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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).
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.
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.

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

• 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).

• 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.

• 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?

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.

Yes, blueberry smoothies are heart healthier than those without blueberries, but can't replace blood pressure meds.

In today's installment of the waredownloadsoft short news we will take a look at a bunch of recent studies that have been published in the open-source journal Nutrients in the last months. Some of them deal with foods, others with behavioral aspects that are related to one's diet and its effects on body weight and health.

I will try to adapt the length of the summary to the appeal of the article, but if you feel that a specific topic has not been covered "in-depth enough" for your liking, you can always type the title of the study from the references into google and take a closer look, yourself.

• We don't see the dietary mistakes we make (Sproesser. 2015) - In contrast to our perception of physical weaknesses like love-handles and co our perception of our eating habits is often not critical enough. According to a recent study from the University of Konstanz in Germany, people considered what they ate always healthier than what others ate, even if an objective assessment said that there were no significant differences.
  

  Figure 1: Annotated photo of the foods subjects chose from when they put together the meals for themselves and their peers (Sproesser. 2015).

  What is particularly interesting is that this became a self-fulfilling prophecy, when the participants were asked to compose a meal for their peers and chose (a) more energy for a peer than for themselves (M = 4983 kJ or 1191 kcal on average for the peers’ meals vs. M = 3929 kJ or 939 kcal on average for the own meals) and (b) more high-caloric food items for a typical meal - a behavior that is highly indicative of a so-called "self-other bias", which would confirm that at least many of us really think they were eating healthy even if that's in stark contrast to epidemiological data indicating overall unhealthy eating habits.
• Egg yolk protein delays, egg ovalbumin (the white stuff) boosts the recovery of your iron levels (Kobayashi. 2015) - In spite of the fact that the study at hand was conducted in female rats, it's safe to assume that the yolk and white protein will have different effects on iron absorption and thus the the induction of iron deficiencies in man and women on low iron diets, too.
  

  Figure 2: Body weight gain, food intake, hematocrit, hemaglobin and red blood cell count in response to different iron deficient diets compared to control = iron sufficient diet (Kobayashi. 2015).

  In other words, if you are eating 20 full yolks per day and your iron-levels are suppressed, you may reconsider this practice. If it's just the occasional egg yolk, let alone egg protein powder (which is usually ovalbumin, only), don't worry. 
• Blueberries are good for the heart, but they are no replacement for your blood pressure meds (Stull. 2015) - ed. In a recent double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). The subjects were randomized to receive a blueberry or placebo smoothie twice daily for six weeks.
  

  Table 1:  Nutritional composition and ingredients in the smoothies (Stull. 2015).

  A snack that didn't have any effects on either the blood pressure or the insulin sensitivity of the >20 year-old subjects suffering from metabolic syndrome. That the blueberry smoothie still had beneficial effects on the endothelial function of the subjects can be seen by the improvements in reactive hyperemia index (RHI - an index that is among other things used for the noninvasive identification of patients with early coronary atherosclerosis" | Bonetti. 2004), which remained statistically significant even after adjusting for confounding factors, i.e., the percent body fat and gender.
  
  Accordingly, the study does support the notion that eating blueberries - even in form of a smoothie - can have beneficial effects on your heart health. In view of the fact that in this particular study a comparison of no-blueberry vs. blue-berry smoothies was conducted, you could also argue that the inclusion of blueberries in a smoothie may smooth out the negative effects of another (unnecessary) snack on your health and suggest: If you want to eat blueberries don't add them as a snack, but use them as a replacement for other foods.

If you put salmon on a high RS bagel that may actually qualify as healthy meal.

Ok, don't get me wrong. I do not recommend making bagels, regular or resistant starch enhanced, a prominent part of your diet, but if you want to take a bagel along to the office, the high RS bagels Sarah A. Dainty baked for the experiment she conducted as part of the thesis she presented to The University of Guelph, may be a better choice - specifically if you fill your bagel with salmon or other high protein foods.

Dainty conducted a randomized, double-blind crossover study to examine the glycemic effects of 8-week consumption of high-RS bagels (25 g RS) or control bagels in adults with a high type II diabetes risk (n=24).
Dainty evaluated the fasting and postprandial (with an oral glucose tolerance test) glucose, insulin and HbA1c were measured before and after each bagel treatment.

Table 1: Recipe for the dough the test bagels were made of (Dainty. 2015).

Her results clearly indicate that the RS bagels, which contained 60% HS Maize (R) 260 (TM) as a replacement for regular wheat flour and 28g of gluten per kg to give the necessary extensibility and elasticity to dough, did not change fasting or postprandial glucose or HbA1c.

Figure 1: Comparison of the effects of the regular and RS bagel on glycemia (Dainty. 2015).

A significant inter-group difference was observed for fasting insulin, 2- and 3-hour insulin iAUC, fasting insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B), though; and the use of resistant starch in the bagels also increased fasting insulin sensitivity (HOMA-%S), significantly.

Table 2: Not all starches are created equal - overview of the 4 major forms of resistant starches (Dainty. 2015).

The only problem that remains, though, was that the subjects liked the RS bagel significantly less than its regular cousin; and even worse - the taste didn't grow onto them (~7 vs. 5 out of 10 points). Since many subjects still reported that they might continue eating the RS bagel, it's not totally impossible that - after a few tweaks to the composition - RS bagels could actually be sold on the US market. If we assume that people actually buy them, their far-reaching effects on the satiety inducing and fat burning incretin hormones PYY and GLP1 (Zhou. 2015) this could tame, but probably wouldn't stop the rampant increase in obesity in the US.
References:

• Dainty, Sarah A. The Effect of Resistant Starch Bagels on Glycemic Response in Adults at Risk for Type 2 Diabetes. Diss. 2015.
• Zhou, June, et al. "The importance of GLP‐1 and PYY in resistant starch's effect on body fat in mice." Molecular nutrition & food research (2015).

Regular wheat (left) and khorasan (right) look almost alike, well, if we go by the reputation of "lighter = unhealthier", the healthy "paleo wheat" would actually look like the worse choice, but studies show, it is the exact opposite.

You all know that cardiovascular Disease (CVD) causes approximately one-third of all deaths globally in both developed and developing countries. In fact, coronary Heart Disease is the largest contributor of CVD, and encompasses Acute Coronary Syndrome (ACS), which is an acute pathology associated with atherosclerotic plaque rupture and interruption of coronary blood to myocardial tissue.

"An eight-week washout period was implemented between the respective interventions. Blood analyses were performed both at the beginning and end of each intervention phase; thereby permitting a comparison of both the khorasan and control intervention phases, respectively, on circulatory risk factors for the same patient" (Whittaker. 2015). 

References:

• Carnevali, Andrea, et al. "Role of Kamut® brand khorasan wheat in the counteraction of non-celiac wheat sensitivity and oxidative damage." Food Research International 63 (2014): 218-226.
• Whittaker, Anne, et al. "An Organic Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients with Acute Coronary Syndrome: A Randomized Crossover Trial." Nutrients 7.5 (2015): 3401-3415.