Gluten Research Update: Cesarean Section, Breast Feeding, Noocebo Effects and the ‘Right’ & ‘Wrong’ Bacterial ‘Poop’

As read on the SV Facebook: Baking makes gluten resilient to digestion, the presence of protein does the opposite. The food matrix makes the difference.

In view of the fact that "gluten" is or isn't (literally) in everyone's mouth or tummy, I thought that it may make sense to keep you up-to-date on the latest interesting research in the area of non-celiac gluten sensitivity and celiac disease.

Don't worry I am not going to bother you with the typical Internet bogus about how cancer, obesity and everything else we are or are not suffering from (yet) is triggered by gluten. What I will do, though, is to summarize and discuss the results of two recent studies and one review on the connection between our microbiome and our very individual susceptibility to gluten-related health problems

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

Fiber for Female Fat Loss

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

Is Gluten Intolerance Real?

• Celiac disease and non-celiac gluten sensitivity may be all about the microbiome and begin at the very moment you're born via cesarean section and worsen when you're not breastfed - In a soon-to-be-published review in Nutrients Cenit et al. try to elucidate whether gluten intolerance and celiac disease are consequences or triggers of significant imbalances in the bacterial composition of the human microbiome and how one or the other may eventually come about..
  
  As the authors point out, there are in fact studies which suggest that the early colonization of the infant’s gut in conjunction with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of our kids' oral tolerance to gluten.
  

  

  Figure 1: Proposed model for celiac disease (CD) pathogenesis. Specific host genetic makeup and environmental factors could promote the colonization of pathobionts and reduce symbionts, thus leading to dysbiosis. Dysbiosis may contribute to disrupting the immune homeostasis and gut integrity, thereby favoring CD onset and aggravating the pathogenesis (Cenit. 2015).

  In that, the early colonization of the intestinal tract is of particular importance, because it programs a normal or abnormal immune reaction to gluten (and other potential allergens). It is thus no wonder that celiac disease and a whole host of other autoimmune diseases have been linked to a lack of, or an improper early colonization of the intestinal tract and the consequential misprogramming of the immune cells. In that, it has been suggested that the resulting dysbiosis may affect autoimmunity by altering the balance between tolerogenic and inflammatory members of the microbiota and, therefore, the host immune response.
  
  Needless to say that the increased risk of autoimmune diseases is a standalone problem. It is after all not a mere reaction to the bacteria, but a bacterially induced phenomenon that involves the epigentic reprogramming of a whole host of genes. This process is however (unfortunately) so complex that we haven't yet fully understood the individual bacteria-gene and gene-gene interactions. Everyone, who tells you otherwise is lying - probably to sell his snake oil or snake oilish lifestyle advise.
  

  

  Figure 2: While there's one outlier, 3/4 studies on the effects of breastfeeding when the first gluten containing foods are introduced show significantly reduced risks of developing celiac disease (Akobeng. 2006).

  Among the few things we do know, though, is that breastfeeding and the way it promotes the early colonization of the gut with Bifidobacterium spp. is associated with a reduced risk of gluten intolerance. This is particularly true, if gluten containing foods are introduced while the kids are still breastfed (-52% according to a meta-analysis by Akobeng et al. 2006).

Breast milk contains a gliadin specific anti-body - What does that mean? Özkan et al. were the first to describe the presence of gliadin-specific IgA antibodies in breast milk (Özkan. 2000). The presence of significant amounts of this anti-body in the breast-milk (and even more in the colostrum) of 105 healthy mothers (aged 17 – 36 years) is generally understood to be one of the potential pathways by which breast milk and colostrum can protect children from celiac disease by educating the immature immune system of newborn children.

• The fact that these benefits do not apply for every breastfed child may be explained by (epi-)genetic polymorphisms of the mother, such as the altered concentration of several immune markers that have been observed by several researchers in the breast milk of mothers with celiac disease (Olivares. 2014). If that's in fact the case, it's hardly astonishing that the number of celiac patients began to rise when the use of formula peaked and is exploding now that more and more women with celiac disease (or non-celiac gluten sensitivity) are feeding their children with "non-protective" breast milk. We must be careful, though, not to jump to conclusions. There are, after all, as Cenit et al. point out "no robust prospective studies revealing how differences in breast milk composition and intestinal microbiota acquisition and evolution early in life might ultimately protect or contribute to CD onset" (Cenit. 2015).
  
  A similar healthy skepticism is necessary with respect to the link of cesarean sections and an increased susceptibility to gluten sensitivity (Dominguez-Bello. 2010). While it would appear logical to assume that the lack of exposure to the vaginal microbiome may contribute to the previously mentioned misprogramming of the immune system, it would be overtly simplistic to assume that gluten wouldn't be a problem if we were all breastfed and born the natural way.
  

  

  Figure 3: Increases in risk of full-blown celiac, intestinal inflamation and the presence of markers of celiac disease in the blood in subjects with previous exposure to antibiotics; in all fairness it must be said that the risk increase decreased when individuals who were exposed within the last 24m were excluded - even then the reduced 30% increase was statistically significant and practically relevant, though (Mårild. 2013)

  In conjunction with the indisputable link between the (early) use of antibiotics (Mårild. 2013 | see Figure 3) and the first successful efforts to ameliorate the chronic inflammation in celiac guts with prebiotics, there is yet little doubt that the "right" microbial make-up may be what distinguishes celiacs from patients with non-celiac gluten insensitivity and the still large number of people who don't appear to react to gluten at all.
• Study in healthy subjects, celiacs and their relatives suggests that the way your bacteria metabolize gluten may make you sick - From the first study, or rather review, I've analyzed in this feature article we've already learned that the inability to digest or handle gluten may be transmitted via certain immune factors in the breast milk from mother to child. It is thus particularly interesting that scientists from the Universidad de Léon in Spain who compared the stool of sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten found that significant differences in how celiac disease patients metabolized gluten.

Good news for celiacs: With the increasing awareness of celiac disease and gluten intolerance and the ever-increasing market shares of gluten-free products, it has become relatively easy to eat gluten-free, these days. Against that background it is all the more important that a recent study shows remission rates of 37% and general improvements in more than 50% of the patients in a recent study investigating the efficacy of gluten-free diets in celiacs over a four-year period (Newnham. 2015). The only potentially "bad" news is that all subjects gained significant amounts of body fat - specifically in the first year. The lean body mass indices, which did also improve, on the other hand, improved only very slowly and irrespective of status at diagnosis.

• 

  Table 1: Cultivable bacteria involved in gluten metabolism isolated from faeces of healthy subjects, active coeliac disease patients and firstdegree relatives (Caminaro. 2015).

  In contrast to healthy volunteers, their feces showed a significantly higher glutenasic activity (FGA), tryptic activity (FTA), SCFA, but lower levels of faecal gluten. That's interesting, yet counter-intuitive. After all, we've previously thought that one of the main problems of celiac disease and non-celiac gluten sensitivity is that the proteins are not broken down. Rather than that the results of the study at hand suggest that celiacs harbour bacteria that generate immunogenic peptides or pro-inflammatory metabolites which are the actual triggers of the problem (otherwise they'd have to poo out at least as much gluten as the other subjects on the gluten-free diets).
  
  Needless to say that this result does, once more, point toward fecal transplants or prebiotics as potential future treatment options celiac disease and non-celiac gluten sensitivity... with the only problem being: We don't know yet which bacteria we want to support and which to annihilate to solve the problem. If you look at the data in Table 1, though, killing the Clostridium and promoting the Lactobacillus population could be a first step to reinstalling a less celiac-prone gut microbiome.
• More 60% of non-celiac gluten patients don't react to gluten in randomized clinical study - That's certainly an impressive number Zanini et al. report in their latest paper in Alimentary Pharmacology and Therapeutics (Zanani. 2015).
  
  

  

  Let's hope aspergillus niger does not produce the wrong proteins when breaking down gluten otherwise it would make NCGS worse not better. Thus, further studies are needed. 

  In the corresponding study the researchers studied 35 non-CD subjects (31 females) that were on a gluten-free diet (GFD), in a double-blind challenge study. Participants were randomised to receive either gluten-containing flour or gluten-free flour for 10 days, followed by a 2-week washout period and were then crossed over. The main outcome measure was their ability to identify which flour contained gluten. Secondary outcome measures of the study from the University and Spedali Civili of Brescia in Italy were based upon Gastrointestinal Symptoms Rating Scale (GSRS) scores (criteria & results see Figure 4).
  
  In contrast to what the Internet experts are trying to make you believe, only 12 and thus hardly more than 34% of the allegedly highly gluten-intolerant patients were able to tell when they were fed gluten-containing flour based on increases in pain, reflux, indigestion, diarrhoea, and constipation.
  

  

  Figure 4: Increased severity of symptoms according to whether subjects were able to distinguish whether they were fed a gluten-containing or gluten-free diet (Zanani. 2015).

  Seventeen participants (49%), on the other hand, swore black and blue that they had been fed the gluten-containing flour when they were on the gluten-free diet (and if you look at the data in Figure 4, they even felt worse than those who were actually sensitive ;-).
  
  Now, what's most intriguing about this is that the study proves that there's a non-negligible noocebo effect involved, when it comes to non-celiac gluten sensitivity. One that's powerful enough to have people experience real increases in pain, reflux, indigestion, diarrhoea, and constipation... that tells you something about how infections reading too much bogus on the internet is, right?

Is Noneliac Gluten Sensitivity Legit? A Recently Published Review of the Latest Scientific Evidence on NCGS by Alex Leaf (Guestpost) May Help You Decide Whether you Even Want to Do the Painstaking Test | more

Bottom line: By including yet another study that puts a huge question mark behind the allegedly ever-increasing prevalence of non-celiac gluten intolerance into this write-up I am not trying to suggest that this pathogenesis does not exist. I am just trying to remind you that there is good evidence that it can also be triggered by the mere assumption that you have NCGS.

With that being said, the actual topic of this feature article is not the noocebo effect of the aggressive gluten-free propaganda, but rather the evidence of the existence of a physiological link between "dysbiosis" (in the broadest sense), the subsequent mal-metabolism of gluten by the "wrong" bacteria in your gut and the occurence of gluten sensitivity and full-blown celiac disease.

As bad as this may sound, the potential existence of this link between the gut microbiome and gluten sensitivity is actually good news: If the influence of your current gut bugs is in fact as huge as some of the scientists speculate, it should be possible to ameliorate, if not annihilate, the symptoms by reinstalling a "corrected" gut microbiome that helps celiacs and individuals with non-celiac gluten sensitivity metabolize gluten "correctly". This in turn could eventually even reverse the epigenetic changes that are causally involved in the inflammatory immune response to gluten and thus alleviate at least the nasty problems that occur if celiacs consume really small amounts of gluten incidentally. Whether it will fully reverse celiac disease, though, appears more than just questionable to me | Comment on Facebook!

References:

• Akobeng, Anthony K., et al. "Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies." Archives of disease in childhood 91.1 (2006): 39-43.
• Caminero, et al. "Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives." British Journal of Nutrition (2015): Ahead of print.
• Dominguez-Bello, Maria G., et al. "Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns." Proceedings of the National Academy of Sciences 107.26 (2010): 11971-11975.
• Mårild, Karl, et al. "Antibiotic exposure and the development of coeliac disease: a nationwide case–control study." BMC gastroenterology 13.1 (2013): 109.
• Newnham, Evan D., et al. "Adherence to the gluten‐free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A five‐year longitudinal study from diagnosis." Journal of gastroenterology and hepatology (2015).
• Olivares, Marta, et al. "Human milk composition differs in healthy mothers and mothers with celiac disease." European journal of nutrition 54.1 (2014): 119-128.
• Özkan, T., T. Özeke, and A. Meral. "Gliadin-specific IgA antibodies in breast milk." Journal of international medical research 28.5 (2000): 234-240.
• Zanetti, et al. "Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity." Alimentary Pharmacology and Therapeutics (2015): Ahead of print.

Anti-Microbial Effects of Artificial Sweeteners in Humans - 2/3rds of a Can of Diet Coke May Have a Sign. Effect on the Gut Microbiome, but the Relevance is Questionable

2/3 of this can may suffice to make a difference. Whether this difference is (a) relevant or (b) irrelevant is yet as questionable as whether the changes the scientists observed will (i) have a negative (ii) a positive or (iii) no effect.

As a SuppVersity user you know that the whole craze about aspartam and sucralose is overblown. You will also know that any potential "pro-insulinogenic" effects occurred only in less than a handful of human studies. If they did, though, they occurred in response to the ingestion of artificial sweeteners and glucose or other insulinogenic carbohydrate sources (learn more). Against that background it's also not surprising that in clinical trials vs. observational bogus, artificial sweeteners have been shown to help people with weight problems lose body fat (learn more).

The one thing about the myth of the bad sweetener that has yet not been completely debunked, though, revolves around their negative effects on the human gut microbiome.

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

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You will remember from my previous post on this topic that - as (unfortunately) usual - all empirically valid data we have is based on rodent trials. In our mammalian cousins, the consumption of artificially sweetened products on top of an obesogenic diet has in fact been shown to have an additional effect on the modulation of the gut bacteria that appears to make turn an already "bad" diet into a nightmare (learn more). It is yet still very questionable, which part of the research can be translated to humans and to which subgroup of the population this would apply. Even if we assume a 1:1 translation from rodent to human, we would after all have to exclude most of you, because none of you will be consuming a hypercaloric, hyper-processed high fat + high carbohydrate diet (at least that's what I'd hope).

If we trust the results of a soon-to-be-published observational study from the George Mason University, though, our gut microbiomes could be in danger - although no one knows for sure.

Sweeteners, pre- and probiotics are not the only foods / supplements that can have a major impact on the bacterial ecosystem in your gut. Only recently scientists have found that the ergogenic effects of glutamine may also be mediated by the gut | more

Why do you have to care about the microbes in your gut? The good guys produce vitamins like vitamin K for you, they digest resistant starches and produce short-chain fatty acids which in are have beneficial effects on your intestine, your satiety and directly or indirectly even on your glucose control. There is unfortunately no way to really tell the good from the bad guys. At the moment, it would seem as if the lactobacilli and bifidobacteria would be the ones you want to have most. On the other hand, the number of bacteria cells in our gut surpasses the number of cells in our body and form a very complex and vurnerable ecosystem, where too much of one and too little of another species may be more of a problem than "having the wrong bacteria". For now, however, supplements containing various strains of the two aforementioned types of bacteria does in fact seem to be the most promising, but certainly not fully proven strategy to improve ones gastro-intestinal health.

Even if the good guys are unconditionally good, the ambiguous results of pertinent research clearly indicates that this doesn't imply that all of use will benefit from exogenous provisions of bacteria. There are for example both positive and negative associations for certain strains of bifidobacterium or lactobacillus species (Million. 2011), so that supplementation is mostly based on guessing which are good based on individual studies. This is also why I personally believe that tweaking the environment and thus steering the gut microbiome into the right direction with prebiotics, is a more viable and promising strategy than the ingestion of bazillions of preformed bacteria aka probiotics.

In their thorough, but small scale (N=31) analysis, Cara L. Frankenfeld and her colleagues analysed the fecal sample of their subjects using Multitag Pyrosequencing. This allowed them to compare the bacterial abundance and bacterial diversity across consumers and non-consumers of aspartame and acesulfame-K using non-parametric statistics and UniFrac analysis, respectively.

To predict some of the consequences of possible difference in the bacterial make-up Frankenfeld et al. applied a phylogenetic investigation of the communities by reconstruction of unobserved states (PICRUSt) in order to predict mean relative abundance of gene function.

Table 1: There were no sign. differences in BMI, energy intake, total carbohydrate and added sugar intake or the "quality" of the diet (as assessed on the Healthy Eating Index) between AS consumers and non-consumers (Frankenfeld. 2015)

Thus, the results of the gene function analysis must be met with a healthy degree of skepticism, because unlike the bacterial counts and diversity, which was also just estimated based on what "left" the subjects in form of feces, the gene assay is a model-based result... think of it like the weather forecast, one of which studies say it's relatively reliable (Langille. 2013).

Don't be a fool, stevia will mess with your microbiome just like if not even more than "unnatural" sweeteners.

Sweeteners could be a bad, but also a good thing. In pigs, SUCRAM® (a mixture of saccharin and neohesperidin dihydrochalcone) will significantly increase the abundance of the allegedly good Lactobacilli by more than 100% (Daly. 2014). In other studies, like the previously discussed study in rodents, saccharin has a negative effect. Whether a 100% increase in Lactobacilli as in Daly et al. (2014) or decreases in other bacteria as they have been observed in several rodent studies is something we'd want or not, is yet totally unknown. It's simply too early to predict the effect. For many of you that may be enough to avoid sweeteners, and I fully understand that.

I just want you to know that stevia is not the "healthy alternative", just because it's "natural". In fact, for stevia we even know that it will kill lactobacilli, i.e. those bacteria of which we think that they are the good guys (learn more about how stevia messes with the gut micriobome).

Among the seven aspartame consumers and seven acesulfame-K consumers (some consumed both), the researchers did indeed find some significant differences in the bacterial make-up compared to those subjects who had abstained from consuming sweeteners in the four days before the fecal samples were collected. I quote from the FT (Frankenfeld. 2015):

• Bacteriodetes and Firmicutes had the highest median abundances and together accounted for the majority of the bacterial class representation in all individuals. 
• The median Bacteriodetes:Firmcutes ratio did not significantly differ across aspartame non-consumers (0.96, range: 0.15-2.97) and consumers (1.08, range: 0.69-1.87), (median test p-value=0.60). 
• There was no overall visual clustering of individuals by acesulfame-K consumption . 
• Overall bacterial diversity evaluated with UniFrac analysis was different across consumers and non-consumers, but there were no significant differences in relative abundance of gene function across consumers and non-consumers (Figure 3).
• There were no observable difference in the three individuals who consumed both aspartame and acesulfame-K (Supplemental Figure 1). 

So, let's briefly sum this up. In line with the overall hysteria about sweeteners, the changes were more significant in the aspartame group (p<0.01) than they were in the acesulfame-K group (p=0.03), but this could be explained by the simple fact that the subjects consumed significantly more aspartame (one can of diet coke contains 150mg, by the way) than acesulfam-K (5.3 mg/day to 112 mg/day vs. 1.7 mg/day to 33.2 mg/day).

Figure 1: Yes, there were differences in the bacterial make-up of the gut microbiome of the four groups, but no one can tell you what these or the vast individual differences in the groups mean for your health (Frankenfeld. 2015) !

Against that background, the "aspartame is the worst" hypothesis could neither be refuted nor supported based on the study at hand, even if the results would signify overall ill-health effects. With all three potentially important markers remaining unchanged, though, this is not the case:

• the ratio of mostly "bad" gram-negative bacteriodetes and "good" gram positive bacteria remained the same - it's thus hard to argue that the subjects who consumed artificial sweeteners had an unhealthier gut microbiome
• there was no general reduction in gut bacteria, which would indicate a general anti-microbial effect of artificial sweeteners as it occurs with antibiotics - it's thus hard to argue that the anti-microbial effects (which don't exist) of artificial sweeteners would leave you similarly defenseless and open to colonization with "bad" bacteria as antibiotics.
• the gene essays say that despite the differences in the numbers of certain bacteria, the gene expression is the same - it's thus hard to argue that there was an epigenetic effect of artificial sweeteners that precipitates us to obesity or even makes us sick / diabetic / whatever

Against that background, there may be an urgent need for future research and technological development that would allow us to go beyond observing changes in the number and ratio of largely unknown gut bacteria that are (as of now) completely meaningless for us. 

Probiotics Inhibit Ill-Health Effects of 7-Day Overfeeding in Man - Does This Make Yakult(R) the Perfect Tool in Your Bulking Toolbox or is it Just Another Marketing Gag? Learn more!

Don't be fooled! Scientists may understand the format of the graph in Figure 1 better, but if they were honest, they would have to admit that they have absolutely no clue what the changes they observed mean. Yes, they can use mathematics to tell you they are statistically significant, but they can't even tell you whether they're rather good or bad for you.

Eventually, the data in Figure 1 shows us only one thing: The gut microbiome is like a finger-print. It's different for all of us and despite changes due to artificial sweetener consumption, there's no clear pattern in any of the artificial sweetener groups that would allow us to predict negative or positive effects based on what we know now.

Against that background I would try not to freak out about the fact that aspartame and acesulfam-k can affect your gut microbiome. There is no, and I repeat, no convincing experimental evidence in humans that would remotely confirm that any potential changes of the gut microbiome that occur in response to the consumption of artificial sweeteners would entail ill health effects. The only thing we have,are observational and epidemiological studies that correlate obesity with artificial sweetener use and are abused by people who don't know or simply ignore the difference between associations and causation as "proof" that artificial sweeteners are (usually together with fructose) at the heart of the obesity epidemic. And even in the study at hand, the dietary control was not rigorous enough to exclude that the observed association was actually due to aspartame and acesulfam-K and not due to other agents in the artificially sweetened drinks or totally different foods, the subjects consumed during the four day lead-in, during the last months, or even chronically for years or decades | Comment on Facebook!

References:

• Daly, Kristian, et al. "Dietary supplementation with lactose or artificial sweetener enhances swine gut Lactobacillus population abundance." British Journal of Nutrition 111.S1 (2014): S30-S35.
• Frankenfeld, Cara L., et al. "High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States." Annals of Epidemiology (2015).
• Langille, Morgan GI, et al. "Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences." Nature biotechnology 31.9 (2013): 814-821.
• Million, M., et al. "Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii." International journal of obesity 36.6 (2012): 817-825.

Nausea, Leaky-Gut & GI Disturbances - Ginger Ameliorates All | May Be the Perfect Addition to Your Workout Nutrition

You will find dozens of ginger + lemon water recipes on the internet - all of them can pimp your peri-workout drinks and make your tummies "exercise proof".

As a regular here at the SuppVersity you know about the beneficial health effects of ginger. It has potent anti-oxidant and anti-inflammatory effects without the usual side-effects of COX-inhibitors (Mashhadi. 2013), has been shown to have anti-cancer effect on it's own (Kim. 2005), as well as to be a perfect adjunct for conventional cancer therapy (Sontakke. 2003).

Ginger has also been shown to exert cardioprotective effects (Ghayur. 2005; Singletary. 2010), strengthens the immune system (Butt. 2011) and significant beneficial effects on the health of the digestive system - including the make-up of your microbiome (Sutherland. 2009).

One thing that should be in your peri-workout (best post-workout) regimen is creatine 

Creatine Doubles 'Ur GainZ!

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Creatine Better After Workout

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Build Your Own Buffered Creatine

Now, it is out of question almost all of these effects would be beneficial to athletes, too. The one I want to focus on, today, though, is directly related to the last-mentioned effect: the beneficial effect on the gut. It is well-known that athletes, in general, and endurance athletes, in particular, are having a hard time keeping their tummy from "leaking" (learn more about the link between exercise and leaky gut). With ginger - that's at least what a recent study from the School of Life Sciences at the Heriot-Watt University in Edinburgh suggests. The scientists went from the observations that

1. the frequency of upper and lower gastrointestinal disturbance as a function of exercise is reported to be between 30 and 70%
2. the severity of symptoms ranging from mild stomach discomfort to severe diarrhoea and 
3. the consumption of beverages either before or during exercise may increase the incidence rate by over 25%

to the hypothesis that spiking said beverages with an agent that has previously been shown to reduce the symptoms of nausea and vomiting could be of great benefit for athletes.

Addendum: Are there pesticides in ginger? Oliver Klettner wants to know if there's a risk that you're intoxicating yourself with ginger. Unfortunately, the data on this subject is scarce. According to an older study in the Journal of Agricultural and Food Chemistry, ginger is yet one of the imported spices that contain relatively little DDT, PCB, Dieldrin, Endrin and BHC residues. The ginger from Nigeria in particular has almost no DDT and BHC, while the products from India contained measurable, but probably uncritical amounts (Sullivan. 1980). Similar and even lower levels were detected more recently by Srivastava et al. (2001) in important ginger powder from India. Data on Chinese ginger, which is what Oliver asked about, in particular, is not available in the literature. What is available, though, is data on commercial ginger powders sold in Germany in the late 1970s. The products of undisclosed origin Boppel (1979) tested contained both lead and cadmium, albeit in low doses (1.9 parts per million and 0.35 ppm). Also, in view of the epidemiological evidence in favor of the health benefits of ginger, it appears rather unlikely that (probably existing) pesticide and heavy-metal residues are a general problem. The average ginger consumer is after all ingesting it with a certain amount of these compounds. If that was a sign. health problem, the health benefits should not exist.

In the present study, this agent was ginger that was added to an isotonic beverage 40 recreational athletes (23 male, 17 female) who had volunteered to participate in the study consumed on one out of three test drinks containing 450 ml of either water or beverage A or beverage B in two 225ml servings before and after their workout:

• 

  Study Underlines Real World Benefits of 2g/day of Ginger for Type II Diabetics - Effects Almost on Par W/ Metformin | more

  Beverage A contained 7·5% glucose, 10 mM NaCl, citric acid, K sorbate and 62·5 ml of ginger root extract per 1 L.
• Beverage B was identical to beverage A but the ginger was replaced with 62·5 ml of carrot extract. 
• The control drink contained nothing but plain water.

During each of the three sessions the volunteers completed a 5 km run around the same course. To minimize unwanted interferences due to the test-drinks or fatigue, the sessions were spaced at least 7 days apart (and the subjects were asked not to change training or lifestyle during the study period).

What's the mechanism behind the exercise induced gastrointestinal disturbances? With exercise it's the reduction in gastrointestinal integrity that's driving the increase in gastrointestinal symptoms. Studies show, the harder you exercise, the more the gut integrity suffers and the more susceptible you become to intestinal disturbances. It's not clear how exactly ginger protects your gut from becoming leaky, but it would appear to be most likely that it's a result of its potent anti-inflammatory effects.

The same 5 item questionnaire that has been successfully used Pfeiffer et al. to probe the effects on nutritional intake on gastrointestinal problems during competitive endurance events in 2012 was used to assess the upper and lower gastrointestinal (GI) symptoms before and after exercise. In said test, the subjects hat to place a mark a 10 cm line to rate the severity / occurrence of symptoms anywhere between 0 (low / never) and 10 (high  / always). 

"Section 1 addressed upper abdominal problems (reflux / heartburn, belching, bloating, stomach cramps/pain, nausea, vomiting); section 2 addressed lower abdominal problems (intestinal/lower abdominal cramps, flatulence, urge to defecate, side ache/stitch, loose stool, diarrhea, intestinal bleeding); and section 3 addressed systemic problems (dizziness, headache, muscle cramp, urge to urinate)" (Pfeiffer. 2012). 

The evaluation of the showed a significnat increase in the incidence of upper GI disturbance (P < 0·05) in response to exercise; stomach problems increased from pre-exercise 1.7 (0.1–6.3) to 2.0 (0.1–8.4) during exercise and nausea increased from pre-exercise 1.1 (0.1–4.5) to 2.0 (01–7.6) during exercise. 

Figure 1: The addition of the ginger root extrac lead to a sign. amelioration of the almost 200% increase of the incidence of gastrointestinal symptoms in the 40 recreational athletes who participated in the study (Ball. 2015).

All other measures of GI disturbance were similar between pre-during and post-exercise and the general consumption of beverages did not exacerbate the GI symptoms during exercise. 

What the ginger containing beverage did, however, was that it reduced the prevalence of stomach problems (4.6 (0.3–6.6)) and nausea (4.5 (0.3–9) decreased significantly (P < 0.05) - an effect that was not observed with either beverage B or water, which were without noticeable effects on stomach problems (5 (0.2–8.2)) and nausea (5 (0.2–7)).  

Bottom line: Overall, the data from the study at hand is the first piece to a puzzle of evidence that could eventually prove the usefulness of ginger as a functional ingredient in pre- and post-workout beverages for endurance athletes - even if it does only ameliorate, not block the dramatic (>100%) increase in gastrointestinal problems.

Ginger is also on the list of supps in this SV Classic: "Supplements to Improve & Restore Insulin Sensitivity - Installment #4" | more

What is still missing, though, are (a) long(er) term studies in larger study populations, (b) evidence that the benefits occur in (1) higher-intensity exercise / longer duration exercise (I am thinking along the lines of Ironman training) and (2) anaerobic exercises like resistance training or sprinting which are similar prone to inducing (temporal) gastrointestinal problems and last but not least (c) insights into the mechanism(s) behind the beneficial effect of ginger - effects of which Ball et al. (2015) speculate that they may be, linked to the antagonist effects on serontonergic 5HT receptors, as they have been suggested by Sontakke et al. in a chemotherapy study (2003) | Comment on Facebook!

References:

• Ball, D., G. Ashley, and H. Stradling. "Exercise-induced gastrointestinal disturbances: potential amelioration with a ginger containing beverage." Proceedings of the Nutrition Society 74.OCE3 (2015): E186.
• Boppel, B. "[Lead-and cadmium-content of foodstuffs 1. Lead-and Cadmium-content of spices and table salt (author's transl)]." Zeitschrift Fur Lebensmittel-Untersuchung Und-Forschung 160.3 (1975): 299-302.
• Butt, Masood Sadiq, and M. Tauseef Sultan. "Ginger and its health claims: molecular aspects." Critical reviews in food science and nutrition 51.5 (2011): 383-393.
• Ghayur, Muhammad Nabeel, and Anwarul Hassan Gilani. "Ginger lowers blood pressure through blockade of voltage-dependent calcium channels." Journal of cardiovascular pharmacology 45.1 (2005): 74-80.
• Kim, Eok-Cheon, et al. "[6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo." Biochemical and biophysical research communications 335.2 (2005): 300-308.
• Mashhadi, Nafiseh Shokri, et al. "Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence." International journal of preventive medicine 4.Suppl 1 (2013): S36.
• Singletary, Keith. "Ginger: An Overview of health benefits." Nutrition Today 45.4 (2010): 171-183.
• Sontakke, S., V. Thawani, and M. S. Naik. "Ginger as an antiemetic in nausea and vomiting induced by chemotherapy: a randomized, cross-over, double blind study." Indian journal of pharmacology 35.1 (2003): 32-36.
• Srivastava, L. P., Roli Budhwar, and R. B. Raizada. "Organochlorine pesticide residues in Indian spices." Bulletin of environmental contamination and toxicology 67.6 (2001): 856-862.
• Sullivan, James H. "Pesticide residues in imported spices. A survey for chlorinated hydrocarbons." Journal of agricultural and food chemistry 28.5 (1980): 1031-1034.

The Gluten Solution: Aspergillus Niger-Derived Enzyme May Make "Gluten-Free" Redundant - Enzyme Supplementation Reduces the Amount of Gliadin in the Duodenum by 80-90%

Can a pill simulate "gluten-free"?

The problem with gluten (if there is one, after all we are not all suffering from coeliac disease) is that its proline-peptides cannot be digested by any of the enzymes in the human intestinal tract. Therefore, the long proline-rich gluten peptides reach the small intestine intact after ingestion where they are the driving motors of coeliac disease in 1% of the population, in whom the specific amino acid sequences of such poorly digested proline-rich gluten peptides triggers an abnormal immune response.

More recently, though, studies have shown that less pronounced adverse reactions to gluten consumption can occur even in subjects who don't suffer from coeliac disease. As Salden et al. point out, "[p]resently non-coeliac gluten sensitivity has been clinically recognised as a separate condition in which neither allergic nor autoimmune mechanisms are involved" (Salden. 2015). Accordingly, the results of the latest study from the Maastricht University Medical Center are relevant for much more than just 1% of the population (West. 2003; Mäki. 2003; Fasano. 2003; Bingley. 2004).

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Now I got you curious, right? Ok, here's what the Dutch scientists did: In their randomized, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days with at least one week washout in-between. On day 2-3, a liquid low or high calorie meal (4 g gluten) with Aspergillus niger prolyl endoprotease (AN-PEP | 6.1 mL of AN-PEP corresponding with 1.600.000 Protease in a total of 100 mL water) or placebo was administered into the stomach.

Table 1: Recipe and nutritional composition of the low and high calorie test meal per 300 g portion (Salden. 2015).

Table 1 shows the composition of the meals. All test meals contained 5.2 g of gluten powder, of which 4.0 g was gluten protein (Syral, Aalst, Belgium). Encapsulated refined olive oil powder (VanaGrasa 80B; FrieslandCampina, Kievit B.V., Meppel, The Netherlands) was used as fat source for the meals and together with maltodextrin as additional energy source for the high calorie meal, and sodium caseinate (DMV, Veghel, The Netherlands) was used to match both meals for protein content. The dry meal powders were dissolved in a total volume of 300 mL tap water of 40 °C by stirring with a spoon and subsequently mixing with a Turrax (Ultra Turrax T25; IKA, Staufen, Germany). Low and high caloric meals were not blinded to the investigator.

The gastric emptying was tracked with acetaminophen and a triple-lumen catheter was used to get the gastric and duodenal samples that were used to calculate the 240-min area under the curve (AUC0–240 min) of α-gliadin concentrations.

Figure 1: Total alpha-gliadin in the duodenum (µg x min | left) and western blot showing degradation of water-insoluble gliadin over time in the stomach and duodenum in low and high calorie meals with and without AN-PEP (Salden. 2015).

As you can see in Figure 1, the addition of the Aspergillus niger prolyl endoprotease worked it's magic on the indigestible gluten peptides and reduced the amount of potentially pro-inflammatory alpha-gliadin that made it into the duodenum by 91% and 81% depending on the size of the meal. That's huge and as the scientists point out the first time that someone observed in vivo that the AN-PEP enzyme efficiently degrades gluten from a meal in the stomach of human subjects.

Is Noneliac Gluten Sensitivity Legit? A Review of the Latest Scientific Evidence on NCGS by Alex Leaf (Guestpost) | more

Bottom line: You probably already realized why the results of the study at hand are important. If one could add sufficient amounts of AN-PEP to gluten-containing products and / or take a supplement that contains Aspergillus niger prolyl endoprotease (AN-PEP) with every gluten-containing meal, we could minimize, probably even totally prevent any pro-inflammatory effects of gluten in both coeliac patients and subjects with non-coeliac gluten intolerance.

Ok, it's questionable whether it's feasible to put a gliadin digesting enzyme into goods without impairing their quality (gluten is after all added for its ability to "glue" things together; putting AN-PEP into the dough may thus ruin it).

A pill with Aspergillus niger prolyl endoprotease (AN-PEP), on the other hand, could make the life of people who risk developing diarrhea or other symptoms of gluten intolerance whenever they eat out significantly easier... ah, and it could be big business in view of the contemporary gluten-scare, which brings me to the sponsors of the study (DSM Nutritional Products AG) who are about to use the study to advertise their AN-PEP products which have already been approved by the French Agency for Food, Environmental and Occupational Health & Safety | Comment on Facebook!

References:

• Bingley, Polly J., et al. "Undiagnosed coeliac disease at age seven: population based prospective birth cohort study." Bmj 328.7435 (2004): 322-323.
• Fasano, Alessio, et al. "Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study." Archives of internal medicine 163.3 (2003): 286-292.
• Mäki, Markku, et al. "Prevalence of celiac disease among children in Finland." New England Journal of Medicine 348.25 (2003): 2517-2524.
• Piper, Justin L., Gary M. Gray, and Chaitan Khosla. "Effect of prolyl endopeptidase on digestive-resistant gliadin peptides in vivo." Journal of Pharmacology and Experimental Therapeutics 311.1 (2004): 213-219.
• Salden et al. "Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers." Alimentary Pharmacology and Therapeutics (2015): Accepted manuscript.
• West, J., et al. "Seroprevalence, correlates, and characteristics of undetected coeliac disease in England." Gut 52.7 (2003): 960-965.

"No Sugar" Foods with Maltodextrin Mess with Your Gut Microbiome - Effects are Significant and Could Explain Rise in IBD, Crohn's, Ulcerative Colitis & Co

No, sugar may not be extra-healthy, but there's accumulating evidence that it's alleged "no-sugar" replacement maltodextrin may be even worse.

I find it quite fitting how Nickerson et al. start their recent review of the potential ill effects of maltodextrin by pointing out that inflammatory bowel disease (IBD | e.g. ulcerative colitis (UC) and Crohn's disease (CD)) is among the increasingly prevalent "complex, chronic inflammatory states associated with altered dynamics between host anti-microbial defenses and commensal microbes" that's plague modern human health.

Scientists have long believed that the ever-increasing number of people suffering from IBD is a consequence of environmental priming or triggering of a genetically susceptible individual to initiate uncontrolled inflammation against commensal bacteria.

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In fact, researchers have meanwhile been able to link many IBD-associated genetic risk loci to interactions between the mucosal immune system and microbes (Jostins. 2012) - in conjunction with a certain disposition to develop IBD, the presence of certain dietary ingredients may thus be critical to the eventual disruption of the host-microbial dynamics in the gut with all its ill health consequences (Spooren. 2013). It is thus only logical that recent studies show that

"IBD patients have alterations in both composition and organization of the commensal microbiome, as well as enhanced mucosal permeability. Overall, the bacterial diversity of the IBD microbiome is reduced, with notable decreases in Bacteroidetes and Firmicutes (especially in specific Clostridium species) and increases in Actinobacteria and Proteobacteria (including Escherichia coli). Additionally, E. coli strains with enhanced virulence have been identified in ileal CD patients.8 These strains, termed adherent-invasive E. coli (AIEC), have enhanced adhesive properties and the ability to invade and replicate within epithelial cells and macrophages" (Nickerson. 2015).

According to the latest science, the IBD microbiome also has an altered metabolic activity, with decreases in butyrate-producing bacteria and increases in sulfate-reducing strains noted in multiple studies and leads to a decreases in mucosal barrier function ("leaky gut") that leads to bacterial colonization directly on the surface of the intestinal epithelium, increased bacterial translocation, and stimulation of the immune system.

Figure 1: MDX enhances AIEC biofilm formation and cellular adhesion and does thus contribute to a decrease in intestinal barrier function and an unwanted increase in bacterial translocation from the gut into cirulation (Nickerson. 2015)

In previous studies, Nickerson et al. have identified maltodextrin, an increasingly common food ingredient the industry loves, because you can (ab-)use tons of it in your products and still label them as "low sugar" foods, as a potent disruptor of the intestinal microbiome. One that impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms.

Figure 2: Concomitant increases in CD incidence and MDX in the American diet (Nickerson. 2015).

There is suspicious, but not conclusive evidence that increases in MDX intakes are fueling the Crohn's epidemic: Epidemiological evidence supports the hypothesis that our increased consumption of maltodextrin (MDX) could be one of the motors that drives the rapid increase in crohn's disease (CD; see Figure 2) irrespective of an increase in gluten exposure by its direct negative effect on the composition of our intestinal microbiome and the subsequent effects on gut health (or rather illness).

More specifically, the cellular exposure to MDX in vitro impaired anti-bacterial responses, as demonstrated by the increased viability of intracellular Salmonella in macrophages and epithelial cells cultured in MDX-supplemented media. Nickerson et al. attribute the increased bacterial viability by (1) a diminished respiratory burst mediated by the NADPH oxidase system, and (2) alterations in bacterial trafficking to a protective niche in enlarged Rab7+ vesicles.

In their latest review, Nickerson et al. do yet go beyond the effects of MDX as the sole motor of the increase in IBD, citing similar and synergistic effects of other dietary additives, such as emulsifying agents or thickeners, which have also been found to have profound detrimental effects on intestinal homeostasis.

"Examples of dietary emulsifiers include carboxymethyl cellulose (CMC), carrageenan, xanthan gum, and MDX, which are derived from natural products and are classified as GRAS. However, carrageenan can be used to induce bacterially-driven intestinal inflammation in rodents and is now under re-evaluation by the FDA. Likewise, in interleukin-10-deficient mice that are genetically predisposed to colitis, CMC consumption synergizes with genetic risk to result in bacterial overgrowth and aggressive ileitis. Further evidence in humans demonstrates the pathogenic potential for these dietary additives when combined with other risk factors, as supplementation of infant formula with a xanthan gum-based thickener induced late-onset necrotizing enterocolitis in premature infants" (Nickerson. 2015).

The purported mechanism by which these emulsifiers act mess with your gut is the way by which they act on the mucosal barrier to decrease viscosity, permitting bacterial translocation and thus potentially driving inflammation.

E171 aka Titanium DiOxide (TiO2) is another common food additive you want to avoid. Just like MDX it does appear to mess w/ the microbiome, but there's more!

So what? IBS is often "treated" (I should better say people try to ameliorate it) a Specific Carbohydrate Diet (SCD) or the IBD-Anti-Inflammatory Diet (IBD-AID), both of which prescribe the removal of of complex carbohydrates, starches, grains, and dairy from the diet and an emphasis on the consumption of specific vegetables, meats, homemade yogurt, and allowing some beans and hard cheeses, their actual efficacy, as well as their often observed inability to reduce the symptoms may well be mediated by their followers (in-)ability to effectively eliminating MDX (and other related emulsifiers and texturizers which are like many other food additives not allowed" on SCD and IBD-AID) from the diet.

For you, who hopefully don't suffer from IBD, Crohn's or ulcerative colitis (yet?), this means that you better stick to "real foods" - regardless of their sugar content - and try to avoid the consumption of processed (and sugar-reduced) industrial food products that require MDX and emulsifiers to be palatable | Comment on Facebook!

References:

• Jostins, Luke, et al. "Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease." Nature 491.7422 (2012): 119-124.
• Nickerson, Kourtney P., Rachael Chanin, and Christine McDonald. "Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin." Gut microbes 6.1 (2015): 78-83.
• Spooren, C. E. G. M., et al. "Review article: the association of diet with onset and relapse in patients with inflammatory bowel disease." Alimentary pharmacology & therapeutics 38.10 (2013): 1172-1187.