exercise (Larson. 2007; Larson. 2010), are pretty recent and have, according to a letter to the editor of the Journal of Applied Physiology by Jon O. Lundberg et al. (Lundberg. 2011), already provoked a case of severe nitrite intoxication in an athlete who obviously wasn't aware of the major difference the "i" which distinguishes the highly reactive nitrite (NO2-) from its harmless precursor nitrate (NO3-) and developed symptoms suggestive of methemoglobinemia (increased oxidation of hemoglobin) after poisoning himself with nitrite salt.

Note! It is unlikely that you will develop methemoglobinemia from reasonable doses of nitrate, even when the lethal dose 50 (LD50 = the dose at which 50% of the subjects / lab rats who ingested the given amount of a chemical die) for nitrite is as low as 100-200mg/kg and thus in the range of cyanide. The reason for that is that, although your body will convert orally ingested nitrates to nitrite, the rate at which this process takes place is limited and this limitation is what avoids the accumulation of nitrite in your blood stream and thus saves the iron-containing oxygen-transport metalloprotein in your red blood cells from being oxidized.

Image 2: Beetroot juice is probably your
safest source of dietary nitrate (NO3-)
(image from planetorganic.com)

This case of unintentional nitrite poisoning goes to show that caution should be exercised, when you are buying and consuming nitrate salts for performance issues. Yet, although salpeter (nitrate salt) is readily available as a food conservative from your local grocery story, I personally would advice against its consumption and tend towards more natural sources of nitrate to elicit the desired ergogenic effects. In fact, the slow controlled release of nitrite from dietary nitrate as it is found in beat root juice (100-200ml would suffice to get into the effective range of 200-300mg nitrate, cf. Ask Dr. Andro: Is Creatine Nitrate Worth It?) may have additional desirable health effects on blood pressure (Larsson. 2006; Lundberg. 2008) and could be used as an adjunct in the treatment and prevention of ischemic conditions such as myocardial infarction and peripheral artery disease.

A final word of caution goes out to the real bros out there: When even nitrite salt can give you hypothension and oxidize your the oxigen carrying metalloprotein in your red blood cells, nitroglycerine and amyl nitrite, both drugs that are prescribed to patients with heart disease, may literally give you the "longest lasting pump of your life" - a pump that lasts until you drop dead to the floor.

Ask Dr. Andro: Are There NO Changes in the New N.O.-Xplode 2.0 Advanced Strength Formula?

The official SuppVersity Supplement Shoot-Out!
The longstanding veteran, NOXplode AVPT,
is challenged by a clone of its own, 
NOXplode 2.0 Advanced Strength -
which will be the last pre-workout standing?

Question Dr. Andro: What the... is BSN trying to scam costumers? At first sight the labels of the old and the new Advanced Strength version of N.O.-Xplode seem to be absolutely identical.

Answer Dr. Andro: I am usually not soliloquizing, but in this case I thought that many of you may have had the same thought, when they spotted the new(?) BSN N.O-Xplode 2.0 - Advanced Strength in the "new products" column of their favorite supplement vendor: a lot of boastful claims in the product description, but no eye-catching changes in the actual formula.... Reason enough to devote a few hours of my precious time to scrutinize the labels of the old N.O.-Xplode AVPT and the purportedly "new" N.O.-Xplode 2.0 Advanced Strength.

N.O.-Xplode AVPT vs N.O.-Xplode 2.0 - Fight!

Well, let's start with the most obvious. The packaging got redesigned! I would not mind, but actually I find the new "darker" design looks a little cooler... well, I guess the ugly blue "now 25% more" sticker was bordering unfair competition, anyway. After all, BSN has been selling this "value" *lol* edition of the AVPT version of NOXplode for years now. So, if you are looking for a nice-looking addition to your supplement stash and red is your favorite color, the new BSN NOXplode 2.0 container could be just what you've always been waiting for  :-)

If, on the other hand, you are more interested in the content of the fancy new container, I suggest you follow my lead, click at the image above and have a look at the labels... let's see, what have we got here?

The basics - Calories, Carbs, Vitamins and Co.

The FDA approved nutritional information is the part of the label that - the information on the carb content aside - will interest people the least, I guess. Nevertheless, I had hoped to see improvements in the types of vitamins the guys from BSN used. An adequate dose of methylcobalamine (B12), some pyridoxal-5-phosphate instead of the inactive pyridoxine HCL, we are bombarded with in all protein containing supplements, anyways, and some active methyl-tetrahydrofolate instead of the folic acid that the FDA is forcing upon you in each in every foodstuff you eat, would have been nice, yet obviously too expensive improvements (cf. table 1)

	AVPT	NOXplode2.0	Dr. Andro's thoughts
Total calories	25kcal	25kcal	identical
Total carbs	6g	6g	identical
Total sugars	0g	0g	wtf! As if a glucose polymer was no sugar
Vitamin B6 from pyridoxine HCL	25mg	20mg	instead of reducing the amount BSN had better invested in some P5P, the bioactive version of pyridoxine
Folate from folic acid	400mcg	300mcg	obviously someone @BSN got wind of the studies which show that the cheap folic acid (in excess) does more harm than good... I guess you know why they did not replace it with a reasonable dose of the active methyl-tetrahydrofolate
Vitamin B12 from cyanocobalamine	120µg	120µg	identical, but still not absorbable (cf. "Want B12? Drink Milk")
Calcium from Calcium Phosphate	75mg	75mg	identical & insignificant
Phosphor from various phosphates	535mg	200mg	someone got wind that the average Western diet already contains way too much phosphate and that the phospates in the original formula were the reason for diarrhea in some people
Magnesium from various phosphates	360mg	60mg	in view of the lack of magnesium in typical Western diets, the higher dose in the old formula was better - as long as your stomach could tolerate it ;-)
Sodium from various phosphates	235mg	300mg	well, isn't that great? Cut down magnesium, ramp up sodium... I guess its more stomach friendly, but is it also healthier?
Potassium from various phosphates	75mg	75mg	it is unfortunate and ridiculous that the FDA does not allow more than this amount per serving
Table 1: Comparison of the fundamental nutrients, vitamins and minerals in the formula (based on nutritional information from BSN and a major online vendor)

The Problem... ahh, I mean "Proprietary" Blend ;-)

Now, things are getting a little complicated. How do you evaluate a supplement where you know that something is in there, but have no clue in which amount? Well, I guess this would not matter if we were talking about the FDA-invented difference between sugar and glucose polymers (isn't it interesting that the FDA let's the supplement companies make a difference, here?), it is however of tremendous importance to know whether the undisclosed overall amount of the AVPT or ASPM (Advanced Strength & Performance Matrix) part of the 18.0g and 19.6g proprietary blend in NOXplode AVPT and NOXplode 2.0 Advanced Strength contain 90% or 30% glucose polymers. With the latter being the first ingredient on the label, we can only be sure that it is the major ingredient in this part of the formula and since we know that we get 6g of non-sugar carbs, there probably is little room for the additional working ingredients in this part of the formula, anyway.

I hope you understand the problem we are facing here. The one (and only) thing, we can do, is to compare the order in which the ingredients are listed (the latter complies to the relative amount of the individual ingredient, with those ingredients with the highest amounts being listed first) and evaluate whether the changes BSN has made in terms of the specific ingredients and their ratios do make sense.

	AVPT	NOXplode2.0	Dr. Andro's thoughts
Total weight of proprietary blend	18.0g	19.6g	this means that BSN has generously rounded up the +1.6g diffrence in what they advertise as "2 more grams of active ingredients" (cf. BSNOnline)
N.O. Meta-Fusion	L-Arginine AKG, L-Citrulline Malate, RC-NOS™ (Rutacarpine 95%), L-Citrulline AKG, L-Histidine AKG, NAD (Nicotinamide Adenine Dinucleotide), Gynostemma Pentaphyllum (Leaves & Stem) (Gypenosides 95%)	L-Arginine-Alpha Ketoglutaric Acid, L-Citrulline-Malic Acid Interfusion, L-Citrulline-Alpha Ketoglutaric Acid, L-Histidine-Alpha Ketoglutaric Acid, NAD (Nicotinamide Adenine Dinucleotide), Gynostemma (90% Gypenosides) (Leaves & Stem)	BSN has removed the rutacaropine, which induces vasodilation via CGRP (Duan. 2007) and added a lower amount of l-histidine AKG which does of course figure in the generation of NO, but has of yet not been shown to independently induce vasolidation; maybe the BSN-guys thought it would fit well with the (probably) extended amount of beta alanine, since β-alanyl-L-histidine, i.e. carnosine is what we actually want
AVPT / ASPM	Modified Glucose Polymers (Maltodextrin), Di-Creatine Malate, Trimethylglycine, Creatine Ethyl Ester -Beta-Alanine Dual Action Composite (CarnoSyn®), Sodium Bicarbonate, Sodium Creatine Phosphate Matrix, Creatinol-O-Phosphate-Malic Acid Interfusion, Glycocyamine, Guanidino Proplonic Acid, Cinnulin PF® (Aqueous Cinnamon Extract) (Bark), Ketoisocaproate Potassium, Creatine AAB (Creatine Alpha-Amino-N-Butyrate)	Modified Glucose Polymers (Maltodextrin), Beta-Alanine (CarnoSyn®), Di-Creatine-Malic Acid Interfusion, Betaine HCL, Sodium Bicarbonate, Creatine-Sodium Phosphate Matrix, Creatinol-O-Phosphate-Malic Acid Interfusion, Glycocyamine, Creatine Ethyl Ester HCL, Guanidino Propionic Acid, Cinnamon Extract (Bark) (Cinnulin PF®), Ketoisocaproate Potassium, Creatine-Alpha-Aminobutyric Acid Matrix (Creatine AAB™)	the same fancy creatines without any substantial research supporting their superiority over creatine monohydrate as in AVPT (personally I see no reason to boast with the slogan "no creatine monohydrate", after all CM is the only form of creatine that has proven in scientific studies time and again that its working!); it seems, though, as if the beta alanine content increased - while this would be a good thing, its mere speculation based on its position within the list of ingredients in the proprietary blend; why BSN replaced the 'real' betaine (trimethylglycine) with the 'digestive aid' betaine HCL eludes me
Ener-Tropic Xplosion™	L-Tyrosine, Taurine, Glucuronolactone, Methylxanthine (Caffeine), L-Tyrosine AKG, MCT's (Medium Chain Triglycerides)[Coconut], Common Periwinkle Vinpocetine 99%, Vincamine 99%, Vinburnine 99% (Whole Plant)	L-Tyrosine, Taurine, Glucuronolactone, Methylxanthine (Caffeine), L-Tyrosine-Alpha Ketoglutaric Acid, MCT's (Medium Chain Triglycerides), Lesser Periwinkle (95% Vinpocetine, 98% Vincamine, 98% Vinburnine [Whole Plant])	BSN is trying to trick you on this one by just using a different name for the same ingredient - the common and the lesser periwinkle denote the same plant, the only difference is that the purportedly improved NOXplode 2.0 contains an inferior extract
Phospho-Electrolyte Replacements / Composite	Di-Calcium Phosphate, Di-Potassium Phosphate, Di-Sodium Phosphate	Di-Calcium Phosphate, Di-Potassium Phosphate, Di-Sodium Phosphate	its telling that the "replacement" in the AVPT became a "composite" in NOXplode 2.0 - I already alluded to the inferior mineral composition of the "new" version in table 1
Glycerol Hydrating Polymers™ / Glycerol Polymer Complex	Potassium Glycerophosphate, Magnesium Glycerophosphate, Glycerol Stearate	Potassium Glycerophosphate, Magnesium Glycerophosphate, Glycerol Stearate	I suppose BSN changed the name to "polymer complex", because it sounds way more sophisticated; in fact, its the same stuff as in the AVPT version
Table 2: Detailed analysis and comparison of the ingredient profile of the proprietary blends of NOXplode AVPT and NOXplode 2.0 Advanced Strength (based on nutritional information from BSN and a major online vendor)

As you can see from the juxtaposition of the ingredient profiles in table 2, the changes are mediocre at best and the potential increase in the beta alanine content is the only improvement I can find... what about you?

Conclusion - Love It or Hate It!

I guess, some of you are expecting me to rip BSN's marketing coup apart. Well, I guess I could, but let's be honest, obviously there was and still is a huge amount of trainees out there who loved the old formula and kept buying it even when everybody told them that arginine was not working, the new XY was all the rave and their first generation pre-workout would not be worth the cost of its container. In case you are one of those patrons who made the old NOXplode the best-selling preworkout supplement of all times, chances are you will like its almost identical twin, as well. If, on the other hand you, you hated the old version and/or are satisfied with your current pre.workout regimen, I see no reason to invest the 35.99$ into a professionally redesigned redesigned red plastic container.

TARFU: LaBrada Nutrition Financed Study Finds no Effect of Super Charge Xtreme N.O. on Training Induced Increases in Muscle Size. Minor Effects on 1RM Max.

As mentioned in previous blogposts, I highly credit all supplement companies which - instead of just putting out untenable claims about the "steroid-like" effects of their products - spend a few bucks of their immense marketing budgets on research on how fantastic their products actually are. In the case of LaBrada Nutrition's Super Charge Xtreme N.O. it does yet seem that it would have been wiser to do some research before formulating their new "NO booster".

Other than the guys over at LaBrada Nutrition probably have hoped or even expected, the study (JSCR. 2011) that was published in the March issue of the well-known Journal of Strength & Conditioning Research found no "significant improvements in LBM over the placebo drink" and only minor increases in bench press 1RM and squat power, which may well be attributed to CNS stimulation due to the hefty 450mg load of caffeine each serving of Super Charge Xtreme N.O. contains.

Other than that, the "15 physically active, resistance trained, college age (19.5 +/- 0.269 yr) males" in the placebo group attained the same changes in body weight, body [as measured via dual-energy X-ray absorptiometry (DEXA)] and maximal strength in the rest of the 8 different exercises of their 3-day/week exercise regimen:

A main effect for time was identified for each of the 1RM strength measures tested (p<0.05) except biceps curls (p = 0.34). [....] Significant main effects were found for lean body mass (F1/22 = 20.32, p<0.001), but there were no significant group x time interactions for changes in LBM (F1/22 = 0.142 p = 0.710).

But let's be honest. Did you still believe an NO booster will improve your gains? I, for my part, take them for the feeling of being pumped up. And although I have not yet had the chance to test this particular product, I am inclined to believe that it will provide similar results as the classics like NO Xplode & Co - that kind of cosmetic pump you either love or hate.

Does Your Pre Workout Inhibit Fat Loss? Study Shows Nitrate Supplements Decrease Metabolic Rate By 4.2%

If you want other to see your pump, you got to be ripped. If not, why care about reductions in BMR?

If you remember my posts about the first generation, arginine-based pre-workout products you will be aware that the only pump they produced was the word "pump" in their name or product description. The reason was and still is simple. The mere provision of l-arginine, which is a precursor to nitric oxide does not lead to an increase in nitric oxide production. Why? Well, think of a building a house: Just buying some concrete won't make you a proud home owner, either ;-)

The bad thing: Arginine didn't work. The good thing: This means it didn't decrease your BMR, either

Against that background it's quite astonishing that arginine and citrulline based pre-workout products have dominated the top-seller lists of the big supplement vendors for decades. A fact that's probably partly due to other potential benefits of these amino acids, of which one - you as a SuppVersity reader know that - could be fat loss | learn more about the potential fat loss effects.

On a side note:  I am pretty sure the fact that the other potential benefit is an increase in sexual stamina didn't hamper the sales either (Neuzillet, 2013; Hotta. 2014 ;-)

With more and more people openly declaring that they would no longer waste money on "good tasting, but expensive and disfunctional products", they industry was yet pressed to develop alternatives. Luckily, our body has two options it can chose from, when producing nitric oxide.

Fortunately, the industry has developed better alternatives...?

You know option #1, the arginine ➲ nitric oxide pathway, and - with all the hype and hyperbole that surrounded the introduction of the first nitrate supplements - I am pretty sure, you know the other one as well, the nitrate-nitrite ➲ nitric oxide pathway

Figure 1: The Arginine- and the Nitrate-Nitrite - NO pathway are the yin and yan of nitric oxide production (Lundberg. 2008).

As the illustration (Figure 1) I have "borrowed" from a comment by Jon. O. Lundberg et al. (2008) illustrates quite nicely, the arginine and nitrite nitric oxide pathway are the yin and yan of NO production.

With the "yan", i.e. the nitrate-nitrite ➲ nitric oxide pathway being a relatively "new kid on the NO block", that recycles (=reduces) inorganic anions nitrate and nitrite to form bioactive NO in blood and tissues during physiological hypoxia.

It goes without saying that there is a bottle neck to this process as well, but the rate limiting availablility of oxygen which hampers the argine-based NO generation by NOS becomes limited as oxygen levels fall is actually a signal for the nitrate–nitrite ➲ nitric oxide to really kick in.

There is more yin and yan, here

If you take a closer look at the results of a study in the America Journal of Clinical Nutrition (Figure 2), you will yet have to realize that there is "more yin and yan", here than you'd probably hope for. According to the data scientists from the venerable Karolinska Institutet in Stockholm, Sweden, present in their paper, "[d]ietary inorganic nitrate reduces the RMR." (Larsen. 2014)

Figure 2: VO2 consumption (marker of fatty acid oxidation) and basal metabolic rate (BMR) relative to means (left), thyroid hormone (T3, T4) levels after 3-d dietary intervention with sodium nitrate (Larsen. 2014)

Whut? Yes, you read Larsen et al. right: In their randomized, double-blind, crossover study, in the course of which the Swedish scientists measured the resting metabolic rate (RMR) of 13 perfectly healthy 18–49 y olds (17 women) via indirect calorimetry after a 3-d dietary intervention with sodium nitrate (NaNO3 @ 0.1mmol/kg body weight) or a placebo (NaCl), Larsen, Schiffer, Ekblom et al. observed a statistically and (probably) physiologically significant reduction BMR reduction of 4.2% which correlated strongly to the degree of nitrate accumulation in saliva (r²= 0.71) and fits in nicely with the reduced O2 consumption of which Bailey et al. were the first to observe it in response to nitrate supplementation during exercise (Bailey. 2009).

Interestingly, these effects were not - as you may have been speculated - brought about by changes in thyroid hormone status. And the subjects insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, as well as their total antioxidant capacity were unaffected, as well.

Suppversity Suggested Read: " The Beat Your Personal Bests W/ Beets 101: How Much? 8.4 mmol Nitrate ~400-1300g Beets! When? 2.5h Pre Workout!" | read more

Bottom line: If the 0.1mmol/kg were not equivalent to only 200–300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate, I would probably say: Here you have it! Another supplement that's not just useless, but actually detrimental to your goals.

The way things are, I will refrain from ranting and rather suggest you simply skip the supps and consume the spinach, beetroot, lettuce and other high nitrate veggies right away. Most of the human studies which support the ergogenic potential of nitrates have been conducted with beetroot juice instead of capped sodium-nitrate.

And let's be honest, the weight loss advantage of having green and not so green nitrate containing vegetables in your is eventually beyond doubt. So, if there was a similar reduction in RMR from your daily serving of spinach, you can be more or less certain that it was compensated by the beneficial weight loss effects of the whole spectrum of nutrients that's present in this edible flowering plant in the family of Amaranthacea.

Reference:

• Bailey, Stephen J., et al. "Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans." Journal of Applied Physiology 107.4 (2009): 1144-1155.
• Hotta, Yuji, et al. "Oral l‐citrulline supplementation improves erectile function and penile structure in castrated rats." International Journal of Urology (2014).
• Larsen, Filip J., et al. "Dietary inorganic nitrate improves mitochondrial efficiency in humans." Cell metabolism 13.2 (2011): 149-159.
• Lundberg, Jon O., Eddie Weitzberg, and Mark T. Gladwin. "The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics." Nature Reviews Drug Discovery 7.2 (2008): 156-167.
• Neuzillet, Y., et al. "A randomized, double‐blind, crossover, placebo‐controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction." Andrology 1.2 (2013): 223-228.

Cell Swelling Keeps Muscles "Pumped" For More Than 52h. Size Increases of Up to 16% After a Single Leg Workout! Plus: Changes in Tendon Water & Collagen Content

I've heard rumors about people who get pumped, just to look pumped ;-)

I guess many of you will already have read Brad J. Schoenfeld's and Bret Contreras' latest review on "the pump"? I know for sure that Jakob read it, because he messaged me on December 29 that is was available for download over at the website of the Strength and Conditioning Journal. What he could not know, though was that I had already downloaded and read the article, when Brad and Bret, who are unquestionable two of the go-to resources for everyone who wants to learn something about the science of "getting big, lean and strong" posted the link on Facebook on December 28 (go to the original post). This link will take you to a downloadable ~2000 word paper in the conclusion of which you will find the following statement:

"[...] it is likely that exercise centered on achieving a “pump” through higher repetition sets combined with shorter rest periods also provides a potent hypertrophic stimulus that is synergistic to heavy compound lifting." (my emphasis in Schoenfeld. 2013)

In view of the fact that this excerpt summarizes the main information the paper provides excellently, I am not going to ruminate Brad's & Bret's overview of the few studies that allow for relevant and at least to some extend reliable conclusions about the real-world effects of the pump and its significance for someone whose main interest is in building size, not strength (just read the review, if you want the details).

There is something about the pump the review doesn't discuss, though

Don't worry, it's not as if Brad and Bret had overlooked the latest paper M.S Kristiansen and his colleagues from the Institute of Sports Medicine, the Section of Sports Science at the Universities of Copenhagen and Aarhus. Rather than that, the paper with the intriguing title "Concomitant changes in cross-sectional area and water content inskeletal muscle after resistance exercise" had (a) not even been published, when they the two were doing the research for their review and is (b) as we are going to see not 100% relevant to the question, whether the pump does or doesn't promote muscle growth.

Collagen loss and (super-)compensation occur in the early and late phase of the post-exercise period. If you don't want to risk injury or chronic overuse, you better remember this whenever you're working on a new workout schedule.

Does exercise also influence the water content of the tendons? In contrast to its effects on the intra-muscular water content the 3-EX regimen in the study at hand lead to "a decrease in the CSA of the central part of the PT [patella tendon]" within the first 52 h post exercise. "A concomitant increase in the water content of the tendon could not be demonstrated, though." (Kristiansen. 2013). Based on the absence of an overall decrease in water content, Kristiansen et al. speculate that previously observed decreases in tendon size (Miller. 2005; Tardioli. 2012) could have been brought up by a net loss of collagen during the early restructuring processes after heavy workouts.

Since the rate of collagen synthesis is negligible within the first 36h after exercise "the breakdown of the tissue driven by catabolic processes [...] may exceed the synthesis" that peaks after 72 h, "if multiple training sessions are too close to one another" (Kristiansen. 2013). The consequences? Acute injuries and / or chronic overuse.

Suggested Read: "Why training over the full ROM counts" | more

Now you may be asking yourselves why the results Kristiansen et al. are about to present in one of the upcoming issues of the Scandinavian Journal of Medicine & Science in Sport still made it into the SuppVersity News, if they don't provide any new insights into the contribution of the pump to skeletal muscle hypertrophy. The answer is simple: They do tell us something that puts a huge "?" behind the results of a whole host of studies on skeletal muscle hypertrophy. Something the average "disco pumper", i.e. a person who works out a couple of hours before he hits the Saturday night life to make sure that his muscles are big and full, knew for years: Your muscle size remains significantly elevated for hours even after comparatively low volume workouts.

What the average disco pumper probably didn't know, though....

... is that the water-induced cell-swelling peaks not 4h after the workout, but actually 52h after the last workout. That's probably good news for everyone who hates being wiped from the afternoon workout, when he is trying to get off with the girls on the dance floor. For the average scientist, on the other hand, that's seriously bad news. He or she has after all made a habit of ignoring the difference between muscle gains and water gains in his / her studies, whenever the measured muscle circumferences support his / her research hypothesis. In other words, until now nobody actually payed attention to the fact that what he / she measured on day 1 after the last workout of an 8 week study may be influenced to a large extend by the last and to a minimal extend by all previous workouts. It's thus totally correct that Kristiansen et al. demand that ...

"[...] post-training changes in CSA [cross sectional area] should be interpreted with caution, as they may adhere to exercise-induced water retention resulting from the last exercise bout." (Kristiansen. 2013)

In view of the fact that few researchers have hitherto exercised the said "necessary caution", it  appears to be more or less certain that a non-negligible proportion of the currently available data on skeletal muscle hypertrophy in training noobs such as Kristiansen et al.'s  ten healthy untrained study participants would have to be revised or at least tested.

Figure 1: Working out leads to increases in water content (left) corresponding increases in muscle "size" (right) at the 10 & 20 cm measuring points of the the quads; all values expressed as relative changes (%) vs. baseline (Kristiansen. 2013)

What's good though, is that it appears reasonable to assume that the cell swelling will be particularly pronounced, when the muscle is exposed to a new training stimulus (just like the DOMS, by the way; learn more) . This, in turn, would mean that the Kristiansen's one (1EX) and three (3EX) training day intervention  consisting of ...

• 2 min recovery between sets, 5 min between exercises
• verbal encouragement during all sessions
• total workout time ca. 45min

• 5 min warm up on a cycle ergometer
• 1x warm up set (5 reps; 50-60% 1RM) for the randomly selected working leg
• 5 sets of single-legged leg presses and knee extensions per workout
• 10 reps at an intensity of 10RM per set

... would probably have different effects in trained and highly trained individuals. Data form one of the few studies with "non-rookie" (aka "recreationally active") subjects does therefore have a much lower chance of having a measuring bias than data from studies with strength training novices. For those, the results of the Kristiansen study could mean that the real-world hypertrophy effects have been largely overestimated.

Figure 2: Schematic depictions and actual axial scan of the M. Quadriceps (Kristiansen. 2013)

Not convinced? Well, you cannot tell me that you actually believe that a single leg workout will increase the actual muscle size in the "teardrop zone" of the quads (see anatomical chart at the top in figure 2) of any trainee - rookie or not - by 16%, right (see figure 1)? I see no one is shaking his / her head.... well, then what do you think: How many researchers waited for a 3 full days or better a whole week after the last workout before they sent their subjects to the magnetic resonance imaging (MRI) device to obtain axial scans such as the one in Figure 2?

I have to admit that I haven't been paying much attention to the time-lag between the last workout and the MRI or measuring tape "powered" assessment of the post-intervention muscle circumference, but I am still convinced that it will be very difficult to find any study, where the post-values were taken more than 54h after the workout.

We must not forget, though that (1) the cellular hydration state is among the fundamental determinants of protein catabolism in health and disease (Häussinger. 1993), that (2) Basco et al. were able to show that the AQP4-dependent water transport into the muscle supports both, muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise (Basco. 2013), and that (3) Brad & Brent's review clearly suggests that the exercise induced cell swelling has a facilitative role in skeletal muscle hypertrophy.

Bottom line: If we also take into account that the vast majority of studies will use the 10cm point (see figure 2, left) to quantify the increase in muscle size, it is well possible that the average resistance training study could have overestimated the hypertrophy effect of the corresponding training (and supplementation!) regimen in novice or "recreationally trained" study participants.

In view of the fact, that very few of the studies had a duration of only three training sessions (1-2 weeks) and against the background that the multiple training sessions in studies with durations of 2-12 weeks will accustom the muscle to the previously novel stimulus, I would yet not go so far as to say that the results of the average study could be up to 10% off... I do, on the other hand, have my doubts that all the hitherto reported increases in muscle size would retain a p-value of p < 0.05 and would thus have to be considered as "statistically significant", if the CSA measurements had been taken 7days+ after the last training session.

References:

• Basco, D., Blaauw, B., Pisani, F., Sparaneo, A., Nicchia, G. P., Mola, M. G., ... & Frigeri, A. (2013). AQP4-Dependent Water Transport Plays a Functional Role in Exercise-Induced Skeletal Muscle Adaptations. PloS one, 8(3), e58712. 
• Miller, B. F., Olesen, J. L., Hansen, M., Døssing, S., Crameri, R. M., Welling, R. J., ... & Rennie, M. J. (2005). Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise. The Journal of physiology, 567(3), 1021-1033.
• Schoenfeld, B. J., & Contreras, B. (2013). The Muscle Pump: Potential Mechanisms and Applications for Enhancing Hypertrophic Adaptations. Strength & Conditioning Journal. 
• Tardioli, A., Malliaras, P., & Maffulli, N. (2012). Immediate and short-term effects of exercise on tendon structure: biochemical, biomechanical and imaging responses. British medical bulletin, 103(1), 169-202.