Shedding Some Light on the Leaky Gut <> Exercise Connection. Plus: 20+ Things You Should or Shouldn't Do to Protect and Restore the Integrity of Your Intestinal Wall

Have you ever felt nauseated after a workout? Or does your protein supplement gives you diarrhea only if you take it right after a workout? Both can be related to the toll  exercise can take on the integrity of your intestinal tract.

To be honest, I was quite surprised that I did not get a hell lot of hatemail in response to the the 'MSG heals the gut study' I posted last Sunday... Be that as it may, I feel sort of awkward to have opened Pandora's box without proving you with some betters tools than mono-sodium glutamate (MSG) to seal the box, or rather your leaky gut, again. Therefore I decided to post this mini-feature on a particular issue all of us will be dealing with: An exercise induced increase in gut permeability. As you are going to see, there are a lot of similarities to the 'classic' leaky gut, which is often implicated in the etiology of chronic inflammatory bowel diseases. In order to understand these similarities, but also the few, yet important differences, we will have to lay some theoretical groundwork.

"What exactly is a leaky gut?"

The easiest way to answer this question would be to say: "That's what everybody and his mama is talking about these days". This definition as concise (and precise) as it may be, is yet about as productive as the talk that's at its heart. So, instead of relying on hearsay, let's rather briefly recap how intestinal wall actually works.

Since the intestines are meant to let nutrients and fluid pass, a certain degree of leakiness is absolutely natural. Problems arise only, when the self-regulatory system is broken and/or the permeability exceeds a normal / healthy threshold (img. by Mariana Ruiz).

The mucosal layer of the intestinal tract is made up of epithelial cells, so-called enterocytes which are connected to one another by specialized proteins. These proteins form the tight junctions (TJ) - a term, you will probably have encountered numerous times before. The main constituents of this kit in between the enterocytes are proteins such as occludin, zona-occludens and claudins. Together, the array of enterocytes and the tight junction form the the intestinal barrier, which allows the absorption of nutrients and water, while preventing the translocation of harmful substances from the gut into the bloodstream.

The integrity of this barrier is influenced by the phosphorylation state of the proteins within the tight junctions.The exact interactions are compilcated and can be looked up elsewhere (Banan. 2005). What's important for you to realize is that during prolonged exercise which is necessarily accompanied by an increase in core temperature, cardiovascular and thermoregulatory responses compromise intestinal blood flow.

With the core temperature usually being lower than the temperature in your intestines, the temperature of your gut can easily approach 41°C during a workout.That's more than your epithelial cells can handle and can lead to structural damage of the 'patches' in the tight junctions + epithelial cell layer (Lambert. 1985).

HIIT veterans or weight lifters are not off the hook

Now, the last paragraph may have sounded as if only long endurance workouts like 10k-runs or marathons could entail damage to the intestinal cells. That's however not the case, since the redirection of the blood away from the splanchnic arteries and to the working muscle that's even more pronounced in high(er) intensity exercise, will initiate an ischaemia reperfusion cycle which can entail oxidative damage not during, but interestingly after the the workout, when the blood rushes back into the intestines (Wijck. 2011).

Take home message: There are two distinct pathways that contribute to the leaky gut during and after a workout (a) heat and (b) ischaemic/reperfusion stress. Both influcne the phosphorylation state of the proteins in the tight junctions and will thus increase the permeability of the gut lining.

It stands to reason that the combination of high intensity and long durations, as you will find it in an ultra-marathon runner, for example, is particularly detrimental to the integrity of the intestinal wall, so that it is not exactly surprising that (ultra-)endurance athletes have the highest prevalence (60-90%) of gastrointestinal distress that which manifests in the form of diarrhoea, nausea, stomach problems, bloating and intestinal cramps (Worobetz.1985; Peters.1999; Jeukendrup.2000)

There is more than one thing you can to to protect, heal and restore your gut integrity

The fact that a "leaky gut" is like an open door not just for exogenous toxins or live bacteria, but also for their 'endotoxic poop' is probably no news for you. In fact, it is also the reason why you want to either prevent the pathological increases in gut permeability, in the first place, and/or (re-)seal the gut as soon as possible after your workouts. In this regards, there are three fundamental and easily implementable strategies that should always be employed before you even think about using specific supplements:

• 

  Figure 1: HSP 70 offers protection against endotoxins (LPS) in vivo (top) and in vitro (bottom; Dokladny. 2010)

  Despite the possible ischaemic / reperfusion stress short high intensity exercise bouts like sprinting are generally less taxing on the integrity of the tight junctions than longer duration medium intensity aerobic workouts. Avoiding these particularly gut-stressing workouts and/or taking special precautions before and after marathons and other endurance events would thus be strategy #1 to keep the epithelial cell layer intact and pathogens and toxins from entering the circulation.
• The natural intracellular expression of heat shock proteins (HSPs) can protect the tight gut junctions during and/or help their restoration after a workout. Just like all our endogenous protection systems the production of HSPs can be trained. Giving your body the time it needs to accommodate by making small, but consistent steps towards longer and/or more intense workouts would therefore be strategy #2.
• That leaves us with strategy #3, of which I hope all of you will be using anyway - even if you have not been aware of its gut protective effect, yet: The provision of adequate fluid supply before, during and after a workout (Lambert. 2008).

As the workout durations become longer and longer and/or the respective intensities higher and higher, solely relying on your bodies self-healing capacity and adequate hydration may seize to work, though. Despite the fact that our bodies accommodate to the ever increasing demand for intracellular protection against heat stress by upregulating the HSP expression (athletes have higher HSP expression to a standardized endurance training protocol than normal individiuals; cf. Fehrenbach. 2000), there is - just as with about every adaptive response - a certain threshold, when hormesis, i.e. the beneficial adaptation to a manageable amount of stress, is no longer an option.

From "A" as in arginine to "Z" as in zinc - a list of things to keep the gut lining intact

While there has been quite a lot of research as of late into which dietary supplements and even regular foodstuff would be able to modulate the heat shock proteins in order to prefer the desired downstream benefits on gut integrity, the number of compounds of which it is reasonable to assume that they can actually make a difference is still very small:

• Colostrum supplementation to cell cultures has been shown to increase the expression of HSP-70 in human epithelial cells; studies with human subjects are rare and ambiguous:  While Marchbank et al., have been able to show that bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes (Marchbank. 2011), Buckley et al. actually observed detrimental effects of 8 weeks of bovine colostrum supplementation on the exercise induced gut permeability in runners (Buckley. 2009).The explanation for these discrepencies is not clear, but may be related to the longer duration / different intensity of the exercise protocols, or differences in the immunoglobolin, peptide or amino acid composition of the supplements.
• Zinc in general and specifically polaprezinc, a zinc based anti-ulcer drug, which has primarily been used in Japan as a means to seal leaky Japanese guts, show some promises, as in the treatment and prevention of increased intestinal permeabilty (Zhang. 2009). It is thought that zinc is critical for tight junction assembly and has been shown to be critical in the protection of the gut lining from the chronic toxic assault of alcohol (Zhong. 2010). That being said, you should keep in mind that alcohol will deplete your bodies zinc stores, so that it cannot be said, if someone with an adequate zinc intake would benefit to the same degree as a zinc deficient alcoholic. Moreover, as "natural" as they may be, even essential minerals like zinc don't come without potential side effects (cf. "After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome", read more).
• Glutamine has been used as treatment for patients suffering from irritable bowel syndrome and Crohn’s disease and has been shown to actively increase the expression of HSP70 in critically ill patients (Jonas. 1999; Ziegler. 2005).  
• Berberine could be an ideal addition to glutamine (thx to Maxim Okhrimenko for pointing that out in the comments); berberine does not only modulate the TNF-alpha response in the intestines and increases AKT, but has also been shown to maintain / rescue intestinal glutamine transport and glutaminase activity (Gu. 2009; Amasheh. 2010; Li. 2010; Niu. 2011)
• Probiotics are still an 'under-researched' newcomer and though there is some preliminary evidence pointing to the efficacy of probiotic therapy as a means of improving gut function and enhancing the integrity of the intestinal tight junctions, the ideal supplement regimen, as well as its long-term effects will still have to be elucidated in human studies. Studies by Ewaschuk et al. have yet already shown that the impact factors released from Bifidobacteria infantis can offer a certain degree of protection against experimentally induced colitis in rodents (Ewaschuk. 2008). As far as exercise specific studies are concerned, a recently published paper by Lamprecht et al. is probably the first peer reviewed human study to report allegedly "borderline significant" beneficial effects on gut permeability (measured only indirectly by quantifiying the zonolin conent of the feces) and TNFalpha expression in response to a multi-species probiotics (1010 CFU/day, Ecologic®Performance orOMNi-BiOTiC®POWER) in 23 trained men (Lamprecht. 2013; the study was partially funded with a grant from Winclov, the manufacturer of the respective supplements).
• Butyrate, yet not all short chain fatty acids, have recently been found to decrease gut permeability (Ferreira. 2013). Both data from human studies, as well as exercise specific data is yet still absent.
• Hydroxypropyl methylcellulose (HPMC), which is a non-fermentable fiber, has been shown to protect rodent guts from a high fat diet induced increase in gut permeability (Kim. 2013), as in the case of butyrate its efficacy (and when you think about athletes, tolerability) will yet still have to be confirmed in human trials.
• L-Arginine (and AAKG) as a source of nitric oxide, which is necessary to protect the gut barrier from invaders could have a protective effect, as well (Quirino. 2013); and though this effect is not exercise specific, we know that arginine requirements increase in states of chronic stress, it would therefore be logical that supplementation with l-arginine, or even better AAKG, which comes with a precursor to glutamine will have beneficial effects on the tightness of the guts of intensely training athletes, as well (suggested read: BCAAs, glutamine and ammonia detox) .
• Oats, maybe due to their beta glucan content and their ability to increase the production of short-chain fatty acids in the large intestine, oats offer protection against alcohol induced increases in tight junction permeability (Tang. 2009); exercise specific studies have yet to be conducted, though.Personally I would yet not be surprised if this would turn out to be very effective (note: as long as they are not cross-contaminated, oats are 100% gluten-free)
• Goats milk (powder) has been shown to be equally effective as colostrum in reducing heat and thus most likely exercise induced gut permeability (Prosser. 2004)
• Lactoferrin, a multifunctional protein of the transferrin family that is present in milk may have protective effects against LPS-mediated intestinal mucosal damage and impairments of the barrier function in intestinal epithelial cells (Hirotani. 2008)
• Vitamin A in adequate amounts is necessary to maintain gut integrity; it is likely that this is all the more true if gut integrity and immune function are additionally challenged by strenuous exercise (Quadro. 2000)

I guess, I could find even more supplements (and foods) that may help you protect or restore your gut lining, but let's be honest: As important and beneficial eating and supplementing the right things may be, all your efforts would be foiled if you eat foods and supplements that will have the opposite effect on your gut lining. So here is the complementary and likewise non-exhaustive list of stuff you'd better avoid (at least in high doses) if you want to keep your tight junctions intact and your gut from becoming leaky:

Figure 2: Gliadin peptides induce the release of zonulin which in turn interacts with the tight junctions and increases the diffusion of small molecules (∼350 Da) across the cell membrane. Whether the tight junctions open up wide enough to allow for free diffusion of whole gliadin peptides, whose molecular weight is at least 2000 Da, remains to be determined, though (Heyman. 2011)

• Alcohol will wreak havoc on the permeability of your intestines; probably in consequence of its depleting effect on ileal zinc concentration (Zhong. 2010).
• Gliadin (in wheat/gluten) does actively promote the release of zonolin and the widening of the tight junctions (see figure 2); whether you will notice that or not, depends on the occurrence and extent of an immune response as it is characteristic for Celiac patients. I guess, it's actually not necessary to say that all sorts of other allergens, respectively the ensuing inflammatory response to being exposed to them will have detrimental effects on the integrity of your gut, as well, right?
• ALA, EPA and DHA the dietary omega-3 fatty which may help sooth tight junction permeability in states of chronic inflammation will actually increase it, when the baseline inflammation is already low or they are consumed in excess (Usami. 2001; Roig-Pérez. 2010)
• Copper and iron increase tight junction permeability of caco-2 cells via distinct mechanisms (Ferruzza. 2002)
• Capsaicin, piperine and other hot spices do not only cause a burning sensation in your mouth, it literally burns your intestinal cell lining, as well (Johri. 1992; Tsakura.2007)
• Quercitin by blocking the increase in HSP-70 will increase the suceptibility of your gut to exercise induced increases in permeablity (Kuennen. 2011)
• NSAIDs like aspirin and ibuprofen increase the permeability of the gut ad amplify the potentially detrimental effects of exercise (Lambert. 2007)

Obviously, only few of the last mentioned offenders are exercise specific, but if you start working out with already compromised gut integrity, you can hardly complain if a couple of grams of glutamine, or whatever else you may have picked from the previous list, don't effectively protect your intestinal wall from damage. What's even more important though is that you understand the Janus-faced nature of anti-oxidants and anti-inflammatory compounds. As beneficial as they may be in situations of chronic or acute pathologic inflammation, NSAIDs, quercitin and even your beloved omega-3 can eventually extinguish the 'controlled fire' your body needs to keep all immune and metabolic functions simmering along nicely (suggest reads: "Are you stressed enough for a longer life?" and "Inflammation is a True Fat Burner").

References:

• Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD. TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling. J Cell Sci. 2010 Dec 1;123(Pt 23):4145-55.
• Banan A,Zhang LJ, Shaikh M,et al. theta Isoform of protein kinase C alters barrier function in intestinal epithelium through modulation of distinct claudin isotypes: a novel mechanism for regulation of permeability. J Pharmacol Exp Ther. 2005; 313:962–82.
• Buckley JD, Butler RN, Southcott E, Brinkworth GD. Bovine colostrum supplementation during running training increases intestinal permeability. Nutrients. 2009 Feb;1(2):224-34.
• Dokladny K, Lobb R, Wharton W, Ma TY, Moseley PL. LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-kappaB. Cell Stress Chaperones. 2010 Mar;15(2):153-63. Epub 2009 Jun 24. 
• Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, Looijer-van Langen M, Madsen KL. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G1025-34. 
• Ferruzza S, Scacchi M, Scarino ML, Sambuy Y. Iron and copper alter tight junction permeability in human intestinal Caco-2 cells by distinct mechanisms. Toxicol In Vitro. 2002 Aug;16(4):399-404. 
• Gu L, Li N, Li Q, Zhang Q, Wang C, Zhu W, Li J. The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells. Fitoterapia. 2009 Jun;80(4):241-8.
• Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2013 Sep;61(9):1355-64.
• Hirotani Y, Ikeda K, Kato R, Myotoku M, Umeda T, Ijiri Y, Tanaka K. Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells. Yakugaku Zasshi. 2008 Sep;128(9):1363-8.
• Jeukendrup AE,Vet-Joop K, Sturk A,et al. Relationship between gastrointestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.Clin Sci (Lond). 2000;98:47–55. 
• Jonas CR, Ziegler TR. Potential role of glutamine administration in inflammatory bowel disease. Nestle Nutr Workshop Ser Clin Perform Programme. 1999;2:217-30.
• Johri RK, Thusu N, Khajuria A, Zutshi U. Piperine-mediated changes in the permeability of rat intestinal epithelial cells. The status of gamma-glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation. Biochem Pharmacol. 1992 Apr 1;43(7):1401-7.
• Kim H, Bartley GE, Young SA, Davis PA, Yokoyama W. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice. Mol Nutr Food Res. 2013 Sep;56(9):1464-76. 
• Kuennen M, Gillum T, Dokladny K, Bedrick E, Schneider S, Moseley P. Thermotolerance and heat acclimation may share a common mechanism in humans. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R524-33.
• Lambert GP, Gisolfi CV, Berg DJ, Moseley PL, Oberley LW, Kregel KC. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J Appl Physiol. 2002 Apr;92(4):1750-61; discussion 1749. PubMed PMID: 11896046.
• Lambert GP, Boylan M, Laventure JP, Bull A, Lanspa S. Effect of aspirin and ibuprofen on GI permeability during exercise. Int J Sports Med. 2007 Sep;28(9):722-6.
• Lambert GP, Lang J, Bull A, Pfeifer PC, Eckerson J, Moore G, Lanspa S, O'Brien J. Fluid restriction during running increases GI permeability. Int J Sports Med. 2008 Mar;29(3):194-8.
• Lamprecht M, Bogner S, Schippinger G, Steinbauer K, Fankhauser F, Hallstroem S, Schuetz B, Greilberger JF. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J Int Soc Sports Nutr. 2013 Sep 20;9(1):45. 
• Li N, Gu L, Qu L, Gong J, Li Q, Zhu W, Li J. Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells. Eur J Pharm Sci. 2010 Apr 16;40(1):1-8.
• Marchbank T, Davison G, Oakes JR, Ghatei MA, Patterson M, Moyer MP, Playford RJ. The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G477-84.
• Musch MW, Sugi K, Straus D, Chang EB. Heat-shock protein 72 protects against oxidant-induced injury of barrier function of human colonic epithelial Caco2/bbe cells. Gastroenterology. 1999 Jul;117(1):115-22. 
• Niu L, Qiao W, Hu Z, Li N, Huang Q, Gong J, Li Q, Zhu W, Li J. Berberine attenuates lipopolysaccharide-induced impairments of intestinal glutamine transport and glutaminase activity in rat. Fitoterapia. 2011 Apr;82(3):323-30.
• Peters HP, Bos M, Seebregts L,et al. Gastrointestinal symptoms in long-distance runners, cyclists, and triathletes: prevalence, medication, and etiology. Am J Gastroenterol. 1999; 94:1570–81. 
• Prosser C, Stelwagen K, Cummins R, Guerin P, Gill N, Milne C. Reduction in heat-induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. J Appl Physiol. 2004 Feb;96(2):650-4.
• Quadro L, Gamble MV, Vogel S, Lima AA, Piantedosi R, Moore SR, Colantuoni V, Gottesman ME, Guerrant RL, Blaner WS. Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins. J Infect Dis. 2000 Sep;182 Suppl 1:S97-S102.
• Roig-Pérez S, Cortadellas N, Moretó M, Ferrer R. Intracellular mechanisms involved in docosahexaenoic acid-induced increases in tight junction permeability in Caco-2 cell monolayers. J Nutr. 2010 Sep;140(9):1557-63.
• Ruiz M. Wikipedia contributors, 'Tight junction', Wikipedia, The Free Encyclopedia, 10 November 2013, 07:58 UTC, <http://en.wikipedia.org/w/index.php?title=Tight_junction&oldid=522300074> accessed 25 November 2013
• Tang Y, Forsyth CB, Banan A, Fields JZ, Keshavarzian A. Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage. J Pharmacol Exp Ther. 2009 Jun;329(3):952-8.
• Tsukura Y, Mori M, Hirotani Y, Ikeda K, Amano F, Kato R, Ijiri Y, Tanaka K. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007 Oct;30(10):1982-6.
• Usami M, Muraki K, Iwamoto M, Ohata A, Matsushita E, Miki A. Effect of eicosapentaenoic acid (EPA) on tight junction permeability in intestinal monolayer cells. Clin Nutr. 2001 Aug;20(4):351-9.
• van Wijck K, Lenaerts K, van Loon LJ,et al. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men.PloS One. 2011; 6.
• Worobetz LJ,Gerrard DF. Gastrointestinal symptoms during exercise in Enduro athletes: prevalence and speculations on the aetiology.N Z Med J 1985; 98:644–6.
• Zhang B, Guo Y. Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets. Br J Nutr. 2009 Sep;102(5):687-93.
• Zhong W, McClain CJ, Cave M, Kang YJ, Zhou Z. The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G625-33. 
• Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP, Galloway JR, Wischmeyer PE. Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med. 2005 Aug;31(8):1079-86

Bigger, Stronger, Faster: CoQ10 for Brain & Muscle in Young & Old. The Optimal HIIT Regimen for Fun & Fat Loss - 8s at 100% 60s Idling! Protein Power From Oats? Plus: Rest Times, Clusters, Form & Hypertrophy Training

I decided against calling this the "Get Big, Green and Look Like the Hulk Quickie" (img. Paramount Pictures)

In view of the fact that most of you apparently enjoyed the "Get Lean and Stay Lean Quickies" I posted in the last weeks, I thought you may also be inclined to read a "Get Big, Green and Look Like the Hulk Quickie", but then decided that the name was too long for the headline and "big, green" and maybe even "hulk" in conjunction with "quickie" may have had the SuppVersity turn up on google and other search engines in too close vicinity to websites I do not exactly want this blog to be associated with (just kiddin' ;-)

Be that as it may, enjoy the ride and let me know whether you do prefer this thematically structured approach over the classic news-potpouris ala On Short Notice.

I mean you can obviously argue in favor of both and since this is a place I want you to look forward to visit everyday, I would be inclined to hear whether "innovations" like this make it better or worse.

• CoQ10 supplementations could offer beneficial effects on brain and muscle in elderly individuals and could - at higher doses - work for youngsters, as well (Shetty. 2013) -- In a rodent trial the provision of a relatively high dose of CoQ10 as part of the diet effectively blunted age-induced 'cognitive decline' (whatever that may be in a mouse ;-) and protein breakdown in heart, liver and muscle tissue of the 17.5 months-old mice.
  
  

  

  Figure 1: Carbonyl levels in liver and muscle of young and old mice.

  This result is also interesting, because the mitochondrial protein breakdown in the brain was the one which was least beneficially affected. What's of greater importance, for this news quickie at least, is that the 2.81mg CoQ10 per gram of chow the high dose group received (the human equivalent would be roughly 33mg/kg or 2-3g per day!) elicited beneficial effects on the skeletal muscle carbonyl content, a marker of protein oxidation, in the young animals, as well (see figure 1).
  
  The notion that coQ10 in appropriate doses could be beneficial not just for statin users, but also for perfectly healthy people, even athletes, is also supported by the beneficial effects the administration of coQ10 had in a recent trial where it blunted the oxidative damage due to a high frequency endurance training program in rodents (Okudan. 2013). It does however stand in contrasts with a recent study by Bloomer et al., n which the supplementation of only 300mg (ca. 15% of the HED used in the study at hand) did not yield the desired effects on the exercise performance of 15 perviously individuals (10 men and 5 women; 30-65 years; Bloomer. 2013). Whether this really is just a matter of the correct dosing, or maybe a fundamental difference between mice and men will still have to be elucidated and I would not spent the bucks for anything that's only "maybe" going to work.
• Rats don't do well with hypertrophy training (Scheffer. 2013) -- According to a recently published paper by Scheffer et al., rodents who are afraid of increases in markers of oxidation should refrain from hypertrophy oriented muscle training and stick to lower volume resistance training.
  
  For their study, the Brazilian researchers had analyzed the effects of three different resistance training protocols, namely  muscular resistance training (RT), hypertrophy training (HT), and strength training (ST), which had to be performed twice a week for 12 weeks on muscle lactate and glycogen content, superoxide production, antioxidant enzyme content, and activities, as well as markers of lipid and protein oxidation.
  

  

  While you certainly don't want a fire inferno, doing too little is not going to yield the results you are looking for either (suggested read "The emerging role of an auto-/endocrine-immune axes")

  "Results showed increased superoxide production (UT = 5.348; RT = 5.117; HT = 8.412 ; ST = 6.354), SOD (UT = 0.078 ; RT = 0.101 ± 0.013; HT = 0.533 ± 0.109; ST = 0.388), GPx (UT = 0.290; RT = 0.348; HT = 0.529; ST = 0.384) activities, and content of GPx (HT = 3.8 times; ST = 3.0 times) compared with the UT group. CAT activity was lower (UT = 3.966; RT = 3.47; HT = 2.276 ; ST = 2.028) in HT and ST groups. Oxidative damage was observed in the HT group (TBARS = 0.082; carbonyl = 0.73; thiol = 12.78) compared with the UT group.

  The way in which the authors' conclusion that these "findings indicate that HT causes an imbalance in oxidative parameters in favor of pro-oxidants, causing oxidative stress in skeletal muscle" does implicitly suggest that this is a bad thing that has to be avoided at all cost, which is obviously totally beside the point - if you don't challenge your body he has nothing to adapt to and neither your conditioning, nor your strength or muscle mass are going to improve. The absence of statistically significant increases in oxidative damage in the low volume strength training routines, on the other hand supports the notion that you can use phases of very low volume training with heavy weights in between intense phases of overreaching to monetize on the muscular gains (which will probably keep coming in these 2-4 weeks) by taking all your lifts to another level and thus lying the foundation for future growth.
• Optimized HIIT regimen for overweight kids: 4s max sprinting + 60s active recovery do the trick - could work four you, as well! (Crisp. 2013) -- Either from the SuppVersity news or from listening to Super Human Radio you may remember that a recent study by Deighton et al. has found that sprinting will increase your appetite more and burn less calories than workload matched steady state cardio training. A novel study from Australia does now suggest that this may well be the case, but probably only as a result of doing it wrong - the sprinting, I mean.
  
  
  In their study Nicole A. Crisp and her colleagues from the School of Sport Science at the The University of Western Australia, describe how the combination of 8s all-out sprints on a cycle-ergometer with 60s of active rest easily outperforms its 30min steady state counterpart (30min moderate pace) and its "little brother" and "big" bother the 8s sprint, 120s active rest and the 8s sprint, 30s active rest protocol, respectively.
  
  

  

  This is not the first study to show the superiority of HIIT training in obese boys. In February 2013, I have already covered a very similar study where a brief HIIT session that burns "only" 360kcal was a major motor to teenage weight loos.

  In that, it's important to note that despite a linear increase in energy expenditure from the 60s to the 30s rest group, the latter failed to reach statistical significance (p = 0.076), ...
  

  "[...] likely as a result of decreased sprint quality as indicated by a significant decline in peak power output from SI₆₀ to SI₃₀ (p = 0.034)" (Crisp. 2013)

  In conjunction with the absence of the overcompensation effect at the following breakfast buffet (which was present in the 8/30s and to a lesser degree even the 30min steady state trial), this makes the 8/60s protocol the superior choice for everyone doing HIIT mainly to get or stay lean.
  
  And aside from its practical value, the 8/60s regimen was also the one the boys enjoyed the most.
  
  "And what about me?" I don't see why doing this very short sprints with large bouts of active recovery in between would not be right for you, as well. At least if the activation of your metabolism and / or fat loss during a diet is your primary goal and not an improvement in VO2 max., you would thus probably get many of the benefits at a smaller risk of overtraining. Just make sure you are actually sprinting all-out for the whole 8s and don't stop, when you are just about to get up to speed ;-)
• Long rest times necessary for high jumpers - with 8-12 min pause your performance on the next jump will increase not decrease (Gouvêa . 2013) -- In a recent meta-analysis that's soon going to be published in the Journal of Sports Sciences André Luiz Gouvêa and his co-workers report that the manipulation of rest intervals seems to affect post-activation potentiation magnitude and jump height.
  
  After analyzing fourteen studies, which met the criteria of having a crossover design, being randomised, or non-randomised and counterbalanced and observed the voluntary muscle action-induced post-activation potentiation on jumping performance, the scientists state that the...
  

  "[...]results demonstrated medium effect sizes for rest intervals 0–3 and 8–12 min (-0.25 for 0–3 min; 0.24 for 8–12 min) and a small effect for other ranges (0.15, CI: -0.08 to 0.38 for 4–7 min; for ≥16 min)." (Gouvêa . 2013)

  Since there was little to no evidence for heterogeneity among the sub-groups and no indication of publication bias, these results clearly suggest that rest intervals of 0–3 min have detrimental, rest intervals between 4-8 min neutral and rest intervals of 8-12 min beneficial impact on jump height. In that, the improvements are likely to be mediated by post-activation potentiation.
• The science of cluster training - Conventional wisdom prevails, 10 deep breaths would yield optimal rest time between reps (Hardee. 2013) -- At lest with respect to proper form, which may also have consequences for optimal muscle recruitment and hypertrophy, the optimal rest time between two reps in a cluster appears to be 20s, which is actually what the good old "10 deep breaths rule" would state, as well.
  
  
  What is a cluster? When you are "clustering" your sets you are doing one (sometimes also 2-3) rep(s), rack the weight, rest, do another rep etc. This is a very good technique to increase your strength and break through plateaus that's useful for powerlifters and bodybuilders alike.
  In order to examine the effects of three different cluster set configurations on power clean technique, the scientists recruited 10 male, recreational weightlifters who had to perform clustered or non-clustered power-cleasn: 3 sets of 6 repetitions at 80% of their individual repetition max with 0 (P0), 20 (P20) or 40 seconds (P40) inter-repetition rest.
  
  In the P0 (no cluster) condition, the scientists observed how the form suffered and got worse and worse from the first to the last rep (the catch and first pull were in a more forward position during repetition 6 as compared to repetition 1). With the long rest times in the P40 condition, on the other hand,  "differences in horizontal displacement were found between repetitions 1 and 6 for the second pull and the loop" (Hardee. 2013).
  
  In the P20 condition the researchers did not observe any differences in horizontal displacement between repetitions 1 and 6 during P20. Reason enough for the scientists to conclude that their results would demonstrate that cluster sets with greater tha 20s of inter-repetition rest would be useful to maintain appropriate form without significantly dropping the density of your workout - whether this did actually facilitate strength or size gains was yet not evaluated in the study.
  
  The evidence for the efficacy of this training regimen (aside from simply providing a novel stimulus, which is obviously always a good thing) does come from a 2011 study by  Hansen et al who compared the response of highly trained rugby players to on traditional vs. clustered leg training program and found the latter to be slightly superior with respect to the increase in peak velocity and strength , while the classic continouus set training had an edge as far as total power increases in the lower limbs were concerned (Hansen. 2011).
• Oats healthy car source with performance protein? (Xu. 2013) Who would have thought that, oats are not just an excellent source of slow digesting carbs and potentially fat-burning beta glucan (listen to the SuppVersity Science Round-Up from two weeks ago), they also contain a non-negligible amount of protein of which researchers from the College of Food Science and Engineering at the Northwest A&F University in Yangling, China, have now shown that it ameliorates the increase in lipid oxidation (MDA) and decrease in antioxidant activity (SOD) during an exaustive bout of swimming in 30 male mice.
  
  After the oat protein had been purified from oat meal thirty male Kun-ming mice were divided kept on either a normal control diet, a diet that was enriched with oatmeal and a diet that contained only the protein fraction of the oats. After 20 days, the rodents were subjected to swim to exhaustion. Their swimming endurance and the major metabolic substrates were measured from serum, liver and muscle.
  

  

  Figure 2: Antioxidant enzymes up, lipid oxidation down. That's the result of a comparison of the detrimental effects of an exhaustive swimming test in mice fed regular, oat enriched or oat protein pimped diets for 30 days (Xu. 2013). What the study cannot answer is however whether identical effects would have been seen w/ any other high quality protein as.

  "The results showed that no significant differences were observed in swimming endurance test between the normal control group and the oat protein group (P > 0.05). Mice in the oat meal group had significantly longer swimming endurance compared to the normal control group (P < 0.05). Furthermore, dietary oat protein increased the levels of liver glycogen, enhanced the activities of lactic dehydrogenase and superoxide dismutase, and decreased the levels of blood urea nitrogen and malondialdehyde in serum." (Xu. 2013)

  Now the good news certainly is that id did work. The "bad" or at least not so good news, on the other hand is that there is no adequate control group, since the addition of both the oats and the oat protein will have increased the amount of essential amino acids in the rodent chow significantly.

That's it! At least as far as news on getting bigger, stronger and faster is concerned. In case yo are also interested in something else, for example...

• how scientists have successfully transformed former breast cancer cells back to benign mammary epithelial cells by placing them in a non-carcinogenic environment like a healthy non-inflamed mouse
• that continously taking 25,000IU of supplemental vitamin A is at least not particularly healthy for young lean and obese women
• why Munuka honey, when Greek or Cypriot Honeys are the more potent antimicrobials?

and whatever else I will still be posting before tomorrow's SuppVersity news, you are alway welcome to visit the SuppVersity Facebook Wall.

References:

• Bloomer RJ, Canale RE, McCarthy CG, Farney TM. Impact of oral ubiquinol on blood oxidative stress and exercise performance. Oxid Med Cell Longev. 2013;2013:465020. doi: 10.1155/2013/465020. Epub 2013 Aug 23. 
• Crisp NA, Fournier PA, Licari MK, Braham R, Guelfi KJ. Optimising sprint interval exercise to maximise energy expenditure and enjoyment in overweight boys. Applied Physiology, Nutrition, and Metabolism, 10.1139/h2013-111. 
• Gouvêa AL, Fernandes IA, César EP, Silva WA, Gomes PS. The effects of rest intervals on jumping performance: A meta-analysis on post-activation potentiation studies. J Sports Sci. 2013 Nov 9.
• Hansen KT, Cronin JB, Pickering SL, Newton MJ. Does cluster loading enhance lower body power development in preseason preparation of elite rugby union players? J Strength Cond Res. 2011 Aug;25(8):2118-26.
• Hardee JP, Lawrence MM, Zwetsloot KA, Triplett NT, Utter AC, McBride JM. Effect of cluster set configurations on power clean technique. J Sports Sci. 2013 Nov 5.
• Okudan N, Revan S, Balci SS, Belviranli M, Pepe H, Gökbel H. Effects of CoQ10 supplementation and swimming training on exhaustive exercise-induced oxidative stress in rat heart. Bratisl Lek Listy. 2013;113(7):393-9. 
• Scheffer DL, Silva LA, Tromm CB, da Rosa GL, Silveira PCL, de Souza CT, Latini A, Pinho RA. Impact of different resistance training protocols on muscular oxidative stress parameters. Applied Physiology, Nutrition, and Metabolism, 10.1139/h2013-115
• Shetty RA, Forster MJ, Sumien N. Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age (Dordr). 2013 Nov 10. 
• Xu C, Lv J, You S, Zhao Q, Chen X, Hu X. Supplementation with oat protein ameliorates exercise-induced fatigue in mice. Food Funct. 2013 Nov 12.