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.

Beet Root Juice Supplementation Improves Exercise Performance. Nitrate Content of the Beets Decreases ATP Turnover in High Intensity Exercise.

Nitrates have long been decried as toxic and dangerous and I bet, before their latest appearance to the supplement market, none of you would even have remotely considered to consciously increase his/her dietary nitrate supply. Yet, recent scientific studies confirm that nitrate (in moderate doses) is not only safe, but also has, its effects on vasodilation aside, quantifiable effects on exercise performance.

A group of scientists from the UK tried to find out the underlying mechanisms of the ergodicity of supplemental nitrate (Baily. 2011). Following a six day supplementation period in the course of which seven males (aged 19-38 yr) consumed 500 mL per day of either nitrate-rich beetroot juice (~300mg nitrate content) or placebo (PL, with negligible nitrate content). What they observed is best described as a "tuning effect" that was observable both, in the course of high, as well as in the course of low intensity exercise training.

During low intensity exercise, the pulmonary VO2 amplitude and thus the oxygen need during this kind of aerobic exercise decreased by -7%. An even more profound effect of nitrate supplementation was observed during high intensity activity (knee extensor exercises) where the ATP turnover decreased by -25%. These results stand in line with an overall increase in exercise tolerance of +25% in the nitrate supplemented group over placebo.

Other than a some other researchers had speculated, Baily et al. did not find any indications of a changed phosphate vs. oxygen (P/O) ratio in the muscle. The changes in ATP turnover a 6-day loading phase with dietary nitrate from beet root juice triggers, must thus be considered the underlying mechanism of the ergogenic effect of nitrates, which, as you may have notices, appear in various forms (amino acid nitrates, creatine nitrates, etc.) in recently released supplements - not without reason, as it turns out.

Taking a Week Off? Sudden 7-Day Exercise Cessation Perceived as a Strain by Highly Trained Athletes. Overtraining is the Culprit!

Did you ever decide to take a week off and felt like hell? Did you feel how the gym, a place of which, only two days before, you thought you would be happy not to see for at least a month, suddenly seemed to draw you in as a giant magnet? Yes? Then you are either an exercise addict or just a highly trained athlete (probably you are both), of whom a recent study (Zeller. 2011) published in the Israel Medical Journal reports that

exercise deprivation is associated with change in non-articular tenderness threshold and reduction in quality of life scores. 

I already hear the exercise junkie within you jubilating: "24/7, 365 days a year! That's the way to go. That's my way." Before you do fall for this misunderstanding, you'd better thing about possible underlying reasons for the sudden tenderness and the decrease in perceived overall health (-4pts out of 100) the 26 asymptomatic healthy athletes who regularly exercise 6.75 ± 3.65 hours a week reported after the 7 days intervention.
In fact, the scientists conclude that it is not the resting that fatigued them, but rather the constant exercise that prevented them from feeling their ever-increasing level of fatigue (keyword: overtraining):

[...] healthy individuals who have hypoactive function of the biological stress response systems unknowingly exercise regularly to augment the function of these systems. 

Aside from falling victim to the mainstream believe in the "more helps more"-principle, this almost pathological behavior, i.e. to blunt exhaustion by exhausting oneself even more, is unquestionably the central mechanism behind the commonly observed tendency of athletes, who are already severly overtrained, to 'naturally' ramp up training volume and/or intensity in order to achieve the short term satisfaction the increased nervous system stimulus provides. In the long run, however, this will inevitably lead to performance declines, total exhaustion, susceptibility to infections and injuries, and so on.

Bottom line: Take a week or two off every now and then. If you crash badly, you know it was about time ;-)

Confusing Study Results: Saliva Testing "Adequate" For Free Testosterone, Yet Way Off For Cortisol!?

Many of us spend a fortune on "hormone optimization", but when it comes to actually testing our levels, most of us are pretty cheap: "200$ for labs? No way I rather buy another test booster for that money - won't hurt, I guess!" And even, if we finally decide to test our testosterone levels, we will usually choose the cheapest and most convenient testing method: saliva testing. But is this an adequate way of assessing one's hormonal status? Although these tests have been around forever, nobody appears to be sure how reliable they actually are. A recent study (Caenegem. 2011) from the University Hospital of Ghent, Belgium, attempts to provide answers.

The researchers tested two saliva collection methods, chewing on a cotton swab (Salivette, Sarstedt) and passive drooling on 30 healthy males with a median age of 27 years (range 19–65 years) and compared their findings against serum levels, which were measured on the same occasion. Here are their results:

For cortisol, we observed a mean positive bias of 65% for passive drooling versus Salivette. In addition, cortisol determined on passive drooling samples correlated much worse with calculated free cortisol than cortisol analyzed on the cotton samples (respectively r=0.34 versus r=0.70). However, for testosterone passive drooling correlated well with the calculated free fraction (r=0.66). A positive bias of 21% for testosterone collected by passive drooling versus Salivette was observed. In contrast to earlier reports, we found no artefactually high testosterone results with the cotton-based collection method.

Obviously, these results seem to indicate that saliva testing for testosterone is a good, while saliva testing for cortisol is a bad idea, BUT these results are in fact intrinsically flawed. By just calculating free serum values instead of using equilibrium dialysis to actually measure them, the scientists' control values and with them their assessment of the "appropriateness" and "inappropriateness" of salivary testosterone, respectively cortisol testing are questionable. 

From what I hear from practitioners like Dr Crisler, it is highly advisable to spend the extra cash to have measured (not calculated) serum testosterone levels as reliable baseline and 4x saliva cortisol profiles to see where your levels are at throughout a 24h period. Arguably, this is yet another case in which a questionable study design leads to results which refute common practice and aggravate a confusion around hormonal testing procedures which affects practitioners and patients, alike.

DHEA the Slimming Hormone? Study Finds: Dehydroepiandrosterone Directly Inhibits Cortisol Synthesis in Rodent Adipocytes

After initially being hailed as the fountain of youth, the pharma-financed medical sciences dropped DHEA, when investors realized that a naturally occurring hormone would not be patentable. This and some discouraging and/or inconclusive results from long-term studies had DHEA literally disappear from the research scene for quite some time. Therefore, I am positively surprised that on the forthcoming European Congress of Endocrinology 2011 researchers from the Kobe University in Japan are going to present a paper (Tagawa. 2011) that shows that there may in fact be more to the initial findings of DHEA induced weight loss than follow-up studies would have it.

Tagawa et al. investigated the possible mechanism behind the weight loss effects of DHEA and found that there is a direct inhibitory effect of DHEA on glucocorticoid (re-)synthesis in adipose tissue:

Using differentiated 3T3-L1 adipocytes, we demonstrated that DHEA inhibited 11β-HSD1 activity at a concentration of 1 μM within 10 min. Inhibition was also observed in a cell-free system comprised of microsomes prepared from rat adipose tissue and NADPH, a coenzyme of 11β-HSD1. A kinetic study revealed that DHEA acted as a non-competitive inhibitor of 11β-HSD1. Further, DHEA did not inhibit 11β-HSD type 2, which inactivates cortisol or corticosterone in tissues involved in water and electrolyte metabolism, in rat kidney microsomes at a concentration <25 μM. Moreover, no conversion from DHEA to other sex steroid hormones or their precursors was observed under the present experimental conditions.

These are three significant observations. Firstly, the presence of DHEA inhibits the synthesis of cortisol via 11Beta-HSD1. Secondly, it does not prevent exogenous cortisol to be converted to the "inactive" cortisone via 11Beta-HSD2 and thirdly, the dreaded conversion into estrogen, testosterone or DHT does not take place. All this would make the naturally occurring hormone DHEA a perfect selective 11β-HSD1 inhibitor, of which Stewart et al. from the University of Birmingham write (Stewart. 2011):

Selective 11β-HSD1 inhibitors lower blood glucose, improve insulin sensitivity and cause weight loss in animal models. Biomarkers have been validated to confirm target inhibition in primate and human studies. Recent clinical trials show reduction in HbA1c and blood pressure in obese patients with diabetes mellitus who have failed on metformin therapy. Potentially the therapy offers a ‘magic bullet’ for patients with Metabolic syndrome with reduced blood glucose accompanying improved insulin sensitivity, lower lipids and blood pressure and reversal of hepatic steatosis secondary to reduced autocrine generation of cortisol in liver, adipose tissue, pancreas and muscle. Liabilities include activation of the HPA axis secondary to increased cortisol clearance with hyperandrogenism, though the extent and significance of this is debated.

One thing, though, before you now go about eradicating cortisol to zero. Your body needs a healthy level of cortisol to function. It goes hand in hand with thyroid hormone, helps you manage stress, perform in the gym and is even necessary to "burn" body fat. Again, moderation is key and you certainly want to know where you stand before you start tweaking your cortisol levels into the wrong direction.

There Are Two Sides to Each Coin: Vitamin D Increases Insulin Sensitivity in Obese, Yet Decreases it in Lean Mice

I am probably repeating myself, but I cannot emphasize enough that a common fallacy of medical research is the focus on pathologies. A recent example with respect to the "omnipotency" (that's what the Internet news could make you believe) of vitamin D comes from researchers at George Town University (GU. Press Release).

The scientists were able to replicate the results of previous studies, where high dose vitamin D supplementation had "significantly reduced development of estrogen receptor-positive (ER+) breast cancer", but for estrogen receptor-negative (ER-) breast cancer they found either no effect (lean mice) or even an increased rate of cancerous growth in the group of obese mice.

What's yet even more interesting that a similar contradiction was evident with respect to vitamin D's widely perpetuated beneficial effects on insulin resistance. In the pathologic model of the obese mice, vitamin D @ 15-25k IU per day was in fact able to ameliorate insulin resistance, in the lean, naturally insulin sensitive mice, however, insulin sensitivity was reduced by supplemental vitamin D.

As I've discussed it in the context of the most recent fish oil study (and will probably repeat for other "super nutrients"), in 99.9% of the cases the effect of - especially high dose - supplementation with ostensibly harmless "vitamins" or "nutrients" vary enormously depending on the subjects current nutritional and health status. To derive one-size-fits-it-all recommendations from individual studies and to transfer results obtained from a pathological model without further scientific investigations to a healthy one is careless and may turn out to be very dangerous.

Victorious Veteran: Creatine Monohydrate Still First Class! Usefulness & Safety of “Innovative” Creatine Formulas Questionable.

If we discount a high protein intake as a regular constituent of a healthy diet, creatine is unquestionable the King of Natural Ergogenics. Its impact on athletics way beyond the Gold’s Gyms of the bodybuilding world is evident from its being cited as “effective and safe” in almost each and every “position stand” published in one of the journals of the various sports & nutritional societies all over the world in regular intervals. Thus, with the (nephro-)toxity myth being finally dispelled, creatine has become a stable in the supplement regimen of both recreational, as well as professional athletes.

Now, the financial revenue you can make from a non-patentable amino acid that is commonly found in fish and meat products is obviously limited. Thus, the steadily increasing number of players on the supplement market is continuously trying to “reinvent the wheel”, by putting forward a new, better-absorbed, more effect, side-effect free or whatever else the marketing guys had on their minds forms of N-(aminoiminomethyl)-N-methyl glycine (=chemical formula of creatine). These “superior” forms of creatine are then put forward as the must have for every seriously training athlete and/or creatine non-responders (these are people, where – due to various not fully understood mechanisms – creatine has no measurable effect on performance, (intracellular) water retention and body weight) and usually disappear from the market just about at the same time, the first batch has been sold and disappointed customers begin to vent their anger on the blogs and bulletin boards of the fitness world.

With reference to the purported superiority of novel forms of creatine R. Jäger, one of the leading researchers in the field writes in a recently published paper (Jaeger. 2011), the results of which have previously been presented at the 2010 Creatine in Health and Sports conference:

[…] the efficacy, safety, and regulatory status of most of the newer forms of creatine found in dietary supplements have not been well established. Additionally, there is little to no evidence supporting marketing claims that these newer forms of creatine are more stable, digested faster, and more effective in increasing muscle creatine levels and/or associated with fewer side effects than CM.

In their extensive review of the literature Jäger et al. dissect many of the commonly held views on the purported “instability” and “low absorbtion rate” of creatine monohydrate, evaluate the different creatine contents of various supplemental forms and their individual solubility, stability and bioavailability. And while some other forms are in fact more soluble…

Creatine monohydrate dissolves at 14 g/L at 20°C resulting in a neutral pH of 7. A saturated solution of tricreatine citrate in water has a pH of 3.2; whereas a saturated solution of creatine pyruvate even has a pH of 2.6 (pyruvic acid is a stronger acid than citric acid). The decrease in pH results in an increase in solubility: 29 g/L creatine citrate at 20°C, and 54 g/L creatine pyruvate at 20°C. Normalized by the relative amount of creatine per molecule (monohydrate 87.9%, citrate 66%, pyruvate 60%), creatine citrate (19.14 g/L) shows a 1.55-fold and creatine pyruvate (32.4 g/L) a 2.63-fold better solubility when compared with the monohydrate (12.3 g/L).

The acidity of your stomach is high enough, anyway, so that even if you just swallow the powder it will eventually dissolve, when it comes in contact with your gastric acid - for monohydrate [CM] Jaeger reports the absorption to be as high as 99%.

Furthermore, pre-solving of creatine in water is counter-indicated, because, as Jaeger et al. write, …

[…] solution precludes the manufacture of shelf-stable standard ingredient. If creatine is not consumed immediately after it has been dissolved in water, it should be stored at a low temperature to retard the degradation.

So you better throw away your liquid creatine - chances are its 99% degraded even before you bought it from your retailer.

The instability is even more of concern in the case of Creatine Ethyl Ester (CEE) which has been found to be “actually less stable than CM.” (Child & Tallon. 2007).

CEE is mostly converted into creatinine under physiological conditions encountered during transit through the various tissues, suggesting no ergogenic effect is to be expected from supplementation of CEE.

The latter, i.e. creatine ethyl esther, is also less bioavailable, 

Figure 1:Changes in total muscle creatine content in response to placebo (PLA), creatine monohydrate (CRT), and creatine ethyl ester(CEE) supplementation (Spillane et al. 2009, cf, fig. 1).

and studies (Spillane. 2009) suggest that its higher rate of degradation to creatinine may pose a possible health risk.

Also, while Jaeger et al. report some evidence for the beneficial effects of co-supplementation with glucose, protein or (low dose) D-pinitol, I personally doubt that either of them is necessary to take advantage of the repeatedly proven ergogenic effects you can get from the cheapest, most researches, safest and easiest to obtain form of creatine – creatine monohydrate.

On a side note: My friends @ironmagazine.com have found an interesting study on the effect of creatine + nitrate, which is currently hyped as “the next big thing”. Although, I suppose that the amount of the carcinogen N-nitrososarcosine, which is a byproduct of their reaction, is hardly high enough to trigger cancerous growth, the lack of direct scientific evidence that creatine nitrate has any beneficial effect over the individual use of nitrates (for pump) and creatine (for performance) at least makes me wonder if you could not eat a buckload of beet roots (high in nitrate) with your creatine monohydrate to achieve the same effect ;-)