Overtraining Research: New Insights into Athlete Triad. Plus: Depression, Palpitations, Urination, Injuries and Weight & Performance Plateaus, the Many Faces of Overtraining

Chronic overtraining is one of the main contributers to the occurrence of often likewise chronic injuries, which persist even, when you finally realized that your own ambition is about to ruin your health.

It's the last day of the SuppVersity Exercise Science Week with a topic of which you actually have read as an aside, or "read up on" note in the previous installments, already: Overtraining and the infamous athlete's triad (read the whole SuppVersity Special here). Since I know that especially the male SuppVersity readers tend to believe they were bullet, or rather overtraining proof by nature, I decided to add a more general follow up to the results of a tightly controlled rodent experiment from the Graduate School of Sport Sciences at the Waseda University and the National Institute of Health and Nutrition University in Japan (Yanaka. 2013), which provide insights into the etiology of the (female) athlete triad phenomenon. A follow up with a potpourrie of studies pertaining to hard to diagnose pathology that goes by the name "overtraining" and is something I guess every training has experienced at least once in his or her career.

The female athlete triad - female only by definition

While Kaoru Yanaka, Mitsuru Higuchi and Yoshiko Ishimi follow the current scientific paradigm and discuss the problem in a female specific context, I want to remind everyone that the athlete triad, which is defined as the triad of eating disorders, amenorrhea, and osteoporosis is in fact female specific (at least I have not yet seen a guy with amenorrhea), but will - in a very different, much more subtle form featuring orthorexic eating patterns, loss of libido and general fatigue - also occur in men.

Figure 1: Time effect of restricted feeding on body weight, food intake and voluntary wheel running in sedentary + ad libitum diet (full filled rhombus; obviously not present in the running distance graph), vol. exercising + ad libitum diet (filled circles) and dietary restricet + ad libitum exercised rats (Yanaka. 2013)

As the data in figure 1 goes to show you, the ergolytic effect on endurance exercise performance was very short-lived and compensated for, when the body weight levels reached a new steady state (see figure 1, left). In other words, once you're caught in the spiral, you will probably not even notice this due to further weight loss and/or noticeable performance declines - specifically if you are not strength training or put an (over-)emphasis on volume training.

Weakening bones and infertility in the presence of (in parts) normal hormonal status

What's even nastier and actually different to human studies, where the "voluntary" exercise is actually compulsive and thus probably way more demanding, is the fact that even some of the hormonal you would expect to be good indicators of the athlete triad, namely estrogen (E2 and osteocalcin (OC), don't differ between the ad libitum and the restricted feeding group.

Figure 2: Levels of estrogen (E2), the bonebuilding protein osteocalcin (OC) and luteinizing hormone (LH) in the sendentary (SED) and voluntary wheel running ad-libitum (RC) and restrictedly fed (RR) rodents (Yanaka. 2013)

That being said, LH remains as the sole, reliable marker of the athlete's triad in response to insufficient food intakes. Whether it is similarly sensitive to overtraining and how the interaction between these two aspects of the athlete triad actually are (beyond increased energy needs in response to exercise) would yet have required a different study protocol, which the rodents being dumped into a container full of water to have them swim to exhaustion on a daily basis. What? That's animal abuse? True. It is however the perfect model for what I see people do at the gym day in and out - the same people who will then tell me that they cannot get rid of their belly fat, although they are "on a calorie deficit, avoid carbs like a plague, eat 100% clean and never miss a workout". My reply in these cases usually is: "You see, and that's why!"

A couple of additional findings on overtraining

Since I know that many of you will simply ignore the above post, because they feel that it does not affect them (don't tell me that's not you, guys ;-), I will summarize a handful of significant findings from general studies revolving around "overtraining" in general.

Table 1: Symptoms of overtraining (Fry. 1992)

• 10 days of 2x daily HIIT induce fatigue and compromise immune system for longer than 5 days (Fry. 1994) -- The five well-trained men (mean(s.d.) age 31.6(3.5) years; members of the Special Air Services Regiment of the Australian Army) who performed 15x 1 min HIIT protocols (2min rest between sprints) and 10 "sets " of the same protocol in the PM for ten days were unable to fully recover from this intermediate overexertion within the following 5 days of active recover.
  
  And while the overall mood disturbance index was remained only nonsignificantly 15% elevtet (p > 0.05), the soldiers felt still 7x more confused, 5x more depressed, 6x more angry.
  
  The exercise performance, on the other hand was restored to normal levels and that despite persistent immune system deficits. This is in line with the findings of the above rodent studies, where the volume of voluntary wheel running was not a reliable criterion to identify overtraining / undereating. So you better be careful about the "well, I did my 10 squats with 250lbs as usual"-mentality that lulls us into the believe that we are fully recovered and just did not sleep long enough and therefore feel fatigued.

• 

  It's not in table 1, but not just in the case report by Uusitalo et al. from 2004, frequent urination (especially nightly) is one of the classic features of severe overtraining.

  Overtraining induced depressive mood state is not related to depressed 5-HT reuptake, but tinnitus, palpitations & frequent urination are additional symptoms of OT (Uusital. 2004 & 2006) -- Contrary to what you could assume the OT induced depressive mood states are not mediated by decreased serotonin reuptake, which means that they will be resistant to the standard treatment with serotonin-reuptake inhibitors (SSRIs). With this study the scientists did by the way refute a hypothesis they themselves had proposed in a study 2 years earlies, where single-photon emission computed tomography (SPECT) of a single patient had suggested that it was a decreased 5-HT uptake that was behind the major depression he had in addition to continuous fatigue, tinnitus in his left ear, disturbing palpitation and pollacisuria (frequent urination) he had developed after upping his training volume by 100% (Uusitalo. 2004)

• High intensity + low rest times = increased risk of overtraining (Szivak. 2013) -- In Szivak et al.'s 2013 study, the 18 trained men (age: 23.5±3.5 years, height: 172.4±4.0cm, weight: 77.8±8.8kg) and women  (age: 22.9±2.0 years, height: 168.4±9.4cm, weight: 68.5±10.4kg) completed high intensity short rest protocol (HI/SR) participated consisting of a descending pyramid scheme (from 10 down to 1 rep) of back squats, bench presses, and deadlifts. The ensuing increases in lactate (IP men: 17.3 mmol·L, IP women: 13.8 mmol·L) and cortisol (+15 men: 1860.2 nmol·L; +15 women: 1831.7 nmol·L) were considerably greater than those produced in typical resistance exercise programs. The scientist interpret this absorvation as indicative of the fact that coaches should implement HI/SR protocols only sporadically, and prefer a gradual reduction in rest interval length with concurrent gradual increase in intensity to minimize potential negative effects such as non-functional overreaching.

• 

  The self-perpetuation viscous cycle of upping your efforts, decreasing your returns and reupping your efforts again is actually the real danger - and I don't care if you call it overtraining or athlete triad + suggest you don' either (learn more)

  Mental exhaustion and vigorous-intensity training are significant correlates of the occurrence of injuries (Vetter. 2010) -- While mental exhaustion during and outside of the competitive season is a risk for chronic injuries in women, in men, only intra-seasonal mental exhaustion correlates with acute injuries, the occurrence of which is likewise increased with the number of vigorous-intensity training days per week, which in turn is a reliable predictor of mental fatigue in the off and on-season. You see, we are going round in circles once more.

• Hitting it hard to frequently will downregulate the beta-2 adrenergic receptor (Fry. 2006) -- If you are fatiqued and stims have long seized working for you, you are likely to be chronically overtraining. That's the practical implication of a 2006 study by Fry et al. who found that subjects who performed 10 x 1 at 100% 1 RM daily for 2 weeks on a squat simulating machine, ended up suffering from a -8kg decrease in their 1-RM max, as well as a -36.3% decrease in mean power at 100% 1-RM loads. While this was to be expected and not actually new, the -37% reduced muscle beta(2)-adrenergic receptor density and 49% increases in nocturnal urinary epinephrine in the overtraining group suggest a
  

  "decreased beta(2)-AR sensitivity for the OT group (2.4-fold increase) [suggesting] that this may be an important contributor to performance decrements due to excessive use of maximal resistance exercise." (Fry. 2006)

  That this will likewise compromise your efforts to lose weight and blunt many of the beneficial fat loss effects you may have in mind, when thinking about brief, hard and frequent training, is not mentioned in the paper and should yet be as obvious as the cardio-protective effect of this adaptations. After all, the beta-adrenergic receptors, which are targeted by endogenous catecholamines and stimulated either directly or indirectly by many stims (most prominently clenbuterol and ephedrine) are responsible for the activation of the sympathetic nervous system, which mobilize the body's nervous system fight-or-flight response, increase the heart rate, widens the pupils, kicks the fat out of the adipocytes to have it available as additional fuel etc.

That's not the breakfast of a champion, that's the breakfast of a complete moron and if that's even remotely to what your breakfast looks like, it's high time to learn about the 3 Simple Rules of Sensible Supplementation

I guess you would like to have some supplement recommendations now, but I won't give you any - aside from the advise to abstain from cortisol blockers and the abuse of stimulants, which are only going to deepen the whole you have been digging (on a related note: I suggest you check out the recent facebook post on the -80% risk reduction for obesity in women with high morning cortisol; Manesh. 2013).

Adequate rest and nutrition cannot be compensated for by any supplements and if you allow yourself both, you won't be overtraining in the first place.

Once you have established that baseline, you are obviously free to use the Three Simple Rules of Sensible Supplementation to optimize your results.

References:

• Fry RW, Morton AR, Garcia-Webb P. Craford GPM, Keast D. Biological responses to overload training in endurance sports. Eur J Appi Physiol 1992; 64: 335-44.
• Fry RW, Grove JR, Morton AR, Zeroni PM, Gaudieri S, Keast D. Psychological and immunological correlates of acute overtraining. Br J Sports Med. 1994 Dec;28(4):241-6.
• Fry AC, Schilling BK, Weiss LW, Chiu LZ. beta2-Adrenergic receptor downregulation and performance decrements during high-intensity resistance exercise overtraining. J Appl Physiol. 2006 Dec;101(6):1664-72.
• Uusitalo AL, Valkonen-Korhonen M, Helenius P, Vanninen E, Bergström KA, Kuikka JT. Abnormal serotonin reuptake in an overtrained, insomnic and depressed team athlete. Int J Sports Med. 2004 Feb;25(2):150-3.
• Szivak TK, Hooper DR, Kupchak BK, Apicella JM, Saenz C, Maresh CM, Denegar CR, Kraemer WJ. Adrenal Cortical Responses to High Intensity, Short Rest, Resistance Exercise in Men and Women. J Strength Cond Res. 2013 May 3.
• Uusitalo AL, Vanninen E, Valkonen-Korhonen M, Kuikka JT. Brain serotonin reuptake did not change during one year in overtrained athletes. Int J Sports Med. 2006 Sep;27(9):702-8.
• Vetter RE, Symonds ML. Correlations between injury, training intensity, and physical and mental exhaustion among college athletes. J Strength Cond Res. 2010 Mar;24(3):587-96. 
• Sedaghat F, Rabiei S, Rastmanesh R. Bassak Nejad S, Poloi Shahpor Abadi F, Davoudi I. The Relationship between Serum Cortisol and Vitamin C Levels with Obesity. Jundishapur Sci Med J. 2013;11(4):341-353 
• Yanaka K, Higuchi M, Ishimi Y. Effect of long-term voluntary exercise and energy restriction on bone mineral density in mature female rats. J Phys Fitness Sports Med . 2013; 1(4): 695-702.

A Double Dose of HIIT vs. Aerobics. Hazelnuts, Mushrooms, Strawberries = Polyphenol Laden Superfoods With Prebiotic, Anti-Cancer & Anti-Diabesity Effects. Plus: Backdoor to DHT

Actually the first post in today's installment of On Short Notice is a direct continuation of the SuppVersity Exercise Science Week with an intriguing novel contribution to the never-ending steady state vs. HIIT debate by scientists from the University of Birmingham (UK)

Hypothyroidism kills and therefore the SuppVersity Figure of the Week comes from a study on the effect of hypothyroidism on all-cause mortality from Denmark (Thvilum. 2013). The respective data comes from an observational cohort study and spans the years between January 1, 1978 and December 31, 2008. With an increased risk of  +52% (after stratification for the figure dropped to "only" +21%)  in the 3587 singletons, +61% in dizygotic twin pairs, but only +7% in monogyzotic twins, it's yet not quite clear, whether it's the being hypothyroid or rather having the disposition of developing respective problems is actually associated with an increased mortality. After all, you would expect similarly high levels in monogyzotic twins as in the rest of the population, if it was "only" about having a high TSH, which still is the only "official" accepted marker of clinical hypothyroidism.

Day 4 of the Exercise Science Week - A Double Dose of HIIT vs. Steady State Aerobics

(Cocks. 2013 & Shephard. 2013) -- If you ignored the titles and just read the first part of the methodological section it seems as if the two studies that were subsequently published in The Journal of Physiology late in 2013 were identical. What's identical, though is just the data set the two papers by scientists from the University of Birmingham are based on. The latter was acquired during a six-week experiment in the course of which 16 previously sedentary young men (BMI ~23kg/m²; age 21.5y) were randomized to a

• 

  34% increase in time to exhaustion, +91% increase in total work & exponentiated lean mass gains in response to HIIT + NAHCO3 (read more)

  classic steady state endurance training regimen - subjects cycled at workloads equivalent to ∼65% of their pre-established VO2peak for 40min in the first 2weeks, increasing to50min in the following 2 weeks, and 60min in the final 2 weeks; their obviously improved VO2peak was reassessed after 3weeks of training and workload adjusted accordingly

• sprint interval training  - subjects performed 30s "all out" (Wingate test) on a cycle ergometer using a load equivalent to 0.075kg per kg of body weight; each of the Wingate tests was followed by a period of 4.5 min of recoery (at 30W; <50rpm); the number of sprints increased from 4 to 6 sprints with one additional sprint every 2 weeks

As the scientists point out, all participants trained three (SIT) respectively five (ET) times a week for 6 weeks, and were excluded from the study if they were absent from more than two (SIT), respectively three (ET) sessions.

Figure 1: Overview of the relative changes of selected outcome variables measured in the "two" studies
(Cocks. 2013; Shephard. 2013)

While Cocks et al. analyzed the microvascular density and eNOS content of the muscles, the Shephard study, which was published a couple of weeks later, took a closer look at markers of intramuscular triglyceride breakdown and the expression of the anti-lipolytic lipid droplet-associated proteins perilipin 2 and 5. In previous studies, the researchers had observed that these proteins which are believed to protect the lipid droplets in adipose tissue from the "fat dissolving" lipase enzymes, appear to have a very different effect in the musculature, where PLIN2 and especially PLIN5 seem to act as key regulators of intra-muscular lipolysis and triglyceride breakdown (Shephard. 2013).

More similarities than differences?!

Figure 2: Selected parameters of body composition and blood glucose metabolism expressed relative to pre-exercise levels. (Shephard. 2013)

If we take a look at the outcomes of the studies (see figure 1, figure 2), it's not difficult to see that despite minor differences, most of the measured parameters in the Shephard study the observed differences, such as an increase of 7% in VO2Peak in the SIT vs. 15% in the ET group did not reach statistical significance. The same is true for the effect on the mitochondrial density, the insulin sensitivity, the maximal power WMax and the changes in body composition (see figure 2). Only the respiratory exchange ratio (RER), i.e. the ratio of carbohydrates to fats that were used during a 60-min endurance regimen at 65% of the VO2Peak, changed only in response to endurance training.

Despite this difference, the usage of intramuscular triglycerides (IMTGs) during exercise was increased after both trials:

"In comparison to pre-training, net IMTG break- down in type I fibres was significantly greater following training (training×time interaction; P<0.05), with no difference in net IMTG breakdown between groups. Both pre- and post-training, the reduction in IMTG content in type I fibres was attributed to decreases in IMTG density after SIT (pre-training, 21±13%; post-training, 38±7%) and ET (pre-training, 20±17%; post-training, 32±8%)." (Shephard. 2013)

The greater increase in IMTG response to exercise in the SIT (HIIT) group appears to be in line with the previously mentioned role of perilipin 5 (PLIN5) as a driving force of intracellular muscle triglyceride mobilization. After all, the PLIN5 expression of the interval training group increased to a significantly greater degree than the one of the endurance training group. A subsequent correlation analysis confirmed strong associations of PLIN2 und PLIN5 with IMTG breakdown and modest associations with muscular insulin sensitivity.

Para- vs. sympathetic overtraining: I would venture the guess that most of you will think of performance decrements, fatigue, depression, increased sleeping needs, constant weight or even fat gain, and lowered heart rate, i.e. the characteristic symptoms of parasympathetic (=addisonoid) overtraining, whenever they hear or read the term "overtraining". Its evil sympathetic twin, which is also known as basedowoid overtraining (named after morbus basedow) and likewise associated with performance decrements and fatigue yet in combination with an almost stimulant like restlessness, disturbed sleeping patterns, weight loss, and accelerated heart rate, is yet way less know. So, if you wake up in the middle of the night sweating like a pig and with a heart rate similar to the one you had during your last HIIT session, you better cut back on the weight lifting and HIIT side of your regimen - w/out necessary increasing the aerobics, though.

Bottom line: If you combine these mechanistic insights, with the main outcomes of the Cocks paper, which found ET and SIT "equally effective at decreasing arterial stiffness and increasing skeletal muscle capillarisation and eNOS content", even HIIT (or SIT, as it's called here) haters will be hard pressed to argue with Shephard et al.'s conclusion that..

"[d]espite the large differences in duration and energy expenditure between SIT and ET, we provide novel evidence indicating that SIT induces similar improvements [in almost all measured parameters and] provides a time-efficient exercise alternative to achieve improvements in aerobic fitness and insulin sensitivity." (Shephard. 2013)

So, now it's up to you 3x per week HIIT or 5x per week SIT? The answer appears to be clear, however, for people who are also strength training on a higher volume / density regimen, the addition of only 2-3 low(er) intensity aerobic sessions may still be the "safer" alternative in order not to overtax the sympathetic nervous system and keep a balance between sympathetic and parasympathetic activation in your routine.

More, really short news

Put introduction here

• Hazelnuts: A polyphenolic "superfood" that's prebiotic by nature (Montella. 2013) -- The skin of hazelnuts has only recently been identified as "one of the richest edible sources of polyphenolic compounds" - a polyphenol source that can compete with green tea and coffee, by the way (Clani. 2013).
  
  

  

  Hazelnut peel is laden with gut friendly prebiotics & antioxidant plyphenols

  In a paper that's soon going to be published in Food Chemistry researchers from the Italy and the United States report that the skin does also contain a whole host of potent pre-biotics:

  "Over thirty complex free oligosaccharides, composed mainly of galacturonic acid and N-acetylgalactosamine, were characterized for the first time in the present study. Their concentration ranged between 16 mg and 34 mg per g of extract." (Montella. 2013)

  And if you find that unfair, because you are allergic, you may be interested in a 2005 paper by Enrique et al. who found that their sublingual immunotherapy for hazelnut food allergy worked quite well in a first randomized, double-blind, placebo-controlled study with a standardized hazelnut extract (Enrique. 2005)

• 

  Inonotus obliquus (chaga mushroom) does actually looks like a tumor, but contains compounds that have the ability to kill prostate and breast cancer cells (photo by Tomas Čekanavičius)

  "Eat your mushrooms!" mothers are probably saying that not often enough (Kalogeropoulus. 2013; Ma. 2013) -- According to a recent study by Nick Kalogeropoulus et al. all five five wild edible mushrooms species (Lactarius deliciosus, Lactarius sanguifluus, Lactarius semisanguifluus, Russula delica, Suillus bellinii) from Lesvos Island, the researchers recently analyzed in their laboratory contained significant amounts of polyphenols, with the more abundant ones being p-OH-benzoic acid, p-OH-phenylacetic acid, o-coumaric acid, ferulic acid and chrysin. Moroever, the Greek scientists were also able to isolate the riterpenic acids oleanolic and ursolic acid (yeah, that stuff that's currently sold as test booster).
  
  If you add to that the not even published results of Ma, Chen, Dong and Lu, who fount that the ergosterol, ergosterol peroxide and trametenolic acid in Inonotus obliquus (chaga mushroom), another mushroom that has been used in TCM for centuries, do not only have potent anti-oxidant activity, but can also kill human prostate and breast cancer cells, the initially raised question, why your mother never told you to "eat your mushrooms" suddenly appears in a very different light, doesn't it?

• Did you know that the aggregate-accessory fruit (with the green dots on its flesh being its "nuts") has the highest total antioxidant capacity, when it's still green (see facebook news), can contain up to 160mg/g of fisetin (Kimira. 1998) and that the latter has been shown to reduce thyroid peroxidase activity (Divi. 1996) and thus to protect against thyroid cancer? Fisetin is also supposed to have anti-allergic and anti-angiogenic (pro - cardiovascular health) effects.
  Strawberry polyphenol fisetin ameliorates hepatic steatosis and lowers circulating glucose concentrations (Cho. 2013) -- While it's still a couple of days until the Strawberry season will begin it's still good to know in time that the fisetin content in strawberries can ameliorate hepatic steatosis and decrease blood glucose levels by increasing GLUT-4 (glucose transporter 4) expression in a rodent model of diet induced obesity.
  
  Unfortunately, the changes the Korean scientists observed in response to a human equivalent dose of 130mg/day was statistically significant yet not uniquely impressive and "thanks" to the increase in PPAR-gamma and the non-selective increase in GLUT-4 receptor expression (measured only on adipocytes), the rodents in the supplemented group got exactly as obese as their unsupplemented pears. Nevertheless, better "weighty" and healthy than skinny fat and sick, right? 

• Scientists find alternative androgen pathway - DHT synthesis from progestorone more effective than from testosterone (Kamrath. 2013) -- Usually it's my friend Carl Lanore who says that he, respectively Super Human Radio has the smartest listeners. I would hovewer argue that listening is easier than reading the stuff I produce (including sentences that are longer than the paragraphs of most other bloggers) and therefore it's no wonder that SuppVersity readers must be at least as smart ;-)
  
  

  

  The alternative pathway to androgen (DHT) synthesis as proposed by Kamrath et al.

  That being said, I just received a facebook message from Rob, who pointed me towards a very recent paper claiming that there was an "alternative androgen synthesis pathway" in human beings. "Alternative pathway?" Sounds like the adrenal gland and the DHEA => Testosterone => DHT pathway, right? That's what I thought, as well, but actually this one is different. As the pediatric scientists from the JLU Gießen (Germany) point out in their review of the literature, there is a hitherto largely overlooked "backdoor" by the means of which 17α-hydroxyprogesteron instead of it's 12,30 lyase product androstendione is 5α-reduced to 17α-hydroxy-dihydroprogesteron, which is then, in a 4-step process converted to 17α-hydroxyallopregnanolon (2α-HSD), Androsteron (12,20-Lyase), androstandiol (17b-HSD) and finally DHT (3α-HSD).

  "This so-called "backdoor" synthesis pathway appears to play an important role especially during the development of male fetuses, since respective defects will result in a suppressed virilization in boys." (Kamrath. 2013)

  Another context that's probably more important for most of you is the role of the "backdoor" in castrate (and probably also androgen suppression) resistant prostate cancer, where this alternative pathway jumps in, when the regulate substrate for DHT synthesis by a mere change in the specific 5α-reductase subtypes.

Now don't tell me you still haven't had enough for today? I mean, with the long article on the sprint vs. endurance study you've just gotten day 4 of the SuppVersity Exercise Science Week, and with the other short notice items, even those of you who have been missing nutrition and other news within the past couple of days should have gotten way more than your money's worth - after all, the SuppVersity is still free!

Since the same also goes for the facebook news, I'd suggest you head over to the SuppVersity Facebook Wall, where you will find roughly half a dozen of additional short news items every day. Examples? This is a selection of what you could already have known if you were already a friend, fan or whatever you call that on facebook, when you click on the "like button" at www.facebook.com/SuppVersity:

Just out: Part II of my interview with Sean Casey. This time about the A-Z of supplements for strength, endurance and all other trainees who want to boost their health and performance (read more)

• Skin protection from within - Orally ingested green tea or rather respective catechin metabolites end up in your skin and protects it from UV radiation (read more)
• Iron deficiency starts in the gut - Epidemiological findings confirm: Even people with mild gastrointestinal inflammatory bowel disease need more iron and co-factors in their diet to prevent deficiency than healthy individuals (read more)
• Hormonal contraception increases risk of HIV infection - Medroxyprogesterone acetate (MPA) suppresses both innate and adaptive arms of the immune system resulting in a reduction of host resistance to invading pathogens (read more)
• Grape seed and peel extracts stop working, when they are "purified" - Another case where man shalt not isolate what nature put together, if he wants to have the active ingredients survive the digestive process (read more)

And when you are done with those and i have not yet posted another handful of news, head over to Part II of my interview on CasePerfomance.com. Afterwards, you hit the power button switch off this damn machine and have a nice weekend with family and/or friends. 

References:

• Calani L, Dall'Asta M, Derlindati E, Scazzina F, Bruni R, Del Rio D. Colonic metabolism of polyphenols from coffee, green tea, and hazelnut skins. J Clin Gastroenterol. 2013 Oct;46 Suppl:S95-9.
• Cocks M, Shaw CS, Shepherd SO, Fisher J, Ranasinghe AM, Barker TA, Tipton KD, Wagenmakers AJ. High intensity interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males. J Physiol. 2013 Sep 3.
• Divi RL, Doerge DR. Inhibition of thyroid peroxidase by dietary flavonoids. Chem Res Toxicol. 1996 Jan-Feb;9(1):16-23.
• Enrique E, Pineda F, Malek T, Bartra J, Basagaña M, Tella R, Castelló JV, Alonso R, de Mateo JA, Cerdá-Trias T, San Miguel-Moncín Mdel M, Monzón S, García M, Palacios R, Cisteró-Bahíma A. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005 Nov;116(5):1073-9.
• Kalogeropoulos N, Yanni AE, Koutrotsios G, Aloupi M. Bioactive microconstituents and antioxidant properties of wild edible mushrooms from the island of Lesvos, Greece. Food Chem Toxicol. 2013 Jan 24. 
• Kamrath C, Hartmann MF, Wudy S. The alternative androgen synthesis pathway in humans. Klin Padiatr. 2013 Jan;225(1):3-7. [Article in German]
• Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese Intake of flavonoids and isoflavonoids from foods Journal of Epidemiology. 1998; 8:168–175.
• Ma L, Chen H, Dong P, Lu X. Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus Food Chemistry. Feb 2013 [in press]
• Montella R, Coïsson JD, Travaglia F, Locatelli M, Bordiga M, Meyrand M, Barile D, Arlorio M.dentification and Characterization of Water and Alkali Soluble Oligosaccharides from Hazelnut Skin (Corylus avellana L.) Food Chemistry. Feb 2013 [in press]
• Shepherd SO, Cocks M, Tipton KD, Ranasinghe AM, Barker TA, Burniston JG, Wagenmakers AJ, Shaw CS. Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5. J Physiol. 2013 Dec 17.
• Thvilum M, Brandt F, Almind D, Christensen K, Hegedüs L, Brix TH. Excess Mortality in Patients Diagnosed With Hypothyroidism: A Nationwide Cohort Study of Singletons and Twins. J Clin Endocrinol Metab. 2013 Jan 30.

Fasted Cardio & Beyond - Optimal 24h Fatty Oxidation: How It Works, Why It Works & Why It Still May Not Be Worth It

Photo of a typical disciple of the cult of the "fat burning zone".

Day 3 of the SuppVersity Exercise Science Week and for some of you maybe about time to have breakfast... hold on, breakfast? But shouldn't you work out before breakfast? I mean this whole cardio in the morning business you have taken up lately is all about doing it before, not after breakfast isn't it? You grab your WIFI-connected iPhone tune in to the Super Human Radio morning cardio mash-up and hop onto your cycle ergometer, treadmill, rowing machine, elliptical, spinning bike, stepper, or whatever else you may be using  - no breakfast no intra-workout supplement - at least no carbs, right? Ah, and of course you are going to work out at the highest intensity possible, to burn more fat later on, after all, you are no disciple of the cult of the "fat burning zone", right? Right! And still you have your doubts, hah?

Now, I can't tell you whether the above has anything to do with your morning routine. What I can tell you, however, are the long and short on 24h energy expenditure by summarizing and expanding on some of the main findings of a recent paper by Kaito Iwayama and Kumpei Tokuyama, two young scientists from the Graduate School of Comprehensive Human Science at the University of Tsukuba (Iwayama. 2013). 

Let's start with the "short", then

I guess you will be familiar with the term "metabolic chamber". That's a small room, where you, as a scientists, lock your subjects up in order to monitor their energy metabolism with your fancy electronic equipment and analytical methods for a prolonged period of time (usually 24h). As Iwayama and Tokuyama point out in their latest paper this technique has long been and in fact still is considered the gold standard as far as 24h energy expenditure measurements are concerned.

"During the last 10 years, experiments with this method have raised interesting observations such as: 1) exercise intensity has no effect on 24 h fat oxidation, 2) exercise has little, if any, effect on 24 h fat oxidation, and 3) exercise before breakfast increases 24 h fat oxidation."

Just in case you are one of those guys / gals who don't read quotations, we are going to spend the major part of today's contribution to the SuppVersity Exercise Science Week recapping what "the short" is telling us about your morning, afternoon and/or evening efforts to lose body fat and extend it into "the long" by adding references an examples, so don't worry.

I. Exercise intensity has no effect on 24 h fat oxidation

If you really want to maximize fatty acid oxidation while do a HIIT session before  a lengthy steady state aerobics.You should be aware though, that we are talking about relative increases, here (read more)

We all know that the amount of energy your body consumes during physical activity will depend on the "workload", which is defined as the mathematical product of force x way. In that, the force during a lift would be gravity g x mass of your weight. For a 10kg weight, this would yield a force of 100N[ewton], let's say you lift that weight from the ground into a hight of 1m. In that case, the workload you applied would equal 100N x 1m = 100Nm. If you move a larger weight, say 20kg, for example you would have done twice as much work... it's as easy as that, but unfortunately pretty useless when it is applied to the human human body. While it may still make sense to compare "work-matched" workouts with each other, the outcome in terms of the energetic demands a "10,000Nm bodybuilding workout" will produce, is very different from that of a "10,000Nm O-lifting workout", let alone a "10,000Nm marathon run". The relation between work and energy physicists often try to explain by stating that "(mechanical) energy is a measure of the ability to do work" is too simplistic to work (all puns intended) out in exercise physiology.

If we had a phyiscal model that described what happens in your body down to the level of the individual cell, things would be different. Currently, however, we are missing 99% of that model, so that we have to find other ways to measure the exercise induced and basal energy expenditure - and this is where the metabolic chamber comes in. It allows scientists to measure the energy expenditure independent of any workload calculations and does even allow for a quantitative estimation of where that energy is coming from, namely from fats or carbohydrates (and glyconeogensis). From previous studies, which availed themselves of this amazing piece of equipment, we know already that

• for low-intensity exercise, below 40-50% of the VO2Max the energy supplied is primarily from oxidation of plasma free fatty acids
• for intensities ranging from 50% to 95% of the VO2Max, the ratio of glucose to fatty acid oxidation, the so called respiratory rate is constantly increasing; in that, a RER of 0.8 tells us that we are fuelling 80% of our energy demands from glucose, already 
• for intensities in the 100% of VO2max range, the RER approaches 1.0 meaning that our bodies satisfy almost 100% of their energetic demands by the oxidation of carbohydrates (glycogen => glucose)

This has, as we have already seen in yesterday's 2nd post in the SuppVersity Exercise Science Week, led to the commonly held belief that low-intensity exercise would be better than high-intensity exercise for increasing fat oxidation and, thus, fat loss (Hill. 1992).

The notion that what happens after your workout is about as, if not more important than the energy, let alone fatty acid expenditure during a workout has unfortunately not reached public awareness, as of yet.

That's a pitty, right? Well at least as far as the rate of fatty oxidation is concerned, I would not be too sure about that, as previous studies suggested that the amount of fat that's oxidized in the post-exercise recovery period following isocaloric exercise performed at high (65% VO2max for 1 h) or moderate intensity (45% VO2 max for 86-89 min) is identical!

"First, consistent with the literature, fat oxidation during exercise was less for high-intensity exercise than for low-intensity exercise. Second, the increase in fat oxidation during the post-exercise period seemed to be greater after high-intensity exercise, although the difference did not reach statistical significance. Third, the sum of fat oxidation during the exercise and post-exercise periods was not significantly different between the two exercise conditions of different intensity." (Iwayama. 2013)

Aside from these fundamental insights, the studies on which this rationale is based on did also provide another intriguing, yet somewhat discriminating insight:

• While women have the edge as far as intra-workout fatty acid oxidation is concerned, their ability to burn fat during rest is low compared to their male counterparts (Hanerson. 2007). According to Iwayama and Tokuyama, this biological fact may also explain why women are typically less successful in achieving their fat loss goals in response to exercise only interventions than men (Ballor. 1991; Donnelly. 2005).

Now think about this for just a second, take a look at the data in figure 1 and now tell me: "What's the best way for women to maximize fatty acid oxidation?"

Figure 1: Fatty acid oxidation in male and female subjects in the 24h period after low /40%VO2Max) and high (70% VO2Max) intensity workouts with a matched energy expenditure of 400kcal; the data was measured in a metabolic chamber by Melanson et al. ten years ago (Melanson. 2002)

Right! That's low intensity long duration workouts. Those will allow them to burn more fat (on a relative basis) during the workout without experiencing the bump in post-exercise fatty oxidation rates Melanson et al. observed in their 2002 study. And yet, neither I nor the researchers who wrote...

“Given that time is a limiting factor for most individuals, if the goal of exercise is to maximize fat oxidation to better regulate body fat mass, then exercise should be performed at the highest intensity that can be comfortably maintained.” (Melanson: 2002)

...would recommend that our female or male readers stick to "training in the zone", only. You will learn why this is the case later in the article. For the moment, I do yet want to address the second and third assertion from the initially cited three-item list, first.

II. Whether you exercise or not has no influence on 24h fatty acid expenditure

At first sight this sounds, bullocks. I mean, it should be out of question that you burn more fat, when you work out, than when you lie around on the couch, right? And in this case you are right - at least, if you include the additional fatty acid oxidation during the workout in your calculation and discard things like standard deviations and statistical non-significance.

Table 1: Independent effects of exercise intensity (low vs high intensity) and exercise itself (control vs exercise) on 24h fat oxidation have been assessed under energy-balanced study design (except for the Lausanne
study, in which subjects were in a state of negative energy balance); "no" denotes not significantly different (Iwayama. 2013)

And still, under "macronutrient-balanced condition[s"], which are a necessary prerequisite to measure the independent effect exercise has on 24-h fat oxidation without having a negative energy balance or the ingestion of some sugary intra-workout drinks skew the results towards higher, respectively lower rates of fatty acid oxidation (cf. Bielinski. 1985; Dionne. 1999).  Exactly this is what has been done in a series of metabolic chamber experiments, Iwayama and Tokuyama reference in their paper (see table 1) to support their assertion that

"fat oxidation on days with exercise doesn’t differ from sedentary control days when the energy balance is maintained." (Iwayama. 2013)

While the results are anonymous it's clear that they do not support the notion that working out would exert an independent effect on the amount of fatty acids that are "burnt" within the same 24h period the exercise bout was conducted in.

Still, as Iwayama and Tokuyama point out, "statistically not significant" does not equate non-existent. You just have to take another look at the data from the Melanson study in figure 1 to see that there is a definitive trend towards increased fatty acid oxidation in the exercise compared to the control condition.

The difference between significant findings and "unreliable" trends reminds me of a previously not mentioned, yet potentially significant disadvantage of an otherwise highly reliable method to measure the total energy expenditure of human beings: The restricted number of participants in studies using indirect calorimetry with a room-sized respiratory chamber. The "trend" in the Melanson study, for example could well have reached statistical significance with a greater number of study participants; and the same obviously goes for the rest of the studies in table 1, as well. Still, as we are going to see in the conclusion, an over-reliance on statistics is not the only reason why "not working out" is not an option. Before we tackle that, I do yet want to address the last point on our check-list.

Exercise before breakfast increases 24h fat oxidation
 
This third and last of the initially cited assertions does not only take us back to the "breakfast problem" from the introduction, it's also the only assertion that's in accordance with the mainstream understanding of the role of exercise in the process of fatty acid oxidation. "Working out on empty", "cardio in the morning" and so on and so forth - you know the whole spiel and actually you do also know the scientific explanation of why working out like this does actually work out. No idea? Well, I did provide part of the explanation in the previous paragraph, already, when I mentioned the potential impact of fasting and feasting on the experimental results.

Gluconeogenic as most of them may be, EAAs still increase GLUT-4 and thus glucose uptake by the muscle - a true yet overlooked nutrient partitioner, so to say (read more)

Did you know that the two essential L's, i.e. leucine and lysine are the only amino acids that cannot be used for glyconeogenesis by the liver? Contrary to the rest of the pack, they are exclusively ketogenic and can only be transformed into ketone bodies.

In view of the built-in glucose repartitioning effect of essential amino acids (EAA), this is yet no reason to be worried about... well, unless you are on a ketogenic diet and make the standard mistake of each and every fitness fanatic to turn a high fat diet into a high protein diet without carbohydrates, so that you end up living on the little glucose your liver is able to produce without ever getting even close to real ketosis.

I see it dawns on you: It's the sheer necessity of burning fat for fuel, in the absence of other, more readily available nutrients like carbs, or glucose the liver would generate from proteins or aminos, for example. So, in the course of your workout you are actually burning more fat than you would if you had breakfast before hopping onto the treadmill, bike or elliptical, but what about the time thereafter?

Figure 2: 24h energy expenditure and fatty acid oxidation (both in kcal/min) on days on which cardio (60min 50% VO2max light steady state) was done before (filled circles) or after (open circles); data based on an unpublished from the same group (Shimada. unpublished)

As the data in figure 2 tells you, there is no difference in the following hours and - what's even more important - the total energy expenditure was identical - 2594kcal/day vs. 2589kcal/day in the before and after breakfast trial, respectively. In addition to that, a detailed analysis of the unpublished study by Shimada et al. the above data was taken from, does also show that

• working out before breakfast reduces the energy expenditure in the time before lunch --  over the whole period the subjects burned about 500 kcal less, when exercise was performed before breakfast
• working out before breakfast burns more glycogen and increases non-oxidative carbohydrate storage during / after breakfast -- with the carbohydrate content of the breakfast being used for glycogen repletion, this does in fact lead to another increase in fatty acid oxidation, simply because the alternative fuel, namely the carbs are not oxidized, but stored

So, 2x thumbs up for cardio before breakfast - at least in the short run and when your goal is to maximize fatty acid oxidation, but ...

Is maximal fatty acid oxidation even what you should be aiming for during a workout?

I guess you will already have read between the previous lines that my answer to this question is a definitive "no". Moreover, most of you are so clever and have been following the SuppVersity posts for so long that they could come up with their own arguments against an overemphasis of intra-, post and total 24h fatty acid oxidation, when getting lean and healthy is your goal. And probably, some of them are even identical to mine:

• Firstly, and most importantly, burning fatty acids for fuel does not equate fat loss. If you follow a real ketogenic diet (not one with tons of protein in it), you'll burn (almost) exclusively fat, but even under these "extreme" conditions most of the fat will come from the fat you eat, while the small amount that's actually taken from your hips, buttocks and whatever, will be restored unless you are in a caloric deficit, when your fatty acid oxidation will increase anyways.

• 

  The "Fat Loss Support Routine" from the Step By Step to Your own Workout Routine guide would be one example of how you can structure your weekly workout regimen to cut body fat.

  Secondly, many of the metabolic benefits of exercise are closely related to the act of glycogen depletion. This is particularly true for the increase in GLUT-4 expression and consequent improvements in muscular glucose uptake, burning only fat for fuel during a workout is thus a questionable ideal.
• Thirdly, working out "in the zone" may burn the most fat but won't have the conditioning effects high(er) intensity workouts have. While obese individuals and people who have been sitting around their whole lives will see improvements in their VO2max (and in the long run their heart-health), anyone who is not totally unconditioned misses out on the structural changes in the musculature, and as you've learned on day one of the SuppVersity Exercise Science Week adipose tissue, as well.

In short, the importance of burning fat for fuel is so overrated that exercise prescriptions that are based on the paradigm of maximal fatty acid oxidation are at least suboptimal for health, fitness and physique purposes. Some people, I guess, would probably even go so far to say that they do more harm than good. I for my part leave it up do you to decide whether you join sides with my carefully worded or the more extreme version of this conclusion, or - and this would be your good right - to wholeheartedly disagree with both of them.

References:

• Ballor DL, RE Keesey. A meta-analysis of the factors affecting exercise-induced changes in body mass, fat mass and fat-free mass in males and females. Int J Obes. 191; 15: 717-726.
• Bielinski R, Schutz Y, Jéquier E. Energy metabolism during the postexercise recovery in man. Am J Clin Nutr. 1985;42: 69-82.
• Dionne I, Van Vugt S, Tremblay A. Postexercise macro-nutrient oxidation : a factor dependent on postexercise mac-ronutrient intake. Am J Clin Nutr69: 927-930.
• Donnelly JE, Smith BK. Is exercise effective for weight loss with ad libitum diet? Energy balance, compensation and gender differences. Exerc Sport Sci Rev. 2005; 33: 169-174.
• Henderson GC, Fattor JA, Horninig MA, Faghihnia N, Johnson ML, Mau TL, Luke-Zeitoun M, Brooks GA. Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period. J Physiol. 2007; 584: 963-981
• Hill JO. 1992. Physical activity and energy expenditure pro-ceedings: national task force on prevention and treatment of obesity. Physical activity and obesity conference – NIDDK, pp.60-65.
• Iwayama K, Tokuyama K. Exercise in a metabolic chamber - Effects of exercise on 24 h fat oxidation. J Phys Fitness Sports Med. 2013; 1(2): 307-316.
• Melanson EL, Sharp TE, Seagle HM, Horton TJ, Do-nahoo WT, Grunwald GK, Hamilton JT, Hill JP. Effect of exercise intensity on 24-h energy expenditure and nutrient oxidation. J Appl Physiol. 2002; 92: 1045-1052 
• Shimada K, Yamamoto Y, Iwayama K, Nakamura K, Ya-maguchi S, Hibi M, Nabekura Y, Tokuyama T (unpublished observation).

Exercise Intensity, Oxidative Damage, Glycogen Depletion and Supercompensation. Plus: Optimal 0-12h Post Workout Glycogen Repletion Protocol For Performance Athletes

Do they train at the right intensity and what is the right intensity? What's right, anyway? Lot's of questions, tons of words, a couple of answers and some interesting revelations in today's 2nd article of the SuppVersity Exercise Science Week.

This is day 2 of the SuppVersity Exercise Science Week -- another day, another news. After you've learned about the various mechanisms by which exercise will induce structural changes to your beer belly, lover handles and other problem and non-problem areas, in yesterday's first article of the SuppVersity Exercise Science Week, today's post does actually pick up on the notion of the superiority of high intensity exercise and takes a look at how low vs. high(er) intensity endurance exercise effects the antioxidant defense system of the body. This will lead us to an issue that was once considered to be a downside of high intensity workouts: their notoriousness to deplete muscle glycogen, of which we now know that it is actually one of their fundamental strengths. When we are done with that, it's about time for the sweet dessert. The latter is going to have three courses and will help you achieve maximal muscle glycogen supercompensation after a workout.

Where does the idea that you better work out at low intensities come from?

I have made it a (enervating?) habit to include a small reminder of the "dark side" the same beneficial exercise stress that elicits muscle gains, fat loss, and improvements in conditioning and overall health can have, whenever you don't allow for adequate recovery and nutrient supply, in almost every of the articles pointing to the superiority of high intensity training vs. training in the comfort zone (click here to read up on a couple of these articles).

Figure 1: A comprehensive study by Carey revealed that the increase in ratio of fat-calories to total energy ependiture, when you train in the "fat burning zone" is 3% for men, 5% for women. The total amount of fat is yet higher above the "zone" and, most importantly, the current research suggests that the glycolytic effect, which is inversely related to the relative fat oxidation, is what triggers most of the beneficial metabolic effects.

The question, how pronounced the differences actually are, on the other hand, is not just rarely addressed here at the SuppVersity, it's also something scientists are still trying to elucidate. Usually you will see creatine kinase, an accepted marker of skeletal muscle damage being accessed before and after a workout, but as I have pointed out in previous articles, my personal experience tells me that an intense strength workout is - despite its ability to increase CK levels in training noops by up to 10,000% (x100, no typo - eg. Sewright. 2008) less prone to send you down into the abyss of the Athlete's Triad, than working out for hours (worst on a daily basis) in the purported fat burning zone, i.e. the target heart rate where you'll satisfy the greatest part of your metabolic demands from body fat and of which Carey has been able to show in "relatively fit" male and female runners that it is at least 30% below the anaerobic threshold (AT: 155Hb/min; Fat Burning Zone: 105Hb/min; cf. Carey. 2009).

Aside from that, Carey's results also support the observation Wilson et al. formulate in their recent review of concurrent training, namely that "most dramatic loss in fat mass occurr[s] from moderately high to very high intensities" (Wilson. 2013). In this context, the scientists' definition of "moderately high" is already way beyond the alleged zone of maximal fat loss. "Dramatic" is by the way also an excellent attribute for the 4.5x higher fat loss effect Wilson et al. computed for the highest vs. medium exercise intensities  (91-100% vs. 61-80% HRMax) based on the data they collected for their review.

"Better fat loss, w/ high intensity, aha... but isn't that at the cost of increased oxidation?"

In view of the fact that will be coming back to the issue of "optimal fat loss" later this week, anyway, I guess it's best we get back to the topic at hand and take a look at the toll endurance workouts at different exercise intensities actually take on your antioxidant defense system. As mentioned before, it is still far from being certain which markers you would actually have to measure to get a clear picture of how much stress and damage a given exercise regimen is inflicting. Compared to the creatine kinase levels, the measurement of markers of the activity and status of the anti-oxidant defense system, which was the main outcome variable in a study by Takahasi et al. does yet appear to be more relevant - if not with respect to exercise performance than certainly with respect to overall and metabolic health.

Figure 2: Changes in myeloperoxidase, heart rate, rate of perceived exertion and trolox equivalent antioxidant capacity (TAEC) in eight healthy and untrained males aged 22.6 ± 1.4 years (mean ± SD), with 67.7 ± 4.1 kg body mass, 175.2 ± 3.7 cm height, and 15.1 ± 2.2% body fat after 20min of exercise at 70%, 100% or 130% of the anaerobic threshold.

On three separate occasions, the Japanese researchers studied the effect of different exercise intensities. The latter ranged from 70% over 100% to 130% of the anaerobic threshold and would thus represent exercising in the "fat burning zone" at moderately high intensities and high intensities.

The first thing the scientists registered was that the pre to post increase in oxidative stress at the low and medium intensities did not even reach statistical significance. The "pro-oxidative" effects of the high intensity trial, on the other hand, were statistically significant. Yet, if you look at the actual data in figure 2, I'd guess that you will - just like me - ask yourselves what all the hoopla was about: The absolute differences are mediocre, at best and their physical not statistical significance is highly questionable; and that's not just because the trolox equivalent antioxidant capacity (TEAC) actually increased from pre to post exercise (from allegedly lower pre levels in the 130% trial than before the other exercise tests.

Training at higher intensities is demanding, yeah... but not overtly demanding!

Now, all these statistical significances were calculated on a pre vs. post basis. Intensity-specific differences on the other hand were not observed. We do therefore have to be cautious not to misinterpret the scientists very own and actually non-judgmental conclusion ...

"We found that plasma concentrations of d-ROMs increased as a result of 20 min of exercise above AT. Exercise above AT also increased enzymatic and nonenzymatic antioxidant capacity. On the other hand, there was no effect after 20 min of exercise at 70–100% AT, suggesting that exercise under the AT level does not produce oxidative stress damage." (Takahashi. 2013)

... as an advice to stick to "exercise under the AT [anaerobic threshold]". There are already way too many people wasting their time on the cross-trainers of this word - don't join them, but don't overexert yourself either.

The "Iranian HIIT Solution" has already proven that a minimalist HIIT regimen in the form of 3x200m sprint sessions per week can make all the difference esp. for someone who has never participated in regular activity before (read more).

A single bout of intense exercise leads to significant improvements in glucose and lipid metabolism in obese individuals, that's the latest result of another very recent study that was conducted at the University of Glasgow (Whyte. 2013). The protocol consisted of nothing more than " four maximal 30-s sprints, with 4.5min recovery between each (HIIT), or a single maximal extended sprint (HIT) matched with HIIT for work done". With 20% higher mean power during the sprints the temporary intensity was higher, in view of the fact that the overall exercise duration was longer and there was no time for in-between sprint glycogen replenishment. Thu it's actually not surprising that the acute increase in insulin sensitivity did reach statistical significance only after the extended sprint session. The overall metabolic benefits (non-significant improvements in glucose and lipid metabolism) on the day after, of which we can assume that they were not brought about by the immediate reduction of muscle glycogen, were identical for both conditions, while the the total and relative increase in fasting fatty oxidation was more pronounced after the HIIT protocol (total: 63% and 38%; relative, based on RER: 11% and 8% ).

Figure 3: Oxidative stress and glycogen depletion are important triggers of the beneficial effects of exercise on glucose metabolism ( (based on Kawanaka. 2013).

If we go a step further and think about whether or not oxidative stress is actually something you would want to avoid at all costs, the figure from Kentaro Kawanaka's recently published alongside review of the regulation of glucose transport in skeletal muscle during and after exercise (see figure 3) can help us make up our minds. If you take a look at my mark-ups it's plain to see that ROS production and the increase in AMP (quasi "used ATP") and decreases in ATP and phosphocreatine (PCr) are major signals for the activation of a hitherto incompletely understood signaling cascade that results in increased glucose uptake by the muscle. That's the same glucose uptake, by the way that makes the most significant difference between the "normal" and, insulin-intolerant individual and makes an ideal stepping stone to full-blown diabesity (=obesity + diabetes type II).

"So, what exactly is the effect size of these improvements? Are the worth the sweating?"

To illustrate the quantity of these effects, Kawanaka uses data from a 2009 study by Koshinaka et al. who subjected rats to an acute bout of 3x20s "high-intensity sprint interal swimming" and measured muscle glycogen levels and glucose transport at different timepoints in the 16h window after the workout.

Figure 4: Insulin and non-insulin stimulated glucose transport in rat epitrochlearis muscle at rest and 4 hours after cessation of HIIT exercise (left); muscle glycogen repletion and supercompensation after a workout (from Kawanaka. 2013 based on Koshinaka. 2009)

If we take into account that 3h(!) of continuous swimming elicited the exact same improvement in glycogen uptake as those 3x20s all out "sprints", I probably don't have to say it "appears" as if the synergistic combination of brief HI(I)T training and an appropriate diet will be more productive than the endless hours on an elliptical way too many (often unfortunately female) trainees are still performing in the desperate hope to finally shed the fat from whatever problem areas they have or believe they'd have.

Glycogen supercompensation: This is how it's done

There is yet more to the Koshinika study than another confirmation of the usefulness of HI(I)T exercise for fat loss, fitness and fabulous health. The data Koshinaka et al. collected does also tell us something about post workout glycogen repletion. Most importantly (at least in my humble opinion) that the first, immediate post-exercise phase is characterized by a rapid non-insulin dependent increase in glucose uptake. The latter is actually just as high (>5µmol/g/20min; respective data is not shown in figure 4) as the maximally measured glucose uptake in phase II, in the course of which the presence of insulin has a dose-dependent beneficial effect on the total amount of glucose that's going to be shuttled into the muscle (see figure 4, left). With phase III being characterized by saturated (in fact more than saturated) glycogen stores, these observations would suggest that an "optimal" glycogen replenishment protocol would look somewhat like this:

When you increase your calorie intake on a bulk, you better go really high carb + low fat, if lean gains are what you're looking for. This is at least what a 2011 study by Mendes-Netto suggests (read more)

1. phase I: immediately post > fast absorbing carbohydrate source -- what's important during the immediate post-workout phase is exclusively the availability of glucose, insulin the presence of extra high insulin levels is more or less unnecessary
2. phase II: post workout phase (<8h) > high GI carbohydrate source -- once the glycogen levels have reached a certain level the supercompensation process requires the presence of additional insulin, therefore your post-workout meal should not be carb-free or extremely low GI
3. phase III: recovery phase (>8h) > low GI carbohydrate source -- the glycogen stores have already reached higher than baseline levels, the presence of high levels of insulin in this phase would be counterproductive as it would actually drive glucose uptake by the adipose, not the muscle tissue

Whether this maximum glycogen repletion protocol does in fact make sense for everyone is yet another question, though. For someone who trains twice a day, like Arnold, it certainly does. The same goes for endurance athletes looking for maximal performance. If Lance Armstrong, for example, would ever be allowed to compete again, he would best go for a fast absorbing carbohydrate source like Vitargo right after the race, a huge bowl of pasta and some sugary grape juice as his first meal after the race and some slow digesting carbs like a couple of bowls of oats later that day to ensure optimal glycogen levels on the next day of the Tour -- what neither Lance nor you should not forget, though, is to add some protein to the equation, even if building muscle is not your goal, the protein will speed up the replenishment of muscle glycogen (Zawadski. 1992)

"But how important is muscle glycogen, anyway?"

For the average trainee it does yet remain questionable whether or not this protocol will actually yield noticeable benefits. While it is important to replete the glycogen stores, the advantages of doing this as fast as possible are actually not really relevant for someone who trains 3-4 times per week in order to promote health, well-being and a leaner, more muscular (but not freakish) physique. Especially with respect to the latter, the majority of the more recent studies clearly suggests that muscle protein synthesis is, in the short run, not impaired by low levels of muscle glycogen (click here to learn more).

What you should never forget, though, is that your body will interpret chronically low muscle and liver glycogen levels as a clear-cut indicator that you're starving. The results are a reduced metabolic rate and the shut down of "auxilliary" and costly bodily functions such as the reproductive machinery, etc. - and we don't want that to happen, right?


References:

• Kawanaka K. Regulation of glucose transport in skeletal muscle during and after exercise. 2013. J Phys Fitness Sports Med, 1(4): 563-572.
• Koshinaka K, Kawasaki E, Hokari F, Kawanaka K. Effect of acute high intensity intermittent swimming on postexercise insulin responsiveness in epitrochlearis of fed rats. Metabolism. 2009; 58: 246-253.
• Takahashi M, Suzuki K, Matoba H, Sakamoto S, Obara S. Effects of different intensities of endurance exercise on oxidative stress and antioxidant capacity. J Phys Fitness Sports Med. 2013 1(1): 183-189.
• Sewright KA, Hubal MJ, Kearns A, Holbrook MT, Clarkson PM. Sex differences in response to maximal eccentric exercise. Med Sci Sports Exerc. 2008 Feb;40(2):242-51.
• Whyte LJ, Ferguson C, Wilson J, Scott RA, Gill JM. Effects of single bout of very high-intensity exercise on metabolic health biomarkers in overweight/obese sedentary men. Metabolism. 2013 Feb;62(2):212-9.
• Wilson JM, Marin PJ, Rhea MR, Wilson SM, Loenneke JP, Anderson JC. Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises. J Strength Cond Res. 2013 Aug;26(8):2293-307. 
• Zawadzki KM, Yaspelkis BB 3rd, Ivy JL. Carbohydrate-protein complex increases the rate of muscle glycogen storage after exercise. J Appl Physiol. 1992 May;72(5):1854-9.

How Working Out Changes the Morphology of Your Body Fat and Why This Explains that Intensity and Explosiveness Hold the Key to Getting and Staying Lean, Fit and Healthy

Can the guy on the right run away from the bloated macrophage coated fat cells on the left? Today's first post in the SuppVersity Exercise Science Week does hold the answer to this existential question.

Those of you who don't just read, but also think about the headlines of these posts will probably already have theorized about the remote possibility that I could have changed my mind and discarded the original plan to do an "exercise quickie" early this week (see SuppVersity post from Saturday). Now, before you are getting mad at me, let me give you the (as I would say good) reason for doing that: Some, if not almost all of the exercise related studies, I have piled up here are actually too interesting to end up as part of a mash-up. That's particularly true in view of the fact that my time budget during the week does not allow me to discuss them in appropriate detail. So, even if wanted to end up writing >10,000 word posts, this would only work on 48h days ;-)

The solution I came up with is easy and in my humble opinion actually quite cool: The world's first SuppVersity Exercise Science Week! In the course of the next days, I will serve you one or two of the latest studies from the realms of exercise science per day - with the rest (if there is one) being "mashed up" in the Short News on Saturday. Cool? No? Well, bad luck, then ;-)

We will kick off the week with the modulatory effect of exercise on adipose tissue

We all know that exercise is a good way to support and control diet induced weight loss. Specifically for those of us who are already on the lean(er) side of a "divide", where obese is soon going to be the new normal (see "Obese is Going About to Become the New Normal"), it's probably even obligatory, if it's not being skinny fat that's our diet goal. That being said, a recent review of Izawa et al. provides a couple of intriguing insights and links between physical activity and the structural changes our white adipose tissue is undergoing (Izawa . 2013). In this first post of the SuppVersity Exercise Science Week I am going to summarize and expand on some of these points and point towards the implications these more or less recent, in parts pretty geeky and abstract findings have on the way we could, should, or might train:

• Training can increase lypolysis: Compared to subcutaneous fat (SAT), visceral fat (VAT) has a higher lipid turnover. Interestingly, the same high lypolytic rates which render people with high VAT so vulnerable to high levels of blood fats, are also responsible for the comparable ease with which you can shake those unhealthy VAT depots melt away, when you're working out and/or dieting. The fat around the organs is not just the easiest to store, it's also the easiest to access and liberate (Ross. 2000). That this is not a location-specific characteristic, has already been proven. What does yet still have to be elucidated, is when and due to which complex mechanisms the genetic differences between the subcutaneous and visceral fat cells are getting programmed and whether there may be a way to reverse them.

• Training will modulate the growth environment: The maturation of stem cells into SAT, VAT, or BAT (brown adipose tissue) cells appears to be highly dependent the specific milieu in which they are in. The latter, in turn, is characterized by the presence of  various growth factors. The best known and allegedly most important ones belong to the transforming growth  factor (TGF) family. It is their presence that will control whether a stem cell turns into a "brown" = metabollically active fat cell with thermogenic abilities or a regular white one (SAT or VAT). While BMP2- and BMP-4 are responsible for the formation of white adipocytes, BMP-7 drives brown fat cell development. Together with FGF21 another of those growth factors, these proteins determine the fate of pre-adipocytes. Unfortunately, the research on the different ways by which exercise controls these factors is yet still in its infancy. We will take a closer look at what we know already in the next paragraph.

• 

  As you know from the "CLA Destroys Body Fat" post, PPAR-γ downregulation is also the main pathway by which conjugated linolic acid strips mice of almost all their body fat (read more). The exercise induced upregulation of the so-called hypoxia-inducible factor (HIF-1α) appears to do the exact same thing: Suppress PPAR-γ and thus hit the off switch on body fat storage.

  Training reduces WAT size and number: According to a 2004 review of the literature it appears as if exercise training (aerobic) specifically in early life reduces the number and size of WAT in rodent (Stallknecht. 2004). These results have been confirmed in a 5-week study designed that was conducted to elicit the underlying molecular mechanisms only recently (Sakurai. 2010); and the results of the Sakurai study suggest that it is one of our old acquaintances that is to "blame": The peroxisome proliferator-activated receptor-γ (PPAR-γ), a central regulator of adipogenesis! It's inhibition by physical activity is what does the trick. Now, as a diligent student of the SuppVersity you will certainly remember that this is also the main pathway by which CLA, rhein (from rhubarb) and other weight loss adjuvants work their "magic" - a blockade of the PPAR-γ receptor is like hitting the "off switch" on the body fat storage control panel. And who is it who hits that switch? Well, according to the current research it appears that this is the prerogative of the hypoxia-inducible factor (HIF-1α) which is in turn controlled by exercise induced WNT and AMPK signaling.

• Training improves angiogenesis in WAT: While you hear about angiogenesis, i.e. the physiological process through which new blood vessels form from pre-existing vessels, oftentimes in the context of various endothelial pathologies, its induction within the white adipose tissue is actually highly desirable. Scientists have long been speculating that the insufficient wiring of the adipose organ with blood vessels and the subsequent hypoxia are at least partly to blame for the constant inflammation in the ever-expanding fat depots of the obese (Ye. 2009). Since HIF-1α (see previous paragraph) also promotes the expression of vascular endothelial growth factors and their receptors (VEGFRs / VEGFs), its downstream activation by preferably intense physical activity should improve the endothelial wiring of the fat tissue and thus help sooth the chronic inflammation, that's at the heart of many, if not all of the key-features of the "metabolic syndrome".

• Training increases the adipocyte size depended release of adiponectin: In the past couple of months, the adipokine adiponectin turned out to do most of the good stuff (esp. improvements in glucose and fatty acid metabolism), of which scientists previously thought it was the prerogative of leptin. It is therefore important that exercise increases the rate at which a given increase in adipocyte size (obviously in response to fat storage) will increase the release of adiponectin (Miyazaki. 2010). If we use the classic notion of the adipokine as a signal the fat cells use to tell the brain and the rest of the body how much fat remains to fuel its energetic demands, you could say: Working out allows your body to see how much fat you actually got. The physiological consequences of this revelation are increases in lypolysis and fatty oxidation, as well as overall metabolic benefits.

So far for the stuff that will make you look smart, when you parrot it in front of your gymbros. In order to not just look smart, but also be smart -- and in this case train smart -- you will yet also have to know the implications of these revelations and this is exactly what the rest of this article is going to deal with:

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  Making HIIT a Hit! learn how in the SuppVersity  Special (read more) and use it to get lean & healthy and, more importantly, stay lean and healthy!

  HIF-1α <> PPAR-γ <> adipocyte crosstalk - an(-other) argument for high intensity exercise: Since the HIF-1α response to a given training stimulus decreases once the body has adapted to the stressor by increasing its exercise capacity (Lundby. 2005). The crosstalk between HIF-1α, PPAR-γ, and your fat cells provide another reason to work out in the higher range of the VO2max continuum and to never neglect the imperative of constant progression (even if it's only a progression of 0.1km/h during your sprints on the treadmill - adaptation means stagnation, if you don't raise the bar appropriately)

• Wnt10B response to stretching - an argument for heavy eccentrics and/or statics to revamp your body (less fat, more muscle!): The findings of Akimoto et al. point towards the existence of another rather strength-training specific contributer to the fat loss and leanness promoting effects of exercise - the stretch-induced activation of the wingless-type (WNT) MMV integration site family member WNT10b, the quasi cousin of an upstream mediator of HIF-1α (Akimoto. 2005). The activation of the WTNs does actually get down to the root of the trouble and will not just inhibit the formation of new fat cells from pre-adipocytes, it will also divert the mesenchymal and not yet specialized stem cells to turn into osteroblasts (bone) or myoblasts (muscle). In fact, research has shown that WNT signaling is a major contributer to both the recruitment of new muscle progenitor cells from the aforementioned pool of yet unspecific stem cells and skeletal muscle hypertrophy (Polesskaya. 2005; Armstrong. 2005).

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  You will also benefit from integrating plyometrics into your existing routine - build the Jack of All Traits Workout
  

  The greater WNT response to power vs. strength training points towards the superiority of a plyometrics to get and stay lea: In view of the results of Leal et al., who report a 3x greater WNT gene response to power compared to strength training in their 2011 paper on the effect of different resistance-training regimens on the WNT-signaling pathway, plyometrics, which have way more in common with the power training protocol in the Leal study (40% lighter weights; faster, explosive contractions) than whatever powerlifting routine you may have been thinking of, should be a superior means to stay lean (Leal. 2011)

• Exercise restores your body's fat gauge: If you wanted to pointedly summarize the exercise induced reductions in leptin expression, the associated restoration of leptin sensitivity in the obese, and the increased adiponectin release relative to the increase in fat cell diameter, you could actually say that exercise restores your body's fat gauge. It allows your brain and the other organs to see how much body fat you still got and have them react appropriately. Funnily this is also why you body will, clever as is is, pull the emergency break, whenever your body fat levels become too low (cf. "The Athlete Triad Series").

Did you know that 10% of the fat cells have to be renewed every year? I know this is speculative and we are not talking about ZERO adipocyte maturation here, but what do you think will happen when a fat cell is due and you just hit the off-switch on adipocyte maturation?

A final word of caution: I am well aware that some of you may take this article as justification for training themselves into the ground. So please(!) keep in mind that hypoxia induced WNT10 and stretch induced WNT10b signaling, as well as most of the other fancy stuff you have learned about in the previous paragraphs are stress responses that require adequate recovery periods for the metabolic and growth responses they induce to take effect. Sleep, Eat, Train, Rest, Sleep, Eat, Train, Rest, Sleep, Eat... do you notice something? Yeah, right that's a 3/1 ratio of non-stressful occupations, namely sleeping, eating and resting to a single stressor, i.e. training. In other words, 25% of your result are "made" in the gym, 75% in bed (don't make it too stressful there ;-), in the kitchen and even, when you spend time with friends and family or simply sprawl out on the couch. Think of that, when you're designing your next training routine.

References:

• Armstrong DD, Esser KA. Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Am J Physiol Cell Physiol. 2005 Oct;289(4):C853-9. Epub 2005 May 11.
• Akimoto T, Ushida T, Miyaki S, Akaogi H, Tsuchiya K, Yan Z, Williams RS, Tateishi T. Mechanical stretch inhibits myoblast-to-adipocyte differentiation through Wnt signal-ing. Biochem Biophys Res Commun. 2005; 329: 381-385
• Izawa T, Ogasawara J, Sakurai T, Nomura S, Kizaji T, Ohno H. Recent advances in the adaptations of adipose tissue to physical activity: Morphology and adipose tissue cellularity. J Phys Fitness Sports Med. 2013:1(3): 381-387. 
• Leal ML, Lamas L, Aoki MS, Ugrinowitsch C, Ramos MS,  Tricoli V, Moriscot AS. Effect of different resistance-training regimens on the WNT-signaling pathway. Eur J Appl  Physiol. 2011; 111: 2535-2545
• Miyazaki S, Izawa T, Ogasawara JE, Sakurai T, Nomura S, Kizaki T, Ohno H, Komabayashi T.  Effect of exercise training on adipocyte-size-dependent expression of leptin and adiponectin. Life Sci. 2010; 86: 691-698.
• Lundby C, Gassmann M, Pilegaard H. Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions. Eur J Appl Physiol. 2006 Mar;96(4):363-9. Epub 2005 Nov 12.
• Polesskaya A, Seale P, Rudnicki MA. Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell. 2003 Jun 27;113(7):841-52.
• Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comor-bid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med. 2000; 133: 92-103.
• Sakurai T, Endo S, Hatano D, Ogasawara J, Kizaki T, Oh-ishi S, Izawa T, Ishida H, Ohno H. Effects of exercise training on adipogenesis of stromal-vascular fraction cells in rat epididymal white adipose tissue. Acta Physiol (Oxf). 2010; 200: 325-338.
• Stallknecht B. 2004. Influence of physical training on adipose tissue metabolism -- with special focus on effects of insulin and epinephrine. Dan Med Bull. 2004; 51: 1-33.
• Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond). 2009 Jan;33(1):54-66.