Wednesday, October 10, 2012

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 ;-)

  • 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.