Stevia Kills Good Gut Bacteria - One Study Enough to Stop Using the Natural Sweetener? Probably Not in View of its Anti-Diabetes, Anti-LDL, Anti-Viral & Anti-Cancer Effects

Study indicates stevia kills healthy gut bacteria. So, how bad is it? Are the effects significant, will they have an impact on your overall health and does this mean you must not use stevia any longer?

A recent study from the Institute of Microbiology and Biotechnology at the University of Latvia in Riga shows the impossible: Stevia, the "natural" sweetener that's everybody's darling, could mess up your gut microbiome by killing large numbers of the beneficial Lactobacillus Reuteri bacteria in your tummy - exactly those bacteria of which several studies have shown that supplementing will help cure acute diarrhea in young children (Shornikova. 1997), is capable of reducing frequency and intensity of antibiotic-associated side-effects during eradication therapy for H. pylori. (Lionetti. 2006), confers broad-spectrum protection against disease in humans and animals (Casas. 2000), has cholesterol lowering effects (Jones. 2012) and much much more.

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

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet

In view of the fact that it would appear as id Lactobacillus reuteri was clearly one of the "good guys" it seems that the results I. Denin a, P. Semjonovs, A. Fomina, R. Treimane and R. Linde report on their latest study in Letters in Applied Microbiology (Denin. 2014) were really bad news:

Figure 1: Influence of stevioside (a) and rebaudioside A (b) on biomass formation in Lactobacillus reuteri strains (24 h | Denin. 2014).

"In samples supplemented with stevia glycosides, the growth of all Lact. reuteri strains was slightly inhibited – however, a statistically significant concentration-dependent inhibitory effect was not observed for all strains (Fig. 1).

Comparing both the glycosides, the inhibitory effect of stevioside was more pronounced for strains 44 and 16, while the effect of rebaudioside A was more pronounced for strains 16 and 19. Statistically significant concentration-dependent inhib itory effect was observed for lactic acid and acetic acid synthesis. The decrease in lactic acid and acetic acid production was observed for both stevioside and rebaudioside A. [...] Although the inhibitory effect of stevioside on pH was observed at different stevioside concentrations, the effect was evident for all strains. Rebaudioside A had a more pronounced inhibitory effect on pH values of certain strains including Lact. reuteri 12, 16, 43 and 44" (Denin. 2014 | my emphasis).

The good news, however, is in the details: The inhibitory effect was "slight" (see quotation above) and the design of the study leaves it open, whether similar effects would occur in vivo and thus outside of a glycoside, stevioside and rebaudioside laden Petri dish.

Previous studies seem to refute significant effects of stevia on the human microbiome! In 2003, Gardana et al. found no effect of stevia on the make-up of human fecal cultures when they were incubated with either stevioside or rebaudioside A. Only the fact that bacteroides, i.e. the "enemies" of lactobacilli, were the most efficient in hydrolyzing Stevia sweeteners to steviol would suggest that there may be an overall effect on the human microbiome form stevia (ab-)use.

And while we have little in vivo evidence that stevia is bad for you, a brief review of the contemporary scientific literature on Stevia yields the following "proven" (mostly only in a handful, if not just a single study) benefits:

• Stevia has been implicated in diabetes and hyperlipidemia treatment and its effects on blood glucose levels are not a mere result of the corresponding reduction in sugar intake.

  

  Figure 2: Effects of stevia vs. diabetes drug Glibenclamide on blood glucose and lipid levels in diabetic rodents; data expressed relative to healthy control (Singh. 2014)

  In a recent rodent study that compared the effects of stevia against those of the often-prescribed diabetes-drug Glibenclamide, the natural sweetener outperformed the drug in many in its ability to reduce LDL and blood sugar and was not far off of what the Glibencamide did for the diabetic lab animals in terms of its effects on HDL and VLDL (see Figure 2).
  
  Previous human studies indicate that stevia extracts will also increase the increased 16 healthy human volunteers whose plasma glucose levels during an oral glucose tolerance tests were significantly lower after having consumed 5 grams of aqueous leave extract at regular 6-h intervals for 3 days (Curi. 1985).

  

  Figure 3: Effects of stevia and aspartame replacement of sucrose in test meals that were fed to obese and normal-weight volunteers on postprandial blood glucose levels (Anton. 2010)

  Moreover, in a more recent study by Anton et al. where stevia was compared to aspartame, it had the same beneficial effects on total energy intake and let to statistically significant reductions in postprandial glucose levels of both obese and lean study subjects (see Figure 3) that did not reach significance when the sucrose content of the test meal was replaced by aspartame.
• In-vitro stevia appears to have anti-cancer effects, as well. That's at least what studies by  Jayaraman et al. (2008) observed with stevia extracts. An effect that may be related to both it's anti-microbial, as well as its potent anti-oxidant activity (Tadhani. 2007) of the whole leaves and leave extracts of which Tahani et al. found that they contain significant effects of folic acid (52.18 mg/100 g) and vitamin C, as well as 130.76 μg catechin and 15.64 μg quercetin for leaves and 43.99 μg catechin and 1.57 μg quercetin for cellus at mg of water extracts, respectively.
  
  Furthermore, Tadhani et al.'s results showed that the leaf extracts contained higher amounts of free radicals, hydroxyl radicals and superoxide anion radical scavenging activities than those of the callus extracts or the anti-mutagenic effects Cariño-Cortés et al. report in their 2007 study. Whether anything similar can be observed with the white "stevia" powder that is used by most people to sweeten their foods is yet questionable - it's after all pure steviosid and thus devoid of all of the previously mentioned compounds.

  

  Figure 1: Several natural constituents of the stevia plant, including steviosides, which are the naturally sweet agents in stevia have potent anti-viral activity against Epstein-Barr virus; values in brackets
  represent % of untreated control dish (Konoshima. 2002)

  Another possible anti-cancer mechanism may be related to stevia's ability to kill viruses like the Epstein-Barr virus that has been implicated in the pathogenesis of Burkitt’s lymphoma, Hodgkin’s disease, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, and lymphomas, as well as leiomyosarcomas arising in immunocompromised individuals.in humans (Thompson. 2014).

Against that background it seems questionable that the new evidence of negative effects on allegedly healthy gut bacteria (just want to remind everyone that we have no clue what the optimal gut microbiome would look like) is significant enough to have us all reconsider our use of tiny amounts of stevia as a sweetener in our foods.

Read more about the effects artificial sweeteners have on the microbiome in a prevoius article | go ahead!

Interim conclusion: While I am not all too scared that stevia will mess with my gut microbiome in a way that makes me sick, fat and what not, I truly believe that the effects of artificial sweeteners on the make-up and density of the human gut microbiome is still massively under-researched - and that in spite of the fact that it could have a significant effect on the health of us all.

As s SuppVersity reader you will also be aware that this is not a stevia-specific effects. Only recently I have written about similar effects for a bunch of artificial sweeteners - an article I can only recommend to anyone who hasn't read it yet | Comment on Facebook.

References:

• Anton, Stephen D., et al. "Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels." Appetite 55.1 (2010): 37-43.
• Casas, Ivan A., and Walter J. Dobrogosz. "Validation of the probiotic concept: Lactobacillus reuteri confers broad-spectrum protection against disease in humans and animals." Microbial ecology in health and disease 12.4 (2000): 247-285. 
• Curi, R., et al. "Effect of Stevia rebaudiana on glucose tolerance in normal adult humans." Brazilian journal of medical and biological research= Revista brasileira de pesquisas médicas e biológicas/Sociedade Brasileira de Biofísica 19.6 (1985): 771-774.
• Deniņa, Ilze, et al. "The influence of stevia glycosides on the growth of Lactobacillus reuteri strains." Letters in applied microbiology 58.3 (2014): 278-284. 
• Gardana, Claudio, et al. "Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora." Journal of agricultural and food chemistry 51.22 (2003): 6618-6622. 
• Jayaraman, Sathishkumar, Muthu Saravanan Manoharan, and Seethalakshmi Illanchezian. "In-vitro antimicrobial and antitumor activities of Stevia rebaudiana (Asteraceae) leaf extracts." Tropical Journal of Pharmaceutical Research 7.4 (2008): 1143-1149.
• Jones, M. L., C. J. Martoni, and S. Prakash. "Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial." European journal of clinical nutrition 66.11 (2012): 1234-1241.
• Konoshima, Takao, and Midori Takasaki. "Cancer-chemopreventive effects of natural sweeteners and related compounds." Pure and applied chemistry 74.7 (2002): 1309-1316.
• Lionetti, E., et al. "Lactobacillus reuteri therapy to reduce side‐effects during anti‐Helicobacter pylori treatment in children: a randomized placebo controlled trial." Alimentary pharmacology & therapeutics 24.10 (2006): 1461-1468.
• Shornikova, Aino-Vieno, et al. "Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children." Journal of pediatric gastroenterology and nutrition 24.4 (1997): 399-404.
• Singh, Sunanda. "Antidiabetic, Antidyslipidymic and Antioxidative potential of methanolic root extract of Stevia rebaudiana (Bertoni) on Alloxan induced Diabetic Mice Sunanda Singh and Veena Garg Department of Bioscience and Biotechnology, Banasthali Vidyapeeth, Banasthali, Rajasthan, India." (2014). 
• Tadhani, M. B., V. H. Patel, and Rema Subhash. "In vitro antioxidant activities of Stevia rebaudiana leaves and callus." Journal of Food Composition and Analysis 20.3 (2007): 323-329. 
• Thompson, Matthew P., and Razelle Kurzrock. "Epstein-Barr virus and cancer." Clinical Cancer Research 10.3 (2004): 803-821.

On Short Notice: Ghrelin & GH Boosting Fats for Intermittent Fasting, 4-AD, 5-AA, Testosterone & Co in "Pod", Too Much Vitamin D for Your Prostate, Estrogens in Milk & More

Image 1 (fidged-group.co.uk): Being average may not be sexy, but one thing I did not mention in the summary of what you are going to learn today is that an average amount of body fat (not the new average American though ;-) could hold the key for a longer life - ah, I almost forgot: This is only valid if it comes with an appropriate amount of lean mass, which is still the best predictor of a long and healthy life!

Somehow these On Short Notice posts become increasingly longer... I had to "outsource" a couple of items, to reduce today's installment to a manageable length, but don't worry a couple of them will turn up in the next installment or make it into the regular news in the days to come. For now you will have to settle for valuable and at least in part surprising insights into the broad range of effects different types and loads of dietary fat can have on your appetite, metabolism and your, or rather your bacterial subtenants' methane production. You will also learn what TAC means and why you want more than 1,080 units of it in every 100g of whatever you are stuffing down your pie-hole. You will be surprised to hear that SuppVersity student FatFree instinctively chose the low estrogen variety of dairy, when he "downed 1l of raw goat's milk" from his local farmer earlier today (see respective comment) and you will attend another lesson of the "what's good for your obese neighbor, is not necessarily good for you" class. All that will be topped of with some testosterone laden, WADA prohibited "pod", too much vitamin D for your prostate to handle and a glass of bone-conserving wine for the habitual drinkers among the ladies ;-)

Fat Interactions - MUFA, PUFA, SUFA and How They Influence Your Metabolism

The idea that "not all fats" are created equal is meanwhile broadly accepted. What is still a matter of constant debate, though, is which of the three main classes, i.e. saturated, mono- and polyunsaturated fatty acids exert beneficial and which of them detrimental effects on our health. A recently published on the differential effects of butter (saturated fat), olive oil (mono-unsaturated; oleic acid + a relative high amount of omega-6), fish oil (polyunsaturated; high omega-3) and soybean oil (polyunsaturated; mainly omega-6 + some omega 3) on the expression of the purported "hunger hormone" ghrelin (note: acetylghrelin, which was measured in this study, is the "active" variety of ghrelin) may yet help to get a better grasp of what exactly we should be looking for (Saidpour. 2012), when it comes to the downstream metabolic effects of high amounts of certain fatty acids - and no, it is not for maximal ghrelin suppression.

Figure 1: Food intake (in g, left), body weight (relative to control group on regular diet, middle) and acetylghrelin levels in the fasting and fed state during the 8-week experimental period (data based on Saidpour. 2012)

As the data data in figure 1 shows, the 5-week old male Wistar rats who had been randomly assigned to either standard rodent chow or calorically identical (3.98kcal/g of food) high fat diets who were fed ad libitum every other day only to maximize the ghrelin response) for 8 weeks did not, as common sense would suggest, eat the least and gain the least on the saturated fat (butter) diet with its long lasting satiety effect (as evidenced by the lowest fasting ghrelin levels).

In fact, the exact opposite was the case: The acute satiety effect of the fish oil and olive oil diets (as evidenced by the plummeting acetylghrelin levels in the fed state) turned out to be the main determinant of the amount of food the rodents, who were effectively intermittently fasted (though with a pretty long fasting window of 24h), consumed.  And while the low ghrelin levels in the fed state reduced the food intake, the fasting induced rise of acetylghrelin to 23% higher levels than in the butter fed animals has probably given them the metabolic advantage of elevated growth hormone levels. At least this is what we must expect based on the ability of ghrelin to directly bind to the GHS receptor and induce the release of the fat annihilating 191-amino acid, single-chain polypeptide from the lateral wings of the anterior pituitary gland (Kojima. 1999).

Bottom line: While this is certainly only another small piece to the oftentimes puzzling effects of fatty acids (check the "On Very Short Notice" items in this installment for more "puzzling" effects ;-), it does not only provide another mechanism by which the original "Mediterranean diet", which is rich in both fish and olive oil and by no means as fat free as its latest mainstream interpretation would suggest, could in fact provide a metabolic edge. And though the "intermittent fasting" feeding pattern may reduce the significance of the results for the "average" inhabitant of the Western hemisphere, who can hardly go 2h without a Snickers bar or at least a sugar-laden coffee, it does suggest that all the "lean gainers" and "intermittent fasters" out there could derive great benefits from a huge piece of salmon and couple of tablespoons of high MUFA olive, macadamia or artichoke oil in their "feeding windows".

A Diet High in Dietary Antioxidant Keeps you Lean & Healthy

Image 2: Clover is among the most potent antioxidant foods.

You know that I am very critical when it comes to the supply of exogenous antioxidants (cf. "Multivitamins, a question of Faith?!"; more on multivatmins), but would never even remotely consider limiting the supply of whole foods that are rich in antioxidants. I was thus not very surprised, when I read that the consumption of high amounts of dietary antioxidants was associated with statistically significant lower body weight and abdominal fat gain in a 3-year longitudinal (this is where scientists analyze data from the same persons on different time-points) study from the University of Medical Sciences in Teheran (Bahadoran. 2012).

Foods	TAC
Cloves (see image), Cinnamon, Oregano, Tumeric, Acai (all dried or grounded)	300,000 -100,000
Cacao, Parsley, Basil, Currry, Sage, Peppercorns, Mustard, Ginger, Marjoram	100,000 -25,000
Rice bran, Chili, Pecans, Paprika, Choke berries, Elderberries, Kidney Beans (dried), Oregano, Walnuts	25,000 -10,000
Hazelnuts, Cranberries, Artichoke hearts, Blueberries, Prunes, Pistachios, Blackcurrant, Artichokes, Plums, Blueberries (cult.) Lemon balm (fresh) Blackberries, Garlic, Coriander,	10,000 -5,000
Raspberries, Basil (fresh), Almonds, Apples, Dates, Strawberries, Figs, Peanuts, Raisins, Cherries, Asparagus, Spinach	5,000 -2,500
Cornflakes, Red Cabbage, Gooseberries, Cashews Avocado, Pears, Peaches, Oranges, Oats, Macadamia, Tangerines, Broccoli, Potatoes, Grapefruit, Red grapes	2,500 -1,500
Carrots, Olive oil, Green grapes, Mango, Lettuce, Radish Eggplant, Kiwi, Banana, Red pepper, Pineapple, Artichoke, Nectarines, Pine nuts, Cauliflower, celery	1,250 -500
Leeks, Lettuce, Baby carrots, Tomatoes, White wine, cantaloupe, Honeydew, Watermelon, Cucumber	500 -100

In particular, Zarah Bahadoran and her colleagues found that the consumption of foods with an average total antioxidant capacity equal to 1,080µmol TAC essay units per 100g - something your would get from oats + blueberries or a handful of pecans and an apple - was associated with a -38 % decrease in the risk of central obesity (note: The TAC essay is an experimental measure of the total antioxidant capacity of food and is independent of whether it's phenols, vitamins, thiols or whatever that contribute to the antioxidant effects of a food; the clear disadvantage of this method is that it does not really tell you what exactly the compounds will do outside of a petri dish, but, but this is the topic for another blogpost ;-)

And while some of the confounding factors have been eliminated from the above hazard risk calculations, it is still worth to take note of the fact that...

• people with the highest antioxidant intake consumed food with the lowest energy density (so they cannot be eating nuts and chocolate only ;-)
• women consumed significantly more antioxidants than men, with +10% more women in Q3 (959-1080µmolTE/100g) and +15% more women in the critical Q4 (>1,080µmol/kg) quartiles
• the more leisure time the subjects had, or I should say allowed themselves, the higher was their antioxidant intake
• high antioxidant consumers were also dairy lovers with 81% more dairy consumption in the highest quartile, exactly those people, thus, who consumed the >1,082 µmolTE/100mg diets
• needless to say that people who are reckless enough to smoke also consumed the least antioxidants

Aside from these significant differences, the non-existence of other differences people often take for granted, such as the notion that education and job activity, or different macronutrient compositions would have an impact on the total amount of antioxidants you consume, is certainly worth mentioning.

  On Very Short Notice

• 

  Figure 2: "Pod" contains a hell lot of steroids. Unfortunately, most of them will be dumped by right into the urine specimen for the WADA agents (data based on Thevis. 2012)

  "Pod" doping could get you banned, but probably won't increase your performance - While I cannot tell you what the swimmers at the Olympics have been taking to break world record after world record (some even in consecutive races on the same day), I can tell you that it were not the reddish-brown musk grains from the dried secretion from the preputial follicles of the male musk deer , which are located in the "pod", a small sac in close proximity to the preputial orifice (see figure XYZ, upper right), because none of these athletes would have passed the WADA doping controls had he or she taken a couple of grams of those steroid-containing staples of Traditional Chinese Medicine.
  Now, despite the fact that we do see "classics" such as 4-AD, Androsterone, Epiandrosterone, DHEA and even minuscule amounts of the "Big T" (1-6µg/g with the highest level in the pod from the zoo animals from Leipzig, Germany - read more about testosterone's ability to build muscle in the "Intermittent Thoughts on Building Muscle") testosterone , the total amount of those compounds which could actually induce noticeable performance increases may be high enough to show up during doping controls as the five cases during the last FIFA Women World Cup show(cf. Thevis. 2012), it does not appear reasonable to assume that the rumored performance enhancing effects of musk (pod) extracts would stand the test in a placebo controlled supplementation trial.

• 

  Figure 3: When administered at a HED of ~750mg/day sodium salicates reduce the glucose (left axis) and insulin (right axis) levels in response to a standardized intraperitoneal glucose injection in obese mice, they do the opposite in lean mice (based on Nixon. 2012).

  Salicates block cortisol expression in fat cells and increase insulin sensitivity in obese mice, but... as we have seen for alpha lipoic acid (see "ALA? You are Better of Without the Purported Nutrient Repartitioner") and tons of other "wonder-supplements", things that are good for your obese neighbor will rarely work out for lean folks like, yourself; and thus it should not come as a surprise that the blockade of adipose tissue 11-beta-HSD, the enzyme that converts cortisone, the inactive form of cortisol into it's active twin, exerts no, if not the exact opposite effect (see figure 3; adapted from Nixon. 2012).
  So, if you are lean and want to stay lean, leave the aspirin, the 7-ketos and other overpriced 11-beta-HSD inhibitors or "cortisol blockers" to those who need them - inflamed, overweight (pre-)diabetics.
• Purportedly anti-carcinogenic high vitamin D levels increase risk of prostate cancer - Swedish scientists found a statistically significant trend towards an increased risk of developing prostate cancer with rising vitamin D levels. In the 7th and 8th decile which corresponds to plasma vitamin D levels of 91-97 nmol/L the calculated risk of developing prostate cancer was 67% higher than in the lowest decile (Brändstedt. 2012). Other than previous studies which reported associations between high calcium intake and prostate cancer risk, Brändstedt et al. observed an association between high serum calcium levels and prostate cancer levels only among men aged 55-65 who had a BMI < 25. It is thus very unlikely that the underlying reason of the pro-carcinogenic effects was an increase in calcium absorption... hmm, I don't have to remind you of (a) the antagonism between vitamin D and vitamin A and (b) last weeks news on the anti-carcinogenic effects of the latter, do I?

• 

  Image 3: Although the scientists controlled the compliance by measuring the serum concentration of fatty acids instead of using unreliable food logs, there are still  a lot of uncontrolled confounding variable, here. Hower, the same can be said of those studies on which the concept of the pro-inflammatory omega-6s is based. Anyway, I will still eat butter, not margarine and if olive oil is one of staple sources of dietary fat, you will be getting plenty of omega-6 from this purported GH booster (see previous new item)

  High omega-6 diet reduces insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides - Helena Bjermo and her colleagues from the Uppsala University in Sweden report that feeding 67 abdominally obese patients (15% were diabetic) either a butter-based high saturated fat diet or a diet that was particularly rich in linoleic acid (omega-6 mainly from sunflower oil; 15% of the total energy intake) for 10 weeks had very differnt effects on the hepatic fat content an other highly relevant markers of metabolic health. Despite the fact that both diets were isocaloric, the butter-based high saturated fat diet increased the hepatic fat content of the study participants (measured by MRS) by 10% while the subjects in the high PUFA group were able to reduce the fat content of their livers by -35%. Similarly, the basal insulin level, triglycerides, as well as total and LDL cholesterol increased in the butter eaters and decrease or remained the same in the 15% linoleic acid group.
  The results are honestly not what I had expected, but in essence only further evidence there is still a lot to learn about the shades of grey that exist between the dichotomous black and white that is still so characteristic of the way we think about fats.
• Goat's milk is the better choice for people concerned with limiting their intake of exogenous estrogens - According to analyses that were conducted at the Laboratory of Proteomics and Analytical Technologies in Frederick (Farlow. 2012), cow's milk contains significantly more estrogens (estrone and 17beta-estradiol) than goat's milk and that irrespective of whether it was organically produced or not. Bad news for the reproductive health of the North Americans and Europeans, where the consumption of cow's milk exceed that of goats milk by several magnitudes and good news for the fertility of the rest of the world, where goat's milk still is the "milk of choice".

• 

  Image 4: Looks like this was not the only potential side effect of methane producing bacteria in your gut.

  High fat diets increase the ratio of methane producing to other bacteria and thus increase obesity risk - Most of you will probably remember the finding that mice without gut microbiome are more or less resistant to dietary induced obesity. A recent study does now suggest that (as it was to be expected) not all bacteria are created evil.. ah, pardon... equal ;-) In the lab mice of Ruchi Mathur and his colleagues, the tendency to develop obesity correlated with the amount of gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, and was independent of the presence of other bacteria (Mathur. 2012).
  With the pro-methanogenic (=allows those little bastards to grow) effects of high fat diets Mathur et al. may in fact have found another potential co-founder in the development of the metabolic syndrome. Interestingly enough Methanobrevibacter smithii is also the predominant methanogen in patients with constipation-dominant IBS and methane breath (Kim. 2012) - so if that is you, this could be one of the few cases where the use of a broadband antibiotic could save you from a lot of ailments, because you would thus not have to care about contradictory results from Million et al., as well as dozens of other studies, each of which identifies another type of bacteria as 'the root cause' of the obesity epidemic - in Million's case the name of the scapegoat is Lactobacillus reuteri, by the way (Million. 2012).
• Mediocrity guarantees a long life - At least when it comes to body fatness being too lean and being too fat are equally detrimental to the life expectancy of male 65+ agers (Toss. 2012). If you are women, though, the results Fredrik Toss and his colleagues published in the latest issue of Age and Ageing suggest that being on the chubbier side of things can actually be life-saving, as long as you carry the fat in the gynoid and not the abdominal area. Most importantly, however, lean mass, or as my buddy Carl Lanore calls it, "metabolic currency" is yet still the most significant predictor of survival in older subjects - in other words: Don't even think of emulating the skinny fat celebrities with their starvation diets and endless cardio sessions if you intend to live your grand- and grand-grand-children, better check out yesterday's news on the "Iranian HIIT Solution for Improved Insulin and Leptin Sensitivity".

• 

  Image 5: If you are concerned about bone health, menopause is not the best time to stop drinking... unless you start weight lifting, of course ;-)

  Don't stop drinking alcohol in menopause! At least if you don't want to increase bone-resorption, i.e. the leeching of calcium from your bones. This is the surprising result of a recently published study by Jill A. Marrone and colleagues, who had  investigated the effects of total abstinence from alcohol in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed the alcohol equivalent of ~1 glass of wine per day (Marrone. 2012). Interestingly, the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) returned to their normal values, once the women resumed their former drinking habits.
  In view of the fact that there was also a significant correlation between baseline bone-density, as measured dual-energy x-ray absorptiometry, and the extent of mild to moderate alcohol consumption, these results raise the question whether "bone health" would be another factor to add to the list of the "minimalist approach" to alcohol consumption.

References:

• Bjermo H, Iggman D, Kullberg J, Dahlman I, Johansson L, Persson L, Berglund J, Pulkki K, Basu S, Uusitupa M, Rudling M, Arner P, Cederholm T, Ahlström H, Risérus U. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr. 2012 May;95(5):1003-12. 
• Brändstedt J, Almquist M, Manjer J, Malm J. Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study. Cancer Causes Control. 2012 Aug;23(8):1377-85.
• Farlow DW, Xu X, Veenstra TD. Comparison of estrone and 17β-estradiol levels in commercial goat and cow milk. J Dairy Sci. 2012 Apr;95(4):1699-708.
• Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., Kangawa, K. Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature. 1999; 402, 656-660.
• Mathur R, Kim G, Morales W, Sung J, Rooks E, Pokkunuri V, Weitsman S, Barlow GM, Chang C, Pimentel M. Intestinal Methanobrevibacter smithii but Not Total Bacteria Is Related to Diet-Induced Weight Gain in Rats. Obesity (Silver Spring). 2012 Jun 7. 
• Marrone JA, Maddalozzo GF, Branscum AJ, Hardin K, Cialdella-Kam L, Philbrick KA, Breggia AC, Rosen CJ, Turner RT, Iwaniec UT. Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women. Menopause. 2012 Jul 9.
• Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, Valero R, Raccah D, Vialettes B, Raoult D. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes (Lond). 2012 Jun;36(6):817-25.
• Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. 2012 Apr;61(4):790-6.
• Saidpour A, Kimiagar M, Zahediasl S, Ghasemi A, Vafa M, Abadi A, Daneshpour M, Zarkesh M. The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats. Gene. 2012 Jul 25.
• Thevis M, Schänzer W, Geyer H, Thieme D, Grosse J, Rautenberg C, Flenker U, Beuck S, Thomas A, Holland R, Dvorak J. Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts. Br J Sports Med. 2012 May 6.
• Toss F, Wiklund P, Nordström P, Nordström A. Body composition and mortality risk in later life. Age Ageing. 2012 Jul 20.

Saturated Fat Kills Gut Bacteria & Modifies Genes in the Distal Small Intestine - Another Reason Why We Get Fat? Plus: Bacteria, Fiber, SCFA, GLP-1 & PYY Revisited

Image 1: Bacteria, there are >100 trillion of them right inside of your digestive track, you can hardly know them all and scientists do neither - the only thing we are beginning to understand, though, is that it may be a good idea to get them to know at least somewhat better ;-)

I guess some of you have already noticed that I was (and probably am now, again) somewhat behind, as far as answering your questions, comments an wise remarks are concerned. Actually it is still more of a coincidence that today's SuppVersity news, which, as you see is not an Adelfo Cerame post (don't forget to keep the fingers crossed for him! This is his weekend!), could actually be interpreted as my somewhat lengthy response to a comment from Vincente on the effects of GLP-1 on chocolate preference in rats and an interesting hypothesis of his, on how this could all relate to my previous post on the fat burning effects of GLP-1 ("Eat More, Burn More and Lose Fat Like on Crack with GLP-1!?"). What, that was Vincente's reasoning, what, if those obese individuals had just messed up their gut bacteria an would lack those beneficial bacteria, which convert the fiber and resistant starch that makes it through your small intestine, right down into your long one to short chain fatty acids?

Does obesity come from within?

I guess by now some of you may already be asking themselves, where all that relates to GLP-1 and eating more, burning more and losing fat like on crack. Well, the missing link if you will is actually not a link, but rather a receptor - the free fatty acid receptor, FFR, which "sniffs" the presence of the short chain fatty acids and triggers the release of GLP-1 and PYY. Those two incretin hormones, of which researchers have found within the past 10 years or so that they are way more than mere "satiety signals. Several research studies in rodents have shown that the anti-obesogenic effects of GLP-1 and PYY are if at all, only partly mediated by reductions in food intake, yet mostly via complex downstream effects on total energy expenditure, glucose and fatty acid oxidation.

Contrary to exogenously administered GLP-1, which is actually being used in the treatment of diabetes an the metabolic syndrome, the in-vivo data from rodent studies, which suggests that high fiber diets protects those little critters from diet induced obesity (Aziz. 2008; Shen. 2008; Zhou. 2008) have, as Robertson et al. pointed out only recently, not yet been confirmed in humans trials (Robertson. 2012). Moreover, the latest results from the Merck Reserach Lab show, contrary to previous evidence from the Cambridge Institute for Medical Research (Tolhorst. 2012), that even our current assumption with respect to the underlying mechanism, could at least be incomplete (Lin. 2012). This does not mean that the short chain fatty acids would not produce the desired increase in GLP-1 nad PYY, but rather that their effects are not solely mediated by  the aforementioned free fatty acid receptor in the gut.

Let's make things even more complicated and bring some long chain fatty acids to the table!

What is yet self-evident though is that the way GLP-1 and PYY modulate energy utilization punches yet another huge hole in the prostrated "calories in vs. calories out hypothesis", one that has little to nothing to o with insulin and one that acquires yet another shade of gray, when we look at the long-chain counterpart of the "bacterial excrements" the dreaded or beloved (depending on the standpoint of the individual) saturated fatty acids (SFA) and a recently published study by scientists from the Wageningen University in the Netherlands (De Wit. 2012), who investigated the long-term effects (8 week, study conducted on mice) of high fat diets with fats from different fat sources

• palm oil - representing the saturated fatty acids,
• olive oil - representing the mono-unsaturated fatty acids, and
• safflower oil - representing the polyunsaturated fatty acids

on body weight gain, liver triglycerides and the whole other standard parameters and their relation changes in the gut microbiome and the amount of fat that "left" the animals undigested.

Figure 1: Fecal fat and energy loss, total energy intake and relative (to control on normal chow) liver triglycerides, oral glucose tolerance and weight gain over the 8 week study period (de Wit. 2012)

A casual look at the data in figure 1 should suffice to see that there is a profound mismatch between almost all classic features of the metabolic syndrome of which we would usually expect that they would be closely associated:

• the rodents in the palm oil group ate the least amount of energy, excreted the greatest amount of fat and total energy in their feces and still gained the greatest amount of body weight and had the highest amount of liver triglycerides (beginning non-alcoholic fatty liver disease)
• the rodents in the olive oil group did not consume significantly more amount of energy or excrete significantly more amount of fat / energy in their feces and still gained ~40% less body weight and did not exhibit similarly high triglyceride storage in the liver as the rodents on the saturate fat (palm oil)
• the rodents in the safflower oil group were comparably ravenous (+20% energy intake), but although they did not excrete more energy and fat than their peers, their bosy weight gain was profoundly reduced and their liver triglycerides were better than in the "non high fat control group" and yet their glucose tolerance was not the best, but the worst of all the three groups

All that does only make sense, when a second parameter, or I should say another 100 trillion bacterial parameters come into play and the SFA induced reduction in microbial diversity and
composition (increased the firmicutes/bacteroidetes ratio) are accounted for, as well. those, this is at least what de Wit et al. believe are namely responsible for the complex changes in genes that regulate the fatty acid metabolism and expression of inflammatory markers, the scientists observed

Chicken or egg, cause of correlation? Or just gut optimization?

Even tde Wit et al. do yet point out that their observations do not provide significant evidence to establish a causal relationship between the bacterial changes, which are a direct result of an overflow of (selectively) antimicrobial saturated fats into the distal part of the intestine, the subsequent disturbances in the bacterial balance and (human!) gene expression in the gut and the  particularly pronounced obesogenic effects of saturated fatty acids.

You could, at least in my humble opinion, even argue that these are simply adaptive effects that ensure that the "host", in this case the rodents, "gets the most" out of his diet - after all, this is exactly what we are seeing here: A modulation of genes related to the conservation and storage of energy, such as the downregulation of the Bcmo 1 gene that predisposes to the development of obesity and non-alcoholic fatty liver disease (Hessel. 2008),  which allows for maximal energy efficiency despite greater fecal energy loss.

Conclusion? Drink safflower oil?

That these results should not be taken as an incentive to guzzle safflower oil (or drop your coconut oil for the latter) should be obvious. Just as obvious, by the way, as the realization that despite all the hoopla and my own excitement about the newly discovered importance of the gut microbiome as one of the possible contributers to the global obesity epidemic. We are understanding way too little about its interactions with its host, i.e. us, to exclude that we are not - yet again - confusing cause and effect, causation and correlation and take our gut microbiome, which is eventually nothing else than a mirror of our healthy or unhealthy lifestyle for the real deal, and try to modulate and fix the mirror image with anti-, pro- or prebiotics without working on what stands right before the mirror: The sedentary, convenience food consumer, who works to jobs and rather watches TV till late at night instead of getting his 7-8h of sleep....

References:

1. Aziz AA, Kenney LS, Goulet B, Abdel-Aal el-S. Dietary starch type affects body weight and glycemic control in freely fed but not energy-restricted obese rats. J Nutr. 2009 Oct;139(10):1881-9. Epub 2009 Aug 19. 
2. Hessel S, Eichinger A, Isken A, Amengual J, Hunzelmann S, Hoeller U, Elste V,  Hunziker W, Goralczyk R, Oberhauser V, von Lintig J, Wyss A. CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. J Biol Chem. 2007 Nov 16;282(46):33553-61.
3. 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.
4. Robertson MD. Dietary-resistant starch and glucose metabolism. Curr Opin Clin Nutr Metab Care. 2012 Jul;15(4):362-7. 
5. Shen L, Keenan MJ, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Zhou J. Dietary resistant starch increases hypothalamic POMC expression in rats. Obesity  (Silver Spring). 2009 Jan;17(1):40-5. Epub 2008 Oct 23.
6. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012 Feb;61(2):364-71.
7. Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Shen L, Danna SC, Tripathy S, Hegsted M, Keenan MJ. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6.
8. de Wit NJ, Derrien M, Bosch-Vermeulen H, Oosterink E, Keshtkar S, Duval C, de Vogel-van den Bosch J, Kleerebezem M, Müller M, van der Meer R. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am J Physiol Gastrointest Liver Physiol. 2012 Jun 14.
9. Zhou J, Martin RJ, Tulley RT, Raggio AM, McCutcheon KL, Shen L, Danna SC, Tripathy S, Hegsted M, Keenan MJ. Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6. 

Nutrition News Quicky: ⤹ Energy Reduction & Metabolic Parameters ⤹ "Macrobiotic Ma-Pi 2" = Diabetes Diet 2.0? Plus: Remember You're Eating Foods, Not Figures

Review suggests: On the SAD American diet only energy restriction saves the average Joes & Janes form diabesity.

Have you ever wondered what actually happens to your body, when you start dieting? I mean on a molecular / signalling protein level? If so, today's "Nutrition News Quicky" is for you, because one of the two studies this quicky is dealing with talks about just that: The type and onset of changes and the realization that Mr. & Mrs. Average Joe on their standard Western diets will gain weight, if they don't subscribe to life-long energy restriction. If you don't like that, it appears as if the "Macrobiotic Ma-Pi 2 Diet" could be a solution - or is this just too good to be true?

Energy Restriction & Metabolic Parameters

With all the hoopla about macronutrient composition, timing, etc. and the realization that the calories in vs. calories out equation is not as simplistic as most dieticians still want to have it, the word "calorie restriction" has gotten quite a bad rep in the Internet health community. 

Table 1 Comparison of the metabolic effects of caloric restriction after a variable period of time on (Soare. ahead of print).

If you take a look at overview of its effects in on body composition, blood glucose, lipids, etc. in Table 1, it does yet become obvious that you must not underestimate what will happen if you simply cut back on calories (based on overview in Soare. ahead of print). As long as the nutrition remains adequate (= you get the necessary micronutrients), eating less will lead to improvements in insulin sensitivity. This in turn triggers a whole cascade of beneficial effects that start with the reduction of fasting blood glucose levels and insulin concentration and end with significant reductions in body fat, type II diabetes rates, blood pressure and chronic inflammation.

Hey Mr. Average Joe, you are going to be fat and sick!

What is quite shocking, is the comparison of overweight dieters to Mr. & Mrs. average in a recent study by Soare et al. (2013).

If you take a look at the data in Table 1 you will see that the "healthy control" group Soare et al. defined in their review of the literature will almost inevitably develop a diffuse combination of obesity-related pathologies we call the "metabolic syndrom". In other words, if Soare's assessment of the situation was correct only the dieters will be able to ward off an insidious increase in body weight, blood glucose, insulin, etc. in the long run.

"What? I am going to be a fat sedentary slob?" Don't worry, you are not going to be either fat or a slob, unless you are sedentary. There is (imho) no debating that you either have to diet for the rest of your life or incorporate a minimal amount of physical activity into your everyday lives. If the focus is on health, recent studies have confirmed: The effects of exercise are more pronounced than that of "healthy dieting" (read more in the SuppVersity Facebook News).

On a more general note, I would like to point out that these "results" (in a way the assumption that everyone who is not dieting is going to become obese is rather a hypothesis) confirms my personal conviction that the ostensibly paradoxical difference between our bodies' inability to compensate for increased vs. decreased energy intakes is also a result of chronic overnutrition - or, to put it differently: If there is a 20% margin in our daily energy requirements within which our weight would be stable, 90% of the weight stable population of the Western obesity belt is consuming those extra 20%, anyway.

This would not just explain why each and every additional cookie people eat ends up on their hips "instantaneously"; it would also provide us with a simple, yet logical explanation that significant weight loss can only be achieved, if you reduce your dietary intake by >20%... but hey, I am getting side-tracked, here ;-)

⤹ "Macrobiotic Ma-Pi 2" = Diabetes Diet 2.0?

In their very recent, hitherto unpublished review of the effects of diet on type II diabetes a group of scientists from the University Campus Bio Medico conclude:

Battle diabesity w/ supplements

"Many dietary regimens are available for patients with type 2 diabetes to choose from, according to personal taste and cultural tradition. [...] Additional randomized studies, both short-term (to analyze psychological responses) and long-term, could help reduce the multitude of diets currently recommended, and focus on a shorter list of useful regimens." (Kahzrai. ahead of print)

A diet that was not (yet?) on the list Kahzrai et al. are referring to, here is the "Macrobiotic Ma-Pi 2" diet. A pretty funky name for a nutritional intervention the efficacy of which has been tested by Francesco Fallucca, Carmen Porrata, Sara Fallucca and Mario Pianesi in recent experiment. The results of this experiment are about to be published in a future edition of the peer-reviewed scientific journal Diabetes/Metabolism Research and Reviews in 2014 with a telling subtitle:

" Gut microbiota, inflammation, diet, and type 2 diabetes"

In conjunction with the word "macrobiotic" in the name of the diet, it should be obvious that the main idea behind this "new" anti-diabesity diet is to tackle the imbalance of the intestinal microbiota of which more and more scientists (e.g.. Musso. 2011; Qin. 2012) believe that it was the cause not the consequence of development of several human diseases, including obesity and type II diabetes (T2DM). As Kahzrai et al. mention in their abstract,

"[t]he main regulators of the intestinal microbiota are age, ethnicity, the immune system, and diet. A high-fat dietmay induce dysbiosis, which can result in a low-grade inflammatory state, obesity and other metabolic disorders. Adding prebiotics to the diet may reduce inflammation, endotoxaemia, and cytokine levels as well asimproving insulin resistance and glucose tolerance." (Kahzrai. ahead of print)

In their overview of the currently available literature, on the effects the administration of prebiotics such as fermentable dietary fibers has on the production of incretins (~satiety hormones), i.e.

• glucagon-like peptide 1 (GLP-1; fatty acid oxidation, glucose control ↑)  and 
• peptide YY (PYY; anorexigenic = hunger ↓), 

as well as its anti-ghrelin (orexigenic = hunger ↑), they highlight a very recent 21-day, intervention study in patients with T2DM. It is one of only few contemporarily available human studies of which the researchers say that they

"have not given robust results because of their limitations; most randomized controlled trials have been  short-term studies (no more than six months), with small sample sizes ( less than 50 subjects), and have focused on surrogate markers rather than clinical end points". (Kahzrai. ahead of print)

Many of these studies, which confirmed the previously referenced beneficial effects on GLP-1 and PYY have been conducted with pregnant women. These studies were able to show that the frequency of gestational diabetes is significantly reduced by probiotic intervention - immediate downstream effects on the children’s growth rate, on the other hand, were not observed (Luoto. 2010a).

"A unique follow-up study (Luoto. 2010b) has suggested that gut dysbiosis during the first stages of life may be associated with the development of obesity; this study investigated the bifidobacterial numbers in infant fecal samples and showed they were higher in children of normal weight than in overweight infants." (Kahzrai. ahead of print)

Luoto et al.'s follow up study is unfortunately does yet share one of the central limitations 90% of the currently conducted experiments have in common: They did not include all the factors that may be involved in the development of obesity, in particular dietary habits.

Table 2: Macrobiotic Ma-Pi 2 Diet typical composition (Porrata. 2009)

This takes us back to the previously mentioned "recent" series of studies, the results of which have not yet been fully evaluated, yet.

As you can see if you take a look at the typical diet composition of the subjects in the first, prospective trial (Porrata. 2009; see Table 2), the "macrobiotic" intervention was exclusively food based. It was composed of 40–50% whole grains (rice, millet and barley), 30–40% vegetables (carrots, kale, cabbage, broccoli, chicory, onions, red and white radish, parsley),  and 8% legumes (adzuki beans, chickpeas, lentils, black beans), plus gomashio (roasted ground sesame seeds with unrefined sea salt), fermented products (miso, tamari, umeboshi) and seaweeds (kombu, wakame, nori).

Bancha tea (tannin-free green tea) was the main source of liquid. The food intake was measured using the weight method for 7 consecutive days in the 2nd and 4th months of the intervention. The same goes for the compliance with the recommended (100% idiotic) macronutrient composition, according to which the subjects had to consume 15%, 20% and 65% of total energy in form protein, fat and carbohydrates, respectively.

Figure 1: Changes in body composition and glucose & fat metabolism after 6 weeks on Ma-Pi 2 (Porrata. 2009)

If you take a look at the data in Figure 1 there is yet still no debating: The tons of macrobiotic whole foods worked magically - irrespective of the suboptimal protein intake (66g per day, only), the study participants lost tons of fat weight and increased their lean body mass - certainly not bad, if you asked me.

There is yet still one question that needs to be answered: Is this a results of the macrobiotics or a result of the obligatory switch from the Western "convenience" to a whole foods diet that induced these changes? If you asked me, it's the latter. This does not exclude the beneficial influence of an increased macrobiotic content of the diet and corresponding changes in the bacterial make-up of the gut. In the end, this is yet a necessarily result of the enforced revisions the sixteen 60-year old adult type II diabetics who were all treated with insulin made to their food selection.

Bottom line: It may be hidden in plain sight, but the two studies I discussed in today's news quicky do have something in common. Something that's not just the term "type II diabetes": It's the way they can remind you of the things that actually matter: Food selection and quantity (well and exercise, or I should say "physical activity" - although it's not directly mentioned in the studies).

If I read the questions about diet I receive on an almost daily basis, the majority of them is concerned with irrelevant details that revolve around insignificant changes in macro- and micro-nutrient composition. At times it sounds as if you were eating figures, not foods. No wonder that this does not produce the weight loss or hypertrophy effects you could achieve if you started to count the number of eggs, potatoes and tablespoons of oil you consume instead of obsessing about the different effects of eating 300 and 324 rice corns... Ok, I am exaggerating, but if this exaggeration made you feel insulted, you are probably one of those people who would benefit most from letting go of the fractional digits in his or her food logs.

References:

• Luoto, R., Laitinen, K., Nermes, M., & Isolauri, E. (2010a). Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. British journal of nutrition, 103(12), 1792-1799.
• Luoto, R., Kalliomäki, M., Laitinen, K., & Isolauri, E. (2010b). The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years. International journal of obesity, 34(10), 1531-1537.
• Musso, G., Gambino, R., & Cassader, M. (2011). Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annual review of medicine, 62, 361-380.
• Porrata, C., Sánchez, J., Correa, V., Abuín, A., Hernández-Triana, M., Dacosta-Calheiros, R. V., ... & Pianesi, M. (2009). Ma-Pi 2 Macrobiotic diet intervention in adults with type 2 diabetes mellitus. MEDICC review, 11(4), 29-35.
• Soare A., Weiss E.P., Pozzilli P. (2013) "Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk". Diabetes/Metabolism Research and Reviews [ahead of print]
• Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., ... & Yang, H. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55-60.

Oleic Acid Modulates Gut Bacteria and Induces Weight Loss on HFD Diet. Wondertoothpaste w/ 32 Herbals Promises Cancer Protection. 2% Cholesterol Diet Bad For the Testes.

While Adelfo did not have the time to write a whole update, he still send me some current progress pics, I am allowed to publish. I guess you would agree that the his "carboholism" has not done signficicant damage to his physique, won't you? If  you want to know more about his current workouts click here. For some info on his diet check out this post or simply go through all of his recent and not so recent guestgposts, here.

Just in case you have not already figured it out based on the longish, 3-item title title and the absence of a "Plus: Sneak Preview on the SuppVersity Science Round-Up" at the end: There is no SuppVersity Science Round-Up, today: When I emailed him yesterday to say that I would not make it in time to the show today, it turned out that Carl was just about to let me know that he would not be in the studio and we would be doing the next installment of the Science RoundUp next week - strange coincidence, right? Anyway, now you can blame whomever you want for not being able to listen to my catastrophic German accent today ;-)

That being said, I guess some of you may have thought that there would be an update from Adelfo Cerame Jr. today. Unfortunately, that's not the case either. What I have to offer today is nothing more, but also nothing less than two impressive progress pics of our common friend and a triplet of news that I had lying around here for you to educate yourself in Carl's and my radio and Adelfo's blog absence. Judged by the huge interest the "Saturated Fatty Acids Cause Post-Prandial Endotoxemia" post generated the other day, I suppose many of you will like the first one best. Don't fret about the rest, though, but take it as a generous giveaway ;-)

Oleic acid supplementation prevents obesity by modulating gut flora

With 60-80% olive oil is one of the best sources of oleic acid. And the additional polyphenols make it an even better choice as a staple of your diet (read more about the polyphenol content of regular and extra virgine olive oil, here at the SuppVersity); also don't forget macadamia oil, which has >60% oleic acid

(Mujico. 2013) Once again, we are back to Saturday's post on the influence of different fatty acids on the gut microbiome and and your health. Today, we are yet not talking about pigs and saturated fats, but about rats and oleic acid, a monounsaturated omega-9 fatty acid, which has - at least according to this recent study by scientists from Spain and Brazil the ability to prevent the formation of an obese phenotype in response to high fat feeding via its obviously beneficial effect on the composition of the gut bacteria.

"Consumption of a HFD induced changes in the faecal microbiota (an increase in all the tested groups of Firmicutes, as well as the order Enterobacteriales, and a decrease in Bifidobacterium spp. and the phylum Bacteroidetes), which were associated with the appearance of an obese phenotype.

Correlation analysis revealed that body weight correlated positively with the phylum Firmicutes and clostridial cluster XIVa, and negatively with the phylum Bacteroidetes. Supplementation of the HFD with S1 counteracted HFD-induced gut dysbiosis, together with an improvement in body weight." (Mujico. 2013).

In that supplement group 1 (S1) denotes the administration of an oleic acid-derived compound at 1500 mg/kg per day, which did - much contrary to supplement group 2 (S2), a fish oil based n-3 fatty acids (EPA and DHA, 3000 mg/kg per day) do an awesome job as far as the decrease in weight gain is concerned (see figure 2).

Figure 1: Bacterial composition of the feces at the end of the supplementation period (Mujico.2013).

Interestingly, the most notable change in the gut microbiome in response to oleic acid supplementation was an increase in bifidobacteria and bacteroidetes (as mentioned in the quotation above the latter was significantly correlated with the reduced obesity), the otherwise often hailed amount of lactobacilli, on the other hand, did increase only in the fish oil group and it did, as the data in figure 1 goes to show you not have any ameliorative effect on the weight. Moreover, the rodents who received the high fat diet in conjunction with the oleic acid had by far the highest count of total faecal bacteria.

Figure 2: Weight development of the pre-fattened rodents in week 0-7 of the supplementation phase (Mujico. 2013)

Bottom line: Now despite the fact that all that sounds great and more than promising, you should keep two things in mind: (a) you are (hopefully) not over-consuming a diet that's both high in fat and carbohydrates (which is the standard HFD in rodent experiments) and (b) it still remains to be seen if and to which degree results from a rodent model can be transferred into the human reality. Still, maybe the benefits of the Mediterranean which is per se high in oleic acid (way higher than it is in omega-3, by the way) are actually related to it's effects on the gut microbiome and not to it's direct effect on the fatty acid composition of either the blood lipids or the cell membranes as we have long been speculating.

Wondertoothpaste contains herbal overkill, is supposed to protect from oral cancer

(Chowdhury. 2013) If you are into "kitchen sink" approaches, you will probably love the toothpaste a group of scientist from the West Bengal University of Technology in India have just formulated. It does contain not one, not two and not three herbals, but alongside baking soda (teeth whitener), egg shell powder (calcium source), clove oil (sensitivity), glycerin (preservative), and other basic ingredients, but rather 32 ranging from popular and well-known stuff such as

Choti elaichi (green cardamon) is - as exotic as it may sound actually still the most straight forward ingredient of the "kitchen sink" toothpaste. After all, it has a well established anti-microbial activity.

• curcumin - as an anticarcinogen,
• green tea - as free radical scavenger, and
• echinacea - as an immune stimulant

to more exotic herbals such as

• nayantara -as an anti-mitotic and anti-microtubule agent,
• choti elaichi (green cardamon) - as a desinfectant for the oral cavity and
• ajwain - usually used to prevent kidney stones, it's also supposed to have anti-cancer effects

I am not sure, whether I would be inclined to buy this toothpaste, but having the sentence "the toothpaste is theoretically as well as experimentally serve the basic properties of general toothpaste with an advantage of having the medicinal properties of 32herbs which makes it unique in its category" from the conclusion of the paper as a marketing argument would probably call peoples' attention. I mean, the kitchen sink, even caught mine ;-)

Excess dietary cholesterol is bad for your testes

Just to make sure you don't get scared hat all the healthy eggs you're eating would all of a sudden damage your testes. An egg has 0.4% cholesterol, so that it is 100% impossible to get the equivalent amount of cholesterol from eggs, even if you ate them all day. Plus, eggs have all your body needs to make best use of the cholesterol (learn more)

(Moustafa. 2012) --- While I would hope that most of you do know that all your hormones are eventually manufactured from  cholesterol and you would end up without any sex hormones, if you ate a cholesterol free diet and your body did not have the raw material it needs to manufacture its own cholesterol, a recent study from the Al-Azhar University in Cario, Egypt, clearly shows that having too much of it in your diet - in this case 2% - will lead to alterations in spermatogenesis and morphoogical changes in the epdididymal sturcture.

Interestingly, the provision of the essential amino acid methionine (0.5% of the diet) ameliorated some of the negative side effects (remember: methionine is the precursor to cysteine; learn more about the sulfur amino acids, here). Contrary to what common sense would dictate, this beneficial effect of methinonine was not dose dependent and decreased, when the dose was escalated to 2%.

References:

• Chowdhury, BR, Garai A, Deb M, Batthacharya S. Herbal toothpaste-A possible remedy for oral cancer. Journal of Natural Products. 2013; 6:44-55.
• Mujico JR, Baccan GC, Gheorghe A, Díaz LE, Marcos A. Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br J Nutr. 2013 Jan 10:1-10.
• Moustafa NA, Elnga A. Effect of Cholesterol and /or Methionine on the Testis of Rats. The Egyptian Journal of Hospital Medicine. 2012; 49: 857-878.

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.

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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.