New Studies on the Gut, Microbiome and Dietary Fiber: 25% Reduced Glucose Response to White Bread, Fiber for the Health of Our Youngest & Oldest -- Nutrients September '16

When the average Westerner hears the word fiber, his marketing indoctrinated brain will associate "cereals"... thanks to the marketing campaigns of Kellog's and co. we have been brainwashed to forget that even the less processed cereals have a comparatively low fiber/kcal ratio compared to veggies, for example.

Initially, I wanted to add the word "all" into the headline of today's article, but that would have promised a bit more than today's article will deliver. It's not "all" as in "all the articles I haven't discussed, yet", but rather "all" as in all the articles from the albeit very recommendable peer-reviewed scientific journal Nutrients.

I promise, though: Even this version of "all" is going to have at least one "gem"that will awake SuppVersity reader's interest. You want examples? Here you go: (a) oat bran preload before high carbohydrate meal reduces post-prandial glucose excursions by ~25%; (b) Dietary fiber (DF) intake in infancy is good for cardiometabolic health - especially if the DA comes from potatoes; (c) fiber and metabolic / bacteria produced metabolites may help centenarians pass the 100-years-age-mark.

Dietary fiber is much more popular in the mainstream than protein - rightly, so?

Practical Protein Oxidation 101

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Protein Oxidation = Health Threat

Protein Timing DOES Matter!

More Protein = More Liver Fat?

• Oat bran preload before high carbohydrate meal reduces post-prandial glucose excursions by ~25% (Steinert. 2016) -- It has been long-established that viscous dietary fibers, including oat β-glucan, are one of the most effective classes of functional food ingredients for reducing postprandial blood glucose. Intriguingly, however, the mechanism of action is not fully understood.
  
  Scientists believe, though, that the increase in viscosity of the stomach contents will delay gastric emptying and thus reduce the mixing of food with digestive enzymes, which, in turn, retards glucose absorption. As Steinert et al. point out, "[p]revious studies suggest that taking viscous fibers separate from a meal may not be effective in reducing postprandial glycemia" (Steinert. 2016).
  

  

  Table 1: Nutrient composition of the test meals (Steinert. 2016).

  It is thus only logical for them to to (re-)assess the effect of consuming a preload of a commercially available oat-bran (4.5, 13.6 or 27.3 g) containing 22% of high molecular weight oat β-glucan (O22 (OatWell®22)) mixed in water before a test meal consisting of white bread (GI = 100) on the glycemic responses of 10  healthy normal-weight, overweight and obese subjects (5 male/5 female, mean age (years): 48.0 ± 15.3 (range 22–65), BMI (kg/m2): 29.5 ± 4.4 (range 23.2–36.9)) subjects.
  

  

  Figure 1: Figure 1. Panel (A): Blood glucose concentrations after taking 0, 4.5, 13.6 and 27.3 g, respectively, of OatWell®22 (O22-0, O22-4.5, O22-13.6 and O22-27.3) at −5 min followed by 50 g available carbohydrate from white bread at 0 min. Values are means ± SEM for n = 10 subjects. a–c Means at the same time containing different letters within the superscripts differ significantly by Tukey’s test p < 0.05; (B,C): Percentage reduction from control in incremental areas under the curve (AUC); (B) and peak rise in blood glucose; (C) after taking 0, 4.5, 13.6 and 27.3 g of OatWell®22 (0, 0.9, 2.6 and 5.3 g oat β-glucan, respectively) at −5 min followed by 50 g available carbohydrate from white bread at 0 min | Steinert. 2016).

  As the data in Figure 1 goes to show you, the researchers found a significant effect of dose (meaning: more helps more) on blood glucose area under the curve (AUC) (p = 0.006) with AUC after 27.3 g of O22 being significantly lower than white bread only. Their linear regression analysis showed that each gram of oat β-glucan reduced glucose AUC by 4.35% ± 1.20% (r = 0.507, p = 0.0008, n = 40) and peak rise by 6.57% ± 1.49% (r = 0.582, p < 0.0001).
  
  What the scientists forget to mention in their conclusion, though, is that this effect, as good as it may be for the average sedentary slob, may hamper the strategic use of readily digestible carbohydrates to refuel your glycogen stores in athletes. Nevertheless, even athletes, who don't react like the one outlier the scientists removed before plotting the data in Figure 1, can benefit from "the use of oat bran as nutritional preload strategy in the management of postprandial glycemia" - not necessarily during or right after competitions, though.
• Dietary fiber (DF) intake in infancy is good for cardiometabolic health - especially if the DA comes from potatoes (van Gjissel. 2016) -- "Dietary fiber (DF) intake may be beneficial for cardiometabolic health. However, whether this already occurs in early childhood is unclear," that's the first sentence in van Gjissel et al.'s 2016 investigation of the associations between DF intake in infancy and cardiometabolic health in childhood among 2032 children participating in a population-based cohort in The Netherlands.

  "Information on DF intake at a median age of 12.9 months was collected using a food-frequency questionnaire. DF was adjusted for energy intake using the residual method. At age 6 years, body fat percentage, high-density lipoprotein (HDL)-cholesterol, insulin, triglycerides, and blood pressure were assessed and expressed in age- and sex-specific standard deviation scores (SDS). These five factors were combined into a cardiometabolic risk factor score. In models adjusted for several parental and child covariates, a higher DF intake was associated with a lower cardiometabolic risk factor score."

  When the Dutch scientists examined individual cardiometabolic factors, they observed that a 1 g/day higher energy-adjusted DF intake was associated with 0.026 SDS higher HDL-cholesterol (95% CI 0.009, 0.042), and 0.020 SDS lower triglycerides (95% CI −0.037, −0.003), but not with body fat, insulin, or blood pressure - most intriguingly with potatoes having by far the most significant effects of all individual fibers the scientists examined.
  

  

  Figure 2: Covariate- and energy-adjusted association of dietary fiber intake from cereals, from potatoes, from fruits and vegetables, and from legumes (per 1 g/day) and cardiometabolic outcomes.

  Now, obviously that is not earth-shatteringly much, but since the overall results were similar for DF with and without adjustment for energy intake, it does, as the scientists point out suggest that a "higher DF intake in infancy may be associated with better cardiometabolic health in later childhood" (van Gjissel. 2016).
• Fiber and metabolic / bacteria produced metabolites may help centenarians pass the 100-years-age-mark (Cai. 2016) -- Scientists often pay too much attention to sick and too little attention to healthy people. Studies in centenarians are one of the few exceptions to this rule, as they are designed to elucidate what it is that allows these individuals to live for 100 years and more and still be in better health than many of us who are 20-40 years younger.
  
  Our knowledge of the relationships between diet and metabolites as well as element profiles in healthy centenarians, as important as it probably is, remains inconclusive. Therefore, scientists from the Guangxi University conducted a new study to potential role of short-chain fatty acids (SCFAs), total bile acids and ammonia in feces, phenol, p-cresol, uric acid, urea, creatinine and ammonia in urine, and element profiles in fingernails on the health and life-expectancy in 90 elderly people, including centenarians from Bama county (China)—a famous longevous region—and elderly people aged 80–99 from the longevous region and a non-longevous region.
  To identify relevant patterns, the authors used a partial least squares-discriminant analysis that revealed a distinct metabolic pattern with seven characteristic components: acetic acid, total SCFA, Mn, Co, propionic acid, butyric acid and valeric acid.
  

  

  Figure 3: No, it's not all about the microbiome, but it appears as if substances your gut tenants are going to produce from fiber in your colon are on of the reason centenarians make it past the 100 year mark.

  The concentration of these metabolites and minerals were significantly higher in the centenarians group (p < 0.05). How does that relate to fiber? Well, the dietary fiber intake was positively associated with the butyric acid contents in the feces of the subjects (r = 0.896, p < 0.01), which suggests "that elevated dietary fiber intake[s] should be a path toward health and longevity" (Cai. 2016 | my emphasis) - and I deliberately underlined and italicized the word "a", here, because a high fiber intake, alone, affects only butyric acid, propionic acid and short-chain fatty acid levels. With manganese, copper and valeric acid, which has a similar structure as GHB or GABA, even the obviously incomplete list of longevity promoters from the study at hand contains elements that are not directly related to your fiber intake. 

Summary of the relationship between rice bran intake, microbial dysbiosis and colorectal cancer (So. 2016).

What else is in the news? Three other studies that didn't make it into the previous overview but are at least something for the bottom line add to the ever-increasing evidence of the health-relevance of fiber <> microbiome interactions in your gut.

In this regard, So et al. prove that evidence of the protective effect of ricebran against the carcinogenic effects of microbial dysbiosis (So. 2016). And Collins & Reid (2016) have written a free full-text review of how prebiotics (like fiber) will work their health magic far away from their destination in the gut - e.g. in / on your bones, brain and CNS, immune system, skin and serum lipids | Comment!

References:

• Cai, D.; Zhao, S.; Li, D.; Chang, F.; Tian, X.; Huang, G.; Zhu, Z.; Liu, D.; Dou, X.; Li, S.; Zhao, M.; Li, Q. Nutrient Intake Is Associated with Longevity Characterization by Metabolites and Element Profiles of Healthy Centenarians. Nutrients 2016, 8, 564.
• Collins, S.; Reid, G. Distant Site Effects of Ingested Prebiotics. Nutrients 2016, 8, 523.
• So, W.K.W.; Law, B.M.H.; Law, P.T.W.; Chan, C.W.H.; Chair, S.Y. Current Hypothesis for the Relationship between Dietary Rice Bran Intake, the Intestinal Microbiota and Colorectal Cancer Prevention. Nutrients 2016, 8, 569.
• Steinert, R.E.; Raederstorff, D.; Wolever, T.M.S. Effect of Consuming Oat Bran Mixed in Water before a Meal on Glycemic Responses in Healthy Humans—A Pilot Study. Nutrients 2016, 8, 524.
• van Gijssel, R.M.A.; Braun, K.V.E.; Kiefte-de Jong, J.C.; Jaddoe, V.W.V.; Franco, O.H.; Voortman, T. Associations between Dietary Fiber Intake in Infancy and Cardiometabolic Health at School Age: The Generation R Study. Nutrients 2016, 8, 531.

Taurine Boosts Good Gut Bacteria & Short-Chain Fatty Acid Prod. | 1st Study to Show Natural Beats Synthetic Taurine

The bacteria in our guts are the latest rage in medical sciences... and taurine, especially natural taurine, may be a way to modulate them in beneficial ways.

It has been some time since the last taurine article on the SuppVersity (read all articles). There was simply a lack of interesting studies... until now, or rather until the latest study of scientists from the Zhejiang University of Technology which suggests that taurine "might be of benefit to health by inhibiting the growth of harmful bacteria, accelerating the production of SCFA and reducing LPS concentration" (Yu. 2016).

As the authors of the paper point out, taurine is a necessary amino acid that taurine plays an important role in the regulation of neuroendocrine functions and nutrition.

In previous studies, taurine was shown to improve immunity, resist oxidation, delay senility, reduce blood pressure, promote recovery from acute hepatitis, etc. (Averin. 2015; Wang. 2013; De Luca. 2015; Ito. 2012). In addition, taurine can also improve the metabolism of the nutrients and play an important role in the regulation of neuroendocrine (Cuttitta et al. 2013; Camargo et al. 2015).

You can learn more about taurine & other amino acids at the SuppVersity

Taurine Pumps Up Strength & Recovery?

Taurine Improves Insulin + Glucose Metabolism

Taurine ➲ 180% Testosterone Increase

Taurine + BCAA Work Hand in Hand

43% Reduced Performance W/ BCAAs

3g Taurine Boost Glycogen Re-synthesis Sign.

With their latest study, the Chinese scientists Haining Yu, Zhengzhao Guo, Shengrong Shen , an Weiguang Shan were now able to add yet another beneficial health effect of taurine to the previous, impressive list: taurine's effect on gut microbes and metabolism.

Food	Amount	Taurine (mg)
Cheese	3 ounces	1000
Cheese,cottage	1 cup	1700
Milk,whole	1 cup	400
Yogurt	1 cup	400
Wild game	3 ounces	600
Pork	3 ounces	540
Granola	1 cup	650
Oatmeal flakes	1 cup	500
Chocolate	1 cup	400
Meat (luncheon)	1 cup	390
Wheat germ,toasted	1/4 cup	350
Egg	1 (medium size)	350
Turkey	3 ounces	240
Duck	3 ounces	240
Chicken	3 ounces	185
Sausage	3 ounces	185
Avocado	1/2 (medium)	75
Table 1: It doesn't always have to be supplements - Taurine content of selected foods (USDA Handbook #8)

As you'd expect it for a "first of its kind" study, the researchers used a rodent model to evaluate the effects of a human equivalent dose of ~1g of taurine in BALB/C who were randomly divided into three experimental groups:

• the first group was administered saline (CK),
• the second group was administered 165 mg/kg natural taurine (NE) and
• the third group one administered 165 mg/kg synthetic taurine (CS).

With the NE and CS group, this is also one of the few studies to distinguish between "natural" and "synthetic" taurine, which is obtained from isethionic acid (2-hydroxyethanesulfonic acid) and not extracted from animal bile, usually that of the ox, and subjected to a series of purification procedures by several different methods (Gioacchini. 1995).

Figure 1: Effects of taurine on gut bacteria abundance (Yu. 2016).

To assess the effects, the gut microbiota composition in mice feces was analyzed by metagenomics technology, and the content of short-chain fatty acids (SCFA) in mice feces was detected by gas chromatography (GC), while the concentrations of lipopolysaccharide (LPS) and superoxide dismutase (SOD) were detected by a LPS ELISA kit and a SOD assay kit, respectively.

Studies Confirm: Natural and Synthetic Vitamins Can Differ in Quantity & Quality of Effects! Vitamins A-E, B's & More | read more

Is "natural taurine" the "better taurine"? In the study at hand, it seems as if this was the case. The only evidence from other studies that suggests that the source of taurine matters, however, is 1995 paper by Gioacchini et al. who developed a method to distinguish the two and may thus have a vested interest in stating that "[n]atural taurine is an essential constituent of formula milk for infants and, because of the inferior nutritional value (δ), of synthetic forms, it is important to discriminate between these and taurines derived from a natural source" (Gioacchini. 1995). Another study shows that the allergy risk for synthetic taurine appears to be elevated (Lee. 2013).

Why this is the case or what triggers any differences in the effect on the microbiome is something I cannot tell you: if the molecules were structurally different, Gioacchini et al. would after all not have had to use the 13C/12C ratio that is also used to date bones and other relicts. It could eventually be solely a question of dosage - with "inferior nutritional value" the synthetic taurine may have to be dosed much higher... as high as in most previously published human studies which generated the most impressive results with 3-6g and thus 3-6x more taurine per day than the human equivalent dose (learn more about the HED concept) of the study at hand.

As the data in Figure 1 indicates, taurine had profound effects on gut microbiota could reduce the abundance of Proteobacteria, especially Helicobacter (see Figure 1, bottom right). In that, it is interesting to see that the natural taurine ...

• had more pronounced beneficial effects on the count of good bacteroidetes and was more potent than the synthetic version when it comes to reducing proteobacteria and helicobacter, and even more intriguingly
• had opposite effects on firmicutes which make up the largest portion of the mouse and human gut microbiome, can't be described as "beneficial" or "bad" as a whole, but have been shown to be involved in energy resorption and obesity

In line with the last-mentioned increase in firmicutes is the scientists' observation that the SCFA content was increased in feces of the NE group, but not the CS group that received the synthetic taurine supplement.

Figure 2: Short-chain fatty acid (SCFA) and Activity of superoxide dismutase (SOD) levels in response to natural (NE), synthetic taurine (CS) and saline control (CK) supplementation in mice (Yu. 2016).

That's interesting, also because this change went hand in hand with a 'natural exclusive' LPS content was decreased, but similar increases in the activity of the antioxidant SOD enzyme in serum and livers of the both taurine groups.

None of the previous taurine studies declared whether the chemical they used was "natural" or "synthetic", I thus suspect that a synthetic version was used in most if not all of them - that this could make a difference is still both surprising and intriguing.

Bottom line: While it is correct that both "natural taurine and the synthetic taurine could regulate the gut micro-ecology, which might be of benefit to health by inhibiting the growth of harmful bacteria" (Yu. 2016), it is quite intriguing that only the natural taurine accelerated the production of SCFA and reducing LPS concentration, while the synthetic taurine did not.

Unfortunately, I have no studies to tell you if there's (a) a general advantage of natural over synthetic taurine (see red box, too), or (b) whether your taurine is natural or synthetic. If the previous quote (see red box) from Gioacchini et al. is accurate, though, it would appear that (a) 'natural' was superior and that (b) your taurine supplement was almost certainly nor extracted from ox-bile or another expensive natural source | Comment on Facebook!

References:

• De Luca, Annamaria, Sabata Pierno, and Diana Conte Camerino. "Taurine: the appeal of a safe amino acid for skeletal muscle disorders." Journal of translational medicine 13.1 (2015): 1.
• Gioacchini, Anna Maria, et al. "Differentiation between natural and synthetic taurine using the 13C/12C isotope ratio." Rapid communications in mass spectrometry 9.12 (1995): 1106-1108.
• Ito, Takashi, Stephen W. Schaffer, and Junichi Azuma. "The potential usefulness of taurine on diabetes mellitus and its complications." Amino acids 42.5 (2012): 1529-1539.
• Lee, Seung-Eun, et al. "A case of taurine-containing drink induced anaphylaxis." Asia Pacific Allergy 3.1 (2013): 70.
• Yu, Haining, et al. "Effects of taurine on gut microbiota and metabolism in mice." Amino acids (2016): 1-17.

Walnuts, Beans & Cacao - Anti-Cancer, Anti-Colitis, Anti-Diabetes (Super-)Foods that May Fail the Reality Check

Walnuts, cacao and beans, 3 superfoods that are super only in super-high quantities.

Today's SuppVersity Food Science Research Update is all about three so-called "superfoods". It's an article from which you cannot just learn that walnuts, beans and cacao are "superfoods" as they protect you from cancer, improve your gut health and ameliorate diabetes.

It's yet also an article that puts the (rodent) science into perspective. A perspective you won't see taken very often, because it has the "superfoods" look much less "super" than they appear to be without a reality check.

Read more short news at the SuppVersity

Exercise Research Uptake Nov '14 1/2

Exercise Research Uptake Nov '14 2/2

Weight Loss Supplements Exposed

Exercise Supplementation Quickie

Squat 4 Min B4 Workout, Chains & Bands + More

Read the Latest Ex. Science Update

• Dietary walnut suppression of colorectal cancer in mice: Mediation by miRNA patterns and fatty acid incorporation - As a SuppVersity reader you are well aware of the beneficial health effects of regular walnut consumption. As far as the mechanisms are concerned, many of you may have speculated that it is related to omega-3s, but do walnuts even have enough omega-3s to make a difference? A recent study from the Beth Israel Deaconess Medical Center at the Harvard Medical School (Tsoukas. 2015) seems to have found the answer is "yes", but it takes some serious walnut eating.
  
  To investigate the protective effects of a high walnut diet, the scientists injected rodents with HT-29 colon cancer cells. 7 days after the injection, the mice were randomized to either control or walnut diets for 25 days of diet treatment. After the study period, thirty samples of tumor and of omental adipose were analyzed to determine changes in lipid composition in each dietary group in response to diets containing either no or 10% (of weight) walnuts.
  

  

  Figure 1: Gas chromatography analysis of fatty acids in colorectal tumors (left) and omental adipose tissue (right) in 30 mouse samples (Tsoukas. 2015). *P<.05.

  In the tumors of the walnut-containing diet, the scientists found significant increases in α-linolenic, eicosapentaenoic, docosahexaenoic and total omega-3 acids, and a decrease in arachidonic acid, as compared to the control diet.
• More importantly, however, the final tumor size measured at sacrifice was negatively associated with percentage of total omega-3 fatty acid composition (r=−0.641, P=.001). MicroRNA expression analysis of colorectal tumor tissue revealed decreased expression of miRNAs 1903, 467c and 3068 (P<.05) and increased expression of miRNA 297a* (P=.0059) in the walnut-treated group as compared to control diet... and YES! This is the epigenetic "magic" everyone is talking about.
• Beans are SFCA-precursors and colon protectors - Short-chain fatty acids are all the rage these days. SFCAs are the fatty acids that are produced by our bacterial subtenants when we eat resistant starches.
  
  Beans are an excellent source of resistant starches and, according to a recent study from the Agriculture and Agri-Food Canada (Monk. 2015), both cooked white (WK) or dark red kidney (DK) bean flour can, when it is added at 20% to a rodent diet  for 3 weeks, can protect rodents from the pro-colitic assault of dextran sodium sulfate.
  

  

  Figure 1: Effect of kidney bean diets on (A) SCFA concentrations, (B) cecum size and (C) colon histomorphology in healthy mice + representative images (40×) of  stained colon sections stained highlighting the increased crypt height in the bean-fed mice are shown (scale bar=50μm | Monk. 2015).

  Not only did the "bean preload" (a) reduce the disease severity. It did also ameliorate (b) the colonic histological damage and (c) increase the mRNA expression of antimicrobial and barrier integrity-promoting genes (Toll-like Receptor 4 (TLR4), MUC1–3, Relmβ and Trefoil Factor 3 (TFF3)) and reduce proinflammatory mediator expression [interleukin (IL)-1β, IL-6, interferon (IFN)γ, tumor necrosis factor (TNF)α and monocyte chemoattractant protein-1], which correlated with reduced colon tissue protein levels.
  
  In conjunction with their beneficial effects on IL-17A, IFNγ, TNFα, IL-1β and IL-6, there's little doubt that bean floor can enhance the microbial-derived SCFA metabolite production, gut barrier integrity and the microbial defensive response in the healthy colon, this making it more resilient to artificial and natural assaults.
• Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats  - While the latest "eat chocolate to lose weigh" paper has been busted, findings of a recent study from the Ciudad Universitaria suggest that cocoa, not chocolate, has the potential to alleviate both hyperglycemia and hepatic insulin resistance in type 2 diabetics - in rats, it already works (Cordero-Herrera. 2015).
  
  In the study, male Zucker diabetic fatty (ZDF) rats which are a common model for "lifestyle" diabetes were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. ZDF rats supplemented with cocoa (ZDF-Co) showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance and insulin resistance.
  

  

  Figure 1: Effect of the cocoa-rich diet on glucose tolerance and insulin resistance in ZDF rats. (A) Time-course changes in the basal level and after glucose loading (1 g/kg) of blood glucose. (B) AUC calculated from GTT data. (C) Time-course changes in the basal level and after glucose loading (1 g/kg) of serum insulin. Each point represents the mean±S.D. from 8 determinations. (D) HOMA-IR was determined as described in Materials and Methods (p < 0.05 | Cordero-Herrera. 2015).

  The cocoa-rich diet also ameliorated the hepatic insulin resistance by abolishing the increased serine-phosphorylated levels of the insulin receptor substrate 1 and preventing the inactivation of the glycogen synthase kinase 3/glycogen synthase pathway in the liver of cocoa-fed ZDF rats - or put simply, it kept the glycogen storage (and thus another way to store glucose and normalize the blood glucose levels) in the liver intact.
  
  The authors believe that this anti-hyperglycemic effect of cocoa must at least partly be mediated through the decreased levels of hepatic phosphoenolpyruvate carboxykinase which will have the liver pump out more glucose (made mostly from amino acids) although the glucose levels in the blood are already in the red zone while increasing the values of the previously mentioned glucokinase and glucose transporter 2 in the liver which will allow cacao aficionados to store the superfluous glucose as glycogen, not fat. The additional suppression of the c-Jun N-terminal kinase and p38 activation which is usually elevated in response to insulin resistance may also protect you against cancer.

Broccoli No Superfood? Fem. Orgasm, What's It Good For? Can Piperine Make You Lean? Skinfold Thickness & Insulin Sensitivity? Exercise, Cortisol, BDNF, Fatigue, IGF, Pollution, NOPE, EGCG & More | more

So what have you learned today? You've learned that walnuts, beans and cacao are what other people may call "superfoods". Since this is the SuppVersity and not your next-best "natural * whatever * bogus * blog" I will now tell you that there's a huge caveat with these impressive data: DOSAGE! In the walnut study, for example, the food contained 100g/kg cacao powder that's 10% of the diet being pure cacao. The same goes for the walnut diet in the Tsoukas study. 10% walnuts in the diet, that's 65% of the total energy intake from walnuts and would equal 205g of walnuts for someone on the standard 2000kcal/day diet that's also used for the calculations on the nutrition labels.

If you think you can stomach that and - at the same time - cut the caloric equivalent of those 205g of walnuts from your "regular diet" in order not to get fat, go for it, but let's be honest: You don't really want to eat that "super", do you? No, you don't, but that's not a problem. Food is food and the aforementioned foods are still healthy, even if you don't eat them in the quantities that would be necessary to achieve "medicinal" effects | Comment on Facebook!

References:

• Cordero-Herrera, Isabel, et al. "Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats." The Journal of nutritional biochemistry (2015).
• Monk, Jennifer M., et al. "White and dark kidney beans reduce colonic mucosal damage and inflammation in response to dextran sodium sulfate." The Journal of nutritional biochemistry (2015).
• Tsoukas, Michael A., et al. "Dietary walnut suppression of colorectal cancer in mice: Mediation by miRNA patterns and fatty acid incorporation." The Journal of nutritional biochemistry (2015).

Ramp Up Your Short-Chain Fatty Acid Production With Fermentable Starches Within 6 Days. Longterm Fat Loss, Gut Health & Cancer Protection Possible

You cannot handpick several billion lodgers in your intestine, but you can attract the right one by providing them with the foods they like. Contrary to the current probiotic hype, the key to gut and metabolic health lies in the prebiotics you are stuffing down your piehole.

It's quite funny, only 5 years ago, everyone was still smiling at people who spent extra bucks on yogurts and other dairy products that were enriched with certain bacteria strains - strains, which were and obviously still are supposed to have health-promoting effects. The fact that probiotic yogurts and similar stuff have meanwhile made it into the store brand line-up of the large discount-markets (at least here in Germany) is however clear cut evidence that the previously laughed at idea that gut bugs are something you want to foster and promote has meanwhile turned into another of those partly highly questionable, but widely accepted pieces of "nutritional wisdom". The question that remains is, will they join the ranks of other scientific hypothesis that have made it n allegedly oversimplified from the bench to the store-boards before their time was ripe? Hypotheses such as the "cholesterol is bad for your heart", the "pasta and rice will keep you lean" and the "fat makes fat" hypotheses?

Don't worry, I am neither going to rant, nor am I suggesting that the whole idea about the importance of the gut microbiome is similarly flawed as the "eat fat and get fat"-hypothesis. The thing I do yet want to point out, before I tell you more about the latest scientific findings, is that our knowledge about the good and the bad guys in our intestines, about the ways they interact and about the short- and longterm effects of these interactions are so limited that my gut tells me (all puns intended) that everything that goes beyond the classics, i.e. the consumption of a diet rich in various types of fibers and a reasonable amount of fermented foods could well turn against us in a not very distant future.

Feeding the good guys: Does it work? And how does it work?

Based on the currently available evidence, it does however in fact look like the shift towards short-chain fatty acid producing bacteria, the scientists from the University of Minnesota and the scientist from the Fred Hutchinson Cancer Research Center initiated in their 20 study participants (ten men and ten women) who had been recruited via flyers around the University campus (that alone goes to tell you how "mainstream" the notion of beneficial gut bacteria has become). The subjects were health and aged between 18 and 60 years, they were non-smokers and were not taking any prescription meds and contrary to the average American (cf. "How Fat We Have Become") their BMIs were in the normal range.

Table 1: Macronutrient composition of the test meal on day 1 and the supplemental cereal bars and beverages the subjects consumed in the course of the 6-day study period on four occasions every day (Klosterbuer. 2013)

"Participants consumed five treatments in a double-blind, cross-over design with treatment periods of 7 d followed by a 21 d washout period. On day 1 of the study, following a 12 h fast, participants arrived at the GCRC and consumed either a low-fibre control breakfast or one of four fibre-containing breakfasts. Meals consisted of a muffin, hot cereal, and fruit-flavoured beverage. For the next 6 d, participants consumed the study products at home. Treatments were provided as cereal bars and a beverage mix, which was pre-measured into 500 ml water bottles. Participants were instructed to consume four cereal bars and one beverage over the course of each day." (Klosterbuer. 2013)

Obviously the test breakfast, as well as the bars and beverages the dietary composition of which you can see in table 1 contained additional "functional" additives. As indicated by the titles above the respective columns in table 1, these were

• 

  Figure 1: Short-chain fatty acid content of the stools (top), number of stools and consistency (1=hard, 4=diarrhea, middle), gastrointestinal symptoms (bottom, Klosterbuer. 2013)

  for the breakfast, 25 g SCF or RS alone or in combination with 5 g pullulan (SCF+P and RS+P),
• for the beverages and bars in the treatment groups, 20g SCF or RS alone or in combination with 5 g pullulan (SCF+P and RS+P) for the beverages and bars and
• for the beverages and bars in the control group, fully digestible maltodextrin

• the short chain fatty acids (SCF) were produced via hydrolysis of maize starch, followed by
  cooling to form a branched structure, 
• the resistant starch (RS) was a type 3 (RS3) retrograded starch roduced from heat moisture-treated, high-amylose maize starch, and 
• pullulan is a linear glucose homopolysaccharide that's formed during the fermentation of dextrin by the yeast Aureobasidium pullulans.

All test products were provided by Tate and Lyle, Inc. and - as you can likewise see in table 1 matched for macronutrient and energy content. All bars and beverages were meant to be consumed along with participants regular diets.

Astrology was yesterday, feceology (=poopology ;-) is the future!

Aside from the obligatory protocols on the state of their digestive health the subjects also had to collect stool samples, which were then analyzed by the researchers who were looking at the RNA and DNA content of the samples to identify any changes in the makeup of the gut microbiom, without exact quantification of individual strains. What they found was that ...

"[a]mong the treatments, the control was significantly different from the SCF (P<0.001) and SCFþP(P<0.0002) treatments. The SCF treatment was significantly different from the RS treatment (P<0.007), and the SCF+P treatment was significantly different from the RS+P treatment (P<0.002). The GMC [gut microbial community] following the consumption of the SCF and SCF+P treatments was not significantly different." (Klosterbuer. 2013)

Now this certainly does not sound very informative, right? It in fact isn't but let's be honest, what's the additional value of me telling you that the scientists were able to associate a certain peak in the bacterial make up with either Anaero-coccus vaginalis or Parabacteroides goldsteinii and another one with either Parabacteroides distasonis or Parabacteroides merdaeusing anisilico?  Not much, right.

"I know that we know nothing" An adequate description of the "state of the art"

My casual observation that knowing the funky names of the individual bacteria that felt specifically cosy in the acidified short-chain fatty acid loaden milieu that formed in response to the dietary intervention is about as useful to you as knowing all the names of the tiny insects in the Amazon Delta. In view of the fact that this is not much different for the scientists who were not even able to tell exactly which bugs they were looking at here. In fact, we have not even come so far to say "little do we know" - the current state of our "understanding" of the complexity of the gut microbiom is simply far from allowing any reliable prognosis statements on which bacteria we want in which ratios.

Figure 2 (first published in "Waxy Maize Reloaded"): Changes in postprandial energy expenditure (left) and fatty acid oxidation (right) after the ingestion of regular and WM-HPD pancakes (data adapted from Shimotoyodome. 2011)

That being said the net increase in SCFA production that was achieved by all treatments in the study at hand is an endpoint that may provide at least some orientation. After all, you will probably all remember the impressive results of theh Shimotoyodome study from 2011 (see figure 2) I discussed in conjunction with the post on WM-HDP, back in the day. While this is likewise still speculative, it's still highly likely that the increase in fatty acid oxidation the researchers observed in their human subjects after the consumption of pancakes that had been enriched with resistant starch (RS4) is a direct consequence of the increased short chain fatty acid production in the colon.

There is yet an important "on the other hand" we must not forget

GLP-1 is also partly responsible for the profound weight loss after bariatric surgery. In this case it is yet not the rise in short chain fatty acids, but as the scientists speculate the mechanical stretch and the influx of dietary fat that would otherwise have been absorbed earlier during the digestive process that triggers the release of the "satiety hormone" glucacgon-like peptide 1 (GLP-1, read more)

In fact, the aformentioned beneficial effects on the fatty acid metabolism and the concomitant reductions in insulin, which were brought about by an increase in GLP-1 (learn more about the potent fat burning effect of GLP-1) and decreases in GIP, respectively, have recently been traced back directly to the influence of SCFA in the long intestine. In a cleverly designed study, Lin et al. were able to show that the expression of these quasi-hormonal peptides, appears to be mediated by a direct interaction of bacteria-generated (or simply ingested) short-chain fatty acids in the gut with a speficic free free fatty acid receptor 3 (FFAR-3) in the gut lining (Lin. 2012).

As far as this part of the equation goes, we do therefore actually "know" something, what we do not know, but there are obviously a couple of my beloved "on the other hands" we still have to take into account. The most significant of these is unquestionably that impressive results as those that were observed in the very short run in the Shimotoyodome study will only arise in scenarios, in which the regular sugars and starches 90% of the Western population literally lives on are replaced with fermentable alternatives.

As long as you keep on the twinkies and dingdongs diet, the composition of your gut microbiome won't save you - no matter how good the critters are in turning fermentable starches into short chain fatty acids.

Figure 3: Different resistant starch content of various foods (% dry matter; based on Goni. 1996)

After all none of the simple sugars and easily digestible starches will even make it to the colon before they are either directly or after being disassembled by the enzymes in your gut taken up into the blood stream - the couple of  SFCA you either ingest as a supplement or your gut bacteria may be producing from additional pre-biotics (the term used in a very broad sense here and in the following paragraphs) you may be taking won't save you from the "fat" consequences.

Remember: If A → B & A → C, this does not imply B → C

Epidemiological studies such as Layden et al.'s 2012 analysis of the body composition of young, obese women in which the researchers found a negative correlation between body fatness (esp. visceral obesity) and the SCFA production in the colon do therefore not necessarily tell us that having a certain gut microbiome protects you from obesity (Layden. 2012). Observational studies like these, but also all experiments in which the human or rodent "participants" had the chance to compensate for the intake of fermentable starches or other supplements by skipping on foods they'd otherwise consume, simply tell us that eating fermentable starches is better than eating sugary junk - not more, but also not less.

Can saturated fat cause endotexemia? Learn the answer here!

If the ladies with the lower visceral fat in the Layden study consumed a diet that was devoid of fermentable starches, they would not produce any short chain fatty acids no matter how the composition of their gut microbiome may look like (in fact it would soon look like a "ghetto" full of unwanted bacterial tenants not paying their rent in form of healthy SCFA ;-). It should be obvious that the same goes for the anti-cancer effects of the SCFAs butyrate, propionate and acetate (Matthews. 2012), as well as all the other beneficial health effects which have been linked back to the bacterially manufacture two- to six-carbon chain FAs.

All the aforementioned benefits require the reguar ingestion of more than just trace amounts of fermentable starches. These pre-biotics will automatically have the "beneficial" bacteria in your gut get the better of the "bad guys" and it is a necessary prerequisite that any probiotics you are consuming either in pill form or from enriched foodstuff can take full effect. In other words:

Pre-biotics don't support probiotics, it's the other way around. Probiotics can support and accelerate the desired permanent change the regular consumption of prebiotics will bring about.

I know the product descriptions on the shiny websites of the snake oil industry will conceal that, but without a consequent and permanent change in your dietary habits, you can as well flush your super-potent 100 billion bacteria per serving probiotic directly down your toilette.

---

Even the nicest subtenants can become a real problem, when they come over without being asked day by day. Unfortunately, all sorts of gut bacteria (even the "good" ones) have as imilarly nasty habit of translocating through a leaky gut wall into parts of your body, where you certainly don't wont them... read about the nasty consequences, here

Long story short: All the current hoopla about probiotics, the tons of "enriched" products on the shelves of the supermarket, the capped super-*place your favorite strain here* with bazillions of "life-bacteria" in them and for which you would have to spend half your monthly salary, if you wanted to consume enough of them to override the baseline effect your diet, all of them are about as useful as a stimulant based fat burner on a hypercaloric diet.

You are what you eat, not what your supplement! The same goes for the composition of the bugs in your gut and if you want them to produce short chain fatty acids for you you better make sure they get the raw materials on a consistent basis. That this works like a charm within no more than 6 days is evidenced by the study publication of which triggered this lengthy discussion.

Whether all the purported health benefits will become visible in the short, long or very long term will yet still have to be elucidated... and that this is probably not going to happen, when you try to get your fermentable starches from bread only (0.25g per slice vs. navy beans 10g per 1/2 cup and even bananas 5g per banana)

References:

• Goñi I, García-Diz L, Mañas E, Saura-Calixto F. Analysis of resistant starch: a method for foods and food products  Food Chemistry. 1996; 56(4):445–449.
• Layden BT, Yalamanchi SK, Wolever TM, Dunaif A, Lowe WL Jr. Negative association of acetate with visceral adipose tissue and insulin levels. Diabetes Metab Syndr Obes. 2012;5:49-55. 
• Klosterbuer AS, Hullar AJH, Li F, Traylor E, Lampe JW, Thomas W, Slavin JL. Gastrointestinal effects of resistant starch, soluble maize fibre and pullulan in healthy adults. British Journal of Nutrition. 2013 [Epub ahead of print].
• Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240.
• Shimotoyodome A, Suzuki J, Kameo Y, Hase T. Dietary supplementation with hydroxypropyl-distarch phosphate from waxy maize starch increases resting energy expenditure by lowering the postprandial glucose-dependent insulinotropic polypeptide response in human subjects. Br J Nutr. 2011 Jul;106(1):96-104.
• Wroblewska M, Brzuzan L, Jaroslawska J, Zdunczyk Z. Effect of buckwheat sprouts and groats on the antioxidant potential of blood and caecal parameters in rats. Int J Vitam Nutr Res. 2011 Sep;81(5):286-94.

Vitamin A Regrows Liver Tissue. Polydextrose Makes Dieting a Breeze. Exercise Blunts Negative Effects of High Fructose Diet. Diabetes Precipitates Female Sexual Dysfunction.

I did miss my own 1000-posts jubilee!

This week it's pretty easy to find the SuppVersity figure of the week. It's 1011 and that's the number of individual posts this "blog" currently holds. Actually, the very moment I hit the "publish" button on this one, it's going to be 1012 (see image on the right). I guess, I should have 'celebrated' that twelve posts before, but you know how I am, it's about the quality, not the quantity and though I am aware that the latter is unquestionably fluctuating, I would hope that each of you has found one or two 'pearls' - I mean, if you didn't why are you coming back regularly, then?

Apropos regularly, it's Saturday and thus about time for a couple of "On Short Notice" items. So let's not waste any time flattering and get to the science news business:

Vitamin A essential for liver regeneration. Plus: β-carotene and cancer even in non-smokers

So much for the vitamin A vs. D antagonism - in fact, one can't go without the other: Vitamin A & D synergize against liver cancer and increase survival rates by more then 75% (read more)

(Blaner 2013) -- Other than SuppVersity readers, the average slef-proclaimed health-conscious citizen probably thinks of (false) horror stories about vitamin A laden polar bear livers killing a handful of ravenous arctic explorers. The fact that the active form of vitamin A is actually one of the most important hormone-like substances in your body that's essential for the maturation process of stem cells, on the other had, got lost at least since vitamin D the supposed vitamin A antagonist became all the rage in the past decade. Scientists from the Coumbia University in New York and the Chernivtsi National University in Chernivtsi, Ukraine, are now going to publish a paper that should remind everyone (including the science community) that the contemporary black and white painting on D & A may well impair the progress we make in our understanding of our own physiology.

Missing half your liver? Not a problem if you got enough "liver building" vitamin A ;-)

In a mouse model which has been genetically modified so that the rodents weren't able to store adequate levels of retinoids  (yeah, there is a whole family of "vitamins A") in the liver, showed a delayed and incomplete regenerative response to partial hepatectomy (cutting away parts of the liver; PHE). As the scientists point out,

"[t]he requirement for proper retinoic acid signaling to allow for normal liver regeneration is underscored by studies of hepatocyte-specific RXRα-null mice [mice lacking the retinoid receptor]. When RXRα is ablated there is reduced hepatocyte lifespan, which is accompanied by premature hepatocyte death and the appearance of necrotic areas. RXRα ablation also results in delayed hepatocyte proliferation following PHE." (Blaner 2013)

At first sight this observation goes again the often cited liver-toxicity of vitamin A. In view of nature's favorite dose-response curve, which is bell-shaped and indicates that bad things (often similar or even identical ones) happen in both deficiency and toxicity states, it's only logical, though. Plus, similar effects have been observed for wound-healing decades ago (Gerber. 1982) and Ehrlich and Hunt report in a 1968 paper in the Annals of Surgery that the administration of vitamin A blunts the negative effects on cortisol on wound healing and appears to be necessary for optimal tissue regeneration (Ehrlich. 1968).

So, another good reason to pop vitamin A supplements?

Supplementation with very high doses of isolated beta-carotene could in fact induce a state of "vitamin A resistance" in response to the formation of a metabolite that blocks the RXR receptor just like a SERM like clomiphene citrate block the estrogen receptor (read more).

For a healthy person living on a paleo-esque diet supplements should not be necessary. The amount of vitamin A and its pre-cursor beta-carotene you get from a whole-foods diet is usually adequate, even if you don't consume liver or organ meat on a regular basis. The use of what you will generally get, when you go to a healthfood store and buy a "vitamin A" supplement, i.e. a high dose beta carotene, only, product is probably counter-indicated not just for smokers, where it appears to increase the risk of lung cancer development, but also in normal healthy individuals who usually get plenty of beta-carotene from the myriad of fortified foods your local supermarket has to offer - after all, one of the most recent meta-analyses showed that 20-30mg/day increase everyone's risk of lung cancer development by 16% and that of stomach cancer by 34% (Druesne-Pecollo. 2010).

Polydextrose has non-noticeable, but significant satiety effects

(Astbury. 2013) -- I know the headline sounds confusing, but basically that's the long and short of the results, Astbury, Taylor and MacDonald present in their most recent isse in the British Journal of Nutrition. The scientists fed 12 male and 9 female healthy university students (mean age 23.2y; BMI 22.3kg/m²) who had consumed identical breakfasts at 8:00am with isocaloric (210kcal) "preload" mid-morning snacks at 10:45am and 90min before they had a pasta-based test meal, of which they were supposed to eat as much as it would take to feel comfortably full.

Figure 1: Food intake (in kcal) after mid-morning snack with different amounts of polydextrose (left); caloric intake on the subsequent meals of the day (right; Astbury. 2013)

As the data in figure 1 indicates, the consumption of the liquid preload which contained either 0, 6.3, 12 or 21g of the sweet tasting polysaccharide that reaches the colon largely undigested, where 50% of the polydextrose molecules will be fermented to yield CO2 and volatile SCFA such as propionate and butyrate and the rest will be excreted intact in the feces lead to dose-dependent reductions in the amount of food that was consumed in the subsequent meal.

50% energy availability, a source of SCFA, tasty & easy to process - perfect diet 'food'?

With only 50% energy availability and 50% being fermented to short chain fatty acids (SFCA),  the 89% dextrose, 10% sorbitol & 1% percent citric acid molecule, polydextrose could actually be a better choice for dieters than WMHDP (learn more about the SCFA based fat burning effects of resistant starches and how to make fat burning pancakes)

Interestingly, the reduced energy intake was not brought about by a consciously noticeable reduction in either fullness, hunger or desire to eat in response to the test meal (the scientists assessed that by questionnaires). And despite the fact that the effect was only transient, it's actually good and important news that the men and women did not accommodate for the 12-23% (male participants) and 6-18% (female participants) reduction in energy intake on the subsequent meal.

If that worked with every meal and you could achieve a ~20% reduction in energy intake, this alone should help you shed some weight pretty effortlessly. And as if that was not enough, already the polydextrose drinks was even more palatable than the sugary original; with the highest polydextrose content being perceived as most "creamy" - bon appetit ;-)

Even shorter news - "On real short notice", so to say  ;-)

I am well aware that what began as short news has as of late turned into a bunch of regular news - well, almost. So I decided to try and cut the last two items in today's installment short, in order to have them fit into what you would actually expect from a "on short notice" ;-)

• Exercise nullifies bad effects of high fructose diet (Moraes-Silva. 2013) -- A paper by scientists from the University of Sao Paulo puts the "lack of exercise / insuficient activity" hypothesis of obesity back on the radar. Even with an otherwise highly detrimental liquid fructose overload of 100g/l in their drinking water, the rodents in the study Moraes-Silva et al. conducted, did have normal (within statistical limits) glucose tolerance, blood pressure and heart disease risk as the rodents in the sedentary and the exercised control groups.

  

  Figure 2: Regular exercise maintains insulin sensitivity, cardiovascular disease risk and blood pressure even in the presence of pathologically high liquid fructose ingestion (Moraes-Silva. 2013)

  The regular treadmill running also blunted the autonomic dysfunction that was characterized by "an approximate 50% decrease in baroreflex sensitivity and 24% in HR variability", as well as increases in sympathovagal balance (140%) and renal sympathetic nerve activity (45%). Now you tell me "it's all about diet", only. Let alone: "Exercise just makes you hungry!"

• Diabetes and female sexual dysfunction correlate (Pontiroli. 2013) -- We already know that diabetes is a, if not the #1 risk factor for male sexual dysfunction, these days. Now a recent meta-analysis that's going to be published in one of the future issues of The Journal of Sexual Medicine found a 150% increase in sexual dysfunction in type II diabetes. Whether or not this was related to the higher depression rates in diabetic women cannot be said. What is certain, though, is that the BMI was a positive predictor of the effect size. In other words, the negative impact on sexual function increased with the degree of adiposity.
  
  Additional read for those women who feel it's their husband's performance that's to blame for their anorgasmia: "Pedalium murex Linn. fruits more effective than sildenafil in the long run and increases testosterone by 125%" (read more)
   

Now that's it for today, but I am now going out on a limb and promise another serving of short news with a focus on exercise early next week - something like the previous "Health & Exercise"- or the "Get Lean & Stay Lean" quickies and for once I can even tell you about one news that's definitely going to be in there - something about working out with and without breakfast.

---

The obligatory reminder: In the mean time I'd suggest you devour the latest SuppVersity Facebook News @ www.facebook.com/SuppVersity. As usual they will receive a couple of updates way before the next official SuppVersity post is going to see the light of the day. Let's see, some of the most recent news are even remotely related to the On Short Notice items of today:

• Penis pumps - Scientists believe they are going to make a revival as a means of penile rehabilitation after surgery for prostate cancer (read more)
• Stress renders cancer immortal - What has just been observed in a rodent model of prostate cancer could have important implications for other cancers, as well (read more)
• PDE5 inhibitor for him, PDE-4 inhibitor for her? Study suggests: PDE-4 inhibitors could improve female sexual function (read more)
• Goose liver for the liver - When it's high in selenium goose liver could protect your liver from the assault of excessive alcohol consumption (read more)

As promised, there will be more. So in case you have not done so already,  you best like the SuppVersity right now so that the latest news will always appear in your news-feed.... ah, and about all that geeky science reading, don't forget that there is more to life than dieting and working out ;-)

References:

• Astbury NM, Taylor MA, Macdonald IA. Polydextrose results in a dose-dependent reduction in ad libitum energy intake at a subsequent test meal. Br J Nutr. 2013 Jan 23:1-9.
• Druesne-Pecollo N, Latino-Martel P, Norat T, Barrandon E, Bertrais S, Galan P, Hercberg S. Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int J Cancer. 2010 Jul 1;127(1):172-84.
• Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg. 1968 Mar;167(3):324-8.
• Gerber LE, Erdman JW Jr. Effect of dietary retinyl acetate, beta-carotene and retinoic acid on wound healing in rats. J Nutr. 1982 Aug;112(8):1555-64.
• Moraes-Silva IC, Mostarda CT, Moreira ED, Silva KA, Dos Santos F, De Angelis K, Farah VD, Irigoyen MC. Preventive role of exercise training in autonomic, hemodynamic and metabolic parameters in rats under high risk of metabolic syndrome development. J Appl Physiol. 2013 Jan 17.
• Pontiroli AE, Cortelazzi D, and Morabito A. Female Sexual Dysfunction and Diabetes: A Systematic Review and Meta-Analysis. J Sex Med. 2013 [e-pub ahead of print]

Shedding Some Light on the Leaky Gut <> Exercise Connection. Plus: 20+ Things You Should or Shouldn't Do to Protect and Restore the Integrity of Your Intestinal Wall

Have you ever felt nauseated after a workout? Or does your protein supplement gives you diarrhea only if you take it right after a workout? Both can be related to the toll  exercise can take on the integrity of your intestinal tract.

To be honest, I was quite surprised that I did not get a hell lot of hatemail in response to the the 'MSG heals the gut study' I posted last Sunday... Be that as it may, I feel sort of awkward to have opened Pandora's box without proving you with some betters tools than mono-sodium glutamate (MSG) to seal the box, or rather your leaky gut, again. Therefore I decided to post this mini-feature on a particular issue all of us will be dealing with: An exercise induced increase in gut permeability. As you are going to see, there are a lot of similarities to the 'classic' leaky gut, which is often implicated in the etiology of chronic inflammatory bowel diseases. In order to understand these similarities, but also the few, yet important differences, we will have to lay some theoretical groundwork.

"What exactly is a leaky gut?"

The easiest way to answer this question would be to say: "That's what everybody and his mama is talking about these days". This definition as concise (and precise) as it may be, is yet about as productive as the talk that's at its heart. So, instead of relying on hearsay, let's rather briefly recap how intestinal wall actually works.

Since the intestines are meant to let nutrients and fluid pass, a certain degree of leakiness is absolutely natural. Problems arise only, when the self-regulatory system is broken and/or the permeability exceeds a normal / healthy threshold (img. by Mariana Ruiz).

The mucosal layer of the intestinal tract is made up of epithelial cells, so-called enterocytes which are connected to one another by specialized proteins. These proteins form the tight junctions (TJ) - a term, you will probably have encountered numerous times before. The main constituents of this kit in between the enterocytes are proteins such as occludin, zona-occludens and claudins. Together, the array of enterocytes and the tight junction form the the intestinal barrier, which allows the absorption of nutrients and water, while preventing the translocation of harmful substances from the gut into the bloodstream.

The integrity of this barrier is influenced by the phosphorylation state of the proteins within the tight junctions.The exact interactions are compilcated and can be looked up elsewhere (Banan. 2005). What's important for you to realize is that during prolonged exercise which is necessarily accompanied by an increase in core temperature, cardiovascular and thermoregulatory responses compromise intestinal blood flow.

With the core temperature usually being lower than the temperature in your intestines, the temperature of your gut can easily approach 41°C during a workout.That's more than your epithelial cells can handle and can lead to structural damage of the 'patches' in the tight junctions + epithelial cell layer (Lambert. 1985).

HIIT veterans or weight lifters are not off the hook

Now, the last paragraph may have sounded as if only long endurance workouts like 10k-runs or marathons could entail damage to the intestinal cells. That's however not the case, since the redirection of the blood away from the splanchnic arteries and to the working muscle that's even more pronounced in high(er) intensity exercise, will initiate an ischaemia reperfusion cycle which can entail oxidative damage not during, but interestingly after the the workout, when the blood rushes back into the intestines (Wijck. 2011).

Take home message: There are two distinct pathways that contribute to the leaky gut during and after a workout (a) heat and (b) ischaemic/reperfusion stress. Both influcne the phosphorylation state of the proteins in the tight junctions and will thus increase the permeability of the gut lining.

It stands to reason that the combination of high intensity and long durations, as you will find it in an ultra-marathon runner, for example, is particularly detrimental to the integrity of the intestinal wall, so that it is not exactly surprising that (ultra-)endurance athletes have the highest prevalence (60-90%) of gastrointestinal distress that which manifests in the form of diarrhoea, nausea, stomach problems, bloating and intestinal cramps (Worobetz.1985; Peters.1999; Jeukendrup.2000)

There is more than one thing you can to to protect, heal and restore your gut integrity

The fact that a "leaky gut" is like an open door not just for exogenous toxins or live bacteria, but also for their 'endotoxic poop' is probably no news for you. In fact, it is also the reason why you want to either prevent the pathological increases in gut permeability, in the first place, and/or (re-)seal the gut as soon as possible after your workouts. In this regards, there are three fundamental and easily implementable strategies that should always be employed before you even think about using specific supplements:

• 

  Figure 1: HSP 70 offers protection against endotoxins (LPS) in vivo (top) and in vitro (bottom; Dokladny. 2010)

  Despite the possible ischaemic / reperfusion stress short high intensity exercise bouts like sprinting are generally less taxing on the integrity of the tight junctions than longer duration medium intensity aerobic workouts. Avoiding these particularly gut-stressing workouts and/or taking special precautions before and after marathons and other endurance events would thus be strategy #1 to keep the epithelial cell layer intact and pathogens and toxins from entering the circulation.
• The natural intracellular expression of heat shock proteins (HSPs) can protect the tight gut junctions during and/or help their restoration after a workout. Just like all our endogenous protection systems the production of HSPs can be trained. Giving your body the time it needs to accommodate by making small, but consistent steps towards longer and/or more intense workouts would therefore be strategy #2.
• That leaves us with strategy #3, of which I hope all of you will be using anyway - even if you have not been aware of its gut protective effect, yet: The provision of adequate fluid supply before, during and after a workout (Lambert. 2008).

As the workout durations become longer and longer and/or the respective intensities higher and higher, solely relying on your bodies self-healing capacity and adequate hydration may seize to work, though. Despite the fact that our bodies accommodate to the ever increasing demand for intracellular protection against heat stress by upregulating the HSP expression (athletes have higher HSP expression to a standardized endurance training protocol than normal individiuals; cf. Fehrenbach. 2000), there is - just as with about every adaptive response - a certain threshold, when hormesis, i.e. the beneficial adaptation to a manageable amount of stress, is no longer an option.

From "A" as in arginine to "Z" as in zinc - a list of things to keep the gut lining intact

While there has been quite a lot of research as of late into which dietary supplements and even regular foodstuff would be able to modulate the heat shock proteins in order to prefer the desired downstream benefits on gut integrity, the number of compounds of which it is reasonable to assume that they can actually make a difference is still very small:

• Colostrum supplementation to cell cultures has been shown to increase the expression of HSP-70 in human epithelial cells; studies with human subjects are rare and ambiguous:  While Marchbank et al., have been able to show that bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes (Marchbank. 2011), Buckley et al. actually observed detrimental effects of 8 weeks of bovine colostrum supplementation on the exercise induced gut permeability in runners (Buckley. 2009).The explanation for these discrepencies is not clear, but may be related to the longer duration / different intensity of the exercise protocols, or differences in the immunoglobolin, peptide or amino acid composition of the supplements.
• Zinc in general and specifically polaprezinc, a zinc based anti-ulcer drug, which has primarily been used in Japan as a means to seal leaky Japanese guts, show some promises, as in the treatment and prevention of increased intestinal permeabilty (Zhang. 2009). It is thought that zinc is critical for tight junction assembly and has been shown to be critical in the protection of the gut lining from the chronic toxic assault of alcohol (Zhong. 2010). That being said, you should keep in mind that alcohol will deplete your bodies zinc stores, so that it cannot be said, if someone with an adequate zinc intake would benefit to the same degree as a zinc deficient alcoholic. Moreover, as "natural" as they may be, even essential minerals like zinc don't come without potential side effects (cf. "After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome", read more).
• Glutamine has been used as treatment for patients suffering from irritable bowel syndrome and Crohn’s disease and has been shown to actively increase the expression of HSP70 in critically ill patients (Jonas. 1999; Ziegler. 2005).  
• Berberine could be an ideal addition to glutamine (thx to Maxim Okhrimenko for pointing that out in the comments); berberine does not only modulate the TNF-alpha response in the intestines and increases AKT, but has also been shown to maintain / rescue intestinal glutamine transport and glutaminase activity (Gu. 2009; Amasheh. 2010; Li. 2010; Niu. 2011)
• Probiotics are still an 'under-researched' newcomer and though there is some preliminary evidence pointing to the efficacy of probiotic therapy as a means of improving gut function and enhancing the integrity of the intestinal tight junctions, the ideal supplement regimen, as well as its long-term effects will still have to be elucidated in human studies. Studies by Ewaschuk et al. have yet already shown that the impact factors released from Bifidobacteria infantis can offer a certain degree of protection against experimentally induced colitis in rodents (Ewaschuk. 2008). As far as exercise specific studies are concerned, a recently published paper by Lamprecht et al. is probably the first peer reviewed human study to report allegedly "borderline significant" beneficial effects on gut permeability (measured only indirectly by quantifiying the zonolin conent of the feces) and TNFalpha expression in response to a multi-species probiotics (1010 CFU/day, Ecologic®Performance orOMNi-BiOTiC®POWER) in 23 trained men (Lamprecht. 2012; the study was partially funded with a grant from Winclov, the manufacturer of the respective supplements).
• Butyrate, yet not all short chain fatty acids, have recently been found to decrease gut permeability (Ferreira. 2012). Both data from human studies, as well as exercise specific data is yet still absent.
• Hydroxypropyl methylcellulose (HPMC), which is a non-fermentable fiber, has been shown to protect rodent guts from a high fat diet induced increase in gut permeability (Kim. 2012), as in the case of butyrate its efficacy (and when you think about athletes, tolerability) will yet still have to be confirmed in human trials.
• L-Arginine (and AAKG) as a source of nitric oxide, which is necessary to protect the gut barrier from invaders could have a protective effect, as well (Quirino. 2012); and though this effect is not exercise specific, we know that arginine requirements increase in states of chronic stress, it would therefore be logical that supplementation with l-arginine, or even better AAKG, which comes with a precursor to glutamine will have beneficial effects on the tightness of the guts of intensely training athletes, as well (suggested read: BCAAs, glutamine and ammonia detox) .
• Oats, maybe due to their beta glucan content and their ability to increase the production of short-chain fatty acids in the large intestine, oats offer protection against alcohol induced increases in tight junction permeability (Tang. 2009); exercise specific studies have yet to be conducted, though.Personally I would yet not be surprised if this would turn out to be very effective (note: as long as they are not cross-contaminated, oats are 100% gluten-free)
• Goats milk (powder) has been shown to be equally effective as colostrum in reducing heat and thus most likely exercise induced gut permeability (Prosser. 2004)
• Lactoferrin, a multifunctional protein of the transferrin family that is present in milk may have protective effects against LPS-mediated intestinal mucosal damage and impairments of the barrier function in intestinal epithelial cells (Hirotani. 2008)
• Vitamin A in adequate amounts is necessary to maintain gut integrity; it is likely that this is all the more true if gut integrity and immune function are additionally challenged by strenuous exercise (Quadro. 2000)

I guess, I could find even more supplements (and foods) that may help you protect or restore your gut lining, but let's be honest: As important and beneficial eating and supplementing the right things may be, all your efforts would be foiled if you eat foods and supplements that will have the opposite effect on your gut lining. So here is the complementary and likewise non-exhaustive list of stuff you'd better avoid (at least in high doses) if you want to keep your tight junctions intact and your gut from becoming leaky:

Figure 2: Gliadin peptides induce the release of zonulin which in turn interacts with the tight junctions and increases the diffusion of small molecules (∼350 Da) across the cell membrane. Whether the tight junctions open up wide enough to allow for free diffusion of whole gliadin peptides, whose molecular weight is at least 2000 Da, remains to be determined, though (Heyman. 2011)

• Alcohol will wreak havoc on the permeability of your intestines; probably in consequence of its depleting effect on ileal zinc concentration (Zhong. 2010).
• Gliadin (in wheat/gluten) does actively promote the release of zonolin and the widening of the tight junctions (see figure 2); whether you will notice that or not, depends on the occurrence and extent of an immune response as it is characteristic for Celiac patients. I guess, it's actually not necessary to say that all sorts of other allergens, respectively the ensuing inflammatory response to being exposed to them will have detrimental effects on the integrity of your gut, as well, right?
• ALA, EPA and DHA the dietary omega-3 fatty which may help sooth tight junction permeability in states of chronic inflammation will actually increase it, when the baseline inflammation is already low or they are consumed in excess (Usami. 2001; Roig-Pérez. 2010)
• Copper and iron increase tight junction permeability of caco-2 cells via distinct mechanisms (Ferruzza. 2002)
• Capsaicin, piperine and other hot spices do not only cause a burning sensation in your mouth, it literally burns your intestinal cell lining, as well (Johri. 1992; Tsakura.2007)
• Quercitin by blocking the increase in HSP-70 will increase the suceptibility of your gut to exercise induced increases in permeablity (Kuennen. 2011)
• NSAIDs like aspirin and ibuprofen increase the permeability of the gut ad amplify the potentially detrimental effects of exercise (Lambert. 2007)

Obviously, only few of the last mentioned offenders are exercise specific, but if you start working out with already compromised gut integrity, you can hardly complain if a couple of grams of glutamine, or whatever else you may have picked from the previous list, don't effectively protect your intestinal wall from damage. What's even more important though is that you understand the Janus-faced nature of anti-oxidants and anti-inflammatory compounds. As beneficial as they may be in situations of chronic or acute pathologic inflammation, NSAIDs, quercitin and even your beloved omega-3 can eventually extinguish the 'controlled fire' your body needs to keep all immune and metabolic functions simmering along nicely (suggest reads: "Are you stressed enough for a longer life?" and "Inflammation is a True Fat Burner").

References:

• Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD. TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling. J Cell Sci. 2010 Dec 1;123(Pt 23):4145-55.
• Banan A,Zhang LJ, Shaikh M,et al. theta Isoform of protein kinase C alters barrier function in intestinal epithelium through modulation of distinct claudin isotypes: a novel mechanism for regulation of permeability. J Pharmacol Exp Ther. 2005; 313:962–82.
• Buckley JD, Butler RN, Southcott E, Brinkworth GD. Bovine colostrum supplementation during running training increases intestinal permeability. Nutrients. 2009 Feb;1(2):224-34.
• Dokladny K, Lobb R, Wharton W, Ma TY, Moseley PL. LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-kappaB. Cell Stress Chaperones. 2010 Mar;15(2):153-63. Epub 2009 Jun 24. 
• Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, Looijer-van Langen M, Madsen KL. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G1025-34. 
• Ferruzza S, Scacchi M, Scarino ML, Sambuy Y. Iron and copper alter tight junction permeability in human intestinal Caco-2 cells by distinct mechanisms. Toxicol In Vitro. 2002 Aug;16(4):399-404. 
• Gu L, Li N, Li Q, Zhang Q, Wang C, Zhu W, Li J. The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells. Fitoterapia. 2009 Jun;80(4):241-8.
• Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2012 Sep;61(9):1355-64.
• Hirotani Y, Ikeda K, Kato R, Myotoku M, Umeda T, Ijiri Y, Tanaka K. Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells. Yakugaku Zasshi. 2008 Sep;128(9):1363-8.
• Jeukendrup AE,Vet-Joop K, Sturk A,et al. Relationship between gastrointestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.Clin Sci (Lond). 2000;98:47–55. 
• Jonas CR, Ziegler TR. Potential role of glutamine administration in inflammatory bowel disease. Nestle Nutr Workshop Ser Clin Perform Programme. 1999;2:217-30.
• Johri RK, Thusu N, Khajuria A, Zutshi U. Piperine-mediated changes in the permeability of rat intestinal epithelial cells. The status of gamma-glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation. Biochem Pharmacol. 1992 Apr 1;43(7):1401-7.
• Kim H, Bartley GE, Young SA, Davis PA, Yokoyama W. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice. Mol Nutr Food Res. 2012 Sep;56(9):1464-76. 
• Kuennen M, Gillum T, Dokladny K, Bedrick E, Schneider S, Moseley P. Thermotolerance and heat acclimation may share a common mechanism in humans. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R524-33.
• Lambert GP, Gisolfi CV, Berg DJ, Moseley PL, Oberley LW, Kregel KC. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J Appl Physiol. 2002 Apr;92(4):1750-61; discussion 1749. PubMed PMID: 11896046.
• Lambert GP, Boylan M, Laventure JP, Bull A, Lanspa S. Effect of aspirin and ibuprofen on GI permeability during exercise. Int J Sports Med. 2007 Sep;28(9):722-6.
• Lambert GP, Lang J, Bull A, Pfeifer PC, Eckerson J, Moore G, Lanspa S, O'Brien J. Fluid restriction during running increases GI permeability. Int J Sports Med. 2008 Mar;29(3):194-8.
• Lamprecht M, Bogner S, Schippinger G, Steinbauer K, Fankhauser F, Hallstroem S, Schuetz B, Greilberger JF. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J Int Soc Sports Nutr. 2012 Sep 20;9(1):45. 
• Li N, Gu L, Qu L, Gong J, Li Q, Zhu W, Li J. Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells. Eur J Pharm Sci. 2010 Apr 16;40(1):1-8.
• Marchbank T, Davison G, Oakes JR, Ghatei MA, Patterson M, Moyer MP, Playford RJ. The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G477-84.
• Musch MW, Sugi K, Straus D, Chang EB. Heat-shock protein 72 protects against oxidant-induced injury of barrier function of human colonic epithelial Caco2/bbe cells. Gastroenterology. 1999 Jul;117(1):115-22. 
• Niu L, Qiao W, Hu Z, Li N, Huang Q, Gong J, Li Q, Zhu W, Li J. Berberine attenuates lipopolysaccharide-induced impairments of intestinal glutamine transport and glutaminase activity in rat. Fitoterapia. 2011 Apr;82(3):323-30.
• Peters HP, Bos M, Seebregts L,et al. Gastrointestinal symptoms in long-distance runners, cyclists, and triathletes: prevalence, medication, and etiology. Am J Gastroenterol. 1999; 94:1570–81. 
• Prosser C, Stelwagen K, Cummins R, Guerin P, Gill N, Milne C. Reduction in heat-induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. J Appl Physiol. 2004 Feb;96(2):650-4.
• Quadro L, Gamble MV, Vogel S, Lima AA, Piantedosi R, Moore SR, Colantuoni V, Gottesman ME, Guerrant RL, Blaner WS. Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins. J Infect Dis. 2000 Sep;182 Suppl 1:S97-S102.
• Roig-Pérez S, Cortadellas N, Moretó M, Ferrer R. Intracellular mechanisms involved in docosahexaenoic acid-induced increases in tight junction permeability in Caco-2 cell monolayers. J Nutr. 2010 Sep;140(9):1557-63.
• Ruiz M. Wikipedia contributors, 'Tight junction', Wikipedia, The Free Encyclopedia, 10 November 2012, 07:58 UTC, <http://en.wikipedia.org/w/index.php?title=Tight_junction&oldid=522300074> accessed 25 November 2012
• Tang Y, Forsyth CB, Banan A, Fields JZ, Keshavarzian A. Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage. J Pharmacol Exp Ther. 2009 Jun;329(3):952-8.
• Tsukura Y, Mori M, Hirotani Y, Ikeda K, Amano F, Kato R, Ijiri Y, Tanaka K. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007 Oct;30(10):1982-6.
• Usami M, Muraki K, Iwamoto M, Ohata A, Matsushita E, Miki A. Effect of eicosapentaenoic acid (EPA) on tight junction permeability in intestinal monolayer cells. Clin Nutr. 2001 Aug;20(4):351-9.
• van Wijck K, Lenaerts K, van Loon LJ,et al. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men.PloS One. 2011; 6.
• Worobetz LJ,Gerrard DF. Gastrointestinal symptoms during exercise in Enduro athletes: prevalence and speculations on the aetiology.N Z Med J 1985; 98:644–6.
• Zhang B, Guo Y. Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets. Br J Nutr. 2009 Sep;102(5):687-93.
• Zhong W, McClain CJ, Cave M, Kang YJ, Zhou Z. The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G625-33. 
• Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP, Galloway JR, Wischmeyer PE. Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med. 2005 Aug;31(8):1079-86