Science Round-Up Seconds: PGC-1 Alpha 4 Unlocks Muscle Growth, Alpha Lipoic Acid & Dietary N-6 Overload, Aspirin & Other NSAIDs Your Liver & Overall Mortality

Myotubes under the microscope - vehicle (top, normal size), clenbuterol (+100% protein content, middle), clenbuterol + PGC1a4 inhibition (+50% protein content, bottom)

Actually I would hope that you have by now already listened to yesterday's installment of the SuppVersity Science Round-Up. If you did, you are one of a group of highly privileged trainees who already knows why not all PGC1-alpha is created equal and how the alpha-4 isoform does appear to be the missing link between myostatin, on the one hand, and IGF-1 on the other. If you have already listened to the show, you may also have noticed that I was pretty excited about the publication of the Ruas paper (Ruas. 2013). Firstly this study has almost everything you could expect from cutting edge science: A in-vitro tudy to elucidate the basic mechanisms, an in-vivo rodent study involving both wild-type and genetically modified mice and - much to my own surprise - an in-vivo exercise part. And secondly, the results provides the missing link I personally have been looking for, when I wrote the Intermittent Thoughts on Building Muscle Series (click here for the summary and overview of the individual parts) - the link between IGF-1 and myostatin and the reason working out will always make you stronger and bigger and not bigger and weaker, as it is the case in the poor myostatin-knockout mice. Ah... I almost forgot: Third- and lastly, the fact that the researchers induced their hypertrophy effects in a specific part of their study by administering clenbuterol, which then did what I have likewise written about before (see "The Clenbuterol Myostatin Connection"), which is decreasing the expression of myostatin and thus producing skeletal muscle hypertrophy, yet as we now know not directly, but rather in consequence to its PGC-1 a4 promoting effects (+400%!) and the respective downstream effects on myostatin, which were non-existent, when the scentsts blocked PGC-1 a4 expresson (see images on the right)... 

I guess, you need to be somewhat geeky to find that exciting, but anyway. If you don't I'd still recommend you take a listen to the show - it's well worth it, even for totally normal exercise enthusiasts ;-)

And now for the actual seconds

Since the Ruas study appeared on my "radar" quasi in the last minute. We did not get to talk about several of the things I have announced and just to make sure you are not going to be disappointed, once you have gone through the following findings, I will address the acidity / alkalinity issue in a separate post in the future. It requires some more detailed elaborations - but the wait is going to be worth it ;-)

ALA rescues the liver from toxic N-6 overload

Actually this item would have fitted in pretty neatly with the things I explained about the different isoforms of PGC-1 alpha and how they appear to be regulated by diet / energy energy intake and expenditure via AMPK, on the one hand, and MAPKs, i.e. 'switches' that are triggered by stress, as the wear and tear of exercise, for example would be one. Now, we have already talked about the latter aspect, so that I guess I can get right to the not so novel, but still intriguing insights a  group of scientists from the Cerrahpaşa Medical Faculty Medical Biology Department at the Istanbul University  bring to the table as far as the former pathway is concerned (Kaya-Dagistanli. 2013).


In their 8-week experiment, Kaya-Dagistanli and her colleagues confirmed two things, of which I don't even know what would be the more important result:

Figure 1: Fibrosis and fatty degeneration scores in the control group (normal diet) and the high omega-6 group w/ and w/out ALA Kaya-Dagistanli. 2013)

1. The administration of a diet that contained 60% fat from safflower oil, 20% kcal carbohydrate and 20% kcal protein (51% of the fat from n-6, n-6:n-3 ratio of 15.4) did produce major changes not only in the GSH levels, a measure of the total antioxidant capacity in the livers of the 24 Wistar rats, the relatively short time span was even enough to increase the fibrosis and fatty degenration scores by ~10x (see figure 1) compared to the rodents on the low fat standard chow in the control group (only 12% fat total, 39.1% n-6, n-6 : n-3 ratio of 9.3).
2. The addition of 35 mg/kg DL-alpha lipoic acid (human equivalent: 5.7mg/kg; ~500mg/day) from week 4 to week 8 reduced both the negative effects of the omega-6 overload on GSH and the pathological degeneration of the liver, but could not fully restore it to normal levels.

Not just in view of the fact that ALA could not totally blunt the detrimental effects of the n-6 diet, but also in view of the fact that rodents on the regular diet did not see any benefits (remember: if you are not fat and metabolically deranged ALA ain't necessary, probably counterproductive; "Lean & Muscular W/ alpha lipoic acid?"), I personally gravitate towards (1), as far as the more significant finding is concerned. After all, it goes to show you that you simply have to the absolute (and relative?) amount of omega-6 fatty acids in your diets and can go without any such supplements as high dose fish oil and/or alpha lipoic acid. Bottom line: Don't bang your head against the wall and you won't need a helmet ;-)

NSAIDs liver cancer, chronic liver disease and other nasty ways to die

It's quite a happy coincidence that the December issue of the Journal of the National Cancer Institute held yet another intriguing study on the potentially beneficial health effects of the use of NSAIDs, which had been addressed in August already, when Jacobs et al. have gotten quite some public attention with their paper on aspirin use and the decrease in all-cause mortality (Jacobs. 2013). The novel paper that's based on prospective data on 300,504 men and women aged 50 to 71 years who had participated in National Institutes of Health-AARP Diet and Health Study and has been written by a group of scientist who actually work at the National Cancer Institute (Sahasrabuddhe . 2013), did not deal with a slightly different research question, i.e. does the use of aspirin and other NSAIDs offer protection against liver cancer (hepatocellular carcinoma) and death due to chronic liver disease, it also offers a slightly more sophisticated analysis of the (a) the frequency of NSAID use and potential interactions. Still, I decided to summarize the main findings of both, also in view of the fact that we are dealing  wih different cohorts (study subjects in the Jacobs paper were 100,139 men and women with no history of cancer in the Cancer Prevention Study II Nutrition Cohort).

Figure 2: Main results (hazard ratios) of two of the latest epidemiological studies into the effects of aspirin and other NSAIDs on liver cancer, death due to chronic liver disease (left) and aspirin alone on all cause mortality (right; data based on Sahasrabuddha. 2013 & Jacobs. 2013)

With the "demarcation lines" being present at 1.0 (meaning normalized risk) it is pretty easy to see that at least with respect to liver health and all-cause-mortality and solely based on epidemiological evidence, aspirin appears to be one of those "miracle drugs" everyone can benefit from. We have to be cautious however, when we compare everyone with ourselves, after all - and pretty much stands out of question - the protective effects of aspirin and the slightly less unambiguous and as far as hepatic cancer goes, even detrimental effects of other NSAIDs are mediated by...

• the modulation of inflammation via inhibition of the COX enzymatic pathways necessary for the synthesis of prostaglandins
• the ensuing decreases in epithelial proliferation and angiogenesis, as well as an
• increased apoptosis (regular cell death) and ameliorations in the inflammatory response and inflammatory cytokines via non-COX mediated pathways

Now, if you remember the previous study about ALA and how useful it can be if you are the kind of person who hammer his head... ah, I mean who still has not gotten the message that the formerly hailed omega-6 PUFAs from the "healthy corn and vegetable oils" are not a bit healthy, on the one hand, and how superfluous (if not detrimental) the same supplement is for someone who does not exhibit exuberant inflammation to begin with, this certainly does put the results into perspective.

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Apropos perspective, I am not quite sure how you like the perspective that this is it, for today, but I would be pleased if you took that as an incentive to come back tomorrow and check out the next installment of SuppVersity On Short Notice and for the time being, I still have a couple of facebook news, I am sure you will enjoy:

• Scientists from the UK and New Zealand do pretty damn good job pimping the sales of low fat products - learn what the press release does not tell you (read more)
• German scientists find: Bisphenol A clogs calcium channels - don't know if you'd agree with them that the good news is that it appears to be reversible (read more)
• Grazing is for fat cows, only  - women who want to be lean better eat like a human, i.e. three square meals not more that's it - this will also help with blood triglyceride management (read more) 
• more, much more ;-) 

Any you know, facebook is a fast media, so expect more news to be posted even before the official next SuppVersity article will hit the main site ;-)

References:

• Jacobs EJ, Newton CC, Gapstur SM, Thun MJ. Daily aspirin use and cancer mortality in a large US cohort. J Natl Cancer Inst. 2013 Aug 22;104(16):1208-17.
• Kaya-Dagistanli F, Tanriverdi G, Altinok A, Ozyazgan S, Ozturk M. The effects of alpha lipoic acid on liver cells damages and apoptosis induced by polyunsaturated fatty acids. Food Chem Toxicol. 2013 Nov 28.
• Ruas et al. APGC-1aI soform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy. Cell, December 7, 2013; 151:1319–1331. 
• Sahasrabuddhe VV, Gunja MZ, Graubard BI, Trabert B, Schwartz LM, Park Y, Hollenbeck AR, Freedman ND, McGlynn KA. Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma. J Natl Cancer Inst. 2013 Dec 5;104(23):1808-14.

Adelfo Cerame: Carbophobia a Thing of the Past - How a Love-and-Hate Affair Turned into a Productive Friendship

The very latest progress pictures from "Your's Truly"; Adelfo Cerame Jr. posted only a couple of hours ago on Facebook - I guess there is no doubt about the success he has with his old fiend and new friend - in "moderation" as he says ;-)

It's Thursday and about time for another update of "Your's Truly" Adelfo Cerame Jr. from the photo Adelfo posted on facebook earlier today (see image on the right), you can see already that he actually not approaching, but more or less already in contest shape, but before I hand the virtual microphone (actually I should type keyboard ;-) over to Adelfo, here is the brief primer on today's SuppVersity Science Round-Up on Super Human Radio.

As you should really know by now, you have three options (not listenting to it is not among them ;-)

1. listen live at 1PM EST,
2. download the show ~2h later either from the "Physical Culture for Your Ears" menu in the sidebar of the SuppVersity, or
3. download the podcast load it right over right over at www.superhumanradio.com

And just to make sure that you know that it will be well worth it, here's the sneak peak on the topics Carl Lanore and I have lined up for you, today:

• the real-world benefits of caloric restriction - what's that all about?
• intermittent fasting works - regardless of whether you do it w/ liquid or solid foods
• alpha lipoic acid (ALA) - still a potent supplement - but who benefits?
• the usual suspects - omega-3, omega-6 & vitamin D
• acidity, diabesity, muscularity and ... ahm, there is no "-ity" for chronic fatigue, I guess

As you should know by now, additional topics and things I mentioned that ended up not making it into the show due to time constraints will be part of tomorrow's SuppVersity Science Round-Up Seconds... that's it. Let's go Adelfo!

Fully and completely getting over my phobia of carbohydrates

It's plain to see and hard to deny: Me + Carbs a.k.a. Mrs. Jones = Got a Thang Goin’ On…

In light of some of the comments I’ve been getting on FB about my carbohydrate intake being very high, I thought it would be prudent to address the issue in my weekly blogpost. Firstly, this saves me hours of precious time, since I don't have to answer the same questions dozens of times, and secondly - my gut tells me I would have benefited, if someone had written a post like this in the past: an article that would have had me rethink my own nutritional regimen, which and this is something I want to point out before I even get into any details clearly isn't "high carb"! With 150-200g of carbohydrates and thus <800kcal of my daily energy intake from carbs this may be high for a "carbophob", as I've been one myself before, but it would still be considered "low carb" both, in the mainstream, as well as in the context of classic bodybuilding diets. Be that as it may, I personally feel a huge relief now that I have finally liberated myself from my personal fears of carbohydrates and have learned to embrace "carbs" in all its forms - my diet has become more flexible, I have a greater variety and - what's most important - I see nothing but benefits from it.

I’ll be the first to tell you that Mrs. Jones (I’ll refer to her as that because this is how I felt about carbs for a while) and I were not on the best terms. It was a 3-year love hate relationship. Just like cash, I thought she was the root of all evil. The first time I ever downloaded and read Dr. Mauro DiPasquale’s Anabolic Solution, I for sure thought I found the Holy Grail to dieting and bodybuilding (true story!), and that’s where my phobia and our tragic love-hate relationship actually began. I thought that I would be shredded year round if only I lived the low carb lifestyle. It worked for a while but then eventually the magic I thought I was experiencing, when I started out, didn’t work any longer. 

Even during my bulk I thought I would still manage to look ripped because I was on low carbs, but again I was wrong! Lol. But I still insisted that carbs were evil just because… honestly, I don't even know why!? Probably because for 2 years I had avoided my Mrs Jones like the plague and only devoured her on my refeeds, cheat days and special social events, which eventually turned into binge fests and late nights in my bed being in a fetal position because I would eat myself silly.

No, carbs just had to be bad,... otherwise I would have had to admit that I'd a mistake, yet not only once, but 365 days a year!

Suggested read: Adel's old post "Carbohydrate Shortage in Paleoland" The article explains pretty well why 150g CHO is something any not 100% sedentary diabetic can easily handle.

If you have a closer look at Not until last year did my opinion start to change towards carbohydrates. My relationship with Mr. Jones gradually improved ever since I started using Intermittent Fasting a la Leangains last year to prepare for my 2013 bodybuilding shows. But even then I still shied away from breads, oats, grains and even rice and just stuck to your typical sweet potatoes and yams. I guess you could say that she and I were at a truce, but not necessarily friends, like secret lovers we knew our boundaries and kept our distance… I stayed away for the majority of the week with the exception of 1-2 days of debauchery out of the week (refeeds).

During the last year, however, a revelation started to dawn on me. Finally, I began to understand the importance of carbohydrates, when it came to performance and the importance of performance, when it comes to making progress - regardless of whether we are talking, cutting, bulking or becoming stronger! More and more foods I had avoided or restricted, because I deemed them "bad" or "extremely detrimental" for my physique found their way back in my diet and not one of my fears about what would happen, when I consumed them more than maximally once per week materialized.

Me + Carbs = Best Friends

Though carbohydrates are not an essential nutrient like fats and amino acids; I’ve realized when it comes to performance and bringing in your best physique… carbs are necessary.

I really kept an open mind when approaching my 2013-2013 contest preparations. Just as I had an open mind with giving intermittent fasting a go last year for my prep, I’ve also had an open mind with giving IIFYM a try this year and combining the two, and needless to say I am very happy that I did. I thought that I enjoyed the perks of Intermittent fasting last year?... Well I’m really enjoying the perks of applying both IF & IIFYM this year! A

Admittedly, it certainly helped to have a coach I can trust. It gave me a lot of reassurance in keeping an open mind – especially when you’re still trying to grasp the fact that all foods are OK to eat in moderation - and yes this includes ice cream, beer and bacon (before some of you new readers out there go nuts and tell me how unhealthy my new protocol is, please refer to my last article and the follow up discussion, so you’ll understand what I’m taking about).

My Take Away: As I always say, balance, moderation & consistency are the keys to a long-term successful diet. Though carbohydrates and I are pals now, I still show the same amount of love to protein and fats as I did before; the only difference is that carbohydrates is treated as an equal now ;-)

Grass-Fed Pork? Not Really. Still the Difference in Fatty Acid Composition & Micronutrient Content Are Profound & Not Accounted for by Food Databases - Let Alone Epidemiology

You often hear that pigs are pretty closely related to us humans, but "are all pigs created equal"? Or what may be a more appropriate question for the SuppVersity: Is all pork really created equal?

If you like databases like nutritiondata.com or the USDA's very own detailed nutrient database in order to evaluate whether your diet is actually delivering all the nutrients you need you are probably missing half of the picture. At least as far as the more sophisticated details go, a recent paper from the Instituto de Ingeniería de Alimentos para el Desarrollo at the Universidad Politécnica de Valencia clearly indicates that you would at least have to consider what the animals, in this case pork, were fed and from which muscle of the animal the piece of meat you are eating has been cut, in order to get an approximate idea of how much of unquestionably health relevant micronutrients, such as coQ10, carnosine, anserine, taurine, creatine glutamine or haem you get - and in some cases the differences can be way larger than 100%!

If pizza salami equals pork...

... in epidemiological studies, how can these studies on the fallacies and advantages of eating red meat, which usually get a hell lo of media attention, be accurate, given the fact that the amount of unquestionably beneficial coQ10, for example, would differ by 60 percent, even if you would only ignore the difference between loin that was cut from the trapezius (= high coQ10 content) and the longissimus dorsi (=low coQ10 content)?

Figure 1: Content of selected amino acids and micronutrients in cuts from different muscle; data expressed relative to respective mean (total value is given in mg/100g above the bars) of all tested muscle samples (data based on previous studies by the co-authors that have been compiled for Reig. 2013).

Moreover, if you take a look at the complete data in figure 1 it should be clear that coQ10 is only one of several micro-nutrients / amino acids that are highly dependent on which muscle your particular steak or whatever you are about to eat was cut from. Let's take taurine as yet another example. A prolonged low dietary intake of taurine has been observed to be linked to a number of disorders including retinal degeneration, retardation of growth and development, cardiovascular dysfunctions, CNS abnormalities, immune impairment and hepatic disorders (Abebe. 2011). If you eat meat (fish & other animal products) only occasionally and are therefore at risk of not getting adequate taurine in your diet, eating sausages from a butcher you trust would be a better choice than a piece of ham, since the former do include the high taurine meat from the masseter (cheeks) of the animals, while ham does not.

Let's get to the obvious: Grass-fed is... ah, wait a minute

"Grass fed is best" as you will people say about beef obviously won't be the case for pork, because pigs, just like humans, by the way, are omnivores. The simple formula, grass-fed = most beneficial fatty acid and micronutrient profile that may (in general) be valid for beef doesn't apply and we will have to take a closer look at the actual data first to decide what would be the "best" feed for pigs, if the goal was not a maximal yield of lean meat (in that case adding some clenbuterol, like the Chinese like to do it would be the least you should do; cf. The China Post. 2011), but rather to produce the meat with the most beneficial fatty acid  composition.

Figure 2: Fatty acid composition (primary axis) and omega-6 to omega-3 ratio of pork from pigs fed different diets (corrected version of data Reig et al. re-pupublished based on previous studies; spec. the figure for the n6:n3 ratio in the "standard feed" group that's based on Enser et al. was off - a ratio of 1.54 is obviously unrealistic)

I we define "most healthy" as having the lowest omega-6 to omega-3 ratio - a practice that seems appropriate given that 95% of the inhabitants of the so-called 'Westernized World' consumes way too much of the former and (comparably) way too little of the latter type of polyunsaturated fatty acids, the data in figure 2 clearly argues in favor of *surprise* the standard feed - at least if you define that by the feed the animals the meat of which (50 samples) Enser et al. bought in British supermarkets in 1996 (note: these values are still higher than for the conventional beef samples from the same study, which had a n-6:n-3 ratio of ~2.2; cf. Enser. 1996). There are however more intricate patterns that are not evident from the overview in figure 2, but could have implications as far as the direction into which "pork production" could or should head to in the future is concerned (summarized based on Reig. 2013):

Do you notice a pattern? I guess even based on the data in figure 2 you will already have noticed that the "grainier" the diet, or in other words, the more corn and soy there is in the diet of the swine the less favorable is the fatty acid composition of their meats going to be. Now, I am asking an outrageous question: If swine are such a good model for human metabolism, what do you believe your belly was going to be made of, if you copied the pigs' diets and lived on "healthy grains", their oils and the uber-healthy soy beans for the (probably pretty short) rest of your life?
• more food (yet no excess) can produce overall leaner muscle meat in the type II fibers, while the total body fat is increasing
• aside from local desaturation and elongination effects, the overall muscular fatty acid pattern does (much like in humans, by the way) mirror the dietary intake
• canola or linseed oils produce a substantial increase in the content of linolenic acid (C 18:3), and slightly increase the eicosapentaenoic (EPA, C 22:5) and docosahexaenoic (DHA, C 22:6) acid contents in pork mea
• soy, peanut, corn, and sunflower increase the content of linoleic acid (C 18:2; omega-6), increase the n-6:n-3 ratio and reduce the content of mono-unsaturated fats (MUFAs)
• fish oils or algae added to the feed substantially increases the content of EPA and DHA and thus reduce the n-6:n-3 ratio
• a high saturated fat content as in tallow (see figure 2) increases the levels of palmitic, palmitoleic, stearic and oleic acids in pork meat and reduces the PUFA:SFA ratio 
• CLA supplementation can increase the CLA content of the fatty portion of the meats (1% CLA results in 5.5 mg CLA/100g) and the adipose tissue (2% CLA yields 1,490mg CLA/100g fatty acids).

As you can see, the same rule applies for humans, pigs and, as you know from a previous SuppVersity post, mice who are fed inferior, since soy-fed salmon, as well: You are what you eat, folks!

Wallowing, roaming, routing: Work out like a pig

Since pigs make a pretty decent model of human metabolism and in view of the fact that - aside from our diets - the amount of exercise we get is one of the fundamental determinants of the total and relative levels of body fat, it should not be forgotten that "exercise" or rather the ability to range freely and be as active as any swine should be, is another determinant of the quality of the meat you are buying at the supermarket, grocery store, butcher or your local farmer. In this context, Reig et al. point out that

If you have no idea of the different cuts and location of the individual muscle, I suggest you download the "Meat Cuts Manual" from the website of the Canadian Food Agency. It's free and bilingual.

"[i]t has been reported that pigs maintained in free-range conditions in the Mediterranean forest had subcutaneous and intramuscular fats with higher monounsaturated fatty acids and lower saturated fatty acids than those pigs housed individually and receiving acorns as feed. The subcutaneous fat depth increases with exercise being 15.9 mm for exercised pigs in comparison to 11.5 mm depth for those kept in confinement. The same applies for the intramuscular fat content where 3.36% for extensive vs 1.44% for intensive raised pigs have been reported in the semimembranosus muscle." (Reig. 2013)

And if you really intend to overcomplicate things, you would also have to ask your butcher, whether the sausages you are about to buy were made of the meat of male of female pigs. After all, meat from barrows typically contain more fat and marbling and a thicker subcutaneous fat layer than meat from gilts (Armero. 1999). But let's face it: If you start stressing about things like this, the quality of your meat is probably your least problem.

If you want to know read more about epidemiological overgeneralization andthe effects of "pork" and red meat on your health (spec. the prostate) I suggest you go back to the Meat-Ology post.

So what's the bottom line, then: I guess the bottom line of the above insides is twofold. As far as you as an individual are concerned, it would be yet another argument for getting your meats (pork or whatever else) from a farm nearby, where you know what you are getting. It is yet also evidence of the fact that meticulous nutrient counting as I often see it in former calorie counters who have nor grasped the notion that "a calorie is not a calorie" is of little avail - at least if you expect to be able to calculate them as precisely as you can read them on the nutrition labels of the 90% artificial and 100% standardized convenient foods that's probably much more the answer to the question "Why are we fat?" than the non-descript statement "insulin".

In fact, the real significance of these results lies elsewhere. It concerns the way epidemiological studies are conducted (I may remind you of the metaphorical pizza salami being red meat or pork), their over-generalizing interpretations and the conclusions on what the optimal human diet should look like. So, once the next study is telling you "red meat" or "pork" is bad for you - you may want to remind yourself of some of the things you have learned in today's blogpost and ask yourself (and if you incidentally have the chance, the researchers as well): What kind of "pork" are we talking about?

References:

• Abebe W, Mozaffari MS. Role of taurine in the vasculature: an overview of experimental and human studies. Am J Cardiovasc Dis. 2011;1(3):293-311.
• Armero E,  Flores M,  Toldrá F,  Barbosa JA,  Olivet J,  Pla M,  Baselga M.Effects of pig sire types and sex on carcass traits, meat quality and sensory quality of dry-cured ham.  Journal of the  Science of  Food  and  Agriculture. 1999; 79:1147-1154.
• Enser M, Hallett K, Hewitt B, Fursey GA, Wood JD. Fatty acid content and composition of english beef, lamb and pork at retail. Meat Sci. 1996 Apr;42(4):443-56.
• Reig M, Aristoy MC, Toldra.Variability in the contents of pork meat nutrients and how it may affect food composition databases. Food Chemistry. 2013 [ahead of print]
• The China Post. Clenbuterol-tainted pork latest China food scandal. March 18, 2011. < http://www.chinapost.com.tw/china/national-news/2011/03/18/295146/Clenbuterol-tainted-pork.htm > retrieved Dec 06, 2013.

Chromium Picolinate Worsens Insulin Sensitivity in Healthy, Non-Diabetic, Non-Obese Individuals by Up to 25%

The more supplements you take the more likely you are to get way more than the 200mcg of chromium of which previous studies have shown that they are useless for healthy people, but at least not detrimental (cf. Lukaski 1996 & 2007; Vincent. 2007). Especially people who like the  'poly-supplementary' approach are yet at risk of getting so much of a this trace mineral that it will hamper not improve their insulin sensitivity.

I don't have to tell you that you would already be dead if you were following all the bro-scientific advice that's out there on the Internet and still I usually recognize a certain reluctance to give up on what X suggests and Y has tried an what has worked so well for Z. One of the instances, where I have hitherto been missing a 100% convincing argument to argue that this is just another instance where common wisdom would in fact be better called "common stupidity" is the "insulin mimetic" or "insulin sensitizer" (or whatever your favorite bro-expert may call it) chromium picolinate. With the recent publication of the result of a study on the effects of chromium supplementation in healthy individuals there is now finally a human study that confirms that chromium, which has never been an "insulin sensitizer", but rather an "insulin release amplifier" that reduced blood glucose in diabetics by simply having them produce even more insulin is not a supplement any healthy man or woman, let alone athlete should consider a staple of his or her regimen.

The long and short: Chromium hampers insulin sensitivity in normoglycemic individuals

For their experiment lead author Umesh Masharani and his colleagues from the UCSA recruited a group of 27 non-obese, non-diabetic, healthy subjects between the ages of 20 and 50 with a body mass index of less than 27 kg/m² and <24 kg/m² for subjects with Asian heritage (the cut-off limits were set so that they would be below a BMI that has not yet been shown to be an independent risk factor for insulin resistance; cf. Clausen. 1996; Newell-Morris. 1998).

To evaluate whether chromium picolinate (ChrPic) supplements, which contributed with $150,000,000 to the revenue of the supplement industry in 1996 (Nielsen. 1996), could come up to the claims that they would exert beneficial effects on glucose tolerance and insulin sensitivity, the study participants were randomized to take either a placebo or a high dose 500µg CrPic supplement twice daily for 4 months (the dosage was selected in view of previews studies reporting greater benefits of 1,000 vs. 200mcg of CrPic in - you already guessed it - diabetic subjects; cf. Morris. 2000).

Figure 1: Insulin sensitivity measured by euglycemic clamp before and after the 16 week intervention (left); change in insulin sensitivity of the individual subjects plotted against serum chromium levels at the end of the study (Masharani. 2013)

As the data in figure 1 goes to show, the results of the CrPic intervention were more or less the exact opposite of what the ~10 million US consumers of respective supplements probably expect from the pills many of them are taking almost religiously. Despite the fact that all subjects had very low chromium levels at the beginning of the study, the previously non-significant minimally benificial relation between both serum and urinary chromium, on the one hand, and insulin sensitivity (r = 0.24, p=0.1; r=0.08, p=0.79 respectively), on the other hand, had turned into a very significant negative correlation between high(er) urinary and serum chromium concentrations and lower insulin sensitivity at the end of the 16 week intervention period (figure 1, right).

"Due to the apparent variation in the degree of chromium absorption between subjects, we examined the relationship between serum chromium and change in insulin resistance. After controlling for baseline patient characteristics, results of a multiple regression analysis showed a strong association between serum chromium and worsening of insulin–mediated glucose disposal (β= -0.83, p<0.01), where subjects with the highest serum chromium had a decline in their insulin sensitivity. To further explore the association between chromium absorption and insulin resistance, patients within the chromium group were divided (based on  a medial split at 3.10 µg/L) into a high (n=6) and low (n=8) serum chromium group [...] There were no group differences at baseline; however, at post-assessment participants in the high serum chromium group (> 3.1  µg/L) were more insulin resistant than participants in the low serum chromium group (≤3.1  µg/L) or the placebo group (p=0.02, p=0.05 respectively) (Figure 3)." (my emphases in Masharani. 2013)

Due to the fact that the scientists did not observe any differences between the placebo and low serum  chromium groups (on a side note, contrary to many other studies insulin Masharani et al. measured the insulin sensitivity in a very reliable way with an euglycemic hyperinsulinemic clamp; cf. Defronzo. 1979), the scientists also conducted a post-hoc analysis to identify potential confounding factors that may have influenced the outcome of the trial. Neither changes in triglycerides levels LDL, BMI, or truncal fat were yet associated with the differences they observed between the supplemented and non-supplemented participants. Interactions that would reduce the significance of the observed correlations were likewise absent:

"Furthermore, when changes in triglycerides, LDL, BMI, and truncal fat were individually added to the model, none were independent significant predictors of change in insulin sensitivity, and chromium absorption remained a significant predictor of reduced insulin sensitivity in each model." (Masharani. 2013)

Against that background the scientists conclude that there must be a "direct effect of chromium on changes in insulin action". A mechanism, by the way, which is totally independent of classic markers of insulin resistance such as high serum lipids and abdominal / truncal adiposity .

Being healthy is a good predictor of increased chromium absorption and more pronounced negative effects, so if you are healthy and want to stay this way don't even think of taking high dose chromium supplements.

Despite the fact that the changes in insulin resistance did not depend on changes in serum lipids and other markers of metabolic health, Masharani and his colleagues were able to show that the increase in chromium levels in response to supplementation did. With the already mentioned statistically significant correlation between increases in serum chromium levels (higher response to supplementation = higher increase), on the one hand, and the worsening of insulin sensitivity, on the other hand, this means that the healthiest subjects, namely ...

"[...] subjects with lower triglycerides, and those with lower levels of homocysteine [who had] a greater likelihood of being in the high absorption group" (Masharani. 2013)

... were at the same time those who were at the greatest risk of the ill side-effects high dose chromium supplements exert on the insulin tolerance of healthy, non-diabetic, normal-weight individuals.

No matter if it may have helped you produce insulin back in your obese days, once you have accomplished this you better avoid high dose or multiple (hidden) sources of supplemental chromium like a plague - unless you can't afford new jeans, of course ;-)

Bottom line: Unless you are not a type II diabetic or feel the urgent desire to become one, you better steer clear of exuberant amounts of supplemental chromium the RDA is enough. This is particularly true, if you are already taking a multi (which is almost guaranteed to have 200mcg in it), or any BB-style supplements. After all, "broscience" wants it that chromium is in everything that's even remotely related to insulin / nutrient uptake or whatever. With the use of only one of these products and 200mcg of supplemental dietary chromium per day, you may still argue that it probably won't do much harm. When you add another 200mcg from your "nutrient partitioner" on top of the 200mcg you get from your multi and the 200mcg of which you probably did not even realize yet that they are part of your pre-workout supplement, however, you can hardly complain about simply not being able to tolerate carbohydrates - I mean, what's your body supposed to do if you are dumb enough to believe in the promises of fat loss and lean mass increases that have been debunked in the late 1990s, already (cf. Lukaski 1996 & 2007; Vincent. 2007), and simply chose to ignore the latest scientific evidence that chromium picolinate supplements are not just useless, but actually detrimental to your health?


References:

• Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, Pedersen O. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of  the impact of gender, body fat, physical fitness, and life-style factors.  J Clin Invest. 1996;  98(5):1195– 1209.
• Defronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–E223. 
• Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr. 1996 Jun;63(6):954-65.
• Lukaski HC, Siders WA, Penland JG.  Chromium picolinate supplementation in women: effects on body weight, composition, and iron status. Nutrition. 2007; 23(3):187– 195.
• Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2013 Nov 30;12(1):31.
• Morris BW, Kouta S, Robinson R, MacNeil S, Heller S. Chromium supplementation improves insulin resistance in patients with Type 2 diabetes mellitus.  DiabetMed. 2000; 17(9):684–685.
• Newell-Morris LL, Treder RP, Shuman WP, Fujimoto WY. Fatness, fat distribution, and glucose tolerance in second-generation Japanese-American (Nisei) men. Am J Clin Nutr. 1989; 50(1):9–18.
• Nielsen FH. Controversial Chromium: Does the superstar minearal of the mountebanks receive appropriate attention from clinicians and nutritionists?  Nutr Today. 1996; 31(6):226–233.
• Vincent JB: The nutritional biochemistry of chromium (III). Amsterdam, Boston: Elsevier. 2007.

Docosahexaenoic Acid (DHA) Blunts Negative Side Effects of Conjugated Linoleic Acid (CLA) W/out Hampering Its Effects on Body Fat Loss & the Expression of Obesity Genes

She already knew what scientists have recently discovered and now confirmed: You better stack CLA and DHA if you want lean and health offspring ;-)

Conjugated linoleic acid (CLA) is not only an omega-6 fatty acid, it's also a trans-fat (though a natural one) and still even scientists believe that it could contribute to the solution of the diabesity epidemic, if it (a) finally yielded the same extreme fat loss (yep, just the blubber, nothing else) results in human beings as in rodents (cf. "CLA Annihilates Body Fat and Increases Endurance") and (b) anywhere near appropriate doses would not hold he risk of inducing fatty liver disease and insulin resistance (Clément. 2002). At least with respect to (b) a "bodybuilding approach" to CLA supplementation which is based on the "if hammering your head against the wall hurts, you better make sure you wear a helmet" principle of stacking CLA and PUFAs, esp. the long-chain omega-3 fatty acid DHA, has already yielded some promising results in a study that has been published earlier this year (Fedor. 2013a).

Since, the deposition of fat in the liver in response to CLA supplementation is in the end only the logical consequence of CLA's lipolytic (=fat releasing) and anti-lipogenic (=inhibition of fat storage) effects in the adipose tissue, the absence of adequate data on the amount of fat in adipose tissue and muscle or the fatty acid composition of liver, adipose tissue, and muscle, nor did we monitor the changes in the expression of genes involved in fatty acid metabolism in adipose tissue and muscle in the respective study did not allow for the conclusion that the co-supplementation of DHA would not blunt the beneficial fat loss effects of CLA, as well.

Is it possible that high dose DHA blunts the negative and the positive effects of CLA?

In a paper that's going to be published in the next issue of Metabolic Syndrome And Related Disorders Dawn M. Fedor et al. describe the results of a follow up study, which dealt with this very question and I guess I am not giving away more than what you will already inferred from the headline of this post, when I tell you that the answer to the question in the subheading is "No, DHA does not blunt the beneficial effects of conjugated linoleic acid on adipose tissue!"

Figure 1: Relative body weight, liver weight, periuterine fat mass, muscle weigh, liver total lipid weight, adipose total lipid weight, and muscle total lipid content of the mice after 4 weeks on a 0.5% CLA, 0.5% CLA + 1.5% DHA or 1.5% DHA diets expressed relative to respective data from mice on the standard chow (Fedor. 2013b)

If you take a closer look at the data in figure 1 you will realize that the provision of a diet that contained 0.5% CLA (only the "active", but potentially hazardous t10, c12 isomer was used in the study) and 1.5% DHA did not blunt the beneficial effects on total and periuterine body fat mass in eight-week-old, pathogen-free female C57BL/6N mice. On the other hand, it did mitigate the negative effects on liver weight and (and this is actually quite remarkable) had identical beneficial effects on liver fat as the DHA only diet.

DHA + CLA = perfect synergists

Although the "equation" above may sound as if I had taken it right from one of those shiny adds in a muscle mags, it does in fact look, as if the combination of CLA + DHA was the silver bullet for healthy body fat (and I repeat only body fat not lean mass!) reductions in the absence of any dietary and/or exercise interventions.

Figure 2: Expression of selected genes involved in the synthesis, storage and release of fatty acids from the adipose tissue; the respective values (in a.u.) of the control group were all 100, so you can thing of these as percentages, as well (Fedor. 2013)

Moreover, the analyses of the expression of pro- and anti-obesity genes in the adipose tissue does actually support this claim:

"CLA significantly decreased the expression of LXRb, PGC1a, PPARg, SREBP1C, ACOX1, and CD36 adipose mRNA when compared to the control group. We also observed a trend for CLA to decrease the expression of HSL (P=0.08). DHA was not able to prevent any of these decreases in gene expression. CLA significantly increased UCP2 mRNA expression when compared to control group; DHA again had no effect." (Fedor. 2013b)

If we translate all these acronyms the scientists use to describe the data I've plotted for you in figure 2 into plain cause and effect relations, we could simply state: CLA induced changes in the expression of genes in the adipose tissue of the rodents that would prevent the maturation of adipocytes and the synthesis and accumulation of fatty acids, while increasing their release into circulation,  and DHA did not effect these changes.

DHA takes care of the energy that's released / not stored in fat cells

What the co-administration of DHA did, however, was to prevent the deposition of the energy that was released, respectively not even stored in the adipocytes in the liver -- and it did that so effectively that the overall weight of the liver of the mice in the CLA + DHA group was not greater than the the liver weight of the rodents in the control group.

Figure 3: Liver fatty acid composition (µmol/g) and omega-3 : omega-6 ratio after 4 weeks on regular (control), 0.5% CLA, 0.5% CLA + 1.5% DHA and 1.5% DHA diets (Fedor. 2013b)

In fact, the co-administration of conjugated linoleic acid and DHA did even reduce the total fatty acid content of the liver (not to a statistically significant degree, though) and brought about profound changes in its fatty acid content - most prominently, a whopping +975% increase in the omega-3 : omega-6 ratio (see small graph in figure 3) that were even slightly more pronounced in the CLA + DHA group than in the DHA only group (you do remember that CLA is an omega-6 trans-fat, right?).

Finally a stack that works -- but will it work in humans, as well? 

I don't know if it dawned on you, already, but dairy and butter from grass cows already has both CLA and DHA in it - what a lucky coincidence, isn't it? Still, there is one downside: You simply cannot eat enough of it to get anywhere close to the human equivalents of the amounts that are used in rodent studies.

Now, although both the changes in body fat levels in the CLA + DHA group were consistent with those observed in the CLA only group and the effects of the combination treatment on the changes in hepatic fatty acid composition were consistent with those observed in the DHA only group, there is still one question we have to answer: Are we going to see similar esults in humans?

To be honest, I still cannot answer this question, but if you take into consideration that no previous human trial used dosages in the 20-30g range simply because that would be unethical given the associated side effects, we may soon get an answer to this question - as soon as scientists dare to slowly escalate the dosage, trusting on the ability of supplemental DHA to blunt the negative, while conserving the beneficial effects of CLA.


References:

• Clément L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S, Staels B, Besnard P. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J Lipid Res. 2002 Sep;43(9):1400-9.
• Fedor DM, Adkins Y, Mackey BE, et al. Docosahexaenoic Acid prevents trans-10, cis-12-conjugated linoleic Acid-induced nonalcoholic Fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation.Metab Syndr Relat Disord. 2013a;10:175–180
• Fedor DM, Adkins Y, Newman JW, Mackey BE, Kelley DS. The Effect of Docosahexaenoic Acid on t10, c12-Conjugated Linoleic Acid-Induced Changes in Fatty Acid Composition of Mouse Liver, Adipose, and Muscle. Metab Syndr Relat Disord. 2013b Nov 21.

The Counterintuitive Catabolic & Pro-Diabetic Effects of Leucine Supplementation in Rodents on Corticosteroids

Not the mice from this study, but still a nice example of the effects of dexamethasone on skeletal muscle (right; Quin. 2013)

"Leucine-laced water + stress = insulin resistance" - This simple equation is the net result of a recent study by Nelo Eidy Zanchi and his colleagues from the Laboratory of Applied Nutrition and Metabolism at the School of Physical Education and Sports of the University of Sao Paulo in Brazil. Inspired by previous research which clearly indicated that leucine does not only have pro-anabolic, but also insulin sensitizing effects, Zanchi et al. speculated that the provision of adequate amounts of leucine would blunt the catabolic and pro-diabetic effects of 7 days of intraperitoneally injections of  dexamethasone, an artificial corticosteroid that's used to treat all sorts of inflammatory diseases.

Remember SuppVersity Rule of Smart Supplementation No. 2? Right. Specificity!

In order to test their hypothesis that leucine supplementation either in low doses in the drinking water or as higher dosed oral gavage would ameliorate the negative side effects of DEXA treatment, the scientists randomized groups of 10 male Wistar rats to six groups receiving either low dose or high dose leucine supplements with and without dexmethasone.

"During  the duration of the experiment, which lasted  seven  days,  DEXA (a synthetic glucocorticoid analogue that does not bind to plasma binding proteins) was given daily (at 9:00 a.m.) through intraperitoneal injection (5 mg/kg/day); control groups received  an equivalent volume of saline (0.9% NaCl). As DEXA was reported to decrease food intake, all groups were  fed the same amount of food (in terms of caloric intake) equal to the DEX group. Thus, differences among groups did not originate from different food intakes. We measured the caloric content of our standard chow (16.32 kJ/g) as well as leucine (25 kJ/g) in a calorimetric bomb (FTT Oxygen Bomb Calorimeter) in  order to avoid differences in the caloric ingestion between experimental groups and observed that the total caloric consumption was not statistically different among groups." (Zanchi. 2013)

The leucine was administered either in dosages of 0.068g/kg body weight per day (low dose) or 1.35 g/kg per day (high-dose) twice daily at 8:00  a.m. and  2:00  p.m. through gavage over seven days. And while the scientists had selected the high dose (LH) "to induce a maximal increase in muscle protein synthesis and insulin plasmatic levels", the dosage in the LL (=low leucine) group was too low to increase either muscle protein synthesis or plasma insulin levels. The third, non-supplemented control group received an NaCl (sodium) placebo, the volume of which was identical to the supplement to make sure that any possible volume-induced effects of oral gavage that could for example be induced by gastric expansion would not skew the study results.

"But leucine has been shown to be anabolic! So it must help."

Aside from the usual basal fasting glucose, insulin, tryacilglycerol (TAG) and HOMA-IR values, the scientists did also assess the motor performance of the animals by the means of two standardized strength and ambulation tests (Kennel. 1996; Anderson. 2004; Viera. 2008).

Figure 1: Effect of 7 days of low (LL) and high (LH) dose leucine supplementation with and with out dexamethasone on total body mass, soleus (slow twitch) and EDL (fast twitch) muscle mass in male Wistar rats (left; values expressed relative to non-supplemented control) and corresponding changes in mean ambulation and grip strength (right; Zanchi. 2013)

As you can see in figure 1 the supplemental leucine failed to reduce the negative side effects of dexamethasone. As far as the total body weight and the fast-twitch muscle mass (EDL) are concerned, you could even argue that the high dose treatment (DEX-LH) did even amplify the catabolic effects of the synthetic corticosteroid:

"Thus, leucine supplementation at both low and high doses did not counteract body weight loss in both food restricted (control groups) and DEXA-treated animals. Soleus muscle mass did not differ among groups. Leucine supplementation at  high doses  attenuated food  restriction-induced EDL muscle loss (CON-LH group) when compared with the CON-NS group  (p < 0.05). All DEXA-treated animals presented reduced EDL muscle mass when compared with the CON-NS group (p < 0.05), and leucine supplementation at both low and high doses of amino acid did not attenuate it." (Zanchi. 2013)

Now, you may well argue that the mere fact that the muscle weight was "statistically significant" reduced, this does not mean that these reductions would be physiologically significant and that the minimal differences between the DEX groups would not matter, anyway. If you just go by the data on the left side of figure 1, this is certainly right, if you do yet also consider the significant reductions in muscle function (figure 1, right) and the fact that all that happened within no more than 7 days, the overall result should actually remind you of the "Three Simple Rules of Smart Supplementation" - and here specifically the 2nd one: Specificity!

Figure 2: Time course of the dexamethasone-induced detoriations in fed serum glucose levels and ameliorative effect of low and high dose leucine supplementation (left) and effects of the treatment on fasting insulin levels and HOMA-IR (index of insulin resistance) at the end of the study (Zanchi. 2013)

In fact, the data in figure 2 only confirms the notion that things that you cannot define "good and bad", "black and white" and "beneficial or detrimental" without a context and the outcome you are expecting. If you are trying to keep the postprandial blood sugar in check, for example he addition of an effective (high dose) of leucine to the diet would appear to be a good idea. If, on the other hand, you are more concerned about insulin resistance, you would be better advised to use minimal amounts of leucine or simply refrain from supplementation altogether.

Figure 3: If the ingestion of bolus amounts of leucine is not helpful, lacing the water of the rodents DEXA treated rodents with leucine turned them into full-blown diabetics (Zanchi. 2013)

As these results clearly demonstrate the provision of additional leucine is not useful to counter the negative side-effects of synthetic corticosteroids. On the contrary, the negative effects on insulin resistance are apparently even augmented and the muscle function is further compromised by the purpotedly anabolic high dose leucine supplement.

And while the overall effects of the bolus administration may still be negligible, the scientists ingenious idea that the provision of similar amounts of leucine in the drinking water in a second follow-up experiment turned out to be "capable of inducing a massive diabetic state" (Zanchi. 2013; see figure 3 for the ensuing surge in fasting blood glucose levels) while decreasing the mass of the fast-twich EDL muscles even further.

Bottom line: Overall these results only confirm the simple, but often neglected truth that inductive reasoning is a futile undertaking in the realms of exercise and nutrition sciences: What is good for an athlete is rarely optimal for an obese person, the same diet that helps the obese lose weight, will make the athlete feel miserable, and lacing the drinking water of rodents on corticosteroids with the exact same amount of leucine that has had highly beneficial effects on the insulin sensitivity of diabetic rodents in previous studies (Guo. 2010) will not only fail to ameliorate the glucocorticoid-induced detoriations in blood glucose, it will even exasperate them.

So, does that mean you should not take your whey protein or BCAAs any longer? No, if you did that you would make the exact same mistake as someone who laces his water with leucine in order to avoid the catabolic effects of the synthetic corticosteroid he is taking for medical reasons. On the other hand, the results of the study at hand should make you re-evaluate the necessity and even benefits of guzzling BCAAs all-day long, at least if the reason for doing so is that you believe that you are so stressed that you would otherwise fall into a catabolic black hole.

That said, there may even be implications for the average pre-diabetic inhabitant of the Western hemisphere who is eating his hamburger and French fries on the parking lot of the local fast food restaurant, because he cannot make room to prepare and consume a real meal somewhere in his busy and stressful schedule. I mean, despite the fact that the aforementioned specificity principle does not allow for anything but a still to be verified hypothesis, it does at least appear not to far-fetched that this chronic endogenous stress, despite being very different from the "stress" that's induced by the administration of a synthetic corticosteroid that does not bind to serum proteins, could have similar negative modulatory effects on the purported benefits of chronic leucine supplementation ... but as I've said before, this would be something to investigate in another study. So unless you are actually taking dexamethasone for medical reasons, you are probably not at risk of developing diabetes due to a high amount of leucine in your diet.

In the unfortunate case that you are actually on synthetic corticosteroids, a previous study by the same group of scientists, in the same rodent model does suggests that three workouts with three sets of squats (10 reps each) per week may offer the protection against corticosteroid induced muscle loss decreased skeletal muscle GLUT-4 expression and insulin resistance, leucine does not have to offer.... well, at least as long as you abstain from leucine supplementation, because the latter had the exact same detrimental effects in the 2011 study where it was administered to one of the experimental groups in conjunction with resistance training as it had in these more recent experiments in the absence of any type of workout (Nicastro. 2011). 

References:

• Anderson,  K.D.; Abdul, M.; Steward, O. Quantitative assessment of deficits and recovery of
  forelimb motor function after cervical spinal cord injury in mice.  Exp. Neurol.  2004,  190,
  184–191.
• Kennel,  P.F.; Fonteneau, P.; Martin, E.;  Schmidt,  J.M.; Azzouz, M.; Borg, J.; Guenet,  J.L.;
  Schmalbruch, H.; Warter, J.M.; Poindron, P. Electromyographical and motor performance studies
  in the pmn mouse model of neurodegenerative disease. Neurobiol. Dis. 1996, 3, 137–147.
• Nicastro H, Zanchi NE, da Luz CR, de Moraes WM, Ramona P, de Siqueira Filho MA, Chaves DF, Medeiros A, Brum PC, Dardevet D, Lancha AH Jr. Effects of leucine supplementation and resistance exercise on dexamethasone-induced muscle atrophy and insulin resistance in rats. Nutrition. 2013 Apr;28(4):465-71. Epub 2011 Nov 12.
• Qin J, Du R, Yang YQ, Zhang HQ, Li Q, Liu L, Guan H, Hou J, An XR. Dexamethasone-induced skeletal muscle atrophy was associated with upregulation of myostatin promoter activity. Res Vet Sci. 2013 Aug 29.
• Vieira, N.M.; Bueno,  C.R., Jr.; Brandalise, V.; Moraes,  L.V.; Zucconi, E.; Secco, M.; Suzuki, M.F.; Camargo, M.M.; Bartolini, P.; Brum, P.C.; Vainzof, M.; Zatz, M. SJL dystrophic mice express a significant amount of human muscle proteins following systemic delivery of human adipose-derived stromal cells without immunosuppression.  Stem Cells  2008,  26, 2391–2398.  
• Zanchi NE, Guimarães-Ferreira L, de Siqueira-Filho MA, Felitti V, Nicastro H, Bueno C, Jr, Lira FS, Naimo MA, Campos-Ferraz P, Nunes MT, Seelaender M, de Oliveira Carvalho CR, Blachier F, Lancha AH, Jr. Dose and Latency Effects of Leucine Supplementation in Modulating Glucose Homeostasis: Opposite Effects in Healthy and Glucocorticoid-Induced Insulin-Resistance States. Nutrients. 2013; 4(12):1851-1867.

5-10% Weight Reduction From Set to Set For Hypertrophy, Heavy Leg Workouts for Cyclists, Garlic For 400% Higher Test/Cortisol Ratios & Max(!) 1g Vitamin C for Muscle Gains

7% increase in breast cancer risk for every 500g above "normal" birthweight for Scandinavian women. Weight is yet not all that counts, mommy's gestational diabetes and even a large body size also precipitate to later disease.

7% per 500g that's the increase in breast cancer risk, the female offspring of Scandinavian women will have, if they are born heavier than normal. This figure is the SuppVersity Figure of the Week and comes from a study I came across a couple of days ago (Troisi. 2013). The statistics are based on birth register data of women from Norway, Sweden or Denmark who were subsequently diagnosed with primary, invasive breast cancer (n=51419) and 10 controls for each case from the birth registries matched by country and year of birth (n = 514,190).

Contrary to what you may think, the birth weight does yet not pose as much of a risk to become obese later in life as being larger than "appropriate" for your gestational age does (Eyzaguirre. 2013). If you also consider that gestational diabetes has been linked with increased risk of metabolic syndrome in the offspring (Davis. 2013) and that obesity in itself is an independent risk factor for breast cancer (Patterson. 2013), these should be more than enough good arguments not to surrender to your occasional food cravings and laziness - pregnant or not.

It's not all in your genes, but most in your hands

Although some people would love, if this was the case, because they could blame their own misery on the mistakes other  may have made, our lives and health are not fully determined by our genes and/or the mistakes our mothers may or may not have made. As Poston and Foreyt wrote in 1999, already: "Obesity is an environmental issue." And we are lucky: It is in our hands to change the environment we are exposing ourselves to and thus influence which of our genetic disposals will become active and are  promoted and which of them won't. Now that's obviously not just the case for obesity, muscular hypertrophy would be another example. Irrespective of your genetic make-up your strength and muscle gains stand and fall with the way you train, eat and supplement... and guess what, all of these points will be addressed in today's installment of On Short Notice.

• Experimentally validated: 5-10% drop in weights per set is "optimal" for hypertrophy training (Medeiros. 2013) -- Scientists from the Laboratory of Physiology and Biokinetic at the Faculty of Biological Sciences and Health on the UNIG Campus V at Itaperuna in Brazil find: The average resistance trainee - in this case a young man aged 24.0±4.5 years with a body mass of 78.3±10.2 kg and a height of 177±7 cm - can remain in the hypertrophy range (10-12 reps to failure) for most of his sets, when he reduces the weight by 5-10% after each set.
  
  Whether this will also yield optimal gains was yet not within the scope of this 5-week study. What these results do however tell you is that you are not training hard enough if you perform all your sets with the exact same weight in the exact same rep range - well, unless you don't just like to listen to Super Human Radio, but are actually related to Superman himself ;-)

• 

  Sir Chris Hoy's legs are not as hilarious as those of the German Robert Forstemann (Robert is the right guy), but I am pretty certain their size and strength played a very important part in becoming the most successful Olympic track cyclist of all times (six gold and one silver Olympic Medal + 11 times world champion)

  Heavy leg training could make the difference between victory or defeat at the end of a cycling race (Hansen. 2013) -- In a soon-to-be-published paper, Ernst A. Hansen et al. report that the addition of 12-weeks of heavy resistance training in the form of 4 lower body exercises (3 × 4–10 repetition maximum) which had to be performed twice a week enhanced the cycling performance of highly trained cyclists by 7% compared to the training outcome of the subjects in a control group who simply followed their regular endurance-only, protocols:
  

  "Performance was determined as average power output in a 5-min all-out trial performed subsequent to 185 min of submaximal cycling. The performance enhancement, which has been reported previously, was here shown to be accompanied by improved pedaling efficacy during the all-out cycling. Thus, E+S shortened the phase where negative crank torque occurs by ~16°, corresponding to ~14%, which was more than in E (P = .002)" (Hansen. 2013)

  Since the test was conducted at the end of a 3h cycling session, it should be plain obvious that those 15% increases in torque will catapult the strength trained endurance athlete to the forefront on every final sprint.

• Human dose equivalent of ~0.1g/kg garlic per day could not just boost your testosterone and lower the high protein diet induced increases in cortisol, it could also improve the way your body utilizes dietary protein (Oi. 2013)-- Actually this is not a new study, but since Maxim was not happy with things "so yesterday" as the increases in HDL and LDL the Arabian scientists observed in the garlic study I have been talking about at the end of Thursday's SuppVersity Science Round-Up on SHR, I thought others may be as happy as Maxim will hopefully be to hear that there is more to garlic than "just" its beneficial effects on your heart.
  
  

  

  Figure 1: Higher testosterone levels, an amelioration of the high protein induced increase in corticosteroids and a 40% increase in net protein balance are unquestionably impressive results given the fact that the all those differences were brought about within 28 days and by no more than 0.1g/kg (HED) of "supplemental" garlic in form of heat dried powder that was added to the chow (Oi. 2001)

  In fact, I am almost sure that the >400% increase in the testosterone to cortisol ratio you will see if you take a closer look at the data in figure 1, is probably rather what Maxim would have liked to hear me talk about. Especially in view of the fact that this endocrine effects went hand in hand with a highly significant +60% increase in protein retention (figure 1, top right). Think about it, if only part of he protein that was now no longer excreted in the urine / feces would be used for protein synthesis this would entail exactly those hypertrophy effects you don't see with your average "scientifically proven" herb-based testosterone booster.
  
  Unfortunately, the scientists did only measure the body weight and visceral fat pads, not the actual muscle mass of the rodents,. But if you go by their ratios it is obvious that the high protein + garlic group were not just the heaviest, but also the leanest.
  
  With +11 % vs. +5% in both the medium and high protein diets, the animals on the low protein did yet exhibit the most profound benefits as far as the body weight / visceral fat ratio goes. Against the background that their net protein balance remained the same, this observation does actually suggest that the pro-anabolic effects of garlic are not solely a result of a decreased protein excretion (see figure 1).

  

  Table 1: Principal sulphur compounds of garlic preparations (Hammami. 2013)

  Warning: Don't live on garlic alone! While the provision of 0.8% garlic powder did have beneficial effects on testosterone production in the study at hand, there are a couple of studies which suggest that a diet with 15-30% of crude garlic (Hammami. 2008 & 2009), as well as the administration of Diallyl trisulphide in isolation (Qian. 1986) and raw garlic juice (e.g. 600mg/kg per day for 21 days in Fehri. 1991) can compromise testosterone production and/or testicular function. In view of the difference between 0.8% garlic powder in the diet of the rodents in study at hand and 15-30% of pure garlic in the diet of the animals in the Hamami studies, it is most likely that the effects were dose-depended, but in case you are interested in health benefits of specific sulfor compounds in garlic, the data in table 1 on the left may still come handy to pick "your" preferred form of garlic.
  Rather than that, it appears as if the human equivalent of 0.1g/kg body weight of heat dried garlic powder that contained a total amount of 5.05 mg/g of total diallylsulfide (0.05 mg of monosulfide, 1.0 mg of disulfide, 3.4 mg of trisulfide, 0.6 mg tetrasulfide) had the ability to improve the incorporation of dietary protein into muscles (and other organs).

 

• Study shows: Vitamin C supplementation does reduce skeletal muscle hypertrophy in response to chronic overload (Makanae. 2013) -- Despite the fact that it has not even been published yet, the paper by Yuhei Makanae et al. actually only confirms what more and more scientists have been speculating about within the last couple of years. The provision of high does of active antioxidants, and as it seems in particular vitamin C, blunts the hypertrophy response to skeletal muscle overload.
  
  

  

  Figure 2: 14-day of 500mg/kg  (HED 0.08g/kg) supplemental vitamin C blunt skeletal muscle hypertrophy in rodents (Makanae. 2013)

  As you can see in figure 2 the effect size was relatively small, but statistically highly significant (p < 0.01) and that despite the fact that the supplementation regimen (500mg/kg body weight; HED: 0.08g/kg body weight) was not even that much higher than what some "vitamin C enthusiasts" are taking on a daily basis in the futile (and useless) effort to boost their serum vitamin C levels to a concentrations your body does - probably not without reason - try to counter by increasing renal vitamin C clearance.
  
  As the data in figure 2 shows, the same homeostatic mechanism we know from humans worked in the rodents, as well - well, at least with respect to the serum levels. In the plantaris muscle of the supplemented group, on the other hand, there was a significantly higher accumulation of vitamin C than in the placebo group. This increase went hand in hand with an attenuation of the repressive effects the chronic overload of the muscle had on the expression of the catabolic protein atrogin-1 and the increases in the pro-anabolic protein Erk1/2 (p < 0.01) in the non-supplemented animals. Based on this observations and with reference to the results of previous studies and the fact that neither the water content of the muscle, nor a significant reduction in food intake in the vitamin C group could explain the observed differences, Makanae et al. conclude "that oral vitamin C administration attenuates plantaris muscle hypertrophy induced by chronic mechanical load." (Makanae. 2013).
  
  What the study does not answer, though, is the question whether the effects would be identical in a real-world training scenario, where the temporary, yet more intense wear and tear on the muscle could in fact be sufficient to induce skeletal muscle hypertrophy human despite vitamin C supplementation. But let's be honest in view of the fact that scientific evidence for ergogenic benefits of more than 1g of supplemental vitamin C  per day (in humans) is simply non-existent, the take away message from the study at hand should actually read: Do not escalate your vitamin C beyond the 1g per day, if you don't want to risk compromising the results of all the hard work you are investing into your training.

That's is, another installment of On Short Notice and the first day of the weekend approaching it's peak. If you still have some time before whatever your plan for Saturday night may be and feel like you could use some seconds on today's short news, I suggest you head over to the SuppVersity Facebook Wall and check out the latest news on

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  Ever thought about what green tea, grape seed, curcumin, cranberry, and tons of other Super Food have antimicrobial effects? Considering the LPS-influx from the gut turns out to be a major contributor to all sorts of diseases, I am curious about how much of their effects are actually mediated by the gut microbiome.

  The differential role of intramuscular lipids in trained athletes and sedentary slobs and how the difference between performance enhancement and insulin resistance it all comes back to getting your as off the coach (learn more)
• Metformin 2.0? Scientists have developed a hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose lowering agent called ETC-1002 (learn more)
• Confirmed: Grape seed could be the go-to neuroprotector for diabetics - GSE administration was found to be able to ameliorate most of the biochemical altered parameters in diabetic rats (read more)
• Fermenting your own dairy? Just add some catechin rich teas and the lactobacilli will strive. Makes you wonder about the 'internal' probiotic effects of green and black teas, as well. Doesn't it? (learn more)

There will be more, don't worry - so feel free to check for updates either directly on the SuppVersity Facebook Wall or simply by taking a look at the navigation in the right under "SuppVersity Facebook Wall" from time to time. Obviously, you can also simply "like" the SuppVersity on facebook to make sure you don't miss anything.

References:

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• Eyzaguirre F, Bancalari R, Román R, Silva R, Youlton R, Urquidi C, García H, Mericq V. Prevalence of components of the metabolic syndrome according to birthweight among overweight and obese children and adolescents. J Pediatr Endocrinol Metab. 2013;25(1-2):51-6. 
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• Hammami I, El May MV. Impact of garlic feeding (Allium sativum) on male fertility. Andrologia. 2013 Sep 3.
• Makanae Y, Kawada S, Sasaki K, Nakazato K, Ishii N. Vitamin C administration attenuates overload-induced skeletal muscle hypertrophy in rats. Acta Physiol (Oxf). 2013 Nov 26.
• Medeiros Jr HS, Mello RS, Amorim MZ, Koch AJ, Machado M. Planned Intensity Reduction to Maintain Repetitions Within Recommended Hypertrophy Range. Int J Sports Physiol Perform. 2013 Nov 19. 
• Oi Y, Imafuku M, Shishido C, Kominato Y, Nishimura S, Iwai K. Garlic supplementation increases testicular testosterone and decreases plasma corticosterone in rats fed a high protein diet. J Nutr. 2001 Aug;131(8):2150-6.
• Patterson RE, Rock CL, Kerr J, Natarajan L, Marshall SJ, Pakiz B, Cadmus-Bertram LA. Metabolism and Breast Cancer Risk: Frontiers in Research and Practice. J Acad Nutr Diet. 2013 Nov 2. doi:pii: S2212-2672(12)01426-8.
• Qian YX, Shen PJ, Xu RY, Liu GM, Yang HQ, Lu YS, Sun P, Zhang RW, Qi LM, Lu QH.  Spermicidal effect in vitro by the active principle of garlic. Contraception. 1986; 34:295–302.
• Troisi R, Grotmol T, Jacobsen J, Tretli S, Toft­Sørensen H, Gissler M, Kaaja R,Potischman N, Ekbom A, Hoover RN Stephansson O. Perinatal characteristics and breast cancer risk in daughters: a Scandinavian population­based study. Journal of Developmental Origins of Health and Disease, Available on CJO 2013.