Inulin, the Latest on a (Functional) Food Ingredient + Dietary Supplement: From Autoimmune to Metabolic Disease & Co

Globe artichokes have the most highly polymerized inulin fibers. They can be served cooked or oven-roasted.

The journal Molecular Nutrition & Food Research is probably food designers' favorite bedtime reading because the articles about various functional food ingredients inspire them to dream up ever-new [(dys-)functional)] food formulas you will soon find on the shelves at your local supermarket.

With inulin, a fructose-based polysaccharide fiber, which is the object of several papers in the latest issue of said scientific journal, I want to address one of these ingredients that has already made it from bench to bedside... ah, I mean from bench to protein bars and other functional foods such as dairy products, frozen desserts, table spreads, baked goods and breads, breakfast cereals, fillings, dietetic products or chocolate for today's research update... an update that focuses on beneficial effects, but won't conceal the potential issues people w/ FODMAP intolerance may experience.

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Inulin is classified as a non-viscous fiber with a relative sweetness (compared to sucrose) of 0-0.3 and an energy content of 1.5kcal/g. It is a complex of sugar that's present in the roots of various plants (most notably Jerusalem artichoke and chicory). It is a polysaccharide based on fructose and has both, functional and therapeutic potential (Ahmed 2017). Inulin has been successfully used as fat replacer in quite a wide range of products as dairy and baked products and known to impart certain nutritional and therapeutic benefits that extend apart to improve health and reduce the risk of many lifestyle related diseases - most likely by acting as a prebiotic and thus promoting good digestive health, influencing lipid metabolism and having beneficial effects on glucose and insulin levels. Speaking of those...

• Long-chain structure and fermentability is key to inulin's anti-diabetes effects (Chen 2017)-- It's not news that dietary fibers capable of modifying gut barrier and microbiota homeostasis. What is not as well-known is that these effects of dietary fiber could slow down the progression of type 1 diabetes (T1D) and whether and to which extent this effect depends on the fermentability (in turn a function of the degree of polymerization | Van De Wiele 2007) of the fibers.
  
  In a recent study, scientists probed the effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice: Female nonobese diabetic mice were weaned to long- and short-chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic-gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D.

Avoid inulin if you respond to FODMAPs with bloating, intestinal distress or systemic IBS-like symptoms of FODMAP intolerance! For most of us, inulin is a healthy fermentable fiber you want to have in your diet. Just like other dietary FODMAPs, i.e. "Fermentable, Oligo-, Di-, Mono-saccharides And Polyols", which are either naturally present in our foods, as in include barley, yogurt, apples, apricots, pears, and cauliflower, or added to make them "functional", can be a severe problem for some of us. If you experience abdominal pain, bloating, distension, constipation, diarrhea and flatulence when consuming these foods, or suffer from downright irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), it may thus be best you forget about the health-benefits of inulin and stick to an inulin- and otherwise FOODMAP-free diet, of which a recent meta-analysis by Marsh et al says that it improves the IBS-specific quality of life-scores by 85% (that's in RCTs, in non-randomized trials the number is 218%!) and to improve symptoms like abdominal pain, flatulence, bloating and co by 81%.

• This treatment promoted modulatory T-cell responses, as evidenced by increased CD25+Foxp3+CD4+ regulatory T cells, decreased IL17A+CD4+ Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase-1-p20-IL-1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide as well as short-chain fatty acid production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance, and enriched modulatory Ruminococcaceae and Lactobacilli.
  
  With the short-chain variety having no effect on the immune system, though, the most important message of the study at hand clearly isn't that inulin has the potential to ameliorate pathological decreases in gut barrier function and immune factors that contribute to the development of type I diabetes,  but rather that it takes the long-chain variety of this prebiotic to do the trick.
• Inulin appears to work, at least partly, by reducing the lipid and (chole)sterol uptake (Han 2017) -- While there's a fundamental difference between the ketogenic diet and the high-fat diets that are used in rodent studies (with HFD being also "high" in carbohydrates), it is still worth mentioning that a recent study from the Obihiro University suggests that the lipid-lowering effect inulin depend on the fat content of the diet with its ability to reduce serum lipid levels being particularly pronounced on a high-fat diet.
  
  

  

  Figure 1: Fasting serum lipid levels in rats fed a diet of 20% fat with 5% cellulose or 5% HP-inulin (average degree of polymerization = 24) for 28 days (high-fat diet). Values represent mean ± SEM (n = 5). Cellulose - filled, inulin - open cycles (Han 2017).

  In the study, rats were fed a diet of 5% fat with 5% cellulose or 5% HP-inulin (average degree of polymerization = 24) (low-fat diet) or of 20% fat with 5% cellulose or 5% HP-inulin (high-fat diet) for 28 days. Total, HDL, and non-HDL cholesterols, and triglyceride concentrations in the serum were measured along with total lipid content of liver and feces. Furthermore, hepatic triglyceride and cholesterol, and fecal neutral and acidic sterol concentrations in total lipid were assessed. In addition, cecum SCFA levels and bacterial profiles were determined.

Chicory is not naturally the best source for highly polymerized inulin, that's the globe artichoke (Van Loo 1995).

Is chicory inulin special? While chicory inulin is naturally higher polymerized than oligofructose (2.5-fold more polymerized), it's not necessary the "chicory" that makes it special.

In this context, it is however important to be aware of the fact that studies often use a special version of chicory inulin, so-called "high-performance inulin" based on but not identical to what your tummy will extract from chicory roots.

With a degree of polymerization (DP) that is 2.5-fold higher than regular chicory inulin and thus 5-fold higher than the more commonly used oligofructose (Den Hond 2000) "high-performance inulin" will also have more pronounced prebiotic effects (Van De Wiele 2007). For supplements, it is thus not just the average degree of polymerization of the raw material that counts, but rather what the supplement producer made of it.

• As previously hinted at, the hypolipidemic effect of HP-inulin differed depending on dietary fat content (5% versus 20%). Specifically, 5% inulin instead of cellulose in a semi-purified high-fat diet reduced serum lipid levels, significantly.
  

  

  Figure 2: The analysis of the feces shows sign. (138%, p = 0.001 and 117%, p = 0.03) increases in total sterol and total lipid contents in response to inulin on a high-fat diet (none on low-fat | Han 2017).

  In rats, this reduction was strongly associated with increased total lipid and neutral sterol excretion. In other words: The effect can probably be ascribed mostly to the non-absorption of dietary fat and (chole)sterols. What is interesting, here, is that this effect occurs only if the diet is high in fat ( - a risk that you may not get enough fat and/or (chole)sterols from your diet because of inulin is thus unwarranted.
• Inulin is probably best supplemented with probiotics (various) -- Only recently, US scientists have observed that 225 mg of inulin with 10 billion colony-forming units of LGG but not 325 mg of inulin alone administered in the first 6 months of life almost halved the incidence asthma of newborns when they were 5 - the corresponding calculated risk reductions for asthma are -12% and only 5% for eczema.
  That's  neither 100% protection nor an earth-shattering difference to inulin, alone, but it's one of many examples that show that the combination pre- plus pro-biotic in order to ensure that the "right" bacteria are fed is the way to go - also against diabesity (Beserra 2015).

More evidence that inulin doesn't need to be taken with probiotics to help weight loss: In response to the daily supplementation of 8g oligofructose-enriched inulin  (vs. placebo), scientists from the Universities of Calgary and Alberta observed a significant alteration in intestinal microbiota (more Bifidobacterium, decreases in Bacteroides vulgatus) as well as significantly reduced body weight z-scores, body fat percentage (-2.4%), trunk fat percentage (-3.8%), and serum level of interleukin 6 (-19%) in overweight or obese 7-12 years olds in a 16-week single-center, double-blind, placebo-controlled trial.

• In this context, it may, however, be worth noting that the effects of fiber, especially in the short run, do not depend on the co-supplementation of probiotics. That's something a recent study from Kuwait showed quite convincingly: In the study,

  "...[f]orty college age females received either a fiber drink with 16 g of inulin in 330 ml water or placebo. On the 8th day of the study, appetite sensations were assessed using visual analogue scale (VAS) along with food intake. Repeated-measures ANOVA were performed comparing VAS ratings during test day. Energy consumption was compared using paired t-tests. Significance was determined at p<0.05" (Salmean 2017).

  On the 8th day, the fiber group reported lower ratings for hunger, desire to eat, and prospective food consumption with significantly higher ratings for satisfaction and fullness.
  Subsequently, the fiber group consumed 21% less kcal from food at lunch (453 ± 47 kcal) compared to controls (571 ± 39 kcal) (p<0.05).
  
  As Salmean et al. point out, it is thus clear that inulin alone is sufficient to "curb[...] appetite sensations and help[...] reduce food intake during lunch" (ibid.). It is thus no wonder that previous studies report weight loss in response to increased intakes of inulin-type fructans and link the latter to reduced ghrelin and increased peptide YY satiety hormone levels (Parnell 2009) - an effect that cannot be observed with every type of fermentable fiber, by the way (guar gum, for example, doesn't share the beneficial effects of inulin - whether that's because it is, unlike inulin, viscous, is not clear, yet | Weitkunat 2017).

A recent study by Halmos et al. (2014) should remind you not to cut FODMAPs from your diet if you tolerate them well. 

So how much inulin is there actually in our foods? I don't know that for sure, but what I can tell you is that it is used (albeit often in small amounts) in dairy foods like yogurt, kefir, cultured buttermilk, cultured cream, koumiss, ice-cream, mozzarella cheese, petit-suisse cheese, soy beverages, bakery products like bread, biscuits, cookies, orange cake, chocolate cake, muffins, chocolates and confectionery like chocolate mousse, milk chocolates, sugar-free confections, etc., in conjunction with sweeteners like xylitol, sorbitol, maltitol, mannitol, erythritol, lactitol, isomalt, or hydrogenated starch hydrolysate and even in the meat industry, namely (a) in sausages, meat patties, bologna sausage, hamburgers, cooked sausages, dry fermented sausages and (b) what the raw material for the sausages and patties is fed, i.e. broilers, pigs, calves, etc.

In 1999,  the American diet provided on average 2.6 g of inulin and 2.5 g of oligofructose -when standardized for the amount of food consumed, the intakes showed little difference across gender and age. The major food sources of naturally occurring inulin and oligofructose in American diets were wheat(!), which provided about 70% of these components, and onions, which provided about 25% of these components (Moshfegh 1999).

If you want to increase your dietary inulin intake without processed foods (always a good idea) aim for higher intakes of chicory root, dandelion root, asparagus, leeks and onions, bananas and plantains (especially when they’re slightly green), sprouted wheat (such as the kind used in Ezekiel bread), garlic, artichokes, fresh herbs, and yams. If, on the other hand, you have problems with so-called "FODMAPS" (yes, inulin is one of them), you'll obviously want to avoid these and all inulin-enhanced functional foods - for most healthy individuals inulin's effect on gas in the colon is yet not a problem (Murray 2014) as the summary from Halmos et al. I included in the bottom line shows, it's rather the opposite: for those who tolerate them well FODMAPs are downright healthy | Bon appetit!

References:

• Ahmed, Waqas, and Summer Rashid. "Functional and Therapeutic Potential of Inulin: A comprehensive review." Critical Reviews in Food Science and Nutrition just-accepted (2017).
• Beserra, Bruna TS, et al. "A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity." Clinical Nutrition 34.5 (2015): 845-858.
• Cabana, et al. "Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial." Pediatrics. 2017 Aug 7. pii: e20163000. doi: 10.1542/peds.2016-3000. [Epub ahead of print]
• Chen, K., et al. "Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis." Mol. Nutr. Food Res. 2017, 61, 1601006. https://doi.org/10.1002/mnfr.201601006
• Den Hond, Elly, Benny Geypens, and Yvo Ghoos. "Effect of high performance chicory inulin on constipation." Nutrition Research 20.5 (2000): 731-736.
• Halmos, Emma P., et al. "Diets that differ in their FODMAP content alter the colonic luminal microenvironment." Gut (2014): gutjnl-2014.
• Han, K. et al. "Dietary fat content modulates the hypolipidemic effect of dietary inulin in rats." Mol. Nutr. Food Res. 2017, 61, 1600635. https://doi.org/10.1002/mnfr.201600635
• Marsh, Abigail, Enid M. Eslick, and Guy D. Eslick. "Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis." European journal of nutrition 55.3 (2016): 897-906.
• Moshfegh, Alanna J., et al. "Presence of inulin and oligofructose in the diets of Americans." The Journal of nutrition 129.7 (1999): 1407S-1411s.
• Parnell, Jill A., and Raylene A. Reimer. "Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults." The American journal of clinical nutrition 89.6 (2009): 1751-1759.
• Salmean, et al. "Acute fiber supplementation with inulin-type fructans curbs appetite sensations: a randomized, double-blind, placebo-controlled study." Food Nutr Res. 2017 Jul 2;61(1):1341808. doi: 10.1080/16546628.2017.1341808. eCollection 2017.
• Van De Wiele, Tom, et al. "Inulin‐type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects." Journal of Applied Microbiology 102.2 (2007): 452-460.
• Van Loo, Jan, et al. "On the presence of inulin and oligofructose as natural ingredients in the western diet." Critical Reviews in Food Science & Nutrition 35.6 (1995): 525-552.
• Weitkunat, Karolin, et al. "Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice." Scientific Reports 7 (2017).

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

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• 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.

Whey Protein Alone Won't Cover the EAA Requirements of Hard Working Athletes, Study Says. Plus: US Whey More Digestible & 88% Higher in Leucine than Brazilian Whey

Not all protein supplements are created equal. And this goes for whey supplements from different countries, too.

In their accepted manuscript for LWT - Food Science and Technology, Cristine Couto Almeida and her colleagues write: "When the calculated AAS and PDCAAS based on the suggestion for adult athletes were considered, both [US & Brazilian whey protein] supplements exhibited suboptimal score values for several EAA [... and] were unable to supply the suggested adult athlete EAA requirement" (Almeida. 2014).

Shocked? I'd hope not. I mean, you don't even know what the scientists base their conclusion on - right? So before we even try to put things into perspective, it would be wise to take a look a the design of this in vitro study.

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While the researchers from the Universidade Federal de Rio de Jaieiro acknowledge that whey protein, in general, is an effective adjunct to the diet of strength and even endurance athletes, they insist that there is too little "information regarding the WP supplement protein quality" and thus set out to "to investigate the protein quality of commercial WP supplements produced by U.S. and Brazilian companies based on in vitro digestibility (IVPD) assay, EAA, AAS and [protein digestibility-corrected amino acid] PDCAAS." (Almeida. 2014)

To this ends, the researchers acquired fifteen samples of whey protein (WP), soy protein, and caseinate isolate powder from a commercial retailer specialized on nutritional supplements. The supplements had been manufactured at different countries - eight from USA companies (WP-USA), and seven from Brazilian companies (WP-BRA). The supplements manufactured with soy protein and caseinate isolate powder were used as references in a study that yielded quite surprising results.

Figure 1: Essential amino acid composition of two commercial whey protein supplements (Almeida. 2014).

As you can see in Figure 1 the amino acid composition of the whey proteins from Brazil and the US varied significantly. The US whey, for example had significantly higher amounts of leucine, while the Brazilian whey was loaded with the essential amino acid lysine. While it is possible that the variations in the other amino acids are a result differences that were present in the milk, already, I would guess that the US whey was either openly (the scientists don't disclose the brands, otherwise I'd check) or secretly spiked with leucine to promote muscle anabolism.

Figure 2: Relative loss (%) of amino acids during simulated (in vitro) digestion in US and Brazilian whey (Almeida. 2014).

What are the numbers based on: Whether the amount of aminos is sufficient or not was calculated based on the WHO recommendation (WHO. 2007), assuming a normal (=comparatively low) protein intake.

If you consume twice the WHO suggestions for athletes, you are thus not at a risk of being deficient in any of the EAAs, but could maybe optimize the ratio of the individual amino acids by not covering your protein needs from a single protein source.

Even if we assume the latter was the case and the producer added free form amino acids to the whey, though, this does not explain the other differences, because if you add say 20g of leucine to 100g of EAA and measure the amino acid content of the 100g of your new mix, the content of all other amino acids would be lower.

 As you can easily see in Figure 1, though, this was not the case in the study at hand. Plus: There were also significant differences in the protein digestibility-corrected amino acid composition, i.e. the marker of whether or not the content of a certain essential amino acid per gram of protein was sufficient or not. In that, values <1.0 indicate there is too little of this amino acid in the mix.

Figure 3: Amino acid score and protein digestibility-corrected amino acid composition for the commercial
US and Brazilian whey supplements (Almeida. 2014).

As you can see in Figure 3, the latter was the case for threonine and valine in the US whey and for isoleucine and leucine in the whey protein from Brazil.

Figure 4: According to the standardized in vitro digestion assay (AOAC. 2012) the scientists used soy protein has by far the lowest digestibility and will thus be effectively delivering the lowest percentage of the amino acids it contains into your circulation (Almeida. 2014).

What does this mean? I must admit this sounds awful, but in practice it means only that you would end up getting your EAAs at an allegedly suboptimal ratio (I doubt we know what this ratio is, though) if you covered your complete protein needs with whey protein. In that, it is interesting that you would get too little threonine and valine form US wheys and too little leucine and isoleucine from Brazilian wheys.

Actual deficiency symptoms as you may have expected them, when you've read the statement that whey protein supplements were "unable to supply the suggested adult athlete EAA requirement" (Almeida. 2014), however are unlikely, because (a) I assume most of you won't live off whey protein as their only protein source and (b) even if you did, you would probably consume more than the WHO recommendation for athletes (WHO. 2014) that's at the heart of Almeida et al.'s calculation suggests | Comment of Facebook!

References:

• Almeida, Cristine Couto, et al. "In vitro digestibility of commercial whey protein supplements." LWT-Food Science and Technology (2014). 
• AOAC International, and George W. Latimer. Official Methods of analysis of AOAC International. AOAC International, 2012.
• Hsu, H. W., et al. "A multienzyme technique for estimating protein digestibility." Journal of Food Science 42.5 (1977): 1269-1273.
• WHO. "Protein and amino acid requirements in human nutrition." World Health Organization technical report series 935 (2007):

Whey Protein Hydrolysates are the Past! Salmon Protein Hydrolysate Can Deliver Protein Even Faster, But Does This Also Mean They Are More "Anabolic"?

That's salmon, yes, but it's not processed enough to compete with any hydrolysate. Well, unless you decide to eat and regurgitate it - after some time, obviously, 'cause "hydrolyzed" proteins are in the end only pre-digested proteins.

As a SuppVersity reader you know that the amount of protein is not the only determinant of the potential muscle building effects of a given protein source. The digestion time and thus the amount of protein that is released into the bloodstream on a "per minute"-basis, as well as the amino acid profile (preferably all essential amino acids (EAAs) and a high amount of leucine) are also important determinants of the "anabolic" qualities of a given protein source.

Using a quite unique multi-compartmental dynamic model that closely simulates in vivo gastrointestinal tract digestion in humans scientists from the Institute of Nutrition and Functional Foods (INAF) at the Université Laval in Quebec, did now determine that salmon not whey protein hydrolysates are the "numero uno", when it comes to digestion speed.

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If you take a closer look at the data in Figure 2 at the bottom of the article, you will notice that salmon and whey hydrolysates were not the only products the scientists tested (I would love to help you along with the amino acid compositions, but unfortunately the full text does not provide any details and Hofseth  Biocare the producer of the salmon protein hydrolysate does not disclose if it's made from fish heads or salmon filets... I am not kidding, scientists have been investigating methods to produce salmon protein hydrolysates from the waste material for years; cf. Gbogour. 2004).

In view of the fact that we don't really know if salmon has similar real-world pro-anabolic effects, it may thus be at least as interesting to compare the digestion speed of whey hydrolysates and isolates.

Figure 1: Nitrogen distribution throughout the TIM-1 compartments at the end of the 2 hour digestion. SHP, salmon protein hydrolysate; WPH-High, whey protein hydrolysate extensively hydrolysed; WPH-Low, whey protein hydrolysate weakly hydrolysed; WPI, whey protein isolate (Framroze. 2014)

The latter is, as you can see in Figure 1, only significant if the hydro-whey is "extensively hydrolyzed". The difference between regular hydro-whey and the two whey isolates, on the other hand, is too to assume that it may - by any means - be relevant.

Figure 2: Data shows how much of the protein content is released in the course of a 120min digestion period (Framoze. 2014).

Let's not jump tp conclusions, here: In spite of the fact that the nitrogen digestibility data in Figure 2 supports the notion that salmon is not just the faster digesting, but also the more bioaccessible protein source. The currently available evidence on the effects of salmon protein hydrolysates on skeletal muscle hypertrophy, fat loss, blood pressure and inflammation - all things where we have plenty of evidence for beneficial effects of whey protein - is non-existent. Considering the fact that salmon protein hydrolysates are probably even more disgusting than their whey counterparts, I would thus not go and buy the next best product you can possibly find on the Internet.

Reference: 

• Framroze, Bomi, et al. "Comparison of Nitrogen Bioaccessibility from Salmon and Whey Protein Hydrolysates using a Human Gastrointestinal Model (TIM-1)." Functional Foods in Health and Disease 2014; 4(5):222-231  
• Gbogouri, G. A., et al. "Influence of hydrolysis degree on the functional properties of salmon byproducts hydrolysates." Journal of food science 69.8 (2004): C615-C622.

True or False: High Volume + Nutrient + Low Energy Foods Keep You Lean. Bonus-Q: Will a High Volume Make Your Stomach Go Baggy & Mess Up Your Satiety Response?

There are millions of ways to con- sume 100kcal and volume isn't the only difference (img greatist.com)

I have repeatedly pointed out that filling yourself up on vegetables and other high volume, high nutrient (vitamins, minerals, polyphenols, etc.), low energy foods is one of the fundamental principles of weight management. The question that remains, though, is whether this principle is so effective because of the food we eat (tons of veggies), or rather due to the fact that there is no room for the foods we thusly don't eat (the typical processed junk)?

I guess, it's not debatable that replacing trashy foods with healthy ones is the most important factor. We have all heard about the beneficial effects "high volume foods" and the downsides of the average high energy + low nutrient 100kcal junk-food snack. But how important is the volume, actually? Isn't food "quality" (whatever that may be) all that counts?

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It's surprisingly difficult to answer this question and after reviewing the most important studies, I have to say that I still can't tell for sure how important the volume is.

Figure 1: Effects of pylorectomy (removal of the part of the stomach that contains the vagal nerves) and vagal deafferetation on the ability of CCK to affect liquid food intake in rats (Moran. 1988)

What I can tell you, though, is that it appears to be certain that the mechanical stretch will be detected by vagal affarent endings in the stomach (Phillips. 2000; Berthoud. 2001). These "stretch detectors" are hard-wired to your brain, where they are processed in the so-called "nucleus tractus solitarius" (Näslund. 2007). Unfortunately, the exact role of the "nucleus tractus solitarius" in the satiety response is not even partly understood.

What we do know is that electrophysiological recording studies as well as behavioral studies have found that the effect of a given dose of cholecystokinin (CCK) is increased in the presence of stomach stretch (Schwartz. 1993 & 1995) and disrupted, when the vagus nerve is damaged or the NTS lesioned (Edwards. 1986; Moran. 1988; Smith. 1985).

With CCK being a major satiety hormone (and on top one that actually does what it's name implies, i.e. signal satiety) it appears to be quite certain that the multiplying effect the mechanical stretch exerts on the satiety effect of CCK is one of the secondary mechanisms by which eating high volume foods keep you lean.

Do you remember? You've read about a couple of things that will increase the release of CCK and would thus synergize with the effects of what I would like to call "high volume eating": (1) The pre-ingestion of protein before a meal | learn more, (2) Arginine, lysine and glutamic acid | learn more, and lastly and unsurprisingly a gastric bypass operation | learn more. Another well-known trigger of CCK release is the ingestion of fatty acids (low amounts suffice; long chain polyunsaturated fatty acids are particularly effective; Gribble. 2012) - is not satiating.

In view of the fact that the NTR, ie. the nucleus tractus solitarius, integrates (adds up and processes) a whole host of signals from the gastro-intestinal tract, it's also hardly surprising that a gastric bypass surgery and the corresponding increase in stretch per volume unit of food that has just recently been shown to change not just the satiety response to food but also the way foods taste and smell for patients who have undergone Roux-en-Y gastric bypass surgery (learn more in the SuppVersity Facebook News).

Figure 2: Model depicting signals that influence food intake. Not all elements are relevant in the context of this article - focus on the way the satiety signals that are generated in the gastrointestinal (GI) tract during meals provide information about mechanical (e.g., stomach stretch, volume) and chemical properties of the food to the brain (Woods. 2004)

Other mechanisms by which the gastric stretch may contribute to an increase in satiety / reduction in food intake and, via the release of GLP-1 and other glucose regulating satiety hormones (learn more about GLP-1) are the reduction of gastric emptying (Read. 1994), and other interactions between the vagus nerve and the brain, which include aside from directly satiety related mechanisms also the activation of serotonergic neurons (remember: serotonin is the happy hormone) in the brain (Mazda. 2004).

Bonus question: Is high volume eating setting you up for obesity? You could argue that the constant gastric distension and consequently increased postprandial gastric accommodation will reduce the satiety response to small calorie dense meals. Now aside from the fact that you will get fat, no matter what if you eat those on a daily basis, a study from the Gastroenterology Research Unit in Rochester and the Mayo Clinic did not find a sign of increased postprandial gastric accommodation or reduced satiety in any of of their 13 obese subjects (Kim. 2012).

So, yes! There is more to eating tons of veggies than not eating tons of other food. Moreover, although we don't yet know exactly what this "more" is, we can already say that all the existing evidence appears to support that it the high food volume, the stretch of the stomach and the vagally mediated downstream effects on the release and effect of our satiety hormones (incretins) is one of the factors that contribute to the ability of high volume, high nutrient, low energy foods to keep you lean.

On it's own, the multi-layered stretch-response is probably significantly less important than the reduction in junk-food intake. In conjunction with the synergistic effects of a high protein diet, and a reasonable amount of long-chain fatty acids in the diet, it could yet be what distinguishes people who have to resort to a gastric bypass as a last resort to save their lives from those individuals, who manage to flip the switch, turn their life around and lose their life-threatening overweight without the help of a surgeon.

References:

• Berthoud, Hans-Rudolf, Penny A. Lynn, and L. Ashley Blackshaw. "Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 280.5 (2001): R1371-R1381.
• Edwards, et al. "Dorsomedial hindbrain participation in cholecystokinin-induced satiety." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 251.5 (1986): R971-R977. 
• Gribble, Fiona M. "The gut endocrine system as a coordinator of postprandial nutrient homoeostasis." Proceedings of the Nutrition Society 71.4 (2012): 456. 
• Kim, Doe‐Young, et al. "Is there a role for gastric accommodation and satiety in asymptomatic obese people?." Obesity research 9.11 (2001): 655-661.
• Mazda, Takayuki, et al. "Gastric distension-induced release of 5-HT stimulates c-fos expression in specific brain nuclei via 5-HT3 receptors in conscious rats." American Journal of Physiology-Gastrointestinal and Liver Physiology 287.1 (2004): G228-G235.
• Moran, Timothy H., et al. "Pylorectomy reduces the satiety action of cholecystokinin." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 255.6 (1988): R1059-R1063.
• Näslund, Erik, and Per M. Hellström. "Appetite signaling: from gut peptides and enteric nerves to brain." Physiology & behavior 92.1 (2007): 256-262.
• Phillips, Robert J., and Terry L. Powley. "Tension and stretch receptors in gastrointestinal smooth muscle: re-evaluating vagal mechanoreceptor electrophysiology." Brain research reviews 34.1 (2000): 1-26.
• Read, Nicholas, Stephen French, and Karen Cunningham. "The role of the gut in regulating food intake in man." Nutrition reviews 52.1 (1994): 1-10.
• Schwartz, Gary J., et al. "Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 265.4 (1993): R872-R876.
• Schwartz, Gary J., Gervais Tougas, and Timothy H. Moran. "Integration of vagal afferent responses to duodenal loads and exogenous CCK in rats." Peptides 16.4 (1995): 707-711.
• Smith, Gerard P, et al. "Afferent axons in abdominal vagus mediate satiety effect of cholecystokinin in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 249.5 (1985): R638-R641.
• Woods, Stephen C. "Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake." American Journal of Physiology-Gastrointestinal and Liver Physiology 286.1 (2004): G7-G13.