Beyond Celiac: Study Sheds New Light on Obesogenic Effects of Gluten - Are PPARs & Bacteria Both Involved?

Cornflakes peanut butter cookies - guaranteed not gluten free ;-)

With Christmas Eve being over, and grandma's cookies, Christmas stollen, and all sorts of other stuff from the bakery in front of you (literally), Christmas Day may actually prove to be a way more "dangerous" than Christmas Eve - not just because of the total amount of calories, but also because of the low satiety effect of these sweet treats.

A recent paper by scientists from the Universidade Federal de Minas Gerais in Belo Horizonte in Brazil does now point to another reason you better give those bakery products a wide berth - not just, but especially with the energy overshoot on Christmas day: Gluten!

Study confirms for the first time what scientists and laymen alike have been speculating about

In what the scientists claim is the first well-controlled study of the effects of gluten intake on metabolic health in a non-celiac, but Western-style diet scenario, Fabíola Lacerda Pires Soares and her colleagues put two groups of C57BL/6 mice on identical, iso-caloric high fat (hypercaloric) diets that differed only in terms of the amount of gluten that was added to the chow (0% gluten vs. 4.5% gluten).

Interestingly, the gluten diet did not influence any of the usual suspects, like food intake, total fat-free mass, fecal lipids excretion, blood lipid profile, blood total protein and ectopic (liver and muscle) lipid concentration (if you look closely you will realize that the gluten-free group actually had higher TRIGs, although the difference did not reach statistical significance).

Figure 1: Usual suspects and closer look at the effects 8 weeks gluten supplemented vs. gluten-free diets had on serum markers of metabolic syndrome and visceral fat parameters (Soares. 2012)

The data in figure 1 (right) does yet also show that the gluten content of the diet did nevertheless have a significant impact on the total body mass, visceral fat mass, lipid content and most importantly the adipocyte size.

Figure 2: Absolute adipokine levels (left) and fasting glucose and insulin levels, as well as Homa-IR (Soares. 2012)

Add to that the blunted expression of the anti-inflammatory and anti-diabetic fat hormone adiponectin and the increased the >5x higher expression of leptin (figure 2). And mix that with the reduced expression of PPAR-alpha and gamma of which Soares et al. argue that they may well be the key factor in the detrimental modulatory effect the addition of gluten had on the visceral fat structure and the lowered expression of the fat liberating enzymes LPL and and HSL, as well as reduced levels of the fat burning proteins ACC and CPT-1 (figure 3).

Figure 3: PPAR-alpha, -gamma, LPL, HSL, ACC and CPT-1 expression compared to rodents on regular chow (left); crown like structures in stained slices from visceral fat, inflammatory markers TNF-alpha and IL-6 (Soares. 2012)

So, even if the initially mentioned blood markers (aka the usual suspects) would suggest that both the gluten-consuming and gluten-free rodents were similarly bad off, the profound difference in inflammatory markers within the adipose tissue and the presence of comparatively many necrotic and inflammatory adipocytes in the crown like structures stand in line with increases in HOMA-IR, fasting glucose and insulin and an already compromised glucose clearance which are well-known harbingers of the metabolic syndrome.

These observations do not simply shed a whole new light on a hitherto largely ignored contributer to the etiology of the metabolic syndrome, they do also show that one of the reasons it has not been identified before is an over-reliance on BMI, total fat mass and serum lipids in the early stages of diabesity.

Reardless of whether the gut microbiome is part of the mechanism by which gluten predisposes the development of metabolic syndrome. Eating more inulin- and beta-glucan rich foods like Jerusalem artichokes, agave, bananas, onion, steel cut oats, wild yams, yacon, etc. certainly won't hurt your efforts to get lean, stay lean and leave the role of the obese diabetic to the other (read more)

Bottom line: The study at hand provides a good reason to limit your intake of "healthy whole grains" and other gluten containing foods, regardless of whether you suffer from celiac or not. Whether the established detrimental effects of gluten on the integrity of the intestinal wall and the increased leakage of bacterially produced endotoxins from the highly unfavorably changes in the gut microbiome in response to the high fat diets (Hildebrandt. 2009) are part of, or even the primary cause of these observations still has to be elucidated. The same goes for strategies to counter the translocation of the endotoxins across the gut lining (cf. "Shedding some light on the leaky gut") and the dose response relationship between the total amount of gluten in your diet and its effects on your metabolism. With 7% of pure gluten, it goes without saying that you would basically have to live of wheat in order to get to anywhere similar amounts of gluten in the diet... that said: Is it possible that the effects occur only in the presence of the high fat diet? After all, this alone has been shown to favor a pro-inflammatory gut microbiome.

You see there are enough questions to be answered in 2013 and the SuppVersity is going to be the place you will read the respective answers first ;-)

References:

• Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009 Nov;137(5):1716-24.e1-2.
• Soares FL, de Oliveira Matoso R, Teixeira LG, Menezes Z, Pereira SS, Alves AC, Batista NV, de Faria AM, Cara DC, Ferreira AV, Alvarez-Leite JI. Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression. J Nutr Biochem. 2012 Dec 17.

Sucralose, Hazardous or Innocent? Part II: Appetite, Gut Health & Food Reward | Sucralose, Gluttony & Adiposity?

Plain mineral water is still the best thing to quench your thirst.

Today we are going to continue our thorough, educated reading of the recently published overview over the biological issues with sucrolase, a "popular" artificial sweetener most of you will probably know by its brand name Splenda. The focus of part I of this series was on the potential pro-diabetic effects of this agent that belongs to a class of molecules that has originally been hailed as a solution to the diabetes problem (it goes without saying that I am talking about artificial sweeteners here, right?). In a way we are thus only continuing the discussion, when we are trying to verify Schiffman's & Rother's argument that the consumption of sucralose is associated with an increase in obesity risk... or, put more simply that using sucralose is going to make you fat, not lean.

The good old "energy in" vs. "energy out" argument

As SuppVersity readers you are well aware that the oversimplified concept of an "energy balance" is fundamentally flawed. My recent post "Anorexia study suggests: Your body can easily reduce its resting metabolic rate by 10%" in the SuppVersity Facebook News is only one out of thousands of scientific papers you could quote to point out that replacing 420kcal of energy from pure sugar, i.e. three cans of regular coke, with its diet variety is not going to produce a net weight, let alone fat loss of 420g per week (suggested read: "Busting the 3,500kcal = 1lbs Weight Loss Myth!" | learn more).

This is part II of a multi-part series:

Sucralose, insulin, glucose, GLP-1

Appetite, Obesity & Gut Health

Cancer, Drug & Hormone Interact.

I know that Mark Sisson likes to says this, but this website is not written by a machine, but by a man who has the same "short" 24h days you have... basically, what I am trying to say is that I had to split this review of the review into a "trilogy" - and be honest, you wouldn't want an article thrice as long as this one, would you?

Thus being "in the know", you can only shake your head, when you read how Schiffman and Rother (ab-)use a recent study by Ruyter et al. (2012) to support the non-significant, not sufficiently differentiated data from epidemiological studies which inform us that obese people are more likely to consume artificial sweetened products than lean ones, to subliminally imply that artificial sweeteners would not help, in some cases even hinder weight loss.

"In an 18-mo trial with children, participants were randomly assigned to receive an 8-oz can per day of either a noncalorically sweetened or a sugarsweetened beverage that provided 104 kcal (de Ruyter et al., 2012). [...] The calorie consumption from these beverages was 46,627 kcal greater for children in the sugar-sweetened group than in the sucralose-sweetened group (5.8 × 77.3 × 104). In spite of this highly significant difference in calories consumed from the beverages, the total weight gain over this 18-mo study was only 1 kg greater for children in the sugar-sweetened group compared to sucralose group. No explanation was provided to account for the small difference in weight gain given the large difference in caloric consumption from the beverages." (Schiffman. 2013)

Despite the fact that Schiffman & Rother acknowledge that the scientists would not have been able to detect, if the children who consumed the sugar-sweetened beverages compensated by reducing their food intake, the reviewers fail to point out that neither this, nor the second "evidence" they cite, a 2-year study by Ebbeling et al. (2012), where Schiffman & Rother simply ignore the fact that the mere provision of diet sodas to the families of the adolescent subjects did reduce the weight gain in the active intervention period (1st year, see Figure 1, below), would confirm a negative real-world effect on body weight.

Figure 1: Change in body fat percentage (vs. basleline) of adolescents during the intervention & follow up period in the Ebbeling study (2012), of which the reviewers only cite the results of the follow up.

Let's be honest: If you actually take a look at the results from the Ebbeling study (Figure 1), you will have to concede that this study refutes the claim that artificial sweeteners make you fat. During the active treatment period, in the course of which the adolescent participants were...

• 

  "What Really Happens, When Nutrition Science Meets Real Life" | more

  ... supplied with noncaloric beverages (e.g., bottled water and “diet” beverages for the whole family) every 2 weeks, getting monthly motivational telephone calls with parents (30 minutes per call), 
• ... having three check-in visits with participants (20 minutes per visit), and 
• ... receiving written intervention messages with instructions to drink the delivered beverages and not to buy or drink sugar-sweetened beverages, were mailed to participants

...they do exactly what we originally expected them to do: They ameliorate the body fat gain in the adolescent subjects. In other words: As long as respective products are available, and dietary adherence is encourages, replacing regular sugar sweetened with artificial sweetened or unsweetened beverages can have a significant ameliorative effect on the body fat gains of adolescents - irrespective of the fact that they were obviously free to compensate with chocolate, cookies, etc..

Contemporary evidence from RCTs suggest either no, or beneficial effects

If you follow Schiffman's and Rother's lead and discard potential differences between sucrose and other sweeteners, acknowledge the fact that the results from previous rodent experiments have repeatedly failed to translate to human beings and take into account that this data is "inconsistent and conflicting" (Schiffman. 2013), anyways, you will be hard pressed to find arguments to support the claim that artificial sweeteners could hinder weight loss.

"No-Carb Foods, Artificial Sweeteners & The Cravings" | more

Potential mechanisms for the obesogenic effects: In a very detailed review Mattes & Popkin list a whole host of hypothesis ranging from the disproven stimulation of insulin and differences in the GLP-1 response, over osmotic effects and increase food palatability, up to the "Zero sugar, great, I'll have 10 instead of one of those cookies!" effect and the development of an extremely sweet tooth. What's important, though, is that none of this mechanisms is "supported by the available evidence, although some warrant further consideration" (Mattes. 2009).

In fact, the vast majority of RCTs clearly supports the assumption that non-nutritive sweeteners (NNS), artificial or not, promote weight loss and blunt weight (re-)gain (De la Hunty. 2006; Bellisle. 2007). The argument that these effects do satisfy the calories in vs. calories out hypothesis is pathetic, to say the least. Even a 100% controlled diet won't comply to an equation that is about as accurate as "1+2=343". We can thus register that:

1. There is ample evidence to support the beneficial effects of artificial sweeteners (including sucralose) as a tool during controlled dietary interventions.
2. There is insufficient evidence to support the claim that their regular consumption has a negative effect on body weight.

With respect to (2) we would even have to say that the limited amount of useful* evidence we have would rather suggest beneficial than detrimental effects (*a 'useful' study is not a study that tells me that obese individuals are more likely to consume artificially sweetened products than lean ones like the often cited epidemiological data). This is particularly true, for controlled interventions where sugar-sweetened beverages were replaced by their artificially sweetened counterparts.

The great unknown: Hunger, appetite and food reward

If data on the real-world effects of sucralose consumption on body weight gain is "scarce", consistent, experimentally verified hypotheses that would explain the potential underlying mechanism are quasi non-existent... or, I should clarify: They are still in their infancy. Against that background it's quite astonishing that more and more people appear to take it for granted that the consumption of artificially sweetened foods will mess with both, (a) your ability to control your energy intake and (b) the hedonistic response you derive from foods.

Table 1: Sweetness, dose to stimulate the sweet taste receptor (EC50; based on Matsuda. 2011) and correlation of sweetness and EC-50 value.

It goes without saying that there is no sucralose-specifc data out there, but the decrease in hypothalamic sweet taste receptor density I mentioned in the first installment of this series is something I'd expect to see in response to all artificial sweeteners that make it across the blood brain barrier (Note: Even Schiffman & Rother acknowledge that we do not know if they even do that!) - probably "sweetness" dependent,  by the way.  This would imply that sucralose would be the worst, cyclamate the least offender among the common artificial sweeteners in Table 1. With a sweetness that's 300x higher than that of sucrose, stevia would end up being the "(un?)happy medium".

Despite the fact that Schiffman & Rother don't really address this issue in their paper, I still want want to address the practical and thus relevant aspect of the various proposed theories for potential sweetener-induced increases in energy consumption.

Figure 2: Mean effective change in energy intake (%) in RCTs investigating the degree of energy compensation in response to the provision of artificial sweetened products (De la Hunty. 2006)

As the data from De La Hunty's 2006 meta-analysis of 32 study outcomes in Figure 2 clearly demonstrates, there is a statistically highly significant (p < 0.001) trend towards reduced energy consumption in the RCT [randomized controlled trial]. In that, the degree of compensation for the sudden energy reduction due to ingestion of calorically less dense, since artificially sweetened product ranged from statistically non-significant 18% to statistically highly significant 86% in trials such as Porikos et al. (1982), where 6 men lost and gained 0.8kg of body weight within 2x12 days in a metabolic ward on artificially sweetened and sucrose sweetened ad-libitum diets, respectively.

Non-nutritive sweetener (NNS) intake 1965-2004 (Mattes. 2009)

So, sweeteners can't ever make you hungry? I would not necessary subscribe to this idea. While the consumption of artificial sweetened foods as part of your regular diet, e.g. diet coke with your dinner, does not seem to be a problem, Mattes & Popkin (2009) rightly point out that "non-energy-yielding products may heighten appetite", when they are not "ingested in conjunction with other energy sources". So, if you are guzzling diet coke all day, this may very well trigger binge eating. With an ever increasing consumption of sweeteners from partially / totally artificially sweetened beverages (see table to the left), this could thus well be part of our obesity problem.

Just like the previously discussed (relatively short term) effects on insulin, GLP-1 and co, the #2 on the list of most frequently heard objections against the use of artificial sweeteners, i.e. dietary overcompensation, does thus appear to have little basis in fact. What we do not know, though, is whether the results will be identical for all types of sweeteners, or whether sucralose may be the toxic (this aspect will be covered in the next installment) or gut microbiome disrupting exception to the rule.

Sucralose induces changes in the gut microbiome

The last issue I want to address in this second installment of the "Sucralose, Hazardous or Innocent Trilogy" will thus revolve around the question, whether a modulatory effect of sucralose on the microbial composition of your gut could induce potential negative long-term effects that would not show up in the hitherto discussed RCTs.

Under the headline "Effect of Sucralose on the Number and Relative Proportions of Different Intestinal Bacterial Types", Schiffman & Rother argue that it has long been known that bacteria from the oral cavity and soil cannot use sucralose as a growth substrate. If the same was true for the bacteria in our guts the replacement of regular sugar with sucralose would thus starve our (beneficial) subtenants.

Table 2: Differences (%) in bacterial counts in feces of rodents on diets containing what in human terms would be ~14mg, 43mg, 71mg and 156mg of sucralose per day after 12 weeks treatment and 12 weeks into "recovery" (Abou-Donia. 2008)

Based on the fecal bacterial count of rodents on diets that would be equivalent to 14mg, 43mg, 71mg and 156mg of sucralose per day in human beings (see Table 2), Schiffman & Rother argue that chronic (12-week) ingestion of relatively low amounts of sucralose (a single can of Diet Crush Cream Soda, for example, has 42mg of sucralose) lead to highly significant reductions in the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria.

In view of the fact that Abou-Donia et al. (2008) observed the most significant losses in bifido- and lactobacillus strains, i.e. those strains that have repeatedly been implicated as the driving forces of the beneficial health effects of probiotic supplementation, this and not the previously discussed pro-diabesity effects should be the point where people start to freak out.

Table 4: Other sweeteners are preferred food for certain bacteria and may also alter the gut microbiome (Payne. 2012).

This is particularly true if you take into account that at least part of the beneficial effects of lactobacilli may be related to their ability to keep the number of enterobacteria, a large family of Gram-negative bacteria that includes both harmless symbionts, as well as a whole host of familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella, Proteus, Enterobacter, Serratia, and Citrobacter in check (Liévin-Le Moal. 2006) - exactly those bacteria, which produce the nasty lipo polysaccharides (LPS) that have been associated with inflammation and its downstream metabolic effects, such as obesity, diabetes, heart disease, gastrointestinal cancer etc. and, as the data in Table 2 tells you. Now, unfortunately, the these villains are all part only type of bacteria that was not significantly decimated by the sucralose challenge.

As Schiffman et al. point out these reductions are not, as Brusick et al. (2009) suggest simply a result of "normal variation". In fact, the probability to see a similar random reduction in bifidobacterial count occur "naturally"within 12 weeks would be 1/5000. It is thus more than just unlikely that the71.9%, 76%, and 77.7% reductions in bifidobacteria counts Abou-Donia et al. observed at dosages of 3.3, 5.5, and 11 mg/kg/d were coincidental.

Prebiotics, anyone? In view of the alleged neg. effects on your gut microbiome, you may feel inclined to increase your prebiotic intake. If that's the case, this top 10 list of food items with prebiotic fiber contents of up to 65% of total weight may help:

1. Chicory root - 65%
2. Jerusalem artichoke - 32%
3. Dandelion greens - 24%
4. Garlic - 18%
5. Leek - 12%
6. Onion - 9% 
7. Cooked Onion - 5% 
8. Asparagus - 5% 
9. Wheat bran - 5% 
10. Banana - 1% 

Remember: These are the "richest" not necessary the "best" sources ;-)

If there is reason to be concerned it's about your gut health and its downstream metabolic effects: In view of the important role of bacteroides for the health of the intestinal eco-system (Lee. 2013) and their persistent reduction even after the 12-week recovery period, the selective antibiotic activity of sucralose is as of now the by far most disconcerting negative health effect discussed in this series.

If the changes Abou-Donia et al. observed in their rodent studies were to be confirmed in human studies, where the subjects consumed a balanced whole foods diet with a high prebiotic content. The profound changes the researchers from the Duke University Medical Center report in their paper from September 2008 would be reason enough to revise my previous conclusions about a potential contribution of sucrose to the diabesity (=obesity + diabetes) epidemic.

In fact, a revision of the potential long(er) term downstream effects of sucralose on your metabolic health could be all the more indicated, if it turns out that the alleged toxic and endocrine-disrupting effects I will discuss in the next installment of this series turn out to be substantiated, as well.

Reference:

• Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health, Part A, 71(21), 1415-1429.
• Bellisle, F., & Drewnowski, A. (2007). Intense sweeteners, energy intake and the control of body weight. European Journal of Clinical Nutrition, 61(6), 691-700.
• De la Hunty, A., Gibson, S., & Ashwell, M. (2006). A review of the effectiveness of aspartame in helping with weight control. Nutrition Bulletin, 31(2), 115-128.
• de Ruyter, J. C., Olthof, M. R., Seidell, J. C., & Katan, M. B. (2012). A trial of sugar-free or sugar-sweetened beverages and body weight in children. New England Journal of Medicine, 367(15), 1397-1406.
• Ebbeling, C. B., Feldman, H. A., Chomitz, V. R., Antonelli, T. A., Gortmaker, S. L., Osganian, S. K., & Ludwig, D. S. (2012). A randomized trial of sugar-sweetened beverages and adolescent body weight. New England Journal of Medicine, 367(15), 1407-1416.
• Liévin-Le Moal, V., & Servin, A. L. (2006). The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota. Clinical Microbiology Reviews, 19(2), 315-337.
• Mattes, R. D. (1996). Dietary compensation by humans for supplemental energy provided as ethanol or carbohydrate in fluids. Physiology & Behavior, 59(1), 179-187.
• Mattes, R. D., & Popkin, B. M. (2009). Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. The American journal of clinical nutrition, 89(1), 1-14.
• Payne, A. N., Chassard, C., & Lacroix, C. (2012). Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity. Obesity Reviews, 13(9), 799-809.
• Porikos, K. P., Hesser, M. F., & Van Itallie, T. B. (1982). Caloric regulation in normal-weight men maintained on a palatable diet of concentional foods. Physiology & behavior, 29(2), 293-300.
• Schiffman, S. S., & Rother, K. I. (2013). Sucralose, A Synthetic Organochlorine Sweetener: Overview Of Biological Issues. Journal of Toxicology and Environmental Health, Part B, 16(7), 399-451. 

The Latest Gut Microbiome Modulators: Beneficial Effects of Cacao, Negative Effects of Acidic Water and Preliminary Evidence of the Negative Impact of Gluten & Whole Grains

Pancakes al cacao & your gut: Bad grains and good cacao?

There is an increasing amount of interesting scientific publications on the role of the gut microbiome in health and disease. Unfortunately, the evidence on what exactly influences the number and types of bacteria in our gut in a beneficial way and even what exactly a "beneficial way" actually is, is yet largely unknown.

In today's installment of the SuppVersity Short News, I am going to take a closer look at a selection of recent studies that may shed at least some light at the previously mentioned questions.

You can learn more about the gut & your health at the SuppVersity

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet

• Cacao as a gut microbiome modulator - The first study we're going to look at deals with cacao. Cacao and its effect on the gut microbiome. In said study, 3-week-old Wistar and Brown Norway rats were fed, for 4 weeks, either a standard diet or the following three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0·2 % polyphenols (from conventional defatted cocoa), and two others with 0·4 and 0·8 % polyphenols (from non-fermented cocoa, very rich in polyphenols).
  
  

  

  Only the regular theobromine containing cacao did also reduce the weight gain in the three-week study (Massot-Cladera. 2014).

  What the scientist found, when they analyzed the serum Ig concentrations, faecal IgA levels, microbiota composition and IgA-coating bacterial proportion at the end of the study and compared them to those at the beginning was a significant beneficial effect on the mucosal IgA levels and microbiota composition from all supplements. The 0.2 % cacao diet which contained a higher proportion of theobromine and fibre, however, had a more profound impact on the aforementioned parameters - in spite of the fact that there was less cacao in the diet. Obviously, the caffeine-like bitter alkaloid from cacao is contributes to the beneficial effects of cacao in a similar way as the polyphenols.
  
  As the body weight data in Figure 1 shows, the theobromine containing conventional cacao was also the only one that was able to reduce the diet induced weight gain in the rats. This could, but does not necessarily have to be related to the higher levels of Bacteroides, Bifidobacterium and Lactobacillus bacteria in the gut of the rodents that received the "cheap" conventional cacao.
• Acidic water triggers type I diabetes - probably by modulating the gut microbiome - No, I am not trying to advertise bicarbonate, here. I am just reporting the results of a recent study from the Medical University of South Carolina which found that a stain of mice that's particularly susceptible to type I diabetes developed insulitis and hyperglycemia rapidly, only when the mice were maintained on acidic pH water (AW).
  
  

  

  Suggested Article: "High Dietary Acid Load Doubles Risk of Type II Diabetes in Lean Individuals! Causative or Corollary? Plus: Are Grains, not Meats the Main Offenders in Our Diet?" | read more.

  The scientists also observed that this effect could be countered by fecal transplants and was obviously triggered by changes in the diversity of the gut flora that occurred, when the pH of drinking water was in the acidic range and were probably related to the proinflammatory cytokine response in the intestinal mucosa.
  
  As you as a SuppVersity reader know previous studies in humans have already shown that a "High Dietary Acid Load Doubles Risk of Type II Diabetes in Lean Individuals!" (read more) - Who knows, this could also be related to the effect on the gut microbiome!?
• Gluten and whole grains as modulators of the gut microbome - In two recent randomized cross-over trials, researchers from the University of Copenhagen determined the impact of dietary gluten or whole grains on the gut microbiome and host metabolic health.
  
  What the researchers found was what the recent backlash against gluten and "healthy" whole grains on the internet would suggest the already overweight "[p]articipants had slightly elevated fasting glucose levels and increased waist circumference" (Ibrügger. 2014).
  

  

  Table 1: Overview of the products used in the randomized controlled cross-over trials (Ibrügger. 2014)

  Whether that's related to the effects on the gut microbome is unfortunately something I can't tell you, yet. Why? Well, the currently available paper refers to a future publication that would outline the detailed results. All I can tell you now is that the study used the products listed in Table 1 and, more importantly, that it is its high statistical power, which, due to the large sample size and the crossover design, "allows detecting even small diffrences in the outcome variables" (Ibrügger. 2014).

Suppversity Suggested: "Stevia Kills Good Gut Bacteria - One Study Enough to Stop Using the Natural Sweetener? Probably Not in View of its Anti-Diabetes, Anti-LDL, Anti-Viral & Anti-Cancer Effects" | more

Bottom line: It's a pity that we still can't tell for sure what the "optimal" gut microbiome looks like. Moreover, the currently available scientific evidence suggests that what is considered "optimal" may well depend on your type of diet and / or your metabolic health.

Against that background the previously presented results offer nothing but a brief glimpse at what may become one of the hottest topics in obesity and diabetes prevention in the future. At the moment, though, all the results and any recommendations that are based on these results have to be considered preliminary. And this is also true for the gluten + whole grain study of which you will certainly read again, here at the SuppVersity | Comment on Facebook!

References:

• Ibrügger, S., et al. "Two Randomized Cross-Over Trials Assessing the Impact of Dietary Gluten or Wholegrain on the Gut Microbiome and Host Metabolic Health." J Clin Trials 4.178 (2014): 2167-0870.
• Massot-Cladera, Malen, et al. "Impact of cocoa polyphenol extracts on the immune system and microbiota in two strains of young rats." British Journal of Nutrition 112.12 (2014): 1944-1954.
• Sofi, M. Hanief, et al. "pH of drinking water influences the composition of gut microbiome and type 1 diabetes incidence." Diabetes 63.2 (2014): 632-644.

Weight Loss Supplements Exposed: Green Tea & Probiotics. Fat Loss, Energy Expenditure, Fat Oxidation, Sex & More

Yesterday at Starbucks: "I just ordered a bottle of probiotics!"

In view of the fact that all the feedback I got in response to the re-installment of the Short News was positive, I guess you won't mind if I use the chance and bundle the two soon-to-be-published weight loss studies from the British Journal of Nutrition into a Weight Loss Supplement Mini-Special of the SuppVersity Short News.

If you were actually sitting next to you, I would probably ask you, whether you'd prefer the good, or the bad news, first!? Well, I guess I'll start with the bad one, then: Green tea sucked - again!

ZERO effect of EGCG supplementation in overweight women

To examine the effects of green tea epigallocatechin-3-gallate (EGCG) on the changes in body composition (! not just weight), energy and substrate metabolism, cardiometabolic risk factors and liver function enzymes after an energy-restricted diet intervention in obese women, a group of researchers from the University of the Basque Country in Spain recruited a group of 83(!) obese (BMI 30-40 kg/m2) pre-menopausal women (Mielgo-Ayuso. 2013).

The women were randomly assigned to consume either 3x100 mg/d of EGCG or placebo (lactose) with each of their three main meals for 12 whole weeks. During those twelve weeks, all women followed a specifically designed low-energy mixed (55 % carbohydrates, 30 % lipids and 15 % proteins) diet that provided ca. 600 kcal/day energy less than the women would need to maintain their body weight. The energy content and macronutrient composition of diets were designed to achieve a weight loss of 0.5 to 1 kg per week, as it was observed by Davis et al. (2006) and Bantle et al. (2008) on very similar regimen. As the scientists point out, the "dietary instructions were reinforced weekly by a dietitian" (Mielgo-Ayuso), to optimise compliance.

Figure 1: Changes in body composition, energy expenditure and fat oxidation, left; changes in glucose, cholesterol metabolism and inflammation, right (Mielgo-Ayuso. 2013)

I am not sure how compliant the participants actually were, but in view of the fact that the women were advised not to change their physical activity habits during the energy restriction program, the relatively meager and statistically non-significant changes in body weight (-0·3 kg, p > 0.05) and fat mass (-0·7 kg, p > 0.05) are probably not really surprising. It is nice to see, though, that the women lost more fat than total mass - muscle loss was thus not an issue for the ladies.

What was not to be expected, though, - at least if you believe a single word of the hype about green tea supplements - were the non-existent effects of the purported weight loss supplement on  energy expenditure, fat metabolism, HOMA-IR (insulin sensitivity), total cholesterol, LDL-cholesterol, or triglycerides. In fact, the only good thing about the whole EGCG intervention was that the recently observed negative effects on the liver did not occur, either.

SIGNIFICANT Effect W/ 16 Million CFU of Nestlé's Lactobacillus rhamnosus strain

Want to check out the patent?

Despite the fact that the overall results are much more exciting than those in the previously discussed green tea study, I'd advise you to keep calm. We are after all dealing with another Nestlé study on a patented strain of Lactobacillus rhamnosus (LPR), i.e. "CGMCC1.3724" (date patented: 2012-05-10; #20120114622), and cannot tell how many never published negative study results the Nestlé guys had to dispose of, before Marina Sanchez et al. finally produced study results that pleased the marketing division of this multinational corporation.

What? Ok, ok... let's get back to the facts: The scientists from the Laval University and the Nestlé Research Center randomized a group of one-hundred fifty-three 18 to 55 year-old obese men and women to receive either a placebo or the said LPR formulation with 1·6 × 10⁸ colony-forming units of LPR and additional oligofructose and inulin per cap for a total of 24 weeks.

In the course of the first 12 weeks (phase 1), each participant received a personalised diet plan that would have him or her consume 500 kcal/d less than he or she'd need for weight maintenance (just as an aside, that's 100kcal more than for the subjects in the green teas study). During phase 2, each participant received a personalised diet plan without energy restriction. The good thing, the resting energy expenditure (REE) was actually measured: after a 12 h overnight fast in subjects having had rested for at least 15 min in a standardised supine position. This procedure was repeated thrice: (1) At baseline, (2) after the weight-loss and (3) after the second phase weight-maintenance periods using indirect calorimetry.

Figure 2: Changes in body composition (all data in kg) in men (left, blue) and women (right, orange) after weight loss (ΔW12) and weight maintenance (ΔW24) phase (Sanchez. 2013)

The data in figure 2 confirms what the abstract says: "The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks, mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered."

Figure 3: Changes in metabolic parameters, i.e. energy intake (kcal/day), resting energy expenditure (REE, kcal/day) and respiratory quotient (RQ, remember: low RQ = high fat, low carb oxidation) after 12 and 24 weeks (Sanchez. 2013)

It does yet also confirm - and that there was a significant treatment × sex interaction, observed with the women in the treatment group losing significantly more weight than those in the placebo group (P= 0·02). More importantly, though...

"[...w]omen in the LPR group continued to lose body weight and fat mass during the weight-maintenance period, whereas opposite changes were observed in the placebo group."

For the unlucky men, on the other hand, the (unquestionably expensive) supplement didn't do sh*t: Their "changes in body weight and fat mass during the weight-maintenance period were similar" irrespective of whether they received the placebo or the active treatment.

Whether this was the reason or a consequence of the fact that the the men didn't show similar significant reductions in circulating leptin, as the women is questionable. Based on the fact that the relative abundance of bacteria of the Lachnospiraceae family in faeces increase only in women, we do yet have to assume that the missing reduction in leptin, as well as the absence of the significant body fat reductions, the researchers observed in their female subjects was simply a results of ...

• under-dosing - the same the 1·6 × 10⁸ colony-forming units of LPR that was sufficient for the average woman (body weight ~89kg) could have been too low for the guys (body weight ~104.3kg) 
• dietary interference - there could have been something in the diets of the guys that ruined the effects of the supplementation (lactobacilli are not exactly friends of meats and we all know that men love their meat ;-)
• different baseline gut microbiome - it goes without saying that you cannot place a group of rabbits in forest full of predators and expect them to survive; similarly the LPR spores may have come off second in the guts of the men, because they have a less "LPR-friendly" baseline colinization
• fundamental sex differences - at the moment I am not sure what the underlying reasons could be, but it's not impossible that hormonal difference could have played a role as well

I am pretty sure that I could come up with a whole host of additional, increasingly bizarre ad-hoc explanations for the null-effect Marina Sanchez and her colleagues from the Laval University and the  Nestlé Research Center in Lausanne observed in their male study but would rather conclude this news-item with the scientists own funky, but not unlikely explanation: Men are simply too good at dieting!

True: Women have a harder time losing weight even with high protein | more

As the authors point out, we know from previous trials (and corresponding SuppVersity posts, read more) that men are generally more prone to respond to a negative-energy balance intervention than women - and that's true irrespective of whether it is an exercise-training programme (Tremblay. 1984), a diet– exercise programme (Doucet. 1999), or a session of exercise and of mental work (Pérusse-Lachance. 2013). Plus, if you look at the data in figure 2, you'll see that this is actualy "concordant with the results of the present study that shows higher weight loss in men in the placebo group than in the women". Sanchez et al. do now believe that the high baseline success "abolished this difference" (Sanchez. 2013).

In view of the fact that there was a difference in a single low-abundance taxonomic group  (Prevotellaceae) between the baseline gut microbiome of the male and female study participants, I would still not exclude that the different baseline gut microbiomes could at least have added to the 'effect abolishing effect' of the sex-specific ease of weight loss in men. I mean, why wouldn't the feces of the men show an increase in lactobacillus spores, if the supplement worked?

Bottom line: Today's installment of the short news is very characteristic of the dilemma with weight loss supplements. We are just realizing that the classic thermogenic 'rodent fat burner' don't really work in humans. Against that background the rise of supplements that target the gut microbiome and exert much more complex body recompositioning effects comes in the nick of time.  Unfortunately, our understanding of the complex interactions between the gut microbiome and our immune system in the context of the emerging science of immunonometabolism is so incomplete (Mathis. 2011) that we are more or less groping in the dark, whenever we supplement subjects, patients or even ourselves with allegedly healthful bacteria.

All alleged benefits aside,  "specificity", the 2nd Principle of Sensible Supplementation, should keep you away from the next best GNC or online supplement store. The two studies at hand do after all not warrant the use of either green tea or lactobacillus supplements as weight loss aids in lean, healthy and active  men or women.

Accordingly, the observation that green tea supplements won't help sedentary over-weight women to lose weight appears to be much more reliable than the allegedly impressive weight loss effects of the probiotic during the "maintenance phase" of the Sanchez study.

We must however not forget the respective constraints of the research design and irresponsibly over-interpret the results of the EGCG study to (a) the potential benefits of regular 'whole' tea consumption in the average, non-obese individual (Wu. 2003) or (b) visceral fat loss in diet + exercise interventions in obese individuals (cf. Maki. 2009). Similarly, the fact that obese women will lose weight on a LPR supplemented maintenance diet is very unlikely going to translate to lean, athletic folks like you and me. According to the 2nd Principle of Sensible Supplementation, which is "specificity" (learn them all), I don't see you or me heading over to the next best online shop to buy LPR or EGCG supplements - irrespective of the promising results of the Sanchez trial.

References: 

• Bantle JP, Wylie-Rosett J, Albright AL,et al.(2008) Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care31, Suppl. 1, S61– S78.
• Davis NJ, Emerenini A & Wylie-Rosett J (2006) Obesity management: physician practice patterns and patient preference. Diabetes Educ32, 557 – 561. 
• Maki, K. C., Reeves, M. S., Farmer, M., Yasunaga, K., Matsuo, N., Katsuragi, Y., ... & Cartwright, Y. (2009). Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. The Journal of nutrition, 139(2), 264-270.
• Mathis, D., & Shoelson, S. E. (2011). Immunometabolism: an emerging frontier. Nature Reviews Immunology, 11(2), 81-83.
• Mielgo-Ayuso J, Barrenechea L, Alcorta P, Larrarte E, Margareto J & Labayen I (2013). Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial. British Journal of Nutrition, available on CJO2013. 
• Tremblay, A., Despres, J. P., Leblanc, C., & Bouchard, C. (1984). Sex dimorphism in fat loss in response to exercise-training. Journal of obesity and weight regulation.
• Wu, C.-H., Lu, F.-H., Chang, C.-S., Chang, T.-C., Wang, R.-H. and Chang, C.-J. (2003), Relationship among Habitual Tea Consumption, Percent Body Fat, and Body Fat Distribution. Obesity Research, 11: 1088–1095.

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.

Inulin & Beta Glucan Reduce Body Fat Gain By -50% & -33%! Both Have Similar Effects on the Gut Microbiome, But Only Inulin Appears to Be More Than An Appetite Suppressant

What do these Jerusalem artichokes, agave, bananas, burdock, camas, chicory, coneflower, costus, dandelion, elecampane, garlic,jicama, Leopard's-bane, mugwort, onion, wild yams, yacon and a whole host of other foods have in common? Right! They contain inulin. Whether you will be able to get a whopping amount of 10% inulin in your diet w/out the use of supplements or "enriched" foods, is yet as questionable as how beneficial this actually is for friends of physical culture.

The gut microbiome is not just one of the hottest topics in the (health-)blogosphere, it is also a subject of ongoing research. Research, however, that is, if we are honest, still very much in its infancy. As impressive as the results from the latest studies into the metabolic downstream effects of the administration of fermentable fiber to rodents may be and as obvious as their relation to certain changes in the gut microbiome of the animals may appear - in the end, our understanding of the underlying mechanisms does not allow any reliable prognoses like "double the amount of lactobacilli and you will eventually be able to lose that pouch of body fat you've been carrying around for years now". And yet, if the results from the latest rodent experiments at the Imperial College in London, could be reproduced in humans, I can already foresee that both, the consumption and use of the foods I listed in the caption of the image to the right, as well as related products, extracts and supplements, which contain more or less significant amounts of the naturally occurring polysaccharides, we usually refer to as inulin, will increase in the months and years to come.

Fermentable fiber and the gut-brain-axes: The key to lifelong leanness?

If this is not your first visit to the SuppVersity, you will certainly be aware that the idea of a magic pill (or fiber) that will allow you to eat whatever, whenever and in whichever amounts without having to cope with the metabolic consequences is illusive. When the addition of 10% inulin (or beta glucan) to the diets of 36 male C57BL/6 mice had an "anti-obesogenic" effect, this does not mean that the poor critters who were kept on a hypercaloric high fat (41.8%) diet for 8 weeks did not get obese. What it does mean, though, is that the addition of 10% fermentable (=being food for certain gut bacteria) fiber in the form of

*the producers of these products did not fund or support the study (at least the scientists don't mention that in the respective disclosure ;-)

• inulin from Synergy(TM)*, a fructan based preparation containing both long and short chain
  fructooligosaccharides, or
• beta-glucan from Glucagel(TM)* a highly rich (,80%) barley derived b-glucan preparation

to their otherwise iso-caloric diet (the HFD control contained cellulose) was not without helped to mitigate the negative effects of this diet - a fact the majority of you, of whom I would expect that they are not on a fast-food diet should keep in mind, before they head over to their favorite online supplement vendor and type "Synergy inulin" into the search box.

Figure 1: Effect of addition of 10% fermentable fiber as inulin or beta glucan to the high fat diet of male mice on cumulative weight gain (left), body composition and fatness (middle) and food intake (right) over the course of 8 weeks (data adapted from Arora. 2012)

In spite of that, the results are simply too impressive not to think about their implications in otherwise healthy and even more so previously obese individuals. This is particularly true, because the same microbial changes about which the authors write in a previously published paper from May 2012 that the ...

"[...] increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA) [went hand in hand with] increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In [inulin] supplementation" (Anastasovska. 2012)

do not (and this is a result of the researchers very latest experiments) simply blunt the rodents appetite. If that was the case, the rodents that received the beta glucan supplemented chow and consumed 12% less energy should have had the most favorable body composition. A cursory glance at figure 1 will yet tell you that this was not the case, though.

Inulin beats beta glucan when it comes to body fat reduction / repression

If we take a closer look a the differential effects of inulin and beta glucan, there yet only one figure that really sticks out and that's the accumulation of fat within the musculature of the animals. The "beautiful marbling" people are looking for in their steaks, however, usually is a harbinger of impeding or even existing skeletal muscle insulin resistance. A muscle fat content above the high fat control (it's certainly a weakness that we don't have a "real" control group on standard rodent chow, here) as Arora et al. observed it in the tissue samples of the beta glucan group, does thus tell you something about its potential usefulness, or rather uselessness of this specific type of fermentable fiber.

Figure 2: Effects of the different types of fermentable fiber on cecal microflora groups (figures are in scientific notation, this means "1E+6" equals 1mio, "1E+9" would be 1 billion etc.; data based on Arora. 2012)

In conjunction with the information about the corresponding changes in the gut microbiome (see figure 2), which appear virtually identical in both groups (specifically the extreme increasesin in both Bifidobacteria (BIF) and Lactobacillius (LAB) really stick out), this does however suggest that the modulatory effect on the composition of the gut flora, or at least the part of it the scientists evaluated in the study at hand, cannot be the only driving force behind the beneficial metabolic effects of inulin.

Inulin or beta glucan? This is not a question... 

While the latter, i.e. inulin, which has by the way been found to directly suppress lipogenesis in a 2011 study by Belgian scientists in a similar HFD rodent model (Dewulf. 2011), appears to be promising for everyone, regardless of whether he or she is poisoning him- or herself with the standard American diet (which is, with its high fat and high carbohydrate content de facto an identical twin of the so-called "high fat diet" in rodent studies), the ingestion of larger amounts of the former, i.e. beta glucan, does at least appear questionable.

If you want to use inulin to your metabolic advantage, you better make sure you get your self a more comfortable place to answer the call of nature - it could call thrice as often! Moreover, large amounts of inulin and other fermentable fiber can induce gastrointestinal distress-

The question is therefore not so much whether it's worth supplementing (it's certainly worth to incorporate some of the initially mentioned foods into your diet, as most of them contain a whole list of other advantageous micronutrients) with inulin or beta glucan - the answer would obviously be inulin - but rather whether it's worth adding larger amounts of inulin to an already healthy diet. And while we cannot answer this question based on the results of the previously cited rodent studies, we could argue that Marwa Zenhom and her colleagues from the Christian Albrecht University in Kiel have already supplied relevant evidence that this would be the case (Zenhom. 2011). After all, the German researchers have been able to show that the PPAR-gamma related anti-inflammatory effects (significant reductions IL-12 secretion in Caco-2 cells and gene expression of IL-12p35, IL-8, and TNFa as well as NF-kB) of oligosaccharides are not (exclusively) brought about by their effects on the gut microbiome, because bacteria simply were not present in their in-vitro study with human Caco-2 cells (cells from the gut lining). Bassaganya-Riera et al. even argue that this effect could be beneficial for IBS patients (Bassaganya-Riera. 2011).

Whether having 10% of your diet in form of inulin, or to make this more conceivable, having 1 tablespoon of plain inulin for every 9 tablespoons of whatever else you eat is either feasible or reasonable, is a whole different story (to put that into perspective: The average inulin intake of Westerners is 1-10g per day (van Loo. 1995). Even 10g would yet only be enough if you ate only 100g of food within 24h!)... and I must forewarn you, if you go by the fecal volume of the mice in the Arora study, it is possible that you will spend >3x more time on the toilette than usual ;-)

References:

• Arora T, Loo RL, Anastasovska J, Gibson GR, Tuohy KM, Sharma RK, Swann JR, Deaville ER, Sleeth ML, Thomas EL, Holmes E, Bell JD, Frost G. Differential effects of two fermentable carbohydrates on central appetite regulation and body composition. PLoS One. 2012;7(8):e43263.
• Anastasovska J, Arora T, Sanchez Canon GJ, Parkinson JR, Touhy K, Gibson GR, Nadkarni NA, So PW, Goldstone AP, Thomas EL, Hankir MK, Van Loo J, Modi N, Bell JD, Frost G. Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment. Obesity (Silver Spring). 2012 May;20(5):1016-23.
• Astegiano M, Pellicano R, Terzi E, Simondi D, Rizzetto M. Treatment of irritable bowel syndrome. A case control experience. Minerva Gastroenterol Dietol. 2006 Dec;52(4):359-63.
• Bassaganya-Riera J, DiGuardo M, Viladomiu M, de Horna A, Sanchez S, Einerhand AW, Sanders L, Hontecillas R. Soluble fibers and resistant starch ameliorate disease activity in interleukin-10-deficient mice with inflammatory bowel disease. J Nutr. 2011 Jul;141(7):1318-25.
• Dewulf EM, Cani PD, Neyrinck AM, Possemiers S, Van Holle A, Muccioli GG, Deldicque L, Bindels LB, Pachikian BD, Sohet FM, Mignolet E, Francaux M, Larondelle Y, Delzenne NM. Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J Nutr Biochem. 2011 Aug;22(8):712-22.  
• van Loo J, Coussement P, de Leenheer L, Hoebregs H, Smits G. On the presence of inulin and oligofructose as natural ingredients in the western diet. Crit Rev Food Sci Nutr. 1995 Nov;35(6):525-52.
• Zenhom M, Hyder A, de Vrese M, Heller KJ, Roeder T, Schrezenmeir J. Prebiotic oligosaccharides reduce proinflammatory cytokines in intestinal Caco-2 cells via activation of PPARγ and peptidoglycan recognition protein 3. J Nutr. 2011 May;141(5):971-7.