Leucine Only Tops Ergogenic Effects of BCAAs: Increased Alanine Cycle Activity Spares Muscle Glycogen, Boosts Endurance Performance - BCAAs Have Opposite Effect

Alanine is the liver's favorite gluconeogenic amino acid and leucine appears to increase its usage.

Being among the first to learn about the "Glucose-Repartitioning Effect of Iso-Leucine" in February 2013 (read up on it), you, as SuppVersity reader, belong to the selected few who know that valine and isoleucine may be more than unnecessary props in the leucine-powered BCAA show. With the recent publication of a rodent study from the University of Sao Paulo in Brazil (Campos-Ferraz. 2013), however, it looks as if you had to revise your perspective on the purportedly auxiliary BCAAs - at least, with respect to their ability to reduce fatigue, and muscle and liver-glycogen degradation, in trained rats and possibly (!) humans.

So what did the Brazilian researchers do?

Basically, the idea Campos-Ferraz et al. had in mind, when they came up with their 8 week exercise + 2 week supplementation protocol (see Table 1) was to ...

Table 1: Exercise progression; suppl. was initiated in w7 after lactate test

"evaluate effects of the use of supplementation with leucine or a mixture of BCAAs in trained rats submitted to an exercise-induced protocol of glycogen depletion.

Furthermore, we attempted to investigate muscle and liver biochemical parameters that were not performed in the previous study in order to elucidate the role of BCAAs in glycogen depletion. " (Campos-Ferraz. 2013)

In other words: The researchers wanted to find out whether or not leucine would exert identical, less or more pronounced effects on muscle glycogen use and endurance performance in rodents that the full spectrum of branch-chained amino acids, i.e. leucine, valine and isoleucine.

Contrary to what bro-science and the shiny ads of the supplement industry are suggesting, the scientists' fundamental hypothesis was that the BCAAs supplementation would impair the rodents endurance capacity, because the branched-chain amino acids would be used in muscle to yield acetyl-CoA. This, in turn could reduce the activity of the glucose-alanine cycle, by which the muscles are supplied with alanine-derived glucose from the liver and (once the BCAAs got burne) result in an earlier onset of fatigue.

BCAAs are "glycogen depleters"?!

If you take a look at the data Campos Ferraz et al. gathered in the testing sessions at the end of the supplementation period, in the course of which the rats received an oral gavage of 166mg/kg per day (in human terms this would be ca. 3-3.5g per day) of BCAAs or leucine, it is quite obvious that the  the leucine group had a significantly lower muscle and liver glycogen degradation ratios than the BCAA group.

Figure 1: Liver & mucle glycogen degradation and time to exhaustion (expressed relative to placebo); muscle TCA intermediate content and enzyme activity / concentration (Campos-Ferraz. 2013)

Compared to the placebo group, only the ratios were different.  While the placebo group had the lowest liver glycogen use and a high muscle glycogen use, the supplemental leucine induced a shifted from muscle to liver glycogen and did thus exert muscle specific glycogen sparing effects.

As the researchers point out, these observations stand in line with their original hypothesis: Leucine can spare a significant amount of muscle and liver glycogen and thus produce a highly significant increase in resistance to exhaustion compared to the mixture of BCAAs (P<0.001).

This is not the first study to cast a bad light on BCAA supplementation. As a SuppVersity veteran, you will remember my November 2012 article "Chronic High Dose BCAA Supplementation Reduces Endurance Performance by 43%" | read more, as well as the more recent investigation into the  "Neurotransmitter Depleting Effects of Branched Chain Amino Acids (BCAAs) and Their Potential Ergolytic, Anxiogenic & Depressive Downstream Effects" | read more.

If we compare the endurance performance of the leucine rodents to that of the placebo group, this does yet cast a slight shadow on the overall image of the glorious ergogenic, and, even more so, the purported performance enhancing effects of BCAAs. Despite measurable differences in the time to exhaustion, the actual endurance increase in response to the leucine supplement is relatively small.
 
If you take another look at the data in Figure 1 you will probably notice the significant increase in TCA cycle intermediates (citrate and malate) in the BCAA group. These changes provide further evidence that the provision of all three branch-chain amino acid emphasized the use of glucose as a main substrate to sustain the endurance activity.

"Mouse vs. man": Can we ignore the differences in BCAA metabolism?


At this point, it may however be about time to point out that the activity of the BCAA catabolizing enzyme branched-chain keto acids dehydrogenase complex (BCKD) in humans is quite different from that in rats.

"In the latter [the rat], liver BCKD is almost completely unphosphorylated (activated) in basal state, making it possible to metabolize more rapidly BCKA from the portal blood; in humans, BCKD in liver is normally phosphorylated (inactivated) in order to spare BCAAs for protein synthesis." (Campos-Ferraz. 2013)

In other words: While rodents use BCAAs mostly as an energy source, the human body spares them as a potential protein anabolic.

In view of the fact that the BCAAs are not used to the same degree as an alternative substrate in the human vs. the rodent liver, it is actually not very surprising that the results of the study at hand appear to conflict with data from a previous study by the same laboratory (Gualano. 2011). In the corresponding experiment, Gualano et al observed measurable increases in exercise capacity and lipid oxidation in human subjects during endurance exercise after muscle glycogen depletion in response to the provision of 300mg/kg BCAAs per day.

So, the study is totally irrelevant, right? Not really, no. The fact that we are not able to use BCAAs as a readily available energy source like rodents does after all not mean that they must necessarily have the opposite effects on us. In fact, you all know that the vast majority of studies investigating the beneficial effects of BCAAs on endurance performance in humans yielded a null-result (!) - despite the fact fact that generations of researchers have been convinced that the inhibition of tryptophan uptake must blunt the exercise induced onset of fatigue (learn more in the articles cited in the red box).

Don't forget the endurance reducing increase in glucose usage that appears to be caused by isoleucine (and maybe valine) can also be beneficial: "The Glucose Repartioning Effects of Isoleucine" | read more.

The actual new information this study brings to the table is thus not that BCAAs are not ergogenic. It's rather the previously overlooked leucine induced acceleration of the glucose alanine cycle in liver. It is the activation of this (catabolic!) powerhouse by the means of which leucine "might have an interesting use in physical performance in prolonged or submaximal exercise, where muscle glycogen stores are more likely to be depleted" (Campos-Ferraz. 2013). It should be noted, though, that these effects are probably only observed after the glycogen levels are fully depleted - after an intense workout, towards the end of a race or after an fasted training - in those situations, the performance benefits may even be more more significant than in the study at hand.

Reference:

• Campos-Ferraz PL, Bozza T, Nicastro H, Lancha AH Jr. Distinct effects of leucine or a mixture of the branched-chain amino acids (leucine, isoleucine, and valine) supplementation on resistance to fatigue, and muscle and liver-glycogen degradation, in trained rats. Nutrition. 2013 Nov-Dec;29(11-12):1388-94.
• Gualano AB, Bozza T, Lopes De Campos P, Roschel H, Dos Santos Costa A, Luiz Marquezi M, et al. Branched-chain amino acids supplementation enhances exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion. J Sports Med Phys Fitness 2011;51:82–8

The Oiling of the Liver: The Good & Bad Short- & Long-Term Effects of Tocotrienol + Carotenoid Laden Red Palm Olein, Regular Palm-, Corn- and Refined Coconut Oil

I would not expect "red palm olein wonders", but more RPO and less corn oil in the American diet may at least buffer the liver disease burden in the US (the figure is based on data provided by the American Liver Foundation)

On Turesday, November 19, 2013, you've learned from a study by Subermaniam et al. about the "anti-rust" effects of coconut oil (if you missed that, you can catch up here), today, we are going back to Malaysia and the Universiti Kebangsaan Malaysia and the results of another team of researchers to learn about the effects the various oils have on the "oiling of the liver" (Dauqan. 2013).

I guess most of you will remember my previous comments about the critical role of the liver (and its health or disease) in the development of the metabolic syndrome (read it up). It is thus by no means irrelevant, whether the chronic ingestion of a certain type of oil will result in MDA levels of 92µmol/g or  27.3µmol/g.

Boring!? No, rather surprising!

If you think this sounds boring and are by no means surprised that the malondialdehyde levels of the liver samples the researchers harvested after 4 weeks were 27.3µmol/g, 92µmol/g, 54µmol/g, 47.4µmol/g and 72.6µmol/g for the control diet with mixed fats, red palm oloein (RPO), regular palm oil (PO), corn oil (CO) and the previously celebrated coconut oil (COC), respectively, I would suggest you have a closer look at the the "magic" that happened over the following 4 weeks of on 15% RPO, PO, CO and COC diets.

Figure 1: MDA levels (µmol/g) of liver tissue as a marker of lipid oxidation after four and eight weeks on control diet or control diet with 15% of red palm olein, palm oil, corn oil or coconout oil (Dauqan. 2013)

Well, you see, the way the effects of red palm olein came full circle after another months on the 15% RPO diet is hardly "boring", is it? The MDA levels, a relatively reliable indicator of local lipid oxidation, of the rodents on the 15% red palm olein diet is now, 4 weeks after peaking at 92µmol/g down to 25.2µmol/g, indicating that the level of lipid peroxidation in the livers of the RPO group is now significantly lower than that of any other group (43.4µmol/g, 50.1µmol/g and 48.3µmol/g for control, palm oil, corn oil and coconut oil).

Short term detriments, long term benefits!

I know it sounds more than awkward, but eventually every SuppVersity student should be aware of the fact that the extrapolation of long-term effects from short-term data is a 'risky' business. Unfortunately, even 'experts' often disregard this fundamental rule, when they formulate their recommendations on nutrition, supplementation and exercise.

Table 1: Carotenoid  and vitamin E composition (in %) of crude palm oil and red palm olein; the data is from a different study by Bonni & Choo who tested commercially available products (Bonni. 2000)

The statement, "Prefer coconut oil and avoid red palm olein!", for example would have been a reasonable dietary if we did not know about the turn-around in the second part of the study, when the beneficial effects of the saturated fat content of the coconut oil begin to fade and the absence of natural anti-oxidants in refined coconut oil begins to show its ugly face. At this point, the moderate amount of unsaturated fats in red palm olein (13% omega-6, 0% omega-3; see Bonnie. 2000), of which I am honestly not sure if it is the actual reason of the initial increase in lipid peroxidation (remember: corn oil has more PUFAs!), or whatever other underlying cause of the initial rise in inflammation is overriden by the accumulating amounts of vitamins E and carotenoids from the red palm olein, which rendered the liver of the oxidation-proof, or "rustless" if you will - similarly rustless as the hearts of the rogents in the previously cited study by Subermaniam et al. (learn more).

200g of palm fruits have the same amount of tocotrienols as 4kg of oats. Learn more "tocotrienol" and red palm oil facts in "Tocotrienols: What They Are, What They Do & How They Work + Why the RDA of Palm Olein is NOT 1xCup Per Day " | more

Bottom line: I would like to formulate two take home messages for today's SuppVersity article. Firstly, a theoretical one, which shall remind you of the fact that you can do more harm than good, if you (accidentally) terminate a study in a transitional state and formulate long-term dietary recommendations based on short-term observations, because the study at hand clearly indicates that some effects - in this case the antioxidant effects of the tocopherols, -trienols and carotenoids - take their time to become measurable. And seconfly a very practical one, which is eventually only a reminder of the existence of red palm oil (see article referenced on the right) - an excellent source of dietary antioxidants and probably your only chance to get your tocotrienols and high(er) amounts of some of the rarer carotenoids from regular foods.

References: 

• Bonnie, T. Y. P., & Choo, Y. M. (2000). Valuable minor constituents of commercial red palm olein: carotenoids, vitamin E, ubiquinones and sterols. Journal of Oil Palm Research, 12(1), 14-24.
• Dauqan, E., Abdullah, A., & Sani, H. A. (2013). LIPID PEROXIDATION IN RAT LIVER USING DIFFERENT VEGETABLE OILS. Malaysian Journal of Analytical Sciences, 17(1), 300-309.
• Valls, V., Goicoechea, M., Muniz, P., Saez, G. T., & Cabo, J. R. (2003). Effect of corn oil and vitamin E on the oxidative status of adipose tissues and liver in rat. Food Chemistry, 81(2), 281-286.

Arginine Blunts Growth Hormone Response to Resistance Training: Will the -41% Reduction in Post-Workout Growth Hormone Release Hamper Your Strength & Size Gains?

Arginine-based pre-workout products are more popular with guys than with girls. Could this be the reason that only women complain about unlovedly rapid muscle gains? ;-)

No, this is not a typo! The verb in the headline of today's SuppVersity article really is "to blunt", as in "to neutralize partially" (OED Online 2013). I have to admit that I was also surprised, when I spotted the study over in the "ahead of print" section of the International Journal of Sports Nutrition and Exercise Metabolism. Unless Forbes, Harber and Bell, of whom you will learn later that they've already conducted another 'arginine study', messed up, the results of their most recent experiment do yet leave little doubt: Arginine, an amino acid that is used to test the function of the GH-releasing somatotropic cells within the lateral wings of the anterior pituitary, does - when it is administered at a dosage of 0.075 g·kg-1 body mass right before an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM) attenuate the post-workout growth hormone surge in strength trained individuals (Forbes. Nov 2013).

You want more details? Here you go...

With ~5-6g of arginine being taken before a workout that consists of 3 sets of 8 classic strength training exercises that are performed for 10 repetitions and at an intensity ~75% of the personal 1RM of the 14 strength trained men [age: 25±4 y; body mass: 81.4±9.0 kg; height: 179.4±6.9 cm; and training experience: 6.3±3.4 y], the researchers from the Faculty of Physical Education & Recreation at the University of Alberta in Edmonton, Alberta, Canada designed an experimental setup which comes "shockingly" close to what the average and extraordinaire gymrat is doing, when he or she is hitting the grind.

Figure 1: Level of arginine, GHRH and IGF-1 at T = 0, 15, 30, 60 min of rest-recovery + integrated area under the curve for growth hormone (iAUC GH); all values expressed relative to placebo control (Forbes. Nov 2013)

Against that background the question whether you and the rest of the millions of hobby athletes who spend hundreds of bucks on pre-workout products every year have been hampering their own progress is, as hilarious as it may sound, not a totally unwarranted one. I mean, we can hardly ignore the statistically highly significant -41% reduction in total growth hormone secretion in the one hour "anabolic window" after the workout, Forbes and his colleagues measured - can we?

What do we make of these results?

Most of you will probably remember the often referenced results of West & Phillips, whose 12-week resistance training intervention in the course of which the researchers from the Exercise Metabolism Research Group at the Department of Kinesiology of the McMaster University in Hamilton, Ontario,  made the following observations (West. 2012):

• 

  Suggested Read: "Anabolic Workouts Revisited!" | more

  No correlations between GH, testosterone or IGF-1 and the lean mass gains of their 56 recreationally active young men, who were not actively participating in any weightlifting
  activities <8 months before the study.
• Significant correlations between GH and the increase in type I (slow twitch, oxidative) muscle fibers, but no correlation between testosterone, IGF-1 and cortisol.
• Significant correlations between GH, as well as cortisol and the increase in type II (fast twitch, gylcolytic) muscle fibers, but no correlation between testosterone and IGF-1.

Unlike Forbes, Harber and Bell in the study at hand, West and Phillips measured the hormone levels for up to 2h after the workout. It is thus possible, but in view of the progression of the GH levels in the Forbes study relatively unlikely, that we'd see a rapid increase in the 2nd hour of the rest period and thus an increase in the total amount of GH that's released in response to the combination protocol (arginine + exercise).

Is the decrease the result of a previous GH "overload"?

With respect to the possible involvement of an auto-negative feedback, which is another, previously suggested explanation for this phenomenon, of which I had to realize during my research for this article that it has been covered in the literature before (Kanalay. 2008), Forbes et al. remark that their data would basically exclude the possibility that "the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop." (Forbes. Nov 2013)

It may not be the perfect muscle builder and maybe not even something you want to take in the vicinity of a workout, but there is still promising data on the metabolic effects of arginine esp. for (pre-)diabetics | more

In other words, Forbes et al. exclude the possibility that the subjects experienced a rapid increase in growth hormone as we would see it in response to the intravenous injection of arginine (10x increase with 20g/m² surface area of the 12 normal men in a 1996 study by Rahim et al.) that would then have shut down the GH production just as the exogenous administration of steroids would shut down your natural testosterone production.

If we focus on the available data, the conclusion of the researchers from the University of Alberta is certainly right. If we do take into account that we are talking about post workout supplementation and remind outselves that "the somatotrope is also known to have a refractory period" (Kanaley. 2008), it should be obvious that post-workout measurements, alone, cannot exclude the possibility that the GH spike that's responsible for the auto-negative feedback occurred during, not after the workout.

In other words: Instead of focusing exclusively on the post-workout GH levels, Forbes, Harber and Bell would actually have had to measure the pre & intra-workout GH response, as well. The GH spike that would cause the auto-negative feedback could after all have been caused by a sudden drop in blood glucose in response to the insulin sensitizing effects of arginine and the 'glucose hungry' strength training session.

Auto-negative feedback is still possible, but isn't there something else?

An alternative explanation for the lowered growth hormone response may come from a closer reading of the 'prequel' to this study. In January, Forbes et al. published a paper with the same supplement, but a different exercise protocol. Instead of hitting the weights, their 15 aerobically trained male subjects cycled for 60 min at 80% of their personal VO2_max - again, immediately after ingesting 5-6g of l-arginine (0.075g/kg body weight).

Is there anything arginine is good for, if it's not a muscle builder and it's effects on nitric oxide are overblown? There is a previous SuppVersity article that would suggest so: "Arginine a BAT Building WAT Killer & Repartitioning Agent?" | more

Contrary to the strength training routine, the (relatively) high intensity cycling had identical effects on the hormonal, metabolic and cardio-respiratory markers of the subjects, the two things that differed, though, were

• the rate of fatty acid oxidation at the onset of the workout, which was reduced in the l-arginine group, and
• the levels of the sugar alcohol glycerol at the 45-min time point, which were slightly, but significantly increased

These observations stand in line with the effects McConell et al.  observed in a 2006 study in response to the infusion of l-arginine.

The arginine infusion increased the glucose uptake and blunted the increase in nonesterified fatty acid and glycerol concentrations during 120min of cycling at 72% of the VO2max which were followed immediately by a 15-min "all-out" cycling performance bout (McConell. 2013). Whether it also changed the GH response is however something I can't tell you, because reseachers from the The University of Melbourne did not measure the effect the arginine infusion had on the growth hormone levels of their study participants. I would yet guess that it will have been similar to the one on the cycling study Forbes did. This, in turn, would suggest that the effect depends on (a) duration and energy expenditure, or (b) the substrate utilization during the workout (lifting weights = glycolytic; cycling = rather oxidative). In the end both of these are related to the reliance on fat, not glucose / glycogen to fuel the energetic demands of your workout and as you all know the acute provision of  glucose is the prerogative of glucocorticoids (i.e. cortisol), not GH.

There may be another reason arginine does not make you "big": It's one out of three amino acids that have an especially pronounced satiety effect | learn about the others!

I can't exactly tell you why, but I can tell you that... I openly admit that I was surprised by the results of the study at hand. I  surprised that I missed this (side) effect of arginine, before, but I am not worried that the arginine supplements you may be or may have been taking are / were  hampering your training success.

 If that was the case one of the many "real-world" arginine supplementation studies, where the study outcome wasn't some funky hormonal marker of which we still don't know whether / to which extent it actually affects skeletal muscle hypertrophy, would have shown a trend for decreasing performance, lean mass and strength gains with arginine supplementation - this, I can assure you was not the case.

In fact, those of you who remember one of my posts on the 'arginine powered' VPX preworkout products (learn more), will remember that the scientists observed, if anything, opposing, i.e. beneficial effects from complex preworkout products as most of you will be using. A somewhat different picture emerges for the 'arginine only studies' where "only" three out of five acute supplementation and four out of eight chronic supplementation studies showed measurable, but in many cases negligible performance gains (Alvares. 2011). And the null-effect the authors of the other papers observed is no reason to be concerned, either.

References:

• Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. 2011 Mar 1;41(3):233-48.
• "blunt, v.". OED Online. September 2013. Oxford University Press. http://www.oed.com/view/Entry/20664?rskey=iZQVcA&result=3&isAdvanced=false (accessed November 19, 2013).
• Forbes SC, Harber V, Bell GJ. The acute effects of L-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists. Int J Sport Nutr Exerc Metab. 2013 Aug;23(4):369-77. Epub 2013 Jan 8.
• Forbes SC, Harber V, Bell GJ. Oral L-Arginine Prior To Resistance Exercise Blunts Growth Hormone in Strength Trained Males. Int J Sport Nutr Exerc Metab. 2013 Nov 13. [Epub ahead of print]
• Kanaley JA. Growth hormone, arginine and exercise. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):50-4. Review.
• McConell GK, Huynh NN, Lee-Young RS, Canny BJ, Wadley GD. L-Arginine infusion increases glucose clearance during prolonged exercise in humans. Am J Physiol Endocrinol Metab. 2006
• Rahim A, Toogood AA, Shalet SM. The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf). 1996 Nov;45(5):557-62.
• West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702.

Rustless Hearts: Adding 15-20ml of Virgin Coconut Oil to Your Diet May Counter the Oxidative Stress From Partially Oxidized Fats and Keep Your Heart Rust-Free

Could a daily dose of virgin coconut oil really be all it takes to escape the #1 leading cause of death (CDC data) - despite French fries and co?

Originally I wanted to post the results of this study from the Universiti Kebangsaan Malaysia as a short news item in the Facebook News. Then I decided that it may actually be worth to allow you to have a look a the surprisingly pronounced effects the addition (not replacement!) of 3-4 tablespoons of virgin coconut oil had on the in vivo lipid oxidation levels of rodent hearts in the course of this 4 months study at the end of which the researchers did not simply measure the systemic, but the more significant local malondialdehyde (MDA) levels. With the direct analysis of the presence of lipid oxidation production in the heart being a more reliable indicator of whether or not the changes the researchers observed in the study at hand are physically relevant...

Ah, I don't want to give it all away. So let's rather take a look at Subermaniam et al.'s attempt to "to investigate the influence of virgin coconut oil on the malondialdehyde level in the heart tissue of rats fed with heated palm oil." (Subermaniam. 2013)

Palm oil is ubiquitous

I am not sure if you are aware of that, but the regular palm oil (not the red PO with the high carotene and tocotrienol content), with its saturated - unsaturated fatty acid ratio close to one, has become the most widely used "vegetable oil" worldwide. In fact, if the product label says "vegetable oil" and there is a significant amount of saturated fats in a product, it's likely that what you are about to eat contains palm oil, which is easy to process and, with its 1:1 ratio of saturated to unsaturated fats relatively stable.

Rejection points of various oils (Marikkar. 2007; Berger. 2005; Casai. 2010)

Cooking with Virgin Coconut Oil (VCO) - good or bad idea? The answer to this question is not as straight forward as you may think. On the one hand frying the "virgin" oil, will have it lose it's virginity, i.e. most of those molecules that are responsible for the beneficial health effects. On the other hand, a study by Marikkar et al. (2007) shows that these molecules act as a buffer, due to which VCO has a 30% higher rejection point (13h vs. 10h of frying at "only" 180°C; compare to the other oils in the table to the right) than regular coconut oil (CNO) and refined corn oil (CO). After those 13h the concentration of newly formed compounds (TPCs) that have higher polarity such as oxidized triglycerides, diacylglycerides and fatty acids is >25% and downright unhealthy.

Despite being less prone to oxidation, the way the oil is reheated and (ab-)used for deep frying by the food industry can cause changes in the fatty acids composition of palm oil that may have significant health consequences.

"Repeatedly heated oil undergoes changes in physical appearance and a series of chemical reactions such as oxidation, hydrolysis and polymerization that eventually alter the fatty acid composition . Therefore, when the degree of unsaturation in fatty acid is greater, it is more vulnerable to lipid peroxidation (Choe. 2007)." (Subermanian. 2013)

In mouse and man, the ingestion of this chemically altered oil has been found to increase the levels of ,alondialdehyde  (MDA), one of the major end products of lipid peroxidation which causes endothelial damage, vascular inflammation and cell membrane injury (USDA. 2007).

Virgin coconut oil to the rescue?

Studies by Harrison and Ng have shown that the increases in MDA levels in response to the ingestion of oxidated palm oil causes "oxidative stress" and increases in blood pressure that cannot be countered by the ingestion of common antioxidants such as vitamin C and E (Harrison. 2007). Now, Subermaniam et al. were interested, whether the same would be true for the sunsaponifiable components in virgin coconut oil.

SuppVersity Suggested Read: True or false - Eating tons of medium chain triglycerides (MCTs) will make you lean | learn the truth!

In previous studies, these molecules, which are lost when the milk is not extracted under controlled temperature, have been linked to a host of beneficial health effects, e.g.

• anti-inflammatory and anti-thrombotic properties,
• the ability to reduce the oxidation of LDL cholesterol, or
• beneficial effects on the immune factor and cytokine response to endotoxins,

of the increasingly popular medium-chain-triglyceride rich oil from Cocos Nucifera Linn - an oil of which Figure 1 tells you that it has a lower peroxide value than freshly extracted palm oil even after processing and storage.

In view of its already established health benefits, the assumption that virgin coconut oil can ameliorate the pro-oxidative effect of diets that were fortified with 15% pre-heated palm oil, when it is administered to rodents at a daily dose of 1.43 ml/kg of body weight/day by oral gavage does not appear to be too far-fetched.

Figure 1: Left - MDA level in heart tissue after 4 months of feeding with basal diet (control), five times heated palm oil (HPO), basal diet and VCO supplementation (VCO) and five times heated palm oil with VCO supplementation (HPO+VCO; left); right - baseline peroxide value (in mEQO2/kg) of the oils used in the study (Subermaniam. 2013)

The rats stayed on these regular palm oil, pre-heated palm oil, regular palm oil + VCO, pre-heated palm oil + VCO and an unmodified control diet for 4 months. Thereafter, the thirty two rats were sacrificed and their heart tissues were harvested in order to measure the level of lipid oxidation. The results? Well, you just have to look at Figure 1 to see that there was a significant (p < 0.05) decrease in MDA (and peroxide / data not shown) values in the rodents which received the supplemental coconut oil on top of their heated palm oil diets.

Bottom line: It is unquestionably impressive that the effects of what would have been ca. 15-20ml commercially available virgin coconut oil for a human being were so pronounced that the oxidative stability of the lipids in the cells of the rodents on the HPO + VCO ended up being virtually identical to that of the rodents which received the regular chow. I must still warn you not to expect any of the meanwhile literal "Coconut Miracles".

In view of the fact that the benefits of the 'VCO supplement' did not depend on the presence of a "junk food" diet, it is still obvious that the addition of one or another tablespoon of virgin coconut oil may be one of the 1001 pieces of your personal "healthy lifestyle" puzzle - along with a protein- and vegetable-rich whole foods diet, exercise and more than just an occasional night of good night's sleep, of course ;-)

References

• Berger KG. The use of palm oil in frying. Malaysian Palm Oil Promotion Council. 2005.
• Casal S, Malheiro R, Sendas A, Oliveira BP, Pereira JA. Olive oil stability under deep-frying conditions. Food Chem Toxicol. 2010 Oct;48(10):2972-9.
• Choe E, Min DB. Chemistry and reactions of deep-fat frying oils. Journal of Food Science. 2007; 72(5):R77-R86.
• Harrison DG, Gongora MC, Guzik TJ, Widder J. Oxidative stress and hypertension. Journal of the American Society of Hypertension. 2007; 1(1):30-44.
• Marikkar et al. Assessment of the stability ofvirgin coconut oil during deep-frying. Cord 2007; 23(1).
• Ng CY, Kamisah Y, Faizah O, Jubri Z, Qodriyah HM, Jaarin K. Involvement of inflammation and adverse vascular remodelling in the blood pressure raising effect of repeatedly heated palm oil in rats. Int J Vasc Med. 2012;2012:404025.
• Subermaniam K, et al. Virgin Coconut Oil (VCO) Decreases the Level of Malondialdehyde (MDA) in the Cardiac Tissue of Experimental Sprague-Dawley Rats Fed with Heated Palm Oil. Journal of Medical and Bioengineering. 2014; 3(2).
• World  Vegetable  &  Marine  oil  Consumption,  World  Statistics, USDA, 2007, pp. 10

Sugar Sweetened Beverages & Total Energy Intake: Studies Suggest That Normal-, Overweight & Obese Women CAN Compensate for 168 Additional Sugar Calories Per Day

Usually they are touted as the reason for weight gain: Sugar-containing soft drinks like the Scottish brew Irn Bru. In the study at hand, however, they helped 41 obese women lose weight - how come?

Despite the fact that it is not the first of it's kind, I decided that the paper Roy Nelson sent me the a couple of days ago may still be worth being covered in a brief article. Marie Reid and her colleagues were after all able to show that we can, theoretically and without conscious effort, compensate for the additional energy intake from sugar-sweetened beverages.

As I already mentioned, this is not the first study Reid and her colleagues from the Hull, Ulster and Herriot-Watt Universities in the UK conducted, but it is the first one where the subjects, obese women, with previous diet experience, came right from the subgroup of the population of whom we simply assume that their weight problems would (partly) result from these "empty calories".

Would the women "recognize" the 168kcal of pure sugar in their diets?

After exclusion and dropouts, Marie Reid et al. were left with a total of 41 healthy obese (BMI 30– 35 kg/m²) 20-50 year-old women who were randomly assigned to consume sucrose (n=20) or aspartame (n=21) drinks over 4 weeks in a parallel single-blind design.

Based on the previously mentioned experiments with normal- and overweight women, the researchers knew women with higher body weights had a harder time to compensate for the 168kcal the sugar-sweetened drinks delivered than their lean peers. It was thus interesting to see, whether the obese women (1) would compensate for the additional energy intake and (2) whether the compensation would be less pronounced than in the lean and overweight participants of the previous studies.

What's missing from the study at hand are the really important things, i.e. the changes in blood glucose and lipid metabolism and the differences in waist circumference and / or body fat levels. So whatever the scale of the subjects said, this and the previous studies by Reid et al. don't provide the basis for an acquittal of sugar sweetened beverages (learn more about the debate the role of Pepsi, Coke & Co in the diabesity epidemic).

Instead of simply having their subjects fill dietary records, the scientists used the weight response to judge, whether or not the women fully or partly compensated for the additional energy intake from the sugar sweetened beverages (note: the beverages contained regular sugar, no HFCS). Reid et al. did yet also analyze the changes in macronutrient composition to elucidate, whether the expected reduction in regular (food) energy intake would go at the expense of any particular macronutrient, i.e. carbs, proteins or fats.

Figure 1: Macronutrient and energy intake of the sugar (left) and aspartame (right) group (Reid. 2013)

The test drinks the scientists used came in 250 ml bottles. The women were instructed to consume four of these bottler, the content of which was sweetened with plain sucrose (fructose + glucose) or aspartame. Of the latter, the commercially available soft drinks (Irn Bru) contained

• 10.5g of sucrose, but no aspartame in the regular and (sugar)
• 0g of sucrose and a miniscule amount of aspartame in the diet variety (aspartame)

If you  do the math you can easily calculate that the regular Irn Bru provided an additional energy intake of 4x10.5g/day x 4kcal/g = 168kcal/day and a total of 4704kcal if we take the whole 4-week study period. According to the faulty rule of thumb that informs us that 1lbs of fat would equal 3,500kcal (learn why this is *bs*), the women in the "regular" Irn Bru group (sugar) should end up with "exactly" (*rofl*) 672g of additional fat on their hips.

Sugar doesn't make you fat and artificial sweeteners seem to hamper weight loss!?

I guess (or hope) that you will not really have expected to see those 672 extra grams of fat on the hips of Reid's, subjects at the end of the study. Still, most of you will probably have expected that the ladies did gain weight, right? Much to my own surprise, this was not the case: In fact, the vast majority of the ladies missed the predicted weight gain by more than 1kg (1.72 (SD 0.47) kg).

Figure 2: Illustration of the results of the study at hand (obese women) and previous studies with normal- and overweight women all of which showed sufficient energy compensation for the 4x250ml soft drinks  (Reid. 2007, 2010, 2013); note the listed "weight loss", e.g. -1.72kg, denotes the difference between the actual and the predicted body weight, see red box!

Now, being part of a study like this certainly is a confounding factor that could precipitate to conscious energy restriction. If this was the reason the ladies didn't gain weight, though, the women in the aspartame group would actually have had to lose a significant amount of weight.

It's not like the lean or overweight  women did not gain any weight at all.

This is not "sugar induced weight loss"! If you look at the graphs from the previous studies (left) in which Reid et al. did not use the "compared to expected weight gain" trick, it's obvious that only the lean women got away without weight gain.  In the overweight and obese women, there was a small, but due to the large outliers statistically non-significant increase in body weight.

I mean, you would certainly expect the women in the placebo group to take the same measure to make sure the potentially sugary (remember this is a randomized, blinded study) brew they were drinking would not end up on their hips.

A brief glance at the total energy intake in Figure 1 appears to confirm that: The women in the aspartame group did also reduce their energy intake. Due to significant differences among the study participants this did however not lead to a net change in body weight. From a statistical perspective, this means that the body weight of "Mrs. Average" did not change - neither in response to the sugar- nor in the aspartame sweetened drinks. 

Wtf? Sugar does not make you fat!? There are a couple of good reasons we got to be cautious with generalizing assessments like "sugary drinks are not the problem!":

1. 

   In contrast to the study Sartor et al. found that their participants gained 1kg of fat in only four weeks "on" Lucozade energy drinks | more

   Neither this study nor the previous studies measured the health-relevant changes in body composition of which the 2012 study by Sartor et al. clearly shows that they will occur if you simply add a bunch of sugary energy drinks to your diet (learn more).
2. With its 100% plain sugar content, the beverage the scientists used is not representative of the "average" soda. It is thus unwarranted to conclude that the lean, overweight and, in the study at hand, obese subjects would also be able to compensate for beverages with HFCS, dextrose or whatever other funky caloric sweeteners the industry uses.

Even if (2) was not true and similar compensatory effects wouldn't be observed with sweeteners, the data from the study at hand clearly weakens the "empty calories" argument. It does so, however, without being the first class acquittal Sugar Nutrition UK was probably hoping for when they decided to provide the financial means for this study.

References

• Reid M, Hammersley R, Hill AJ, Skidmore P. Long-term dietary compensation for added sugar: effects of supplementary sucrose drinks over a 4-week period. Br J Nutr. 2007 Jan;97(1):193-203.
• Reid M, Hammersley R, Duffy M. Effects of sucrose drinks on macronutrient intake, body weight, and mood state in overweight women over 4 weeks. Appetite. 2010 Aug;55(1):130-6.
• Reid M, Hammersley R, Duffy M, Ballantyne C. Effects on obese women of the sugar sucrose added to the diet over 28 d: a quasi-randomised, single-blind, controlled trial. Br J Nutr. 2013 Oct 29:1-8. [Epub ahead of print]

Beta Alanine Fails to HIIT Back: No Increased Training Effect in Response to Nine 4x4 Min HIIT Workouts W/ BA Preload, But Evidence in Favor of Chronic Supplementation

Contemporary scientific evidence suggest that you have to pick the right type of (short intense) exercise if you don't want your beta alanine supplement to end up as another "false starter" in your closet.

In the past couple of weeks beta alanine (BA) has gotten some bad press, here at the SuppVersity. While some conspiracy theorists may already have smelled a personal vendetta of a sodium bicarbonate advocate like myself against its 'high tech competitor', the actual reason for the negative, or at least not necessarily exciting news is the exercise specificity of beta alanine (BA) supplementation.

The most recent BA study from the  University of Bern and the Swiss Federal Institute of Sport in Switzerland and the Karolinska University Hospital in Sweden is yet another rather disappointing BA study to support my previous assertion that the benefits for the average gymrat are largely overblown.

What did the researchers do

As Gross et al. point out, the aim of their two-part intervention study was to alter the physiological systems discussed above in ways that could improve severe exercise performance. In that, their hypotheses were that

1. 

   If we look at the results of previous studies, it appears that the question, whether BA ↪ promotes or ↪ blunts the ergogenic effects of baking soda does also depend on the type of exercise.

   ... HIIT, by improving VO2max and VO2 kinetics, would enhance aerobic energy contribution during severe cycling exercise
2. ... beta-alanine supplementation, by increasing intramuscular carnosine, would improve buffering capacity and reduce pH disturbance, or otherwise dampen muscle fatigue during severe cycling exercise; and 
3. ... prior supplementation with beta-alanine would allow for greater training load and better recovery during HIIT,which would enhance benefits of training on physiological determinants of severe exercise performance. 

As a seasoned SuppVersity veteran you know about the profound training effect of high intensity (if you don't educate yourself). You will also know / have expected that the 38-day preload in the course of which the participants consumed either

• * supplements were provided as 400-mg gel capsules and taken with the 3 main meals and before bed
  4 x 800mg/day "purified beta alanine"* (BA), or
• 4 x 800mg/day maltedextrin (PLA),

would increase the intramuscular carnitine stores of the participants in the BA group. What you don't know, however, is whether the eight endurance, team, or combat sport athletes in the active study arm would also display lower serum pH levels, experience less fatigue, and record greater improvements in VO2max than the remaining nine subjects in the placebo arm of the study.

Let's take a look at the results

I guess, it doesn't make sense to keep you on the tenderhooks any longer, so let's see what happened  during and after the obligatory nine 4 x 4 minute interval HIIT sessions on a cycle ergometer (10 min warm-up; heart rate 90-95% of max; 3min light cycling between intervals).

Simply taking your beta alanine supplements with food increases the absorption of BA more effectively than fancy "time-release" caps or tablets | read more

Chronic vs. cyclic BA supplementation: It is an interesting side-finding of he study at hand that 9 HIIT sessions and a 7-day rest-period can reduce the carnosine overload in the vastus lateralis and vastus internus (the teardrop muscle) by statistically significant 6.5% and 12.2%, respectively. This would mean that a chronic high intensity overload can very well induce significant reductions in carnosine levels within less than a month. A workout fanatic who wants to keep his muscles supersaturated with carnosine on all 365 days of the year should thus not follow my previous suggestion to do 6-weeks on, 4-weeks off cycles. In view of the results of the study at hand, I will yet leave it to you to decide whether you feel this is actually worth the effort / money.

The sessions were performed as follows: Sessions 1-3, 1 day rest, sessions 4-7, one day rest, sessions 8-9; and all participants had been following their habitual training and nutrition regimen during the 38-day "preload".

Figure 1: Changes in VO2max, peak power output, max. blood lactate, and power at second ventilatory threshold in from baseline (pre) to post-supplementation (before HIIT) and from baseline (pre) to the end of the study (after HIIT +7-days)

If you read the text in Figure 1, you will be aware that the changes the scientists observed in response to the exercise regimen look impressive, but lack statistical significance. In the end, the results are thus way less exciting than the relative performance increases in the 10 ± 5% range would suggest.

It is difficult to say if the overall effect size is the reason that there were no significant inter-group differences. Since there were not differences at all (not even borderline or non-significant ones), it is however unlikely that a longer study duration and correspondingly more pronounced increases in VO2Max, peak power and co, as well as the likewise identical post workout glycogen synthesis and muscle fiber cross-sectional area would have yielded a significant advantage on part of the BA supplemented trainees. The fact that the increases in skeletal muscle buffering capacity reached significance only in the placebo group, would even support the exact opposite hypothesis, i.e. more pronounced long-term adaptive effects without beta alanine supplementation.

The 2012 meta-analysis by Hobson et al. demonstrated two things (a) BA produces predictable performance increases only in the 60-120s range and (b) the overall effect size is much smaller than what most people are (mis-)lead to believe, when they read the advertisements... ah "write-ups" on the Internet.

What do we make of these results? In view of the overall rather disappointing results, I am not sure if you feel that the 1.3% increase in aerobic activity and -5% decrease in O2 deficit is convincing enough to subscribe to idea that beta alanine powered carnosine loading is a viable strategy to improve the adaptive response to long(er)-duration interval training (here "longer" is 4-min).

In my humble opinion this is not the case. Not necessarily because I feel that BA is a supplemental non-starter, but rather in view of its exercise- / duration-specificity, of which Hobson et al. wrote in their 2012 meta-analysis that it restricts the usefulness of beta alanine to sports where the overall duration of high intensity muscular contractions is longer than 60s, but shorter than 240s. This is a pretty narrow margin and even within this "performance zone" the mean effect size of 2.85% does not come remotely close to what you'd expect to see when you read the boastful promises in the "write-ups" of the supplement industry.

References:

• Hobson RM, Saunders B, Ball G, Harris RC, Sale C. Effects of β-alanine supplementation on exercise performance: a meta-analysis. Amino Acids. 2012 Jul;43(1):25-37.
• Gross M, Boesch C, Bolliger CS, Norman B, Gustafsson T, Hoppeler H, Vogt M. Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise performance. Eur J Appl Physiol. 2013 Nov 9. [Epub ahead of print]

TReaTing Diabesity With Testosterone!? If You Keep DHT in Check + Stay Away From Aromatase Inhibitors, It May Work

It probably won't turn an overweight pre-diabetic into a fitness model, but a getting a TRT script has the potential of changing a man's physical and psychological health for the better.

Despite the fact that more and more men recognize the benefits of supervised testosterone replacement therapy (TRT) and the bodybuilding and fitness community cherishes 'their BIG T' as the be-all-and-end-all, many medical practitioners look at the administration of exogenous androgens as a potential health hazard. I would even bet that it won't be difficult to find one or two MDs who would say that Patricia S. Juang et al.'s idea to administer testosterone to obese men with normal, but low baseline testosterone levels to improve their body composition and insulin sensitivity borders physical injury - and that irrespective of adjuvant 5α-reductase (dutasteride) or aromatase (anastrazole) inhibitor administration.

TRT w/ or w/out aromatase or 5α-reductase inhibitor?

It goes without saying that the bodybuilding enthusiasts will think very differently about the usefulness of the 10 g testosterone gel (Testim) the fifty-seven 24–51-year old men with free testosterone levels in the lower 25% of normal range (<0.33 nmol/L) and a body mass index of ≥30.0 kg/m² in this recent  98-day randomized, double-blind, parallel group, placebo-controlled trial from the Universities of California and the Boston University Medical Center (Juang. 2013). In fact, I am pretty sure that, contrary to the scientists who put their subjects on either

• + subjects received a gonadotropin releasing-hormone antagonist to suppress endogenous T production
  10g Testim per day,
• 10g Testim + 1mg Arimidex (anastrazole) per day, or
• 10g Testim + 2.5 mg Avodart (dustasteride),

some of the physical culturists may even have suggested to use both, the aromatase inhibitor Arimidex and the 5α-reductase inhibitor Avodart to make absolutely sure that the T remains T and is not converted to estrogen or DHT.

Figure 1: Change in hormone levels (left) and body composition (right) after 98 days on 10g t-gel (Testim) with / without aromatase (Arimidex) or 5α-reductase (Avodart) inhibitor (Juang. 2013)

If they looked at the data in Figure 1, the estrogen-phobic bodybuilding enthusiasts would yet have to admit that the "bad estrogen" cannot be so bad as broscience would have it. Only minimal decreases in body fat, and significantly lower increases in fat free mass in the presence of a 5cm! (+4%) increase in waist circumference is certainly not what the bros are looking for.

Looking for natural ways to boost your testosterone levels? Look no further! You can learn about 10 ways to up your testosterone levels in my previous article "Natural Hormone Optimization Made Simple & Cheap: Avoid These 10 Anti-Androgens to Boost Testosterone & DHT" | read more

As surprising as the magnitude of the 'waist gain' may be, I personally have been more surprised by the effects the 10g of Testim had on the DHT levels of the overweight subjects. In both, the T-only and the T + Arimidex group the DHT level literally exploded and blunted the 25%, respectively 30% increase in glucose disposal during  minutes 120–180 and 240–300 of the euglycemic hyperinsulinemic glucose clamp test the scientists performed before and after the intervention period (Juang. 2013).

Despite a -40% decrease in PSA (vs. +9% in the T-only group), the 5α-reductase inhibitor dustasteride did not prevent the ~10% increase in prostate size that occurred in both the T-only (12%; +9% PSA) and T + Acodart (10%; -40% PSA) group. Other safety markers, such as AST (liver) or haemoglbin (iron overload) did not change.

The fact that dustasteride does not blunt testosterone induced lean mass gains is something you may have read in a previous article | more

Bottom line: I guess there are three things we can take away from this study:

1. TRT can help overweight men with impaired insulin resistance improve their body composition.
2. The administration of an aromatase inhibitor blunts the beneficial effects and causes a surprisingly pronounced increase in waist circumference.
3. The glucose sensitivity increases only, when the excessive reduction of testosterone to DHT is blocked by dustasteride.

In other words, if you want the T accept the E, but watch your DHT; but remember: Don't do it without blood work!

References:

• Juang, P. S., Peng, S., Allehmazedeh, K., Shah, A., Coviello, A. D. and Herbst, K. L. (2013), Testosterone with Dutasteride, but Not Anastrazole, Improves Insulin Sensitivity in Young Obese Men: A Randomized Controlled Trial. Journal of Sexual Medicine.

LDL-P Drops by 27nmol/L With Every 1% Reduction in Trans Fat Intake. Plus: "Trans-Fat Free" Does Not Mean Risk Free!

In contrast to the message "trans fats = bad". The information that cookies and bakery, not cooking oil, margarine, chips & co are the main trans fat offenders in our diet has reached only a very small group of people.

There are only few 'nutritional wisdoms' out there that are actually 'wise'. One of them is the notion that "trans-fats are bad for you". By now that's something every fifthgrader knows. What most people don't know, though, is how bad "bad" actually is and whether the small amounts of trans fatty acids, the industry is cleverly hiding in their products by downsizing them in a way that "one serving"contains less than 0.5g of transfats - that's the magic loophole in the FDA regulations according to which transfats don't have to appear on the label, as long as the total amount per serving is less than 0.5g.

The question I would like you to remember, when you read more about the most recent strudy from the Preventive Cardiology Program at the Columbia University Medical Center/New York-Presbyterian Hospital in 2013 is: 

Do those 0.5g/serving the FDA is turning a blind eye on matter?

Within the past decades, the ill health effects of transfats have been addressed by countless studies. The study at hand, however, is the first one to directly assess and quantify the influence of transfats on LDL particle number (LDL-P = particle number, not LDL-C = LDL content!).

This is not about CLA & Co: Most of you will be aware that the "bad" trans-fat this article is not about CLA, but about the trans-fats from partially hydrogenated vegetable oils and other industrially processed fats and oils. If you want to know how much trans-fats (in % of total fat) the french fries and chicken nuggets at "your" Mc Donald's or KFC contain, just take a look at the table on the left (data from Stender. 2006)

As Garshik et al. point out, compared to the standard measure LDL-C the exact number of LDL particles, i.e. LDL-P, has been found to be a superior indicator of heart disease risk compared.

"Studies have suggested that increased LDL-P leads to progression of CVD and that the predictive value of LDL-P for future CVD events is equal to or greater than more traditional lipid measurements such as LDL-C." (Garshik. 2013)

That alone is a huge plus, but guess what: M. Garshick, H. Mochari-Greenberger and L. Mosca have been working with real patients - no rodents.. ah pardon, strings attached ;-)

This is not just another rodent study

Having the advantage of actually working in a hospital, not a sterile lab setting, the researchers picked participants from the Family Intervention Trial for Heart Health (FIT Heart), a National Heart Lung and Blood Institute (NHLBI) sponsored randomized controlled clinical trial that enrolled 501 family members of patients who were admitted to the cardiovascular service of the New York Presbyterian/Columbia University Medical Center, as their subjects. In the course of a previous study, the subjects had been assigned to two different groups:

• 

  Table 1: Subject characteristics at baseline (Garshik. 2013)

  An intervention group, the members of which were invormed about the CVD risk factor screening results and education about diet and physicalactivity to prevent CVD, with regular contact and feedback by a health educator for up to 1-year, and
• A control group, that did not receive the information about their own CVD risk factor and was not part of the organized education program that did obviously include the advise to reduce your trans-fat intake as much as possible

In the course of this study the control group made similar lifestyle changes as the intervention group - despite a lack of formal information / education (Moska. 2008). The reduction in trans-fat intake, in particular, was virtually identical. Therefore, the scientists could pick any of the men and women from the original cohort, as long as there was no lack of information or implausible dietary data for the 1 year study period.

Is it bad, if you get 2.5% of your daily energy intake from trans-fats?

When all was said and done, M. Garshick, H. Mochari-Greenberger and L. Mosca ended up with a "participant pool" the characteristics of which you I've summarized in Table 1. If you stop gazing at Table 1 and take a look that the data in Table 2, you will see that the average subject consumed approximately 2.5% of his or her daily energy intake from trans-fats.

Table 2: Dietary intake (% of kcal/day) and corresponding serum lipid measures in the subjects of the Garshick study.

"Is 2.5% much?" I guess it depends on what you take as a reference. If your reference is the "average" European in the TRANSFAIR study from 1999, this is much. Only the Icelanders, who have the highest trans-fat consumption of all Europeans (2.1% of total calories) come remotely close.

The Greeks on the other hand, live up to their reputation as the fathers of the often-hailed Mediterranean Diet: With a mean trans-fat intake of 0.5% and 0.8% in men and women, respectively, they are compliant with the recommended maximal daily allowance (RDA) of 2.2g trans-fats per day (this statement is based on the assumption that their average caloric intake was 2,000kcal).

You don't have to move to Greece though, to reduce your personal trans-fat intake even further. It is, after all, another flawed urban nutrition myth that you could produce trans-fatty acids in your kitchen by heating whatever type of oil / fat you use to cook (if you never change the oil you use to fry at very high temperatures, things look different, though). Industrially produced junk... ah, pardon "food" - specifically cakes, cookies, etc. - is thus your most if not only significant source of dietary trans-fats. Eliminate those and you are good to go.

Remember: Higher baseline intake = greater relative effect size!

Figure 1: Linear associations between baseline dietary composition and LDL particle number (top) and between change in dietary trans-fat intake and LDL particle number in the course of 1-year (bottom); data based on Garshik, 2013.

Assuming that you are not the cookie monster and consume mostly fresh foods, your transfat exposure is probably much lower than 2.5% of your total calorie intake. The average reduction in LDL particle count per for each 1% of trans-fats you cut from your diet is thus most likely less pronounced than it was in the study at hand.

If we discard the effect size and focus on the general trend, the results of the Garshik study are still highly relevant for all of us; and what's more, most of us will have friends or relatives with similar transfat intakes, a low activity level, a low MUFA and omega-3 intake and way too little protein in their diets - and as Figure 1 can tell you, MUFAs, n-3s, protein and obviously exercise / physical activity are all factors that have been found to be associated with low(er) LDL particle counts and a correspondingly increased risk of arteriosclerosis and heart disease in the Garshik study (see Rosenson. 2002 & 2010; Prado. 2011 for the link between LDL-P and heart health).

Eggs are trans-fat free and heart-healthy | learn why.

So! How dangerous are those 0.5g of trans-fat in "trans-fat free" foods? If we consult the results of a 2011 study by Prado et al., symptom-free individuals with LDL-P levels in the 1953–3560 nmol/L tertile are 3.7x more likely to exhibit coronary artery calcification than those in the 620-1530 nmol/L tertile and take into consideration that the RDA for trans-fats is < 2.2g/day, it should be obvious that those 0.5g of trans-fats, i.e. ~25% of the your maximal daily allowance, are a problem we must not ignore.

If we assume that there is a linear relationship between LDL-P and trans-fat intake (obviously this is a gross simplification) and make a rough and scientifically highly questionable estimate of the consequences, we will find that those unlabeled 0.5g of transfats could boost your LDL levels from the first into the third tertile of LDL-P values in the Prado study (+by 675nmol/L).... that this would also mean that a daily dose of only 0.5g of hidden trans-fats could triple your likelihood of arteriosclerotic plaque should be obvious, right?

References: 

• Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, et al. LDL particle number and risk of future cardiovascular disease in the Framingham offspring study-implications for LDL management. J Clin Lipidol 2007 Dec;1(6):583-92. 
• Cromwell WC, Otvos JD. Low-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler. Rep 2004 Sep;6(5):381-7.
• Garshick M, Mochari-Greenberger H, Mosca L. Reduction in dietary trans fat intake is associated with decreased LDL particle number in a primary prevention population. Nutr Metab Cardiovasc Dis. 2013 Oct 4.
• Hulshof KF, van Erp-Baart MA, Anttolainen M, Becker W, Church SM, Couet C, Hermann-Kunz E, Kesteloot H, Leth T, Martins I, Moreiras O, Moschandreas J, Pizzoferrato L, Rimestad AH, Thorgeirsdottir H, van Amelsvoort JM, Aro A, Kafatos AG, Lanzmann-Petithory D, van Poppel G. Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study. Eur J Clin Nutr. 1999 Feb;53(2):143-57. Review.
• Mora S. Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use. Circulation 2009 May 5; 119(17):2396-404. 
• Mosca L, Mochari H, Liao M, Christian AH, Edelman DJ, Aggarwal B, et al. A novel family-based intervention trial to improve heart health: FIT Heart: results of a randomized
  controlled trial. Circ Cardiovasc Qual Outcomes 2008 Nov; 1(2):98-106.
• Prado KB, Shugg S, Backstrand JR. Low-density lipoprotein particle number predicts coronary artery calcification in asymptomatic adults at intermediate risk of cardiovascular disease. J Clin Lipidol 2011 SepeOct;5(5):408-13.
• Rosenson RS, Otvos JD, Freedman DS. Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am J Cardiol 2002 Jul 15;90(2):89.94.
• Rosenson RS, Davidson MH, Pourfarzib R. Underappreciated opportunities for low-density lipoprotein management in patients with cardiometabolic residual risk. Atherosclerosis 2010 Nov; 213(1):1-7. 
• Stender S, Dyerberg J, Astrup A. High levels of industrially produced trans fat in popular fast foods. N Engl J Med. 2006 Apr 13;354(15):1650-2.

Blocking Inflammation is Like Choking the Fire: Long Term Weight-, Visceral- and Android-Fat Gain in Human Study Emphasizes Essential Role of TNF-α in Metabolic Control

Can cooling down the inflammation make your belly grow!?

(Mito-)Hormesis and the important and beneficial role of "inflammatory" cytokines, molecules etc. are one of my favorite topics. It's simply intriguing that health, performance and longevity apparently depend on the presence of a healthy amount (whatever that may be) of inflammation. Even the provision of low dose arsenic does not - as you may expect - shorten, but prolong the lifespan of several common model organisms (Schmeisser. 2013).

Findings like these don't just conflict with common sense, they are also in opposition to the still prominent free radical theory of aging and it's central message: Oxidation and inflammation are bad for you! No matter what! 

Too little is just as bad as too much

Most of you will remember one of my previous articles on (mito-)hormesis - if if that's not the case, I'd recommend you start with the "Inflammation is a True Fat Burner" article (read it!), because it (a) contains a lot of links and references to previous articles and (b) discusses a topic that is directly related to the study at hand. Whence you've refreshed your memories, you should actually be able to tell that it may not be a total idiotic undertaking to  ...

"[...] evaluate the long-term consequences of TNFα-inhibitors on body composition, especially on the android/visceral region, in patients with RA [rheumatoid arthritis] or AS [ankylosing spondylitis]." (Toussirot. 2013)

Ok, rheumatoid arthritis and ankylosing spondylitis, that's not you. I understand that, but it's neither a rodent nor a nematode study and despite the fact that the patients in the study suffer from chronic inflammation the data Toussirot et al. collected can provide us with a glimpse on what could happen to any of us, if we subscribe to the "the-less-inflammation-the-better" hypothesis and consume high amounts of drugs or natural substances to suppress cachexin (aka TNF-alpha), of which the corresponding Wikepedia entry tells you that it is "an adipokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction." (wikipedia)

Figure 1: Markers of inflammation, health and joint function after 24 months treatment in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients (Toussirot. 2013)

As you can see both, the provision of a TNF-alpha blocker lead to significant reductions in inflammation (CRP ↓) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients (Figure 1, ESR + CRP). The overall reduction in non-specific inflammation (assessed by ESR), on the other hand, reached significance only in the patients with "classic" rheumotoid arthritis - for our purpose, i.e. drawing inferences with respect to our situtation, this difference is not that relevant. What is relevant the total annihilation of C-reactive protein (CRP), an acute phase protein which is elevate immediately after a strenuous workout - just like IL-6, by the way (see "IL-6 True Muscle Builder or Just a Measure of Workout intensity?" | read more).

Weight gain right due to the absence of inflammation?!

Contrary to the previous post on IL-6 we are not dealing with muscle hypertrophy, here. The thing that's growing is the belly - the android fat mass, visceral fat and total BMI of the study participants in both groups and and additional significant increase in total (subcutaneous + visceral) fat mass in the ankylosing spondylitis patients (see Figure 2).

Figure 2: Changes in body composition after 24 months (Toussirot. 2013)

Said increase in total fat mass was significant (p=0.02) and came hand in hand with a gain in total body weight. It is thus not surprising that the scientists found ...

"[...] a significant increase inbody weight (+1.9 %; p=0.003), body mass index (+2.5 %; p=0.004), total fat mass (+11.1 %; p=0.007), and fat in the android region (+18.3 %; p=0.02) [...]" (Toussirot. 2013)

... when they calculated the mean changes in body composition for both groups. In this context, it's probably worth mentioning that the success of a few outliers who managed to keep the visceral fat off, masquerades the "substantial, albeit nonsignificant" (Toussirot. 2013) +24.3%  increases in visceral fat and thus diabetes and cardiovascular disease risk among the rest of the study participants.

Bottom line: While I do hope that you don't have to take a TNF-α inhibitor to make it through the day, the general messages of this paper are still relevant for all everyone - even, or maybe especially for the for the healthiest of us:

Human study: Antioxidant supps hamper "gains" in elderly individuals, as well. Get all the details → here!

• The total annihilation of inflammation by the means of drugs or supplements (whenever I hear TNF-α, I personally think of curcumin) is not necessarily beneficial.
• The negative side effects will hardly be felt right away. They will rather sneaking up on you after initial health improvements that, when your baseline inflammation went back into the "green zone".

In other words, the lower your baseline inflammation the lower your need for anti-inflammatory agents. This does not mean that you must not keep an eye on an adequate nutritional antioxidant intake, but it should remind you of something people tend to block out, when they go on their supplement shopping sprees:

It's often the pro-inflammatory effect that turns "foods" into "superfoods"!

Take everyone's favorite "health food" as an example: Broccoli and other Brassica vegetables perform their cancer killing magic by the means of sulforaphane, a metabolite of dietary glucosinolates that has been shown to depend on the generation of reactive oxygen species for cancer cell elimination(Singh. 2005).

References:

• Schmeisser S, Schmeisser K, Weimer S, Groth M, Priebe S, Fazius E, Kuhlow D, Pick D, Einax JW, Guthke R, Platzer M, Zarse K, Ristow M. Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension. Aging Cell. 2013 Jun;12(3):508-17.
• Singh SV, Srivastava SK, Choi S, Lew KL, Antosiewicz J, Xiao D, Zeng Y, Watkins SC, Johnson CS, Trump DL, Lee YJ, Xiao H, Herman-Antosiewicz A. Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem. 2005 May 20;280(20):19911-24.