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. 2012; 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. 2012). 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. 2012), 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. 2012); 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. 2012 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. 2012 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. 2012 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 2012, 07:58 UTC, <http://en.wikipedia.org/w/index.php?title=Tight_junction&oldid=522300074> accessed 25 November 2012
• 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

Pigs Would Pick MSG - Glutamate Seals the Gut, Decreases Liver & Muscle Fat & Increases Plasma Amino Acids in Swine

Piglets would buy MSG food ;-)

Mono-sodium glutamate (MSG) and the "Chinese restaurant syndrome", obesity and overeating are often thrown together into a single psedo-scientific crock pot with the result being a brew that's 50% hear-say, 40% fear and 10% science. The study we are going to look at today is unquestionably part of the latter ingredient and its results do stand in line with my previously stated concern "that MSG is one of those substances that is usually found in foods with a whole host of other nutrient-poor ingredients, anti-nutrients and proven obesogenic, pro-inflammatory and otherwise unhealthy substances and food additives" ("MSG, NFALD, Leaky Gut & Brain ...") and could thus rather be corollary to, than causative of the toll the fast, convenient and nutrient deficient foods in the Western diet are taking on our health.

Published ahead of print in the online version of the journal Amino Acids you will find a study by a group of researchers from the Texas A&M University. The study was, according to the authors intended to "fill [the] important gap of knowledge about glutamate nutrition and metabolism in animals" (Rezaei. 2012). Luckily their study subjects were pigs, allegedly young pigs, but still omnivores like us and one of the best models of the human digestive tract we have:

"Both humans and pigs are highly dependent on dietary quality since symbiotic microorganisms within the gut play a relatively minor role in modifying the nutrients that are ingested. Intestinal  transit times and digestive efficiencies are comparable. Postabsorptive metabolism is also similar in many respects, although the wide differences in length of gestation and the numbers of young born introduce a potentially significant divergence in nutrient needs for reproduction. [...] Nevertheless, when minimum nutrient requirements of swine and established recommended daily allow­ ances of humans are expressed per kilogram of dietary dry matter (assuming an intake of 500 to 800 g of dry matter per day by teenagers and adults), these values are highly related. It is only reasonable that one not draw unsupport­able inferences from one species to another, but with the possible exception of nonhuman primates, it is apparent that the omnivorous pig is one of the best models for study of nutrition issues in the omnivorous human." (Miller. 1987)

Against that background it is quite intriguing that Rezaei. et al. did not find any of the suspected negative side effects of MSG up to a dosage of 4% in the diet of their piglets.

Figure 1: Weight development and feed intake and effciacy in pigs on diet containing different amounts of supplemental MSG (data based on Rezaei. 2012)

In fact, instead of eating more, the pigs that received the MSG-supplemented diets consumed slightly, but significantly less food than their peers. Despite these appetite suppressing effects of the diet, the piglets in the high MSG arm of the study still gained the most body weight and thusly had the 'optimal' (for lovers of Chines restaurant probably rather 'most detrimental') gain:feed ratio.

The amino acid modifying effects of MSG

When we are seaching for the underlying reasons of these changes, it may be worth taking a look at the amino acid composition of the plasma of the piglets after 21 days on diets supplemented with different amounts of MSG at 1 and 4 h after feeding. During this prostprandial phase, the scientists observed

• 

  More about MSG in human health

  significant increases  in aspartate, glutamate, glutamine, histidine, citrulline, arginine, taurine, alanine, methionine, valine, phenylalanine, isoleucine, leucine, proline, cysteine, ornithine, and lysine in plasma at both time points, i.e. one and four hours after feedin,
• highly significant increases in asparagine, serine, threonine, tryptophan, and tyrosine 1h after feeding and
• significant increases in alanine, citrulline, glutamate, methionine, ornithine, phenylalanine, proline, and tryptophan in the first hour of the postprandial window

If we also take into account previous rodent studies which have shown that MSG reduces the deposition of fatty acids in white adipose tissue (Kondoh. 2008), it cannot be ruled out though that these increases in weight gain were related to increases in lean- not fat tissue (remember: muscle is heavier than fat); after all we are dealing with growing young pigs, in which you would expect an increase in essential and non essential amino acid availability to help with skeletal muscle metabolism (Mahan. 1998).

Figure 2: Total lipid content in percent of control in response to MSG feeding at different doses (left) and the modulatory effects of sodium intake (NaCl) on the effects of MSG (right; data based on Rezaei. 2012)

As the data in figure 2 goes to show this hypothesis appears to stand in line with the decreased fatty acid deposition in liver and skeletal muscle, which will at the same time prevent negative side effects of intra-hepatic and -skeletal lipid accumulation on liver and muscle glucose uptake.

Does salt modify the effects of MSG? And what's the role of the gut in all this?

Against that background it is actually a pitty that we don't have data on the fatty acid content of liver and muscle tissue in response to the different levels of dietary salt in the diets (figure 2, right). I mean, at first sight it appears that more salt could 'ameliorate' the detrimental effects of MSG feeding on the body weight of the rodents, but if the latter was not detrimental, but beneficial, this would certainly entail the question if it's not MSG per se, but rather it's co-appearance with too much, or due to it's ability to boost all taste perception to little sodium in the previously mentioned fast, convenient and nutrient deficient foods, way too many people have gotten addicted to.

You see, just as so many times before things are way more complex than they may seem at first sight and if the interactions of body weight, lean mass, intrahepatic and intramuscular lipids and dietary salt with MSG was not already enough, the data in figure 3 brings another (side?) effect into play the importance of which must not be underestimated - the effect of MSG on the intestinal morphology of the pigs:

Figure 3: Jejunal morphology and jejunal concentrations of DNA, RNA, protein, ATP, and glutathione in 28-day-old pigs weaned at 21 days of age (Rezaei. 2012)

I don't know if you remember the side effect of the chronic ingestion of zinc on the intestinal structure of rodents that caused quite a stir in the zinc-loving bodybuilding community back in June!? In essence, the effects of mono-sodium glutamate on the microvilli, which are responsible for the absorption of nutrients look very similar to the ones that were observed by Taneja et al.in response to Zinc supplementation (SuppVersity: June 13, 2012). As previously mentioned this is per se not a bad thing and could in fact come very hand to people with chronic inflammatory conditions suffering from a "leaky gut" or people who want to protect their gut from the side effects of the chronic use of NSAIDs, where MSG has only recently been implicated as a viable tool to prevent and heal mucosal damage (Amagas. 2012).

Figure 4: Postprandial glucose levels (left) and intestinal morphology (right) of mice on diets with different concentrations of mono-sodium glutamate (Rezaei. 2012)

As figure 4 goes to show this could actually work with MSG without the zinc-induced increases in insulin and blood glucose (see figure 2 in previous article). Whether these effects are directly related to the ingestion of MSG or its glutamin-sparing effects n the gut cannot be said for sure, though:

"Grant alert" Despite the fact that I am pretty sure that the actuall data in this study is accurately reported, I still want to point out that the scientists received "a grant from the International Glutamate Technical Committee". It's explicitly listed in the "acknowledgments" and probably not much of an issue outside of the discussion in which you will obviously miss references to potential negative side effects (which have not been observed in the study, though).

"Thus, dietary supplementation with glutamate may enhance the availability of dietary glutamine in plasma. As a versatile amino acid, glutamate participates in both synthetic and oxidative pathways in the small intestine, resulting in the production of proteins, ornithine, citrulline, proline, arginine, alanine, aspartate, glutathione, CO2, and ATP. Therefore, dietary supplementation with glutamate increased the plasma concentrations of these amino acids  and jejunal concentrations of glutathione in weaned pigs. Compelling evidence shows that dietary glutamate is a major energy substrate for the small intestine, which is an organ with a particularly high met- abolic rate. In support of this notion, we found that dietary MSG supplementation increased jejunal concentrations of ATP in weaned pigs. Additionally, glutamate is an excitatory neurotransmitter, thereby regulating the motility of the gastrointestinal tract. Thus, when a weaning diet is deficient in glutamate, gut atrophy occurs and the efficiency of utilization of dietary protein for growth and other physiological functions is greatly decreased." (Rezaei. 2012)

As evidence from previous studies by Kondoh et al. suggests, the effects of glutamate do not end at the intestinal brush border. Its centrally mediated downstream effects after interacting with l-Glutamate receptors in the intestines are however still not fully understood and could either be beneficial (as the work by Kondoh et al. would suggest; Kondoh. 2008 & 2009), be without physiological consequences or - as the mainstream myth suggests - "be the devil"; with the latter being much more likely in people with genetic or already established metabolic problems which result in a deficiency of glutamate dehydrogenase (Stanley. 2009).

Bottom line: The last mentioned problems certain individuals who have inherited or acquired problems with the enzymatic conversion of glutamate are yet not the only reason why I strongly caution against taking the results of the study at hand as a free ticket for limitless MSG consumption. If it's not the MSG that's going to make you fat, I can assure you that those 'foods' in which it is used will be getting the job done pretty quickly and will thus compensate for any possibly existent improvements in intestinal and whole body amino acid metabolism.

Parmigiano Reggiano aside from seaweed the #1 "real food" offender in terms of MSG and still good for your bones (Pampaloni. 2011) - one of many examples of the fallacy of black-and-white thinking. To heal your gut, glutamine would yet still be your better choice, I suppose ;-)

That said, there are still unresolved issues related to the negative effects of MSG on the immune system and the thymus. The dosages that are required to observe toxic effects may be hilarious if you take into account how much of it you find in an individual food item, and even if you started supplementing with MSG, or lived on fast- and convenient food, only, you will probably be hard pressed to get up to the 50g+ human equivalent of mono-sodium glutamate which was sufficient to significantly decrease thymus cell viability in rats (Pavlovic. 2009). In case you feel you are endangered and belong to the people who rather wear a helmet than stop hammering their head against a wall, you could try to counter that with an additional 6-7g of vitamin C (for the rodents that worked)... but let's be honest, wouldn't your life be much easier, if you simply stuck to whole foods and don't worry about the occasional piece of aged Parmesan cheese with 1680 mg glutamate per 100g. It could not just be good for your gut, but has been shown to be good for your bones (Pampaloni. 2011), probably not because, but at least despite the high MSG content.

References:

• Amagase K, Ochi A, Kojo A, Mizunoe A, Taue M, Kinoshita N, Nakamura E, Takeuchi K. New therapeutic strategy for amino acid medicine: prophylactic and healing promoting effect of monosodium glutamate against NSAID-induced enteropathy. J Pharmacol Sci. 2012;118(2):131-7.
• Kondoh T, Torii K (2008) MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats. Physiol Behav 95:135–144.
• Kondoh T, Mallick HN, Torii K. Activation of the gut-brain axis by dietary glutamate and physiologic significance in energy homeostasis. Am J Clin Nutr. 2009 Sep;90(3):832S-837S.
• Mahan DC, Shields RG Jr. Essential and nonessential amino acid composition of pigs from birth to 145 kilograms of body weight, and comparison to other studies. J Anim Sci. 1998 Feb;76(2):513-21.
• Miller ER, Ullrey DE. The pig as a model for human nutrition. Annu Rev Nutr. 1987;7:361-82. 
• Pampaloni B, Bartolini E, Brandi ML. Parmigiano Reggiano cheese and bone health. Clin Cases Miner Bone Metab. 2011 Sep;8(3):33-6.
• Pavlovic V, Pavlovic D, Kocic G, Sokolovic D, Sarac M, Jovic Z. Ascorbic acid modulates monosodium glutamate induced cytotoxicity in rat thymus. Bratisl Lek Listy. 2009;110(4):205-9.
• Stanley CA. Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children. Am J Clin Nutr. 2009 Sep;90(3):862S-866S.
• Rezaei R, Knabe DA, Tekwe CD, Dahanayaka S, Ficken MD, Fielder SE, Eide SJ, Lovering SL, Wu G. Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids. 2012 Nov 2.

Probiotics for Athletes: The Supplemental 10 Billion CFS Leaky Gut Solution for the Fermented Food Refusinek?

Yogurt is probably the best known probiotic food, but there are way more traditional fermented foods that have been part of the human diet for centuries. No wonder that the combination of being "ancestral" and being supported by the latest research renders them so appalling to the "paleo community". I do yet suspect that the average gymbro will be more inclined to buy a pill or powder than Kefir, Kimchi and Kraut... and why not? It's convenient and as long it works... it does, doesn't it?

The gut microbiome and its effect on metabolic and overall health are all the rave these days. As I already pointed out in previous posts on this matter, we are yet only beginning to grasp the complex interactions between the nasty and not so nasty intestine and the way we look, feel or perform. That this does not hinder hundreds of companies to make all sorts of partly warranted, partly unwarranted claims about the myriad benefits the ingestion of their product would have on your health, I actually don't mind too much that the 2x2g servings of probiotics (Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W22, Lactobacillus brevis W63, and Lacto-coccus lactis W58) the 23 healthy male triathletes, runners and,cyclists (age 30–45 years) who participated in one of the latest studies from the Centre for Physiological Medicine at the Medical University of Graz, consumed for 14 weeks in addition to their regular diets were, just like the study itself, sponsored by Winclove, a European producer of "high potency" probiotics (Lamprecht. 2012).

A sponsored study is better than no study and all the more outrageous claims, right?

The  5×10^9 colony forming units (CFU) of bacteria each serving of the powdered supplement provided had to be dissolved in 100-125ml of plain water an were to be ingested one hour prior to meals twice daily. Other than that, the subjects who had been randomly assigned to a supplement and a placebo group were simply instructed not to make any significant changes to their dietary or training regimen.

Before the first (week 0) and second (week 14) exercise test that consisted of three incremental cycle ergometer exercise tests, in the course of which the workload was increased every by 20 W every minute until voluntary ex-haustion (this usually took 15-18min) that were followed by 2x15 minutes of cycling at 60W (80rpm; 1st and 2nd) three minute cool down at the same light intensity, the participants received identical breakfasts containing

Cycling eergometer tests now (left) and then (right) - the colors are not the only thing that differs ;-)

• Coffee w/ milk (low fat) or Tea w/ lemon & honey (10g)  
• 3 slices wheat or rye bread 
• Butter 20 g 
• Marmalade/jam 30 g 
• One slice low fat ham 
• One piece of cheese 
• 250 mL fruit juice 
• 250 mL water

The three days before the tests the participants had to abstain from any type of strenuous exercise. Activity and dietary intake were controlled by training and food logs, respectively.

So how actually do you measure "leaky gut" or a beginning leaky gut? Zonolin & cytokines

It stands to reason that  Lamprecht et al. did not simply gut the tummies of their subjects open in order to take tissue samples and analyze the integrity of the gut wall. Moreover, even if the had done so, they may not even have been able to see the subtle changes and differences in the permeability of the intestinal wall that occur after only 14 weeks in trained athletes whose bodies and thus digestive tracts were already well-accustomed to their habitual training load. Therefore the researchers picked several well known markers of oxidation and inflammation, namely

• protein carbonyl (CO) groups, as they have also been observed in other inflammatory disease, including Alzheimer’s disease (AD), rheumatoid arthritis, diabetes, sepsis, chronic renal failure, and respiratory distress syndrome etc. (Dalle. Donne. 2003),
• TNF-alpha, which modulates the acute phase of inflammation and has long been identified as a potential mediator of the transition from Crohn's Disease to "leaky gut" (Hollander. 2002), and
• IL-6, the chronic overexpression of which is and - despite its recently reevaluated importance as an important signalling in the energy sensing pathway of the musculature (cf. Pedersen. 2012)- will remain problematic

as well as the gut specific haptoglobolin zonolin to elucidate the status of the gut lining and the impact of the supplementation regimen. Contrary to the TNF-alpha and IL-6 even of which these days everybody appears to have gotten wind they are in one way or another involved in the "bad inflammation we all have to avoid", only the friends of Rob Wolf's podcast will probably have an idea of what zonolin is and what it dies in the human body. Produced in the liver and intestinal epithelial cells, zonolin  is thought to be the main physiological modulator of intercellular tight junctions (Fasano. 2011). Actually it's pretty straight forward: 

The more zonolin your body produced the "leakier" your gut will become. 

Unfortunately those "leaks" in-between the cells are about as indiscriminate as the open back door of your house, in terms of whom they let pass through. This can come handy, when you want certain molecules, such as medications (e.g. Salama. 2006), to pass into the blood stream, it's exercise, or I should say stress induced over-expression, however, opens the doors to whomever or rather whatever is hanging around in your digestive tract,  including pathogens and their toxic byproducts, such as lipopolysaccharides (Groschowitz. 2009). These large molecules(LPS) consisting of a lipid and a polysaccharide joined by a covalent bond which are (among others) produced by the same gram-negative bacteria which have been shown to over-populate the intestines of obese people  act as endotoxins and elicit strong immune responses in animals and human being. Next to their involvement in the etiology of the metabolic syndrome, LPS have also been implicated in chronic fatigue syndrome , and similar pathologies (Maes. 2008), which are brought and maintained by the constant endotoxin influx from the stomach.

Tighter gut, lower oxidation and correspondingly lower "inflammation"

After this somewhat lengthy dissertation about the zonolin <> LPS <> all sorts of pathologies connection it should be clear that the most important change the 11 participants in the probiotics group experienced during the 14-week treatment period was the ~30% reduction in zonolin expression in the stool (cf. figure 1):

Figure 1: Zonolin in stool and markers of protein oxidation (carbonyl proteins) and inflammation (TNF-alpha and IL-6); all values expressed relative to average of both groups at baseline, i.e. week 0 (data calculated based on Lamprecht. .2012)

It is certainly difficult to quantify the downstream effects of this changes in zonolin in the stools of the participants on "gut integrity", but since the analyses of all other markers was carried out in the blood, the changes in protein carbonyl levels, TNF-alpha and IL-6 expression are indicative of ..

*Note: in view of the role IL-6 plays as a regulator of exercise induced changes in energy metabolism (Pederson. 2012), it is actually a good thing that the IL-6 levels post exercise did not differ between groups, while the baseline levels (=chronic = "bad inflammation") did.

• reduced oxidation (which is actual damage) to the proteins and a (10% lower carbonyl protein before, 48% lower protein carbonyls after the exercise test in week 14), as well as a
• correspondingly reduced baseline response of the immune system (32% and 28% lower  TNF-alpha and IL-6 before and 31% and identical* TNF-alpha IL-6 response after the exercise test in week 14)

which are in turn most likely brought about by reduces LPS exposure due to a "tighter gut" and / or a reduction of the gram-negative bacteria and other LPS producing intruders in response to the probiotic supplement.

Bottom line: As I've already pointed out in the introduction and as the "and / or" statement in the last sentence of the previous paragraph suggests, we are still far away from a true understanding of the diverse effects the good and the bad subtenants in our digestive tract exert on our metabolic and overall health.

For those who have already forgotten about this - glutamine can also help keeping your gut intact during phases of intense training + it keeps the nasty subtenants in your gut from eating away the amino acids in your food and supplements.

It is therefore too early to say that "every hard training athlete will benefit from the long term or even better chronic usage of a probiotic supplement!". If we do however take into account how much money way too many trainees spent on absolutely useless supplements, the 105€ you would currently have to pay for the exact same (pretty expensive) probiotic that was used in the study, are probably well-invested.

I would however expect that consuming larger quantities of fermented will not just have similar effects on the integrity of your intestines; and what's more, in view of the fact that they are also replacing other (for most people less healthy) foods in your diet, they are way more likely to have beneficial "side effects" on your body composition and performance than 2x2g of powdered probiotics ;-)

References:

• Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 2003 Mar;329(1-2):23-38.
• Fasano A: Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011, 91:151–175.
• Groschowitz KR, Hogan SP: Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 2009, 124:3–20
• Hollander D. Crohn's disease, TNF-alpha, and the leaky gut. The chicken or the egg? Am J Gastroenterol. 2002 Aug;97(8):1867-8.
• Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.
• 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. 2012 Sep 20;9(1):45.
• Pedersen BK. Muscular interleukin-6 and its role as an energy sensor. Med Sci Sports Exerc. 2012 Mar;44(3):392-6.
• Salama NN, Eddington ND, Fasano A. Tight junction modulation and its relationship to drug delivery. Adv Drug Deliv Rev. 2006 Apr 20;58(1):15-28. Epub 2006 Mar 6.

Caffeine Protects Brain Function Against Stress & SAD Diet; Coffee Withdrawal, Anxiety & More; Giardia, Messy Subtenant W/ Gusto For Arginine; Vit B6 & n6:n3 PUFA Ratio

19 Billion Euro that's the estimated 2011 financial burden due to lung cancer, alone, here in Europe and the On Short Notice figure of the week (information based on ESMO2012 press release)

Those of you who are also following the SuppVersity facebook news, will probably recognize the figure on the right: 16,000,000,000€ or $24,419,000,000, that's the estimated economical burden due to lung cancer, alone, here in Europe (cf. "Who cares if people are dying as long as the economy is thriving?"). An enormous financial loss, and still not the reason that this is my figure of the week. Rather than the financial damage, itself, it is the tragic fact that only the latter, yet not the fate of the patients and their families, would make a valid argument, when policy makers were debating a long overdue, total and all-encompassing public smoking ban... but now for a couple of more sciency, yet not less intriguing news from the past week.

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Problems thinking straight? Guess what: 3-4 cups of coffee could help :-) According to a soon-to-be-published paper by scientists from the Jordan University of Science and Technology in Irbid, Jordan, the ingestion of the human equivalent of approximately 3.8mg caffeine per kg body weight or 3-4 cups of coffee per day, can inhibit both, the stress, related as well as diet induced (we are talking of the "typical" Western diet (WD), that's both high in carbohydrates and fat) cognitive impairments (Alzoubi. 2012)... well, at least in the researchers 3-months rodent study it worked like a charm

• learning trial: animals in the caffeine/stress, caffeine/WD, and caffeine/stress/WD groups made fewer errors, than non-supplemented stressed or WD animals; overall their performance was comparable to those of the control
• memory tests: treatment reduced the number of error and restored short-term memory and long-term memory during chronic stress and/or WD (P < 0.05) to normal levels

With respect to the underlying mechanisms the scientists speculate that caffeine may "act mainly by inhibiting adenosine receptors" (Alroubi. 2012), which has in turn been shown to to inhibit long term potentiation (LTP) in rat hippocampal slices and disrupt the process of learning and memory at the synaptic level by blocking release of glutamate (de Mendonca. 1994).

Additionally, caffeine has also been shown to increases the expression of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor, which is impaired in response to chronic stress and a hypercaloric Western diet (Aleisa. 2006; Molteni. 2004) and leads to deteriorations in cognitive performance. In the long run those effects could also contribute to the anti-dementia and anti-Parkinson's effects, I mentioned in the recent SuppVersity post on the insulin sensitizing effects of coffee.

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Figure 1: While the Hedonic tone and alertness reduced to baseline on day 5 of caffeine withdrawal, the habitual caffeine consumers had >15% higher anxiety scores on day 7 after giving up on their daily dose of methylxanthine (data calculated based on Smith. 2012).

Don't worry, caffeine will also work for humans. And what's best, upon short-term withdrawl (8 days) your cognitive performance is not going to suck - at least not as much as when you are stressed or living on pizza and French fries, only. All that and a couple of interesting other results have been published ahead of print in the online version of the Journal of Pharmacology (Smith. 2012).

To probe the effects of acute caffeine ingestion on cognitive performance and the influence of previous caffeine consumption and withdrawal, Andrew P Smith, Gary Christopher and David Sutherland recruited 70 volunteers (25 male, 45 female; mean age 22.8 years). The 35 consumers (>100mg caffeine /day, mean 300mg; range 110–600 mg) were put on withdrawal and tested on day 2, alone and without caffeine, and day 8 together with the non-consumers in a double-blind placebo-controlled fashion. During the caffeine challenge, the cognitive performance was tested twice, once before and once 30min after the provision of the caffeinated beverages.

Anxious, but smart: Caffeine gives you the edge

The results of the trial clearly indicate that the ingestion of 2 mg/kg of caffeine, which were served in decaffeinated coffee or tea 30min before the testing procedures, were associated with faster simple reaction times, fewer long responses, greater detection of targets in the cognitive vigilance task, and faster encoding of new information.

"The results confirmed previous findings, with ingestion of caffeine being associated with a faster simple reaction time, fewer long responses, more targets detected and faster encoding of new information. There were no main effects of consumer status, nor were there any significant interactions between caffeine and consumer status." (Smith. 2012)

Notwithstanding, I believe that many of you will probably be more interested in the effects of caffeine withdrawal on overall withdrawal symptoms (figure 1, top), as well as the alertness, hedonic tone and anxiety (figure 1, bottom) and the cognitive performance on day 2 of the withdrawal period (figure 2, left), than in any of the well-established performance cognitive performance boost, right?

Figure 2: Performance on day 2 of withdrawal phase (w/out caffeine) and on day 8 before (w/out caffeine) and after (w/ caffeine)the ingestion of decaffeinated tea or coffee with 2mg/kg caffeine in it (data based on Smith. 2012)

As you can see on the left-hand side of figure 2 there was a minimal performance decline on day 2 of the withdrawal phase, but the latter was statistically not significant and all measured markers of cognitive function had returned to normal on day 8 (remember longer response times = worse performance!), when the resumption or first time provision of caffeine spiked the reaction times and lowered the mistakes in all tests, irrespective of whether the subjects were former habitual consumers on withdrawal, or not.

Outside of controlled experiments "real" coffee and tea do at least as well

Since a large cup of coffee contains about the same amount of caffeine the scientists simply added to decaffeinated beverages, to ensure that the drinks could not be distinguished (by their smell for example), you can simply stick to your regular coffee and if you want to enjoy similar benefits. And to be honest, in view of the plethora of benefits of chronic low dose coffee consumption, I would not even think for a second about whether or not you may be missing out on the occasional boost, when you are not "going on withdrawal" from time to time...

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Figure 3: W/out arginine (Arg-) intestinal epithelial cells can't proliferate (graph based on Stadelmann. 2012)

Giardia eats away your guts arginine supply and makes itself at home within an increasingly morbid digestive tract! As a group of scientists from Sweden and Argentina reports in their latest paper, the protozoan parasite, Giardia intestinalis, feasts on the arginine your gut cells need to proliferate (Stadelmann. 2012). This will lead to reduced polyamine levels and upregulated cell cycle inhibitory genes, which will eventually disrupt the the cell cycle of the intestinal epithelial cells. The reduced intestinal epithelial cell proliferation, on the other hand, allows the gut pathogen to thrive and will, in the long run, disrupt the intestinal tissue homeostasis and thus initiate the decay of the intestinal epithelium  - a central feature of so many of the wide-spread gut pathologies.

Provision of additional arginine + citrulline can help ... in the short run

Now, the good news about all that is that the in-vitro data in figure 3 clearly suggests and anecdotal, as well as the effective therapy of diarrhea patients with arginine/citrulline actually confirm that the provision of supplemental arginine (or citrulline) constitutes a cheap and readily available way to ameliorate the decay, until the bugs have been eradicated by antimicrobial drugs.

A pros pos, antimocrobial drugs, with regard to latter, Noa Tejman-Yarden and Lars Eckmann write in a recent review of the latest drug innovations, that despite the fact that metronidazole and other antimicrobials are usually effective, "treatment failures are common and antimicrobia resistance occurs" (Tejman-Yarden. 2011), so that it would appear as if complex derivatives of 5-nitroimidazole and benzimidazole, which form the core structure of the most widely used antigiardial drugs, will replace them in the short-run. At least for so long, until several new classes of antigiardial drug candidates that have already been identity by high-throughput screening of large compound libraries, will eventually hit the market (Tejman.Yarden. 2011)

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More about vitamin B6: Helps with neurotransmitters synthesis; is involved in nerve function and necessary for normal brain development & function; influences mood, and melatonin production; effects circadian clock; is needed for B12 absorption and thus red blood cell production

When low: "Pins and needles" in extremities, mental disorders, seborrheic dermatitis, estrogenic PMS, dizziness, irritability, kidney stones, abnormal EEG, anemia, convulsions, edema (water retention), hypothyroidism, migraine-headaches, glossitis, lymphopenia

When high: Depression, suicidal tendencies, severe fatigue, mood swings, low blood sugar, migraine-headaches, heart palpitations, thyroid abnormalities (hyper- in the short, hypo in the long term), numbness in hands and/or feet, spinal / nerve degeneration, muscle spasms / cramps, osteoporosis, arthritis, higher blood pressure (short-term suppl.), lower blood pressure (long-term suppl.), mineral imbalances (high phosphor & magnesium vs. low sodium & calcium), restlessness, insomnia, vivid dreams, decreased estrogen & prolactin, depressive PMS.

RDA (adults): 1.3 mg*
*higher for pregnant women & >50y

Upper tolerable limit: 30-100mg*
*depending on the source of information

Food sources: chicken, turkey, tuna, salmon, shrimp, beef liver, milk, cheese, lentils, beans, spinach, carrots, brown rice, bran, sunflower seeds, wheat germ, and whole-grain flour

n6:n3 ratio does not depend on dietary intake alone: A marginal deficiency in vitamin B6 will skew your serum PUFA levels towards the N6-side That's the long and short of the results of a study that's going to be published in the October issue of the Journal of Nutrition.

Mei Zhao and her colleagues analyzed the fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy men and women who had been fed a low-vitamin B-6 (pyridoxine) diet for 28 days and observed that contrary to the plasma HDL and LDL cholesterol concentrations, the amount of free fatty acids (FFA) in the blood and the erythrocyte and PBMC membrane fatty acid compositions, neither of which showed any statistically significant changes, the amount of all long-chain polyunsaturated fatty acids, i.e. arachidonic acid (n6) and EPA and DHA (n3) decreased from 548 ± 96 to 490 ± 94 μmol/L, 37 ± 13 to 32 ± 13 μmol/L, and 121 ± 28 to 109 ± 28 μmol/L, respectively.

The subsequent 8% increase in the total n6:n3 PUFA ratio from 15.4 to 16.6 is not alarming, but if this trend would continue linearly, it would certainly become problematic, in the long run. Moreover, the decrease in both n6 and n3 long-chain PUFAs (of which people tend to forget that the "inflammatory" arachidonic acid is as vitally important as its "anti-inflammatory" omega-3 counterparts) could provide an alternative / complementary mechanistic explanation for the increased cardiovascular disease risk that has been associated with vitamin B-6 deficiency.

In view of the fact that the RDA is not exactly high and can easily be achieved from dietary sources, along (as long as you follow a diversified whole foods diet), and considering the fact that high levels of B6 have been associated with more negative side-effects than B6 deficiency (see infobox on the right; please note that I collected the information on a couple of trustworthy websites on RDAs & co and did not verify the research on each of them!), I would however caution against the typical Western "more helps more" supplementation mentality.

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Figure 4: Easy come, easy go - the mass you gain and the fat you lose by doing nothing than simply injecting testosterone is lost / regained within 6 months after discontinuation of the "testosterone therapy" (Forbes. 1992); read more about the role of testosterone in skeletal muscle hypertrophy in the Intermittent Thoughts on Building Muscle

In view of the fact that (a) today's short news items are pretty long(ish) and you still got a couple of interesting facebook news to check out, such as...

• health related: "Vitamin D: We probably won't know before 2017, whether supplementation is advisable", "Aromatase inhibitors to treat endometriosis", or 
• muscle related: "The muscle sparing effects of CLA + Omega-3" and a true classic "Muscle mass gained on injectable testosterone is lost, when injections are seized", 

... and a plethora of additional gems from the realms of health, exercise, nutrition & supplementation, I will call it a day for today and save the exercise and a couple of other exciting On Short Notice items for later next week.


References:

• Aleisa AM, Alzoubi KH, Gerges NZ, Alkadhi KA. Chronic psychosocial stress-induced impairment of hippocampal LTP: possible role of BDNF. Neurobiology of Disease 2006;22:453–62. 
• Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet. Behav Brain Res. 2012 Sep 20.
• ESMO. Press releases related to the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
• Forbes GB, Porta CR, Herr BE, Griggs RC. Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped. JAMA. 1992 Jan 15;267(3):397-9.
• de Mendonca A, Ribeiro JA. Endogenous adenosine modulates long-term potentiation in the hippocampus. Neuroscience 1994;62:385–90.
• Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F. Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience 2004;123:429–40.
• Smith AP, Christopher G, Sutherland D. Acute effects of caffeine on attention: a comparison of non-consumers and withdrawn consumers. J Psychopharmacol. 2012 Sep 19.
• Stadelmann B, Merino MC, Persson L, Svaerd SG. Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells. PLoS ONE. 2012; 7(9): e45325. 
• Tejman-Yarden N, Eckmann L. New approaches to the treatment of giardiasis. Curr Opin Infect Dis. 2011 Oct;24(5):451-6.

Leaky Gut & Gluten Belly: Bacterial Firebugs Translocate from Your Gut to Your Ever-Growing Visceral Fat Depots

Image 1: Gluttony or a victim of bacterial translocation from an unrecognized gluten-sensitive leaky gut (img from COPD Lighthouse)

"Leaky gut", for decades one of those concepts, the belief in which divided self-proclaimed "real scientists" from their "hippie" counterparts, has eventually found its way to mainstream science. What began with a few tentative studies into the role of a pathologically increased gut permeability in Crohn's disease and co., is about to become a recognized research area with about 150 related publications within the first 9 month of 2011, alone. Out of these 150 publications, a study by Professor Pierre Desreumaux, and his colleagues from the Universitè Lille Nord de France (Desreumaux. 2011) is unquestionably among those, which could have a major impact on the established image of the gut and its biota as an isolated system that sustains the rest of the body with nutrients and has - due to the insulating epithelial layer - little or no direct impact on all the ailments and illnesses by which the Western civilization has been befallen in the course of its quest for highly palatable, optically pleasant, economic and convenient (franken-)food.

The study comprised 22 patients with Chron's disease, 17 patients with ulcerative colitis and 21 controls, who were normal weight, had no history of diabetes mellitus and were not being treated with speci fic medications known to modulate visceral fat. All patients had been scheduled for operations, during which - with their consent - the required subcutaneous/mesenteric fat specimens were taken and the ileal and colonic transparietal biopsies were performed.

Figure 1: CRP mRNA expression [arbitrary units] in mesenteric and subcutaneous fat pads of control, Crohn's disease (CD), and ulcerative colitis (UC) patients (data adapted from Desreumaux. 2011)

While the result that the mRNA expression of c-reactive protein (CRP) in the Crohn's disease group was 83x higher than in the patients with ulcerative colitis (UC) and 3000x higher than in the control group, alone would probably have been worth the whole procedure, a way more interesting result is that the 83x increase over the UC group is fat-depot specific. This means, only the mesenteric fat that is situated right next to the organs of the intestinal tract produces this 83x exaggerated amount of the acute phase protein CRP that is released in response to acute profound inflammation and has been implicated as a marker for peripheral vascular disease (Abdellaui. 2007), liver inflammation (Rodrigez-Leal. 2006), and other unwanted metabolic consequences of the rampant obesity-pandemic (Oda. 2008). This novel observation led the scientists to believe that CRP expression may be enhanced by inflammatory and bacterial stimuli related / subsequent to the pathologically increased gut permeability in Chron's patients.

Image 6: Could Glutamine be
the cheap colostrum?

Can you take measures to decrease your gut permeability and spare your visceral fat e.coli and other bacterial infections? Yes you can! And if you are a diligent student of the SuppVersity, who does not miss a single "course" (i.e. blogpost), you already know that

• glutamine (e.g. dos Santos. 2010), and
• colostrum (Marchbank. 2011)

have been shown to increase gut integrity and to reverse the negative effects of strenuous exercise (such as heavy weight lifting and marathon running ;-) on intestinal permeability.

And in fact, Desreumaux et al. were able to show that in Crohn's disease patients, bacterial translocation, which is usually defined as the migration of bacteria from the gastrointestinal tract to mesenteric lymph nodes and then to peripheral organs such as the liver and spleen, can also affect the mesentric fat pads and increases during experimental ileitis (i.e. inflammation of the ilium, of which a permanently increased mucosal permeability is a characteristic feature; Kroesen. 2008):

Bacterial translocation to mesenteric adipose tissue occurred in 80% of indomethacin-treated rats [model for inflammatory bowel diseases] compared with 11% of control rats. Higher rates of bacterial translocation to mesenteric lymph nodes were also noted in rats following intraperitoneal administration of indomethacin when compared to control animals (67% vs 22%, p < 0.089). The rates of bacterial trans-location were broadly similar in mesenteric adipose tissue and mesenteric lymph nodes (80% vs 67%) in indomethacin-treated rats, as well as in control animals (11% vs 22%).

With 27% the rate in the Crohn's patients was lower, yet still more than two 2x higher than in the "healthy" controls (13%). Basically, this means that a healthy gut keeps >87% of the bacteria from wreaking havoc on your visceral fat depots (and other organs) a "leaky" one, on the other hand, may allow up to 80% of these tiny firebugs to make themselves at home in the fat tissue next to your digestive organs. Now, that would not be a problem, if the local "fire" your new subtenant are sparking within those fat pads would not results in chronic and systemic inflammation (the scientists were able to show a linear relation between visceral CRP and systemic CRP levels) and thus predispose you to obesity, diabetes, heart disease, Alzheimer's, cancer and all the other plagues of the 21st century.

On Short Notice: Worst Transfat Offenders Cookies & Co + Cinnamophilin For Joints + Tomato Powder Battles Cancer Like Aspirin + Creatine Protects Cell Walls + Carboholism Starts in the Womb, Intermittent Fasting Helps... + More!

Image 1 (lecker.de): They may look cute and harmless, but they are just one of the many incarnations of the worst transfatty acids offenders in the diets of the "average American" cake, cookie and pastry lovers. Believe it or not: Some of them manage to eat almost 100g of the proatherogenic fats per day (!)

Saturday and therefore time for a handful of "On Short Notice" news. We've got some ground to cover, today, so let's get started right away: We will start out by taking a look at the joint-healing / -protective effects of cinnamophilin, a compound from the roots of the cinnamomum trees. We will reconsider the importance of adiponectin for the non-obese physical culturist, switch from aspirin to tomato powder as our cancer prevention "drug" of choice and re-appreciate the newly discovered cell-protective value of a supplement 90% of you are probably already taking: creatine! Once we are done with that we revisit the potential connection between chronically low blood glucose, chronic catecholamine over-expression and the chronic fatigue syndrome. We will then take a look at how high carb diets and intermittent fasting of pregnant rats program the orexin A expression in the brains of their offspring and how that can predispose them to become obese.

During a brief water-break we will discard the idea of hyperhydration as idiotic and decide against carrying another kg of water weight around for the rest of this installment of "On Short Notice". Eventually we will reject pulses as a new staple diet food due to their potential to damage our gut mucosa and their strange gender-specific effects on insulin release and shake our heads over the average and not so average American's daily trans-fatty acid intake, which borders - in some cases - the 100g (!) ceiling of unhealthy absurdity.

• 

  Image 2: I must admit that I am not 100% sure if you would see similar benefits from regular cinnamon, not just because it is probably not from Cinnamomum philippinense, but also because the active ingredieant cinnamophilin has originally been extracted from the roots of the tree, not it's bark, which is what regular cinnamon is made from - it is obviously likely that some, yet probably lower amounts, would also be contained in the bark and a teaspoon of regular cinnamon probably won't hurt, anyway (cf. Wu. 1994 and Lu. 2012)

  Do your joints a favor and dig up some cinnamomum roots. While I am honestly not sure if cinnamophilin content of regular cinnamon (-bark) vs. Cinnamomum philippinense (nor whether this stuff is even in the bark, which is the raw material for "regular" cinnamon - a paper by Wu would suggest that it is extracted from the roots; cf. Wu. 1994), as it was used in a recently published study from College of Medicine, Taipei Medical University, will be sufficient, it is relatively certain that the anti-inflammatory effects of this highly lipophilic antioxidant and free radical-scavenging agent, which has also been shown to inhibit thromboxane synthase and the thromboxane A2 receptor (means it will reduce unwanted blood clots; Yu. 1994), to block Na+ and Ca2+ inward currents in rat cardiac cells (means it helps to protect the contractile function of your heart; Su. 1999), and to reduce brain infarction and protect against transient focal cerebral ischemia (rodent studies by Lee. 2005 & 2009), would silence any ongoing joint inflammation.
  And while Ju et al. can only speculate about the exact mechanism it appears to involve the modulation of NF-κB or ERK/p38 MAPK downregulation and/or suppresion of p-c-Jun pathways. Since both are involved in the etiology of other inflammatory, degenerative diseases, as well, it appears almost certain that there will soon be more exciting applications for yet another medicinal component from your kitchen cupboard.
• Adipokines are not necessarily your friend - not even adpinonectin: Despite being the latest and (supposedly) greatest of the powerful cytokines that are released from your body fat, may keep you healthy when you are fat, it's negative correlation Pisto et al. observed in an epidemiological cross-sectional study involving 54 normotensive, non-smoking men with normal OGTT, clearly suggests that increasing adiponectin expression probably ain't the best way to get big and buffed (Pisto. 2012). Rather than that, you better diet and work out till you are big and buffed and wait for adiponectin (and leptin, which was by the way not significantly correlated with muscle size after adjustment for total adiposity) to fall in place.

• 

  Image 3: Tomato(powder)'s aspirin-like anti-cancer effects could be another reason for the health benefits of the so-called Mediterranean Diet

  Tomato powder mimics aspirins cancer protective effects At least in the gastrointestinal tract the COX-2 inhibition of tomato powder appears to exert similar protective effects against colorectal cancer (Tuzcu. 2012); and in view of the fact that the rodents in the Turkish study were fed a 5% enriched chow you would however not even have to consume tons of it - 90g or 1.14g/kg body weight would suffice ;-) If that's still more than you want or can stomach, just eat more tomatoes and/or (even better) tomato paste, which is quasi the water-containing version of the dry extract.
  And if you can't do tons of either, don't forget: Just like all the bad junk that may not be a problem if you ingested just junk A and maybe junk B, from time to time, becomes really nasty once C, D, E, etc. join the assault, it may be the pound of tomatoes you ate over the course of the last 2 weeks that helped you to avoid that the literal last straw that would otherwise not have broken the camel's but your back.

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  Figure 1 : Lipid vesicle permabilization after exposure to melittin + (1) NaCl , (2) 100 mM DMBG), (3) Creatine, or (4) PCr (Tokarska-Schlattne. 2012).

  (Phospho-)Creatine protects lipids in cell walls! In their latest paper a group of French and Swiss researchers report that they demonstrated for the first time that phosphocreatine (PCr), the explosive power, short-term energy substrate you are trying to increase, when you are taking creatine (monohydrate or whatever else), is more than just an energy source (Tokarska-Schlattne. 2012). As the data in the figure 1 shows, it has direct protective effects on the lipid fraction of your cells as well. And while this observation does not make creatine a bit more effective, it does provide another piece to the puzzle that explains why it is also useful in so many sports-unrelated areas such myopathies and a plethora of neurodegenerative diseases.
• Constant subphysiological glycemia (= hypoglycemia without symptoms) could be the reason that you centrally fatigue, after all the constant elevation of epinephrine and glucagon, Ana María Arbeláez and her colleagues observed in a cleverly conducted study, where they limited the glucose levels in 8 healthy human volunteers to 65 mg/dL (3.6 mmol/L) for two hours showed a constant elevation of epinephrine and glucagon (Arbeláez. 2012). That the latter will only work for so long hardly suffice to keep you functioning normal (by no means optimal) should be clear... So how do you prevent that? Don't overtrain, don't undereat, don't eat only protein and don't be f***ing scared of eating as much carbs and fats, as you need to fuel an active lifestyle (Arbeláez. 2012).

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  Figure 2: Orexin A expression in the PvNP in the offstring of rat dams on different pregnancy diets

  You have the choice: Obese or normal kids? It all depends on the way you eat during pregnancy, at least that is the result of a soon-to-be-published study in Brain Research (, which found that compared to the normal pregnancy diet, a diet with an extra load of carbohydrates lead to a lower body weight at birth, but increased orexin A expression in the parvocellular part of the paraventricular nucleus (PvNP) which predisposed the rat pubs of the high carb dams to gain weight at a faster rate and catch-up and overtake the rodents from the control group after no more than 9 weeks.
  Another 10 weeks later, the rodents born to rats in the high carb group were already the heaviest of the four experimental groups and still as hungry as before.
  Now that alone would not necessarily make a SuppVersity news, if the scientists had not, without even noticing made a (imho) very relevant discovery. In addition to the group with free access to normal chow, they had another group which mimicked the time-restricted feeding pattern in the high fat and high carb groups, who received their chow only within a fixed 6h window, which would essentially equate to intermittent fasting; and while I doubt that the results reach statistical significance, it is still quite telling that the pubs born to the intermittently fastest (IF) rats on the regular diets, were normal weight at birth, had the lowest orexin A (hunger signal expressed in the brain) expression in the PvNP and were subsequently the lightest at the 19 week weight in...
  I still wouldn't suggest you start to fast intermittently, just because you notice you are pregnant, after all we don't know whether or how this translates to humans and if the pubs of the IF-dams were not simply undermuscled and therefore exhibited a lower body weight.

• 

  Image 4: As long as you got a couple of tables with water, sugary electrolyte bevarages, or even better salted coconut water along the roadside, you don't need to carry another 2lbs of water weight with you on your 1/2 marathon races.

  If you want to carry another kilo of useless weight around in the heat, go on and practice hyperhydration, otherwise you better stick to a bottle of water with some salt and sugar in it on your next 18km TT run in the heat (and cold). This is the actually not very surprising take home message of a recently conducted randomized cross-over trial from the University of Sherbrooke, in Canada, in the course of which Pierre-Yves Gigou and his colleagues investigated the effects of hyperhydration (=water loading) with 26 mL/kg bodyweight of a 130 mmol/L sodium solution before four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient on a treadmill (Gigou. 2012).
  For the well-trained triathletes in the study, it did not make a difference whatsoever, as long as they could guzzle away their 500ml of gatorade during the 80-90min of running they were fine.
• Are pulses superfoods, for women only or simply not suitable for daily consumption? It appears that similar to their nasty brethren, the soybeans, yellow peas, chickpeas, navy beans and lentils have the potential to become e hip diet food that could do more harm than good, especially to its male consumers. In a recently conducted study, a group of researchers from the University of Toronto found that pulses can help both men and women lose weight without prescribed caloric restriction (Mollar. 2012).

  

  Image 5: Pulsing of protein is something you are familiar with, but what about eating pulses.. yeah, we are talking about yellow peas, chickpeas, navy beans and lentils; that stuff your grandma maybe told your patents to eat from time to time. Are they the good twin of the evil soy bean?

  Contrary to the subjects in the calorically restricted "control" arm (-500kcal/day) of the study, the overweight or obese (mean BMI 32.8 kg/m²) adults in the pulse group, who were provided with a whopping dose of five cups of pulses per week (on average 896 g/week), had reduced their energy intake ad-libitum to about the same level as their peers "involuntarily" and accordingly seen similar reductions in body weight, waist circumference, systolic and diastolic blood pressure (statistical significance for intergroup differences were non-significant, i.e.  p >> 0.05, for all). At the end of the 8 week period there were however a couple of unwanted side-effects: While the minimal increase in HDL form the pulses would certainly count as a plus, increasing  C-peptide levels already suggest that there appears to be a problem with the glucose management in the pulse-eaters.
  And in fact, while the average female participants insulin AUC (the area under the insulin curve is a measure for the total amount of insulin the pancreas spills out in response to an oral glucose tolerance test, as it was performed in the study at hand) did go down by 13.9%, there was a profound increase (27.3 % in males) in the male pulse eaters.

  

  Figure 3 (radiancenutrition.com): Daily consumption of pulses appears appears to entail the risk of developing leaky gut.

  And even the women would have been better off (at least from a glucose tolerance perspective) without their yellow peas, chickpeas, navy beans and lentils - on the classic diet, they lost the same amount of weight and improved their insulin response by 24.2% and thus still 19.4% more than the men (the men had a reduction of -4.8 % in insulin AUC) and 10.3% more than with the pulse diet. I am therefore not convinced whether the scientists' euphoric conclusion that the "frequent consumption of pulses in an ad libitum diet reduced risk factors of the MetSyn [metabolic syndrome] and these effects were equivalent, and in some instances stronger, than counselling for dietary energy reduction" is not a little too optimistic - and that despite the fact that the HOMA-IR Mollar et al. reference as their indicator of improved insulin sensitivity suggests that they may be right...
  And before I forget it, the significant, but still meager improvements in LDL scientists from the University Saskatchevan report in another pulse diet study from the same supplement to the British Journal of Nutrition involving only elderly subjects would not convince me to eat 2x150g of beans, chickpeas, peas or lentils every day, either (Abeysekara. 2012) - why? Contrary to Whitlock et al. who are apparently not very concerned about the "abrasive" effect of pulses on the thickness of the mucosa in the gut (-25% in rodent experts; cf. Whitlock. 2012), I am not going to open up my "internal doors" to foreigners for a minuscule reduction in LDL, alleged improvements in glucose metabolism (see above) and some weightloss that comes about because you are so bloated that you become anorexic by twice let alone thrice daily pulse consumption.

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  Figure 5: Fat, TFA intake across age groups and sources (Kris-Etherton. 2012)

  Transfats (TFA): Cakes, cookies, pies and pastries are the worst offenders That's the unsurprising finding of the latest analysis of data from the National Health and Nutrition Examination Survey (NHANES; data from 1999-2002; Kris-Etherton. 2012). Among the 16,669 individuals (age ≥3 years) the median TFA intake was 2.3 % of calories (5 g/day) with 0.9–4.5 % of energy (1.5–13.1 g/day) over different quintiles of intake. The mean (that's the arithmetic mean vs. just the value right in the middle, which is the median) TFA intake was 2.5 % of energy (6.1 g/day).
  The overall range of TFA intakes in the highest quintile was almost crazily broad and ranged from already health compromising 8.8 up to 92.4 g/day. In view of the fact that the lions-share of this shit (sorry, but I just can't find a better name for it) came from cakes, cookies, pies, and pastries, the easiest solution to the problem and a major relief to the future public health insurance system in the US would be to ban this junk from the supermarkets or at least require the use of TFA-free and heat-stable fats in their production... but I think we all know that this is not going to happen, anytime soon.

"What? That's it, already?" If that's what you are just thinking I suggest you take a detour to the SuppVersity Facebook Wall and check out how Citrulline may protect your brain from aging, how your heart might protect itself by becoming insulin resistant and many other recent news from the realms of exercise, nutrition and health science!

References

• Arbeláez AM, Rutlin JR, Hershey T, Powers WJ, Videen TO, Cryer PE. Thalamic Activation During Slightly Subphysiological Glycemia in Humans. Diabetes Care. 2012 Aug 13.
• Abeysekara S, Chilibeck PD, Vatanparast H, Zello GA. A pulse-based diet is effective for reducing total and LDL-cholesterol in older adults. British Journal of Nutrition. 2012; 108:S103-S110.
• Beck B, Richy S, Archer ZA, Mercer JB. Early and persistent up-regulation of hypothalamic orexigenic peptides in rat offspring born to dams fed a high-carbohydrate supplement during gestation. Brain Research. 17 August 2012.
• Gigou PY, Dion T, Asselin A, Berrigan F, Goulet EDB. Pre-Exercise Hyperhydration-Induced Bodyweight Gain Does Not Alter Prolonged Treadmill Running Time-Trial Performance in Warm Ambient Conditions. Nutrients. 2012; 4(8):949-966.
• Kris-Etherton PM, Lefevre M, Mensink RP, Petersen B, Fleming J, Flickinger BD. Trans Fatty Acid Intakes and Food Sources in the U.S. Population: NHANES 1999-2002. Lipids. 2012 Aug 18.
• Lu YC, Hsiao G, Lin KH, Hsieh MS, Jayakumar T, Wu TS, Sheu JR. Cinnamophilin Isolated from Cinnamomum philippinense Protects against Collagen Degradation in Human Chondrocytes. Phytother Res. 2012 Aug 18.
• Lee EJ, Chen HY, Lee MY, et al. Cinnamophilin reduces oxidative damage and protects against transient focal cerebral ischemia in mice. Free Radic Biol Med. 2005; 39: 495–510.
• Lee EJ, Chen HY, Hung YC, et al. Therapeutic window for cinnamophilin following oxygen-glucose deprivation and transient focal cerebral ischemia. Exp Neurol. 2009; 217: 74–83.
• Mollard RC, Luhovyy BL, Panahi S, Nunez M, Hanley A, Anderson GH. Regular consumption of pulses for 8 weeks reduces metabolic syndrome risk factors in overweight and obese adults. British Journal of Nutrition. 2012;108:S111-S122.
• Pisto P, Santaniemi M, Turpeinen JP, Ukkola O, Kesäniemi YA. Adiponectin concentration in plasma is associated with muscle fiber size in healthy middle-aged men. Scand J Clin Lab Invest. 2012 Sep;72(5):395-402.
• Su MJ, Chen WP, Lo TY, Wu TS. Ionic mechanisms for the antiarrhythmic action of cinnamophilin in rat heart. J Biomed Sci. 1999;6: 376–386.
• Tokarska-Schlattner M, Epand RF, Meiler F, Zandomeneghi G, Neumann D, Widmer HR, Meier BH, Epand RM, Saks V, Wallimann T, Schlattner U. Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects. PLoS One. 2012;7(8):e43178. 
• Tuzcu M, Aslan A, Tuzcu Z, Yabas M, Bahcecioglu IH, Ozercan IH, Kucuk O, Sahin K. Tomato powder impedes the development of azoxymethane-induced colorectal cancer in rats through suppression of COX-2 expression via NF-κB and regulating Nrf2/HO-1 pathway. Mol Nutr Food Res. 2012 Aug 1.
• Whitlock KA, Kozicky L, Yee AJH, Ha C, Morris J, Field CJ, Bell RC, Ozga JA, Chan CB. Assessment of the mechanisms exerting glucose-lowering effects of dried peas in glucose-intolerant rats. British Journal of Nutrition. 2012;108:S91-S102. 
• Wu TS, Leu YL, Chan YY, Yua SM, Tenga CM, Sua JD. Lignans and an aromatic acid from Cinnamomum philippinense. Phytochemistry. June 1994;36(3):785–788
• Yu SM, Ko FN, Wu TS, Lee JY, Teng CM. Cinnamophilin, a novel thromboxane A2 receptor antagonist, isolated from Cinnamomum philippinense. Eur J Pharmacol. 1994; 256: 85–91.