Saturday, August 19, 2017

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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Always Hungry? Here's Why...
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!
  • 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.
  • 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.
  • 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).