Fat Content Per Energy Drink 0g, Body Fat Gain Per Energy Drink 18g! Human Trial Confirms: +1kg of Body Fat in 4 Weeks From Less than 2x Energy Drinks per Day!

Image 1 (NYC Dept. of Health & Mental Hygiene): The words on this poster from a 2009 campaign in the NY subway must be taken literally!

There is a reason for me to always begin my "dietary advice" with the statement "there is NO WAY that you ever again drink any soft, energy drinks or fruit juices on a daily basis". And though I would not have needed a study to confirm skipping, lemonade, coke & co is one of the simplest, for many people yet not easiest steps to a healthier and leaner physique, I must admit that I was pretty surprised how rapid both your health and body composition deteriorate, once you reintroduce this junk into your diet. +1kg of pure body fat in 4 weeks, that was the amount of weight the 11 healthy men and women in a recently published study by scientists from the UK, Italy and the US gained within just 4 weeks in the course of which they drank on average two more or less tasty Lucozade Energy drinks per day (Sartor. 2013).

Fat content of energy drink 0g, body fat gain per energy drink 18g!

Figure 1 (gsk): Nutritional information of the energy drink the subjects drank during the 4-week study period

Sartor et al. about whose study on the "habituation effects" of sweet beverage you may already have read in one of the installments of the Insulin Resistance Saga (cf. "Where Has All the Sweetness Gone? Plus: Bullied to Eat Twinkies") had recruited 11 healthy young men (n=5) and women (n=6) with a mean age of 26 years, who were handed a month's supply of GlaxoSmith Kline's yummy Lucozade Energy of which they had to drink ~2 bottles per day (2x 380ml; in fact the average intake was only 760ml and was matched to deliver 2g carbohydrates per kg body weight; for detailed "nutritional" information based see figure 1) - just to make that clear, I suspect the results would not have been much different if this had not been Lucozade, but plain Coke, if the daily consumption (1.2l) had delivered the same amount of sugary carbs.

Apropos effects, if you take a look at the actual data in figure 2 it is quite obvious that the increase in body fat did not occur in the absence of the rise of other characteristic features of the metabolic syndrome, i.e. changes in blood glucose and lipid metabolism.

Figure 2: Changes in body composition, HOMA markers of insulin resistance, sensitivity and pancreatic function, as well as blood lipids after 4 weeks of sugar-sweetened beverage consumption (based on Sartor. 2013)

A particular reason of concern - at least in my humble opinion - are the rapid (remember these deteriorations occurred within only 4 weeks!) reductions in HOMA measure insulin sensitivity / increases in HOMA based insulin resistance measures. Which would only exponentiate the detrimental effects of the daily glucose overload.

High blood glucose, high RER, high insulin, but no increase in energy intake

Together with the significantly increased fasting glucose (+6%) and fasting insulin levels (+25%) and the accompanying reversal of the fat-to-carbohydrate oxidation rates from 2:1 to 1:3 in the fasted state this does already suggest that this is once more not solely an effect of an increase in energy intake as conventional wisdom would have it!

Figure 3: Changes in macronutrient composition and non-existent changes in total caloric intake over the course of the 4 weeks of sugar-sweetened beverage consumption (based on Sartor. 2013)

If you take a closer look at the data in figure 3 you can even drop the "solely" from the previous sentence and state: "the obesogenic effect of sugary beverages has no relation whatsoever to an increase in overall energy intake!"

Its not so much about how much, its about what and which!

It stands to reason that this increasingly accepted "violation" of the rules of thermodynamics *rofl* did not go unnoticed by Sartor et al., who had also analyzed the expression of several genes in samples of the skeletal muscle tissue of their subjects and found that there were statistically significant

• increases in glyceraldehyde-3-phosphate dehydrogenase (GAPH), acetyl-CoA carboxylase alpha (ACC) and MonodA mRNA expression, which are indicative of increased glycolysis, decreased fatty acid oxidation and an increased cellular awareness of blood sugar abundance, respectively, as well as a significant
• decrease in peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1a), of which you have read in relation to Irisin in "If a High Fat Diet was a Pill, the Lay Press Would Celebrate it as Exercise in a Pill!" that it is responsible for increases in mitochondrial firepower and fatty oxidation capacity

Much more so than the 1kg of body fat, which should be relatively easy to shed by simply pouring energy-, soft-drinks & co down the sink, instead of downing them with a gulp, these transcriptional (epigenetic) changes and the previously reported deteriorations in taste perception in response to the consumption of sugar (not fructose!) sweetened beverages (Sartor. 2011), are the real alarming results of this 4-week trial. After all, they are the ones that predispose to future fat gain, diabetes and hyperlipidemia!

So, what can be done?

Image 2: OTC solution to the problem? Water + Workout

Luckily there is a tried and proven non-pharmacological solution to this problem, an OTC double-whammy, if you will that is not just free, but will actually save you truckloads of money! Initially for all the energy drinks and soft-drinks you are not buying anymore and for all the medication the medical bill's and the XXL coffin for your funeral in the weeks, months, years and decades to come. What? You want to know what this OTC double-whammy is? Plain water and regular exercise! While the former is equally if not more thirst-quenching than the differently colored sugar waters, the latter will help to gradually reverse the epigenitic changes and restore a healthy glucose and fatty acid metabolism.

References:

1. GlaxoSmithKline (gsk). Lucozade Official Shop. Lucozade Energy - Original. 2013 < http://www.lucozadeshop.com/lucozadeenergy/lucozadeenergyoriginal > Received on June 30, 2013.
2. Sartor F, Donaldson LF, Markland DA, Loveday H, Jackson MJ, Kubis HP. Taste perception and implicit attitude toward sweet related to body mass index and soft drink supplementation. Appetite. 2011 Aug;57(1):237-46. 
3. Sartor F, Jackson MJ, Squillace C, Shepherd A, Moore JP, Ayer DE, Kubis HP. Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes. Eur J Nutr. 2013 Jun 26.

Topical Fat Loss: Capsaicin Cream Blunts Weight Gain in Rodent Model and Increases Leptin, Adiponectin, Lipolysis and Fatty Acid Oxidation in Visceral Fat Depots

Image 1: If you infused your ice-water with an extract of those, that could supercharge your "cold thermogensis" (see "Ephedra vs. Cold Thermogensis" ;-)

Those last 1-2lbs of stubborn fat have been and still are the focal point of countless of discussions among trainees, trainers and  magazines even average Joes and Janes who would not even remotely consider to go to the gym to get rid of those love handles - interestingly, all these groups are similarly susceptible to one message: "Revolutionary breakthrough in topical fat loss: "Whatever-Our-Marketing-Department-Came-Up-With-Burn will obliterate the stubborn body fat that's still covering your abs, obliges, butt, and whatever else you hate about yourself in record time!" Sounds and, as the countless disappointed testimonies on the Internet confirm, is usually too good to be true.

How many scoville (SHU) does it take to burn 1lbs of body fat?

A soon to be published study by researchers from the University of Ulsan in Korea does however show that many of the companies which advertise with the afore "cited" slogans could in fact be on the right track - at least with respect to one of the key ingredients many of those topical fat-burners contain: Capsaicin, a major pungent molecule that is found in hot chilies and other peppers and has already been shown to exert direct effects on isolated adipocytes in vitro (Kang. 2007; Hsu. 2007) and anti-obesity activity in animal models (Yoshioka. 1999; Zhang. 2007). Interestingly enough, epidemiological (Wahlqvist. 2001) and controlled human trials (Bloomer. 2010) suggest that these effect do - despite the often-touted differences in the thermogenic capacity of humans and rodents - in fact manifest in all the usual steps of scientific experimentation in the medical field, i.e. the petri dish, the animal model and the controlled, randomized, placebo-blinded human trial.

From the mouth onto the skin

As far as its topical usage is concerned the main focus of scientific research has yet been on the ameliorative effects of capsaicinoids on painful neuropathies and neuralgia (Harding. 2001; Roberts. 2011) and Lee et al. claim that their study is the first one to investigate the effects of in vivo application of 100mg of a 0.075% hydrophillic capsaicin cream applied to the shaved abdominal skin of pre-fattened mice who were pair-fed (=equal caloric intake for rodents in both groups to exclude reduced appetite as a cause for the observed effect) for 7-weeks.

Figure 1: Body composition (left) and adipocyte size (right) after 7-weeks on HFD with our without topical appliaction of 100mg 0.075% capsaicin cream to the abdomen of obese mice (based on Lee. 2013)

As the data in figure 1 clearly shows, the topical application of capsaicin elicited similar beneficial effects on the blood lipids (not shown) as its oral ingestion in a previous HFD rodent trial (Kang. 2010). What is however particularly striking is that it did at the same time totally blunt further increases in body weight and reduced body fat storage in both the mesenteric, as well as the epididymal, visceral fat depots. The latter went hand in hand with profound changes in the adipocyte morphology of both fat depots which shifted from fewer large, to many small adipocytes - a feature which is usually associated with lower adipocyte inflammation and thus reduced risk of cardiovascular disease & co.

Topical application, systemic effects?

Both results, the improved lipid profile, as well as the reduction in visceral (intra- not super-abdominal) obesity appear to suggest that the effects of the capsaicin cream was by no means as localized as the producers of respective "supplements", would have it.

Figure 2: Adiponectin, leptin, TNF-alpha, lipoprotein lipase, UCP-2 and PPAR expression in mesenteric fat pads of the animals at the end of the 7-week study period (based on Lee. 2013)

The localized decreases in TNF-alpha, a central regulator or inflammation and the profound increases in adipokine expression (adiponectin + leptin), lipoprotein lipase, as well as UCP-2 and all three varieties of the peroxisome proliferator receptors (PPARs), Lee et al. observed in the mesenteric fat pads of the animals do yet confound this theory - capsaicin is, at least partially, a topical fat burner in the literal sense.

Caution! Stimulant-laden fire hazard!

Aside from the fact that its certainly non-negligible effects on visceral fat should not be of great interested for any avid trainee who is following a wholesome whole-foods diet, as those last slabs of body fat that are covering your abs belong to your subcutaneous and not visceral fat depots, there are two more things you should be aware of before you (most likely) waste your money on one of those products.

1. The capsaicin itself will make the body part you rub the product on look like a tomato on fire and burn worse than stinging nettle and that usually for hours!
2. The systemic effects of the stimulants most of these products contain can become an issue especially for leaner folks, as the dosages are usually adjusted for customers with a thick "insulation" that has to be penetrated, first. 

If you still feel that you have to give one or another of those preparations a shot, start with a moderate dose first and wait for a couple of hours to see what it does (don't expect it to do anything to your body fat in that time - if your waistline goes down within the first days of application that's simply water loss!).

My personal recommendation would still be to keep away from any of these products. Regardless of your personal tolerance to stimulants or the specific composition of the different formulas that are currently on the market - 99% of the feedback I have heard and read about states that these products are much better money- than fat-burners  ;-)

References:

1. Bloomer RJ, Canale RE, Shastri S, Suvarnapathki S. Effect of oral intake of capsaicinoid beadlets on catecholamine secretion and blood markers of lipolysis in healthy adults: a randomized, placebo controlled, double-blind, cross-over study. Lipids Health Dis. 2010 Jul 15;9:72.
2. Kang JH, Kim CS, Han IS, Kawada T, Yu R Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages.FEBS Lett. 2007;581:4389-96. 
3. Kang JH, Goto T, Han IS, Kawada T, Kim YM, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity (Silver Spring). 2010 Apr;18(4):780-7.
4. Lee GR, Shin MK, Yoon DJ, Kim AR, Park NW, Yu R, Han IS. Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high-fat diet (HFD)-induced obese mice. Obesity (Silver Spring). 2013 Jun 18. doi: 10.1038/oby.2013.166. [Epub ahead of print]
5. Hsu CL, Yen GC Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells.J Agric Food Chem. 2007;55:1730-6. 
6. Wahlqvist ML, Wattanapenpaiboon N Hot foods--unexpected help with energy balance? Lancet. 2001;358:348-9.
7. Yoshioka M, St-Pierre S, Drapeau V, Dionne I, Doucet E, Suzuki M, Tremblay A Effects of red pepper on appetite and energy intake.Br J Nutr. 1999;82:115-23. 
8. Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, Yan ZC, Wang LJ, Zhao ZG, Zhu SJ, Schrader M, Thilo F, Zhu ZM, Tepel M Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity.Circ Res. 2007;100:1063-70.

Adelfo Cerame - After the Wheelchair Nationals (+Video!): Another Lesson Learned, Thousands Yet to Come!

Video 1 (click to play): Adelfo Cerame Jr, at the Wheelchair Championships 2013; posedown for the overall

I guess most of you will have heard it already. Adelfo won the title at the Wheelchair Nationals (I had expected nothing else), but came off second best - at least in the eyes of the judging panel - in the posedown for the Overall (see video 1). Allegedly, this was not the best Adelfo we have seen. And as he is going to point out in today's SuppVersity post, 4-days before, he looked so much better that I am pretty sure that he would have taken that pro-card home, if... well, I will let him tell you the story, but before I do so, let me say this: I am proud of you Adelfo! Even more now (after reading this post), than before. You have everything it takes to be a pro, don't care about that sheet of paper you will pick it up somewhere along your way!

Learning From my mistakes and moving on & forward

As much as I was disappointed in losing the overalls, I was more disappointed in myself, because I knew that I f#cked it up! After evaluating pictures from this past weekend, I realized that I looked much better 4 days out, than I did the day of the show… Then it hit me… I realized that I did the one thing that I thought I would never, ever make the mistake of doing; and that’s making drastic changes during the final days of my peak week.
 :
Though it may have not seemed as drastic at the moment; using a water pill in between those 4 days to try and flush out the last bit of water, may have hindered my physique leading up to Saturday – To be honest I really didn’t need to take the water pill, I would have been fine just pounding gallons of water all the way till Saturday morning, but stupid me… always wanting to do more decided to take it anyway.

Image 1:  4 days out from Saturday (left) vs. Saturday morning (right) - Something definitely went wrong in between those 4 days, and I suspect I fell victim to my own urge to do more than 100%

As you can see from the images above, I was a lot sharper 4 days out than I was the day of the show. I didn’t look as full and hard as I did 4 days out. I don’t know whether it was the plane ride or the water pills that I took, or a combination of both, but all I know is that something I did went out of whack in between those 4 days.

So what's the take home message here? Stick to what got you to the dance! If you looked good 4 days out before a show, then you’ll look good the day of show, so no need to change anything. Unfortunately, I did not listen to my own advice and I played for it!

Moving Forward and into the "Off Season"

My sponsor, Myotropics Physique Nutrition, has just released Thermicarb the WM-HDP based dual-action carbohydrate source from Physique 2.0 as a standalone. This is a 100% non-insulinogenic nutritionally engineered resistant starch and could be of interest to all of you who are reconsidering their peri- or intra-workout carbohadrate supplementation after reading Adel's SuppVersity post on high GI intra-workout cabs, yesterday.

You live and you learn – All I can do is learn from my mistakes, and make the necessary adjustments so I do not repeat that same mistake. To leave this show behind, will allow me to move forward, improve, get better and expect great things for the future.

As far as the near future is concerned, this means going into the "off season" - not a particularly long one, since I will have to start prepping again around October for the Florida show in March, but a couple of months to try and put on some descent size before October. Even though I’m going to miss the dieting down and prepping, to be honest, it’s kind of a relief getting a couple months off. I can focus more on school and trying to finish my degree much earlier than expected (hopefully graduate in October), since I have the time now, and I can also try and look for another gig, so I can earn some more extra income to support my bodybuilding habit! *lol*

Learn and grow - personally, professionally and physically!

There’s only 2 goals I have in mind at the moment, and that’s to learn and grow! You can never stop learning. I don’t claim to know everything, and I never will claim to know everything, there is a lot of learning that needs to be done in this game of fitness and nutrition and I intend on learning as much as I can. In order for me to gradually improve my training and nutrition, I must keep learning – whether it is my late night “pick Dr. Andro’s brain” conversations with Adel, or if it’s just finding interesting topics that I can do some research on… which usually provides me with new stuff to discuss on yet another of those late night sessions; it's a constant struggle or, as a matter of fact, it's more of a constant pleasure to expand your knowledge and gather new insights on a daily basis.

The idea of learner, by the way, segues nicely into another decision I've made, which is to work with a seasoned prep coach for my next show. I am not really sure what to expect, but I feel that it may help me to take it to the next level - and if it doesn't the help from someone who has more experience and more knowledge about peaking right on time, than I do will certainly broaden my horizon and help me to avoid stupid decisions, which I, had I been my own coach, probably advised against.

Let me briefly make something clear: This is by no means a knock on Adel. He knows how much I value his opinion and he has helped me tremendously with reaching my goals (and will continue to help me), but I understand that he is a busy man and can’t always respond to my frantic e-mails, bombardments of questions, and always asking him to evaluate my physique (especially in the final weeks of my prep when I get really anxious and it will sooth my guilty conscious to know that I am paying for those emails to be answered!) In the end I owe it to him that I've had such a wide-open forum to share my story and experiences with fitness and nutrition (thanks for listening, or I should say, "reading", by the way :-) It was also him, who has hooked me up with my sponsor, Myotropics Physique Nutrition, and his constant support was and still is one of the main reasons I am getting so much public exposure. So, by no means, do I mean to be disrespectful! It is in fact the exact opposite: I am trying to take some load off his shoulders, so that he doesn’t have to worry about me all the time! And you know what? This leaves more time for you, as well ;-)

My choice fell on the guys at 3DMuscle Journey, who will be helping me with my prep for next years 2013 Wheelchair Nationals in March. These guys are experienced natural bodybuilders with years of experience under their belt, which makes me believe that I can learn one or two - probably rather three *lol* - things from them that will not just help me excel at the next competition, but also to expand my own knowledge as a trainee and coach.  

I need to be bigger, stronger, and... well, not necessarily faster, though ;-)

But now on the physical growth – Obviously I need to get bigger! Every time I ask judges for an evaluation on what I need to improve… they always tell me  “You need to get bigger” Lol. And every single person that has beaten me has always been... guess what? Yeah! Bigger than me – I get it!

Image 2: Right before the pre-judging; at least on the picture on the right its pretty obvious that the water pill did me no good; well, unless that was a "water pill" meant to increase water ;-/

So the focus for the next couple months is to get bigger – well obviously right!? Lol (that’s what the off-season is for) but I still really want to focus and put an emphasis on my back – I feel that I’ve made some big improvements on it this season and would like to continue to keep improving on it; especially my lower back – if ever figure out a way to stimulate my lower trunk and really get that Christmas tree to come in, I think my back can be my strongest body part

I’d also like to bring up my chest, I’m thinking that it may be one of my weak points, or at least lagging body part now, but overall and most importantly, I want to put on some size with an emphasis on my back and chest. And last but not least, my strength could use another bump as well - that's it from your's truly today I am off into the off season... and don't forget to check back for further details on my training, nutrition and supplementation regimen in he weeks to come :-)

700% Increase in Insulin, Elevated Blood Glucose + Identical Cortisol & CK Levels Challenge Usefulness of Intra-Workout High GI Carb Ingestion in Advanced Strength Trainees

Image 1 (IndiaToday): If you insist on ingesting 3x cans (=sugar equivalent of the maltodextrin supplement in the study at hand) of a not-to-be-named energy drink during your workouts and don't die from caffeine poisoning, you may gain more, but I suspect not in those areas, where you ant it ;-)

Whether you should or should not supplement with carbohydrates is a matter of constant debate among strength trainees. While some swear that they cannot perform if they aren’t guzzling a glucose-laden “intra-workout” supplement or energy drink from the supermarket, others prefer to get the lion's share of their carbs from whole foods, settle for BCAAs or plain water as their workout beverage of choice and wash down a sweet ripe banana with a tasty protein shake after their workouts. And while a previous paper by Bird et al. suggested that the former practice, i.e. the ingestion of a carbohydrate supplement (6%, preferably with 6g of EAAs) during your workouts, could significantly blunt the exercise induced cortisol spike (CHO alone -116%, CHO + EAA -112% vs. placebo), a very recent study, which was conducted by a group of scientists from the University Federal of Paraíba in Brazil, yielded very different results (de Oliveira Quirino. 2013)

To carb-guzzle or not that is the question!

Contrary to Bird et al., who had recruited previously untrained subjects for their study, de Oliveira Quirino's team picked 7 healthy young men (BMI 25.4kg/m²; age 27.3y) who had been training for at least 6 months with a minimum 3 resistance training sessions per week – this is important to note, because it should, for most of you, increase the real-world significance of the data, as I assume that many of you will have been following a similar protocol for probably longer than 6 month, already. What may be less in line with your own exercise regimen, though, is the exact training protocol, which comprised ten exercises for the upper limbs, i.e.

bench press, inclined press, dumbbell pullover, back lat pulldown, back lat push-down,

front press, bar-bell curl, pushdown, preacher curl, and lying triceps extension

which were performed for 3 sets of 12-15 reps to voluntary failure (60% RM) and at a cadence of 2-0-2-0 (2s concentric, 2s eccentric; no transition time between phases). Obviously all participants performed this protocol twice (in random order) and with a 96h interval in-between the supplemented (1,080ml of an 8% carbohydrate solution =86.4g of maltodextrine, ingested at regular intervals every two exercises) and the placebo (sucralose) trial.

Figure 1: Plasma glucose levels (in mg/dl) at rest, after the first, second, third, fourth and fifth pair of exercises (left) and increases in insulin and cortisol from pre to post exercise (de Oliveira Quirino. 2013)

As you can see in figure 1 the ingestion of  ~350kcal of readily available energy was more or less unnecessary, as it did not blunt, but rather augment the cortisol response (effect was not statistically significant, though); and that in the presence of profound elevations in blood glucose and insulin levels, and without any effect on circulating creatine kinase levels (a marker of muscle damage, not shown in figure 1).

A "substantial" increase in "anabolic hormone activity"?

Now in the absence of concrete data on protein synthesis / degradation, mTOR activity & co and without any information on confounding factors such as an increased training intensity during the carbohydrate trial, it is difficult to provide a conclusive answer to the initially raised question, whether the provision of fast acting carbohydrates during a strength training session would, as the scientists conclude, provide an "additional [benefit] for those engaged in this type of exercise with the aim of hypertrophy”. After all, it may be correct that the findings of the study …

[…] show that carbohydrate ingestion during the course of a training session comprising resistance exercises does not affect catabolic activity, but does increase substantially anabolic hormone activity. (De Oliveira Quirino. 2013)

but the „anabolic hormone“ the Brazilian scientists are talking about is insulin, which is beyond doubt among the most "anabolic” hormones in our body, but unfortunately, not exactly muscle specific, as it is simply a matter of fact that skeletal muscle is not the only tissue that’s going to benefit from insulin’s facilitative effects on nutrient uptake (Timmerman. 2010). It thus appears more than reasonable to assume that two other major players in the complex orchestrate of our metabolism will avail themselves of the superfluous amount of glucose that would be floating around in our bloodstream if we mimicked the supplementation protocol in the de Oliveira Quirino study. Their names? Your liver and your body fat stores!

So what are the implications?

Image 2: Another recently published study by Wax et al. suggest that slow digesting starches can help to maximize workout intensity and volume (read more in my article for Physique Magazine)

If you are not training fasted (the participants worked out on 11am on both occasions) and/or low-carbing without regular re-feeds, so that you have adequate muscle and liver glycogen stores, when you hit the gym, and you are no rookie anymore (cf. Bird. 2008), so that working out is no longer a totally novel stressor for your body, my personal interpretation of the study data is that you simply don’t need the additional fast acting carbohydrates! Neither to stabilize your blood sugar, nor to ward off any exorbitant increases in cortisol.

And as far as the increase in insulin is concerned, it appears more than questionable whether the latter would actually exert significant additive effects on muscle protein synthesis or could not even negate the nutrient repartitioning effects of your workouts (Poehlman. 2000; Hawley. 2008) by diverting the obviously superfluous energy to places where you’d rather not have them stored ;-)

A note on the "importance" of insulin to build muscle: One of the most comprehensive reviews on the role of insulin in skeletal muscle anabolism states it quite aptly "the full response of translation initiation and protein synthesis to either effector is not observed in the absence of a minimal concentration of insulin", but - and this is important - "the amount of insulin required for the effects is low, and a concentration of the hormone that approximates that observed in fasting animals is sufficient for maximal stimulation." (Kimball. 2002)

Bottom line: Avoid the unnecessary insulin spike from the ingestion of high GI carbs before and/or during a workout, but make sure that you have an ample amount of muscle glycogen before you hit the gym via an adequate total and post-workout carbohydrate intake (the lion's share in form of low GI carbs) and planned carbohydrate re-feeds (esp. for low carbers). This practice will not necessarily augment post-exercise protein synthesis (cf. "Glycogen-Free Muscle Growth"), but it is certainly going to help you to increase or at least maintain your workout intensity and overall training volume (Wax. 2013).

References:

1. Bird SP, Tarpenning KM, Marino FE. Liquid carbohydrate/essential amino acid ingestion during a short-term bout of resistance exercise suppresses myofibrillar protein degradation. Metabolism. 2006 May;55(5):570-7.
2. de Oliveira Quirino EL, da Conceição Rodrigues Gonçalves M, de Oliveira CVC, Porto dos Santos E, Silva AS. Influence of carbohydrate supplementation during resistance training on concentrations of the hormones cortisol and insulin. Sport Sci Health (2013) 7:93–97
3. Hawley JA, Lessard SJ. Exercise training-induced improvements in insulin action. Acta Physiol (Oxf). 2008 Jan;192(1):127-35. Review. 
4. Kimball SR, Farrell PA, Jefferson LS. Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise. J Appl Physiol. 2002 Sep;93(3):1168-80.
5. Poehlman ET, Dvorak RV, DeNino WF, Brochu M, Ades PA. Effects of resistance training and endurance training on insulin sensitivity in nonobese, young women: a controlled randomized trial. J Clin Endocrinol Metab. 2000 Jul;85(7):2463-8.
6. Timmerman KL, Lee JL, Dreyer HC, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, Volpi E. Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling. J Clin Endocrinol Metab. 2010 Aug;95(8):3848-57.
7. Wax B, Brown SP, Webb HE, Kavazis AN. Effects of carbohydrate supplementation on force output and time to exhaustion during static leg contractions superimposed with electromyostimulation. J Strength Cond Res. 2013 Jun;26(6):1717-23. 

Are Elevated Iron and Uric Acid Levels Too Much of a Price to Pay for a Creatine-Induced 11% Performance Increase?

Video 1 (GSSI): Notre Dame's Michael Floyd goes all out on the Wingate test (click to watch)

I guess you could say that these are the "classic days", here at the SuppVersity, contrary to my previous post on choline, which is - judged by the few people who still use it today, an "old school supplement" (cf. "Choline: Stronger, Faster, Leaner & More Muscular, or Just Another Dumb-and-Barbell Story?") - yesterday's post on caffeine highlighted the efficacy of a potent ergogenic aid and metabolic activator, with the effects of which most of us are so familiar that we are alway tempted to turn to useless crap like raspberry ketones, when what we are already doing is not only tried and proven, but based on respectable scientific data even more effective than the latest "innovation" from the snake oil industry. And let's be honest, haven't we all been tempted by one or another "new creatine", as well?

+11% peak performance in one week, solely from 5x4g of creatine per day!

A a matter of fact, creatine monhydrate does in fact share the same fate of being proven, but "boring" staple supplement and although that alone should be incentive enough to address the unquestionably outstanding +11% in anaerobic peak performance, +5% in continuous anaerobic performance and a +6% increase in total workload in a classic wingate anaerobic performance test speak, Barros et al. observed in a group of trained male subjects in response to a 7-day creatine loading protocol (20g creatine monohydrate, in 5 doses spread across the day, not glucose / sugar added; cf. Barros. 2013) After all, my gut tells me that the contemporary changes in the concentration of iron in the blood of the subjects in the the creatine arm of the study could revoke the mainstream-media fearmongerish hoopla over the purported dangers of the #1 natural ergogenic.

Figure 1: Basal iron, FRAP, malondialdehyde (MDA) and uric acid levels before and after 7-day supplementation with 5x4g of creatine monohydrate per day (based on Barros. 2013)

I mean, there is no debating, the level of iron in the blood of the creatine supplemented undergraduate students (age, 23.1 ± 5.8 years; height, 175.4 ± 2.3 cm; weight, 81.1 ± 9.3 kg) all of whom had been avid trainees for at least 6 months did increase by no less than 94.3%, while the subjects in the placebo group experienced a -21% reduction of these highly reactive molecules (Just as an aside, the decline in serum iron in the placebo group and the significant difference in baseline levels between the random groups, alone, render any implications at least questionable; I mean, wouldn't you expect the serum parameters to stay the same, when you do nothing extraordinary, aside from popping some sugar pills?).

Figure 2: Changes in wingate anaerobic performance (left) and exercise induced changes iron, FRAP, malondialdehyde (MDA) levels during the wingate test at the end of the supplementation period (based on Barros. 2013)

In conjunction with the likewise highly significant increase in uric acid levels, conventional (blogosphere-)wisdom, which constantly ignores the antioxidative nature of uric acid, which acts as efficient antioxidant and chelating agent for iron ions (Karlsson. 1997), limits the oxidation of polyunsaturated fatty acid in the erythrocyte membrane and prevents hemolysis (= the rupture of red blood cells) in vitro (Einsele. 1987), would suggest that taking creatine takes a close second to fructose on the list of the villains of the bad, bad "neolithic" century.

How dangerous is the creatine induced increase in iron?

Image 1 (Paramount Pictures): I guess, it must have been creatine monohydrate, then, that turned Robert Downey Jr. into Ironman ;-)

Now, despite the as of late publicly propagated concerns about increased iron levels and their potential causative role in the etiology of insulin resistance and diabesity (obesity + diabetes), recent scientific evidence suggests that "high iron", such as all previous scapegoats people like to hold liable, just to make sure not to admit that it is the sickening combination of laziness, convenience and unsound dietary advice that is at the heart of the current obesity epidemic.

Huang et al., for example, did observe a direct effect of iron overload on diabetes risk - the latter was however a result of hereditary hemochromatosis (a genetic defect in iron metabolism) in their 2011 rodent trial (Huang. 2011). Results from two more recent studies by Silva et al. also indicate that the metabolic disturbances lead to differential expressions of the proteins involved in the metabolism of iron and thus substantiate the associative (and not causative) nature of the relation between high iron / ferritin and the metabolic syndrome (Silva. 2011; Silva. 2013).

Iron not causative? So why does phlebotomy help, then? If you read my post on the recently published data from the first controlled human trial that investigated the effects of phlebotomy on markers of blood glucose management, you will be aware that the measures they took, e.g. the HOMA-IR, are not really appropriate to assess the effects of this particular treatment (cf. "Phlebotomy: Can You Bleed Yourself Healthy and Lean?"). Furthermore, it is only logical that the removal of some of this "highly inflammable stuff" from an inflamed body will provide health benefits, even if the latter was totally benign for someone who has a lot less inflammation going on.

What is even more important, though, is that the difference between exercise-induced increases in serum iron and diet and diabesity-related increases in the storage form of iron, ferritin, in the liver. This is particularly true in view of the fact that our understanding of the former, i.e. the exercise induced release of iron into the blood stream is more than limited (Roberts. 1989; Smith. 1994). What we do see in the Barros study, however, is that the overall effect of creatine is rather anti- than pro-oxidative, since the increase in overall antioxidative capacity (as indicated by the changes in the iron-specific FRAP essay; cf. figure 1) did not just...

• negate the potential negative effects of increased basal iron levels (see lowered baseline MDA levels post supplementation in figure 1), it also 
• countered the exercise-induced lipid oxidation during the 2nd wingate test (as indicated by lower MDA levels; cf. figure 2). 

Eventually, the scientists say, the increase in antioxidant activity that is brought about by the ingestion of 20g/day creatine irrespective of whether you exercise or not could actually yield "general health benefits" (Barrios. 2013); and I would like to add that evidence for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, recovery from ischemia and, guess what, diabetes already exists (Tarnopolsky. 2000;"Creatine Ameliorates Type II Diabetes")! Certainly not bad for one of those bodybuilding supplements, "anabolics" or "gateway drugs", as creatine is often mislabeled , when a 100% clueless "journalist" tries to get the attention of his editor-in-chief, wouldn't you agree?

Suggested readings (some also mentioned in the text):

• The Pharmacology of Creatine (Part 1 and Part 2) 
• Supercharging Creatine With Baking Soda (click here to read)
• 5g/day Creatine for Type II Diabetics? (click here to read)
• All posts tagged with "creatine" (click here to read)
• Phlebotomy: Can You Bleed Yourself Healthy and Lean? (click here to read)

References:

1. Barros MP, Ganini D, Lorenço-Lima L, Soares CO, Pereira B, Bechara EJ, Silveira LR, Curi R, Souza-Junior TP. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. J Int Soc Sports Nutr. 2013 Jun 12;9(1):25. 
2. Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel ED, Cooksey RC, McClain DA. Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes. 2011 Jan;60(1):80-7.
3. Orozco MN, Solomons NW, Schümann K, Friel JK. Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men. Food Nutr Bull. 2013 Mar;33(1):53-62. 
4. Roberts D, Smith DJ. Effects of high-intensity exercise on serum iron and α1-antitrypsin in trained and untrained men. Clin Sports Med 1989, 1:63–71.
5. Silva M, Bonomo Lde F, Oliveira Rde P, Geraldo de Lima W, Silva ME, Pedrosa ML. Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator-activated receptor-α expression. J Clin Biochem Nutr. 2011 Sep;49(2):102-8.
6. Silva M, de Brito Magalhães CL, de Paula Oliveira R, Silva ME, Pedrosa ML. Differential expression of iron metabolism proteins in diabetic and diabetic iron-supplemented rat liver. J Biochem Mol Toxicol. 2013 Mar;26(3):123-9. 
7. Smith DJ, Roberts D. Effects of high volume and/or intense exercise on selected blood chemistry parameters. Clin Biochem 1994, 27:435–440.
8. Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):497-502.

Raspberry Ketones? Why, if Two Grande Caffe Americano Could Suffice To Keep Your Belly & Liver Fat Free and Your Heart Healthy, Even on a +40% Hypercaloric Crap Diet?

Image 1: If I had the choice to have a tasty cup of coffee with the beautiful young lady or a couple of overpriced  raspberry ketone caps with Dr. Oz, I would not even need scientific studies to make my choice ;-)

I am a huge fan of innovation, but when the name of the innovation begins with “raspberry” and ends on “ketones”, is pimped by TV doctors and sold on the 24h shopping channels, I can do well without it and better drink another cup of coffee and eat a couple of lycopene-laden tomatoes, whenever I feel the need to prevent hepatic steatosis on an obesogenic diet. I know this may not be as hip as investing 30-50 bucks in an underdosed “scientifically proven” (by exactly two dubious rodent trials, i.e. Miromoto. 2005, Wang. 2013) raspberry ketone supplement, but, on the other hand, it is also half as stupid and probably at least as efficient (Bahcecioglu. 2010; Vitaglione. 2010; Birerdinc. 2011; Molloy. 2011).

And what's more, picking cafeine over raspberry ketones would not only protect me and my virility from potential anti-androgenic effects of the latest nutraceutical rip-off (Ogawa. 2010), it could, according to a recently published study from the Department of Biological and Physical Sciences at the University of Southern Queensland in Toowoomba, Queensland, Australia, also help me to stay lean by simply blocking fatty acid synthase (FAS) in my adipose tissue (Panchal. 2013).

Caffeine? how boring is that!?

Contrary to the, as of late, often-cited study by Wang et al. on raspberry ketones (Wang. 2013), which is by the way one out of two peer-reviewed in vivo studies (the other one is Morimoto. 2005) to support the claim that raspberry ketones do anything, when they are not administered in unrealistic amounts to cells in a petri dish, Panchal et al. did not just measure a couple of serum markers, but investigated a host of metabolic parameters and structure and function of the heart and the liver of their 6-8 week old male Wistar rats that had been randomly assigned to what you might jokingly call the “pest or cholera” diets for 16 weeks: Corn starch diet (control), corn starch diet plus caffeine (CC), high-carbohydrate, high-fat diet (H), or high-carbohydrate high-fat diet plus caffeine (caffeine supplementation with 0.5g per kg chow took place only in the last 8 weeks of the 16-week study period).

Figure 1: Final body weight and body composition after 8 weeks without and another 8 weeks with caffeine supplementation (based on Panchal. 2013)

If we assume that the cornstarch only diet is pest and the high fat high carbohydrate diet is cholera, the data in figure 1 clearly indicates that 28.1mg/kg body weight caffeine ARE sufficient to reverse the effects of the pest and that 47.9mg/kg body weight caffeine are potent enough to survive any cholera epidemic; or put straight, the rodents on the

• standard cornstarch diet, which consumed 28.1mg caffeine per kg body weight (~360mg for a human being) per day, were leaner than their peers in the “control” group and that despite a 20% increase in energy intake
• high carbohydrate + high fat diet, which consumed 47.9mg caffeine per kg body weight (~612mg for a human) per day, were about as lean as the rodents on the standard diet and that despite a 40% higher energy intake (3% more than their peers in the high carbohydrate high fat diet without caffeine supplementation)

I guess none of you but maybe a few less educated minds could now reply: "Whatever... Dr. Oz said raspberry ketones are healthy; and everyone knows caffeine is not!" So, is this another case where Dr. Oz was at least partially right (cf. "Every Dog Has His Day: Dr. Oz Was Right, Exercise Does Not Just Make You Hungry, But Reduces Energy Intake!")? The increased glucose clearance and the reduction in visceral fat pad weight do speak a different language (cf. figure 2):

Figure 2: Parameters related to glucose and lipid metablism as well as visceral fat depot weight expressed relative to the non-supplemented rodents in the cornstarch control level (based on Panchal. 2013)

The same goes for the cardiovascular and liver parameters who give a damn about the increases in total cholesterol, free fatty acid and triglyceride levels, if those are the result of increased lipolysis (release of fattty acids from aidpose tissue), decreased fatty acid deposition in adipose tissue and an overall increase in metabolic rate, which is a long-established consequence of methylxanthine (=caffeine) intake in rodents and human beings (Bracco. 1995):

"[...] there was removal of fat from the abdominal area, and this fat was not transported to the
other fat-storing areas, including subcutaneous fat [...] The increase in plasma lipid components, especially NEFA, reflects the removal of fat from the abdomen [...with] the excess plasma
lipids are being metabolized rather than stored in the organs [...]" (Panchal. 2013)

The fact that the fat is simply "burned off" also explains that the increased non-esterified fatty acid concentrations, scientists usually associate with cardiovascular dysfunction and hepatic steatosis (fatty liver) did not lead to any of these complications in the study at hand. On the contrary, ...

[...] despite much higher plasma concentrations of NEFA in the caffeine-supplemented rats [..t]hese rats showed decreased infiltration of inflammatory cells, decreased collagen deposition, and decreased diastolic stiffness in the left ventricle, attenuation of non-alcoholic steatohepatitis [...]

Now, the question still remains: Why, are not all Starbucks customers lean then? The answer is pretty simple and "visualized" in image 2, it carries names such as "Peppermint White Chocolate Mocha" contains the sugar equivalent of 8½ scoops Edy’s Slow Churned Rich and Creamy Coffee Ice Cream and is "America's Worst Espresso Drink" - at least according to foodfacts.com. And while you can easily make it worse by adding some caramel syrup or junk, the average normal weight woman (if those still exist today) would almost get the +40% caloric intake the rodents in the high fat high carbohydrate diet consumed from that one "coffee" alone!

2-3 cups of black coffee would suffice!

Image 2: Starbucks Peppermint White Chocolate Mocha with Whipped Cream, 660kcal, sugar equivalent: 8½ scoops Edy’s Slow Churned Rich and Creamy Coffee Ice Cream (foodfacts.com)

If you pass those diabolic sugar bombs and pick up one Grande Caffe Americano (225mg caffeine per serving) in the AM and another one in the afternoon or before your workout (cf. "Pre-Workout Caffeine: Fat Liberator, Substrate Modulator, Trans-Fatty Acid Eliminator & Performance Upregulator!"), make sure to get your 20g+ of protein with every meal and refrain from drinking 100 bottle of Pinot Noir every day, to make sure to  get your share of fat-burning, strength building and endurance enhancing resveratrol (cf. "Resveratrol from 100l of 1994 Pinot Noir Could Increase Fat Oxidation by 71%, Strength by 18-58% and Endurance by 20%"), your liver, heart and metabolic health will thank you for that. Your belly and the raspberry ketone producers and snake oil vendors, on the other hand, will probably be offended - but I guess, you can live with that, right?

References:

1. Bahcecioglu IH, Kuzu N, Metin K, Ozercan IH, Ustündag B, Sahin K, Kucuk O. Lycopene prevents development of steatohepatitis in experimental nonalcoholic steatohepatitis model induced by high-fat diet. Vet Med Int. 2010
2. Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013 Jan;35(1):76-82. doi: 10.1111/j.1365-2036.2011.04916.x. Epub 2011 Nov 7.
3. Bracco D, Ferrarra JM, Arnaud MJ, Jéquier E, Schutz Y. Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women. Am J Physiol. 1995 Oct;269(4 Pt 1):E671-8.
4. Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology. 2013 Feb;55(2):429-36. doi: 10.1002/hep.24731. Epub 2011 Dec 22.
5. Morimoto C, Satoh Y, Hara M, Inoue S, Tsujita T, Okuda H. Anti-obese action of raspberry ketone. Life Sci. 2005 May 27;77(2):194-204. Epub 2005 Feb 25.
6. Ogawa Y, Akamatsu M, Hotta Y, Hosoda A, Tamura H. Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4. Epub 2010 Feb 21.
7. Panchal SK, Wong WY, Kauter K, Ward LC, Brown L. Caffeine attenuates metabolic syndrome in diet-induced obese rats. Nutrition. 2013 Jun 19. [Epub ahead of print]
8. Vitaglione P, Morisco F, Mazzone G, Amoruso DC, Ribecco MT, Romano A, Fogliano V, Caporaso N, D'Argenio G. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology. 2010 Nov;52(5):1652-61.
9. Wang L, Meng X, Zhang F. Raspberry ketone protects rats fed high-fat diets against nonalcoholic steatohepatitis. J Med Food. 2013 May;15(5):495-503.

Resveratrol from 100l of 1994 Pinot Noir Could Increase Fat Oxidation by 71%, Strength by 18-58% and Endurance by 20% - At Least, If You Could Afford and Drink It Every Day!

Image 1: Itadori (Japanese Knotweed) and selected varieties of red wine are the best yet vastly 'underdosed' sources of resveratrol (see red box, below)

At least in rodents, resveratrol, the red-wine polyphenol, has been shown to act as an exercise mimetic, exerting profound effects on PGC-alpha expression which protect muscle from wasting due to mechanical unloading (also know as extreme couch-potato-ing ;-) and rodents from the negative side-effects of obesogenic diets by directly modulation gene expression, lipid transport and fatty acid oxidation in skeletal muscle (Chen. 2011; Momken. 2011). Still, most of the oftentimes publicly puffed up data on resveratrol comes from in-vitro studies with dosages of which even the researchers often believe that they are not attainable via oral supplementation.

Rodents or petri dishes? Humans would be too expensive...

Compared with the aformentioned in vitro data, the numbers and gene essays in a recently published study by scientists from the University of Alberta are actually of great practical relevance (Dolinsky. 2013), because Dolinsky et al. administered their resveratrol orally* (4g in 1kg chow) to healthy rats and - what's even more important for the average trainee - 50% of those rats were exercised for 60min, 5x per week on a treadmill (10m/min to 20m/min; cf. Fenning. 2003) for 12 weeks.

Figure 1: Resveratrol content of selected red-wines and Itadori (Japanese knotweed) tea (based on Burns. 2005; equivalent consumption based on dose used in Dolinsky. 2013)

*Can I get my resveratrol from wine or food: I cannot emphasize enough that with ~75% of orally administered resveratrol being excreted via feces and urine and an oral bioavailability of resveratrol of almost ZERO (Vitaglione. 2005; Wenzel. 2005), there is no reason whatsoever to cope with any of the ~100 in-vitro studies that are published on a monthly basis hailing resveratrol for this and that and praising it as the god-sent natural remedy for every ailment, except the consistent ignorance towards the profound difference between a cell in a petri dish and a complex organism that is so prevalent among the human lab rats in their white coats, these days. And the data in figure 1 should make it pretty clear that similar benefits as they were observed in the study at hand are not just unlikely, they are simply impossible to be achieved without highly concentrated supplements - or do you want to drink 105+ liters of wine a day to get your daily dose of ~2g of resveratrol?

Let's assume you got the ~350$ for your 2g/day of resveratrol powder** to mix with your food (**calculated based on the current price of >90% pure bulk powder in Europe), what would be the results? Would you lose weight? Unlikely. Would you lose body fat? Possible! Would you gain muscle? Very unlikely. So what's all the fuss about then?

Figure 2: Body weight (in g), time to exhaustion (in min) and distance covered (in m) during a treadmill exercise test at the end of the 12-week study period (based on Dolinsky. 2013)

Much ado about nothing? Not really, no. After all, the ~20% increase in endurance (time to exhaustion and distance covered; cf. figure 2)  did not come out of nowhere and do - and this is actually the main reason this study did actually make it to SuppVersity - add to the benefits of regular training. The "resveratrol rats" had ...

Image 2 (ADAM): Resveratrol has already been shown to prevent pathological hypertrophy of the heart muscle by AMPK / AKT modulation (Chan. 2008)

• greater strength gains +18% tibialis anterior twitch force and +58% and +22% tetanic and twitch force, respectively, in soleus vs. training alone
• improved cardiac function as assessed by statistical significant improvements in left ventricular ejection fraction and decreased isovolumic relaxation time, as well as increased ratio of the peak mitral flow velocity (E-wave) to the peak velocity of the late filling wave of atrial contraction
• decreased cardiac stress due to a -30% reduction in left ventricular wall stress vs. training alone
• higher VO2 ~10% during the active period 
• increased PPAR signalling and fatty acid metabolism in the heart (+8.8% and +10.3% respectively; p < 0.00001)

Sexier than the strength gains and the utterly unsexy (but vitally important) improvements in cardiac performance are yet the statistically significant reduction in triglycerides which should help insulin sensitivity (not measured in the study) and are probably a beneficial downstream effect of the  resveratrol induced shift towards higher fatty acid and lower glucose oxidation (-6% respiratory exchange ratio, RER; cf. figure 3) that went hand in hand with a highly significant +71% increase in fatty acid oxidation:

Figure 1: Triglyceride levels, free fatty acids, respiratory exchange ratio (higher values = lower fat oxidation, higher glucose oxidation) and total fat oxidation at the end of the 12-week study period (all data expressed relative exercised control; based on Dolinsky. 2013)

Along with the +50% increase in AMPK (vs. exercise alone) and the 20% increase in the "mitochondrial builder" PGC1-alpha (cf. "Two days on High Fat Diet Increase the Activity of Irisin Releasing Transcription Factor PGC1-α") it is obvious that, taken at the right dosage, resveratrol is not the supplemental non-starter everyone is let to believe who spent $30 for 60 100mg caps of resveratrol and took a 3-day dose (3x 2g!) spread across a whole month - obviously without the desired outcomes result.

At the moment resveratrol is still an expensive toy for scientists

Table 1: Significant changes in heart muscle gene expression (based on Dolinsky. 2013)

As a tool to study (epi-)genetics and the downstream effects and interactions of reduction of cytokines, such as the inteferon-induced proteins, which regulate immune functions, cell growth and apoptosis (Sen. 2000), increases in mitochondrial uncoupling protein 3 (UCP3) and UCP1, higher expressions of adiponectin and thyroid responsive protein and the steroyl-coenzyme A desaturase-1 enzyme, which converts saturated to mono unsaturated fatty acids and plays an important role in controlling inflammation, preventing atherosclerosis, steatohepatitis (fatty liver) and pancreatic beta cell dysfunction (Brown. 2010) resveratrol is a must have. As one of the most expensive currently available supplement with little to no actual human data from studies on healthy subjects, its usefulness for physical culturists is questionable and its cost-benefit ratio is abysmal, to say the least.

References:

1. Brown JM, Rudel LL. Stearoyl-coenzyme A desaturase 1 inhibition and the metabolic syndrome: considerations for future drug discovery. Curr Opin Lipidol. 2010 Jun;21(3):192-7. 
2. Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. Plant foods and herbal sources of resveratrol. J Agric Food Chem. 2002 May 22;50(11):3337-40. 
3. Chan AY, Dolinsky VW, Soltys CL, Viollet B, Baksh S, Light PE, Dyck JR. Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt. J Biol Chem. 2008 Aug 29;283(35):24194-201. Epub 2008 Jun 18.
4. Chen LL, Zhang HH, Zheng J, Hu X, Kong W, Hu D, Wang SX, Zhang P. Resveratrol  attenuates high-fat diet-induced insulin resistance by influencing skeletal muscle lipid transport and subsarcolemmal mitochondrial β-oxidation. Metabolism.  2011 Nov;60(11):1598-609. 
5. Dolinsky VW, Jones KE, Sidhu RS, Haykowsky M, Czubryt MP, Gordon T, Dyck JR. Improvements in Skeletal Muscle Strength and Cardiac Function Induced by Resveratrol Contribute to Enhanced Exercise Performance in Rats. J Physiol. 2013 Apr 2. [Epub ahead of print]  Epub 2011 May 31.
6. Fenning A, Harrison G, Dwyer D, Rose'Meyer R, Brown L. Cardiac adaptation to endurance exercise in rats. Mol Cell Biochem. 2003 Sep;251(1-2):51-9.
7. Momken I, Stevens L, Bergouignan A, Desplanches D, Rudwill F, Chery I, Zahariev A, Zahn S, Stein TP, Sebedio JL, Pujos-Guillot E, Falempin M, Simon C, Coxam V, Andrianjafiniony T, Gauquelin-Koch G, Picquet F, Blanc S. Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat. FASEB J. 2011 Oct;25(10):3646-60.
8. Sen GC. Novel functions of interferon-induced proteins. Semin Cancer Biol. 2000 Apr;10(2):93-101.
9. Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, Fogliano V, Marchelli R. Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res. 2005 May;49(5):495-504.
10. Wenzel E, Somoza V. Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res. 2005 May;49(5):472-81.

Work Out 'Till You Drop: After 1h+ of Intense Exercise or an Energy Equivalent of >800kcal Leptin Begins to Plummet!

Image 1: Losing consciousness is very different from losing body fat and while the former may require "burning" more than 800kcal, the latter does not.

Sometimes you read an abstract like that by Mahmoud Hesar Koushki et al. and think "Hmm... that sucks!" Then, you come to think about it and realize "Yeah! That really sucks!" And the thing that sucks in this particular case is the message studies like that are sending out to the public, when they end on statements like "Rising the energy costs of the exercise through increasing the exercise duration, can be one of the factors affecting negative energy balance, leading to positive changes in leptin concentrations." (Hesar Koushki. 2013).

What's good for your obese neighbor...

... must not be good for you! I know, I am repeating myself here, but in view of the fact that my voice obviously has not been heard in Iran, as of yet, I will repeat my novel mantra as often as it takes for people to get it into their stup... ah, I mean stubborn heads and stop sending healthy people into misery.

Figure 1: This is what the study particpants in the Hesa Koushki study had to endure - a "exhaustion exercise session" on the treadmill (Hesar Koushki. 2013)

A good way to achieve that is known as "exhaustive running session" (cf. figure 1), but as you have heard before was still "insufficient" to induce significant decreases in leptin levels in the 23 male students (age 19.58 ± 2.12 yr, BMI 1.63 ± 2.7 kg/m²) who volunteered to participate in this study (cf. figure 2):

Figure 2: Serum leptin, insulin, blood glucose, cortisol and lactate levels of young healthy, but untrained men before and after exhaustive exercise session (Hesar Koushki. 2013)

But what does that tell us? If we were dealing with women, it would probably mean that this type of exercise was insufficient to induce amenorrhea (Chou . 2011), that, when performed once(!), it was not excessive enough to induce a profound enough starvation signal to trick the bodies of athletes or gymrats to believe that they were running the risk of becoming underweight (Köpp. 1997) and that it was not the first step towards muscle and bone loss (Kaufman. 2002). But does this mean that it's safe and effective?

When much is not yet too much, more must not be better either!

Figure 3: If you don't want to burn more energy, more glucose, more fat, and reduce your intramuscular and liver triglyceride stores to ramp up insulin sensitivity and ward off NAFLD, you better stick to 60min+ exercise and 800kcal+ energy expenditure per workout - without eating any carbs, at all, of course! After all, those could negate these "beneficial effects" *sarcasm mode off!*

If we apply standard paradigma of "working out to lose weight" to the finding that short-term intense exercise with an energy expenditure way below 800kcal did not reduce circulating leptin levels and switch off our brains, the (un!)reasonable conclusion would be that

"According to the findings of this study [...] exercise longer than 60 minutes with energy expenditure higher than 800 kcal can be recommended for the reduction of leptin concentration in non-athletes." (Hesar Koushki. 2013)

If we use our brains, though, the take home message would be very different an should rather read like:  "NEVER! Expend more than 800kcal in one workout if you are not leptin resistant and want to make sure that you don't forestall fat loss and mess up your endocrine system." (Dr. Andro ;-)

Fat loss training for non-obese individuals should focus on keeping leptin levels steady!

Once you acknowledge the importance of normal leptin levels for fat loss and overall metabolic health in lean, not leptin resistant individuals, the same review (Bouassida. 2010) the Iranian scientists cite to support their (misleading!) conclusion that it would be basically nonsensical to do intense short bouts of exercise, since those do not reduce circulating leptin levels has to be interpreted in a completely different way.

Just as the complete failure to produce insulin would not just hamper your gains, but have you literally shrivel away, lowering leptin levels in an already lean, if not very lean individual even further will sooner or later whack your metabolism and endocrine system (infertility, low testosterone, amenorrhea, you name it...). Not to mention that you will obviously not be able to derive any of the metabolic benefits of adequate leptin levels and receptor activity (figure 3).

So what can or must be done to keep healthy leptin levels and sensitivity?

Lean, athletic individuals should thus focus on shorter (below 1h), intense and glycolytic workouts (HIIT, lifting weights) and regenerative 'cardio' work in the << 800kcal energy expenditure range and make sure that they...

• get enough sleep - even a moderate sleep debt will increase the production and systemic circulation of TNF-alpha and IL-6 and reduce the expression of adiponectin and leptin in the adipose tissue (Padilha. 2011)
• strategically cycle & refeed on carbohydrates - it stands out of question that a reduction in carbohydrate intake is an effective means to get rid of body fat, but it will work optimally only, if you strategically cycle (higher carb intake on workout, lower carb intake on non-workout days) your carbohydrate intake, integrate regular refeeds (with a 20% caloric deficit every other week) and always eat as much green leafy veggies as it takes to fill you up without ever counting their quasi non-existent carbohydrate content

And while there is some evidence (Teta. 2007, Rodríguez-Carmona. 2013) that would suggest that sodium bicarbonate (baking soda, NaHCO3) to counter the reduction in leptin expression and the use of 12g of ALCAR /day to increase leptin sensitivity (particularly, in older people; cf. Iossa. 2002) could help, as well. Working and eating right for your current metabolic needs will always be the most important factors.

References:

1. Bouassida A, Chamari K, Zaouali M, Feki Y, Zbidi A, Tabka Z. Review on leptin and adiponectin responses and adaptations to acute and chronic exercise. Br J Sports Med. 2010 Jul;44(9):620-30.
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