SuppVersity - Nutrition and Exercise Science for Everyone

"No pain no gain?" No, that ain't the blood dropping from you wound hands.Those are the remnants of your next goto PWO drink. A Bloody Mary!

While I have been covering all sorts of testosterone-related stuff within the past couple of weeks, one thing has still been missing: The classic herb from the darkest jungle that'll increase the testosterone levels of one out of the two testers the respective company claims to have beta-tested their product on by whatever incredible percentage. Ok, I must admit, I don't have such an herb at hand at the moment, but what about Bloody Mary? No, not for the tomato juice, although that would be an awesome addition (learn more about "TomatoRade(R)") to the alcohol!

Alcohol? You're kiddin' me... right!?

At least at first glance it certainly looks as if you could hardly find better news for all the partying muscle heads out there, than the soon-to-be-published paper by Jakob L. Vingren, David W. Hill, Harsh Buddhadev, and Anthony Duplanty from the Department of Kinesiology, Health Promotion and Recreation at the University of North Texas (Vingren. 2013). After all, the four Texans discovered that the ingestion of booze instead (and probably also along with) your protein shake after your workout will prolong and amplify the "anabolic state" you're in once you leave the gym fo a couple of hours. Bullshit? No, it's not April the first, yet.

The participants were 8 healthy previouly resistant trained men (21-34 years; 87.7kg, 177 cm, 15.1 % body fat) who performed 6 sets of 10 repetitions of Smith machine squats starting at 80% of 1RM and 2 min of rest between sets (assisted forced reps, when necessary) after an appropriate warm-up:

Figure 1: Relative changes in free and total testosterone, SHBG, the testosterone to cortisol ratio and estradiol levels; data expressed relative to values at rest (Vingren. 2013)

You see? No changes in SHBG, cortisol and only a statistically non-significant increase in estradiol, but a persistent elevation of free and total testosterone. How that works? Well, you just pick a drink of your choice (the scientists obviously simply dilluted ethanol in water so that the mixture would have 19%) and drink as much of it as would be necessary to cover your "post workout ethanol requirements" of 1.09g/kg of lean body mass.

Want to know more about the net gains / fat loss testosterone produces? Or are you interested in the negative consequences of really low testosterone levels? Click here to learn more.

Did you know that a very recent study from the University of Chile shows that testosterone works its muscle building magic via the very same PI3K/Akt and mTOR pathways you are targeting with your hitherto non-alcoholic post-workout nutrition (Basualto-Alacon. 2013)? Since testosterone does yet also act on the androgen receptor, it can't be excluded that the effects are (a) additive / synergistic or (b) a certain degree of T-induced androgen receptor activation is necessary for the PI3K/Akt pathway to work. If you want to learn more about post workout browse through previous article on the matter, here.

A guy with a lean body mass of 65kg, for example would need ~71g of pure alcohol. That's about 668ml of regular red wine or drink enough Bloody Mary's to his TBA (testosterone boozing allowance) of ~165ml of vodka (100% proof). If we further assume he gets his Bloody Mary mixed according the standards of the International Bartenders Association, he would have to make room for 4x Bloody Marys in his gymbag ;-)

Sound easy right? But does it help at all?

You probably did not start boozing already, right? Otherwise you would not pose smart questions like the one in the above subheading. Obviously, the researchers asked themselves a very similar question: Can this poison really be ergogenic? Unfortunately, their answer does not really go beyond serving us the same old paradigm of the "anabolic milieu", the validity of which is more than questionable (suggested read: "Does the "PWO Elevation of Testosterone Influence Muscle Growth?"):

Strength, cardio or both for the optimal T:C ratio? (learn the answer)
"Although the T:C [ratio between testosterone and cortisol] is a crude measure, it response shows that the elevated in testosterone in the latter stages of recovery following ethanol ingestion is not associated with a corresponding elevation in cortisol, a hormone with catabolic and anti-anabolic physiological effects. The results for the T:C ratio suggest that a more anabolic milieu exists during the latter stages of recovery from resistance exercise following ethanol ingestion." (Vingren. 2013)

In the researchers defense, it does yet have to be said that they do not simply ignore the fact that the significance of workout induced changes in the "anabolic milieu" in terms of immediate skeletal muscle growth may have been overrated.

Now, while we do not have any studies on the "the effect of post-exercise ethanol ingestion on protein accretion" (Vingren, 2013), we do have studies showing that the ingestion of alcohol in general appears to hamper the recovery from resistance training (Barnes 2010; Barnes 2012) and increases the suppressive effect of exhausting endurance exercise on testosterone production (Heikkonen. 1996). The logical conclusion, Vingren et al. draw is thus that it "remains unclear" how the ethanol induced maintenance of high free and total testosterone levels in the hours after a workout would affect the muscular adaptation processes and their downstream effects on muscle size and strength in response to resistance exercise.

Bottom line: Personally I don't believe that 1.5 pints of red wine make the ideal post workout drink, not just because they are lacking protein, but rather in view of the previous research from Barnes and Heikkonen which may not disprove the possibility that 1.06g of ethanol after a workout could potentially exert "anabolic" effects that will eventually manifest in greater gains in muscle size or strength, but should suffice to rate an already highly questionable hypothesis "very unlikely".

Click on the image above to read my previous article series called "Chest Fat, Bitch Tits, Chesticles, Gynecomastia, Lipomastia and Co.: Infinite Ways to Name it, 45 Ways to Prevent It". Plus: Is your gyno in fact just too much body fat? (read more)

We should also take into account that the mechanism by which this increase or, to be precise, the absence of a decrease in total testosterone and the 2nd spike in free testosterone come about, may very well decide whether it's a good or bad thing. When I think of alcohol I usually think of the liver and, when I think of the liver, alcohol and testosterone, I think of the accumulation of estrogen in heavy drinkers with a alcoholic fatty liver, which renders them prone to develop gynecomastia. Why? Simply because their liver cannot get rid of the end-products of the hormonal cascade. So, if the higher testosterone levels are simply the result of a temporarily hampered hormone metabolism in the liver, it stands to reason that the results are unlikely to increase your strength and muscle growth, right?

Overall the study at hand is thus nice for some intellectual masturbation, but should not serve as an excuse for regular alcohol consumption. Physical culture and booze were, are and will always remain incommensurable.

References:

Barnes MJ, Mundel T, Stannard SR. Acute alcohol consumption aggravates the decline in muscle performance following strenuous eccentric exercise. J Sci Med Sport. 2010; 13(1):189-93.
Barnes MJ, Mundel T, Stannard SR. The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function. Appl Physiol Nutr Metab. 2012; 37(1):63-71.
Basualto-Alarcón C, Jorquera G, Altamirano F, Jaimovich E, Estrada M. Testosterone Signals through mTOR and Androgen Receptor to Induce Muscle Hypertrophy. Med Sci Sports Exerc. 2013 Mar 6.
Heikkonen E, Ylikahri R, Roine R, Välimäki M, Härkönen M, Salaspuro M. The combined effect of alcohol and physical exercise on serum testosterone, luteinizing hormone, and cortisol in males. Alcohol Clin Exp Res. 1996 Jun;20(4):711-6.
Vingren JL, Hill DW, Buddhadev H, Duplanty A. Post-Resistance Exercise Ethanol Ingestion and Acute Testosterone Bioavailability. Med Sci Sports Exerc. 2013 Mar 6.

No ~~pain~~ inflammation, no gain? In the long(er) run this could in fact be true.

All of you who followed my advice to "like" the SuppVersity Facebook page and are thus keeping up with the numerous additional news I am posting there, should actually have seen the news item on the non-significance of the exercise-induced interleukin-6 (IL6) response for the exercise induced improvements in glucose metabolism (read more). The mere fact that the glucose metabolism of IL6(-) mice, which are mice who simply cannot express IL6, is still improved by "working out" does yet by no means preclude that the demonized cytokine does play a fundamental role in the exercise-induced systemic and local benefits. In fact, an even more recent rodent study would suggest that a certain degree of inflammation and the respective increase in IL6 immediately after a workout is even essential for persistent skeletal muscle hypertrophy.

As you may remember from the Intermittent Thoughts on Building MuscleSeries there is more to skeletal muscle hypertrophy than the simple messages such as "increases protein synthesis by X%" that are printed in shiny letters on the boxes of hundreds of the currently available "natural muscle builders" on the real and digital shelves of the supplement vendors. One of these "mores" is the recruitement of satellite cells, muscle stem cells that are incorporated into the musculature to replace damaged myonuclei or increase the myonuclear density to allow for greater protein accretion (learn more).

Decreasing domain sizes = better function + higher growth propensity

"Hold on those are rodents and rodent studies are not relevant!" While it is a good thing to critically assess whether the results of a certain study can be species specific. The contemporary practice to question all rodent studies which are not part of your own cherry picked arsenal is getting onto my nerves. So, please check out the pretty analogues (short term unfortunately) human study by McCay from 2009 (McCay. 2009), before you stop reading after spotting the word "rat" in this article.

It is this process of satellite cell activation and incorporation of which Gwenaelle Begue and her colleagues from the University of Montpelier have now confirmed that it depends on the activation of the IL-6/STAT1/STAT3 signaling pathway in a prolonged 10 weeks resistance training scenario. In the course of the latter, 36 male Wistar rats were randomly assigned to one out of the following six groups:

CTL2, CTL4, CTL10 (CTL = non-training controls, n = 6 in each group) and
TR2, TR4 and TR10, which were rats trained for 2, 4 and 10 weeks.

The rodents in the TR-X groups were supposed to climb an apparatus with initially 50% later up to 210% of their body weight strapped to their back, five times a week. The load was increased every two days, if the rodents still managed to do "10 reps" = climb 10 steps and reached quite impressive levels of 120% of the body weight after two, 150% of the body weight after four and 210% after ten weeks of training.

Where is the rodent squat machine?

No rodent squat in the study at hand, but the "stair climbing" is a better full-body workout, anyways.

Now, this may not be as "realistic" a program as the rodent squat Aguiar et al. used in their 2012 study, but is is - and this is interesting - very similar to a test that has been done by many researchers with myostatin negative mice. As you will remember from the Intermittent Thoughts on Building Muscle Series (click here to read the pertinent part) those heavily muscled mice are unable to lift their own bodyweight, mainly because of the fact that the myonuclear domains within their muscle grew beyond a threshold where they absence of an adequate number of myonuclei per volume unit enders the muscle useless.

"Healthy" muscle growth does therefore require both, protein synthesis (increase in volume), as well as structural adaptations, so that the domain size does remain constant - at least!

"10 weeks of resistance training did not affect the myonuclear domain"

Against that background the last subheading, which is in fact a direct citation from the full text of the Begue paper is - contrary to what a non-SuppVersity reader could believe - good news. Very good news, to be precise:

Figure 1: Changes in fiber type ratios (left), cross sectional diameter according to fiber type (middle) and fiber area per myonucleus (right; Begue. 2013)

As you can see in figure 1 (right hand side), there was even a small, yet statistically non-significant decrease in the fiber area each myonucleus had to control and that despite quite impressive increases of 77%, 92% and 100% in the cross-section of the type-I, type-IIa and type-IIx fibers of the animals (figure 1, middle).

Satellite cell recruitment, necessary of optional if you want to get big?

In this context, Begue et al. speficially point out that the "recruitment of additional nuclei derived from SC incorporated into muscle fibers" occurs parallel to the better known "resistance training induced enhancement of protein synthesis" that occurs "after the training session and last[s] up to 24–48 h in humans" (Bengue.2013).

"Indeed, several works in humans have evidenced an increase in the number of myonuclei per fiber when fiber size increases approximately more than 25% (Kadi. 2004; Petrella. 2008). Thus, the myonuclear domain (i.e. the theoretical amount of cytoplasm supported by a single myonucleus in a muscle fiber) remained constant although a large increase in fiber CSA via the addition of SC-derived nuclei occurs." (Begue. 2013)

Since estrogen plays an important role in the regeneration of the satellite cell pool, it's pretty likely that you can literally "SERM your growth potential away" (learn more)

Notwithstanding the heavily quoted results of the 2011 study by McCarthy et al. in which the reasearchers were able to demonstrate that rodent muscle can grow even when it is satellite cell depleted, my personal conviction is that the latter process, i.e. the incorporation of new (not just even the replacement of damaged myonuclei is an obligatory prerequisite for persistent gains.

With +40% increased domain sizes, after only two weeks, it would have been interested to see how things would have developed in the subsequent weeks. I bet(!), the normal mice would have kept growing while their satellite cell depleted peers would have hit a plateau, where their own body woul have pulled the emergency brake aka myostatin (in this context, it's also interesting to remark that myostatin stops the proliferation of satellite cells and does thus indirectly divert the existing ones towards differentiation and incorporation into the muscle, cf. figure 2)

Bottom line: The study at hand delivers further evidence for the intimate connection between "inflammation" or rather the expression of the still demonized inflammatory cytokine interleukin-6 and the incorporation of "fresh" satellite cells into the muscle. With the latter being a necessary prerequisite to keep the domain sizes within functionally optimal limits while the cross section of the fibers is expanding (the muscle is growing), it is likely an (I want to emphasis that!) not yet disproven that continuous muscle growth requires satellite cell recruitment.

Basically you can think of it like the Army. While it is (or at least has historically been) relatively easy to find any recruits (=increase protein synthesis), people who are qualified to become officers and coordinate the actions of the rank and file are hard to find and without an adequate number of them you will end up with a chaotic mess instead of a powerful army. That's actually pretty much what happens to the myostatin negative mice, who may be able to recruit officers,... ah, I mean to recruit satellite cells, but simply outgrow the maximal pace of satellite cell incorporation.

Figure 2: IL-6 is the first myokine you should remember, it "wakes" the quiescent satellite cells up, he COX-2 activated IL-4 is myokine #2 and initiates the differentiation / incorporation process which will eventually result in the formation of a new nucleus. .

What, oh yes, of course! I had almost forgotten the unfortunately quite complicated connection to IL-6. If you take a parting look at the figure on the right, you will realize that a diagram explains things much better than I could. In fact, the "motor" of the whole growth business is the contraction induced expression of serum responsive factor, of which Guerci et al. have found in 2012 that it is the previously missing link between muscular contractions on the one hand and the expression of myokines, who happen to be the same molecules we know as "inflammatory cytokines" in other contexts. Il-6 and the COX-2 activated IL-4 are then getting things rolling (Guerci. 2012)... what? No, I cannot tell you whether taking antioxidants will block that, but I can promise you that you will learn more about this tie-in within the next 7 days, so stay tuned ;-)

What I can tell you in advance, though, is that strength and size gains of IL-6(-) mice are compromised (Serrano. 2008). So even if I would have to qualify my previous statement that satellite cells are necessary for continuous growth - one thing is sure: Their activation by IL-6 is necessary for optimal growth.

References:

Begue G, Douillard A, Galbes O, Rossano B, Vernus B, Candau R, Py G. Early Activation of Rat Skeletal Muscle IL-6/STAT1/STAT3 Dependent Gene Expression in Resistance Exercise Linked to Hypertrophy. PLoS One. 2013;8(2):e57141.
Guerci A, Lahoute C, Hébrard S, Collard L, Graindorge D, Favier M, Cagnard N, Batonnet-Pichon S, Précigout G, Garcia L, Tuil D, Daegelen D, Sotiropoulos A. Srf-dependent paracrine signals produced by myofibers control satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2012 Jan 4;15(1):25-37.
Kadi F, Schjerling P, Andersen LL, Charifi N, Madsen JL. The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J Physiol. 2004; 558: 1005–1012.
McCarthy JJ, Mula J, Miyazaki M, Erfani R, Garrison K. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle. Development. 2011; 138: 3657–3666
McKay BR, De Lisio M, Johnston AP, O'Reilly CE, Phillips SM, Tarnopolsky MA, Parise G. Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans. PLoS One. 2009 Jun 24;4(6):e6027. doi: 10.1371/journal.pone.0006027.
Petrella JK, Kim JS, Mayhew DL, Cross JM, Bamman MM. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J Appl Physiol. 2008. 104: 1736–1742
Serrano AL, Baeza-Raja B, Perdiguero E, Jardí M, Muñoz-Cánoves P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008 Jan;7(1):33-44.

It's efficacy in situations like this has more scientific back-up than any of the muscle building of fat burning promises some Tongkat Ali supps come with.

By now, most of you should have read the article on the testosterone "boozing" effects of alcohol and realized that the post workout Margarita probably comes off second best, when we compare it to whey and may - at least until we don't know otherwise - actually be pathological (=the result of a disturbance of the normal hormone metabolism in the liver). That being said, we better go back the "tried(!) and proven(?)" stuff. I mean a herb that goes by the name "Long Jack" does already sound way more promising than a "Blood Mary" doesn't it?

"Long Jack? ;Malaysian viagra? Ok, I am in!"

As the popular name already implies, the root of Eurycoma longifolia Jack, an evergreen plant that belongs to the family Simaroubaceae has a long (all puns intended) tradition in folk medicine. For which purposes? Well, in Malaysia, where people obviously like it a little more explicit, it's called "Tongkat Ali" (TA) and means (literally translated) "Ali's walking stick"... if that ain't explicit enough for you, just call it the "bushman's viagra", or whatever you like.

What's interesting and important to know though is that medicinal value highly of the root extract depends on the soil the plant was grown on. Tongkat Ali from the Malaysian Peninsular, for example, has higher concentrations of phytochemical compounds, such as eurycomaride, tannins, high molecular weight polysaccharides, glycoproteins, mucopolysaccharides and alkaloids of the quassinoid group, than TA from Thailand, Vietnam or Indonesia (Jiwajinda. 2001; Miyake. 2009). This is an important fact to keep in mind, when you buy your TA and a potential reason why you (a) may require way higher dosages than science would suggest to see any effect or (b) may not experience any of the benefits you may have hoped for (e.g. raging libido, increased testosterone and, as you are about to learn in today's article, loss of belly fat).

"Did I hear fat loss?" Yeah, you did!

I have to concede, the hitherto unrecognized fat loss effects Solomon et al. report in their latest paper that's about to be publishe in the peer reviewed journal andrologia were actually the main reason the 14-day rodent experiment the South African researchers conducted eventually made it into the SuppVersity news. The meager testosterone increase of +30% alone doesn't give me a kick, at all. I mean there are way more potent natural testosterone boosters out there that don't exert any beneficial downstream effects on your physique. So why should we bother?

Figure 1: Relative (in % of pre values) body weight, testes weight, prostate weight, weight of the epididymal and omental fat pads, the gastrocnemius muscle and the testosterone levels of the rodents after 14 days on the high or low dose of the extract (

And in fact, the 5.7% reduction in body weight the rodents in both the low (200mg/kg) and high dose (800mg/kg) arm of the study experienced would be quite the opposite of what you'd usually expect as a downstream effect of increased testosterone levels in otherwise healthy rodents. With a statistically significant increase in sperm vitality in the low dose and a less pronounced statistically non-significant increase in sperm vitality in the high dose group, as well as the highly significant increases in sperm count in both groups, it is yet very unlikely that the already small amount of body weight the rodents lost in the course of the 14-day experiment was a sign of toxicity or whatever.

What's more likely is that the overall weight loss effect is simply the result of the highly significant -31.9% reduction in omental and probably other not explicitly measured body fat (not the epididymal fat, i.e. the fat around the reproductive organs, though).

"How much of this stuff do I need?"

Don't be fooled: The testosterone and libido boosting effects we see in the study at hand is something dozens of other herbs can do as well, thin of the study on Nigella Sativa from one of the past installments of "On Short Notice", for example.

Provided you can get your hands on a correspondingly potent extract, it probably would not be necessary, and certainly a waste of valuable ressources to take more than the low dose regimen (HED 4g/day) , which is, compared to what we have hitherto seen in human trials, still hilariously much.

For the fertility part of the equation, way smaller doses of as little as 300mg of a freeze dried water extract from TA (brandname Physta(R)) have shown quite astonishing results in a group of 30-55 year old male subjects who achieved a 44.4% higher sperm motility, 18.2% higher semen volume and subjectively improved erectile performance after 12-weeks on this commercially available product (Ismail. 2012).What you should at least keep in mind though is the fact that financing of the study was provided by Biotropics Malaysia Berhad, the producer of Physta.

Similar fertility related results were also reported by Tambi et al. in 2010 (another "proprietary extract" ;-) and a handful of older and in some cases non-peer reviewed studies. As far as more physical culture related effects are concerned, a recent review by Chen et al. concludes that

"Eurycoma longifolia Jack, or 'tongkat ali', has not appeared to elicit any ergogenic effect on endurance performance in a limited number of studies of these herbs. However, future studies of this herb are definitely warranted because there might be a dose-dependent response and the supplementation duration of the previous studies might have been too short." (Chen. 2012)

It would therefore appear as if TA was more of "classic" libido & testosterone booster than an ergogenic. Something like tribulus and maca and just as those two probably of very dubious usefulness for young athletic men in the prime of their reproductive years.

Bottom line: That being said, Long Jack could be worth a try for everyone with already (or temporarily ;-) reduced testosterone levels, at least if we trust the judgement of Tami et al. who conclude their 2012 study into the effects of 1 month on 200g of a water-soluble TA extract with the words: "The standardised water-soluble extract of Tongkat ali proved to be a suitable herbal supplement in overcoming symptoms of LOH [late onset hypogonadism]." (Tambi. 2012)

The veterans among the SuppVerity readers may remember that I also covered the 2012 study by Tambi et al. on the usefulness of TA for men hypogonadal men (learn more)

If you still insist to try it, you should keep an eye on the eurycomanone and 13α(21)-dihydroeurycomaone content of whatever product you are buying, because these are the two fractions which will increase LH and FSH production and are thus probably responsible for jacking up your testosterone and sperm production (Low. 2013).

What? You cannot find a product that's standardized for those? Not even a supplement producer losing a word about their existence? Well, that's how this business works. Cite the studies and discard all the nasty details you don't like...

References:.

Chen CK, Muhamad AS, Ooi FK. Herbs in exercise and sports. J Physiol Anthropol. 2012 Mar 8;31:4. doi: 10.1186/1880-6805-31-4. Review.
Ismail SB, Wan Mohammad WM, George A, Nik Hussain NH, Musthapa Kamal ZM, Liske E. Randomized Clinical Trial on the Use of PHYSTA Freeze-Dried Water Extract of Eurycoma longifolia for the Improvement of Quality of Life and Sexual Well-Being in Men. Evid Based Complement Alternat Med. 2012;2012:429268.
Jiwajinda S, Santisopasri V, Murakami A, Hirai N, Ohigashi H. Quassinoids from Eurycoma longifoliaas plant growth inhibitors.Phytochemistry. 2001; 58:959–962
Low BS, Das PK, Chan KL. Standardized quassinoid-rich Eurycoma longifolia extract improved spermatogenesis and fertility in male rats via the hypothalamic-pituitary-gonadal axis. J Ethnopharmacol. 2013 Feb 13;145(3):706-14.
Miyake K, Tezuka Y, Awale S, Li F, Kadota S.Quassinoids fromEurycoma longifolia. J Nat Prod. 2009; 72:2135–2140.
Solomon MC, Erasmus N, Henkel RR. In vivo effects of Eurycoma longifolia Jack (Tongkat Ali) extract on reproductive functions in the rat. Andrologia. 2013 Mar 6.
Tambi MI, Imran MK. Eurycoma longifolia Jack in managing idiopathic male infertility. Asian J Androl. 2010 May;12(3):376-80. doi: 10.1038/aja.2010.7. Epub 2010 Mar 29.
Tambi MI, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia. 2012 May;44 Suppl 1:226-30.

Since it's Thursday my voice is back and I am already looking forward to today's SuppVersity Science Round-Up in which Carl Lenore an I are going to "attack" the following topics (tune in live at 1PM EST),

That pills can rarely compete with whole foods is something you've heard on SHR and read on the SuppVersity often, but that pills - in this case beta alanine pills - are better, when the content is mixed into the food instead of being prepared in form of time-released or whatever else caps may be news to some of you.

Summer time and the jet-lag is there... the effects and idiocy of daylight saving.
Stevia an anti-fertility sweetener, carcinogen and yet another welcome root of all evil?
Dairy & weight loss revisited, when even the abstract contradicts the conclusion.
Does too much protein make you fat? Yes it does - at least that's what the latest epidemiological data says.
Fish oil makes women hungry, exercise satisfies their cravings and improves gut hormone signalling.
High dietary restraint makes women lose their nocturnal progesterone surge

I decided to pick a fast, put practically relevant topic as the SuppVersity news of the day: Beta Alanine Supplementation; or, to be even more precise: "Optimal" beta alanine supplementation.

The less tingles the better!?

What type of food did the subjects eat? In the acute test the data in figure 1 (left + right) is based on, the subjects consumed a standardized breakfast consisting of 4 slices of white bread with chocolate-hazelnut paste, 200ml semi-skimmed milk, 1 banana and 125gr fruit yogurt, and a second meal with 150gr baguette topped w/ 40gr young cheese, 30gr mayonaise and vegetables with a 33cl orange juice (data not shown in figure 1). In the chronic ingestion study (figure 1, middle) participants in the w/ meal groups had 1x800mg cap with their three regular main meals and the fourth with a snack.

As a diligent student of the SuppVersity you will know that a major problem with beta alanine in scientific studies is that even the "time-released" tabs, the scientists usually use can produce this tingling sensation in all sorts of the body (I can tell you about that, from my more is more days back in the day; you really won't believe in which places you can "tingle" ;-) After my initial excitement and putting some thought into the hitherto still not 100% understood origin of the tingles, I did yet realize that they are not just unnecessary for the BA to work but could in fact be a negative (also physiologically negative) side effect of too much of the potentially toxic substance floating around in your blood stream (cf. Beta Alanine Suffocates Cardiomyocytes; other previous posts on BA).

Don't worry, it is totally unlikely that you will ever achieve serum concentrations that could do any harm, but one thing you should remember is that what you are striving for is not a high amount of beta alanine (BA) in your body. Your goal is to ramp up the intramuscular carnosine stores and that works only if the BA does recombine with the essential amino acid histidine and is subsequently stored within the skeletal muscle.

Food as an "advanced delivery formula"

The recombination / incorporation process is likely to be rate limited, so that it is only logical that any "overshoot" of beta alanine (again nothing your body likes to have floating around in the system) is going to be cleared before it can do its carnosine loading job. A job that is therefore facilitated by "packaging" the BA molecules with fillers & co in tabs, or - much cheaper and obviously way more natural - by simply ingesting it with food.

Figure 1: Selected time-frame of 8h blood profile of plasma insulin and beta-alanine (BA) after ingestion of 800mg of BA after meal in between meals or with meal (left and right). Effect of chronic ingestion of 4x800mg/day BA for five weeks with or w/out food in regular and sustained released form ( Stegen. 2013)

As the data in figure 1 that's based on the results of a soon-to-be-published study by Stegen et al. goes to show you, the "food advantage" is (as usual ;-) the 34 male and female subjects (age 19.4y; weight 66kg, daily BA intake at baseline ~230mg/day) derived from ingesting the BA with meals may not be earth shattering.

Still, the subjects who took the BA with a meal did not just have higher muscular carnosine levels than those who took the pure powder, at least in the slow-twitch fibers of the soleus, which are actually not that beta alanine affine as their counterparts in the gastrocnemius, the cheap and ingeniously simple "take it with food" solution to BA supplementation also outperformed the obviously pricier pre-prepared slow-release formula.

Where does the beta alanine go to, if not into the carnosine stores?

The scientists did yet also make another interesting observation, while only 1.6% of the beta alanine was excreted in the urine (slow release formula) the muscular uptake and the incorporation efficiency of exogenous BA into carnosine is actually so low that "the vast majority (~160g or 95-96%) of the ingested BA is neither going into muscle carnosine nor into the urine" (Stegen. 2013).

While respective scientific studies would still have to be conducted, the most likely hypothesis to explain the "disappearance" of beta alanine are:

Oxidation and use for energy production: While the contribution of alpha-amino acids to energy delivery in muscle and other tissues is usually quite low, as compared to carbohydrates and fat, their usage increases (up to 10% of total energy usage) with increasing amounts of the AA in the bloodstream. Evidence suggests that this is also the case for beta-amino acids, where and "excess" would obviously be achieved with dosages as they were used in most of the previous research on beta alanine supplementation (Harris. 2006, Hill. 2007; Baguet. 2009).

This hypothesis is also supported by the recent revelation that GABA transaminase activity, the enzyme that's required to initiate the oxidation of beta alanine increases upon BA supplementation (Everaert.2012)

Alternative pathways including uptake and incorporation into carnosine in other tissues: While it is not impossible that other organs (e.g. the kidney, liver or brain) avail themselves of small quantities of BA to up their own carnosine levels it is, as the scientists point out " unlikely that the conversion of BA into carnosine in other (non-muscle) tissues is of any quantitative significance, because presence of carnosine and carnosine synthase in non-muscle tissues is several orders of magnitude lower than in muscle" (Stegen. 2013)

Now that we have gotten that straight, the one question that remains is actually pretty simple, unlike the answer unfortuntately....

How does the meal improve the the bioavailability of BA

Personally I still feel that the main effect is the prolonged elevation of beta alanine, the scientists themselves however propose another (at least confounding) factor, which would also explain why simply taking the slow release formula won't work even if it is released just as slow as regular BA with food:

While BA still is often named in the same breath with creatine, the effect size and the likelihood that athletes will see any benefits at all is much smaller than in the case of the supplemental top dog (learn more in "Beta-Alanine Does not Make it From Bench to Pool Side: Are the Effects Too Short-Lived? Is Swimming the Wrong Sport? Or Was the Dosage of 3.2g/day Simply Too Low?")
"Clausen et al.showed that Na+/K+ pumps in skeletal muscle are stimulated by insulin over a range of concentrations down to low physiological levels (Clausen. 2003). Therefore, it is possible that meal-induced elevations in serum insulin are capable of triggering the sodium-dependent transporter TauT. In our study, a meal-induced effect could only be confirmed in soleus muscle. Considering the fact that this is a more insulin-sensitive muscle, it is not unlikely that the soleus responds better on insulin induced BA uptake. In addition Lavoie et al. demonstrated that insulin-induced translocation of Na+/K+ ATPase subunits to the plasma membrane (Lavoie. 1996), one of the two possibilities to increase Na+/K+ ATPase activity, is restricted to oxidative fiber-type skeletal muscles which are predominantly present in soleus."

Sounds more than logical and can also explain the differential effect on the oxidative = slow twitch fibers of the soleus (cf. figure 1, middle). With the insulin enhanced "pump activity" you have a mechanistic increase in BA uptake, no wonder that this improves the bioavailability, right?

Bottom line: From now on you buy your beta alanine in bulk and spoon-feed yourself with your 4x800mg of BA (the dosage used in the study at hand) after your preferably carb-containing meals and snacks. Don't worry BA is one of the few amino acid supplements that don't have a disgusting taste to them. You can actually add it directly to the food, but I would refrain from doing that before you prepare your meal. As simple as the BA molecule may be, we still don't know what kind of chemical reaction it may be exposed to if you actually cook it or do whatever other "nasty" things to it ;-)

References:

Baguet A, Reyngoudt H, Pottier A, Everaert I, Callens S, Achten E, and Derave W. Carnosine loading and washout in human skeletal muscles. J.Appl.Physiol. 2009; 106:837-42.
Clausen T. Na+-K+ pump regulation and skeletal muscle contractility. Physiol Rev. 2003; 83:1269-324.
Everaert I, De Naeyer H, Taes Y, Derave W. Gene expression of carnosine-related enzymes and transporters in skeletal muscle. Eur J Appl Physiol. 2012 Nov 4.
Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, and Wise JA. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino.Acids. 2006; 30:279-89.
Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, and Wise JA. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino.Acids. 2007; 32:225-33.
Lavoie L, Roy D, Ramlal T, Dombrowski L, Martin-Vasallo P, Marette A, Carpentier JL, and Klip A. Insulin-induced translocation of Na+-K+-ATPase subunits to the plasma membrane is muscle fiber type specific. Am.J.Physiol. 1996; 270:C1421-C1429.
Stegen S, Blancquaert L, Everaert I, Bex T, Taes Y, Calders P, Achten E, Derave W. Meal and Beta-Alanine Coingestion Enhances Muscle Carnosine Loading. Med Sci Sports Exerc. 2013 Mar 5.

Other news: Classic cardio ramps up GLP-1 and "posing" increases your maxes by up to 8%.

If you have already downloaded and listened to yesterday's installment of the SuppVersity Science Round-Up, you will probably be aware that the first thing I am going to do in today's Seconds is to (re-)address the stevia issue (read up on previous stories about Stevia here at the SuppVersity).

If I recall that correctly, I did in fact forget to mention something that's actually important if you want to get the whole picture - the gut microbiome! But before we tackle this one, let's not forget that there are a couple of other news stories which did not make it into the 60min show, news on the effects of LISS on GLP-1 and the potentiation of the post-activation potentiation effect. Sounds interesting, then let''s go for it!

Is stevia toxic, does it cause cancer and infertility?

Let me start with the bottom line first. The currently available scientific evidence clearly suggest that stevia is safe to consume. Or, as "real" scientists (not that I would not consider myself a scientist, but without a single published paper in this domain of science, I am certainly not an authority ;-) write in their papers:

What was that about the microbiome? I forgot to mention that the "bad" aglycol aka "steviol" is also produced from the benign and usually not even absorbed pure steviosides and is thus not something you'll find only in "natural" stevia products. That being said, Wingard et al. observed in 1980 already that steviol is readily excreted via the billary pathway in the feces (Wingard. 1980; confirmed by Nakayama. 1986). You may thus be exposed to small amounts of steviol no matter what, but that's nothing your body cannot dispose of.
"The recent suggestions that steviol glycosides present a muta-genic – and therefore carcinogenic – risk to consumers are not sup-ported by actual test results. The paper making this claim by Matsui et al. (1996a) was published prior to most of the papers assessing the genotoxic risk of steviol glycosides as well as several expert panel reports and a review by Brusick in 2008. The database of genotoxicity studies for steviol glycosides and steviol as it currently stands, combined with a lack of evidence for neoplasm development in rat bioassays (Aze et al., 1991; Xili et al., 1992; Toyoda et al., 1997; reviewed by Carakostas et al., 2008, 2012; EFSA, 2010), is adequate to establish the safety of these food ingredients with respect to their genetic/carcinogenic potential." (Urban. 2013)

And with respect to the infertility claim, Geuns et al. write in their very detailed review from 2003:

"The results of a decrease of live birth rate in rats (Planas and Kuæ, 1968) by Stevia decoctions were refuted by Shiotsu (1996) who did more reliable experiments with many more animals using methods as similar as possible to the methods used by Planas and Kuc. No effect on general condition, body weight, water consumption, live birth rate or litter size was found. No effects of stevioside were found on fertility or reproduction in mice (Akashi and Yokoyama, 1975), rats ( Mori et al., 1981, Xili et al., 1992 and Sinchomi and Marcorities, 1989) or hamsters (Yodyingyuad and Bunyawong, 1991).

No significant effect was found on spermatogenesis, nor on the interstitial cell proliferation and tumor formation in the testes of F344 rats fed a ration containing up to 1% stevioside (95.2% purity) for 22 months (Yamada et al., 1985).

If you are either a newcomer to the SuppVersity or simply cannot remember the summary of selected stevia research from September last year, I suggest you go back in the archives and read up on "More Than Super Sweet: More Scientific Evidence, More Potential Implications for Weight Loss & -Maintenance, Anti-Diabetic & -Autoimmune and Even Pro-Anabolic Effects" (learn more) Some of the benefits are btw. mediated by the same stuff that's toxic in in-vitro studies...hormesis, you know ;-)
Whereas Melis (1999) suggested a possible decrease of the fertility of male rats by a very high dose of Stevia extract, Oliveira-Filho et al. (1989) who administered extracts with similar stevioside content stated that there is certainly not an effect on male fertility. It is not sure that the observed effects were due to the stevioside present in the extract. It should also be mentioned that the used extract concentrations were extremely high, at the start of the experiments even 5.34% of the body weight (or around 5.3 g stevioside/kg bw). For an adult person of 65 kg this means 3.47 kg of dry Stevia leaves or about 34.7 kg fresh leaves/day, i.e. more than 50% of the body weight! The significance of such experiments where only one extremely high concentration was tested, should be questioned. Melis' results are also in contradiction with the above and below cited studies that could not reveal any effect on fertility of male or female animals." (Geuns. 2003; my emphases)

Much ado about nothing? Well, in the end it may seem so and the preponderance about freakin' out over every potential and 0.5% marginal possibility that something you do or eat could be wrong or toxic certainly ain't healthy. On the other hand, it's always good to exhibit a certain degree of suspiciousness - just do me favor: Do that towards both the good and the bad news!

Scheduled news that did not make it into the live show

The fat burning benefits of hydroxypropyl-distarch phosphate from waxy maize starch (WMHDP) are - at least in part - also mediated by increases in GLP-1 production (read more)

Short and long-term effects of exercise on appetite and metabolism regulating hormones -- (Ueda. 2013) As a SuppVersity reader and SHR listener, you are no stranger to the acronym GLP-1 and the effects the "satiety hormone" it stands for has on your desire to eat and, more importantly, your metabolisms willingness to use not store the energy from the food you consume (learn more).

In a soon to be published paper, Shin-ya Ueda and colleagues report that chronic exercise, in this case 3x/week 60min of light intensit (65% of VO2max) cardio on a treadmill and/or cycle ergometer results in a statistically highly significant increase in GLP-1 in response to exercise.

Usually I don't like to repeat myself, but I would probably have missed the main important message here, if I were just skimming the above: The 20 healthy middle-aged women who participated in the 12-week experiment did not simply have higher GLP-1 levels after a meal. No, the post-exercise levels of GLP-1 and the other satiety hormone PYY increased hours before the ladies even got their next meal.

Figure 1: GLP-1 (pmol/ml; left) and PYY (pmol/ml; right) response to exercise before and after (0, 30, 60 min) a 80min (60 min effective training + 20min warm-up, cool-down etc.) supervised workout before (untrained) the 12-week exercise intervention and after (trained) the 12-week exercise intervention (Ueda. 2013)

In conjunction with the significant correlation of GLP-1 with the reduction in body weight the study participants achieved over the course of the course of the 12x3 = 36 supervised exercise session, this was reason enough for the scientists to hypothesize that...

"[...] that the ability of exercise training to create a negative energy balance relies not only directly on its impact on energy expenditure, but also indirectly on its potential to modulate energy intake." (Ueda. 2013)

So, does exercise "just make you hungry". No, it turns you into a satisfied fat burning machine - and that even if it's just 3x60min of LISS per week.

Training increases the efficacy of 5-6s maximal contractions to before a maximal voluntary effort (Miyamoto. 2013) I guess you will be aware that Superman usually does a 5-6s maximal voluntary contraction (MVC) while checking out if everybody is watching before he eventually does the deed and lifts the car that has just overrun the beautiful blond bombshell with a "single-armed deadlift", right? Good, because if you know that, I don't have to explain why the scientists from the Waseda University in Japan 21 healthy male subjects perform a 5s MVC before they did their maximal voluntary concentric knee extensions 1, 3 and 5 minutes, thereafter.

Figure 2: Voluntary concentric torque on knee extensions after previous peak contractions before (left) and after (right) in the trained and untrained study participants.

What I probably still have to tell you though is that the "after" values you see in figure 2 were taken after 12-weeks of doing 5x 8 reps with 80% of the one-repetition max in a standard knee extension machine. Ok, I have to admit that the actual training effect is not really impressive, but since most of you have it already built in (after all, you probably train for more than 12-weeks already, right?) doing a single 5s maximal voluntary contraction before a max-effort trial is an easy and time-efficient (1 min!) way to increase your performance by superman-like 8%! What this funky technique is called like? Postactivation Potentiation - nice alliteration, isn't it?

That is it, for the day - at least for the Seconds. If you don't know what to do before the weekend begins, browse over to the SuppVersity Facebook Wall and check out news on

If you have not done so, already, click here and teach yourself "How to Make the Correct Fish choices"? There is luckily way more swimming around in our oceans than farmed salmon with it's more than 4x elevated n6:n3 ratio (compared to wild salmon, learn more)

Salmon in the vicious cycle of soy supplementation - Scientists try to come up with a certain bacteria that could protect farmed salmon from the junk, ah... soy it's fed (read more)

Alpha lipoic acid (ALA) helps otherwise healthy schizophrenics on heavy anti-histamine regimen to lose weight - 2x 1gram of regular ALA does the trick (read more)

People who were breastfed as kids have healthier eating habits in their adulthood - Interestingly, this effect did not depend on social class at birth or later in life and occurred irrespective of smoking status, alcohol intake or reported physical activity.

Once you've done that, you first make sure that you did not miss part three of my interview with Sean Casey and then get off the screen and into the night, family or whatever real life, I'd hope you did not give up on after you bought your latest iPhone ;-)

References:

Akashi H, Yokoyama Y. Security of dried-leaf extracts of Stevia. Toxicological tests. Food Industry. 1975; 18:34–43.
Aze Y, Toyoda K, Imaida K, Hayashi S, Imazawa T, Hayashi Y, Takahashi M. [Subchronic oral toxicity study of stevioside in F344 rats]. Eisei Shikenjo Hokoku. 1991;(109):48-54.
Carakostas MC, Curry LL, Boileau AC, Brusick DJ. Overview: the history, technical function and safety of rebaudioside A, a naturally occurring steviol glycoside, for use in food and beverages. Food Chem Toxicol. 2008 Jul;46 Suppl 7:S1-S10.
Geuns JM. Stevioside. Phytochemistry. 2003 Nov;64(5):913-21. Review.
Matsui M, Matsui K, Kawasaki Y, Oda Y, Noguchi T, Kitagawa Y, Sawada M, Hayashi M, Nohmi T, Yoshihira K, Ishidate M Jr, Sofuni T. Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays. Mutagenesis. 1996 Nov;11(6):573-9.
Melis MS. Effects of chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol. 1999; 167:157–161
Miyamoto N, Wakahara T, Ema R, Kawakami Y. Further Potentiation of Dynamic Muscle Strength after Resistance Training. Medicine & Science in Sports & Exercise. Publish Ahead of Print
Mori N, Sakanoue M, Takcuchi M, Shimpo K, Tanabe T. Effect of Stevioside on fertility in rats. J Food Hyg Soc Jpn. 1981; 22:409–414.
Nakayama K, Kasahara D, Yamamoto F. Absorption, Distribution, Metabolism and Excretion of Stevioside in Rats. Shokuhim Eiseigaku Zasshi. 1986; 27(l):l-8.
Oliveira-Filho RM, Uehara OA, Minett CASA, Valle LBS. Chronic administration of aqueous extract of Stevia rebaudiana (Bert.) Bertoni in rats: endocrine effects Gen. Pharmac. 1989; 20:187–191.
Planas GM, Kuæ J. Contraceptive properties of Stevia rebaudiana Science. 1968;162:1007.
Shiotso S. Fertility study of Stevia decoction in rats. Tech J Food Chem Chemicals. 1996; 4:108–113.
Sinchomi D, Marcorities P. Etude de l'activité anti-androgénique d'un extrait de Stevia rebaudiana Bertoni. Plantes médicinales et phytothérapie. 1989; 23:282–287.
Toyoda K, Matsui H, Shoda T, Uneyama C, Takada K, Takahashi M. Assessment of the carcinogenicity of stevioside in F344 rats. Food Chem Toxicol. 1997 Jun;35(6):597-603.
Ueda SY, Miyamoto T, Nakahara H, Shishido T, Usui T, Katsura Y, Yoshikawa T, Fujimoto S: Effects of exercise training on gut hormone levels after a single bout of exercise in middle-aged Japanese women. SpringerPlus. 20132:83.
Urban JD, Carakostas MC, Brusick DJ. Steviol glycoside safety: is the genotoxicity database sufficient? Food Chem Toxicol. 2013 Jan;51:386-90.
Wingard RE Jr, Brown JP, Enderlin FE, Dale JA, Hale RL, Seitz CT. Intestinal degradation and absorption of the glycosidic sweeteners stevioside and rebaudioside A. Experientia. 1980 May 15;36(5):519-20.
Yamada A, Ohgaki S, Noda T, Shimizu M. Chronic toxicity of dietary Stevia Extracts. J Food Hyg Soc Jpn. 1985; 26:169–183.
Yodyingyuad V, Bunyawong S. Effect of stevioside on growth and reproduction. Human Reproduction. 1991; 6: 158–165.
Xili L, Chengjiany B, Eryi X, Reiming S, Yuengming W, Haodong S, Zhiyian H. Chronic oral toxicity and carcinogenicity study of stevioside in rats. Food Chem Toxicol. 1992 Nov;30(11):957-65.

Certain "behaviors" during spring break can give your brain a neuro-anabolic break.

13% and 15% that's the number of Canadian University Students who claim to do what it takes to keep their brain volume at least stable over the spring break. 13% of the female and 15% of the male studentand female students, respectively, that's also the SuppVersity Figure of the Week and at the same time the relative number of students who openly declared that they were about / had previously engaged in "casual sexual activity" on the upcoming / past springbreak trip to Daytona Beach, Florida (Maticka-Tyndale. 1998)

Who said our youth did not know what's good for them?

Since the pertinent study preceded the Glasper study addressed in the current installment of on short notice by 15 years, these results just go to show you that we know instinctively what's necessary to counter the effects of the alcohol over spring-break ;-)

Selenium and skin cancer (Cassidy. 2013) -- I guess you will remember the debate that arose after the data from the selenium + vitamin E large scale trial hit the mainstream media news. Hell broke lose and people did (unfortunately) not only start questioning the usefulness, but also the safety of all vitamin supplements - and that quite frantically (cf. "Ask Dr. Andro, Are Vitamin Pills Bad for Me?").

The results of a recently published study by scientists from the Huntsmen Cancer Institute (no that's not "Paleo" ;-) in Salt Lake city could shed at least some new insights into the very mixed results we are seeing in the studies on vitamins and/or minerals with anti-oxidant prowess:

"Taking A Multivitamin is a Question of Faith", above all (read more)
"We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts." (Cassidy. 2013)

In other words, in as much as they are able to postpone / prevent the occurrence of cancer by protecting the healthy cells, their protective effect is not tissue specific and will - once the bad guys have appeared on the scene protect the cancer from your bodies own, as well as the pharmacological inflammatory anti-cancer machinery.

Alpha lipoic acid does not hamper exercise induced intramuscular ROS production & DNA damage (Fogarty. 2013) -- I know this does not really sound like good news to some of you, but you will be surprised that even the authors of the study at hand feel that it is.

While this is not directly related to the intramitochondrial ROS production, I still reccomend, you read my previous article on the purported "nutrient partitioning effects" of ALA before you go and buy a year's supply. (learn more)

The scientists from the University of Ulster recruited 12 of this in the world of scientific paper "rare specimen" of healthy male study participants (age 28 + 10 years, stature 177 +/-12 cm and body mass 81 +/-15 kg) and had them take either 2x1,000mg of regular alpha lipoic acid twice a day or placebo.

Wouldn't it be better to use R-ALA? I am telling you this now for the 1124th time: There is no reliable evidence for the superiority of R-ALA over regular ALA, the majority of the studies showing benefits of ALA supplementation has been conducted with the 50% r-enantiomer and 50% s-enantiomer version and if you have ever heard of the hormesis hypothesis (=low (eu-)stress induces beneficial adaptation) you would rather ask, "isn't it likely that taking R-ALA would not have yielded the same beneficial effects?"

The caps were to be taken in addition to the regular diet, the young men were following and were supposed to build up a protective anti-oxidant belt against the exercise induced oxidative assault of 100 isolated and continuous maximal knee extensions in the non-dominant leg after 14 days of supplementation.

"[The ALA preload] increase[d] plasma antioxidant status and attenuates lipid peroxidation and DNA damage following maximal, eccentric muscle contractions[, but] had no protective effect on muscle mitochondrial DNA damage."

Now this is actually awesome news, because it shows that ALA blunts the systemic oxidative damage only, while leaving the local intra-muscular oxidative damage of which the researchers rightly point out that "a substantial body of literature documents" the beneficial effects of ROS on "cell adaptation associated with exercise training" (Fogarty. 2013). In other words: It's unlikely ALA will hamper your gains.

Eccentric training for bigger stronger muscles? (Hody. 2013) -- At first sight the conclusion of a soon-to-be-published study from the University of Liège in Belgium, which says:

"Our data suggest that the eccentrically biased contractions in mice induced specific adaptations in protein expression and muscle fiber composition which may reflect a more oxidative muscle phenotype." (Hody. 2013)

appears to suggest that the longstanding wisdom that eccentric reps are (given you get adequate rest) profoundly anabolic was inaccurate. If you use your knowledge about the enormous degree of type I fiber hypertrophy in bodybuilders (cf. fig.1here), however, the information that eccentric training causes a shift in the muscular phenotype towards a predominantly oxidative slow-twitch fiber make-up, would at least the part about the muscles becoming "bigger" will remain intact.

Figure 1: Effect of five training sessions of variable duration (75-135 min / increasing from session to session) with 48h breaks between sessions on the muscle fiber make-up of mice (Hody. 2013)

Now, don't be afraid that your eccentric biceps curls could eventually make you weak. There are some "on the other hands" attached to the study results. The first and most important one of these is the mere fact that the largest increase occurred in type IIa fibers which are also often referred to as "oxidative" muscle fibers, but are actually more of an "jack-of-all-traits" fiber type, which happen to do most of the work in the BB-relevant 6-15 rep range. Secondly, the training downhill-running protocol the adult C57BL6 mice were exposed to. Downhill-running, may be eccentric, but it is also an endurance and no strength training regimen, and will thus have a tendency to promote the

No ~~pain~~ inflammatory signaling, no gain? In the long(er) run this could in fact be true (learn more). And what would be more fitting to induce the former if not eccentric training?

That being said, it is only logical that whatever growth / genera adaptation mechanism a given exercise regimen may be triggering, the trained muscle group and in this case also the trained fiber-type will benefit the most. Moreover, scientists and laymen tend have a very different understanding of a "shift in fiber type composition" by which the former don't imply loss of any fibers, while the latter misunderstand the ratios for absolute values and fool themselves to believe that results like the ones of the study at hand were about "losing precious type II" (=fast twitch, glycolytic, "lift heavy, but short") muscle fibers. What they are really about, is yet the accentuated ability of the highly stressing eccentric reps to induce more than just a "balooning up" of the muscles and induce profound structural adaptations, the importance of which I have highlighted only a couple of days ago in the context of my post on satellite cells (read up on that one).

Only regular sexual intercourse keeps your brain healthy and in shape (Glasper. 2013) -- No, I am not going to start this comment with a reference to certain old men who met a couple of days ago in Rome. I will rather stick to the relevant facts and inform you that you better make sure you get laid this weekend. Why? Easy, a recent study by scientists from the University of Maryland and Princton University shows quite impressively that our body notices that we are useless once we give up reproducing. So useless, in fact, that he even does not bother to repair our brains any longer:

In a past installment of On Short Notice you have already learned what the female orgasm could be for, remember? Which brings up the question will the women benefit, as well? Likely.
"Sexual experience enhanced the number of newly generated neurons in the dentate gyrus with both single and repeated exposures in middle-aged rats. Following continuous long-term exposure to sexual experience, cognitive function was improved. How-ever, when a prolonged withdrawal period was introduced between the final mating experience and behavioral testing, the improvements in cognitive function were lost despite the presence of more new neurons." (Glasper. 2013)

You want a bottom line? Well, let's make it fast, I feel I got to do something for my brain, now! Have sex, have it regular and have plenty of it (the rodents did it at least once a day) and when the new pope calls, tell him it's just for your brain health ;-)

Note: Although I deliberately wrote this part of On Short Notice, I hope that you are all old enough to know that getting drunk and having unprotected sexual intercourse with the next best person you can find "spring break style" is an absolute no-go. Not just for Catholics, but for any sane human being who has not already drowned his last neuron in alcohol.

That's it for today, and I guess with the Glasper study in the back of your head, I don't have to tell you that there are other things than hanging out in front of the computer, TV or even the gym that can be done on the weekend, right? Enjoy!

References:

Cassidy PB, Fain HD, Cassidy JP, Tran SM, Moos PJ, Boucher KM, Gerads R, Florell SR, Grossman D, Leachman SA. Selenium for the prevention of cutaneous melanoma. Nutrients. 2013 Mar 7;5(3):725-49.
Fogarty MC, Devito G, Hughes CM, Burke G, Brown JC, McEneny J, Brown D, McClean C, Davison GW. Effects of α-Lipoic Acid on mtDNA Damage following Isolated Muscle Contractions. Med Sci Sports Exerc. 2013 Mar 6.
Gasper ER, Gould E. Sexual Experience Restores Age-Related Decline in Adult Neurogenesis
and Hippocampal Function. Hippocampus. 2013 [Epub ahead of print]
Hody S, Lacrosse Z, Leprince P, Collodoro M, Croisier JL, Rogister B. Effects of Eccentrically and Concentrically Biased Training on Mouse Muscle Phenotype. Med Sci Sports Exerc. 2013 Feb 22.
Maticka-Tyndale E, Herold ES, Mewhinney D. Casual sex on spring break: Intentions and behaviors of canadian students. Journal of Sex Research. 1998; 35:3.

Adelfo Cerame Jr. after winning his weight class, the overall and the pro-card (leave him a message).

The first "True or False?" today, does not really pertain to diet and nutrition science, but it is still highly relevant for the SuppVersity:

Adelfo Cerame Jr. did eventually win his well deserved pro-card at the Wheelchair Nationals in Florida, yesterday. - True!

Ok, I have to admit that this may have been too easy with the picture of Adelfo holding the trophies for his weight class and the overall in his hands on the right, but it was the best way to include this important news "seamlessly" *rofl* into today's SuppVersity article.

You want some more difficult stuff? Well, let's see what you know about tea, coffee, MCTs and heated soy bean oil, then.

Caffeine (probably) is the main stroke protectant in coffee and tea

True. As a recent study from the Universidade Federal de Santa Maria in Brazil clearly indicates, the "bad" caffeine is at least one, if not the main anti-oxidants that's responsible for the neuroprotective effects of coffee, tea and co (Souza. 2013).

Caffeine is also part of the classic CCC fat loss stack (learn more)

According to the results of the paper MA Souza et al. are about to publish in one of the future issues of Neurochemistry International, a 2-weeks front-load with 6mg/kg caffeine per day increases the glutathione (=master antioxidant of the mammalian body) levels in the brain and protects rats from the oxidative damage and subsequent seizures in response to the administration of pentylenetetrazol-induced seizures (pentylenetetrazol is a circulatory and respiratory stimulant that overtaxes the brain, when it is administered in high doses).

What you should keep in mind, though, is the fact that Souza et al. used a dosage that was way lower than the amount of caffeine the average stim-junkie is consuming. It is thus not unlikely (in fact it is quite the opposite ;-) that we are dealing with a hormetic effect that occurs at human equivalent doses of 0.97mg/kg (~1 small cup of coffee) and turn against you when you escalate the doses to four or five MonterBullDrinks(TM) per day... I mean, the mere willingness of spending money on products like this goes to show you that drinking them compromises people's brain function, doesn't it? No, well I guess you have to reread the "Fat Content Per Energy Drink 0g. Fat Gain Per Energy Drink Drink 18g Study", then (reread it).

Most recent epidemiological human data supports these findings

And in case you don't believe this was relevant, check out the latest study in Stroke, in which Kokubo et al. which does not only confirm the stroke protective effects of green tea and coffee (Kokubo. 2013), but also yields some insights into what may be the "optimal" intake. After all, it takes 2x more green tea to achieve the effect you get from >2x cups of coffee per day, which is another hint at caffeine as the major driving force behind the anti-stroke effects of tea and coffee. Why? Well a large cup of Starbucks' green tea has 80mg of caffeine, the same amount of their regular coffee has roughly 290mg of caffeine in it.

Figure 1: Age and multivariable-adjusted hazard ratios of cardiovascular disease and its subtypes according to coffee (left) and green tea consumption in 82 369 Japanese (aged 45-74 years; without cardiovascular disease [CVD] or cancer in 1995 and 1998 for Cohort I and II, respectively) who received 13 years of mean follow-up through the end of 2007 (Kokubo. 2013)

Yet despite the validity of the "more caffeine = more brain protection" eqation the catecholamine surge of high amounts of green tea, but even more so coffee is not what you would call "heart healthy" (see figure 1; I would love to tell you the caffeine equivalents, but the scientist don't disclose the serving size). Just another reason to take it easy on stims in pill and drink form and keep your daily caffeine intake in the < 400 mg range (suggested read especially for the smokers: "Putting an "N" as in "nicotine" into "EC" amplifies the negative effects of ephedrine and caffeine on your heart"; read more)

Eating tons of medium chain triglycerides (MCTs) will make you lean

Are we, or rather you, my American friend eating too much fat or simply the wrong type of fats? According to a study that was in the SuppVersity news in Nov. 2012, it's the latter the "SAD Diet Has the Optimal Ratio to Induce Diabesity" (learn more)

It depends. While it may be that you can derive certain benefits by kicking out junkfood from your diet and replacing it with MCTs the "fat-burning" effects of medium chain triglycerides (MCTs) wear off after one to two weeks (White. 1999). Unfortunately, this is way longer than the usually cited studies on the direct metabolic effects lasted, so that a cursory look at the research easily fools you to believe that you could effectively burn fat by simply using MCT oils instead of whatever "bad" fat you had been using before.

Moreover, in the aforementioned study that was published in the American Jorunal of Nutrition roughly 14 years ago the postprandial total energy expenditure was already only 3% higher after the MCT meal in the first week. And it's not only that this advantage disappeared within the next 7 days, the respiratory ratio, a measure of the ratio of carbohydrate to fat oxidation, total fatty acid oxidation and carbohydrate oxidation were also identical in the 32% MCT and 32% LCT diets (both diets contained additional 8% of fat from other sources).

But what about all the other research?

While the transient benefits of the MCT feeding on energy expenditure alone are unlikely to have practical relevance there are a good handful of trials, which show some real world benefits in various dieting scenarios. Unfortunately, they are usually too short (Alexandrou. 2007), compare MCTs to beef tallow & co only diets, observe increases in fatty oxidation, which don't translate into changes in body composition (St-Onge. 2003), or have the subjects in the control group use relatively fragile control oils, such as olive oil for frying and cooking (St-Onge. 2008).

Accordingly, you should not be too surprised that the latest review of the effects of dietary intake of medium chain triglycerides on body composition, energy expenditure and satiety concludes: "

Curried Carrot Soup w/ coconut oil certainly qualifies as a good food choice, also bc. it's made with coconut oil, not plain MCTs (more).
"In the present review it was possible to verify that data related to increased satiety after consumption of MCT are quite controversial. Most studies showed no significant difference as to increased satiety and/or satiation related to lipid consumption. [...] A relevant fact in the lack of consensus among the studies concerns the large variation in the amount of MCT provided in different studies due to lack of reference values for a minimum, ideal and maximum consumption in literature. Moreover, there isn’t enough to long-term studies to identify either beneficial effects or potential harmful effects." (Souza. 2013)

If you go through the list of studies included in the review there are a couple other interesting patterns emerging: (a) the effects - if there were any - originated from the gut (mostly greater satiety effects), (b) if there were effects on body composition those often reached statistical significance in the obese individuals, only, (c) the benefits were more pronounced the less the subjects ate (esp. on those 800kcal hunger diets), (d) when the control was not nasty corn oil, or saturated long chain triglycerides (Atkins diet style), the effects were non-existent.

So, if your are lean, your current diet is balanced and your main fat source is neither corn oil nor beef tallow, the chances that you will be better off with expensive MCT oils than with a couple of spoons of coconut oil in your diet probably border zero. You see, it's just as so often not so much about "adding something in", as it is about leaving something else out / replacing it with a better food choice.

Soy bean oil offers a shortcut to metabolic disease even in the absence of obesity

True. I guess that this "true or false" item was actually way too easy to answer, but the recently published study by Potu et al. is simply too intriguing not to add it to the huge heap of existing evidence that the overabundance of "healthy" polyunsaturated fats from purportedly healthy plant oils is a major contributer to the fat mess we are dealing with.

Figure 2: Effects of 16 weeks on non-heated and heated soybean oil diets rodent food intake, weight gain and body fat (EWAT & IWAT) levels (Penumetcha. 2013)

Now, pro-obesity and pro-diabetic effects of corn oil, soy oil & co are actually no news. Penumetcha et al. do yet emphasize that they are the first to observe that soybean oil which has been heated on a hot plate at 190°C for 3 hours (think of the huge pots, frying pans & co that are used to produce convenient and fast foods) before it was added to the rodent chow has the unique ability to increase its consumers body fat levels without increasing their total body weight. Excellent, right?

Thats it for today! Ok, I guess that was too easy, as well. Still, it's true and I hope you enjoyed the last week and are already looking forward to the next week of exercise and nutrition science news here at the SuppVersity.

In the mean time you can kill some time by surfing over to the Suppversity Facebook Wall, where you will find news such as

Even if you align them like that, it is at least debatable whether capped fish oil is much more natural than the structurally modified 16 -carbon saturated fatty acid tetradecylthioacetic acid (TTA).And the usefulness of the longterm use of both remains questionable (learn more).

Beware of omega-3s unless you have the right genes -- New Inuit study confirms: If n-3 fatty acids are good or bad for you is in your genes (read more)

Muscular imbalances commonly overlooked factor in lower extremity sports injuries -- Scientists observe significant relationship of the coordination between muscle strength (ankle plantar flexor/ dorsi flexor), (hip addactor/abdactor), (knee flexor/ extensor) with muscle injuries (read more)

Arteriosclerosis is not a "neolithic" disease that occurred with the advent of agriculture -- Lancet paper debunks the myth of the "agricultural origin" of atherosclerosis (read more)

and when you are at it, don't forget to congratulate the one and only Adelfo Cerame Jr for finally bringing home those two small muscular statues you see in the image on the top of the page.

References:

Alexandrou E, Herzberg GR, White MD. High-level medium-chain triglyceride feeding and energy expenditure in normal-weight women. Can J Physiol Pharmacol. 2007 May;85(5):507-13.
Kokubo Y, Iso H, Saito I, Yamagishi K, Yatsuya H, Ishihara J, Inoue M, Tsugane S. The Impact of Green Tea and Coffee Consumption on the Reduced Risk of Stroke Incidence in Japanese Population: The Japan Public Health Center-Based Study Cohort. Stroke. 2013 Mar 14.
Rego Costa AC, Rosado EL, Soares-Mota M. Influence of the dietary intake of medium chain triglycerides on body composition, energy expenditure and satiety: a systematic review. Nutr Hosp. 2012 Jan-Feb;27(1):103-8.
Souza MA, Mota BC, Gerbatin RR, Rodrigues FS, Castro M, Fighera MR, Royes LF. Antioxidant activity elicited by low dose of caffeine attenuates pentylenetetrazol-induced seizures and oxidative damage in rats. Neurochem Int. 2013 Feb 26.
St-Onge MP, Bourque C, Jones PJ, Ross R, Parsons WE. Medium- versus long-chain triglycerides for 27 days increases fat oxidation and energy expenditure without resulting in changes in body composition in overweight women. Int J Obes Relat Metab Disord. 2003 Jan;27(1):95-102.
St-Onge MP, Bosarge A. Weight-loss diet that includes consumption of medium-chain triacylglycerol oil leads to a greater rate of weight and fat mass loss than does olive oil. Am J Clin Nutr. 2008 Mar;87(3):621-6.
White MD, Papamandjaris AA, Jones PJ. Enhanced postprandial energy expenditure with medium-chain fatty acid feeding is attenuated after 14 d in premenopausal women. Am J Clin Nutr. 1999 May;69(5):883-9.

It won't spare you the sweat, but carnitine could make it even more worthwhile by ramping up the anabolic and shutting down the catabolic signals.

Until 2006 l-carnitine has been known as a fat-burner, an in-effective fat-burner and an expensive and pretty useless supplement (depending on whom you were asking). Then, in July 2006, Kraemer et al. published a paper (a human study, above all!) in the journal Medicine & Science in Sports and Exercise a consequential paper so to say; a paper in which the authors report that l-carnitine l-tartrate supplementation at a dosage of 2.933g/day (this amount of LCLT contains 2g of pure carnitine) led to a statistically significant increase in androgen receptors in the vastus lateralis after a heavy resistance training protocol in previously strength trained male subjects (Kraemer. 2006).

Still, the evidence has always been inconclusive to say the least

Despite the fact that the concomitantly elevated post-workout luteinizing hormone levels (+19%) Kreamer et al. observed would tell you that the testosterone that would have been necessary to activate those receptors was already on its way, I have never considered thisstudy as convincing evidence of the anabolic prowess of l-carnitine. Plus, let's be honest, differences in whatever serum markers in response to an acute bout of resistance training have failed us way too often, not to look at studies like these with appropriate skepticism.

Do you remember the Ratames study from 2005? The one that showed that high volume training lowers the no. of androgen receptors on the trained muscles? This certainly makes l-carnitine sound like the perfect addition to high volume routines, right? (learn more)

That the same principle of "calm down and don't get too excited over the results of a single trial" does all the more apply to rodent studies should be self-evident and still, science is all about taking each and every experimental result into account to form a theory that can explain all of them, or, alternatively, is able to bust short-comings in previous studies that don't comply with the predictions of the respective theory.

Now, the soon-to-be-published paper by Janine Keller and her colleagues from the University of Giessen (Germany) certainly qualifies as part of the evidence we simply cannot ignore, when we are looking for evidence in support of the theory that l-carnitine could be an overlooked muscle builder or repartitioning agent.

After all, their observation of decreased levels of the proteolytic (=catabolic) MuRF1 protein, as well as the ubiquitin-protein conjugates, which are increased in catabolic states such as starvation and atrophy denervation (cf. Wing. 1995) , alone, would signify that l-carnitine could make a valuable addition to everybody's supplementation regimen.

Lower catabolism + increased anabolism = ???

There is more, however, the addition of 1250 mg L-carnitine/kg to a basally "low carnitine" vegetarian diet also led to significant increases in systemic IGF-1 concentrations in plasma and a local increase in the activity of the PI3K/Akt/FoXO-1 signalling pathway (see figure 1)

Figure 1: IGF-1 mRNA and serum levels, as well as the muscle specific expression and phosphorylation (ph) Akt, mTOR & co after four weeks on the low or high carnitine diets (Keller. 2013)

These results do yet not stand in isolation as the ones by Kraemer et al. still do. Other recent studies by the same research group in Giessen, as well as colleagues from the University of Barcelona have already confirmed the anti-catabolic effects of l-carnitine in piglets and a cancer cachexia model in rodents, respectively (Keller. 2012; Busquets. 2012).

"And you are telling me that works in humans, as well? "

What's the best form of carnitine to take to elicit these effects: I knew you would ask this, so I react to two facebook questions by adding this red box willingly admitting that I just cannot tell you what the best form of carnitine is. There simply is no study that would compare e.g. acetyl-l-carnitine (ALCAR) and l-carnitine l-tartrate (LCLT) in a scenario that would be relevant to the above question. What I can tell you though, is that it appears as if you were better off with LCLT than with ALCAR, if your goal is to top off your intra-muscular carnitine levels. That being said, even normal creatine can do that - you will just have to take more of it. If you are looking for more information you can check out the part of the Amino Acids for Super Humans Series that's dealing with "the carnitines", here.

In this context it does yet also have to be mentioned that the effects of l-carnitine are at least in part species specific. How we know that? Well, in contrast to the said study by Basquets et al. the provision of an carnitine to piglets (Keller. 2012) did not only reduce the MuRF-1 expression, but also the level of its likewise catabolic E3 ligase cousin atrogin-1.

"It has been shown that myofibrillar proteins, like myosin light chain proteins are the main targets of MuRF1for ubiquitination. Thus, carnitine might suppress particularly the degradation of myofibrillar proteins, which under physiological conditions comprise around 60% of total muscle proteins. In contrast to MuRF1, atrogin-1 tags primarily proteins for degradation which are important for controlling protein synthesis and myoblast differentiation, like myogenic factor MyoD, myogenin and the eukaryotic initiation factor of protein synthesis eIF3-f." (Keller. 2013)

With pigs usually being a superior model of the human physiology, this would suggest that the anti-catabolic effects l-carnitine could have on humans are probably more, not less pronounced than those that were observed in previous rodent studies.

Whether the same goes for the IGF-1 response cannot be said, but just like the anticatabolic effects, the pro-anabolic increase in IGF-1 has been observed in previous trials, including a human trial by Di Marzio et al. who observed a significant increase in IGF-1 in HIV patients in response to the provision of 3g/day of acetyl-l-carnitine (Di Marzio. 1999). In the absence of the existing evidence from animal studies, these results would yet have little significance for healthy human beings, whose growth hormone and IGF-1 levels are not rock bottom to begin with (Viganò. 2003).

Bottom line: Irrespective of the absence of human data on the IGF-1 boosting effects from non-HIV patients - or even better in training scenarios - it would warrant future studies if an adequate amount of carnitine in the diet can exert beneficial effects in non-obese human beings. For the "sedentary", or let's rather say non-exercised rodents in the study at hand, the latter was a mere fat loss effect - despite the elevations in p-AKT, m-TOR, IGF-1 and the overall more "anabolic" state the rodents were in their lean body mass was not increased compared to their peers on the low carnitine diet.

"Just another set!" ... "I don't know man, we've already pumped away 100,000kg today... do you really believe that's productive, I mean, yeah, we are cuttin', but still" ...learn what this dialog is all about and whether and if / when "another set" is / isn't a good idea (read more)

The lean-to-total mass ratio of the rodents, on the other hand was ~7% higher in the rodents in the high carnitine group. If we do however take into consideration that most of you will not be vegetarians and thus not similarly carnitine deprived as the rodents in the control group on the <1mg/kg carnitine diets, it is highly questionable if the addition of the human equivalent of the 1.25g/kg chow, i.e. 15mg/kg body weight (HED) would actually yield any measurable benefit to non-vegetarians - irrespective of whether they train or not. After all, even the average omnivore human being consumes 100-300mg of carnitine per day (Broquist. 1994), so that the difference between your basal carnitine intake and the supplemental equivalent dose of 1050-1500mg/day is more than 100x lower than the exorbitant difference between the low (if not deficient) carnitine diet in Keller's rodent study at hand (remember: the basal diet had less than 1mg/kg chow; the supplemented diet hat 1250mg/kg diet!).

So what's the verdict then? I guess, I will leave the final words to Burke et al. who reviewed the usefulness of carnitine as an ergogenic aid in one of the first installments of the "A-Z Supplement Review" in the British Journal of Sports Medicine and wrote "future work with l-carnitine may also find some useful outcomes" (Burke. 2009) - needless, to say that the SuppVersity is going to be the place, where you will read about it first ;-)

References:

Broquist HP. Carnitine. In Shils ME, Olson JA, Shike M (eds): "Modern Nutrition in Health and Disease." Malvern, PA: Lea & Febiger, 1994. 459– 465.
Burke LM, Castell LM, Stear SJ, Rogers PJ, Blomstrand E, Gurr S, Mitchell N, Stephens FB, Greenhaff PL. BJSM reviews: A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 4. Br J Sports Med. 2009 Dec;43(14):1088-90.
Busquets S, Serpe R, Toledo M, Betancourt A, Marmonti E, Orpí M, Pin F, Capdevila E, Madeddu C, López-Soriano FJ, Mantovani G, Macciò A, Argilés JM: l-Carnitine: An adequate supplement for a multi-targeted anti-wasting therapy in cancer. Clin Nutr. 2012;31:889–895.
Di Marzio L, Moretti S, D'Alò S, Zazzeroni F, Marcellini S, Smacchia C, Alesse E, Cifone MG, De Simone C. Acetyl-L-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Clin Immunol. 1999 Jul;92(1):103-10.
Glass DJ: Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol. 2003; 5:87–90 .
Kraemer WJ, Spiering BA, Volek JS, Ratamess NA, Sharman MJ, Rubin MR, French DN, Silvestre R, Hatfield DL, Van Heest JL, Vingren JL, Judelson DA, Deschenes MR, Maresh CM. Androgenic responses to resistance exercise: effects of feeding and L-carnitine. Med Sci Sports Exerc. 2006 Jul;38(7):1288-96.
Keller J, Ringseis R, Koc A, Lukas I, Kluge H, Eder K: Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets. Animal. 2012;6:70–78.
Keller J, Couturie A, Haferkamp M, Most E, Eder K. Supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway and down regulates the E3 ligase MuRF1 in skeletal muscle of rats. Nutrition & Metabolism. 2013; 10:28.
Lösel D, Rehfeldt C. Effects of l-carnitine supplementation to suckling piglets on carcass and meat quality at market age. Animal. 2013 Mar 11:1-8.
Salama AF, Kasem SM, Tousson E, Elsisy MK. Protective role of L-carnitine and vitamin E on the testis of atherosclerotic rats. Toxicol Ind Health. 2013 Feb 13.
Viganò A, Mora S, Brambilla P, Schneider L, Merlo M, Monti LD, Manzoni P. Impaired growth hormone secretion correlates with visceral adiposity in highly active antiretroviral treated HIV-infected adolescents. AIDS. 2003 Jul 4;17(10):1435-41.
Wing SS, Haas AL, Goldberg AL. Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation. Biochem J. 1995 May 1;307 ( Pt 3):639-45.

Would she still look so happy, if she knew that thee treadmill just lied to her?

I have written, said and, in person, even shouted it out often enough: Once you start to rely on the figures certain formulas generate (and this includes what your treadmill, your heart rate monitor etc. will produce, 'cause they use the same flawed formulas), you are lost.

The message of today's SuppVersity article is therefore by no means a new one. What's pretty new, though, is the study by V. Bonghana and colleagues from University of Campinas who have compared five predictive equations that are supposed to predict your and everyone else's basal (=excluding physical activity) energy demands (Bonghana. 2013).

"Start with a 15% energy deficit" - based on what?

The above, i.e. to start dieting by consuming ~15% less energy than you usually do, is my usual suggestion for anyone who's not in the "so fat that your health is in danger" zone, someone like you, maybe - someone who wants get rid of his/ her belly to finally see a at least the uppermost portion of his / her abs.

Table 1: The five equations the researchers used to calculate the predicted resting metabolic rate (RMR) that was then compared to the measured RMR (indirect calorimetry by respiratory gas analysis) of the 43 participants (Bonganha. 2013)

Now, what do you think would happen if this person was a postmenopausal women (of whom many, as we all know, love to "diet" exactly as they are told to, counting calories and what not) who is too lazy to follow my even more important advice to track her caloric intake for 2 weeks in order to get a "baseline reading"? What would happen if this woman, instead of doing just that simply used one of the calculators on the Internet and build her diet right according to the number the machine vomits out?

Figure 1: Comparison of the predicted resting metabolic rates and the mean difference to the "real" (=measured) RMR of the 43 healthy postmenopausal women who participated in the study (Bonghana. 2013)

Actually a cursory look at the data in figure 1 should suffice to tell you what the result would be. If she was lucky and the calculator used the rather uncommon Mifflin-St Jeor equation she would not lose a single pound, because she would end up right at the 1,063 kcal/day she, a 52-year young women, who's 159cm small has a totally age-appropriate BMI of 25kg/m², but a slightly high body fat level of 33%, just like the "average subject" in our experiment, needs to fuel her most basic metabolic demands (measured those are 1063.8 kcal/day). The former obviously implies that she did also take into account that she spends a few extra calories, even when she does not exercise.

Use the WHO calculation and you are lost

Guess how she got in in shape? Right! The EDC Program (learn more)

If she was not just as lucky and used the WHO equation as a baseline, she would not only overestimate her basal energy requirements by more than 30%. No, even with the 15% reduction she would be continuously gaining gaining wait... now, imagine she had also started to work out and had for once heard received some good advice, which is not to freak out about the weight gain, because it's all muscle. What? Right, she would be working away instead of towards her goal to lose weight and fat, 'cause one thing is sure.

Unless you expend more energy than you eat it is almost impossible to get rid of the belly. Unfortunately, simplistic calories in vs. calories out calculations won't help you find out whether this is the case..

The notion that exercise "alone" can, especially for those who are pretty chubby to begin with, have a "repartitioning effect" may still hold here, but it is more likely that our imaginary post-menopausal training rookie is - if anything - gaining more muscle than fat and that's certainly not going to give her the look she is aspiring. In fact the situation would probably not be much different from the one in the study I had in the Facebook News a couple of days ago (Tibana. 2013).

Adding exercise on top of a proven (your N=1 experience) obesogenic diet rarely helps

In the course of this 8-week intervention study, the subjects, a group of 14 middle-aged (33.9 ± 8.6 years) overweight/obese women (body mass index - BMI 29.6 ± 4.1 kg/m²) underwent 24 sessions (3 times per week) of a whole body RT program with 3 sets of 8–12 repetitions maximum (RM). Unfortunately, for them without any dietary advice / incentive to modify the baseline diets that were obviously to blame for the extra-weight they were carrying.

Figure 2: Body mass, waist, hip, neck circumference, body adiposity index and visceral fat volume in middle-aged women before and after an 8-week 3x/week full body weight training intervention (Tibana. 2013)

The net result of this "intervention" was thus by no means representative of what you can achieve, when you really commit. If you discard the diet component, or even worse, fall for the common idea that you've worked out for an hour and could thus "afford" that piece of pizza, pie or panacotta, you are effectively bulking. Therefore, you should thus not be surprised, if you got strong and bulky, but don't see improvements in your body fat level, your waist line and any of the biochemical variables, i.e. fasting glucose, HbAIc, insulin, triglycerides, HDL, and the TG/HDL ratio (not shown in figure 2), your doctor will be eyeballing.

Without taking a "baseline reading" and accessing where you want to go, you ain't going to succeed (read more)

Bottom line: In conjunction, the results of the Bonghana and Tibana papers only underline the necessity to (a) make a baseline assessment of your current, individual food quantity and quality(!), before you embark on any kind of diet and (b) that the notion of "exercising the fat away" is only useful when you are not making the mistake to chart your dietary intake up against whatever you believe your exercise induced energy expenditure would look like. Even if it's not pizza, pasta and panacotta you are thinking of, when you look at the figure your treadmill or heart rate monitor calculated based on similarly whacky formulas as those used for the RMR, you are still lost whenever you put more faith into a impersonal arithmetics than the signals of your own body... and this, gentleman,is true irrespective of your age and sex.

If you still insist on calculating something, you may also want to take a look at Part III / III of the Female(?) Athlete Triad Series, but please be aware that I am not liable for the damage this type of calorie counting is going to do to your physique and your psyche.

References:

Bonganha V, Libardi CA, Santos CF, de Souza GV, Conceição MS, Chacon-Mikahil MP, Madruga VA. Predictive equations overestimate the resting metabolic rate in postmenopausal women. J Nutr Health Aging. 2013;17(3):211-4.
Tibana RA, Navalta J, Bottaro M, Vieira D, Tajra V, Silva AD, de Farias DL, Pereira GB, de Souza JC, Balsamo S, Cavaglieri CR, Prestes J. Effects of eight weeks of resistance training on the risk factors of metabolic syndrome in overweight /obese women - "A Pilot Study". Diabetol Metab Syndr. 2013 Feb 28;5(1):11.

Better lean than strong? Why not both?

Anyone remember the allegedly not very popular post on the "anti-creatine" β-Guanidinopropionic Acid (GPA) and it's ability to increase AMPK, decreases blood glucose& insulin, induce weight loss without dieting, increase skeletal muscle oxidative capacity and delay the development of mammary cancer (read up on the news)? I thought so...

Even I had was just about to forget about it, when I stumbled upon a recently published Brazilian study which found that the "real" - not the anti-creatine - does in fact what you would expect from the "evil twin" of GPA: It blunts the exercise induced fat loss in highly trained amateur athletes (Manjarrez-Montes de Oca. 2013).

"What!? Creatine makes me fat?"

Now, before you start freaking out, let me say this: There are also studies which suggest that creatine supplementation does the exact opposite, i.e. that it can (combined with an intense exercise protocol) decrease body fat level (van Loon. 2003; Volek. 2004). If you dig deeper, you will yet find that most studies actually don't report any changes in the ratio of fat to total body mass most of you know as "body fat percentage" (Kreider. 1998; Volek. 1999; Becque. 2000).

Whatever the results of the individual experiments may be, in the end only studies like the one done by Jeff Volek et al. at the University of Connecticut or the study at hand, i.e. studies in the course of which the scientists actually measure/d the total amount of lean and fat mass can provide an adequate idea of what exactly supplemental creatine can do for our physiques. If the data includes only body fat percentages, maybe even measured with bio-impedance (→ yesterday's Facebook news on "losing" 1.4% of body fat in a single session), this does not suffice to say, whether the absolute amount of body fat changed. Or in other words, whether any observed increase / decrease in body fat (%) was simply a result of the fact that the ratio of lean to total body mass increased faster than the rate of fat to total body mass, wile the subjects abs still disappeared under a nasty layer of blubber.

Figure 1: Changes in body mass, bone free lean mass, fat mass and body fat percentage (left), as well as individual "fat gain" response to creatine supplementation in the 14 subjects (Manjarrez-Montes de Oca. 2013).

The study at hand is in fact a perfect example for the way body fat levels alone can fool you. A brief glance at the data in figure 1 confirms that. While the body fat percentage says that the 12 non-smoking, non-vegetarian, red and black belt male recreational taekwandoo players must effectively have lost weight in the creatine phase of this, the total fat mass reveals that adding 50mg/kg creatine to their sports drink (30 g of sucrose, artificial flavor, 500ml) lead to an increase, the addition of the same amount of maltodextrin to a decrease in DEXA measured total body fat.

If it were not for the results of of 2002 paper by Huso, I guess, I would just tell you to simply forget about the hoopla and discard the notion that creatine would have any effect on body fat levels, at all (Huso. 2002). Huso et al. had investigated the influence of creatine supplementation (20 g/day for 4 days, then 2 g/day for 17 days) on substrate utilization during rest using a double-blind crossover design. To this ends the researchers recruited 10 active men who participated in a 12 wk resistance training protocol (3x /week full body resistance training; 3 sets, 10 reps) involving a placebo and a creatine trial that were separated by a 4-wk washout.

Figure 2: Changes in body composition (body mass, body fat and fat free mass) and 1RM strength on the bench press and leg press in the 12-week double-blind randomized cross over trial by Huso et al. (Huso. 2002)

Very similar to Manjarrez-Montes de Oca et al. in the study at hand, Huso et al. observed a significant decrease in fat mass (-2.4kg) in the placebo trial, while there were no significant changes in either of the two parameters, when the subjects were "on creatine".

So how come that creatine does even have the ability to inhibit fat loss?

Just like the identical change in lean mass (in fact, only the strength increase speaks in favor of the creatine loading + maintenance regimen) the inhibition of the fat loss in the trial of the Huso study was actually only a "side finding". Originally, Huso et al. had set out to elucidate, whether the "anecdotal evidence of weight gain, including a lack of fat loss, in persons taking creatine" (Huso. 2002) could be brought about by creatine induced increases / decreases of the respiratory exchange ratio (RER = the ratio of carbohydrates to fats that are oxidized during a workout). And while the scientists state in their abstract that the "[c]hanges in substrate oxidation" they observed "may influence the inhibition of fat mass loss associated with creatine after weight training" (Huso. 2002), it is at least in my humble opinion not very likely that the small statistically only borderline significant shift from fat to carbohydrate oxidation (+/- 9%, respectively) alone can actually explain the >2kg difference in total fat mass loss. Still, this is exactly what Manjarrez-Montes de Oca et al. feel would be the most likely explanation for the observations they made 11 years later, as well:

I wonder if Usain Bolt consumes creatine supplements. Or is he on GPA, click here to learn what would be more likely.
"It has been suggested that the increase in carbohydrate utilization induced by Cr may be due to an activation of the enzyme phosphofructokinase, which produce an increase in glucose utilization, with elevation of malonyl-CoA and inhibition of carnitine palmitoyltransferase 1 (CPT1) system, which transports fatty acids into the mitochondria for oxidation (Huso. 2002).

If fatty acids are not transported into the mitochondria of skeletal muscle cells to be oxidized, they could be expected to be maintained in blood as triglycerides; and then stored in the adipose tissue.

We observed a higher concentration of triglycerides after Cr supplementation, and also found that subjects after Cr treatment gained fat mass whereas after placebo treatment fat was lost. Therefore, both findings could imply that fatty acid mitochondrial uptake has been inhibited by Cr ingestion, altering the normal fat loss produced by TKD training."

What you should keep in mind though, is that the dietary intake was not controlled for (what if increased glucose oxidation simply made the subjects hungrier?). In calorically restricted scenario the results could thus have been very different, so that it is overall not very likely that creatine would ruin your dieting efforts. Moreover, there is some, allegedly not very conclusive evidence that the addition of a reasonable amount of creatine to your diet could actually help you spare muscle tissue. The fact that the placebo-specific increase in protein oxidation from 11.6% to 15.3% was just as absent in the creatine group as the fat loss, is however hardly a convincing, let alone bullet-proof argument in favor of creatine as a dieting aid. After all the protein oxidation in the creatine group remained stable on the same high levels of roughly 15%.

Bottom line: I don't feel that the evidence "against" taking reasonable amounts of creatine (2-3g per day) is conclusive enough to panic and give up on the possible beneficial effects on lean mass (Nissen. 2003; Poortmans. 2010). Still, if you really have good reason to believe that creatine may blunt your fat loss (it's not impossible, take a look at the "high responders" in figure 1, right), I don't see why you could not give it a try and simply stop taking your creatine for a months or so. If after an initial flattening effect you don't see any other changes in your physique you are at least sure that you don't belong to the unlucky few, for whom creatine monohydrate (not one of the sugar-laden combi products!) could maybe and due to whatever interaction of genes, diet and whatever other confounding factors, forestall fat loss.

References:

Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc. 2000 Mar;32(3):654-8.
Huso ME, Hampl JS, Johnston CS, Swan PD. Creatine supplementation influences substrate utilization at rest. J Appl Physiol. 2002 Dec;93(6):2018-22.
Kreider RB, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinardy J, Cantler E, Almada AL. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc. 1998 Jan;30(1):73-82.
Manjarrez-Montes de Oca R, Farfán-González F, Camarillo-Romero S, Tlatempa-Sotelo P, Francisco-Argüelles, Kormanowski A, González-Gallego J, Alvear-Ordenes I. Effects of creatine supplementation in taekwondo practitioners. Nutr Hosp. 2013;28(2):391-399.
Meglasson MD, Wilson JM, Yu JH, Robinson DD, Wyse BM, de Souza CJ. Antihyperglycemic action of guanidinoalkanoic acids: 3-guanidinopropionic acid ameliorates hyperglycemia in diabetic KKAy and C57BL6Job/ob mice and increases glucose disappearance in rhesus monkeys. J Pharmacol Exp Ther. 1993 Sep;266(3):1454-62.
Nissen SL, Sharp RL. Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol. 2003 Feb;94(2):651-9. Epub 2002 Oct 25.
Poortmans JR, Rawson ES, Burke LM, Stear SJ, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 11. Br J Sports Med. 2010 Aug;44(10):765-6.
van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond). 2003 Feb;104(2):153-62.
Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gómez AL, Pearson DR, Fink WJ, Kraemer WJ. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc. 1999 Aug;31(8):1147-56.
Volek JS, Ratamess NA, Rubin MR, Gómez AL, French DN, McGuigan MM, Scheett TP, Sharman MJ, Häkkinen K, Kraemer WJ. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004 May;91(5-6):628-37.

Can't squeeze out another rep? Not a problem have some intra-set rest and continue pumping thereafter.

I guess, I did this before, but I say it again: "Congratulations, Adelfo Cerame Jr.! You are the man." Obviously, we all knew he is, but as of now, even the judges have finally acknowledged that. Reason enough to do a Science Round-Up Special today, in the course of which Carl Lenore and me are going to pick Adelfo's brain and have him surrender all the secrets that made him finally achieve what he has been chasing for years, now: The status of a wheelchair pro bodybuilder.

Just like the regular show the live show will be kicking off at 1PM EST. If you miss it it's not a problem, there is also going to be a special edition of the "Seconds", tomorrow with Adelfo looking back at how the contest went and how he made sure to peak right on time (edit: you can download the podcast now).

And just to make sure that no one complains: I compiled a couple of news as a surrogate for the regular Science Round-Up, today (this was "last minute", so please ignore any typos and grammatical mistakes).

Rest-pause technique leads to greater strength w/ identical size gains (Oliver. 2012) -- The bad news first, I can't tell you exactly how long the 22 male subjects (25 +/- 5yrs, 179.71 +/- 5.0cm, 82.1 +/- 10.6kg, 13.6 +/- 4.3% fat, 6.5 +/- 4.5yrs training) Jonathan Oliver recruited for the experiment he wrote his dissertation on actually rested withing (=intra) their sets. Usually you would expect something along the 10 deep breaths - just enough to get your game on, so to say.

Figure 1: 1-RM max and power on bench presses and squats before and after 12 weeks of classic (regular sets) and alternative intra-set rest interval (rest-pause) training in 22 young resistance trainees with >2y of training experience (Oliver. 2012)

You got to remember, though, that I cannot guarantee that the 10 deep breath version of the rest-pause technique will yield the same remarkable results you see in figure 1 until the embargo on the dissertation falls or a student of the Texas A&M who I believe should be able to peak into the actual full text gives me a hint on the details of the study protocol. In the mean time, take the increased strength gains (check the percentages above the bars in the post columns), as an incentive to (re-)incorporate rest-pause sets where you perform 2-5 reps, rack the weight, pause, pick it up again and perform another 2-5 reps with the same weight and so on until you hit your target rep range, e.g. 12 reps on the bench with 200lbs, where you usually cannot do more than 5, into your routine.

Dietary variety does not protect us from from becoming fat (Vadiveloo. 2013) -- In a soon-to-be-published systematic review of epidemiological studies researchers from the Steinhardt School at the New York University report that dietary variety does not protect against obesity. In fact, the exact opposite can be the case if "your variety" is a variety of sugar + fat-laden junk foods. In that case you are even more likely to fall victim to the metabolic syndrome than someone who eats just Twinkies and does not switch to Dingdongs once in a while:

If you are interested in buying quality, you may want to revisit the post on pesticide residues in organic and regular produce (go back)
"The present review is an important first step in clarifying the associations between dietary variety and excess adiposity, which is currently limited by the methods used to assess variety.

In the present review, we found that (1) dietary variety within recommended and low-energy foods alone do not increase the odds of overweight and obesity, (2) greater variety within less healthful, energy-dense foods increases the odds of overweight and obesity and (3) the association between total dietary variety and adiposity is mixed and accurate evaluation of this association requires a consistent and theoretically valid measurement tool."

This is, allegedly not a really surprising finding, what may yet surprise you is that the scientists didn't find a positive association for a variety of healthy foods in the diet, either. Sounds like quality and quantity, but not diversity remain what determines our likelihood of becoming obese... but let's be honest, isn't eating - at least from time to time - so much more than just providing your body with the nutrients it needs?

There is no protein synthesis without catabolism (Bentzinger. 2013) -- A very intriguing study that's about to be published in the next issue of Skeletal Muscle found that the constant and isolated expression of MTOR-1C in a rodent model leads to profound muscle catabolism and not as you may have expected exuberant muscle growth. The underlying reasons for this counter-intuitive effects are the m-TOR induced blockade of the p-AKT pathway which is also responsible of keeping the catabolic MuRF1 pathway in check:

The AMPK-mTOR seesaw
"Our study shows that the mTORC1- and the PKB/Akt-FoxO pathways are tightly interconnected and differentially regulated depending on the muscle type. These results indicate that long-term activation of the mTORC1 signaling axis is not a therapeutic option to promote muscle growth because of its strong feedback induction of the E3 ubiquitin ligases involved in protein degradation."

In view of the fact that few of you will be mutants with a constant (over-)expression of mTOR-1C the scientists most recent observation does actually have implications for you as a trainee. It does not only re-emphasize the importance of the cyclic nature and tight inter-regulation of protein synthesis and degradation, but should also remind you no to rely too heavily on studies measuring only increases in protein synthesis without accounting for the net protein retention.

GABA exerts indirect "anabolic" effects on the brain(Thanapreedawat. 2013) -- In yet another advanced publication that happens to overlap with the sudden re-appearance of GABA supplementation within the health and fitness community, Thanapreedawat and colleagues report that the administration of gamma-amino-butyric in the drinking water (0.5% and 1.0%) of young rats lead to highly significant activation of the intra-cerebral mTOR pathway, a subsequent dose-dependent increase in S6K1 phosphorylation and corresponding increases in brain protein synthesis.

Figure 2: Relative changes (compared to control) in insulin, insulin-like growth factor (IGF-1) and growth hormone (GH) in response to 0.5% or 1.0% GABA in the drinking water of 3-week old Wistar rats (Thanapreedawat. 2013)

Now what's really interesting about the study is that these effects were not mediated centrally. In other words, the orally ingested GABA did not pass the blood brain barrier. That this was possible is sometimes touted by producers of respective supplements. Previous studies have yet conclusively shown that orally ingested GABA does not make it across an intact blood brain barrier in vivo, so that any effects GABA may have must originate in the periphery and that's actually what the scientists believe happened here, as well.

The peripheral effects of the orally administered GABA, namely the pronounced increase in growth hormone (GH) (cf. figure 2), a molecule which has previously been shown to be able to cross the blood brain barrier (Bermann. 1994; Ohsumi. 2008) lead to an activation of the intra-cerebral mTOR cascade and the subsequent increase in protein synthesis. If you expand on that, you could even speculate about other GH mediated effect of GABA supplementation... I must yet forewarn you: GABA is not a proven ergogenic of any kind (doesn't build muscle, doesn't make you lean, etc.).

Usually this would be the place to add some references to the latest Facebook news, but since the show is about to start in a couple of minutes (listen live), I'll just refer you directly to the SuppVersity Facebook Wall. With 6-9 studies you won't read about anywhere else every day, it's always worth visiting, anyway ;-)

References:

Bentzinger CF, Lin S, Romanino K, Castets P, Guridi M, Summermatter S, Handschin C, Tintignac LA, Hall MN, Rüegg MA. Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy. Skelet Muscle. 2013 Mar 6;3(1):6.
Bermann M, Jaffe CA, Tsai W, DeMott-Friberg R, Barkan AL. Negative feedback regulation of pulsatile growth hormone secretion by insulin-like growth factor I. Involvement of hypothalamic somatostatin. J Clin Invest. 1994 Jul;94(1):138-45.
Ohsumi M, Tujioka K, Hayase K, Nagata S, Yokogoshi H. The growth hormone affects the brain protein synthesis rate in hypophysectomized aged rats. J Nutr Sci Vitaminol (Tokyo). 2008 Feb;54(1):76-81.
Oliver J. Intra-Set Rest Intervals in Hypertrophic Training: Effects on Hypertrophy, Strength, Power, and Myosin Heavy Chain Composition.Doctoral dissertation, Texas A&M University. 2012.
Thanapreedawat P, Ohsumi M, Hayase K, Yoshizawa F, Yokogoshi H. Influence of GABA on Brain Protein Synthesis Mediated by the Mammalian Target on the Rapamycin Pathway. Biosci Biotechnol Biochem. 2013 Mar 7.
Vadiveloo M, Dixon LB, Parekh N. Associations between dietary variety and measures of body adiposity: a systematic review of epidemiological studies. Br J Nutr. 2013 Feb 27:1-16.

Adelfo at the NPC Sunshine Classic/Wheelchair Nationals '13

In case you missed the live show yesterday, you should by now have had the chance to listen to the podcast of yesterday's SuppVersity Science Round-Up Special in honor of Adelfo Cerame Jr.

If you did, you may have noticed that we talked a lot about the prep, about dieting and training in general, but did not really get to the contest itself... but hey, this is what the Science Round-Up "Seconds" are for and therefore I am now going to copy and paste the content of the latest blogpost Adelfo just shot me.

Before I do that, I do yet want to remind you of the SuppVersity Facebook Wall which holds, among other things news on

the effects of grass and sand on your sprinting ability on different surfaces (read more),
the infection risk that comes with high glucose levels even in non-diabetic women (read more),
Silvestrol, a natural anti-leukemia agent (read more),
how low vitamin D levels could be a sign excessively high insulin levels (read more)

and much more... but for now, that's enough of abstract science. Let's get back to the real world and hear, or rather read how the last 4 days before the show went for your's truly Adelfo Cerame Jr.!

My last hours as an amateur and how I finally won the pro card

This is how the biggest winners look like, when they celebrate ;-)

I didn’t officially start my peak week until Wednesday, so prior to (Monday, Tuesday) everything pretty much stayed the same with regards to training and nutrition.

I felt pretty good going into my peak week. My food was high and energy levels were high as well. I was not dragging ass, hungry, or feeling miserable like some people do coming into the final week – I attribute this to starting my prep early and giving myself enough time to diet down (about 24 weeks). I did most of my intense digs with my diet early in my prep and was prepared or at least lean enough to the point where I was able to start slowly bringing food back up and recover metabolically almost 7-6 weeks out.

All I did from there was made tweaks and minor adjustments and improve, which I have summarized in the column on the right hand side of the following paragraphs.

My numbers heading into peak week

Energy: 2210kcal
Fats: 50g
Carbohydrates: 240g
Protein: 200g

Wed: Start of Peak

Energy: 3130kcal
Fats: 70g
Carbohydrates: 400g
Protein: 225g

Wed: Training

2x horiz. row ex.
4x6-8/8-10 @ 9 RPE
2x vert. row ex.
4x10-12 @ 9 RPE
Biceps curl ex.
4x12-15 @ 9 RPE

Thu: Nutrition

Kcal: 2480
Fats: 40g
Carbohydrates: 350g
Protein: 180g

Thu: Training

2 flat press ex.
4x6-8/ 8-10 @ 9 RPE
2 vertical press ex.
4x10-12 @ 9 RPE
Biceps curl ex.
4x12-15 @ 9 RPE

Fri: Nutrition

Kcal: 2370
Fats: 50g
Carbohydrates: 250g
Protein: 180g

Fri: Training

Horizontal row of choice 2x12-15 @ 9 RPE
Flat press of choice
2x12-15 @ 9 RPE
Overhead press of choice
2x12-15 @ 9 RPE
Biceps curls
2x12-15 @ 9 RPE
Lateral raise
2x10-12 @ 9 RPE

Sat: Nutrition

Kcal: 3190
Fats: 70g
Carbohydrates: 460g
Protein: 180g

Sat: Show Day - Fluids

20 oz water upon waking
16 oz. of water with / between meal

Sat: Show Day - Toolbox

Morton’s lite salt
Bagels
Muffins
Detour bars
Rice cakes
Goober PB&J
Peanut butter cups
Tuna pouches
Beef jerky

Florida, I am on my way!I took the red eye flight (Thursday- midnight), so I basically slept during the flight since it was my habitual bedtime and touched down in Florida around 7 AM. It was a direct flight that took about 4 ½ hours so it didn’t really affect me with regards to jet lag. Since I like keep things simple and as efficient as possible, I had packed a light bag with the bear necessities and decided that I would just do all the groceries, when I arrived at my destination.

Believe it or not, not one chicken breast was eaten during my travels ;-)

As for my protein sources, I stuck to whey protein sample packets, Quest bars, beef jerky, tuna packets and Greek yogurt, solely. While the carbs came from rice cakes, potatoes, bagels, fat free Pringles, cereal, apples and bananas. All that was topped off with some Goobers peanut butter & jelly, as well as coconut oil for the fats..

I arrived on Thursday, at 7 AM. What followed was the usual itinerary of checking in at the hotel, training, sending the latest photo updates to coach Alberto, shopping at at Walmart (I find it much easier to buy most of my foods when I arrive at my destination rather than packing everything all at once), practicing my poses and, not to forget, rest... what? Oh yeah, I almost forgot: Rest and EAT!

So from Wednesday through Friday I kept everything pretty much the same, the only difference was that my food was a lot higher and coach Alberto just made the adjustments with my food on the fly depending on how I looked with update pictures that I sent him throughout the day (again, you find the exact macros in the column on the right).

As you will see, the training volume was a lot higher, but the overall duration of the workouts was still short and the intensity was under tightly controlled via the RPE scale (if you want to learn more about the RPE scale, listen to yesterday's interview on the Science Round-Up Special).

My fluid and sodium intake was habitual – I probably drank a little bit more though than I did in the past Friday nights before the show (around 60-70 ounces more than I was use to)

Saturday, the big day has come

As the overview on the right is telling your my overall energy intake on the day of the show was pretty high. It was therefore all the more critical to time the meals appropriately.

Pre-Judging AM

6-7 hours out = 2 bananas, 2.6 oz. tuna, 2 tbsp. Goobers PB&J
4-5 hours out = detour protein bar + 5 oz. apple
60-90 minutes out = blueberry bagel, pumpkin pie pop-tart, 1 oz. beef jerky, and 1 tbsp. goobers PB&J
15-10 minutes out = 3g sodium + 1 peanut butter cup + big gulp of water

Night show PM

6-7 hours out = 2 bananas, 2.6 oz. tuna, 2 tbsp. Goobers PB&J
4-5 hours out = detour protein bar + 5 oz. apple
60-90 minutes out = slice of pizza
15-10 minutes out = 3g sodium + big gulp of water

On show day I weighed in at 141 lb., so I came in 5 pounds heavier this year compared to last, which was something that really surprised me since I’m usually hovering around at 132-135lbs come show day but I’m not complaining ;-)

5lbs heavier, but still a lightweight compared to the mass monsters

When sizing up the competition, I had an idea of who the 2 main guys that I would probably face in the overalls, they both were in higher weight divisions and both were mass monsters, but I was very confident in my conditioning and overall package that I brought this year to be able to compete.

When I finally won the dang thing, it felt like more of a relief than anything and being able to finally get that monkey off my back!

Lol. It was a surreal moment and it took a while to soak in but when it finally did; it felt great to know that I’m now considered a professional at what I love to do!

How I celebrated this victory? To be honest I really wasn’t craving much or felt the need to binge and stuff my face. I snacked on some of my rice cakes and beef jerky, then went out to the town and had two tall glasses of Guinness, and three slices of pizza and called it a night.

Don't be worried, folks. We will find a good excuse to keep Adelfo "aboard" the SuppVersity! So this is certainly not the last post of Adelfo Cerame Jr, it may be the last of the "Amateur" Adelfo Cerame, but at the same time it's also the first or many posts of the IFBB Pro Adelfo Cerame ;-)

So what will the future bring? I jumped right back to my diet once I arrived back home on Monday evening. My appetite was pretty much under control and I attribute a lot of it to not depriving myself of anything during my whole contest prep, and I also had the advantage to be ready early or lean enough to where I was able to slowly start bringing my food back and recover metabolically.

As of now I plan on taking the whole year off for a long off-season in order for me to make the improvements I need to make in order to compete on the next level with the big boys! So, 2014 would probably be my pro debut.

Before I sign off; I would just like to thank all the SuppVersity readers for all the love and support you all have shown me throughout this journey, and I’m glad I was able to share it with you all.

Your's truly, Adelfo

Judged by the way they are looking at each other they don't care about their differential glucose / insulin response too coffee, but if you do, I suggest you scroll down and read the pertaining news item.

7.3% and 21.4%, those are the SuppVersity figures of the week. Figures that stand for the 2011 youth- and 2010 adult obesity rates in Colorado and they represent the nationwide "optimum" - at least according to CDC data from the respective years. Now, it was already hard to find US states with obesity rates below the nationwide average of 13% (youths) and 27.6% (adults). What is yet even harder or rather impossible is to dig up studies which try to elucidate why Colorado is the "leanest" of the 50 US states. Non-exhausting physical activity, for example, would be a candidate, but according to Wyatt et al. the "[e]ven in Colorado, one of the leanest states, very low levels of physical activity are seen in much of the population." (Wyatt. 2005).

Wouldn't it be worth taking some time to try to elucidate what the citizens in Colorado may be doing, their fellow Americans in Mississippi (highest adult obesity rate of 34.5%) or Alabama (highest youth obesity rates of 17%) ain't doing? Are they maybe having more or less fish oil or drinking only half the amount of caffeine? I don't know, but based on today's installment of "On Short Notice", you should be able to answer whether or not it is likely that factors like these could make a difference ;-)

Coffee, Sex and Your Physique (Gavrieli. 2013) -- The latter two, i.e. sex and your physique are what determines your postprandial glucose and insulin concentrations after escalating dosages of caffeinated coffee. That's at least what Anna Gavrieli from the Harokopio University in Athens and her colleagues from overseas write in a soon-to-be-published paper.

To examine the effects of different amounts of coffee on blood glucose and insulin concentrations in the postprandial phase (after a meal) the scientist recruited thirty-three volunteers [16♀/17♂, 16 normal-weight and 17 overweight/obese, 27.3 ± 7.2 (19–44) y] who came to the lab fasted and obviously without having had a "wake up coffee" early in the morning. When they arrived, the subjects received a standardized meal, i.e. a slice white bread, 5 g of butter and 10 g of white sugar, providing 142 kcal (6.5% of energy from proteins, 62.5% from carbohydrates and 31.0% from lipids) along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight on three different occasions.

Figure 1: Usual and experimental caffeine intake in the subjects (left); effects on glucose metabolism after standardized "breakfast" (=sugar binge) + water or different dosages of instant coffee (Gavrieli. 2013)

As you can see in figure 1, the blood samples the scientists obtained before, immediately after and in regular intervals over the remaining 3 hours after the ingestion of the "breakfast" do support the hypothesis that men and women, light and heavy weights react very differently to the ingestion of 200-500mg.

So what's the verdict then? Is coffee the way to go?

Post workout caffeine supplementation?! Just like dieting, working out is one of the confounding factors which render results like the one at hand valid only in certain scenarios. Against that background it is not surprising that a 2008 study by Pedersen et al., the results of which I have plotted for you in the figure above (Pedderson. 2013), found statistically significant improvements in glycogen resynthesis w/ 8mg/kg caffeine being coingested with 4mg/kg glucose after a workout. Whether this will yield real world benefits is obviously another story ;-)

While coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample, the glucose incremental area under the curve (IAUC) was not just different between the interventions (with both coffee amounts inducing a greater area compared to water, p = 0.009), but also varied according to the sex and body weight of the subjects:

"Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (PIAUC = .05) and overweight/obese participants (PIAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants." (Gavrieli. 2013)

So what do we make of these results, now? Well, first of all, even if your breakfast does not deserve the name food, having a single regular sized cup of coffee is unlikely to to any harm. Reversing the ratio of breakfast to coffee on the other hand and having a "Sex & The City" breakfast with a croissant and a large cup of breakfast will have you run the risk of having high blood sugar afterwards (esp. if you drink that 400mg+ pot of coffee with tons of sugar).

The tissue incorporation of regular triglyceride based fish oils is inferior to their phospholipid bound brethren. Want to learn more? Check out my article on that matter from June 2012 (learn more)

3g of fish oil modulate the eicasonoid production from omega-6 fatty acids in young men (Zulyniak. 2013) -- 2g of EPA and 1g of DHA that was the dosage the 10 young healthy males (23.4 ± 1.7 years) had to consume on every day of the 3-months supplementation period in Zulyniak et al.'s experiment which was designed to "better understand the potential health benefits of fish oil supplementation in young healthy males" (Zulyniak. 2013).

What the researchers observed were the expected decreases in serum triglycerides (-38%), a significant increase in the proportion of HDL-c relative to total cholesterol, as well as - and this is the actual news - an increase in eicosanoids production, namely prostaglandin-F2α (P < 0.0001) and thromboxane-B2 (P = 0.0296), after fish oil supplementation.

The latter two are products of omega-6 metabolism and confirm the replacement of arachidonic acid (AA, the long-chain omega-6 fatty acid and the quasi-analogon to DHA) in the cell membranes of the erythrocytes by EPA and DHA. This process must have triggered the increase in PGF2α and TXB2 production of which the scientists state that

On a side note: The results of this study don't change my opinion as far as the usefulness, let alone necessity of fish oil supplementation in healthy, athletic, fish eating SuppVersity readers is concerned. I don't see any.
"[...]previous work by both Boughton-Smith et al. and Scott et al. suggest that PGE2, PGF2α, TXB2, and 6-keto-PGF1α are the primary products of the COX2 pathway when AA is in abundance. Furthermore, Scott and colleagues suggested that with chronic elevation of AA, PGF2α and TXB2 production is more likely to be up-regulated due to their vasoconstrictive qualities, which would prevent the efflux of AA and other more-damaging eicosanoids from cells into circulation." (Zulyniak. 2013)

Whether this is actually a good thing does yet appear at least somewhat questionable to me and even Zulyniak et al. have to admit that future research was necessary to confirm "the production of eicosanoids capable of regulating vasoconstriction" and thus "substantiate this hypothesis" (Zulyniak. 2013). As you can see, we are still learning new stuff about things of which every disciple of Dr Oz believes he already knew everything.

Study supports hypothesis that regression in adipocyte size during weight loss could be reason for fat loss plateaus and "walls" (Verhoef. 2013) -- As a seasoned SuppVersity veteran, you are probably aware of the possible influence the size of your fat cells could have on weight loss success, failure or stagnation (learn more).

In a previous post on the Yoyo effect, I already discussed some aspects of adipocyte morphology - including the way lower body fat tends to be more stubborn than upper body fat (read more)

A recent study from the Maastricht University does now offer further support for my previously expressed hypothesis that the reduction of adipocyte size that comes with profound weight loss in then formerly obese individuals could be at the heart of the weight loss plateaus and over-pronounced metabolic downregulation formerly obese individuals experience at way higher body fat levels than someone who has never been obese in his / her whole life. Verhoef et al. put a group of twenty-eight overweight (BMI 28-35kg/m²) healthy subjects on a very low energy diet for 2 months. The 500kcal/day period (50g carbs, 52g protein, 7g fat + multi-mineral supplement delivering the RDA of all nutrients) was followed by a 10-month period of weight maintenance.

Over the course of the low energy diet intervention period, the adipocyte size decreased by -16.7%, the body fat level, on the other hand dropped by only 4.7%. Still, the leptin levels plummeted from 20.3 to 13.1 µg/L and did not return to baseline in the course of the "weight maintenance" phase.

Figure 2: Relative changes (compared to baseline) in body composition, adipocyte volume and leptin after the dieting intervention and the miserable weight maintenance phase (Verhoef. 2013)

In how far the suppressed leptin levels were actually responsible for the fact that the "weight maintenance" phase turned out to be a very dirty, fat only bulking phase cannot be said, but we know from previous studies, that the process of shrinking in itself

"has been reported to generate cellular stress and the more [the adipocytes] shrink, the higher will be the resistance against increasing mitochondrial beta-oxidation via HADHsc [hydroxyacyl-Coenzyme A dehydrogenase] during follow-up." (Verhoef. 2013)

And as if that was not enough the slight increase in ATGL (lipolytic protein) and HADHsc in the "weight maintenance" phase are, as the scientists point out, indicative of the appearance of newly differentiated adipocytes that are are metabolically active contribute to an "improved physiological status", but could potentially make future weight loss (esp. the aesthetic one) even more difficult.

"Empty" adipocytes <> lower leptin <> more glucose-to-fat conversion <> rapid fat gain

If CLA worked in humans as it does in rodents, it could solve the "small adipocyte" problem (learn why)

Moreover, the glycolyctic and thus potentially glucose-to-fat conversion promoting enzyme Aldolase-C did not just distinguish the successful weight maintainers (low Aldolase-C) from the yoyo dieters (high Aldolase-C), it also correlated with the leptin production of the fat cells, of which we know from previous studies that it is in turn negatively correlated to their size (Skurk. 2007)... too complicated?

Ok, let's express it the other way around. The "emptier" your adipocytes are (=smaller size), the less leptin they will produce and the more likely they are to convert glucose to fat and stash that away in their empty "tummies".

Suggested read for those who want to dig further into the purported underlying effects of weight regain: Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology's response to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R581-600.

That's it for an allegedly too lengthy installment of "On Short Notice"... about as much a misnomer as the "weight maintenance" phase in the Verhoef study, I guess. Maybe some of today's Facebook news can make up for that? In the end news like

Want to make HIIT a hit for you? Not a problem, the SuppVersity holds all the information you need. Start out with the respective two post article series and descend into the archives, where you are going to find more about HIIT, how it compares to LISS and which different regimen have shown some promise in peer-reviewed research (learn more)

High fat dieting reduces the beneficial effects of resistant starch - Reduction in abdominal obesity with 42% fat diet = zero (read more)
HIIT hits home in 8 young, untrained men - 12 HIIT sessions lead to increased V02 kinetics (read more)
Ice slurries are the new energy gels - Scientists observe significant increases in cycling performance (read more)
Physical therapy as effective as surgery for a meniscal tear and osteoarthritis - Unfortunately patients are too lazy and the revenue for the doctors too small to be used more often (read more)
Evolution is to blame for inflammatory disease - At least that's what the latest "paleo" research would suggest (read more)

are eventually the reason that the saturdaily short news are always so lengthy. The really short stuff is already on Facebook ;-)

References:

Gavrieli A, et al. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism.2013 [ahead of print]
Pedersen DJ, Lessard SJ, Coffey VG, Churchley EG, Wootton AM, Ng T, Watt MJ, Hawley JA. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. J Appl Physiol. 2008 Jul;105(1):7-13.
Verhoef SP, Camps SG, Bouwman FG, Mariman EC, Westerterp KR. Physiological response of adipocytes to weight loss and maintenance. PLoS One. 2013;8(3):e58011.
Wyatt HR, Peters JC, Reed GW, Barry M, Hill JO. A Colorado statewide survey of walking and its relation to excessive weight. Med Sci Sports Exerc. 2005 May;37(5):724-30.
Zulyniak MA, et al. Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men. Metabolism. 2013 [ahead of print]

Histidine as a fat loss adjuvant? Laughable? Not for the obese! For lean folk like her? We'll see...

If I had to guesstimate the number of fitness enthusiasts who have ever heard of histidine at all, I would say that 50% probably don't even know what it is, while the majority of the lightened ones will re-iterate what the supplement business has been preaching them "You get more than enough histidine, anyway. So don't worry our superior beta-alanine supplement will work even if you don't take additional histidine."

Short term studies confirm this notion. It looks as if we usually have more than enough histidine to have it recombine with beta alanine and form carnosine, but long-term studies are missing and let's be honest: How likely is it that an essential amino acid is nothing but a servant to a non-essential amino acid from the 2nd row?

Early results: Histidine modulates feed efficiency

Actually we could have known that histidine could have some merit as a standalone supplement for more than 50 years now, so I am not sure if the recent publications of two studies by Feng et al. in Diabetolgy and Kumi Kimura et al. in Diabetes, the journal of the American Diabetes Association are going to change that over night. What is certain, though, is that they clearly support findings that date way back into early mid 20th century, when Ellison & King found that the provision of a low histidine diet to rodents increased the feed efficiency (=weight gain per energy unit) by 75%, while the addition of 0.75% histidine (per kg chow) to an already histidine sufficient diet (Ellison. 1968) led to a 30% decrease in food efficiency.

About 45 years later, the previously mentioned studies on the effects of histidine on hepatic gluconeogenesis (Kimura. 2013) and insulin resistance (Feng. 2013) in rodents and human volunteers, respectively, could bring the hitherto often depreciated histamine precursor back to the center of scientific attention.

4g/day histidine improve insulin restiance, reduce fat mass and suppress inflammation

In that, the study by Feng et al., which investigated the effect of 4g/day supplemental histidine on the degree of insulin resistance, inflammation, oxidative stress and metabolic disorders in 100 obese women with the metabolic syndrome (aged 33–51 years; BMI≥28 kg/m²), is probably of greater significance for the average physical culturist that the nevertheless enlightening rodent trial by Kimura et al. we are going to address later.

Figure 1: Changes in amino acid levels, glucose & lipid metabolism, body composition and markers of inflammation after 12 weeks on placebo or 4g/histidine per day (Feng. 2013)

The effects the 4g/day of histidine had especially on the markers of inflammation are quire impressive for an amino acid of which you probably thought as either the "abundant" essential amino acid that's only an adjutant to 100% non-essential and on it's own just about as useless carnosine precursor beta alanine or - even worse - as the nasty precursor to the "allergy inducing", "inflammatory" organic nitrogen compound histamine.

"Hold on, but histidine is an allergy causing nasty bitch, isn't it?"

While the former perspective on histidine is laughable anyway, the fact that there were no increases in histamine levels and none of the participants experienced side effects such as headaches, which have been observed in previous trials with whopping amounts of 64g(!) of histidine per day (Geliebter. 1994) as they have been used, when scientists still believed that the main mechanism of histidine on body weight modulation was mediated by appetite reduction, are probably relevant. After all, histamine does play a role in the inflammatory response system of your body that the latter is not negatively, but positively affected by the consumption of pretty high amounts of histidine, is thus an important and in a way counterintuitive observation. On the other hand,

First the glucose repartitioning effects of isoleucine (learn more), now the benefits of histidine - what other secrets are still out there in the world of amino acids?
[h]istidine is a free radical scavenger and can chelate divalent metal ions (Babizhayev. 1994; Lee. 1999). Its effects against oxidative stress have been well investigated in animals and cells. Histidine has beneficial effects on liver and lung injury in rats and has been reported to protect against diabetic complications in a mouse model of diabetes through its actions against oxidative stress (Lee. 2005; Cuzzocrea. 2007; Yan. 2009). It can restrict accumulation of free radicals and delay activation of extracellular signal-regulated kinase and c-jun N terminal kinase in neuronal cells (Kulebyakin. 2012).

Against that background it is actually not surprising that the levels of TNF-α, IL-6 and c-reactive protein (CRP) dropped by 33%, 35% and 33% in the course of the 12 week study period.

Health and weight loss, two independent pairs of shoes?

If histidine is a metal chelator, do I have to be afraid of losing zinc? That's easy to answer and the answer is no and not just because I believe that the importance of zinc is way overrated (cf. "15mg of Zinc are plenty"). Schechter & Prakesh have shown in 1979, already that the ingestion of 4g of histidine on a daily basis influences the excretion of zinc only in the very short run. After 2 weeks the body achieves a new steady state and the zinc excretion returns to normal. What? No you did not pee out all the zinc before. In fact histidine increases the absorption of dietary zinc as well (cf. Freeman. 1977).

Moreover the changes in serum histidine were correlated with the changes in HOMA-IR, NEFA, TNF-α, SOD, GSH-Px, WC, FM and BMI even after further adjustment for age and serum histidine, protein intake, physical activity, alcohol use, current smoking and menopause at baseline.

"Thus, improved insulin sensitivity and alleviation of inflammation and oxidative stress could be due to the increased serum histidine." (Feng. 2013)

What's questionable, though, is how interrelated the modest, but statistically significant weight, or rather fat loss (-6% total fat mass) and the improvements in inflammation are. If we take a peek at the aformentioned rodent study by Kimura et al. who observed that the effects of histidine are mediated mainly centrally via histamine action on the H1 receptors in the brain, which will - independently of insulin (!) - downregulate the hepatic glucose production, it becomes more and more evident that non-obese / insulin-resistant individuals for whom an abundant hepatic glucose production hardly ever is a problem are less likely to benefit than the patients with type 2 diabetes, Kimura et al. implicate as the group that would be most likely to benefit from high histidine diets.

What else do we know about l-histidine?

In the end, we are thus back to square one. But maybe we can find other arguments in favor or against keeping an eye on adequate histidine intake that would be significant for the non-diabetic majority(!?) of the SuppVersity readers, as well. Let's see, what about

Ok, put up or shut up - where is the relation between histidine, histamine and obesity? As so often I have to say in advance that the intricacies of the role the histamine receptors in the brain play in the regulation of food intake and metabolism are not yet fully understood. What we do know is that histidine is the dietary precursor for histamine and that the latter can interact with the same receptors (H1-H3) which participate in the regulation of dopamine, serotonin, and norepinephrine release and exert direct modulatory effects on food intake, meal frequency, adiposity and thermogenesis (Masaki. 2003; Masaki. 2004; Yoshimoto. 2006; Yoshimatsu. 2008).
improved absorption of vitamin B12 and increased liver folate levels (Williams. 1976)
low histidine intake increases carnosine breakdown, so that the ant-inflammatory intra-cellular buffer carnosine you are trying to increase by taking BA would decrease to be used as a histidine source if you actually got too little histidine in your diet (Tamaki. 1984)
increased absorption and excretion of zinc, with a primer on the former, when intakes are low, so that the overall result is an improved management of zinc (Sandström. 1985; Van Wouwe. 1989)
potential anti-Alzheimer's effects; if we simply assume that an increased amount of dietary histidine could ameliorate the histidine and histamine reductions in the brains of Alzheimer patients (Mazurkiewicz-Kwilecki. 1989), it would be logical to assume that the presence of this metal-chelator could prevent the accumulation of toxic levels of copper in the brain
significant increases in UCP-1 activity (+57%) in brown adipose tissue and thus higher energy expenditure, reduced appetite, significantly lower feed efficiency (-30%), reduced insulin levels (-48%) and significantly lowered visceral fat pad weights; allegedly in rodents w/ additional 5% histidine in the diet (Kasaoka. 2004)

Now you could certainly argue that the studies which support the weight loss effects Feng et al. observed in their obese subjects were almost exclusively conducted on rodents... what am I supposed to say? You're right and you know that I am very skeptical that UCP-1 and brown adipose tissue activity play a significant role in human weight / body fat control. Still, the high correlations between the histidine / total protein ratio Okubo et al. observed in a cohort of non-obese 18y-old female Japanese students does clearly suggest that at least part of the effects are not species specific (Okubo. 2005).

Additional health effects

Milk thistle is unquestionably the more prominent liver protectant (learn more)

Furthermore, histidine also prevented colitis by reducing gastric inflammation (Andou. 2009) and exerted ameliorative effects on

LDL oxidation and glycation (Lee. 2005),
alcohol induced liver failure (Liu. 2008),
acetaminophen induced liver injury (Yan. 2009),
diet induced hepatic steatosis (Mong. 2011)

when it was co-administered with carnosine. Unfortunately, none of the studies tested, whether the same results would have been observed if only one of the compounds had been used in the respective rodent trials.

So, no strings attached? Well, not exactly...

As usually the dose-response curve is yet non-linear and an exuberantly high intake of histidine (8% of the diet in rodents → far more than 70g per day for humans) can lead to copper depletion and corresponding lipid disturbances in cholesterol metabolism (Harvey. 1981). Needless to say that for people with a messed up histamine metabolism far lower doses could potentially exert negative effects. It should be mentioned though that the equation"more histidine = more histamine" does not necessary hold - just take a look at the data from the Feng study: More histamine? Yes! Beneficial effects? Yes! Increased circulating histamine? No!

Bottom line: Wile it appears likely that the provision of supplemental histidine in amounts of up to 4g/day could provide a highly beneficial adjunct to exercise and diet intervention in obese and/or diabetic individuals, it remains to be seen, whether or not lean, healthy and insulin sensitive fitness enthusiasts benefit to a similar degree.

Histidine content of various foods; w/ a focus on high histidine food items

While I would exclude that the profound anti-inflammatory effects Feng et al. observed could hamper your performance / gains, I would not exclude that the non-vegetarian majority of the SuppVersity readers is not exactly at risk of running out of histidine anytime soon (see table on the right for good dietary sources). Against that background, you may have to revise your perspective on this rarely talked about amino acid. What you probably don't have to do, though, is to go and buy a pouch of l-histidine to up your histidine intake to exorbitantly high levels... well, at least not until research on human beings confirms the beneficial effects on UCP-1, insulin and the body fat levels Ksaoka et al. observed in non-obese rodents.

References:

Andou A, Hisamatsu T, Okamoto S, Chinen H, Kamada N, Kobayashi T, Hashimoto M, Okutsu T, Shimbo K, Takeda T, Matsumoto H, Sato A, Ohtsu H, Suzuki M, Hibi T. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Gastroenterology. 2009 Feb;136(2):564-74.e2.
Babizhayev MA, Seguin MC, Gueyne J, Evstigneeva RP, Ageyeva EA, Zheltukhina GA. L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. Biochem J. 1994; 304(Pt 2):509–516.
Cuzzocrea S, Genovese T, Failla M et al. Protective effect of orally administered carnosine on bleomycin-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2007; 292:L1095–L1104
Ellison JS, King KW. Mechanism of appetite control in rats consuming imbalanced amino acid mixtures. J Nutr. 1968 Apr;94(4):543-54.
Feng RN, Niu YC, Sun XW, Li Q, Zhao C, Wang C, Guo FC, Sun CH, Li Y. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial. Diabetologia. 2013 Jan 30.
Freeman RM, Taylor PR. Influence of histidine administration on zinc metabolism in the rat. Am J Clin Nutr. 1977 Apr;30(4):523-7.
Geliebter AA, Hashim SA, Van Itallie TB Oral L-histidine fails to reduce taste and smell acuity but induces anorexia and urinary zinc excretion. Am J Clin Nutr. 1981; 34:119–120.
Harvey PW, Hunsaker HA, Allen KG. Dietary L-histidine-induced hypercholesterolemia and hypocupremia in the rat. J Nutr. 1981 Apr;111(4):639-47.
Kimura K, Nakamura Y, Inaba Y, Matsumoto M, Kido Y, Asahara SI, Matsuda T, Watanabe H, Maeda A, Inagaki F, Mukai C, Takeda K, Akira S, Ota T, Nakabayashi H, Kaneko S, Kasuga M, Inoue H. Histidine augments the suppression of hepatic glucose production by central insulin action. Diabetes. 2013 Mar 8.
Kulebyakin K, Karpova L, Lakonsteva E, Krasavin M, Boldyrev A. Carnosine protects neurons against oxidative stress and modulates the time profile of MAPK cascade signaling. Amino
acids. 2012; 43:91–96
Lee JW, Miyawaki H, Bobst EV, Hester JD, Ashraf M, Bobst AM. Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine. J Mol Cell Cardiol. 1999; 31:113–121.
Lee YT, Hsu CC, Lin MH, Liu KS, Yin MC. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J
Pharmacol. 2005. 513:145–150.
Liu WH, Liu TC, Yin MC. Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. Food Chem Toxicol. 2008 May;46(5):1503-9. doi: 10.1016/j.fct.2007.12.013.
Mong MC, Chao CY, Yin MC. Histidine and carnosine alleviated hepatic steatosis in mice consumed high saturated fat diet. Eur J Pharmacol. 2011 Feb 25;653(1-3):82-8. doi: 10.1016/j.ejphar.2010.12.001.
Okubo H, Sasaki S. Histidine intake may negatively correlate with energy intake in human: a cross-sectional study in Japanese female students aged 18 years. J Nutr Sci Vitaminol (Tokyo). 2005 Oct;51(5):329-34.
Sandström B, Davidsson L, Cederblad A, Lönnerdal B. Oral iron, dietary ligands and zinc absorption. J Nutr. 1985 Mar;115(3):411-4.
Schechter PJ, Prakash NJ. Failure of oral L-histidine to influence appetite or affect zinc metabolism in man: a double-blind study. Am J Clin Nutr. 1979 May;32(5):1011-4.
Tamaki N, Funatsuka A, Fujimoto S, Hama T. The utilization of carnosine in rats fed on a histidine-free diet and its effect on the levels of tissue histidine and carnosine. J Nutr Sci Vitaminol (Tokyo). 1984 Dec;30(6):541-51.
Van Wouwe JP, Hoogenkamp S, Van den Hamer CJ. Histidine supplement and Zn status in Swiss random mice. Biol Trace Elem Res. 1989 Oct;22(1):35-43.
Williams DL, Spray GH. The effects of dietary histidine, methionine and homocystine on vitamin B12 and folate levels in rat liver. Br J Nutr. 1976 May;35(3):299-307
Yan SL, Wu ST, Yin MC, Chen HT, Chen HC. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J Food Sci. 2009: 74:H259–H265.

"Men are different women, too..." We all know that, but can we still train together or will women have to do cardio first, while men would be better off starting out lifting weights?

This is not the first and certainly not the last article on what should come first, if you actually have to or want to do endurance and resistance training in single workout session. Today's SuppVersity article is however the one on the study with the most detailed evaluation of the differential effects of "endurance vs. resistance training first" on the endocrine response, neuromascular fatique and power in men and women, I have seen in a while. The pertinent paper is titled "Acute Hormonal and Force Responses to Combined Strength and Endurance Loadings in Men and Women: The 'Order Effect'" and has been written by Ritva S. Taipale and Keijo Häkkinen from the Department of Biology of Physical Activity at the University of Jyväskylä in Finland (Taipale. 2013).

60 minutes LISS + 45 min leg circuit or vice versa - what's best?

The intention of the researchers was to "to examine the acute exercise induced serum hormone and neuromuscular responses and the time course of changes during recovery in response to a combined strength and endurance training session in recreationally endurance trained male and female runners and whether this response would differ if the participants started their workout with a ...

steady state running exercise at an intensity between each subject’s previously determined individual lactate threshold (LT) and respiratory compensation threshold (RCT) for 60 minutes, or

a circuit leg workout with 2 minutes rest between sets that implemented both maximal and explosive strength exercises at loads of 70–85% of the individual 1RM for three sets of 5–8 repetitions, with the final repetition of each set being performed to "near failure" and explosive strength exercises of 8-10reps at a maximal velocity using only 30-40& of the 1EM load on the bilateral leg press (3 sets maximal and 3 sets explosive), the squat (3 sets maximal), loaded squat jumps (3 sets explosive), and calf raises (2 sets maximal).

In short, the question the researchers had in mind when they came up with the research design was: "What's the best way to combine 60min of steady state cardio and an intense 45min leg routine into a single workout"?

Figure 1: Change in maximal voluntary contraction (MVC) in men (left) and women (right) during, immediately after and in the recovery period after the endurance first (ES) and strength first (SE) workouts (Taipale. 2013)

As the data in figure 1 goes to show you, the results were not exactly flattering to the strong sex (=us men), whose absolute maximal bilateral isometric (MVC) strength in the endurance first (ES) trial decreased significantly (28%, p = 0.002) following the 60 minutes of jogging (E), while it remained stable in the 10 female study participants. Luckily, there was still a follow up after which we were back on par (-22% in men and -21% in women).

"The relative loading-induced decreases (D%) in strength between ES and SE differed significantly at mid in men (p<0.001). The relative decreases (D%) in strength in men and women were similar at MID; however, at post, a significant difference between ES men and ES women was observed. The absolute rate of force development (RFD) decreased during both loadings in ES and SE men (at post -19%, p< 0.001 and -22%, p = 0.003, respectively)." (Taipale. 2013)

So once again, the "fairer sex" had an "unfair" advantage, as the rate of force development of the women did not decrease significantly after either the ES or the SE trial. However, it was on ony after the "endurance first" (ES) trial that this effect reached statistical significance.

Level playing field? You must be kiddin' the girls are on dope... ah estrogen ;-)

A similar advantage was observed for the recovery of the initially equally decreased maximum voluntary contraction (MVC) in men and women. Contrary to the ladies who bounced back to normal within the first 24 hours, the MVC of the men remained significantly below the baseline levels in both the strength- (ES) and endurance first (ES) arms of the study 24 h after the endurance first trial (-14% and -15%, respectively) and was still below baseline 48 h post (p < 0.01 -11%).

Figure 2: Endocrine response to endurance (ES) or strength first (SE) workouts in men an women (Taipale. 2013)

If we set these performance outcomes in relation to the endocrine changes the scientists observed, it's quite intriguing to see the that the highly significant increase in post-workout cortisol levels right after the strength-first trial in the men coincides with faster recovery in response to doing strength before cardio workout... or should I rather say in response to doing a steady state cardio session after your strength workout the guys recovered faster?

"Men better start with strength training. Women do whatever they like?! "

The faster recovery after the strength first, endurance second (SE) trial, as well as the 343x higher GH levels after the in this arm of the study appear to speak in favor of doing your strength training first, before you hop onto a recumbent bike or treadmill and add in another 40-60min of light intensity steady state training (LISS), if you are a man! In the fortunate case that you are a member of the estrogen driven fairer sex (= a woman ;-), the study at hand appears to suggest that it would not really make much of a difference, whether you hit the weights first or second.

For people whose main goal it is to shed fat, the reduction in leptin with cardio first may argue in favor of during your cardio first (read more).

The SuppVersity veterans out there may now feel reminded of a 2012 study by di Blasio et al. that was likewise covered in the SuppVersity news. Di Blasio et al. were the first to investigate the effects of "doing cardio in between", i.e. hopping on the treadmill or cardio equipment of your choice after the completion of a strength circuit or any other given time point in your strength workout and returning to the weights, afterwards (learn more). Unfortunately, this still isn't the answer to everthing. In fact, you don't have to browse the SuppVersity archives for posts on exercise order for very long until you hit onto an article that carries the title "Cardio First if You Want to Leave the Gym More 'Anabolic' Than You Were When You Came in?" (read more) and points you into yet another direction...

So, which of the myriad of studies do we trust?

If it were not for one major glitch in the study at hand, I would probably end this article on the note that the singularly long follow up period in the study at hand would clearly suggest that the results Taipale et al. generated in the course of their experiment had more practical value (we all know about the fallacy of the narrow minded focus on the immediate post-workout endocrine response; don't we?) the fact that they did not control for the workload is a real bummer.

Imagine the guys simply lifted way more weight in the strength first, endurance second trial - wouldn't an increased GH response to an identical endurance workout with way more depleted glycogen stores actually be what you would have to expect? Also, we all know that when you put men and women together in the gym, the former train until they drop, while the latter do as they are told and take their time looking at the sweaty guys while fumbling around with the weights... ok, that's a cliché, but there is way more than just the splinter of truth that's at the bottom of every of these commonly held prejudices.

Doing (intense) cardio first could promote anabolism (learn why).

Bottom line: In the end, I can only give you this advice. Try both! Try doing cardio before and after your workouts for 2 weeks each and decide afterwards which exercise order you like best. Things you should base your decision on are (a) the amount of weight you lift, (b) your performance during the cardio part of your workout, (c) how smooth the transition between one and the other goes, (d) how you feel the day after and during your next workout.

And don't forget, a glycogen depleting cardio session before your strength workout could increase the expression of the muscle building isoform PGC-1a (learn more)

References

Di Blasio A, Gemello E, Di Iorio A, Di Giacinto G, Celso T, Di Renzo D, Sablone A., Ripari P. Order effects of concurrent endurance and resistance training on post-exercise response of non-trained women. Journal of Sports Science and Medicine. 2012 Aug; 11:393-39.
Taipale R, Häkkinen K. Acute hormonal and force responses to combined strength and endurance loadings in men and women: the "order effect". PLoS One. 2013;8(2):e55051.

Will the additional butter on top of the potatoes reduce the insulin response? You can find the answer to this and the other questions in today's episode of "True or False?"

If you are a regular here at the SuppVersity you should by now recognize the "True or False" part of the headline of today's SuppVersity article. Therefore it's probably unnecessary to say this explicitly, but this is a new series, where I could use a little help from your side. Well, ... I should say, I believe it would become even more fun, if you lend me a hand and send me short pieces of wisdom or idiocy like "Adding fat to a carby meal reduces the insulin response" you deem worthy of being addressed in the True or False series. I cannot, or rather will not promise that I will address each and every of your suggestions, but if it interests me and can be tackled in a 2-3 paragraph text, your chances ain't bad to get your suggestions dealt with - if you got any ideas, just post them in the comment section of one of the previous installments (including today's, obviously).

Adding Fat to A Meal Will Ameliorate the Insulin Response

False. When you are browsing the Internet it is easy to get the impression that what is wrong or right is not determined by scientific evidence, but by the number of people who repeat it in their blogs, on their facebook walls and in their bulletin board contributions. The common "wisdom" that it would be a good idea to add some fat to a meal to reduce the insulin spike it will give you is one of those paradigms that remain intrinsically flawed no matter how often they are repeated.

Figure 1: Althoug the glucose AUC drops after the addition of fat (slowed absorption of glucose from the intestine), the amount of insulin (2ndary axis) that is needed to stash the glucose away is 8.5x higher (on a per unit base; cf. violet bar) and the absolute insulin response does not decrease at all in lean healthy men and women (Collier. 1983)

If you do take a look at what actually happens, when you add fat to a meal, it is yet not difficult to understand how that myth came about. Just like people don't understand that the GI of a certain carbohydrate source doesn't tell you much about it's effect on insulin, the fact that the addition of fat ameliorates the postprandial spike in glucose gets misinterpreted as "fatty meals are less insulinogenic than low fat meals". In fact, the addition of 50g of butter on top of the 50g of carbohydrates the 8 lean, weight stable men and women (N=4, each) consumed in form of potatoes, did not have any effect on the post-prandial insulin release at all.

GIP Or Not GIP - That is the Question: "Fat intake, in addition to ingestion of carbohydrate, stimulates GIP release. Therefore, during a mixed meal GIP might act to promote the storage of both triglyceride and glucose indirectly via the release of insulin." (Kieffer. 2003)

The amount of the fat storage peptide GIP (learn more), on the . Therefore, Collier and O'Dea are 100% right, when they state in the conclusion of their 1983 paper that...

"despite the apparent improvement in glucose tolerance when carbohydrate is ingested together with fat, the accompanying potentiation of insulin secretion could form the basis of long-term changes in insulin sensitivity which accompany alterations in dietary fat intake." (Collier. 1983)

You may want to remember that, whenever you feel inclined to add a ton of bacon on top of your sweet potatoes in the false believe that this would "mitigate" the effects of the carb-laden tubers the insulin response.

This obviously does not change the fact that having some fat in a meal does have the added benefit of increasing GLP-1 and PYY levels and thus contributing to a longer satiety effect (eg. Knut. 2008)

Skeletal Muscle Hypertrophy Impairs Oxygen Diffusion

"Some HIIT For Life & Less LISS For More!" As the study at hand shows, this mantra is all the more important for the more muscular SuppVersity readers - that does not change that exercising longer to burn more fat won't work for anyone, muscular or not (learn why).

True! Contrary to the previous myth about the beneficial effects of adding fat to a high carb meal, which was not just totally messed up, but also pretty well-known the physical necessity that marked skeletal muscle hypertrophy will have a negative effect on he O2 diffusion of the "balooned up" musculature is something I would guess few of you have ever heard about before.

I have to admit that the 15-20% reduction in maximal oxygen consumption per kg of quadriceps mass a group of researchers from the University of Udine observed in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (body mass ~103kg), when they compared their them to 11 normal controls (body mass ~77kg) looks scary at first.

If you do yet also take into consideration that this decrease in oxygenation was accompanying improvements in ADP-stimulated mitochondrial respiration (+59%; takes place, when the ATP stores are used up) and a tighter coupling of oxidative phosphorylation, it becomes evident that the training induced enhancements in mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O₂ diffusion.

"The net results are an enhanced whole body oxidative function at peak exercise, and unchanged efficiency and O₂ cost at submaximal exercise, despite a much greater body mass." (Salvadego. 2013)

In other words, despite "suboptimal" oxygenation of the musculature a bigger metabolic engine will still burn more fat... but only when it's working at peak intensity. It won't do so at submaximal intensities, where the O2 costs are "identical" (statistically). So, what does that tell us about the usefulness of training in the non-existent fat burning zone for advanced, heavily muscled trainees? Yep, it's even smaller than for the average sedentary housewife.

Low Carb High Fat Diets Lead to Acute Improvements in Muscular Insulin Sensitivity

False. Although the slowly abating low-carb craze does still make it appear as if "just eating less carbs" was the solution to everything, it is only logical that low carb dieting leads to changes in skeletal muscle insulin signaling, i.e. decreases in insulin-stimulated tyrosine phosphorylation of IRS-1 and PI3-kinase activity, which reduce, not increase the ability / willingness of the musculature to suck up glucose from the blood stream within no more than 5 days (cf. Pessin. 2000; Reusch. 2002).

Figure 2: Changes (before vs. after 5-day intervention) in fasting glycemia and lipidemia and glucose rate of appearance and disposal during euglycemic clamp conditions (Wang. 2013)

So even in the absence of significant effects on the body composition or signs of full-blown whole body insulin resistance, the changes Cecilia C.L. Wang and colleagues observed in muscle samples that were taken from their insulin tolerant, but overweight subjects are identical to those you would observe in the early stages of diabetes, and do thus predate "changes in whole body insulin sensitivity" (Wang. 2013).

"But that ain't low carb!" Certainly a valid critism w/30% carbs and 20% protein in the diet it is practically impossible to reach ketosis, but - believe it or not - this is representative of the "low carb" diets you will usually see in the pertinent literature.

Wang et al. base their conclusion on the results of a recently conducted weight loss intervention that involved 18 obese individuals without diabetes who underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after:

5 days of eucaloric diet (30% fat, 50% carbohydrate), and

5 days of a 30% calorie-restricted diet, containing either...

LF/HC: 20% fat, 60% carbs
HF/LC: 50% fat, 30% carbs.

As mentioned in the introduction it's only logical and not necessary a bad thing that the skeletal muscle of the LF/HC group reacted with favorable changes in inulin receptor phosphorylation and lead to improvements in the IRS-1-associated PI3-kinase activity, which also figures in the exercise and nutrient induced increase in skeletal muscle protein synthesis (its among others the main target of IGF-1, of which keto dieters are known to have significantly reduced levels, anyway; cf. Fraser. 2000; Glass. 2003).

In other words, "No, 'just eat no carbs' is not the solution to everything", but will lead to certain metabolic adaptations which are not exactly conducive to returning to a normal carb diet afterwards. Plus, if you are a lean gymrat striving to to maximize your lean mass gains the full-blown hepatic growth hormone resistance and corresponding -50% drop in hepatic IGF-1 mRNA expression Bielohuby et al. observed in a rodent model of ketogenic dieting in 2011 probably won't come handy in the long run (on a side note: The "keto rodents", with their 92.8% fat diet also had a 5% reduction in lean mass and 46%, 56% and 223% higher relative amounts of visceral fat in the inguinal, epididymal and perirenal fat pads; cf. Bielohub. 2011)

Keep in mind this is a physiological form of insulin resistance

Learn how Adelfo lost his carbophobia and saw nothing but benefits from it (read more). That someone in the >30kg/m² BMI region with type II diabetes should keep a close eye on carb intake is a whole different story.

That being said, it is at least in part due to this mechanism that this type of diet works so well for highly insulin resistant individuals. It does not require the body to become insulin sensitive to work, but provides your body with a substrate that would - in and out of itself - require a certain degree of insulin resistance to make sure your muscle don't suck away the little glucose that's floating around and make you feel miserable and hypoglycemic. That you cannot observe those changes with a glucometer at home should be obvious. After all you are not eating carbs, are you?

Would the effect have been different with a true keto diet? The weight loss? Maybe. The transient insulin resistance? More pronounced, if anything. If you are already obese and freakin' insulin resistant to begin with, this does yet hardly matter. Low fat, high fat, keto - I don't care! The weight loss, the ensuing reduction in chronic inflammation and the new room to actually stash away superfluous energy alone will sooner or later also help you to reduce your insulin resistance.

Suggested read on physiological (=adaptation to diet / exercise) insulin resistance: "The Marathon Paradox - How Temporary Exercise-Induced Insulin Resistance Paves the Way for Fat Burning Machines" (complete article)

References:

Berk ES, Kovera AJ, Boozer CN, Pi-Sunyer FX, Johnson JA, Albu JB. Adiponectin levels during low- and high-fat eucaloric diets in lean and obese women. Obes Res. 2005 Sep;13(9):1566-71.
Bielohuby M, Sawitzky M, Stoehr BJ, Stock P, Menhofer D, Ebensing S, Bjerre M, Frystyk J, Binder G, Strasburger C, Wu Z, Christ B, Hoeflich A, Bidlingmaier M. Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats. Endocrinology. 2011 May;152(5):1948-60.
Collier G, O'Dea K. The effect of coingestion of fat on the glucose, insulin, and gastric inhibitory polypeptide responses to carbohydrate and protein. Am J Clin Nutr. 1983 Jun;37(6):941-4.
Fraser DA, Thoen J, Bondhus S, Haugen M, Reseland JE, Djøseland O, Førre O, Kjeldsen-Kragh J. Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation after a ketogenic diet in rheumatoid arthritis patients. Clin Exp Rheumatol. 2000 Mar-Apr;18(2):209-14.
Glass DJ. Molecular mechanisms modulating muscle mass. Trends Mol Med. 2003 Aug;9(8):344-50. Review.
Kieffer TJ. GIP or not GIP? That is the question. Trends Pharmacol Sci. 2003 Mar;24(3):110-2.
Knuth ND, Shrivastava CR, Horowitz JF. Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration. J Appl Physiol. 2009 Jan;106(1):122-9. doi: 10.1152/japplphysiol.90404.2008. Epub 2008 Nov 13.
Pessin JE, Saltiel AR. Signaling pathways in insulin action:molecular targets of insulin resistance. J Clin Invest. 2000;106(2):165–9.
Salvadego D, Domenis R, Lazzer S, Porcelli S, Rittweger J, Rizzo G, Mavelli I, Simunic B, Pisot R, Grassi B. Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training. J Appl Physiol. 2013 Mar 21.
Reusch JE. Current concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome. Am J Cardiol. 2002;90(5A):19G–26G.
Wang CC, Adochio RL, Leitner JW, Abeyta IM, Draznin B, Cornier MA. Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction. Metabolism. 2013; 62:595–603

What if one of those would be displayed prominently on every Snickers bar and other candy - would that be unethical?

I must admit that I probably have a positive bias towards the latest study, Satoshi Odo, Koji Tanabe an Masamitsu Yamauchi who work for Lonza a company that describes itself as "a global leader in life sciences" and the Aichi Gakusen University in Japan have just published in the online Journal Food and Nutrition Sciences. Why? Well, it demonstrates the value of education, motivation and making people take responsibility for their own well-being. Something that's still largely unappreciated and maybe even feared by the medical orthodoxy and it's victims... ah, pardon me, "patients", of course.

Words and wisdom trump pills and meal plans

Actually the researchers did nothing we would not have seen in countless of studies before. They recruited 24 male subjects with an, in US terms, pretty low BMI of 25 - 28 kg/m² and a waist circumference of 85-100 cm who had not been following any kind of regular exercise program before the intervention. The subjects were then assigned to one out of four groups:

L-carnitine does also affect IGF-1 levels (read more)

Car +M: 500mg/day carnitine / no instruction

Car -M: 500mg/day carnitine / plus instruction

Pla +M: placebo / no instruction

Pla -M: placebo / plus instruction

The hypothesis the scientists had in mind was that the motivation program, which comprised (1) a face-to-face 30 min session with the principal investigator at the baseline visit, where the subjects were informed about L-carnitine and its metabolic functions, learned about the beneficial effect of weight loss on the risk of metabolic diseases, and were encouraged to perform daily physical activities like “taking stairs” instead of “using escalators”, (2) wearing a step-counter and evaluating its data on a daily basis, (3) doing a 7-day food log before the intervention began and comparing the latter to a second food log that was to be filled 7 days prior to their last visit at the lab.

"I am so freakin' motivated, but I don't want to eat less..."

All that sounds pretty non-sensical (and I guess there may be a cultural aspect to it, due to which it may be slightly less effective in the US), but the "success" of this "motivational intervention" - as minuscule as it may have been over the course of this 4-week intervention without a prescribed diet / exercise regimen - cannot be denied (see figure 1 & figure 2).

Figure 1: Changes in body composition and daily activity level in the course of the 4-week "intervention" (Odo. 2013)

This is particularly true, if you take into consideration that despite being "motivated to keep daily calorie intake between 1500 and 1,800 kcal", the energy intake of most of the subjects exceeded 2500 kcal/day and did thus not really differ from baseline in figures 1 the scientists also evaluated the effect the dietary / supplement intervention had on glucose and lipid metabolism and found

Keep motivated and add some GTE to the equation, if you want to improve your glucose metabolism. The data above shows, green tea extract is in fact as potent as metformin (learn more)
decreased triglyceride levels in Car +M

no sign. effect on total cholesterol
n.s. increase in LDL in all but the Car +M group
no sign. change in HDL

non-significant increase in adiponectin in Car +M

no changes in HbA1c in any group
significant increases in insulin in the non-motivated groups

And last but not least Odo et al. investigated what they call "safety parameters". Every normal human being would call the latter a standard blood panel, which did, as you would expect, not show and pathological changes (I mean what could exercise and carnitine do to those guys?) and ran a couple of liver and kidney tests, where - and this is interesting - only the non-motivated, non-supplemented group showed a single statistically significant, but physiologically irrelevant change in urea nitrogen levels, which increased from 13.0 to 15.0mg/dL.

Want to add 10 kg to your bench in one session sugar pills and the brocebo effect make it possible (learn how)

Bottom line: Actually there are two messages you can take away from the study at hand. One is that carnitine works. Taken at a dosage as low as 500mg/day alone yielded in parts borderline, but still significant health improvements in the absence of any prescribed dietary or exercise intervention. The more important message, on the other hand pertains to the effect of the "motivational protocol". Despite the fact that you will probably agree that this was not exactly what should become the "gold standard" for future interventions the mere knowledge of why the subjects were supposed to eat less, make healthier food choices and be more active was enough to make a significant difference. And that irrespective of whether the subjects ended up receiving the carnitine or the placebo supplement.

As mentioned before, there certainly is a cultural bias involved here, but is that reason enough to say: "Wtf, this won't work for Americans anyway!" Should results like this not rather be an incentive to try and change a climate, where people rather wait for the next weight loss drug than to start taking their life into their own hands, before their diabetes has made their fingers so numb that this is no longer possible? I would think so and that's actually part of the reason the SuppVersity and the SuppVersity Science-Round Up on Super Human Radio exist.

Does beta alanine hamper instead of improve your sprinting performance?

Did you notice something? Yeah, there have been more news on testosterone boosters as of late than on sodium bicarbonate, here at the SuppVersity. You don't have worry though, I have not been bribed by the supplement industry. The reason that you have not heard about baking soda as of late was merely a pragmatic one: the absence of recent studies. With the soon-to-be-published paper by Kagan Ducker, Brian Dawson and Karen E. Wallman from the University of Western Australia the barren spell has ended - luckily.

Before we delve deeper into the carbonated results of the study at hand, I want to take the chance to briefly remind you that it's Thursday and thus about time to make sure you you don't miss the SuppVersity Science Round-Up at 1PM EST live on SuperHumanRadio. You are not sure if you can make it? Well, in that case you would be missing even more bicarbonate lovin', a discussion on the potential downsides of intermittent fasting, when you are not dieting, some clarifications on yesterday's Facebook news on the potential liver damaging effects of "cortisol blockers", the latest on the effects of DHEA on testicular health and testosterone levels, the optimal omega-6/omega-3 ratio for endocrine health, the life-shortening effects of large amounts of fish oil and much more... and while you are waiting for the show to start why don't you take a peek at what Ducker et al. have found?

Beta alanine added bonus or unworthy opponent?

Inspired by previous yet by far not very conclusive trials which found that the combination of the precursor of the intracellular H+ buffer beta alanine and the often looked down upon alkalizer sodium bicarbonate (cf. Sale. 2011; Bellinger. 2012; read more about the Bellinger study) could yield some benefits over the performance increases baking soda and not beta alanine(!) alone can produce, Ducker et al. wanted to elucidate whether a preload with 3-6g/day of beta-alanine for 28 days either alone or in combined with a pre-exercise dose of 0.3g/kg baking soda would lead to improvements in prolonged repeated-sprint performance in team-sport athletes.

The Australians hypothesized that both, beta-alanine supplementation and an acute dose of sodium bicarbonate, would separately result in improvements in repeated-sprint performance, but that combining both treatments would lead to a greater improvement in repeated sprint ability (RSA) compared to either supplement on its own.

Figure 1: Relative changes in sprint performance (sprint time) for all three and each set of 6x20m sprints (Ducker. 2013)

A brief glance at the data in figure 1 does suffice that the latter was not the case. While it was to be suspected that the 28-day preloading the six of the 24 male competitive football, soccer and hockey players who had been randomized to the NaHCO3 + BA group would yield at least some yet probably not significant performance increase in the during the 3 sets of 6 x 20m sprinting (25 s between sprins, 4 min active recovery between the three sets), the exact opposite was the case.

Contrary to beta alanine, creatine is a perfect match to baking soda... or rather vice versa (learn more)
"Sodium bicarbonate supplementation (alone) resulted in the best repeated-sprint performance, with some improvement also seen (but to a lesser extent) when a combination of beta-alanine and sodium bicarbonate was used. This outcome was surprising, as it was hypothesised that combining supplementation of sodium bicarbonate (extracellular blood buffer) and beta-alanine (intracellular muscle buffer via carnosine) would result in enhanced repeated-sprint performance beyond what is possible with either supplement alone." (Ducker. 2013)

So, contrary to bicarbonate alone, which was "likely" and "very likely" to produce increases in overall total sprint times (TST) for each individual set, as well as for first sprint (Set 2 and 3) and best sprint time, the combined supplement did not only fail to increase the likelihood that these effects would occur in similarly trained athletes / gymrats, but actually reduced to "possible" and "likely".

Squats, 8 x 12, Leg Press 6 x 12, Leg Ext. 6 x 12; that's the Quads routine Serge Nubret (photo) trained twice a week in conjunction with chest – it stands out of question that this is the kind of workout that benefits most from an acid buffer like NaHCO(3) (read more)!

Bottom line: The performance decrements the scientists observed when they combined the 0.3g/kg NaCO3 with a 28-day beta alanine preload is actually pretty surprising and that despite the fact that the short sprints are not actually the strength of the carnosine precursor. Significant but with ~2% still pretty pathetic performance increases effects can only be expected with longer sprints in the 90-150s range, and previous studies by Sweeney et al. and Saunders et al. have already confirmed its useless in similar scenarios (Sweeny. 2010; Saunders. 2012). So while it may be debatable in how far the performance decrease may be reproducible in larger scale studies, there is no debating of the scientists conclusion that

"Supplementation with beta-alanine may not be ergogenic for these sports [football, soccer and hockey], which require repeated short (~2-4 s) sprints with brief (~15 – 30 s) recovery periods." (Ducker. 2013)

What remains to be seen, though is whether adding the BA on top of the bicarbonate does actually "result in a lower magnitude of performance improvements than sodium bicarbonate supplementation in isolation" (Ducker. 2013). And would thus be downright ergolytic. But hey, maybe the guys had just depleted their histidine sources (learn more about histidine) - in that case they would have become fat not slow, or maybe both? Just kiddin' ;-)

References:

Bellinger PM, Howe ST, Shing CM, Fell JW. Effect of combined β-alanine and sodium bicarbonate supplementation on cycling performance. Med Sci Sports Exerc. 2012 Aug;44(8):1545-51.
Ducker KJ, Dawson B, Wallman KE. Effect of beta-alanine and sodium bicarbonate supplementation on repeated-sprint performance. J Strength Cond Res. 2013 Mar 21.
Sale C, Saunders B, Hudson S, Wise JA, Harris RC, and Sunderland CD. Effect of beta alanine plus sodium bicarbonate on high-intensity cycling capacity. Medicine and Science in Sports and Exercise. 2011; 43:1972-1978.
Saunders B, Sale C, Harris R, and Sunderland C.Effect of beta-alanine supplementation on repeated sprint performance during the Loughborough Intermittent Shuttle Test. Amino Acids. 2012; 43: 39-47.
Sweeney KM, Wright GA, Brice AG, and DobersteinST. The effect of beta-alanine supplementation on power performance during repeated sprint activity. Journal of Strength and Conditioning Research. 2010; 24:79-87.

Believe it or not. High dose hydrocortisone can decrease body fat levels (Babikian. 1962; see further down) and the acute administration of prednisolone has repeatedly been shown to have pronounced endurance performance (e.g. +61%; Arlettaz. 2007).

It's not like the Science Round Up was a request show, but I still want to start the Seconds to yesterday's installment of the show (download the podcast) with an honest an sincere apology to one of our listeners. Yeah, there is no debating, Carl and I had promised to talk about the "cortisol blockers can cause necrosis of the liver" study (Zou. 2013) and then simply forgot about it. I guess this was due to the unplanned "copper + HFCS = arrhythmia" excursion at the beginning of the show, but I don't want to give the impression I was looking for excuses here. Instead, I decided to make up for our negligence by taking the opportunity to go beyond simply answering the question whether the recently published data on the pro-necrotic effects of 11beta HSD reductase inhibition is a reason of concern for those of you have been taking respective products in the past and - as a bonus - discuss the effects of cortisol and cortisol inhibitors on body composition, in general.

All clear-signal - You are not going to die!

Let me answer the health related question first: I don't think there is reason to be concerned even if you've been using the 7-oxo's, -keto's and all the other caps and creams that are supposed to annihilate the "bad, bad" cortisol in the past. Due to the fact that Zou and colleagues did not use any of the common OTC supplements, but genetic ablation or UE2316, another 11beta-HSD that's commonly used in pertinent studies, it is not even certain that the DHEA-metabolites you can buy at every supplement store will produce identical / identically pronounced negative side effects.

From a previous installment of the Seconds (go back): Effect of estradiol (E2), DHEA and its metabolites 7-OXO & co on breast cancer cell proliferation (based on Miller 2012)

Since both the genetic ablation and the research drug the scientists used are working by inhibiting the same enzyme as the DHEA-metabolites that are sold as "cortisol blockers", it is yet almost sure that they would have the potential to do so.

That being said, the mere potential of hepatic necrosis, or even liver failure which would yet require the liver to be thoroughly beat up already, should not be a problem for smart SuppVersity readers like yourself, anyway. After all, you do know about the janus-faced nature of cortisol, as well as its physiological importance and would therefore never try and annihilate this powerful fat solvent, right?

"Cortisol a fat solvent? What are you talking about?"

I know, for those of you for whom this is the first visit to the SuppVersity after years of being bamboozled by conventional wisdom, it will probably sound crazy to call cortisol, "the fattening hormone" that's to blame for your belly and your skinny arms at the same time as a "fat solvent". So let's briefly take a look at what cortisol actually does.

Suggested read for the SuppVersity Freshmen (and -women ;-): Scientists cover 6 months contest prep of natural body builder who loses almost exlusively fat despite (or should I say due to?) +100% elevated cortisol and tanking testosterone levels (read more).

Firstly, cortisol is a profound anti-inflammatory. It does not cause inflammation, but rises in response to inflammation (the downside obviously are it's immuno-supressive effects). Secondly, cortisol is a glucocorticoid and makes sure that there is alway enough glucose floating around in your system by (a) digging into the fat and protein stores of your body to fuel your acute energy demands and (b) decreasing insulin release and sensitivity to spare glucose (Andrews. 1999).

While those of you who have already been "on" a cortisol inhibitor may have felt the negative sides of function #1 in their joints, few people acknowledge that the inhibition of cortisol and it's ability to increase the lypolytic rate (=release of fat) in adipocytes by 50% and more (Djurhuus. 2002; Cambell. 2011) could actually hamper, not accelerate weight loss while you are dieting.

There is no debating: Cortisol can be a mean bitch, but...

Now, the last four words of the previous paragraph are in fact what's making all the difference here. As long as you give your body the chance to actually burn off the fat that's getting pushed out of the fat cells by cortisol, the "beneficial" effects cortisol has on adipogenesis are nothing to be afraid of (Campbell. 2011). In the unfortunate case you are constantly stressed, overeating and chronically inflamed, however, the chronically elevated cortisol + insulin levels will however create a "perfect" obesogenic storm.

There is no conclusive evidence for the beneficial effects of OTC 11beta HSD inhibitors as fat loss adjuvants: Even in obese subjects and sponsored studies published in "author pays" journals such as Current Therapeutic Research, neither the body fat loss (p=0.41), nor the change in basal metabolic rate (p=0.86; not change in T3), or the fat free mass changes (p=0.39) were different between those subjects who dieted and exercised with a placebo and those who consumed a commercially available 7-keto supplement (Zenk. 2002). Against that background I was surprised when I was lectured earlier today by someone whose opinion I really respect that for him the use of the current #1 seller made a huge difference. How come? Well, if we also imply the results of the follow-up study by Zenk (Zenk. 2005), this time sponsored by iSatori where the multi-ingredient product Lean System 7 did prevent the drop in metabolic rate in obese (BMI ~33kg/m²) subjects, it would appear that the reason for the benefits are brought about by one or all of the additional ingredients, of whichcoleus forskohlii and piper nigrum are also part of the proprietary blend of the previously mentioned product. That the maintenance of a higher metabolic rate did yet not translate into increased fat loss and the subjects in the active arm actually los lean mass, while those in the placebo arm did not puts yet another question mark behind the "7-keto promotes body recomposition" hypothesis.

This storm is self-perpetuating as the chronically inflamed and ever growing visceral adipose organ, which contributes "approximately two-thirds [...] to splanchnic cortisol production in healthy men" (Andrew. 2005; the rest is produced in the liver), will spill out more and more cortisol. The cortisol, in turn will increase lipolysis and have the free fatty acid and triglyceride levels skyrocket. This, on the other hand, worsens the pre-existing insulin resistance, ... It's a vicious cycle and to my mind the only scenario where the interventional use of an 11beta-HSD reductase inhibitor like 7-keto & co could be a promising strategy.

If we do however take into account that the underlying cause of the pathological upregulation of the 11beta HSD reductase activity and cortisol production in the adipose organ is nothing but the well-known inflammation of the visceral fat stores that's not a consequence, but a in fact the cause of chronically elevated cortisol levels (Lee. 2013), it does not really seem to be prudent to manage the disease by targeting the well-meant (since anti-inflammatory) increase in cortisol. Any promising treatment (vs. management)strategy should thus aim at eliminating the underlying reasons of the inflammation, which are in 90% of the cases an obesogenic diet and a lack of exercise. And instead of supressing the downstream reaction to increased levels of TNF-alpha and its pro-inflammatory cousins with 11beta-HSD inhibitors, anti-inflammatory agents like curcumin, green tea and the like could be used to keep the inflammation while the underlying reasons are taken care of.

... cortisol also drives fat loss on a diet

I guess I don't have to remind you of the recently published SuppVersity article with the title "Scientific BB Contest Prep Coverage" (read more) and the skyrocketing cortisol levels of the subject in the pertinent study. What I guess may be worth mentioning again, though, is the fact that the impressive reduction of body fat to the sub-5% range did not take place despite, but at least in part due to this increase in our bodies' most powerful long-acting fat liberator (the catecholamines are the short-acting ones). A hormone, by the way, which supplied the body of the "starving" athlete with all the fats it needed to keep going in a situation the subject's body must have interpreted as a bad harvest that was accompanied by the disappearance of major parts of the local fauna. A situation which would have left our ancestors "looking for food" (=spending energy working out) all day, while still being rewarded with ~25% less than they would actually need to maintain their unaesthetic, but live-saving energy depots (=body fat).

So, if caloric deficit + diet + training + adequate protein + high natural cortisol = fat loss, you could suspect that using the synthetic glucocorticoids like hydrocortisone, prednisone & co should be a neat way to lose body fat, right? Now, as surprising as this may sound this is in fact exactly what Levon G. Babikian did observe back in the 1960s, when he was able to show that medium and high dosages of 0.12mg and 0.18mg hydrocortisone per day lead to significant increases (medium dose), respetively decreases (high dose) in total and visceral body fat of mature male albino mice (a low dose of 0.09mg of hydrocortisone did not have any effect). And with a -30% total and -40% reduction in visceral body fat mass (not percentage!) those changes were not just statistically, but also physiologically highly significant. After all, the rodents in the high dose arm did thus have 2.4% less body fat than those in the control group (7.4% body fat vs. 10%).

"So does that mean that an increase in cortisol will get you ripped?"

Even if it were not for all the other nasty side effects (high blood pressure, immune suppression, loss of potassium, etc.), a high dose of hydrocortisone certainly ain't the "weight loss adjuvant of choice" for physical culturists who do not have a weight class as a ceiling to his / her overall body mass. After all, the impressive figures from the Babikian cannot hide the fact that it's not all fat mass you'd lose - despite statistically significant improvement in body fat percentage.

What about testosterone? Contrary to a Sep. 2003 1-week trial by Armani et al., where 7g of licorice lead to significant reductions in total (but not free!) testosterone, a larger scale 4-week trial with 100g/day of licorice containing 0.15% glycyrrhizic acid could not find any significant changes in sex steroid hormones (Sigurjonsdottir. 2005)

Against that background, it is somewhat surprising that the consumption of the 3g/day of licorice, a purported testosterone antagonist (see figure) and proven inhibitor of the oxidase of cortisol to cortisone and potentiator of glucocorticoid function (Whorwood. 1993; Asl. 2008), for 4 weeks lead to a ~2% reduction in body fat in 15 normal-weight subjects (7 males, age 22-26 yr, and 8 females, age 21-26 yr) - and that in the absence of of prescribed or voluntary dietary restriction, exercise or overall weight loss (Armani. July 2003). Major side effect were not observed. The increase in extracellular water (5% in men and 1% in women) could yet obscure at least some of the beneficial effects, while you are actually "on" the glycyrrhizinic acid containing herb (whether the effects can be avoided if you keep an eye on adequate potassium intake has, afaik not been studied).

Promising fat loss results (2mm reduction in superficial tigh fat) have also been observed upon topical application of glycyrrhetinic acid, the main active ingredient in licorice, to the tighs of 18 healthy women (20-33 years) in a 2005 by the same Italian researchers. Still, despite the fact that this study used a glycyrrhetinic acid concentrate, we cannot exclude that part of the previously observed weight loss effects are brought about by non-cortisol amplifying components in licorice or the synergism of the latter with the inhibitory effects glycyrrhetinic acid exerts on the inactivation of cortisol.

Bottom line: As I already hinted at towards the end of the last paragraph on licorice, it's beneficial effects on fat loss, as statistical significant as they may be are about as dubious as the meager weight loss (not fat loss) effects in the sponsored 7-keto studies in obese individuals. Aside from the initial message that you probably won't whack your liver, if you use DHEA metabolites as cortisol blockers, the "bottom line" of the above treatise would be: In normalweight, healthy individuals, the use of agents DHEA metabolits to inhibit and skew the natural glucocorticoid metabolism for fat loss or body recomposition purposes is not supported by the currently available literature.

I did decide not to bore you with the issue of transient exercise induced cortisol and testosterone spikes in this article. If you want to learn more about that take a look at this, this (middle) and this (bottom) article. Without giving away too much in advance - this is another instance where the bad guy ain't necessarily as bad as you may have been told.

From a mechanistic perspective, it would even seem counter-indicated, especially in the context of low calorie and low carbohydrate diets, where the skyrocketing cortisol levels, the increase in lipolysis and the decrease in insulin release and sensitivity are actually necessary to maintain stable blood glucose levels by sparing the available glucose and providing enough fat as a substrate to fuel your daily energy demands. If this energy source ain't available any longer, the result is profound fatique (aka adrenal fatique) that will - regardless of all other metabolic effects certainly not help you shed body fat.

I don't want to exclude that certain individuals with whatever pre-existing cortisol issues can benefit from the use of these products, but as it was the case with Isatori's 7-keto product it is not unlikely that additional ingredients (for Lean System 7 these were yerba mate, guarana, citrus aurantium, coleus forskohlii, dandelion leaf, and piper nigrum) and/or the use of other supplements, as well as the concomitant diet and exercise programs people are following are responsible for the rave N=1 reviews some of these products get on the pertinent bulletin boards.

I mean, how will the authors of those reviews know they would not have seen the same effects without 7-keto and co. Everyone who is serious about improving his physique, will tell you that no two diets are the same and comparisons to previous diets are not necessarily objective. And finally, we don't want to forget the influence of sponsored logs, the "rep system" and the "brocebo effect" have on a trainees motivation (if you spend money, you want to make sure you made it right, after all it worked magically for X, Y & Z) and the perceived contribution the ingestion of a couple of pills had to his success, do we?

References:

Andrew R, Westerbacka J, Wahren J, Yki-Järvinen H, Walker BR. The contribution of visceral adipose tissue to splanchnic cortisol production in healthy humans. Diabetes. 2005 May;54(5):1364-70.
Andrews RC, Walker BR. Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci (Lond). 1999; 96:513–523
Arlettaz A, Portier H, Lecoq AM, Rieth N, De Ceaurriz J, Collomp K. Effects of short-term prednisolone intake during submaximal exercise. Med Sci Sports Exerc. 2007 Sep;39(9):1672-8.
Armanini D, De Palo CB, Mattarello MJ, Spinella P, Zaccaria M, Ermolao A, Palermo M, Fiore C, Sartorato P, Francini-Pesenti F, Karbowiak I. Effect of licorice on the reduction of body fat mass in healthy subjects. J Endocrinol Invest. 2003 Jul;26(7):646-50.
Armanini D, Bonanni G, Mattarello MJ, Fiore C, Sartorato P, Palermo M. Licorice consumption and serum testosterone in healthy man. Exp Clin Endocrinol Diabetes. 2003 Sep;111(6):341-3.
Armanini D, Nacamulli D, Francini-Pesenti F, Battagin G, Ragazzi E, Fiore C. Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application. Steroids. 2005 Jul;70(8):538-42. Epub 2005 Apr 12.
Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008 Jun;22(6):709-24. doi: 10.1002/ptr.2362. Review.
Babikian LG. Effect of Hydrocortisone, Corticosterone, and Cortisone on Visceral and Total Body Fat in Albino Mice Physiological Zoology. 1962; 35(4):314-322.
Lee JH, Gao Z, Ye J. Regulation of 11β-HSD1 Expression during Adipose Tissue Expansion by Hypoxia through Different Activities of NF-kB and HIF-1α. Am J Physiol Endocrinol Metab. 2013 Mar 19.
Kerstens MN, Riemens SC, Sluiter WJ, Pratt JJ, Wolthers BG, Dullaart RP. Lack of relationship between 11beta-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients. Clin Endocrinol (Oxf). 2000 Apr;52(4):403-11.
Sigurjonsdottir HA, Axelson M, Johannsson G, Manhem K, Nystrom E, Wallerstedt S. Liquorice in moderate doses does not affect sex steroid hormones of biological importance although the effect differs between the genders. Horm Res. 2006;65(2):106-10.
Whorwood CB, Sheppard MC, Stewart PM. Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology. 1993 Jun;132(6):2287-92.
Zenk, JL, Tami RH, Laurie JK, and Michael AK. The effect of 7-Keto Naturalean™ on weight loss: A randomized, double-blind, placebo-controlled trial. Current therapeutic research. 2002; 63(2): 263-272.
Zenk JL, Leikam SA, Kassen LJ, Kuskowski MA. Effect of lean system 7 on metabolic rate and body composition. Nutrition. 2005 Feb;21(2):179-85.
Zou X, Pellicoro A, Aucott R, Ramachandran P, Clarkson M, Webster1 SP, Iredale JP, Walker BR, Michailidou Z. 11βHSD1 deficiency increases susceptibility to liver fibrosis by activating hepatic stellate cells. Endocrine Abstracts. 2013; 31(P315)

Sarah Reinertsen (click here to visit her webpage) was the first female leg amputee to participate and complete the Ironman (in 15h) and I bet she does not need the recent study by Galy et al. to be reminded of the benefits... no, the necessity of cycling your exercise intensity.

In 2005 Sarah Reinertsen (image on the right) was the first female leg amputee to participate and complete the Ironman and honestly this would probably suffice as a figure of the week, but since this is a historic event, it does not necessarily qualify as the SuppVersity Figure of the Week.

A figure that does qualify is the -15.7% decrease in post-exercise alveolar-capillary membrane diffusing capacity the highly trained triathletes in a soon-to-be-published paper by Galy et al. experienced after a 6-week "deload" (low training volume, intensity and frequency) period. What's interesting, though, is that the control group who remained on the same high training volume, intensity and frequency conditioning program all athletes had followed for the previous 30-weeks showed a similar, but less pronounced decrease in this measure of the diffusing capacity of oxygen and carbon dioxide between the lungs and the blood (-9.3%; Galy. 2013). This goes to show you that avoiding periods of lighter training in fear of the potential negative effects on your performance is no solution (learn more about detraining & co)

Only fillets from "fish-fed catfish" are worth your money

(Faukner. 2013) -- Feeding fish fish oil yields the highest concentration of omega-3 fatty acids in filets. That's the very unspectacular result of a recent study by scientists from the Department of Aquaculture and Fisheries at the University of Arkansas at Pine Bluff. The main reason I still mention it is that feeding the catfish a diet that was "enhanced" with soybean oil, as it is common practice to increase the weight gain of the fish, yielded fillets with exactly zero DHA & EPA and a 3x lower total omega-3 to omega-6 ratio.

Total n-3 & n-6 PUFA content (in % of total fat in the filets) and long-chain PUFA content (in % of PUFA content) + tabular overview of the fatty acid composition of the fillets from catfish on standard diet or diets supplemented with 2% additional fat from soy oil (SO), soy oil enhanced with CLAs (CLA), an algal source of DHA
(Schizochytrium sp.) combined with soybean oil, and reﬁned fish oil (FO; Faukner. 2013)

Now you got to bear in mind that the latter figure includes the short-chain omega-3s which do not display the same health benefits as their long-chain cousins DHA & EPA. If we look strictly at these long-chains, the comparison would yield an n3/n-6 ratio that is at least 120x higher for the fish oil enriched diet (this is based on the assumption that the test had an accuracy of .01% n-3-LC-PUFA / % total fat)... ah, and in case you want CLA in your fish, you better make sure that it is part of the feed, 'cause fish quite obviously don't produce any of these omega-6 trans-fats in their tiny guts (soy-fed or not ;-).

High fat + low carb not the way to go after ischemic heart disease

(Liu. 2013) -- Despite the fact that the scientists from the University of Alabama at Birmingham obviously could not find human volunteers to participate in a controlled study into the effects of low carbohydrate (<10%) + high fat (60%; equal parts from milk fat, lard and vegetable oils) on the recovery of cardiac function after ischemia and reperfusion. The data the scientists gathered in a rodent study clearly suggests: High fat low carb diets are more than sub-optimal right after heart ischemic events.

Diet dependent expression of selected antioxidant enzymes and determinants of mitochondrial biogenesis on day 3 after heart ischemic events in overweight Sprague Dawley rats (Liu. 2013)

Compared to the obese rats in the control groups those being fat a high fat low carbohydrate diet (10%) after an experimentally induced ischemic episode of the heart (low blood / oxygen supply) showed increased ischemic myocardial injury and impaired recovery of function after reperfusion. Moroever, the low carb diet was associated with an attenuation of mitochondrial biogenesis and enhanced oxidative stress in the obese lab animals. And while it will still have to be seen, whether the same negative effects would occur in non-obese rodents, the majority of patients who are treated for ischemic heart disease have at least a couple of pounds too much on their waistline, so that "these findings may [in fact] have important implications for diet selection" (Liu. 2013) for the majority of patients with ischemic heart disease.

Addendum: Just a note on the "must be the omega-6 hypothesis" you are just pondering (a) the ratio of "bad" vegetable oils was as mentioned before 1/3 (the rest was lard and milk fat), (b) there is no chance you blame the observed effects on the "bad" omega-6s, alone, simply because they, or rather the long-chain n-6 PUFA arachidonic acid is a ligand to the PPAR-delta receptor and the latter is responsible for the health of the mitochondria in your heart including the mitochondrial DNA copy number (Wang. 2010)

Endocannabinoid modulation is a prerogative of moderate intensity exercise

Effect of treadmill running at different heart rates on the level of anandamide one of the major and best studied endocannabinoids (Raichlen. 2013)

(Raichlen. 2013) -. Despite all the advantages of high intensity interval training over classic moderate steady state cardio, the latter still yields surprisingly beneficial results especially in those trainees who still carry large amounts of body fat, are insulin resistant, inflamed or suffer from other metabolic derangements. In addition to that there is overwhelming evidence for the beneficial effects this type of exercise has on the psyche and overall cognitive health. A recent study from the School of Anthropology at the University of Arizona in Tucson suggests that this could be result of their ability to restore normal endocannaboid function and thus yield both physiological and psychological benefits (e.g restoration of the reward system, learn more; Glass. 1997).

Now this certainly doesn't mean that you should all of a sudden give up on high intensity exercise completely, after all Rakobowchuk et al. have just demonstrated that HIIT training (learn how it works) will not just improve your aerobic capacity, it will also decrease arterial stiffness and optimize heart rate dynamics (Rakobowchuk. 2013). The results of the Raichlen study should however remind you that working out is exactly like dieting. Training and eating too single-sided is at least sub-optimal in most cases even detrimental.

Huskies will prevail: Heavy sled towing is way more effective than light sled towing

(Kawamori. 2013) -- Huskies will prevail: Heavy sled towing is way more effective than the widely recommended light load sled towing, where the weight of the weight will slow you down by only 10%. That's the result of a recent study from the School of Exercise and Health Sciences at the Edith Cowan University in Joondalup, Western Australia.

Outline of the training protocol used in the study. The groups differed only in the weight that was used on the sled to elicit a slow down of 10% (light group) and 30% (heavy group), respectively. All subjects trained twice per week.

After training with a sled that decreased the velocity by 30% and would thus be three times to heavy (according to the prevalent notion that 10% was best) the 10 physically active men who had been allocated to the heavy (=30% slow down) group increased both their 5- and 10-m sprint time by 5.7 ± 5.7% and 5.0 ± 3.5%, respectively (P < 0.05). The 11 subjects in the light sled (=10% slow down) group, on the other had increased only their 10-m sprint time and this increase was 2% lower than the one observed after heavy sled towing.

That's it for today's installment of On Short Notice! I hope you are all enjoying the Easter weekend and that irrespective of whether this is or isn't a holiday in the the original sense for you, or not. And in case you ever feel the urgent desire to get up to speed with what's going on in the world of exercise, nutrition and supplementation science before the next SuppVersity post hits the Net, feel free to visit the SuppVersity Facebook wall.

References:

Faukner J, Rawles SD, Proctor A, Sink TD, Chen R, Philips H, Lochmann RT. The Effects of Diets Containing Standard Soybean Oil, Soybean Oil Enhanced with Conjugated Linoleic Acids, Menhaden Fish Oil, or an Algal Docosahexaenoic Acid Supplement on Channel Catfish Performance, Body Composition, Sensory Evaluation, and Storage Characteristics. North American Journal of Aquaculture. 2013; 75(2).
Galy O, Maimoun L, Coste O, Manetta J, Boussana A, Préfaut C, Hue O. 6 Weeks of Low Volume, Low Intensity Training Aggravate Pulmonary Diffusing Capacity in Highly Trained Athletes. Int J Sports Physiol Perform. 2013 Mar 26.
Glass M, Dragunow M, Faull RLM. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997; 10:1665–1669
Liu J, Lloyd SG. High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats. Nutrition Research. March 26, 2013 [Epub ahead of print].
Kawamori N, Newton RU, Hori N, Nosaka K. Effects of weighted sled towing with heavy versus light load on sprint acceleration ability. J Strength Cond Res. 2013 Mar 27.
Rakobowchuk M, Harris E, Taylor A, Cubbon RM, Birch KM. Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans. Eur J Appl Physiol. 2013 Apr;113(4):839-49.
Raichlen DA, Foster AD, Seillier A, Giuffrida A, Gerdeman GL. Exercise-induced endocannabinoid signaling is modulated by intensity. Eur J Appl Physiol. 2013 Apr;113(4):869-75.
Wang P, Liu J, Li Y, Wu S, Luo J, Yang H, Subbiah R, Chatham J, Zhelyabovska O, Yang Q. Peroxisome proliferator-activated receptor {delta} is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart. Circ Res. 2010 Mar 19;106(5):911-9.

Ultimate Post-Workout Testosterone Booze: Hard Liquor Increases Late PWO Testosterone Levels by Almost 100%

Understanding Muscle Hypertrophy - Study Sheds More Light on Process of Satellite Cell Recruitement: SRF, IL-6, STAT3, COX2, IL4 + More Funky Acronyms With Important Roles in the Structural Component of Muscle Growth.

Tongkat Ali - Malaysian Viagra W/ Anti-Belly Effect: More Than 30% Reduced Omental Fat Pad Size + Corresponding Increases in Testosterone W/ Human Equiv. of 4g+/Day

Optimal Carnosine Loading: Taking Beta Alanine With Food Renders the Cheap Bulk Stuff more Potent Than Fancy Time-Released Preparations. Preview: Science Round-Up: Daylight Saving, Stevia Toxicity, Protein Excess & More

Science Round-Up Seconds: Stevia, Cancer & Fertility. What is the Verdict? Exercise, Hunger & GLP-1. Can a Workout Fill You Up? Postactivation Potentiation & Personal Bests. 8% More Maximal Power After 5s Max. Voluntary Contraction?

Is stevia toxic, does it cause cancer and infertility?

Scheduled news that did not make it into the live show

Selenium & Skin Cancer. ALA, Inflammation & Muscular Adaptations. Eccentric Training & Oxidative Muscle Fibers. Tip of the Day: Have Plenty & Regular Sex For Your Brain

True or False? Caffeine is The Main Main Stroke Protectant in Tea & Coffee. High MCT Diets Are the Key to Longterm Fat Loss. Soybean Oil Makes You Fat not Heavy.

Caffeine (probably) is the main stroke protectant in coffee and tea

Eating tons of medium chain triglycerides (MCTs) will make you lean

Soy bean oil offers a shortcut to metabolic disease even in the absence of obesity

Carnitine as Repartitioning Agent? IGF-1, p-AKT & mTOR Up, Catabolic Proteins Down + 7% Improvement in Lean- to Total Mass Ratio W/ HED of 1-1.5 of Carnitine/Day

Predictive Value of Equations to Calculate Your Resting Metabolic Rate (RMR) Flawed: Results Can Be 14-29% Off

Does Creatine Blunt Fat Loss? A Recent Study Supports Long-Standing Suspicions, But What Are the Implications?

Greater Strength Without Compromised Size Gains With Rest-Pause. Can Dietary Variety Contribute Cause Obesity? Catabolism & Anabolism Just 2 Sides of the Same Coin. GABA as a GH Promoting Brain Anabolic?

Adelfo Cerame - Finally a PRO: How I Won My IFBB Pro Card. Plus: SHR Audio Interview & All the Details About Adelfo's Nutrition & Training Regimen Before the Show

My last hours as an amateur and how I finally won the pro card

Instant Coffee, Glycemia & Caffeine Powered Post-Workout Glycogen Repletion. Fish Oil, Arachidonic Acid Release & Prostaglandin Modulation. Adipocyte Sizes & Yoyo Dieting

Histidine As a Fat Loss Adjuvant? 6% Fat Loss Without Dietary or Exercise Intervention & More Than Half a Dozen Other Reasons Not To Ignore This Essential Amino Acid

Cardio & Strength Training in a Single Workout: "What Do I Do First?" Plus: Could the Answer Be Sex-Specific?

True or False? Adding Fat to A Carby Meal Lowers Insulin Response. Muscle Hypertrophy Impairs Oxygen Diffusion. Reducing Carb Intake Improve Muscular Insulin Sensitivity

Adding Fat to A Meal Will Ameliorate the Insulin Response

Skeletal Muscle Hypertrophy Impairs Oxygen Diffusion

Low Carb High Fat Diets Lead to Acute Improvements in Muscular Insulin Sensitivity

Motivation Trumps Supplementation! Moderate, Starvation Free Weight Loss With Carnitine & Motivational Support

Beta Alanine Thwarts Baking Soda: Increased HIIT Sprint Performance With NaCHO3 - "Very Likely". Individual Effect of Beta Alanine - "Zero". Synergism? Negative.

Science Round-Up Seconds: All About Cortisol, Fat Loss, Body Composition and the Efficacy & Safety of 7-Keto & Co

No DHA & EPA in Non-Fish Fed Catfish. No Recovery From Ischemia W/ Low Carb. No Endocannabinoid Effects Without Medium Intensity Exercise. No Need to Tow Only Light Sleds

Only fillets from "fish-fed catfish" are worth your money

High fat + low carb not the way to go after ischemic heart disease

Endocannabinoid modulation is a prerogative of moderate intensity exercise

Huskies will prevail: Heavy sled towing is way more effective than light sled towing