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.

Muscle Building Takes Time. Less in Newbies, Though: 9.6% More Muscle in 8 Weeks

"Patience is a virtue!" Many bodybuilders and fitness enthusiasts have to learn this the hard way - even on drugs, muscles won't grow (hypertrophy) within days and visible gains in lean muscle mass will take years or month. Although the results of a recent study (DeFreitas. 2011) done by scientists from the University of Oklahoma won't help to overcome the delay between training induced muscle stimulus and physiological hypertrophy response, the observations of DeFraitas et al. are nevertheless interesting.

By the means of weekly testing the scientists wanted to determine the "precise time course of skeletal muscle hypertrophy" in response to 8 weeks on a specifically designed high intensity resistance training program in 25 healthy, sedentary men. The measured outcomes were whole muscle cross-sectional area (CSA) of the dominant thigh (via computer tomography) and isometric maximum voluntary contractions (MVC). 

After only two training sessions (W1) [=week 1], the mean thigh muscle CSA increased by 5.0 cm² (3.46%; p < 0.05) from the pre-testing (P1) and continued to increase with each testing session. It is possible that muscular edema may have inXuenced the early CSA results. To adjust for this possibility, with edema assumedly at its highest at W1, the next significant increase from W1 was at W3. W4 was the Wrst signiWcant increase of MVC over P1. Therefore, signifcant skeletal muscle hypertrophy likely occurred around weeks 3–4.

While edema, unquestionably, are one possible reason for the sudden increase in "muscle mass" being a 'sedentary newbie' to strength training may well be another factor contributing to the immediacy of the muscle gains (do not expect to see similar results as an experienced athlete!). The scientists reliance on sedentary subjects compromises the significance of the whole study (in view of what athletes and gymrats may expect), thus the measured overall gains, impressive +13.9 cm² (9.60%) CSA, appear hardly transferable to a "reasonably" trained group of subjects, as well.

Figure 1: Development of muscle size (measured as CSA of thigh muscle) and force (measured as MCV) in 25 formerly sedentary subjects on an 8 week high intensity strength training program (DeFreitas. 2011)

Comment: Its really a pitty that out of monetary and organizational reasons all these studies are done on newbies, whom you could send work on a construction site for 8 weeks and see immense gains in strength and muscles, when they do not get hit by a block of concrete. So, do not feel discouraged if - in the course of the whole last year, you did not gain +13.9 cm² in your tigh muscle. You are probably just to athletic already ;-)

Want Bigger Guns? Train Legs Before Arms!

It is quite obvious that an elevation of testosterone and growth hormone facilitates muscle gains by jacking up protein synthesis and ameliorating protein breakdown. Now, intense leg training is famous for increasing both, testosterone as well as growth hormone levels of trainees. It is thus quite logical that Ronnestad et al. found (Ronnestad. 2011) that your arms grow faster, if you train them right after your legs.

The study design the scientists used is quite awkward, but clever. They had 9 (unfortunately) untrained subjects perform 4 workouts per week. On two of the occasions the subjects trained legs + one arm (L + A) on the other two occasions they only trained the other arm. Thus, Ronnestad et al. made sure that "both conditions have the same nutritional and genetic environment".

Figure 1: Plasma testosterone and growth hormone  measured before the strength training session (T-0), immediately after the leg exercises in the L ? A session (T-1), immediately after the arm exercises for both the L + A and A session (T-2), and 30 min after the arm exercises in both L + A and A session (T-3). (Ronnestad. 2011)

As can be seen in figure 1, only leg + arm, but not arm training alone produced measurable elevations of testosterone and growth hormone. Yet, although the cross sectional surface area (CSA, measured by MRA) of the biceps increased in both conditions, the major finding of the study was that...

only L + A increased the elbow flexors’ CSA at the two middle sections where the CSA of elbow flexors was largest.

In other words, the peak of your biceps, this hallmark, every bodybuilder is looking for, comes from training your legs (prior to your biceps).

5α-androstane-3,6,17-trione - Kneller's Trione: Newly Patented Aromatase Inhibitor that Raises Testosterone Without Lowering Estrogen Levels!?

I happened onto an interesting patent (Kneller. 2011), published on 02/10/2011 the author of which, Bruce Kneller, who was arrested in the course of a steroid bust back in 2006, claims to have invented an aromatase inhibitor, 5α-androstane-3,6,17-trione (Kneller's Trione) which produces "substantial and significant increases in plasma testosterone levels in men while inducing no changes outside the accepted normal limits for plasma estradiol levels". This is very different from your usual AI (ATD, Arimidex, Letrozole, etc.) which tend to eradicate estrogen and thus produce nasty side effects. As far as its concrete applications are concerned the author writes:

The oral, daily dose of Kneller's Trione can be from about 25 mg to about 750 mg per day, such as, for example, from about 25 mg to about 500 mg per day, from about 25 mg to about 250 mg per day, or from about 25 to about 100 mg per day. [...] In some embodiments of the invention the composition comprising Kneller's Trione is formulated as a tablet, capsule, caplet, powder, suspension, gel preparation, aqueous solution, solid food form (e.g., chewable bar or wafer), or liquid dosage form such as elixirs, syrups, dispersed powders, granules or emulsions.

Bruce W. Kneller then cites a pilot study in which Kneller's Trione was administered orally to three individuals at dosages of 25mg, 50mg and 100mg.

Figure 1: Tables from patent of Kneller's Trione

As can be seen from the tables in figure 1 the effect of 5α-androstane-3,6,17-trione depends on a) previous hormone levels and b) dosage. Most interestingly administration of 50mg Kneller's Trione to subject 2 who had low estradiol levels to begin with did not reduce these levels any further. With reference to the optimal dosing scheme and potential side effects Kneller reports:

Although dosing of Kneller's Trione went as high as 750 mg per day in this pilot study, no added benefits were seen with dosages this high. Dosages of 250 mg and 500 mg per day also raised total testosterone and bioavailable testosterone levels substantially and safely but did not seem to offer any added benefit over a dose of 100 mg per day. At the 750 mg per day oral dosing level, occurrence of a priaprism caused the subject to withdraw from participation in this pilot study. No other adverse events were noted by any study subject during this pilot study. Observations of every subject's liver function, kidney function, blood lipid levels, blood pressure, heart rate, respirations, and body temperature were made at frequent intervals during this pilot study and were found to be within medically established normal ranges and values.

While my cursory web-search for available OTC supplements with this product did not produce any results, I assume it won't take long until we see a range of these products on the market - even in view of the fact that a constant boner (priapism) may not be the worst, but certainly an annoying and in the long run painful side effect ;-)

As always, I will inform you as soon as there are more recent study results and or product releases. In view of the fact, that Kneller is also the patent-holder of the "OUTLAST" formula in Gaspari Nutrition's cell-volumizer SizeON it's most likely that we will see a "new Novedex XT" hit the market soon.

Edit: Kevin just posted a comment mentioning, he believes that it is already in "some Gaspari products" and in fact. He is right! Its part of Gaspari's Halodrol MT, which I believe is not produced anymore, though. Well, I assume that's what happens to things which work, these days...

The (Re-)Discovery of 17{beta}-hydroxyestra-4,9,11-trien-3-one: Low Dose Trenbolone Safely Promotes Myotrophic Actions in Skeletal Muscle and Provides Partial Protection Against Bone Loss and Visceral Fat Accumulation

Sometimes it is interesting to see how agents that have been around all along reappear back on the medical scene, all of a sudden. A recent study conducted by a group of scientists from Florida (Yarrow. 2011) that compared the effect of different doses of 17{beta}-hydroxyestra-4,9,11-trien-3-one aka Trenbolone on muscle hypertrophy and prostate health of testosterone seems to have the potential to trigger such a "revival":

In both intact and orchiectomized animals, all TREN doses and supraphysiologic testosterone-enanthate augmented androgen-sensitive levator ani/bulbocavernosus muscle mass by 35-40% above Shams (p≤0.001), and produced a dose-dependent partial protection against orchiectomy-induced total and trabecular bone mineral density losses (<0.05) and visceral fat accumulation (<0.05). The lowest doses of TREN successfully maintained prostate mass and hemoglobin concentrations at Sham levels in both intact and orchiectomized animals; whereas supraphysiologic testosterone-enanthate and high-dose TREN elevated prostate mass by 84% and 68%, respectively (<0.01). 

Whether this indicates that "trenbolone therapy" in men would actually be an alternative to the traditional androgen therapy to counter muscle wasting and other medical conditions remains to be elucidated. This is especially valid in view of the fact that the variables controlled in this study did not encompass any of the side-effects steroid (ab-)users tend to report on injectable trenbolone. In other words: Just because it does not enlarge your prostate, this does not mean that it is safe.

Reactive Oxygen Specimen (ROS) Trigger Muscle Hypertrophy via IGF-1 Signaling

I have touched on the "usefulness" of oxidation, only yesterday. Now, a very recent study appears to confirm the notion that a controlled amount of inflammation is necessary in order to achieve metabolic and muscular adaptations.

Figure 1: Eesult of the quantitative analysis of myotube diameter after IGF-I and NAC treatment (Handayaningsih. 2011)

Scientists from Division of Diabetes and Endocrinology and Division of Cellular and Molecular Medicine at the Kobe University Graduate School of Medicine published a paper (Handayaningsih. 2011) describing an investigation into the role of Reactive Oxygen Specimen (ROS) in the IGF1-signaling pathway. In this study N-Acetyl-Cystein (NAC), commonly used by recreational athletes as an "ergogenic" aid, blunted myocyte response to IGF1 and thus inhibited muscle hypertophy (cf. Figure 1):

While treatment with H2O2 significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR-p70S6K was subsequently down-regulated. Furthermore, thephosphorylationof FoxO1by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy.

Before you now go and flush all your vitamins and antioxidants down the toilette, you should consider that this is an in-vitro study with a narrow and limited ROS stimulation and not a large scale exercise supplementation study showing that the 500-1.000 mg of NAC you take on a daily basis will completely forestall muscle growth. If anything, it should remind you that excessive "inflammation" could be the "root of all evil" (cf. Super Human Radio), but excessive antioxidant supplementation certainly ain't a solution.

Creatine + Caffeine = No-Go? Still Nothing but a Myth

You probably have heard both that a) caffeine would negate the ergogenic effects of creatine loading and b) that the latter is nothing but one of those gym-myths which just won't disappear.

A recent study by scientists from the Department of Recreational Sports Management, Yu Da University, Miaoli, Taiwan (Lee. 2011) provides practical evidence that "the no caffeine when on creatine"-advice is garbage. The scientists investigated the effects of acute caffeine ingestion on intermittent high-intensity sprint performance after 5 days of creatine loading and found no detrimental effects of 0.6mg/kg caffeine on the creatine induced increase in exercise performance. What's more the ergogenic effect of caffeine added to that of creatine, so that ...

[...] the mean and peak power observed in the CRE + CAF were significantly higher than those found in the CON during Sprints 1 and 3; and the CRE + CAF showed significantly higher mean and peak power than that in the CRE + PLA during Sprints 1 and 2. [...] Heart rates, plasma lactate, and glucose increased significantly with CRE + CAF during most sprints.

On the other hand, one has to consider that this does not ultimately refute that "caffeine loading", or rather binging on caffeine day by day, may well exhaust your adrenal reserves in a way that after a few weeks of epinephrine overload, you are so drained that it becomes hard to drag yourself to the gym. In this situation all the creatine in the world probably won't help you.

High Dose Caffeine Will NOT Allow You to Curl More Weight

Most PreWorkout products are loaden with caffeine. The reasoning behind that is twofold: Firstly, the caffeine will spike you up and thus may allow you to work more energetically. And secondly, caffeine is believed to be a potent ergogenic in itself, allowing you to lift that extra pound you would otherwise have to take off.

As far as the ergodicity of caffeine is concerned, a recent study which was part of Jared Coburns dissertation at the California State University (Coburn. 2010) suggests that these must be more of a systemic nature. Comparing the effects of a preworkout drink with either 0, 5 or 10 mg/kg caffeine Coburn found

no significant differences for maximal strength, RTD [rate of torque development], EMG [electromyographic] amplitude and frequency, MMG [mechanomyographic] amplitude, EMD [electromechanical delay] and PMD [phonomechanical delay]

in his 14 male volunteers. So, while related studies, such as the one done by Pontifex et al. (Pontifex. 2010), where athletes had to perform several consecutive bouts of sprinting, provide evidence for the ergogenic effect of caffeine, it does not appear to benefit isometric muscle actions of the elbow flexors within a single set - in how far the results would have been different, if, for example, the subjects had had to perform dropsets is another kettle of fish.

1.86 g EPA + 1.5g DHA Augment the Hyperaminoacidemia-Hyperinsulinemia–induced Increase in the Rate of Muscle Protein Synthesis

MPS, the acronym for "muscle protein synthesis", certainly is an eye-catchers for everyone interested in building sleeve bursting arms. Obviously, the at which (dietary) proteins are incorporated into muscle tissue is an important factor in how much and how fast your muscles will grow.

Scientists from the Washington University, School of Medicine (Smith. 2010) have now conducted a randomized placebo controlled trial on the effect of omega-3 (4g/day Lavazza(TM) = 1.86 g EPA + 1.5g DHA) supplementation on muscle protein synthesis in older adults. And despite the fact that omega-3s on their own had no effect on  MPS, the consumption of supplemental omega-3s significantly augmented the MPS-response to Hyperaminoacidemia and Hyperinsulinemia.

Figure 1: Mean (6SEM) concentrations (arbitrary units) of mTORSer2448 and p70s6kThr389 during basal, postabsorptive conditions and during the hyperaminoacidemic-hyperinsulinemic clamp before and after 8 wk of supplementation with either corn oil (n = 7) or omega-3 fatty acids (n = 8). (Smith. 2010)

The results of this study may also shed some light on a 2003 study by Fearon, et.al. (Fearon. 2009), who found that adding fish oil to a protein supplement increased lean mass gains in patients with cancer cachexia.

While, in view of these results, adding some fish oil caps to your post-workout protein + carb drink  seems to be a beneficial, yes, almost obligatory idea, I personally feel that the verdict on the effects of fish oil (especially in particularly high doses) in healthy, or even athletic parts of the population is still out there. Anyway, I will keep you posted.

On a side note: Notice that this study uses a much more "favorable" (my point of view), low EPA:DHA ratio compared to the study I reported on a few days ago, which found no influence of fish oil supplementation on weight and fat loss in obese individuals.