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marylin monroe
Showing posts with label burn fat. Show all posts
Showing posts with label burn fat. Show all posts

Intelligent Weight Loss Workouts: 45 Min of HIT'14 = "High Intensity Thinking" Help Resolve HIS New Year's Resolution

High intensity thinking - intelligent weight loss workouts
It's almost 2014! Actually it is already 2014; at least for my friends in the "Far East" (HAPPY NEW YEAR!) and thus almost too late for the annual "I want to lose weight" new year's resolution. Ok, you as a SuppVersity reader should actually know better, but just in case you are still planning to make the weight loss happen solely by increasing your workout volume, I would suggest that you replace some classic HIT training with the revolutionary HIT 2.0 - high intensity thinking regimen (warning: doing this too often may actually build more brain than muscle mass ;-). 

Well,... now that I take a closer look at the results of this recent study from the University of Quebec here,  I have to realize that this will only work if you are a man. But don't worry, I am pretty sure there is something to be learned for the ladies in the last SuppVersity article of 2014, as well ;-)

All jokes aside, your brain is a sucker for energy!

I guess you will be familiar with the over-cited fact that "the human brain is only 2% of the weight of the body, but it consumes about 20% of the total energy we need every day"... I know that's boring, but actually that's quite an important point, because it tells you that your brain is not just a sucker for energy, but also a sucker for new information, which will in turn increase the energy requirements of the insatiable heap of neurons in your skull. Why? Well, our brains need energy to process each and every of these information chunks - max. 30W per opeartion, if the currently heralded estimations are correct. I know that sounds tremendously much, but if we performed only one of these operations per minute, you would hardly burn the energy equivalent of 1/25 of a 70-85% chocolate bar during your high intensity thinking sessions.

Against that background it's all the more impressive that Emilie Pérusse-Lachance and her Canadian colleagues were able to measure a significant increase in energy expenditure, when they had their 35 subjects (22 men and 13 women; aged 24 ± 3 years) read a 10-page text and write a summary of approximately 350 words using a computer in the "mental work condition" of their study.
Figure 1: Energy expenditure in kcal/45min in the control and the mental work condition, left; energy intake during the buffet ca. 15min after the control and mental work condition, right (Pérusse-Lachance. 2013)
If you take a look at the data in Figure 1, you will also notice that the scientists original hypothesis, which was that they would observe a similar hyperphagic (=hunger ➲ increased energy intake) response to in the "mental work" condition as Chaput et al. who conducted two very similar studies in 2007 and 2008.  The actual study outcome does yet tell a different story: While the female study participant did in fact supercompensate for the extra-energy they had to spent, when they were not watching TV and lolling around like in the control condition, the men were probably so immersed in their thoughts that they simply forgot to eat... ok, I guess you already realized that this was an ad-hoc hypothesis to make sure you don't realize that neither I nor the scientists have any clue what the underlying reasons of this sex-difference were.

I would even guess that the women did not even notice that they were overcompensating. If you take a look at the subjective hunger scores that have been assessed by seven visual analogue scale questionnaires the participants had to fill...
  1. at the beginning (T-60/60 minutes before the buffet), 
  2. after the experimental session (T-15/15 minutes before the buffet), and 
  3. after the buffet-type meal (T0, T60, T120, T180, and T240).
...those will tell you that the ladies either claimed to, or actually weren't more hungry than in the control condition. In view of the irrefutable evidence that they still ate more (see Figure 1) this may look awkward. When it's all said and done, these contradictory result does yet only confirm that you cannot trust people, when they tell you "I am never hungry and actually don't eat that much.... I have really NO clue where that belly comes from". This may even be their own perception, but that does not change that it is usually not in line what happens at the buffets, dinner tables and - most importantly - during the snack breaks people take during not after their high intensity thinking regimen all over the world.
Figure 2: Change in energy balance (kcal) in the "exercise" condition in the course of which the subjects walked on a treadmill for 45 min, waited for 15 minutes and were then allowed to avail themselves of as much food as they wanted at the buffet - further evidence that the "exercise just makes you hungry" hypothesis is bunk.
Bottom line: By now you should have realized that this article must not be taken too seriously. Though,... if this type of heavy brain lifting would have women eat 15.3% (=121kcal/day) more and men 16.1% (=267kcal/day) less every day it would probably have a non-negligible impact on your chances of living up to your new year's weight loss resolution in 2014.

But don't worry, ladies. Life is not so unfair as it may seem. All you have to do to achieve an almost level playing field is to convince him that a 45 min walk in the park with you is much more fun than 45 min of high intensity thinking. And if that's  not convincing enough, show him the data in Figure 3 and tell him that real exercise (in the study 45min of paced walking) will help both of you improve your energy balance - his by -31% (-516kcal) and yours by -23% (-184kcal).
References:
  • Chaput, J. P., & Tremblay, A. (2007). Acute effects of knowledge-based work on feeding behavior and energy intake. Physiology & behavior, 90(1), 66-72.
  • Chaput, J. P., Drapeau, V., Poirier, P., Teasdale, N., & Tremblay, A. (2008). Glycemic instability and spontaneous energy intake: association with knowledge-based work. Psychosomatic medicine, 70(7), 797-804.
  • Pérusse-Lachance, E., Brassard, P., Chaput, J. P., Drapeau, V., Teasdale, N., Sénécal, C., & Tremblay, A. (2013). Sex Differences in the Effects of Mental Work and Moderate-Intensity Physical Activity on Energy Intake in Young Adults. ISRN Nutrition, 2013.

Optimizing the "Fat Burning Zone" : Chronic Endurance Training Boosts Fatty Oxidation - Does More Help More?

You as a SuppVersity reader should know that there is no "instant gratification" with  "doing cardio" and that doing it "in the zone" is totally 90s... 1990s, even ;-)
For decades, the "Fat Burning Zone" has been one of the holy grails of exercise sciences. Then somebody realized that maximizing the ratio of fat : glucose that's are being used as fuel during a workout doesn't really have an effect on weight loss and all of a sudden papers with titles like "Changes in peak fat oxidation in response to different doses of endurance training" (Rosenkilde. 2013) have become a rarity... although, if you look closely, you will realize that this is actually not another investigation into the realms of the "Fat Burning Zone", but an afford to quantify the effect of regular "cardio training" on your bodies ability to oxidize fat, instead of glucose.

Don't worry it's not really about the "fat burning zone"

Luckily Rosenkilde's most recent paper, which happens to be the third spinoff of the high (600kcal/day) vs. medium (300kcal/day energy expenditure from "cardio") training volume that already taught us (you can read more about the exact exercise protocol in the previous SuppVersity articles, below) ...
  • Learn more about the "Fallacy of Working Out To Burn Calories" 
    how futile it is to work out like a maniac if fat loss is your goal ("Some HIIT For Life & Less LISS For More! How to Burn 27,300 Kcal Extra W/out Losing a Single Extra Pound of Fat!" | read more) and 
  • how messed up the die hard belief that "exercise" just makes you hungry actually is and what the effects of endurance exercise on appetite and energy intake are ("Exercise: Does It Really Make You Hungry? The More You Train, The Less Hungry You Are." | read more)
In this second serving of the data, we can now learn whether regular endurance training increases peak fat oxidation in a dose-dependent fashion.
Figure 1: Pre & post respiratory exchange ratio (lower value = higher ratio of fatty acid : glucose oxidation) in sedentary control and 300kcal/day group, left; changes in the expression of mitochondrial enzymes (Rosenkilde. 2013)
As you can see in Figure 1 the outcomes of the experiment were not exactly surprising: While there was a persistent increase in fatty acid oxidation and the expression of the facilitative mitochondrial complexes, i.e. enzymes in the mitochondrial respiratory chain, the daily endurance training volume (MOD: 300kcal/day vs. HIGH: 600kcal/day energy expenditure during endurance training) had no effect on the effect size.

So, if it's not the volume, what determines the increase in fatty acid oxidation?

Rosenkilde have probably asked themselves something similar to the above, when they realized that there were no meaningful differences between the subjects in the medium vs. high dose cardio groups. The statistical analyses the researcher conducted did yet reveal, that
  • VO2peak, generally regarded as a marker of cardio-respiratory fitness,
  • fat free mass, the weight of everything (incl. bones, organs, etc.) that's not fat, 
  • cycling efficiency, the power output at a given VO2 peak, and the
  • mitochondrial complexes II–V, enzymes that facilitate the oxidation of fatty acids,
were all associated with higher increases in fatty acid oxidation, while the observed changes in fasting plasma insulin, glucose, FFA, or glycerol had no prognostic value with respect to the increase in fatty acid oxidation.
Don't forget that HIIT is an even more effective "long-term investment" in VO2 peak an mitochondrial power - just don't do it everyday | learn more
Bottom line: I guess you will start yawning, when I tell you that doing regular cardio training is not useful for its acute effects on energy expenditure (you know that, right?).

If you look around the gym, you will yet notice that "burning energy" is still what 90% of the cardio warriors have on their mind. What they fail to realize is that performing a sane amount of low-medium intensity cardio will be rewarded in the long run only and is (some of you may remember that from the SuppVersity Facebook News) associated with increased muscle strength throughout the life span (Crane. 2013), delays the age of decline in leg strength and muscle morphology (Tarpenning. 2004), improves muscle function in the elderly (Harber. 2009) and can have have minimal hypertrophy effects even in the elderly (Ozaki. 2013).
References: 
  • Crane, J. D., MacNeil, L. G., & Tarnopolsky, M. A. (2013). Long-term Aerobic Exercise Is Associated With Greater Muscle Strength Throughout the Life Span. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 68(6), 631-638.
  • Harber, M. P., Konopka, A. R., Douglass, M. D., Minchev, K., Kaminsky, L. A., Trappe, T. A., & Trappe, S. (2009). Aerobic exercise training improves whole muscle and single myofiber size and function in older women. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 297(5), R1452-R1459.
  • Ozaki, H., Loenneke, J. P., Thiebaud, R. S., Stager, J. M., & Abe, T. (2013). Possibility of leg muscle hypertrophy by ambulation in older adults: a brief review. Clinical interventions in aging, 8, 369.
  • Rosenkilde, M., Reichkendler, M. H., Auerbach, P., Bonne, T. C., Sjödin, A., Ploug, T., & Stallknecht, B. M. (2014). Changes in peak fat oxidation in response to different doses of endurance training. Scandinavian Journal of Medicine & Science in Sports.

Making HIIT a Hit Part I/II: The Quest for the Optimal Interval to Rest Ratio for Your Type & Goals - Warming up: Selected Studies + Individual Take Home Messages to Set the Scene

This series will not readdress the "HIIT and/or LISS debate", but simply try to do what the title says: Help you to determine the "ideal" form of HIIT for your type & goals.
After posting yet another article about the benefits of high intensity interval training (HIIT) training on Wednesday, I thought it may be a good idea to take a look at the pertinent literature to get a better grasp of what exactly high intensity interval training actually is... "What it is? What do you mean?" While almost everyone appears to recommend you do at least some amount of high intensity interval training, these days, the definition of both the "high intensity" and the "intervals" which are more than just eponymous of this type of training are usually pretty wooly. The two questions this article is supposed to answer are therefore: How long should the intervals and rest periods be and at which intensity should they be performed.
Attention, this article turned into a two part series: I must warn you, this "quest" turned out to be hell lot of work and way more than I had expected. So I will have to split it up into a two-part series. With today's first part discussing exemplary "success stories" and the subsequent follow up on next Sunday providing a more comprehensive overview and general conclusions one may draw based on the picture that emerges.

Part I: Success stories - learning from the "best"

I decided that it may be a good idea to initially compile some examples of which you could say that they are examples of a successfully implementation of high intensity interval training. In that, I will put an emphasis on "old" studies that have not yet been discussed on the SuppVersity. This means, if you want more examples before next week's 2nd installment with a more general overview, you can simply click through the archive of articles that are marked with the keyword HIIT - either as HTML or RSS (I recommend the latter if you do not intend to read all of them anyway; opens in all good browsers without a reader).

Untrained participants and non-athletes
  • 5min on, 2min off HIIT to increase fitness (VO2max) alternated with 40 min steady state cardio for 4 + 5 weeks (Hickson. 1981) -- Hard to believe but it's more than 30(!) years ago that Hickson, Hagberg and Ehsani were able to show that a combination of high intensity interval training with 6x5min cycling at 90-100% of the VO2max and 2-min at 30%-50% active rest between intervals on day one and 40 min of steady state "cardio" on a treadmill on day 2 (6 workouts per week) yielded profound increases in VO2max:
    Figure 1: Adaptation to combined HIIT + steady state protocol in "occasionally active" but not "regularly" trained men (n=8) and women (n=1) in the Hickson study (Hickson. 1982).
    For our purpose, the most significant finding of this study may however be that the t1/2, i.e. the amount of time it takes for 50% of the adaptations to take place is only 10 days (on this intense protocol).

    Take home message: If VO2Max and overall conditioning is your goal you should up the intensity every three weeks, to make sure you continue to make progress. If you go by VO2max, this would be an increase in the speed you run or bike - not (!) the duration of the intervals and / or their number.

  • 2 series of 5s sprint cycling (8-13x) with 55s of active rest increase force production and rids subjects of "useless" type IIb fibers (Linossier. 1993) -- The 10 students (8 men, 2 women; age 22y; VO2max = 51.2ml/kg/min, everything below 55 is still considered ) in the Linossier study performed 4 HIIT only workouts consisting of 5s all-out sprints on a cycle ergometer interspersed by 55s of active rest cycling at a heart rate of 130-140bpm per week. The number of sprints in each of the two sessions on a single training day (15 min of rest between) were increased from 8 to 13 sprints over the 7-week study period. The main results were improvements in both peak performances +25%  and in the 30-s total work +16%.

    Figure 2: Unexpected shift in muscle fiber type distribution (Linossier. 1993)
    What's also relevant, though not directly performance related is the 19% increase in phosphofructokinase and a 20% increase in lactate dehydrogenase, both are glycolytic enzymes and are indicative of improvements in the glycolytic pathway, which goes to show you that you don't have to be afraid of the fiber type changes hampering either your ability to handle glucose or your strength - I mean +29% in maximal force production in the sprint tests are everything else but "weak".

    Take home message: Shorter sprints appear to be a valid means to hammer and improve the glycolytic pathway and get rid of the useless type IIb fibers, of which not endurance athletes, but bodybuilders have the lowest amount and sedentary controls the most (cf. figure 1 in the overview of the Intermittent Thoughts on Building Muscle). To actually build muscle the 1% increase in muscle weight the scientists observed, is yet not sufficient enough.

  • 7 sessions of 10x4 min cycling at 90% with 2 min rest ramp up skeletal muscle fat metabolism in young women (Talanian. 2006) -- The 8 healthy recreationally active women (22 yr old, 65.0 kg body wt) who had previously engaged in 2-3 just-for-fun sessions of various activities from weight lifting, soccer and cycling to swimming, or walking, participated in no more than 7 HIIT sessions within 2 weeks (1 day on, 1 day off) which consisted of 10x 4min sprints at 90% of their individual VO2max with two minutes of rest in between.

    Figure 3. Changes in substrate utilization during standardized 60 min LISS test at 60% of the VO2Max (Talanian. 2006)
    Contrary to the previously discussed studies, the scientists were in this case less interested in the performance than in the metabolic benefits, which were - as the data in figure 1 show - surprisingly significant given the short duration of the study. The increases in fat oxidation and decreases in the respiratory ratio (the ratio of glucose to fatty acid oxidation) during a standardized 60min light intensity (60% VO2max) test that was performed at the beginning and end of the study, were a consequence of increases in citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta -HAD) activity.

    Take home message: In view of the important contribution of beta-HAD to the beta oxidation of (esp. medium-chain) fatty acids, the fact that an upregulation of this enzyme has been observed in response to the long duration intervals, but neither light intensitsy exercise (even w/ 2h per day, 5-6 times per week; cf. Phillipps. 1996), nor during a similar 2-week sprint training protocol (30s all-out on cycle ergometer, 4 min rest; cf. Burgomaster. 2005) points towards "long" duration intervals when mitochondrial adaptations that favor fatty oxidation and thus subsequent increases in fat loss with light activity are concerned. 

Highly trained participants and pro-athletes
 

  • 3 sessions of 10 intervals at 96% VO2Max with 60-180s rest increase running economy and relative fatty oxidation during subsequent steady state exercise test (Zavorsky. 1998) -- Twelve highly trained endurance athletes volunteered for this study, four of them qualified for the 1996 Canadian Olympic Trials, and one subject was a Canadian record holder in triathlon. On three different occasions the subject ran 10 x 400-m sprints with active recovery periods of 60, 120, 180s (randomly assigned). 10 min before and afterwards standardized running economy tests were performed.

    Figure 4: Respiratory exchange ratio in RE test before and after the sprinting protocol (Zavorsky. 1998)
    During these running economy tests, which consisted of 2 x 5 min running on a treadmill at 12km/h or 16km/h (5 min total rest in between), the subjects exhibited, much contrary to the research hypothesis, by the way, an increase in the running economy (RE, a measure of how efficiently a person uses oxygen while running at a given pace) and - probably of greater interest for most of you an increase in fatty acid oxidation, as evidenced by the reduced respiratory exchange ratio (RER, figure 4). The latter was particularly pronounced in the "low intensity" RE test at 12km/h.

    As far as the differential effects of the rest intervals is concerned, significant effects were observed for the rates of perceived exertion (60s: 17.7; 120s: 16.1; 180s: 14.4), but not for the performance related measurements velocity, and the time it took the athletes to run the 400m sprints (actually the latter should be self-evident with identical velocities).

    Take home message: Doing ten short sprints (if you are not an athlete, shorter ones will suffice) before you go jogging (or do any other type of steady state cardio) won't hamper your running economy. And since the study at hand suggests that the relative increase in fatty acid oxidation is specifically pronounced in the lower intensities (this is supposedly even more the case if you jog at 10km/h), the combination of sprints + steady state cardio appears to be an ideal "cardio" only day, when you are trying to lose body fat.

  • 8x all-out (100% VO2max) 2.5min intervals with 4 min of active rest increase VO2Max, peak aerobic power and 5k time trial performance regardless rest between sessions (Gross. 2007) -- With the unique twist with respect to the training frequency this study is somewhat unique. While other studies report similar benefits in highly trained collegiate cyclists (13 men, 4 women; VO2Max at baseline 62ml/kg/min) or other endurance athletes, this is one of the few that investigates whether it makes a difference if the athletes implement the 3-days per week HIIT regimen as a block or interspersed by one day of rest into their regimen.

    Percent change in TT5k velocitym TT5k power output VO2peak, and peak aerobic power output in cyclists trainin on consecutive vs. non-consecutive days (Gross. 2007)
    Interestingly enough, neither the performance outcome on the pre- and post tests, i.e. increases in VO2Max (+5.7%), peak aerobic power (+7.2%), 5k time trial performance (+6.9%), nor the actual performance during each of the workouts the subjects performed in the course of the 3-week study period suffered from doing the HIIT sessions back to back. These results refute previous speculations that doing HIIT as a block would trigger greater metabolic adaptations, specifically in athletes (e.g. Padilla. 2000). Even more, though the changes were not statistically significant, the data in figure 5 shows that - with one for endurance athletes important exception, namely the VO2Max - training on non-consecutive days produced marginally better results.

    Take home message: While it appears as if it would not make a difference whether you perform your HIIT workouts blocked or within your training week. The non-significant differences in figure 5 could suggest that endurance athletes intending to improve their already high VO2Max even further would be better off with the blocked training. Everybody else has the choice and I would pick the interspersed variety, whenever my schedule allows me to do this - my personal experience told me that this works better for me... apropos, take another look at figure 5 you see the narrow bars indicating the standard deviations? This goes to tell you that it is very likely that not just the personal preferences, but also the actual outcome will vary from trainee to trainee, which supports the notion that you will have to experiment to find what works best for you.

    That's it for the "success stories"! Don't forget to come back next Sunday for part II and in case you have not done so already, just browse the previous SuppVersity posts on this matter, either as HTML version, post by post, or from the RSS overview (works in every modern browser, yet not in Google spyware ;-). I know you are smart enough to draw your own conclusions. And what's more, this may yield some cognitive input for the comment area of this article, where you can post questions. I will try to tackle those I can answer in the next installment.

        References:
        • Burgomaster KA, Hughes SC, Heigenhauser GJF, Bradwell SN, Gibala MJ. Six sessions of sprint interval training increase muscle oxidative potential and cycle endurance capacity in humans. J Appl Physiol. 2005; 98: 1985–1990.  
        • Gross M, Swensen T, King D. Nonconsecutive- versus consecutive-day high-intensity interval training in cyclists. Med Sci Sports Exerc. 2007 Sep;39(9):1666-71.
        • Hickson RC, Hagberg JM, Ehsani AA, et al. Time course of the adaptive responses of aerobic power and heart rate to training. Med Sci Sports Exerc 1981; 13: 17-20.
        • Linossier MT, Denis C, Dormois D, Geyssant A, Lacour JR. Ergometric and metabolic adaptation to a 5-s sprint training programme. Eur J Appl Physiol Occup Physiol. 1993;67(5):408-14. 
        • Padilla S, Mujika I, Orbañanos J, Angulo F. Exercise intensity during competition time trials in professional road cycling. Med Sci Sports Exerc. 2000 Apr;32(4):850-6.
        • Phillips SM, Green HJ, Tarnopolsky MA, Heigenhauser GJ, Grant SM. Progressive effect of endurance training on metabolic adaptations in working skeletal muscle. Am J Physiol Endocrinol Metab. 1996: 270: E265– E272, 1996
        • Talanian JL, Galloway SD, Heigenhauser GJ, Bonen A, Spriet LL. Two weeks of high-intensity aerobic interval training increases the capacity for fat oxidation during exercise in women. J Appl Physiol. 2007 Apr;102(4):1439-47. 
        • Zavorsky GS, Montgomery DL, Pearsall DJ. Effect of intense interval workouts on running economy using three recovery durations. Eur J Appl Physiol. 1998; 77: 224-30.

        Intra-Workout Supplementation: Increased Carbohydrate Oxidation with L-Arginine, Lower Fat Oxidation with Glucose & Lowest Rate of Perceived Exertion with Plain Water

        Image 1: This bird certainly knows about the importance of adequate hydration ;-)
        Have you been at the gym today? If so, what kind of beverage have you been sipping in the rest-periods between your sets, your sprints or during your regenerative (not fat burning ;-) "classic" cardio exercise? Was it Funky XYZ the latest and greatest intra-workout product on the market? If so, you better check out its ingredients, who knows maybe the "latest and greatest" turns out to be quite counterproductive towards the goals you have been setting after reading one of the last two installments of the Intermittent Thoughts? Let's assume you are the "Peter Griffin"-type of chubby - in that case, I hope that your Funky XYZ did not contain glucose, maltodextrin, waxy maize, or any other of the sugars of which the supp companies are going to tell you that they "superior" to the white poison your granny uses in her delicious muffins. Why? Well, according to a soon to be published study by scientists from the Massey University in Wellington, New Zealand, as little as 12g of glucose will reduce the amount of endogenous fatty acid (i.e. the stuff your body is using to hide your abs ;-) oxidation by -22%! Sounds terrible, doesn't it? Well, let's look at some details to decide whether those -22% will really make a difference and what effects the presence of l-arginine and l-glutamine in your intra-workout supplement could have had.

        150 min @ 177 Watt + Glucose + (Glutamine or L-Arginine) = ???

        Figure 1: Composition of the intra-workout supplement; sodium citrate base + 12g glucose (glucose) and additional 1g l-glutamine (Glu + L-Glutamine) or 0.1g l-arginine (Glu + L-arginine)
        It stands out of question that adequate hydration is of utmost importance, when it comes to maximizing athletic performance (incidentally, the same is true, when it comes to "burning fat"). What athletes should drink before (pre-hydration), during (hydration) and after your workouts (re-hydration) is thusly one of the classic topics of exercise science and the recent study by D.S. Rowlands et al. is thusly probably #1001 on the never-ending list of investigations into the optimal mineral and nutrient composition of intra-workout drinks. For us, it is of interest, because it is one of the few which investigated the differential effect of the amino acids l-arginine and l-glutamine on substrate utilization, plasma glucose, lactate and sodium levels and rates of perceived exhaustion in eight male cyclists and triathletes during 150min (!) of cycling at 50% of the individually predetermined peak power (this is noteworthy, because 50% of their peak power equalled 177 W, which is not exactly "light" exercise), in the course of which the athletes consume 150ml of a fluid containing a 0.95g sodium base and either 12g of glucose alone or a combination of glucose and either 1g of l-glutamine or 0.1g of l-arginine (cf. figure 1).
        Figure 2: Oxygen consumption (L/min) and substrate utilization (g/min) in 8 trained cyclists / triathletes during 150 min of cycling at 177W with 150ml of four different intra-workout drinks (data adapted from Rowlands. 2011)
        As a seasoned student of the SuppVersity, it should not surprise you that the exogenous (i.e. from the outside) supply of glucose produced a -22% shift in substrate oxidation from fatty acids to the now more readily available carbohydrates (cf. figure 2). What you have probably not expected, though, is that the addition of the minuscule amount of l-arginine (which is btw. about what you will get with many of the proprietary blends in the still incredibly popular "NO-boosters") would promote this shift by increasing the total amount of oxidized carbohydrates by another ~10% over the 12g glucose solution alone.
        Figure 3: Comparison of total / relative substrate utilization for the 12g glucose + 0.1g arginine, the 12g glucose and the water + sodium citrate groups (data adapted from Rowlands. 2011)
        Now you are stunned, hah? So after all it is yet not your fault that you cannot see your abs. It's your NO-suppement! Well, not exactly. I mean take a look at the way I arranged the data in figure 3. You will probably acknowledge that the 12g glucose + 0.1g l-arginine group "burned" more energy - if you want it in calories (remember this is stupid ;-) 0.68kcal/min or 102kcal during the whole session and then come back to the -22% reduced fatty acid oxidation and lament: "But Dr. Andro, they burned 22% less fat than the water-only group! Now I know why I don't get lean." If that is your train of thought, I would invite you to continue the idiotic kcal number crunching and calculate on how much fat the poor l-arginine group would have missed to burn... well, it's the "exorbitant" amount of 170mg/min or - for the whole session 25.5g! While this may be more than one tablespoon of coconut oil, I guess you will probably admit that this probably is not the reason your abs are still covered by a thick layer of flabby adipose tissue, won't you?

        Arginine reduces oxygen cost at the expense of glucose

        Now, the real interesting findings of the studies are thusly not the changes in substrate utilization but rather the profound impact the addition of the two amino acids had on the lactate levels during the 150min of cycling (cf. figure 4) and the rates of perceived exertion (RPE).
        Figure 4: Plasma lactate levels (mmol/L) in 8 trained cyclists / triathletes during 150 min of cycling at 177W with 150ml of four different intra-workout drinks (data adapted from Rowlands. 2011)
        The latter (RPE), and this is actually quite surprising, were minimal in the water + sodium citrate group and maximal in the 12g glucose + 1g l-glutamine group (0.8 pts greater on a 0-7 scale). The RPE values of the arginine group, on the other hand, were only marginally elevated and that despite the significant increase in glucose clearance, which, by the way, has also been observed by McConell et al. (McConell. 2006) and Linden et al. (Linden. 2010). 

        In view of recent studies such as Greer et al. (Greer. 2011), who observed a small, but statistically significant decreases in endurance during a strength training circuit in response to Arginine-Alpha-Keto-Glutarate (AAKG) supplementation, it is yet very unlikely that the observed effects of an arginine-enriched glucose containing intra-workout supplement observed in this study "have the potential to benefit endurance exercise performance" (which is what the scientists, much to my surprise, conclude). Another thing is yet more than likely, I would even say it is 100% certain: Neither the results of this nor of any future study will change the sales ranks on Bodybuilding.com & Co., where the purported NO-Boosters (and factual stimulants) still are the front-runners of the "TOP 10 selling products" ;-)

        High Reps vs. 5x5 - Revisiting the "High(er) Reps for Fat Loss"-Myth: Do You Really Believe that "Burning" +13 Extra Calories Will Make a Difference?

        Image 1: Vince Andrich, here at the 1988 Nevada State Bodybuilding Competition, knew it all along: Hard work, not high reps will get you the stage-ready physique everybody aspires... and I mean look at him are you seriously questioning Vince's expertise?
        If you have listened to the latest installments of BodyRX Radio, the idea that strength (and HIIT) training, not calorie restriction and endless cardio sessions pave the way to a leaner, more muscular physique. And although it may be of secondary importance whether you are burning 100kcal or 200kcal during those workouts, it stands out of question that you won't get rid of those damn spare tire, if you do not exert yourself in the gym (something Layne Norton is notorious for, as you may have seen in one of his workout videos or heard on BodyRX, lately) - because, after all, energy expenditure does count, even if the energy equation is much more complex than the simplistic calories in vs. calories out paradigm that is still upheld by mainstream dietitians. The results of a recent study from scientists from the Departments of Health and Sport Sciences at the Salisbury University and the University of South Carolina are may thus come handy to decide, to which extent workout intensity and volume influence acute and post-exercise energy expenditure (Mazetti. 2011). Or, to make it simple, does the good old bro-scientific high volume, high rep, low-weight training during a contest prep make any sense at all?

        Exposed! The absurdity of going to the gym to "burn calories"

        Scott A. Mazetti and his colleagues recruited 10 resistance trained young men (22+/-3.6 years) with an average body mass of 84+/-6.4kg, a height of 180+/-5.1cm, and a body fat percentage of 13+/-3.8% - an adequate model of the "average gymrat", if you asked me. After a 3-week familiarization and testing period, all participants performed every of the following four different explosive strength training regimen in a randomly assigned, but counterbalanced order (cf. figure 1)
        Figure 1: The four training protocols all trainees performed after an initial 3-week familiarization and testing period in a randomly assigned, but counterbalanced order (Mazetti. 2011)
        Now, you may complain that there is neither a "high rep" nor a "heavy group" in the conventional sense of 15+ pump training with an endless amount of sets, or the minimalist 1-2 rep approach of the hardcore HIT faction... granted, you are right. Nevertheless, we should see a significant difference in energy expenditure between a 5x5 and a 4x10 (both normally considered as "hypertrophy training) regimen, already, if the good old saying "high(er) reps" for increased energy expenditure and subsequent fat loss had any merit.
        Figure 2: Energy expenditure (kcal/min) during and after squatting, and bench pressing in the four training groups and total energy expenditure during the whole workout and 60min post-workout window (data adapted from Mazetti. 2011)
        As figure 2 goes to show, there are differences in energy expenditure between the different protocols, during the squat, the deadlift and up to 5 minutes post exercise, nevertheless, the "the differences in total energy expenditure among protocols were not significant". So, even if there were any merit in exercising primarily to burn calories during your workout (a ridiculous way of trying to lose weight, which is predestined to fail, anyway), the -6kcal difference between the -13kcal difference between the least energy consuming form of training, i.e. 5x5 and the one with the highest energy demand, i.e. 4x10, would not even suffice to "make up" (another hilarious idea) for proverbial "apple à day", which keeps the doctor away.
        Image 2: Don't let your lazy love handles decide what type of "cardio" you are doing!
        A brief note on what Lane already pointed out in the last installment of Body RX Radio: Classic low-intensity cardio training may "burn" calories for a week or two. Afterwards, this type of chronic low-grade stressor is yet notorious for shutting down your metabolism and reducing your resting energy expenditure. Of high intensity aerobic exercise with intensities way beyond the 70% VO2max limit (YES! This is aerobic, two - cf. "HIIT is the Hit! Even for Patients with Myocardial Infarctions!"), we have known for decades that it increases your resting energy expenditure by "5 ±15% for 24 ± 48 h" (Hunter. 1998). So, I suggest you get off the stationary bike you are just riding while browsing the web, get your running shoes out and do a couple of sprints. Your spare tire won't like that, but I bet you will like the effect it's going to have on the person you see in the mirror, each morning ;-)
        In view of these results, it appears prudent to reassess the often-heard advice of doing high reps for fat loss. Even if you insist that you need to "burn calories" in the gym, it is very unlikely that those few extra calories would make a noticeable difference in terms of how you look on stage - or just in front of your private mirror. Moreover, even this small advantage vanishes as soon, as you increase the workload by doing 2x7 + 2x6 with a heavy weight, or put simply: Identical workload identical calorie expenditure.

        HIITing Diabetes With the Hammer: 20min of Low-Volume High-Intensity Interval Training is Enough! + Metabolic Benefits and Optimum Interval-Format for Healthy People!

        Figure 1: Number [in millions!] of prediabetics and diagnosed and undiagnosed diabetics in the USA according to data from the American Diabetic Association from January 2011 (ADA. 2011)
        You probably remember Wednesday's news-item on high-intensity interval training (HIIT) for cardiac patients - as it turned out, even 2 weeks after myocardial infarction our central pump needs real exercise to get back in, or to get into even better shape. Today, I do yet want to go beyond infarction patients and address another, ever-growing sub-group of the self-perceived "victims" of the obesity pandemic, the type II diabetics.

        About a month ago, J.P. Little and his colleagues from the University of British Columbia Okanagan published a study in the Journal of Applied Physiology (Little. 2011a), the results of which confirm (once again) the unpopular hypothesis that getting your ass off the couch in order to work it off in the gym hard (!) is the only way to treat a (largely) self-induced health condition that is plaguing 8.3% and threatening another quarter (79 million people with pre-diabetes) of the US population (ADA. 2011, cf. figure 1).

        In the Little study (pun intended ;-), it took 8 type 2 diabetics no more than 60 minutes of intense exercise at 90% of their maximal heart rate (+another 60 minutes of rest in between intervals) to
        [...] rapidly improve glucose control and induce adaptations in skeletal muscle that are linked to improved metabolic health
        120 minutes (!) of which only 60 were spent doing 10x60s intervals on a cyclometer brought about changes, no pharmaceutical (or even supplement) will ever produce (without significant side effects). 120 minutes spread across 6 exercise sessions in the course of two weeks, i.e. 3 sessions of 20 minutes per week - probably 20 minutes the majority of the 8 overweight (BMI 32.6kg/m²) diabetics would otherwise have spent on their couch in front of the TV, or - with comparably small benefit - trampling away at 65% of their VO2Max on a recumbent bike. With intervals at 90% of their maximal heart rate, however, the
        [...] average 24-h blood glucose concentration was reduced after training (7.6±1.0 vs 6.6±0.7 mmol/L) as were the sum of the 3-h postprandial areas under the glucose curve for breakfast, lunch and dinner (both p<0.05).
        More importantly, though, HIIT training set the stage for future improvements by improving the capacity of the trainees mitochondria to handle / burn nutrients, with the >3.5x increase in GLUT-4 acticity indicating a profoundly increased capacity for glucose uptake and the +20% increase in citrate synthase activity indicating an increased capacity for substrate oxidation (energy usage) in the cellular power plants of the 8 diabetics (cf. figure 2).
        Figure 2: Improvements citrate synthase, protein content of 70kDA subunit, complex III core 2 protein, complex IV subunit IV, mitofusion 2 and Glut-4 activity - all markers of mitochondrial capacity / efficiency - after 6 sessions of 10x60s cycling at 90% HRmax in 8 diabetic patients (data calculated  based on Little. 2011a).
        These improvements, and this is a result from a previous study by Little's group (Little. 2011b), were - at least in part - a result of the effects HIIT has on mitochondrial biogenesis, of which Little et al. found that it is profoundly elevated in the first 24h after the exercise bout (3h post: +70% nuclear PGC-1alpha/Tubulin, 24h post: +60% whole muscle PGC-1alpha/Tubulin; +150% increase in p-p38MAPK) - and all that after a single session of a all 4x30s all-out Wingate cycling tests separated by 4 min of rest).

        Now, let me ask you: Do we really ask too much of our fellow (and mostly ridiculously lazy) human being, if we ask them to invest one hour of their life per week to exercise into a, no, their healthier future? I wouldn't think so!

        Figure 3: Fat oxidation in kJ per minute during 60 min of cycling at 60% VO2Max before and after 7 sessions of HIIT training in eight healthy, normal-weight recreationally active women (Talanian. 2006).
        Metabolic benefits of HIIT training: Now, you may well ask yourself, why you should a give a damn about those changes, well... would it convince you, if I told you that in a 2006 study Talanian et al. were able to show that after 7 sessions of serious HIIT training (10x4 min at 90% HRMax with 2 min rest between intervals) the amount of body fat the eight female study participants burned during cycling at 60% of VO2Max was increased by 36% (Talanian. 2006)? in other words, the HIIT sessions primed the bodies of the "recreatinally active women (22+/-1 yr old, 65.0kg body wt, 2.36l/min VO2peak) to burn more fat during subsequent cycling at the lower end of the "fat-burning zone"! As the data in figure 3 shows, this effect was partly, because the subjects switched more readily into "fat burning mode" - a priming effect from the HIIT sessions.


        HIIT, yeah... but how to find the right dosage?

        Both the Moholdt, as well as the Little study have shown that it does not take much to induce profound health benefits - but what would be the optimal dosage for YOU, who, as a diligent student of the SuppVersity, are probably (or should I say hopefully) neither an overweight diabetic nor a cardiac patient?

        Figure 4: Changes in body weight, body fat (%), peak lactate levels, perceived exertion (RPE) and VO2Max (rel. to body weight) after low intensity continuous training or three different HIIT protocols in recreational cyclists (data calculated based on Seiler. 2011)
        Apparently, a group of scientists from Kristinsand (again in Norway, where the descendants of the Vikings obviously are tough enough fore real exercise ;-) asked themselves the exact same question (Seiler. 2011). In the course of a 2 months study they had 29 male and 6 female recreational cyclists, whose VO2Max of 53+/-6 ml*kg/min were ~56% higher than those of the cardiac patients (after the intervention) in the Moholdt study, perform 2 HIIT sessions per week (plus 2-3 weekly low-intensity bouts) of one out of three different interval training programs: 4x4min, 4x8min, or 4x16 min at 94%, 90% or 88% of their respective maximal heart rates.

        Hard, but neither torturous, nor time consuming

        The results, I have plotted in figure 4, confirm that HIIT must be hard, but neither torturous nor time-consuming. Or as the scientists put it:
        The 4x8 min prescription induced greater physiological adaptation than both lower and higher intensity interval programs of 64- and 16-min total duration but was perceived as less stressful than 4x4 min at ~95% HR max . These findings suggest an important interaction between accumulated work duration and work intensity that can be optimized for inducing maximal physiolo gical adaptations at manageable RPE [rates of perceived exertion] in endurance athletes performing interval training.
        Image 1: Spinning at ~90% of your max heart rate
        would be one way to do 4x8 intervals.
        On that note, it may also be interesting that in line with the +91% increase in time to exhaustion Seiler et al. observed in the 4x8 HIIT group (vs. +12% in low intensity and +62% and +63% in 4x16 and 4x4 HIIT programs) and the increased respiratory exchange rate Moholdt et al. observed in their study (cf. Wednesday's news), A.D. Hafstadt and his colleagues from the University of Tromsoe (Hafstadt. 2011) have found in a mouse-model (where cutting out the heart and measuring its weight obviously is not so much of an issue as it would be with human subjects ;-) that despite similar increases in the heart to body weight ratio (+10%), ...
        [...] only HIT altered cardiac substrate utilization, as revealed by a 36% increase in glucose oxidation and a concomitant reduction in fatty acid oxidation, [...] improved cardiac efficiency by decreasing work-independent myocardial oxygen consumption and increased cardiac maximal mitochondrial respiratory capacity.
        These findings lead the scientists to conclude that "high intensity training is required for induction of changes in cardiac substrate utilization and energetics" and that these improvements may be at the heart (pun intended) of its "superior" ability to increase aerobic capacity - or as, I previously phrased it: HIT, not steady state aerobics, is real cardio training! You would not train a 20inch biceps with blue 2pound sand-filled plastic dumbbells, would you? I think, I will leave it on that, for today and wish you all have an intense weekend (whatever your interpretation of that may be ;-)

        Image 2: There is no one-size-fits-it-all HIIT training.
        Addendum of 10/01/2011: In the comments area, Oni posted a quite resonable question: "Doesn't HIIT usually employ shorter (1min) intervals? And how could 8 minute intervals, as in the Seiler study be feasible?" The answer to the first question is easy, as we just have to look at the words "high intensity" and "interval training", now obviously no one questions that the regimen Seiler et al. used, had a high intensity (90%) and employed intervals - and I think Oni does not disagree on that, but rather implies that this type of training is too intense and if the subjects had not been recreational cyclists, this could actually have been the case.

        On the other hand, the results of the Seiler study also showed that shorter intervals at higher intensity lead (in this subject group) to greater rates of perceived exertion. Now, I dare say that 95% of the trainees who are doing the standard ~1min bouts of all-out exercise - are not going "all out" in the sense that they are scratching their real heart rate max. If they did, I am quite sure they would (in line with the results from the Seiler study) confirm that 8min @90% did not wear them out as much as 1min @100% of ALL OUT exercise at their  max. heart. This leaves the question to be answered, whether 4 intervals à 8 minutes are optimal for everyone? And this is fortunately a question that is easy to be answered... 4x8 is obviously for "advanced" athletes (who have been practicing some type of endurance activity already). From my training experience, I know that untrained (or less trained) trainees sometimes do not even reach "target heart rates ~90%" before they feel so exhausted that they give up.

        Image 3: The type of equipment you are using will also have an influence on optimal interval length; doing 8-min all-out intervals on the treadmill certainly are no viable option - even not for highly trained athletes!
        So what does that mean for your training, then? If you like doing the all-out (! don't forget to push yourselves!) 1-minute intervals, keep doing them. There are plenty of studies that confirm similarly beneficial effects on mitochondrial biogenesis with these protocols, e.g.
        If, on the other hand, you are an (endurance) athlete wanting to improve your performance, the available data would suggest that intervals in the +4min range would be the way to go (Seiler. 2004; Driller. 2009; Seiler. 2011), as they are more sport-specific. Overall, it is yet always about balancing duration (individual interval length + number of intervals + rest days in-between) vs. intensity (heart rate) to find your optimal HIIT protocol (Gross. 2007; Zuniga. 2011)

        Fragmented Sleep Reduces 24h Fat Oxidation by > 50% - Not Getting a Good Night's Sleep Sets You Up For Obesity.

        Image 1: It looks awkward, but sleep masks
        and ear-plugs are effective, cheap and
        save ways to improve sleep quality
        (image from lackofsleepsymptoms)
        I think you will be familiar with the idea that an insufficient amount of sleep has been found to correlate (! not induce !) with visceral obesity and other negative health markers (e.g. Strian. 2005). Now a study from a the Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM) at the University of Maastricht in the Netherlands found that not getting a good nights sleep or, in this particular case, waking up every hour, reduces the amount of fat you burn in a period of 24 hours by -52% (Hursel. 2011, cf. figure 1).

        Other than in the initially mentioned epidemiological guesswork ... ah pardon, correlation studies, Hursel et al. had their 15 healthy male volunteers report to the laboratory twice (>2 weeks between the sessions of the randomized, single-blind cross-over study). During each visit, the subjects stayed for 48 h in a respiration chamber, where energy expenditure, physical activity (radar), and substrate oxidation were meticulously measured. On both occasions, the subjects had fixed bedtimes (lights out: 11:00pm; lights on: 7:40am) resulting in 8 h sleeping time per night. On one of the occasions, however, the scientists used induced sleep-fragmentation by the means of "approximately hourly wake-up calls" the subjects had to respond to by turning off their alarm after 2 min.
        Figure 1: Relative differences in carbohydrate and fat oxidation, as well as respiratory quotient (higher quotient = more carbohydrate dependent) in 15 healthy men as a consequence of interrupted sleep (data calculated based on Hursel. 2011)
        Diet-wise, the subjects who had been asked to abstain from strenuous exercise and to sleep for 8 h during the nights before their visit at the lab, were fed a standardized (protein:carbohydrate:fat ratio 12:55:33) diet consisting of "normal, everyday food products" two days before and in the course of their stay in a respiration chamber. The use of the latter, by the way, facilitated pretty exact measurements of the subjects energy expenditure and substrate oxidation (cf. figure 2).
        Figure 2: Relative changes in total, resting (REE) and sleeping energy-expenditure (SEE), as well as absolute changes in activity induced energy expenditure (AEE) and overall caloric balance (data calculated based on Hursel. 2011)
        As the data in figure 2 shows there was no statistically significant difference with respect to the overall calorie balances of the subjects (+0.41MJ/day to +0.41 MJ/day in the normal vs. the interrupted sleep group, respectively). While this appears counterintuitive as the recorded physical activity of the sleep-disturbed subjects had eventually increased, Hursel et al. point out that because of their study design, ...
        we showed an initial increase in physical activity and AEE as an effect of sleep fragmentation, mainly because the subjects had to turn off their alarm clock 7 times during the night. However, the resulting increased exhaustion and sleepiness during the subsequent day might eventually counter-balance physical activity and AEE.
        They go on to point out that the increased activity goes hand in hand with the increase in carbohydrate oxidation, the depletion of glycogen stores and the (this is my assumption) stress-related -52% decrease in fatty acid oxidation (cf. figure 1).

        The real-world results of this unhealthy combination of non-regenerative sleep, daytime exhaustion and sleepiness and the accompanying abstract metabolic shifts are cognitive problems, a lack of motivation (esp. to work out or do any physical work), carb-cravings, snack-attacks & co... In your efforts to (re-)feed a body that is unable to access his well-stocked fat reserves, you end up overcompensate the initially increased energy expenditure, constantly provoking insulin spikes which totally blunt fat oxidation, trigger temporary hyperglycemia (if you are not already diabetic) and induce further snack-attacks. Thus, you are triggering a down-ward spiral that is especially hard to escape from, if your body does not get the chance to reset his insulin and stress levels in the course of a good nights sleep - keep that in mind before you place your cell-phone next to your pillow in order to "keep in touch" with your (facebook-)friends 24/7, as a very recent study published in the journal SLEEP showed that "mobile phone use for calling and for sending text messages after lights out was associated with sleep disturbances independent of covariates and independent of each other" (Munezawa. 2011).

        Tangeritin, Natural Metformin from the Rind of Mandarin Oranges Hits the OFF-Switch on Diet Induced Obesity

        Image 1: Tell me the truth! How much "natural metformin" did you throw away with those mandarine rinds in your life? Update (08/11/2012) Scroll down to the red box on dosing, I added, to check out why you better start saving your mandarine rinds now to be able to do a "tangeritine cycle" in a couple of years ;-)
        I guess it is about time for another longer post on the "Supp" part of SuppVersity and what would be better suited than providing my readers from inside the business to spice up their #1 selling product which has as of late lost yet two other "all natural" ingredients in the never-ending arsenal of funky herbs, spices, -amines and -ephrines. Luckily the supplies nature has in stock are endless and with 5, 6, 7, 8, 40-pentamethoxyflavone (I am not kidding, now that 1,3 DMAA is gone, you will have to remember a couple more numbers ;-) the "next big" thing that's ready to get out of the starting blocks could actually prove to be more than just a stim and an actual weight loss adjuvant! After all, the AMPK boosting effects of tangeretin, which is abundant in the rinds of citrus fruits, such as mandarin orange, rutaceae and yuhu in Korea, appear to be everything but "ordinary" and they are not even the most interesting effect this compound may have on your metabolism.

        Tangeritin, is not be be confused with citrus aurantium, is no stim and could thus actually work!

        In a paper that has recently been published in the Journal of Molecular and Cellular Endocrinology Kim et al. report that the administration of of 200mg/kg (human equivalent 1.3g) of tangeritin per day to mice on a high fat diet did not only slow down weight gain and the development of glucose intolerance and hypercholesterolemia, but also had beneficial modulatory effects on the secretion of the adipokines adiponectin, leptin and resistin, as well as the release of IL-6 and MCP-1.
        Figure 1: Adipocytokine expression and body weight gain of mice after 27 and 55 days on control, high fat (HFD) or high fat diet with 200mg/kg tangeritin (HFD + 200Tan; left) and in vitro glucose uptake of isolated myocytes upon incubation with tangeritin at doses of 25, 50 and 100mMol (right; data adapted from Kim. 2012)
        For Kim et al. the profound effects wich lower leptin, aidponectin, resistin and IL-6 expression in the HFD + Tangeritin group than in the control (I wish we had the body fat levels, I am curious if those were not lower with HFD + tangeritin than in the control group, as well) did yet not come as a surprise.
        Additional figure: How much rind (in g) do you need to produce 1g of tangeritin by water extraction at different temperatures and extraction times (data calculated based on Xu. 2012)
        Update (08/11/2012): In response to questions both on Facebook as well as in the comment section I have compiled the graph on the right, which shows you how much rind (in grams) you need if you wanted to water-extract your 1g daily dose of tangeritin from Satsuma mandarin, which is probably the type of mandarin that is most widely sold here in the West and the more exotic, but tangeritin-rich Ponkan. If you take a closer look at the data from Xu et al. you will yet have to acknowledge that it is probably not feasible to produce your own extract at home - even if you you managed to extract ALL the tangeritin from the Ponkan, which obviously won't work by simply cooking it up, you would still need 232g of rind per day!
        In previous in vitro experiments on isolated muscle cells (C2C12 myotubes), the researchers had already established that tangeritin, when it is appropriately dosed (!), exerts extraordinary powerful effects on the expression of the energy sensor and metabolic switch AMPK, which has as of late gotten quite some attention in  the laypress as the target for "the exercise pill", the "ultimate antiobesity + antidiabetes pill", the "anticancer and longevity pill",... well basically everything that could make a respective drug a pharmacological "bockboster" (read more about AMPK in the SuppVersity Intermittent Thougths Series: "The AMPK/mTOR Seesaw".

        Figure 2: Hand in hand with the beneficial effects on adipocytokine production, the addition of tangerine to the high fat diet also ameliorated the growth and necrosis of adipocytes (Kim. 2012)
        They also knew from previous studies that aside from its role as an inducer of AMPK and GLUT-4 expression in the muscle tissue, tangeretin posses anti-cancer, anti-oxidant and anti-inflammatory properties, as well (Yoon. 2011; Xu. 2008). Kim et al. also point out that
        In addition to its anti-oxidant effects, tangeretin has been reported to inhibit the growth of hepatocytes both in vitro and in vivo via inhibition of mTOR/p70S6 kinase (Cheng. 2011). Regarding tangeretin-mediated effects on neuronal disease, a number of studies have shown that tangeretin reduces dopaminergic neurotoxin-induced neuronal injury and prevents tunicamycin-induced cell death in mice through an increase in glucose-regulated protein (GRP)78 and heme oxygenase (HO)-1 expression in renal tubular epithelium (Takano. 2007).
        Moreover, another recent study by Choi et al. reports that tangeritin also has protective effects against the lipopolysaccharide (LPS) induced nitric oxide (NO) expression in the digestive tract and could thus offer acute and chronic protection from LPS induced cell damage (Choi. 2007).

        Awesome? Well, in a way it may be, but in the end most of what we see is a result of pushing the right switches and in this regards tangeritin appears to be outstandingly good - for a supplement to say the least; that you don't need exercise in a pill if you hit the gym three to five times a week and lead an active life is something I don't have to tell you anyway, right?
        Figure 3: Unlike thiazolidinedione like Rosiglitazone and "harmless" health supplements as fish oil (Neschen. 2006) tangeritin does not work its antihyperlipidemic (=triglyceride lowering) and anti-hyperglycemic (=blood sugar lowering) effects effects by inducing PPAR-gamma and thus allowing your body to stash away even more energy as body fat. On the contrary, reduces ppar-gamma expression and consequently stops the expansion of adipose tissue even in the presence of a hypercaloric high fat diet (cf. figure 1, tissue samples) - the beneficial effects of PPAR-gamma blockade have only recently been investigated by Lohdi et al. who call it an "off switch" for diet induced obesity (Lohdi. 2012).
        Implications: Now, we are certainly not dealing with the "supplemental reinvention of the wheel here", and still: The effect size in the Tan200 group was so pronounced that I felt that the news on tangeritin, which had originally been part of last weeks "On Short Notice" deserved it's own post - not the least, because  it will not have you pay dearly for the improved glucose tolerance and lower blood lipid levels as thiazolidinediones like Rosiglitazone and even fish oil, both of which have been shown to reduce serum glucose and triglyceride levels via PAR-gamma dependent mechanisms (figure 3; specifically for fish oil Neschen. 2006) and thusly promote not block fat loss. Tangeritin, on the other hand decreases the PPAR-gamma activity and therefore acts as an "off-switch" for dietary induced obesity (Lohdi. 2012) .

        Moreover, the reduced obesity was not a mere side effect of a loss of appetite and subsequent anorexia. The animals in the HFD and the HFD + Tan200 group consumed the exact same amount of chow - with the one small but absolutely critical difference that the rodents in the Tan200 group did not store the superfluous energy as body fat. It is this "anti-fat" effect which is not borne by negative health effect as it is the case for conjugated linoleic acid (CLA), for example (cf. "CLA Destroys Body Fat") which makes tangeretin a very interesting candidate for a weight loss supplement for both obese and lean dieters and, when I come to think about it, probably even for people who want to bulk.

        There are however a few potential downsides and questions that remain to be answered before we celebrate the advent of yet another "next big thing" that will then line up with the rest of the supplemental non-starters:
        • First of all, the mechanism of action does remind me of alpha lipoic acid (ALA), which is still a very good supplement for obese or at least insulin resistant dieters, but turned out to be useless, even potentially counterproductive in exactly those lean selectively (muscle) insulin sensitive athletes it is currently heavily marketed to as "repartitioning agent" (see "Lean and Muscular With Alpha Lipoic Acid?"). So the question is: "Is tangeritin only another ALA?" Is it better or worse and will it work fr lean people as well as it did for the mice on the obesogenic diet in the study at hand?
        • Secondly, despite the fact that tangeritin acts in an almost metformin-esque fashion via AMPK and PGC-1alpha, which is much more likely to work in humans as well than your usual beta-3 agonist (e.g. synephrine) or other thermogenic with promising rodent data and absolute no effects in human beings, we still need controlled human trials to see whether or not this nquestionably promising flavenoid does work in humans at all.
        • And thirdly, in view of the fact that only the high dose tangeritin (100mMol) elicited a pronounced increase in glucose uptake in the in-vitro study (cf. figure 1), it will be of utmost importance that future supplements or pharmacological agents are appropriately dosed - and we all know that this is in 90% of the cases where the raw material is more expensive than caffeine anhydrous simply not the case. 
        That said, I would venture the guess that (assuming one of the smaller supplement companies finds a bulk supplier in China) we are going to see "Tange(R)iburn" or a tangerine based substrate repartitioning agent (after all those sell pretty well, too) in the near future - before anyone has a clue what dosages will be necessary to see beneficial effects and probably with way less than the 1g+ of tangeritin in it than Kim et al.'s results would suggest as a minimal daily dose for an adult to see similarly outstanding results as our hairy friends in the study at hand.

        References
        • Cheng Z, Surichan S, Ruparelia K, Arroo R, Boarder MR. Tangeretin and its metabolite 4'-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K. Br J Pharmacol. 2011 Apr;162(8):1781-91.
        • Choi SY, Ko HC, Ko SY, Hwang JH. Correlation between flavonoid content and the NO production inhibitory activity of peel extracts from various citrus fruits. Biol. Pharm. Bull. Choi, S.Y., Ko, H.C., Ko, S.Y., Hwang, J.H., 2007. Correlation between flavonoid content and the NO production inhibitory activity of peel extracts from various citrus fruits. Biol. Pharm. Bull. 30, 772–778.; 30, 772–778. 
        • Lodhi IJ, Yin L, Jensen-Urstad AP, Funai K, Coleman T, Baird JH, El Ramahi MK, Razani B, Song H, Fu-Hsu F, Turk J, Semenkovich CF. Inhibiting Adipose Tissue Lipogenesis Reprograms Thermogenesis and PPARγ Activation to Decrease Diet-Induced Obesity. Cell Metab. 2012 Aug 1.
        • Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006 Apr;55(4):924-8. 
        • Kim MS, Hur HJ, Kwon DY, Hwang JT. Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice. Mol Cell Endocrinol. 2012 Jul 6;358(1):127-34. 
        • Takano K, Tabata Y, Kitao Y, Murakami R, Suzuki H, Yamada M, Iinuma M, Yoneda Y, Ogawa S, Hori O. Methoxyflavones protect cells against endoplasmic reticulum stress and neurotoxin. Am J Physiol Cell Physiol. 2007 Jan;292(1):C353-61.
        • Xu HG, Chen CJ, Liu DH, Minerals, phenolic compounds, and antioxidant capacity of citrus peel extract by hot water. J. Food Sci. 2008; 73, C11–C18. 
        • Yoon JH, Lim TG, Lee KM. Tangeretin reduces ultraviolet B (UVB)-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking mitogen-activated protein kinase (MAPK) activation and reactive oxygen species (ROS) generation. J. Agric. Food Chem. 2011; 59, 222–228