Eccentric Exercise IGF1 & Athlete's Heart; Long or Short Intervals, Both Improve Arterial Stiffness. Plus: Exercise Heals Wounds & Makes You Rust Proof Within One Year!

Controlled exhaustion = positive adaptation; continuous exhaustion = wear and tear = one out of 57,002 who suffer from cardiac arrest during a marathon (data based on Webner. 2013)

As announced on Saturday, already this is a "special edition" of the On Short Notice series, focusing exclusively on exercise related studies. With

• two studies on heart health, 
• one on wound healing and the last one on the 
• bullet proof endogenous anti-oxidant system of trained athletes, 

this installment of the "Exercise News Roundup" and two studies on different HIIT, it does however have both a health, as well as a HIIT focus.

I know that does not sound as sexy as being big and buffed, but what's the use of that if you don't fit the coffin, you're about to need, when your looks are more important to you than your health?

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IGF-Response to exercise implicated in "athletes heart" A group of polish researchers describes in their latest paper that's been published ahead of print in the International Journal of Sports Medicine, how the differential IGF-1 response to eccentric (ECC) and concentric (CON) arm exercise in 10 trained strength athletes (1.5-2.0 h on 3-5 days weekly) and 10 age-matched healthy non-trained subjects could explain the differences in the degree of left ventricular hypertrophy, the scientists had measure via M-mode and 2D Doppler echocardiography beforehand (Zebrowska. 2013).

IGF1 and left ventricular hypertrophy (LVH): The correlation stands out of question, but what about the implications? Is this a causative relationship? And what's more: How dangerous are LVH  and having an athlete's heart, at all?

The athletes with LVH did not only have higher IGF-1 levels at baseline (52±5 nM vs. 46±7 nM for controls, p<0.05), they also showed a significantly more pronounced IGF-1 response during the eccentric (ECC) exercise test, with athletes with LVH exhibiting 30% higher and athletes without LVH 15% higher IGF-1 levels than untrained controls (54±6 nM). Moreover, both CON and ECC exercise resulted in higher serum IGFBP-3 levels in LVH athletes compared to controls (242±57 and 274±58, athletes, vs. 215±63 and 244±67, controls, nM, p<0.05), while no differences in other hormones were found between groups. Yet though the scientists' conclusion that these findings would "suggest a role of IGF-1, possibly released from contracting muscle, in stimulating LV hypertrophy in resistance training" is certainly right, we would be ill-advised to jump to any conclusions, hastily by simply (and faultily) equating correlation and causation, here.

Moreover, we should acknowledge that the previously accepted paradigm that LVH, per se, is a bad thing that has to be avoided at all costs is actually not supported by empirical evidence, or as Florescu et al. have it "'Supranormal' cardiac function in athletes is due to better endothelial and arterial function, related to lower oxidative stress, with optimized ventriculo-arterial coupling; athlete's heart is purely a physiological phenomenon, associated with 'supranormal' cardiac function, and there are no markers of myocardial fibrosis." (Florescu. 2010)... in short: in the absence of myocardial fibrosis, a big heart is nothing you will die from - how IGF-1 could actually prevent the latter, i.e. the occurrence of fibrotic structures due to uncompensated growth of the heart muscle, would yet be the topic for another quite lengthy blogpost ;-)

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This image shows a study participant of another study during a VO2 max test on the exact same bike Rakobowchuk et al. used (WSCU.edu). Wrt to the protocols the researchers remark "the protocols involved an identical total training volume and time commitment but differed regarding metabolic stress" With the HIIT trial inducing greater metabolic stress due to the longer periods at supra-amaximal workloads (cf. Turner. 2006).

Heavy or moderate interval training equally heart healthy - at least if you take their effect on arterial stiffness and heart rate dynamics as a measure. That's the message of an article that was published ahead of print in the European Journal of Applied Physiology at then end of last week. During a six-week experiment, Mark Rakobowchuk and his colleagues from the University of Essex and the University of Leeds investigated which of the following protocols (all performed three times per week, for a total of 18 session; 2min warm-up for each; cf. Rakobowchuk. 2013),

• MIIT - moderate intensity interval training consisting of 10s : 20s cycles at 120% of the pretraining max. workrate : 20W for 30, 35 and 40min (bi-weekly progression), or
• HIIT - high intensity interval training consisting of 30s : 60s cycles at 120% of the pretraining max. workrate : 20W for 30, 35 and 40min (bi-weekly progression),

would elicit more favorable changes in carotid artery stiffness, blood pressure, and heart rate variability in a group of 20 healthy, previously untrained young men and women (n = 7 men and 13 women; age 23.5y; BMI 23).

Trainees who want to increase their VO2max should still do HIIT, because only the subjects in the HIIT training group achieved statistically significant increases with respect to this outcome measure (+14% in HIIT vs. +3% VO2 max in MIIT).

Just as the scientists had speculated, their hypothesis that irrespective of the metabolic stress, which would be higher in the HIIT vs. the MIIT trial, the total volume, which was identical would determine the overall adaptive response. For them it was therefore not surprising that all measured parameters of  heart health, i.e.blood pressure, heart rate dynamics and carotid arterial stiffness, improved without significant inter-group differences. Most notably, though, those with the highest arterial stiffness before the trial saw the greatest reductions!

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Figure 2: Additional exercise sped up the wound healing process only in the obese rodents, not the lean ones (Pence. 2013)

Exercise speeds healing of subcutaneous wounds in obesity. This was allegedly observed only in obese rodents, but since the underlying mechanism was neither mediated by gene or protein expression of proinflammatory cytokines interleukin-1A and tumor necrosis factor-alpha or the anti-inflammatory cytokine interleukin-10 in the wounds, I felt it was still worth mentioning, also because it is, as the scientists point out,

"the first report of an exercise effect on wound healing that is unrelated to alterations in wound site inflammation." (Pence. 2013) 

Future trials will have to elucidate whether clotting and homeostasis, which occur in the earliest stage of wound healing, approximately 30 min after the trauma may be involved in this phenomenon.

In this context, some of you will probably remember my recent post on the "Antithrombotic effects of caffeine blunt platelet activity in response to interval training" that exercise increases the tendency of your blood to clot - a tendency that does obviously come handy, when you are bleeding. That the increase in coagulation factors came into effect only in the obese, yet not in the normal weight control, in turn, could be related to the presence of existing hemostastic imbalances due to obesity which would have been corrected by the 30min of treadmill running the rodents in the exercise groups performed at a pace of 12 m/min on a 5% incline for the final 30 min of the light period (0930–1000 h), three days before until five days after the wounding.

A bunch of maggots on a diabetic wound.

Be that as it may, there are more than enough sedentary, "SAD dieting" (and the standard high fat diet rodents are fed in studies like this is nothing but a clone of the S-tandard A-merican D-diet) full-blown or pre-diabetic obese human beings who could likewise benefit from as little as 30min of daily aerobic activity. I mean think about it, if you could thus avoid having 50-100 maggots being placed on those nasty diabetic wounds (see picture on the right) that would never heal without those tiny critters secreting their salivary juices onto the wound to liquefy and subsequently ingest and further degrade the dead tissue in their gut, you can hardly argue that this is too much to ask for, can you?

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"Rust proof" athletes don't need vitamin pills with copious amounts of anti-oxidants and don't have to be afraid of fruit with their synergistic blend of small, but highly effective and synergistic amounts of vitamins and polyphenols, either.

Oxidation proof after 1 year+ of regular aerobic + anaerobic training. According to a paper that's soon going to be published in Medicine & Science in Sports & Exercise trained athletes between the ages of 21 and 35yrs who had been participating in a structured exercise training program (including both aerobic and anaerobic) for the past 12 months, with each session lasting no less than 45 min per session, as well as no less than three sessions per week, are virtually "rust proof".

That's at least my allegedly nonchalant interpretation of the non-existent increases in serum markers of oxidation the scientists from the University of Memphis observed in their 12 male subjects (BMI 25kg/m², body fat 12.8%; VO2Max 20 ml/kg/min) in response to four training sessions separated by 1 wk.

The Sessions were counterbalanced and included either a no-exercise condition (subjects simply rested for the entire period) or one of the these three:

• MISS - moderate intensity + duration steady state: 70% HR reserve for 60min; total time: 60min with 60min of actual work
• HIIT - high intensity + moderate duration interval sprints: 5x60s at 100% + 225s recovery yielding a 1:3.75 work-to-rest ratio ("Within each interval, subjects were instructed to pedal between 80 and 100 rpm for the first 45 s, and then for the final 15 s, subjects were instructed to pedal as fast as possible"); total time: 20 min with 300s of actual work
• MaxIIT - maximal intensity + short duration interval: 10x15s at a wattage of 200% of VO2max, followed by 116s of recovery (1:7.7 work-to-rest ratio); total time: 20 min with 150s of actual work

All exercise bouts were performed on the same cycle ergometer used for the GXT, and subjects reported to the laboratory in the morning (0600–0900 h) after a minimum 10-h overnight fast. The HR was continuously monitored via Polar (TM) HR monitors and blood was drawn at the end of the 20-min rest period  (corresponding to the immediate postexercise blood samples) and 30 and 60 min after the 20-min rest period (corresponding to the postexercise blood samples).

Figure 3: Total antioxidant capacity (TEAC), SOD, CAT and GPx values immediately (0min), 30min and 60min after the respective exercise bouts (data based on Farney. 2013)

The respective total work performed during the trials was 461.1kJ, 96.9kJ, 96.9kJ for the MISS, HIIT and MaxIIT trials, respectively, the perceived exertion was highest in the MaxIIT trial (16.7 vs. 15.6 for HIIT and 13.5 for MISS), while the maximal heart rate 171.7bpm was achieved in the HIIT trial. Still,

"No differences were noted in malondialdehyde, H2O2, advanced oxidation protein product, or NOx between conditions or across time (P > 0.05) [while the a]ntioxidant capacity was generally highest at 30 and 60 min after exercise and lowest at 0 min after exercise." (Farney. 2013; my emphases)

If you will, you could even go one step further and argue that the total antioxidant capacity increases in well-rested, well conditioned athletes in response to exhaustive exercise bouts. Though, this increase reaches statistical significance in the MaxIIT trial only (see figure 3).

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That's it for today, ... but only as far as SuppVersity posts go. In about 2h at 1PM (EST), to be precise you can - if you want - listen to me on Super Human Radio. I am going to pick up on the topic of the first hour which is "Moderate Alcohol Consumption how (Un-)Healthy is it really" and do my best to provide some insights into the discrepancy that exists between reliable scientific evidence, the media coverage on the topic and Mr Average Joe's interpretation of the latter. And if you ain't into booze, just work out ;-) [update: download the podcast]

References:

• Farney TM, McCarthy CG, Canale RE, Schilling BK, Whitehead PN, Bloomer RJ. Absence of blood oxidative stress in trained men after strenuous exercise. Med Sci Sports Exerc. 2013 Oct;44(10):1855-63.
• Pence BD, Dipietro LA, Woods JA. Exercise Speeds Cutaneous Wound Healing in High-Fat Diet-Induced Obese Mice. Med Sci Sports Exerc. 2013 Oct;44(10):1846-1854.
• Rakobowchuk M, Harris E, Taylor A, Cubbon RM, Birch KM. Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans. Eur J Appl Physiol. 2013 Sep 16.
• Turner AP, Cathcart AJ, Parker ME, Butterworth C, Wilson J, Ward SA (2006) Oxygen uptake and muscle desaturation kinetics during intermittent cycling. Med Sci Sports Exerc 38:492–503.
• Webner D, Duprey KM, Drezner JA, Cronholm P, Roberts WO. Sudden cardiac arrest and death in United States marathons. Med Sci Sports Exerc. 2013 Oct;44(10):1843-5.
• Zebrowska A, Waśkiewicz Z, Zając A, Gąsior Z, Galbo H, Langfort J. IGF-1 Response to Arm Exercise with Eccentric and Concentric Muscle Contractions in Resistance-Trained Athletes with Left Ventricular Hypertrophy. Int J Sports Med. 2013 Sep 7.

Less Than 15mg of DHEA Exert Identical Beneficial Effects on Insulin Sensitivity as 1h of Cardio 5x Per Week. Both Effects Mediated Via Increases in Intra-Muscular DHT

Image 1: It has long been established that diabetics have particularly low DHEA levels (Loviselli. 1994), but what's the chicken and what's the egg here?

It is quite funny, sometimes you don't hear about certain supplements, (pro-)hormones, exercise-modalities etc. in years and then, all of a sudden, there are two studies on the respective topic in one week; and moreover, two pretty interesting ones! Last Friday, exactly 7 days ago, you've read here at the SuppVersity about the muscle-protective effects of low-dose dehydroepiandrosterone (DHEA) supplementation during a 5-day intense multiple-type exercise protocol (cf. "DHEA Blunts Muscle Damage During 5 Days of Combined Endurance, Strength and HIIT Training in Young Men"). Today, I have another interesting set of data for you - data which could not just shed some light onto the underlying mechanisms of the said protective effects against skeletal muscle damage, but also on DHEA's beneficial effects on insulin sensitivity.

Not younger, but leaner with a minimalist dose of DHEA?

In a 6 week trial, and thus over a more than eight times longer timespan than in the previously mentioned human study on skelatal muscle damage, Koji Sato and his (or her?) colleagues from the Ritsumeikan University, the Senshu University and the University of Tsukuba (all in Japan, as you probably already suspected) investigated the effects a low dose of DHEA (human equivalent: 0.16mg/kg per day => 10-15mg/day) supplementation on the insulin, QUICKI (=quantitative insulin-sensitivity check index) and intramuscular DHEA and DHT (dihydrotestosterone) levels in sedentary or exercised dietary obese male rodents.

Figure 1: Relative insulin levels, QUICKI, intramuscular DHEA and DHT content in obese male rodents after 6 weeks of DHEA or combined DHEA + exercise (1h, 5days/week) treatment (data adapted from Sato. 2013)

As you can see in figure 1 the effects of both 5x/week running on a treadmill (ETA: 1h) and orally administered DHEA were profound. If you compare the "exercise only" group (red) to the two DHEA groups (green and violet), you will yet notice interesting parallels. Not only were the decreases in serum insulin and the increases (=improvements of insulin sensitivity) in the QUICKI test very similar, the exercise regimen alone yielded a +56% increase skeletal muscle DHEA content and a +71% increase in DHT.

Exercise increases intramuscular DHEA & DHT...
 

Figure 2: Hormonal cascade from DHEA to DHT; all enzymatic conversions can take place on a systemic and intra-cellular level!)

At least the latter, i.e. the increase in DHT should not be news to you if you have been following the in-depth articles at SuppVersity over the past couple of months. From the Intermittent Thoughts on DHT you know that exercise in general and HIT endurance exercise in particular has been found to boost intramuscular dihydrotestosterone levels, as well. The bros, or friends of bros among you, will probably also have heard the horrific stories about creatine monohydrate leading to increased levels of DHT (van der Merve. 2009), of which every reasonable person must actually assume that they are nothing but a downstream effect of increased training loads and/or improved adaptation... I mean, think about it "paleo style": Why would the mammalian body (rodent and human appear to react alike here) increase the DHEA and, via 5-alpha reductase (cf. figure 2), the dihydrotestosterone levels in response to high volume exercise, if not as a means of adaptation?

Oral DHEA + exercise = double-whammy against obesity

The combined treatment, or I should say the exogenous support of the exercise induced changes had - and this is not visible from the data in figure 1, astonishingly profound effects on the diet induced weight gain of the lab animals. While all other rodents became fatter, those in the exercise + DHEA group remained at a steady body weight level; an observation the researchers comment as follows:

Although DHEA administration and exercise training each produced beneficial effects, 6-weeks of combination treatment were more effective for obesity. The precise mechanisms that reduced abdominal fat weight in the combination group remain unclear, yet we can propose several plausible hypotheses. 2 weeks of DHEA administration has been shown to activate fatty acid metabolism-related enzymes, such as long-chain fatty acyl-coenzyme A synthase, and to increase free CoA levels in liver (Mohan. 1998; Mohan. 1990). In addition, exercise training is  known to reduce adipogenesis via upregulation of fatty acid metabolism and increased energy expenditure (Hou. 2003). Therefore, 6-weeks of combination treatment may have promoted additive reductions in abdominal fat volume.

In other words, while DHEA increases the efficacy of fatty acid oxidation, exercise takes care of the increase in energy expenditure which is - all convictions wrt to "calories don't count" and the "calories in vs. calories out"-hypothesis aside - still a fundamental prerequisite that the fatty acids do actually get burned and are not released into circulation to be restored or replaced a couple of hours later.

"Ok, I am just ordering some DHEA, how much should I take?"

Before you head over to the online vendor of your choice to make sure you get your share of DHEA before the FDA hears that it could hamper the sales of diabetes drugs and removes it from the OTC market, I would like to remind you that despite the fact that Sato et al. rightly claim that a "combination treatment [with DHEA and DHT] may be more beneficial than either therapy alone", a cursory glance on the data in figure 1 should suffice to tell you that those additional benefits as statistically significant as they may be are just that "additional" and that exercise alone yielded about equal results, is free of negative and full of beneficial side effects (update: as long as you don't overtrain; thanks Stapedius for this important note) and does not have the same host of studies refuting its efficacy as DHEA has (Clore. 1995).

It is nevertheless intriguing that a hormone the medical orthodoxy has, more or less all of a sudden, dropped like a hot potato and declared "questionable" and "ineffective" is now, roughly 15-20 years being rediscovered... and I am pretty sure that this was not the last DHEA study you will see and read about here at the SuppVersity ;-)

References:

1. Clore JN. Dehydroepiandrosterone and body fat. Obes Res. 1995 Nov;3 Suppl 4:613S-616S. Review.
2. Hou CW, Chou SW, Ho HY, Lee WC, Lin CH, Kuo CH. Interactive effect of exercise training and growth hormone administration on glucose tolerance and muscle GLUT4 protein expression in rats. J Biomed Sci. 2003 Nov-Dec;10(6 Pt 2):689-96.
3. Loviselli A, Pisanu P, Cossu E, Caradonna A, Massa GM, Cirillo R, Balestrieri A. [Low levels of dehydroepiandrosterone sulfate in adult males with insulin-dependent diabetes mellitus]. Minerva Endocrinol. 1994 Sep;19(3):113-9.
4. van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate  supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clin J Sport Med. 2009 Sep;19(5):399-404.
5. Mohan PF, Cleary MP. Effect of short-term DHEA administration on liver metabolism of lean and obese rats. Am J Physiol. 1988 Jul;255(1 Pt 1):E1-8.
6. Mohan PF, Ihnen JS, Levin BE, Cleary MP. Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity. J Nutr. 1990 Sep;120(9):1103-14.
7. Sato K, Iemitsu M, Aizawa K, Ajisaka R. Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle. Am J Physiol Endocrinol Metab. 2008 May;294(5):E961-8. Epub 2008 Mar 18.
8. Sato K, Iemitsu M, Aizawa K, Mesaki N, Ajisaka R, Fujita S. DHEA administration and exercise training improves insulin resistance in obese rats. Nutr Metab (Lond). 2013 May 30;9(1):47. [Epub ahead of print]

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.

Science Round-Up Seconds: Cytokine Modulating Power Cakes, Endurance & Resistance for Maximal Cardiovascular Benefit, Gluten Degrading Bacteria and Cancer Fighting Green Tea + Levitra Combo. Plus: Sirt-3 & Protein Blends

Not sure if the "Power Cakes" in the Kerasioti study looked like these, but it would sure have been appropriate, after all the poor study participants had to cycle for 3h (in total) - makes you wonder if they are WADA approved, doesn't it?

Today's installment of the SuppVersity Science Round-Up Seconds has some delicious stuff for you in stock. We will start out with an interleukin 6 & 10 modulating CRP reducing cake from Greece as an appetizer, or pre-workout, whatever you like better. When we have finished that one, the table or gym talk will center around debunking the myth that only aerobic training was good for your cardiovascular system. When even the last i**** has gotten that, it's about time to devour the delicious anti-carcinogenic and gluten destroying bacteria stew with green tea and Levitra(R), I've been cooking for ya ;-)

Before you go for the cake, however, I want to apologize that I was somewhat out of it on yesterday's show (click here to listen to the podcast). As a compensation today's Seconds have - as you can see - become pretty "nutritious" at least on a quantitative level ;-)

Looking for the perfect peri-workout meal? What about some cake?

(Kerasioti. 2013) -- It may not really sound like "high performance fuel", but in fact the protein cake a group of Greek scientists fed to their nine physically active and pretty well-conditioned male subjects (age, 28 ± 2 yr; height, 184 ± 3 cm; body fat, 11 ± 2%; body mass index, 23 ± 1 kg/m²) turned out to be much more than just performance fuel after the 2 h of continuous cycling on cycle ergometer at an intensity corresponding to 60-65% of the subjects established VO2max.

Figure 1: Interleukin 6, interleukin 10 and c-reactive protein (CRP) levels before and after the first 2h exercise bout with experimental (EXP) and placebo (PLA) cake; data expressed relative to baseline (Kerasioti. 2013).

As the data in figure 1 goes to show you, the cakes which contained a combination of 0.9g/kg carbohyrates and 0.26g/kg protein did in fact have surprisingly more beneficial effects on the rise and fall of the pro- and anti-inflammatory cytokines IL-6 and IL-10 (IL = interleukin) during the two counterbalanced trials, than the placebo, an identical cake with a different macro-nutrient ratio of 1.1g carbs and 0.1g protein per kg body weight.

Training twice a day? No problem with the power cake ;-)
 
Only four hours later the scientists shooed their subjects onto the bike again for another hour of medium intensity exercise and a 95% VO2max time-trial sprint at the end, "to determine if the cake administration affects performance" (Kerasioti. 2013). Sounds logical, right? What's confusing, though is that Kerasioti et al. don't even mention the performance effects they did or didn't observe in the second bout in the discussion of their results - so I suspect that (a) there were no differences or (b) Kerasioti et al. regard the cytokine response to the second trial as a "performance" marker and stick to that as their "effect on performance" (I don't know about you, bun in my humble opinion the latter would be an even greater flaw than leaving the non-significant information out).

Figure 2: IL-6, IL-10 and CRP response over the whole study period; expressed relative to baseline (Kerasioti. 2013)

If you add the cytokine expression in the steady state 2h trial from figure 1 to the data that was recorded after the completion of the 1h steady state + time trial cycling session four hours later and the 48h post levels of the inflammatory markers, the resulting graph exposes a very neat symmetry with an almost identical rise and fall in the expression of the short-lived cytokines and an eye-catching difference in the intermediate inflammatory response evidenced by the increase in CRP in the recovery phase of the placebo trial (just as a reminder: C-reactive protein aka CRP is the same stuff you will also see chronically elevated in diabesity and all sorts of inflammatory diseases).

A propos protein: We also talked about the benefits of protein blends with fast and slow proteins.Here is the SuppVersity article about the human study on the casein + whey combination I mentioned.

Bottom line: Compared to carbohydrates alone the combination of carbs + whey does not only offer a muscle building, but also an inflammatory edge, especially endurance athletes and anyone with a high training density will benefit from -- just like the 3g glutamine (1.5g pre, 1.5g post workout), Carl and I talked about during yesterday's installment of the SuppVersity Science Round-Up, by the way, with the only difference being that the effects of whey protein are probably mediated by it's glutathione (the master oxidant) repleting glutamylcysteine groups (Bounous. 1991), beta-lactoglobulin, lactoferrin and other anti-inflammatory compounds in whey proteins (Peng. 2009).

Cardio and weights: Your cardiovascular system loves both

(Spence. 2013) -- There is this longstanding and die hard myth that only aerobic training would be good for the heart. With the publication of a recent paper by a group of scientists from the University of Western Australia and the Liverpool John Moores University, you do now finally have something to print out, and tack it to every idiots forehead who still insists that only half-marathon running, but not resistance training could save you from cardiovascular infarction ;-)

For their 6-months experiment, the scientists recruited 23 27±5 year-old healthy male subjects who were then randomized to either either endurance (ET, n=10) or resistance training (RT, n=13) in order to evaluate the long-term effects of these training modalities on brachial, femoral and carotid artery diameter and wall thickness (IMT), as well as femoral and brachial flow-mediated (FMD) and glyceryl trinitrate (GTN) mediated dilation. Ha? Well, let's say they wanted to know how the different exercise protocols, the scientists desribe as follows,

For those of you who want to add something to their regimen that boosts the longevity sirtuin, sirt-3 Carl and I have talked about during yesterday's show, here is the HMB + Leucine study I mentioned.

"[...] the ET intervention consisted of a progressivelyoverloaded programme of walking, jogging and running, inclusive of specified training phases over the 24week period. The focus of the periodized RT programme was Olympic weightlifting with incorporated supplemental exercises (e.g. dead-lift, back squat, front squat, bench press and overhead press) to develop overall strength and technique. Relative intensities for the ET and RT interventions were monitored throughout the sessions, individualized and progressed to ensure that subjects were exercising at prescribed percentages of VO2peak and 1RM, respectively" (Spence. 2013)

would effects the structure and performance of the hearts of their subjects, who completed three 1h training sessions of the respective exercise type per week.

As even resistance training enthusiasts should have expected, the RT group did not see significant improvements in O2Peak (ET yielded +5% increase in this indicator of cardiovascular fitness). On the other hand, the endurance training had no effect on upper body strength, which increased by statistically highly significant +21% in the resistance training group. Both these improvements are yet not really newsworthy and the whole study would not have made it to the SuppVersity Science Round-Up, respectively the Seconds, if it had not been for the high-resolution ultrasound images of the heart, which revealed:

Figure 3: Changes in body composition
relative to pre values (Spence. 2013)

• Resistance training affects the brachial artery, increases brachial artery resting (+8%, P<0.05), peak FMD  and GTN-mediated (P<0.01) diameters
• Endurance training affects the femoral artery, increases resting (+3%, P<0.05), peak FMD femoral artery diameters, and improvements in the femoral FMD-to-GTN% ratio 
• Both forms of training had similar beneficial effects the carotid artery wall thickness

In summary: Despite the fact that the two training forms will have differential effects on your overall conditioning and strength, they both increase lean mass (see figure 3) and decrease the artery wall thickness of the artery which supplies your brain with oxygen (the carotid artery). And with their unique effects on the brachial artery in the upper arm (RT) and the femoral artery in the tigh (ET), they make a perfect team to protect you from cardiovascular disease and stroke.

"I'd like a Levitra(R) enhanced green tea with probiotics..." What?

The last two items from yesterday's list that did not make it into the show are actually not brand new studies. One is a comment from the Journal of Clinical Investigation and the other one is a study that has been around since 2011, already. I picked them up in the course of the week and found them news-worthy, although it is not really sure, a combination of green tea, viagra and rothia bacteria is going to prevent cancer and solve your problems with gluten or whether one or the other or a combination of all is going to kill you ;-) Anyways, here are the details:

• 

  Rothia has hitherto rather been known as a bad guy, which can, if it gets into the wrong places cause endocarditis (heart), meningitis (brain), peritonitis (an inflammation of the peritoneum, the thin tissue that lines the inner wall of the abdomen and covers most of the abdominal organs) and other infections (Photo by Nathan Reading)

  Rothia bacteria in the upper gastrointestinal tract degrade gluten (Zamakharchi. 2011) -- Back in 2011 already a group of researchers from the Boston University Henry M. Goldman School of Dental Medicine published a paper in which they describe the astonishing ability of a common gram positive bacteria called Rothia, which is also present in the oral cavity could degrade 50% of the glyiadin peptides the scientists had added to the petri dish before the they were incubated for 30min.
  
  In view of the fact that the immunogenic parts of the peptides, that cannot be cleaved by our natural digestive enzymes, it does appear like a too happy coincidence that our microbial subtenants from the oral and upper gastrointestinal tract possess the enzymatic machinery to degrade the harmful gluten peptides for us - don't you think so?
  
  One thing is for sure, the presence of a bacteria that deals with the stuff, we cannot deal with on our own in our oral cavity certainly does support what I said in the context of the "bulimia apparatus" - the digestive process with all it's downstream effects on your metabolism starts in the mouth:
  

  "During mastication (chewing) foods are mixed with whole saliva helping to accelerate the break-down by digestive enzymes during the residency time in the oral cavity. Oral microorganisms in the swallowed food bolus may or may not survive and/or continue to exert proteolytic activities during or after gastric passage. Our in vitro data with R. aeria show that its enzymes are not abolished at acidic pH values, and are optimally active under more basic pH conditions. In vivo, this could mean that during gastric passage the enzymes will neither be active nor destroyed, and that enzymatic reactivation would occur upon transfer to the duodenum." (Zamakharchi. 2011)

  Aside from the fact that they could make it into the large intestine, previous studies have already confirmed that R. mucilaginosa can even gain a foothold there (Ou. 2009), so that probiotic supplementation with Rothia mucilaginosa could in fact turn out to be a viable treatment / prevention strategy for celiac disease and other gluten related health problems.

• EGCG + PDE-5 = cancer killer (Yang. 2013) -- Cancer is like the Learnean Hydra from ancient Greek mythology (see image on the right). Whenever you cut off one of its heads it'll grow two new ones... well, i must admit the analogy isn't perfect, but it's still useful to understand why the PDE-5 inhibitor vardenafil worked wonders when it was co-administered with the green tea catechin EGCG.
  
  

  

  You really have to wonder why these ancient heroes who had the cunning to kill the Hydra did not even wear a pair of speedos, when they entered into it's watery realms ;-)

  Just like the many Greek warriors who died in their battle with the Hydra before it was finally slain by Heracles, EGCG is well capable of doing major harm to the cancer cells. Just like the snake-like beast the cancer cells have yet found a way to resist the onslaught. Obviously not by growing new heads, though, but rather by over-expressing PDE-5 in order to repress the EGCG increased cGMP activity that would otherwise initiate apoptosis, i.e. the natural self-destruction mechanism of a cell.
  
  So what could be more straight forward than using a PDE-5 inhibitor just like Iolaus, Heracles cousin, used a firebrand to scorch the neck stumps of the Hydra after each decapitation. Clever and effective, don't you think so?
  
  Well, there still is one downside: Just like the story about the Hydra is nothing but a myth, the studies Yang and Wang reference in their commentary in the latest edition of the Journal of Clinical Investigation are only in-vitro studies and whether drinking green tea and popping one of Bayer's Levitra(R) pills after the other, is going to prevent, let alone kill existing cancer, will still have to be elucidated.

That's if for today! And since I am a bit in a hurry, I will leave it up to you to check out the latest really short news on the SuppVersity Facebook wall. Contrary to the green tea + Levitra treated cancer cells, the facebook news are guaranteed to proliferate even before the official Saturday installment of On Short Notice is going to be posted in ~24h (in fact, it will first have to researched and written ;-)

References:

• Bounous G, Gold P. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med. 1991 Aug;14(4):296-309.
• Kerasioti E, Stagos D, Jamurtas A, Kiskini A, Koutedakis Y, Goutzourelas N, Pournaras S, Tsatsakis AM, Kouretas D. Anti-inflammatory effects of a special carbohydrate-whey protein cake after exhaustive cycling in humans. Food Chem Toxicol. 2013 Jan 26.  [epub ahead of print] 
• Ou G, Hedberg M, Horstedt P, Baranov V, Forsberg G, et al. Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease. Am J Gastroenterol. 2009;104:3058–3067.
• Peng X, Xiong YL, Kong B. Antioxidant activity of peptide fractions from whey protein hydrolysates as measured by electron spin resonance. Food Chemistry. 2009; 113(1):196–201. 
• Spence AL, Carter HH, Naylor LH, Green D. A prospective randomised longitudinal study involving 6-months of endurance or resistance exercise on conduit artery adaptation in humans. J Physiol. 2013 Jan 28. [Epub ahead of print] 
• Yang CS, Wang H. Cancer therapy combination: green tea and a phosphodiesterase 5 inhibitor? J Clin Invest. 2013 Jan 25:1-3. [Epub ahead of print]
• Zamakhchari M, Wei G, Dewhirst F, Lee J, Schuppan D, Oppenheim FG, Helmerhorst EJ. Identification of Rothia bacteria as gluten-degrading natural colonizers of the upper gastro-intestinal tract. PLoS One. 2011;6(9):e24455.