2.1kg Muscle From Fast Food Supplement; No Prolactin, No Fat; Oleic Acid Counters CLA's Inflammatory Effect; Spicy Marinades vs. Salmonella; Flaxseed, Estrogen & Penis Size; TTA in the Emergency Room; Alcohol & Binge Eating

Image 1: Scientifically proven muscle builder - 2.1kg lean mass in 3 months, no post-cycle therapy necessary!

I was just about to write another one of my artistic introductions, trying to incorporate all the exciting On Short Notice news I've piled up for you into a brief narrative, when I realized that you probably don't really appreciate those introductions (I guess, I would skip them myself, so don't worry, this is more of an objective assessment than an accusation). So, I listened to my gut and decided to skip this part of this series, today, and rather spend the time to edit another item I did actually not want to post today. It's the one on the "IIFYM slightly gone wrong fast food bulk" in the Hambre study, to be precise; and I would venture the guess that you won't mind taking that instead of a longer introduction, once you've read and digested the impossible: You cannot only gain muscle with "fast food supplements", you won't even get fatter than you would if you just used a classic whey protein... oh my, I see, you are already scrolling down: What I said, I would have been wasting my time, had I written a longer introduction. But dare you, if you don't at least read the other items, as well!

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  Figure 1: Food intake (top, lef) and energy expenditure (bottom, left) as well as body fat % (top, right) and body weight development of the normal vs. prolactin negative mice after 14 weeks on standard chow (SC) or high fat diet (HFD; Auffret. 2012); btw: taking super-doses of vit. B6 will induce nerve damage, not fat loss!

  Without prolactin mice can't get fat! If that is true for humans as well, this would mean that Julien Auffret and his colleagues would have made a very important finding that could help us solve at least part of the diabesity pandemic, if we found a way to mimick the effects the "beigening" (=making white adipose tissue behae similar to the fact burning brown adipose tissue) effect the genetic ablation of the prolactin receptor on the fat cells of the mice in the Auffret study had on their susceptibility to diet induced obesity (Auffret. 2012).
  In particular, the scientists found that the ablation of the prolactin receptor gene in the mice results in profound increases in the expression of master genes controlling brown adipocyte fate (PRDM16) and mitochondrial function (PGC1α, UCP1), which allow - and this is the actual caveat,, here - for an inrease in thermogenesis.
  The latter, in turn, allows the rodents to burn off a major part of the fat they would otherwise store and thus keeps them relatively lean despite HFD feeding. Aside from the fact that the hyperphagic rodents on the high fat diet were still fat (there is no debating that!), you may savely assume that the effects will be way less pronounced in human beings, where 9/10 "thermogenic" agents that have been successfully tested in rodents do nothing at all, anyway. Against that background the hunger-promoting effects of the prolactin recetor ablation would suggest that it is almost as likely that a drug that block prolactin completely would make obese individiuals even fatter, since that's usually what happens if you eat more - like the mice in the prolactin (-/-) group did (see figure figure 1), without burning more.

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  Figure 2: Comparison of MUFA : CLA ratios in steak and mince from grass fed or conventional beef and milk from mares, sows, women (human milk ;-), goats and cows (based on Dhiman. 1999; Jahreis. 1999; McAfee. 2011); higher values indicate more MUFA per unit of CLA, but more must not necessarily be better - in fact too much MUFA could completely block the fat loss effects of CLA and thus maybe explain why it rarely works in humans - our diets are pretty high in oleic acid and thus the ratio will be much lower, than in the high dose CLA rodent trials

  Conjugated linoleic acid needs oleic acid to work without side effects. That's the main take-home message from a recent study conducted by researchers at the at the University of North Carolina at Greensboro, who found that oleic acid, the mono-unsaturated fatty acid from olive oil & co, does prevent the expression of inflammatory genes in adipocytes treated with the "anti-fat fat CLA"..
  So, until my friends from the supplement industry read this post and come out with yet another SuppVersity science powered product with CLA in olive oil* you simply make sure to have a spoon of the liquid gold from time to time, when you feel that you need to take CLA to burn more fat. Unfortunately, this could not just mean that you can rid yourself of the nasty side-effects as discussed in "CLA Destroys Body Fat! But at Which Costs?", but also that the "body fat destruction" will at least be ameliorated if not totally absent :-(
  * I had hardly written this post, when I browsed the web and found that a certain newcomer and as of late very succesful "yellowish green" company has already a CLA + Olive Oil + Avocado Oil combination on the market, for them this would mean that they didn't even have to change their formula

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  Image 2: It's funny how so many things people (or at least chefs) have been doing forever, here marinating meats, simply make sense, isn't it?

  Antibacterial marinades for your meat! Don't worry this is not yet another dysfunctional functional food that's going to make you sick, but an all-natural mixture of green tea, lemon and turmeric you will have to smear onto your chicken meat if you want to make sure to get rid of the C. jejuni and S. enteritidis it may be contaminated with.
  All it takes are 24h of "incubation", but that's nothing else than leaving your meat lying in the marinade in your fridge and thus something you would do anyway, right? That's what I would call a convenient, effective and above all totally natural and healthy way of gettting rid of Samonella and Campylobacter :-)
• Tons Flaxseed flour in your diet will increase estrogen, but won't decrease the size of your penis, well at least not visible ;-) That's probably the most straight-forward summary of the results, Ludmila Ferreira Medeiros de França Cardozo and her colleagues present in the latest issue of Food and Chemical Toxicology after analyzing the effect of a flaxseed flour containing diet on the expression of hormone levels and penis morphology of male rats (de Franca. 2012)

  

  Image 3: Flaxseed bread won't turn you into an hermaphrodite overnight, don't worry.

  While the rats that were maintained on a diet containing 25g of flaxseed flour per 100g for 250days had significantly elevated estrogen levels in the blood 39.5 vs. 32.5 pg/mL (+22%), the minor drop in testosterone did not reach statistical significance and the reduced diameter of the corpus spongiosum, which helps to maintain the urethea as a viable channel for the ejaculation was obviously no problem for the fertility, either - at least the scientist don't mention anything in this regard; unfortunately, they did not really test it, either, as the poor male Wistar rats that were abused in this experiment were bachelors against their will.
  In view of the fact that flaxseed ain't the best source of omega-3s, anyway, and there appears no other good reason (for men and women!) why you would eat them in large quantities (I am not talking about the occasional tablespoon of flaxseed, here), I would still suggest to stay away from it.

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  Image 4: In farm-raised salmon chronic TTA administration has been shown to improve cardiac function and immune activity; it does however also lead to cardiac growth during viral infections, so that the benefits of chronic administration are still by no means certain (Grammes. 2012a & 2012b); long-term human studies, on the other hand, are not yet available.

  Acute TTA administration soothes the flames and keeps the coronary vessel open You will unquestionably remember my previous posts about the fat burning fatty acid tetradecylthioacetic acid (TTA) and how it's ability to accumulate in various tissues of your body could potentially become problematic. In the short term however, it's anti-inflammatory effects can come very handy. So handy, in fact, that the a recently published study by Pettersen et al. would suggest that we are soon going to see TTA balloons being inserted into coronary vessel walls, in order to deliver the sulfur-containing fatty acid right to an obstructed vessel that's being operated on, in order to suppress the local expression of inflammatory cytokines, as well as the subsequent macrophage infiltration and the unwanted collagen formation, which would precipitate restenosis (=further clogging) of the very heart vessel that has only just been opened operatively.
  You may now rightly ask yourself what this has got to do with you? Well, if it works locally, it could work similarly systemically and other studies such as Bjørndal (2012) do confirm just that: 0.4% TTA reduce TNF-α, IL-1β, and IL-6 in an experimental model of colitis and render the rodents guts more of less bullet..., ah, pardon, dextran sulfate sodium (DSS; a chemical used to induce cholitis) proof. The long-term effects of the continous consumption of ~3g of TTA, which would be the human equavalent of those 0.4% TTA in the rodent diets is yet still not fully established (re-read: "TTA & Fish Oil" and "TTA & Fish Oil - Revisited").

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  Figure 3: Alcohol overrides the inhibitory control over food intake (Chapman. 2012)

  Of TV watching, sleep deprivation and alcohol consumption, booze has the most pronounced negative effect on reward saliency and inhibitory control of food intake! That's the conclusion Colin Daniel Chapman, Christian Benedict, Samantha Jane Brooks, and Helgi Birgir Schiöth mkae based on their latest meta-review of pertinent studies from pubmed (N=23). With an impact factor of 1.03 on a scale from -4 to 4, alcohol is by far the worst the greatest effect on food intake and shows the highest correlation with obesity (Chapman. 2012).
  Compared to booze, both sleep deprivation (50% less) and TV watching (20% less) appear almost harmless. Their contribution in the non-drinking part of the population may yet still not be underestimated, also because the urge to do the latter, i.e. watch TV, when you ought tho sleep, precipitates the former and subsequent derangements in the circadian rhythm (suggested read: "The SuppVersity Circadian Rhythm Series").
• IIFYM was yesterday, ROWFYM is today, but what's going to be tomorrow? If that's all Greek to you, let me first bring you in the loop on the acronyms. While IIFYM designates "If It Fits Your Macros", implies (in the most extreme case) that you give a sh*t about what you eat, as long as you hit your macronutrient ratios for the day ("Carbs? Gimme that pizza!") and is getting increasingly popular among those who are fed up with broccoli and chicken breast and either unwilling or unable to see that those are not the only, and I would say, by far not the most healthy foods you can eat, ROWFYM is my own invention, means "Regardless Of Whether It Fits Your Macros" and would probably end up for way too many trainees in a protocol similar to the one 12 of the 24 subjects in a recent study from the Linköping University in Sweden were following for 12 weeks (Hambre. 2012).

  

  Image 5: "WTF do you want, I am doing ROWIFYM, here! That's serious bulking, man. Scientifically validated." If you want to follow his example, go ahead... but 3 months really is the absolute max and only if you are still healthy - regardless of whether the blood markers return to normal in the course of your next diet.

  While those lucky (?) twelve healthy young men (aged 19–32 years) in what I will from now on call the "fast-food arm" of the study had to add a delicious (???) fast food menu (1350 kcal, 41 g protein) on top of their diets, the other twelve participants had to contend themselves with a blatant protein shake (33g of whey) as their bulking supplement of choice. The reasoning behind this at first sight unquestionably highly questionable experiment was that the Swedish scientists wanted to elucidate, whether it would really make a difference whether you are eating "clean" (=adding a whey protein shake) or simply stuffing yourself with the next best, allegedly protein-laden fast food you can find during a 3-months bulking cycle (at least three lifting sessions per week) and the results were, ... well, let's say surprising.
  As you would expect, subjects in both groups managed to gain some weight. The first surprise is that subjects in both groups gained identical amounts of weight, namely 3.6kg. That's not all, however. Even the lean mass increases 2.1kg did not differ between the groups (measure by DEXA scans) and the sophisticated (compared to a similar calories in vs. calories out calculation) measurement of the resting metabolic rate, the scientists had conducted yielded that both groups had compensated for the overeating by a statistically highly significant (p < 0.0001!) + 10% increase in resting metabolic rate!

  

  Figure 4: Kaplan-Meier plots indicating the percentage of patients that made it to time-point X (see horizontal axes) without adverse event after their first coronary event - patients w/ (thin line) vs. w/out (bold line) metabolic syndrome (top), patients with high (thin line) vs. low (bold line) ApoB leves (bottom; based on Corsetti. 2005); ApoB turns out to be a way better risk predictor than having metabolic syndrome

  Before you do now jump into your car and head for the next drive-in "restaurant" with a big yellow "M" in front of it, you may want to take into consideration that this extended ROWIFYM version of the IIFYM approach, where you may hit the protein but overshoot on the carbs and fats (and certainly not  the good ones), did lead to statistically significant increases in fasting insulin and ApoB, a building block of LDL that has been associated with increased risk of arterial plaque formation (Gebel. 2008), compared to the "clean bulk" (= whey only) group. And while those changes (as well as the increase in RMR) were reversed on the 12 months follow-up, I am not sure if especially those people, who are most fond of bulking approaches like that, i.e. men (and very rarely women) who have been following a junk food diet for way too long already, should take the results of this study as an incentive to do a 3-month fast food bulk during the winter. After all, it could be that one additional LDL molecule that nests in the already existent arterial plaque which will eventually break the camel's, no your neck - or for those who like it more explicitly, which won't let the next mini blood clot pass by and causes a stroke, which could, in the worst case, end deadly!

That's it as far as the official On Short Notice items go, for today. If you don't have enough yet, I suggest you take a glance at the 6-10 news-items I've piled up on the SuppVersity Facebook Wall for you to review. Maybe you've read that sleeping with wife and children in a room would decrease your testosterone levels? False! Maybe it decreases the intellectual capacity of the reporter who wrote the respective news-item you may have read, but what really happens, is an increase in the amplitude of the circadian pattern with higher morning and lower evening testosterone levels (click here to read more). And if you neither have or plan to have children or don't care about your or your significant other's testosterone levels, you may be interested in a study that debunks the use of a "slim belt" for weight loss purposes, the idiotic idea to counter BPA toxicity with soy, the way working out can make depressed old people happy again, and more... ah, I almost forgot, there will also be an exercise special of On Short Notice very soon - and I am not talking about next Saturday, here - so stay tuned, it could be published anytime (Tip: If you subscribe to the SuppVersity Facebook Page you won't miss it ;-)

 References:

• Auffret J, Viengchareun S, Carré N, Denis RG, Magnan C, Marie PY, Muscat A, Fève B, Lombès M, Binart N. Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity. FASEB J. 2012 Sep;26(9):3728-37. 
• Bjørndal B, Grimstad T, Cacabelos D, Nylund K, Aasprong OG, Omdal R, Portero-Otin M, Pamplona R, Lied GA, Hausken T, Berge RK. Tetradecylthioacetic Acid Attenuates Inflammation and Has Antioxidative Potential During Experimental Colitis in Rats. Dig Dis Sci. 2012 Aug 2.
• Chapman CD, Benedict C, Brooks SJ, Birgir Schiöth H. Lifestyle determinants of the drive to eat: a meta-analysis. Am J Clin Nutr. 2012 Sep;96(3):492-7. Epub 2012 Jul 25.  
• Corsetti JP, Zareba W, Moss AJ, Sparks CE. Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome. Atherosclerosis. 2004 Dec;177(2):367-73.
• de França Cardozo LF, Boaventura GT, Brant LH, Pereira VA, Velarde LG, Chagas MA. Prolonged consumption of flaxseed flour increases the 17β-estradiol hormone without causing adverse effects on the histomorphology of Wistar rats' penis. Food Chem Toxicol. 2012 Aug 25.
• Dhiman TR, Anand GR, Satter LD, Pariza MW. Conjugated linoleic acid content of milk from cows fed different diets. J Dairy Sci. 1999 Oct;82(10):2146-56.
• Gebel E. Meet LDL's partner in plaque. ApoB puts the "bad" in bad cholesterol. Diabetes Forecast. 2008 May;61(5):39-40.
• Grammes F, Rørvik KA, Takle H. Tetradecylthioacetic acid modulates cardiac transcription in Atlantic salmon, Salmo salar L., suffering heart and skeletalmuscle inflammation. J Fish Dis. 2012a Feb;35(2):109-17. 
• Grammes F, Rørvik KA, Thomassen MS, Berge RK, Takle H. Genome wide response to dietary tetradecylthioacetic acid supplementation in the heart of Atlantic Salmon (Salmo salar L.). BMC Genomics. 2012n May 11;13(1):180.
• Hambre D, Vergara M, Lood Y, Bachrach-Lindström M, Lindström T, Nystrom FH. A randomized trial of protein supplementation compared with extra fast food on the effects of resistance training to increase metabolism. Scand J Clin Lab Invest. 2012 Aug 30.
• Jahreis G, Fritsche J, Möckel P, Schöne F, Möller U, Steinhart H. The potential anticarcinogenic conjugated linoleic acid, cis-9,trans-11 C18:2, in milk of different species: Cow, goat, ewe, sow, mare, woman. Nutrition Research. October 1999; 19:10. 1541–1549.
• McAfee AJ, McSorley EM, Cuskelly GJ, Fearon AM, Moss BW, Beattie JA, Wallace JM, Bonham MP, Strain JJ. Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers. Br J Nutr. 2011 Jan;105(1):80-9.
• Murali N, Kumar-Phillips NS, Rath NC, Marcy J, Slavik MF. Effect of Marinating Chicken Meat with Lemon, Green Tea and Turmeric Against Foodborne Bacterial Pathogens.International Journal of Poultry Science. 2012; 11(5): 326-332.
• Pettersen RJ, Salem M, Rotevatn S, Kuiper KK, Larsen TH, Bohov P, Berge RK, Nordrehaug JE. Effects of local delivery of Tetradecylthioacetic acid within the injured coronary vessel wall. Scand Cardiovasc J. 2012 Aug 30.
• Reardon M, Gobern S, Martinez K, Shen W, Reid T, McIntosh M. Oleic Acid Attenuates trans-10,cis-12 Conjugated Linoleic Acid-Mediated Inflammatory Gene Expression in Human Adipocytes. Lipids. 2012 Sep 2.

TTA + Fish Oil Revisited - Increased Intramuscular Omega-3 Levels Compromise Heart and Skeletal Muscle Performance: -40% Endurance & -54% Total Work Capacity in 9 Weeks

Image 1: It is hilarious this picture was probably shot and (ab-)used to propagate the unhealthy message that you could never get enough omega-3 fatty acids from your diet, because that would mean you had to eat such nasty stuff as fish - pah, better pop some pills, I mean we are in the 21st century right!?

I guess you will remember my previous blogpost,  "TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants?", on the 2012 study by Vigerust et al. which did show that TTA could ameliorate the hepatoxic side effects of fish oil, which, when it is administered in amounts higher than 1-2g per day over an extended time period, begins to accumulate in the liver (see also "Too Much of a Good(?) Thing: When Fish Oil Starts Clogging Your Arteries and Fattening Up Your Liver"). Moreover, the addition of ~912.4mg (human equivalent) TTA to the "long-term fish oil = fatty liver"-equation turned produced a pretty potent fat burning and anti-obesity stack. Based on previous reports on the unwanted side effects of TTA-based fatburners in the past, I deliberately selected the subtitle "Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run" and explicitly cautioned against the (over-)use of this fat loss combo for an extended period of time - as one of the most recent article in the journal Lipids in Health and Disease suggests, more than rightly so (Strand. 2012)!

TTA a can save your liver, but it will exasperate the shift of n-3 into your heart

Image 2 (Knuuti. 2008): a globally, well-perfused and (top) a compromised heart with a maximum perfusion of 1.3 ml/g/min (bottom)

As the data the scientists from the Haukeland University Hospital in Bergen, Norway, collected clearly suggest. A similar combination of fish oil and TTA of which Vigerust et al. found that it ramps up fatty acid oxidation in the liver and clears your most important detoxification organ from long-chain polyunsaturated fatty acid junk (not or incompletely oxidized omega-3s) fails to elicit similar effect in the heart of 8-10 weeks old male Wistar rats, who were kept for 50(!) weeks on one the following four 25% fat diets which differed only in terms of their individual fatty acid composition:

• control diet - 23% lard, 2% soybean oil
• TTA - 0.375% TTA, 22.6% lard, 2%
• fish oil - 10.4% fish oil (42% EPA / 21% DHA), 12.6% lard
• TTA & FO - 0.375% TTA, 10.4% FO, 12.2% lard, 2% soy

With both, fish oil and TTA being potent peroxisome-proliferator receptor (PPAR) agonists the scientists were mainly interested in the long-term effects of this touted "anti-diabesity" (i.e. countering diabetes and obesity) agents on the deposition and distribution of different fatty acids in various tissues. A special focus was on the heart and the downstream effects of fatty acid metabolism and myocardial function and performance.

N-3 accumulation in the heart? Wait that's a good thing, right? NO!

For the laymen who has been bamboozled by the fish oil craze this may initially sound counterintuitive, but the profound accumulation of omega-3 fatty acids in the myocardium (heart) of the rodents (see figure 1) is about as bad as it can get for the critters heart health.

Figure 1: PUFA composition (wt%) in heart of rats after 50 weeks of diet administration (Strand. 2012)

Similar to what we have seen for Zinc (cf. "Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome") and alpha lipoic acid (cf. "Lean & Muscular With Alpha Lipoic Acid? You Could Be Just as Lean, But More Muscular W/out 'Nutrient Repartitioner'!"), the PPAR-agonists fish oil and TTA, both of which have been shown to exert beneficial effects in certain sick (as of yet still sub-)groups of the population, like diabetics (e.g. Khalid. 2011) and patients with dilated cardiomyopathy (e.g. Nodari. 2011), exert diametrically opposed effects in a rodent model that is probably more accurate for the average healthy human being than his/her sedentary, obese and metabolically deranged peers.

Keep away from your obese neighbors' supplement stash, damn it!

Independent analyses such as a 2009 paper by Dijkstra et al. do not support the commonly held conviction that fish oil or a higher intake of omega-3 fatty acids was beneficial for the general non-diabetic public anyway (Dijkstra. 2009). And it does not take all too long to find numerous reports of in parts serious side effects from the consumption of high-dosed TTA-based fat-burners in the archives of popular fitness and bodydbuilding boards, before the respective supplement producers got scared and pulled them voluntarily and under the pre-text that they had found more effective formulations off the market.

Figure 2: Enzyme activity (nmol/min/mg) in heart of rats after 50 weeks of diet administration (based on Strand. 2012)

Probably a smart move if you look at the combined increases in enzymes that oxidize (ACOX) and enzymes that synthesize and store  fatty acids (FAS and GKAT) in the heart muscles of the rodents in figure 2. Together the synergy of increased storage and increased oxidation could create a perfect storm, which due to the overall "limited capacity of heart to metabolize the poorly oxidizable n-3 PUFA compared to SFA [...] might altogether indicate a reduction in cardiac efficiency" (Strand. 2012).

Reduced cardiac efficacy = reduced muscular efficacy

It's quite funny that we could actually have known that all along, after all, one of my favorite "holy omega-3 vs. bad omega-6" studies by K.J. Ayre and A.J. Hulbert was published in 1997 already. Ayre and Hulbert wanted to elucidate the effects of different dietary fatty acid compositions on the exercise capacity of rodents and found (way before the fish oil craze and therefore not so much to their surprise) that compared to a coconut (EFA deficient) or sesame oil (high omega-6) the n-3 enriched test diet led to a profound decrease in exercise capacity (see figure 3)

Figure 3: Endurance and total work capacity (left) and soleus and EDL fatty acid composition (right) of rats after 9 weeks on diets containing almost no essential fatty acids , a high n-6 or a high n-3 content (Ayre. 2012)

Similar to the detrimental effects on the efficacy of the heart muscle, the decreases in endurance -40% and -54% in endurance and work capacity in the n-3 group went hand in hand with profound increases in the soleus and extensor digitorum longus omega-3 content.

In view of the fact that TTA appears to increase the existing fatty acid recompositioning effects of an overload of dietary omega-3 fatty acids in the diet, and against the background that the observed negative side effects came about in no more than 9 weeks and were not reversed after 6 weeks on standard chow, it appears more than questionable if the few lbs of body fat you may be able to shed with the aforementioned TTA+fish oil double whammy over say 4-8 weeks are actually worth taking the risk of permanent or at least only slowly reversible changes in the intracellular fatty acid composition of your heart and skeletal muscle.

"And what about fish oil supplementation alone?"

Aside from the fact that the usefulness of fish oil caps in healthy individuals is questionable (Dijkstra. 2009) and anything beyond 1-2g of fish oil per day could well lead to increased not decreased oxidative damage in athletes and physical culturists (cf. "Omega-3 Fatty Acids Pro-Inflammatory in Athletes"; Filaire. 2010), you don't necessarily have to throw away your fish oil. After all, I would hope that no one here is getting 50% of his/her daily fat intake from fish oil caps - which was basically what Strand et al. fed their rodents to make sure that the shift in myocardial fatty acid levels would be profound enough. Still the Ayre study, where the n-3 content of the diets was much lower (16% of total fat intake, ~8.8g of fish oil if you consumed 2,000kcal/day), does indicate that the intramuscular changes in fatty acid composition can be profound and not without detrimental consequences even without the addition of TTA and in response to amounts of omega 3 fats of which we all know that thousand of supplement junkies still believe would be nothing but beneficial for their health.

Image 3 (woschie): What would these guys say, if everything they caught was a handful of fish oil caps? "Look! I have caught the best part of the fish. lucky me, so I don't have to take it, squeeze it and bath it in all sorts of chemicals to separate the good fats from the bad protein I would then have to process to fish meal!"

In the end, it all comes, as so often, by the way, back to two very common motifs here at the SuppVersity motif A which I have already implied in one of the subheadings is the simple truth that what has been show to work for the obese type II diabetic does not necessarily work for a healthy human being, let alone such an extraordinary specimen as you are ;-) And that does in fact segue perfectly into motif B which revolves around the notion of balance and is basically the foundation of my repetitive advice to always prefer real foods over supplements, where the latter is possible - and contrary to creatine of which even a meal-loving carnivore like myself could never get enough from his diet to see any of the scientifically well-established benefits, eating fish spending a couple of extra-bucks on grass-fed beef from time to time and simply avoiding the omega-6 laden vegetable oils will make the use of those nasty fish oil caps obsolete, anyways.

References:

1. Ayre KJ, Hulbert AJ. Dietary fatty acid profile affects endurance in rats. Lipids. 1997 Dec;32(12):1265-70.
2. Dijkstra SC, Brouwer IA, van Rooij FJ, Hofman A, Witteman JC, Geleijnse JM. Intake of very long chain n-3 fatty acids from fish and the incidence of heart failure: the Rotterdam Study. Eur J Heart Fail. 2009 Oct;11(10):922-8.
3. Filaire E, Massart A, Portier H, Rouveix M, Rosado F, Bage AS, Gobert M, Durand D. Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes. Int J Sport Nutr Exerc Metab. 2010 Dec;20(6):496-506.
4. Khalid AM, Hafstad AD, Larsen TS, Severson DL, Boardman N, Hagve M, Berge RK, Aasum E. Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2116-22. Epub 2011 Mar 18.
5. Knuuti J, Bengel FM. Technology and guidelines: Positron emission tomography and molecular imaging. Heart 2008;94:3 360-367
6. Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, Gheorghiade M: Dei Cas L: Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol 2011, 57:870–879.
7. Strand E, Bjørndal B, Nygård O, Burri L, Berge C, Bohov P, Christensen BJ, Berge K, Wergedahl H, Viste A, Berge RK. Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat. Lipids Health Dis. 2012 Jun 27;11(1):82.
8. Vigerust NF, Cacabelos D, Burri L, Berge K, Wergedahl H, Christensen B, Portero-Otin M, Viste A, Pamplona R, Berge RK, Bjørndal B. Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks. J Nutr Biochem. 2012 Jan 3.

An Old Dog Learns New Tricks: "Fatloss Fat" Tetradecylthioacetic Acid (TTA) Cardioprotective in Diabetic Rats

Do you remember the acronym TTA? Tetradecylthioacetic Acid? No. Well, I guess then you were not into fat burners in the early 2000s. TTA, a thia-fatty acid, was all the rage back in the day: Supplement producers claimed it would literally melt fat away and it actually turned out that some users had outstanding results megadosing respective supplements. Others, however, got bloated and/or started cramping. In view of these nasty side effects, most companies decided to reformulate their products and - with the exception of a few so-called "non-thermogenic" fat burners - TTA has almost disappeared from the market.

An international team of scientists from Norway and Canada (Khalid. 2011) has now discovered that the artificial fatty acid tetradecylthioacetic acid, which was originally intended as a drug for the treatment of the metabolic syndrome, might have the potential to protect type II diabetics from heart attacks.
In a previous study (Hafstad. 2009) the scientists had already shown that TTA does increase myocardial fatty acid oxidation in normal mice, a finding that would generally suggest impaired cardiac efficiency and thus be considered detrimental. In the current study on hyperlipidemic [high blood lipid levels] type 2 diabetic mice, however, TTA-treatment (0.5%, 8 days) had almost opposite effects on on cardiac metabolism and function

We found that TTA treatment increased myocardial FA oxidation, not only in non-diabetic (db/+) mice, but also in diabetic (db/db) mice, despite a clear lipid-lowering effect. While TTA had deleterious effects in hearts from non-diabetic mice (decreased efficiency and impaired mitochondrial respiratory capacity), these effects were not observed in db/db hearts. In db/db hearts TTA improved ischemic tolerance, an effect that is most likely related to TTA's antioxidant property.

Being a specifically designed (Pan-)PPAR-ligand [TTA seems to activate all PPAR-receptors] the lipid lowering effect of TTA was to be expected. The differential effect on heart function in healthy and diabetic rats, however, comes as a surprise and reminds us, again, that not all that has been shown to help sick people is beneficial - and sometimes its not even safe! - for the healthy part of the population.

Figure 1: Myocardial fatty acid and glucose oxidation in hearts of db/+ (white  545
bars) and db/db (gray bars) mice. Results are mean of 8-9 hearts in each group. (Khalid. 2011)

So, regardless how promising the shift in substrate metabolism from carbohydrates to fats, as it is visualized in figure 1 may appear, if you just want to shed a few pounds of unaesthetic, but healthy subcutaneous body fat, stay away from tetradecylthioacetic acid - for your heart's sake!

TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants? Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run

Image 1: 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). As far as their effects on weight loss are concerned, the latter is certainly more potent,... the debate on the side-effects of both is yet still far from being settled. Despite the mainstream hoopla around the former...

At least for those of you who have been around the supplement world for some time, the acronym TTA, which stands for tetradecylthioacetic acid, a structurally modified 16 -carbon saturated fatty acid (SFA), which has been shown to increase fatty acid oxidation and reduce triglyceride levels via interactions with purportedly all PPAR-receptors, should ring a bell. For the rest, it will yet probably be news that, back in the early 2000s, TTA was all the rave as the new star among OTC-fat burners. And in fact, the weight loss people experienced on respective products was non-negligible... yet so were the side-effects which crept up over time (and with ever-increasing dosages): Headaches, cramps, dehydration and water retention specifically in the abdominal area were only the minor complaints. Unbearable fatigue and even palpitations were at the other extreme of the spectrum and probably the actual reason why company after company  altered the formulation of their "effective" and above all commercially successful tetradecylthioacetic acid containing fat burners.

While TTA works well, but has well-known side-effects,...

A recent long-duration rodent study that was conducted by a group of European researchers and which my friend Sean Casey from CasePerformance has brought back up onto my radar (Vigerust. 2012), did now investigate the long term (50 weeks) effects of supplemental tetradecylthioacetic acid and another purportedly saver PPAR-agonist, with similarly beneficial effects on triglycerides yet hardly noticeable effects on weight management - my all-time favorite fish oil! To this extend, the scientist kept their rats on their infamous interpretation of a "high fat" diet, which, as you will probably already have expected, had a moderate fat content of 25% tons of carbs and little protein and had thusly more of the standard American diet than of what people in the bloggosphere usually refer to as a "high fat" diet, i.e. a diet that is really high in fat (>50%) and low in carbohydrates.

Figure 1: Relative body weight (compared to identical baseline) in rats at different time points during 50 weeks on high fat diet (control) with either TTA, fish oil or both (data calculated based on Vigerust. 2012).

It is thusly not surprising that replacing 10% of the fat by fish oil (~11g EPA + 6g DHA for avg. human) had absolutely no effect on the weight gain of the hyperphagic (overeating) rodents. The miniscule amount of 0.365% TTA, which would be equivalent to a daily intake of ~912.4mg of TTA for someone consuming 2000kcal/day, on the other hand, lead to statistically highly significant reduction in weight gain over the whole 50 week feeding period (cf. figure 1).

Figure 2: Relative expression of uncoupling protein 3 (UCP3, primary axis) and enzymes involved in fatty acid metabolism (secondary axis) at the end of the 50-week dietary intervention; expressed relative to high fat control (data calculated based on Vigerust. 2012).

As evidenced by the elevations in carnitine palmitoyltransferase II (CPT II), which is necessary to shuttle the fat into the cell, HMG-CoA, which is one of the key players in ketogenesis, and peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), which initiates the first enzymatic reaction during beta oxidation, the hepatic fatty acids oxidation in the TTA (and TTA + FO) group was profoundly increased, in conjunction with the exorbitant increase in UCP-3 expression (>1500x in the TTA only, and >1300x in the TTA + FO group) and the subsequent "leakage" of energy in the form of protons, this easily explains the -11% / -19% reduction in total body weight in the TTA and the TTA + FO groups at the end of the 50 week study period.

....fish oil hardly works and has less-known side-effects

In that, it is important to note, that only TTA (respectively its addition to FO), not fish oil, was able to reduce the diet-induced elevations in hepatic triacylglycerol (TAG) levels. This leads to scientists to speculate, that despite similar effects on TAG and cholesterol transport in the liver, ...

[...] animals given the FO diet are less able to metabolize the excess hepatic lipid levels [... so that] FO redistributed lipids without affecting the total lipid level and body weight.

This would also explain the detrimental effects the fish oil supplement had on hepatic cholesterol levels and lipid oxidation, which would suggest that, at least under these dietary conditions (relatively high fat + high carb + high energy = typical western diet), one would be better off taking no fish oil at all, or a combination of fish oil and TTA.

Figure 3: Relative mRNA expression of markers of protein and lipid oxidation in liver and liver mitochondrial fraction of the rodents at the end of the 50-week study period (data calculated based on Vigerust. 2012)

The latter is all the more indicated in view of the fact that the use of the highly oxidizable fish oil alone lead to non-negligible increases in protein oxidative damage (cf. GSA, alpha-AASA, figure 3) and an increase in total hepatic glyco- and lipooxidation, as evidenced by the increase in Ne-Carboxymethyl-lysine (NCL, figure 3) in the whole-liver samples and a corresponding increase in Nɛ-Malondialdehyde-lysine (MDAL), a lipid-specific marker of oxidative damage in whole-liver and the mitichondrial homogenate (liver M-fraction) of the animals in the fish oil (only) group (cf. figure 3).

These detrimental oxidative longterm effects of fish oil supplementation, which "showed a significant positive correlation with DHA content" of the liver (meaning more DHA in tissue = more oxidation), were only ameliorated, yet not totally prevented by co-treatment with tetradecylthioacetic acid (TTA), which reduced the amount of oxidizable PUFA in plasma and tissue and reduced the mitochondrial ROS production via the UCP-3 induced energy leakage and the subsequent relative reduction in oxidative energy production (remember the overall energy expenditure was still increased by TTA, yet not by FO treatment).

Bottom line: Avoid the dietary PUFA burden, eat healthy and exercise...

Image 2: "You told me to eat more protein and this burger has both meat and cheese!" - click here for more info on why dietary interventions fail

As far as the amelioration of negative side-effects of the typical Western high carbohydrate, relatively high fat diet are concerned, the results of this study would argue against the longterm use of omega-3 polyunsaturated fatty acids from fish oil (DHA in particular) and for the use of structurally modified 16-carbon saturated fatty acid TTA in order to reduce weight gain, triglyceride and liver cholesterol levels in individuals who are either unwilling or unable to make the necessary life-style-changes that would, instead of just prolonging their suffering, help them finally escape from the maelstrom of the metabolic syndrome (cf. yesterday's blogpost on "High Carb vs. High Fat, When Science Meets Real Life").

Whether the same holds true for athletes, fitness enthusiasts or at least moderately active human beings, who stick to an overall anti-inflammatory low(-er) carb (not "no carb" and not necessarily, but possibly "paleo") diet, would certainly warrant further investigation. It would nevertheless, my previously voiced concerns over the injudicious (over-)use of omega-3 supplements in the futile effort to "balance" the dietary over-indulgence of omega-6s... after all, the most straight-forward explanation for the increase in oxidative damage in the fish oil only group is the increased amount of PUFAs in the liver tissue, which are - across the board, i.e. omega-6 and omega-3 - much more susceptible to oxidative damage due to radical oxygen specimen (ROS). I thusly stick to my previous recommendation to just watch your overall PUFA intake and resort to alternative fat sources, such as coconut oil (which is, by the way, the topic of the first "non-SuppVersity" article of mine in the all-new article-section of the VPX-website; don't worry I won't neglect the SuppVersity and stick to topics without potential "conflicts of interest and objectivity" ;-), butter, dairy and meat products from grass-fed animals, eggs and obviously real fish!

... and you won't need TTA to lose weight or ward off unwanted body fat

Moreover, I strongly caution against a similar injudicious (ab-)use of large amounts of TTA especially over longer periods of time. The latter was probably the underlying reason for the initially mentioned side-effects, due to which most supplement manufacturers either totally removed tetradecylthioacetic acid from their products or reduced the amounts per servings to levels, where the other ingredients would give you palpitations before you would achieve dosages way beyond the 1g range, which, as previous human trials would suggest, appears to be save at least in the short term (<30days, cf. Lovas. 2009). With respect to longer durations and/or higher dosages, you should yet be aware that the very same depletion of plasma and tissue PUFAs which is partly responsible for the overall reduction in oxidative damage in the study at hand, may well backfire and produce exactly those cramps, the water retention, and the profound lethargy reports of which you will find in the archives of various health and fitness boards, all over the web.