Sucralose, Hazardous or Innocent? Part II: Appetite, Gut Health & Food Reward | Sucralose, Gluttony & Adiposity?

Plain mineral water is still the best thing to quench your thirst.

Today we are going to continue our thorough, educated reading of the recently published overview over the biological issues with sucrolase, a "popular" artificial sweetener most of you will probably know by its brand name Splenda. The focus of part I of this series was on the potential pro-diabetic effects of this agent that belongs to a class of molecules that has originally been hailed as a solution to the diabetes problem (it goes without saying that I am talking about artificial sweeteners here, right?). In a way we are thus only continuing the discussion, when we are trying to verify Schiffman's & Rother's argument that the consumption of sucralose is associated with an increase in obesity risk... or, put more simply that using sucralose is going to make you fat, not lean.

The good old "energy in" vs. "energy out" argument

As SuppVersity readers you are well aware that the oversimplified concept of an "energy balance" is fundamentally flawed. My recent post "Anorexia study suggests: Your body can easily reduce its resting metabolic rate by 10%" in the SuppVersity Facebook News is only one out of thousands of scientific papers you could quote to point out that replacing 420kcal of energy from pure sugar, i.e. three cans of regular coke, with its diet variety is not going to produce a net weight, let alone fat loss of 420g per week (suggested read: "Busting the 3,500kcal = 1lbs Weight Loss Myth!" | learn more).

This is part II of a multi-part series:

Sucralose, insulin, glucose, GLP-1

Appetite, Obesity & Gut Health

Cancer, Drug & Hormone Interact.

I know that Mark Sisson likes to says this, but this website is not written by a machine, but by a man who has the same "short" 24h days you have... basically, what I am trying to say is that I had to split this review of the review into a "trilogy" - and be honest, you wouldn't want an article thrice as long as this one, would you?

Thus being "in the know", you can only shake your head, when you read how Schiffman and Rother (ab-)use a recent study by Ruyter et al. (2012) to support the non-significant, not sufficiently differentiated data from epidemiological studies which inform us that obese people are more likely to consume artificial sweetened products than lean ones, to subliminally imply that artificial sweeteners would not help, in some cases even hinder weight loss.

"In an 18-mo trial with children, participants were randomly assigned to receive an 8-oz can per day of either a noncalorically sweetened or a sugarsweetened beverage that provided 104 kcal (de Ruyter et al., 2012). [...] The calorie consumption from these beverages was 46,627 kcal greater for children in the sugar-sweetened group than in the sucralose-sweetened group (5.8 × 77.3 × 104). In spite of this highly significant difference in calories consumed from the beverages, the total weight gain over this 18-mo study was only 1 kg greater for children in the sugar-sweetened group compared to sucralose group. No explanation was provided to account for the small difference in weight gain given the large difference in caloric consumption from the beverages." (Schiffman. 2013)

Despite the fact that Schiffman & Rother acknowledge that the scientists would not have been able to detect, if the children who consumed the sugar-sweetened beverages compensated by reducing their food intake, the reviewers fail to point out that neither this, nor the second "evidence" they cite, a 2-year study by Ebbeling et al. (2012), where Schiffman & Rother simply ignore the fact that the mere provision of diet sodas to the families of the adolescent subjects did reduce the weight gain in the active intervention period (1st year, see Figure 1, below), would confirm a negative real-world effect on body weight.

Figure 1: Change in body fat percentage (vs. basleline) of adolescents during the intervention & follow up period in the Ebbeling study (2012), of which the reviewers only cite the results of the follow up.

Let's be honest: If you actually take a look at the results from the Ebbeling study (Figure 1), you will have to concede that this study refutes the claim that artificial sweeteners make you fat. During the active treatment period, in the course of which the adolescent participants were...

• 

  "What Really Happens, When Nutrition Science Meets Real Life" | more

  ... supplied with noncaloric beverages (e.g., bottled water and “diet” beverages for the whole family) every 2 weeks, getting monthly motivational telephone calls with parents (30 minutes per call), 
• ... having three check-in visits with participants (20 minutes per visit), and 
• ... receiving written intervention messages with instructions to drink the delivered beverages and not to buy or drink sugar-sweetened beverages, were mailed to participants

...they do exactly what we originally expected them to do: They ameliorate the body fat gain in the adolescent subjects. In other words: As long as respective products are available, and dietary adherence is encourages, replacing regular sugar sweetened with artificial sweetened or unsweetened beverages can have a significant ameliorative effect on the body fat gains of adolescents - irrespective of the fact that they were obviously free to compensate with chocolate, cookies, etc..

Contemporary evidence from RCTs suggest either no, or beneficial effects

If you follow Schiffman's and Rother's lead and discard potential differences between sucrose and other sweeteners, acknowledge the fact that the results from previous rodent experiments have repeatedly failed to translate to human beings and take into account that this data is "inconsistent and conflicting" (Schiffman. 2013), anyways, you will be hard pressed to find arguments to support the claim that artificial sweeteners could hinder weight loss.

"No-Carb Foods, Artificial Sweeteners & The Cravings" | more

Potential mechanisms for the obesogenic effects: In a very detailed review Mattes & Popkin list a whole host of hypothesis ranging from the disproven stimulation of insulin and differences in the GLP-1 response, over osmotic effects and increase food palatability, up to the "Zero sugar, great, I'll have 10 instead of one of those cookies!" effect and the development of an extremely sweet tooth. What's important, though, is that none of this mechanisms is "supported by the available evidence, although some warrant further consideration" (Mattes. 2009).

In fact, the vast majority of RCTs clearly supports the assumption that non-nutritive sweeteners (NNS), artificial or not, promote weight loss and blunt weight (re-)gain (De la Hunty. 2006; Bellisle. 2007). The argument that these effects do satisfy the calories in vs. calories out hypothesis is pathetic, to say the least. Even a 100% controlled diet won't comply to an equation that is about as accurate as "1+2=343". We can thus register that:

1. There is ample evidence to support the beneficial effects of artificial sweeteners (including sucralose) as a tool during controlled dietary interventions.
2. There is insufficient evidence to support the claim that their regular consumption has a negative effect on body weight.

With respect to (2) we would even have to say that the limited amount of useful* evidence we have would rather suggest beneficial than detrimental effects (*a 'useful' study is not a study that tells me that obese individuals are more likely to consume artificially sweetened products than lean ones like the often cited epidemiological data). This is particularly true, for controlled interventions where sugar-sweetened beverages were replaced by their artificially sweetened counterparts.

The great unknown: Hunger, appetite and food reward

If data on the real-world effects of sucralose consumption on body weight gain is "scarce", consistent, experimentally verified hypotheses that would explain the potential underlying mechanism are quasi non-existent... or, I should clarify: They are still in their infancy. Against that background it's quite astonishing that more and more people appear to take it for granted that the consumption of artificially sweetened foods will mess with both, (a) your ability to control your energy intake and (b) the hedonistic response you derive from foods.

Table 1: Sweetness, dose to stimulate the sweet taste receptor (EC50; based on Matsuda. 2011) and correlation of sweetness and EC-50 value.

It goes without saying that there is no sucralose-specifc data out there, but the decrease in hypothalamic sweet taste receptor density I mentioned in the first installment of this series is something I'd expect to see in response to all artificial sweeteners that make it across the blood brain barrier (Note: Even Schiffman & Rother acknowledge that we do not know if they even do that!) - probably "sweetness" dependent,  by the way.  This would imply that sucralose would be the worst, cyclamate the least offender among the common artificial sweeteners in Table 1. With a sweetness that's 300x higher than that of sucrose, stevia would end up being the "(un?)happy medium".

Despite the fact that Schiffman & Rother don't really address this issue in their paper, I still want want to address the practical and thus relevant aspect of the various proposed theories for potential sweetener-induced increases in energy consumption.

Figure 2: Mean effective change in energy intake (%) in RCTs investigating the degree of energy compensation in response to the provision of artificial sweetened products (De la Hunty. 2006)

As the data from De La Hunty's 2006 meta-analysis of 32 study outcomes in Figure 2 clearly demonstrates, there is a statistically highly significant (p < 0.001) trend towards reduced energy consumption in the RCT [randomized controlled trial]. In that, the degree of compensation for the sudden energy reduction due to ingestion of calorically less dense, since artificially sweetened product ranged from statistically non-significant 18% to statistically highly significant 86% in trials such as Porikos et al. (1982), where 6 men lost and gained 0.8kg of body weight within 2x12 days in a metabolic ward on artificially sweetened and sucrose sweetened ad-libitum diets, respectively.

Non-nutritive sweetener (NNS) intake 1965-2004 (Mattes. 2009)

So, sweeteners can't ever make you hungry? I would not necessary subscribe to this idea. While the consumption of artificial sweetened foods as part of your regular diet, e.g. diet coke with your dinner, does not seem to be a problem, Mattes & Popkin (2009) rightly point out that "non-energy-yielding products may heighten appetite", when they are not "ingested in conjunction with other energy sources". So, if you are guzzling diet coke all day, this may very well trigger binge eating. With an ever increasing consumption of sweeteners from partially / totally artificially sweetened beverages (see table to the left), this could thus well be part of our obesity problem.

Just like the previously discussed (relatively short term) effects on insulin, GLP-1 and co, the #2 on the list of most frequently heard objections against the use of artificial sweeteners, i.e. dietary overcompensation, does thus appear to have little basis in fact. What we do not know, though, is whether the results will be identical for all types of sweeteners, or whether sucralose may be the toxic (this aspect will be covered in the next installment) or gut microbiome disrupting exception to the rule.

Sucralose induces changes in the gut microbiome

The last issue I want to address in this second installment of the "Sucralose, Hazardous or Innocent Trilogy" will thus revolve around the question, whether a modulatory effect of sucralose on the microbial composition of your gut could induce potential negative long-term effects that would not show up in the hitherto discussed RCTs.

Under the headline "Effect of Sucralose on the Number and Relative Proportions of Different Intestinal Bacterial Types", Schiffman & Rother argue that it has long been known that bacteria from the oral cavity and soil cannot use sucralose as a growth substrate. If the same was true for the bacteria in our guts the replacement of regular sugar with sucralose would thus starve our (beneficial) subtenants.

Table 2: Differences (%) in bacterial counts in feces of rodents on diets containing what in human terms would be ~14mg, 43mg, 71mg and 156mg of sucralose per day after 12 weeks treatment and 12 weeks into "recovery" (Abou-Donia. 2008)

Based on the fecal bacterial count of rodents on diets that would be equivalent to 14mg, 43mg, 71mg and 156mg of sucralose per day in human beings (see Table 2), Schiffman & Rother argue that chronic (12-week) ingestion of relatively low amounts of sucralose (a single can of Diet Crush Cream Soda, for example, has 42mg of sucralose) lead to highly significant reductions in the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria.

In view of the fact that Abou-Donia et al. (2008) observed the most significant losses in bifido- and lactobacillus strains, i.e. those strains that have repeatedly been implicated as the driving forces of the beneficial health effects of probiotic supplementation, this and not the previously discussed pro-diabesity effects should be the point where people start to freak out.

Table 4: Other sweeteners are preferred food for certain bacteria and may also alter the gut microbiome (Payne. 2012).

This is particularly true if you take into account that at least part of the beneficial effects of lactobacilli may be related to their ability to keep the number of enterobacteria, a large family of Gram-negative bacteria that includes both harmless symbionts, as well as a whole host of familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella, Proteus, Enterobacter, Serratia, and Citrobacter in check (Liévin-Le Moal. 2006) - exactly those bacteria, which produce the nasty lipo polysaccharides (LPS) that have been associated with inflammation and its downstream metabolic effects, such as obesity, diabetes, heart disease, gastrointestinal cancer etc. and, as the data in Table 2 tells you. Now, unfortunately, the these villains are all part only type of bacteria that was not significantly decimated by the sucralose challenge.

As Schiffman et al. point out these reductions are not, as Brusick et al. (2009) suggest simply a result of "normal variation". In fact, the probability to see a similar random reduction in bifidobacterial count occur "naturally"within 12 weeks would be 1/5000. It is thus more than just unlikely that the71.9%, 76%, and 77.7% reductions in bifidobacteria counts Abou-Donia et al. observed at dosages of 3.3, 5.5, and 11 mg/kg/d were coincidental.

Prebiotics, anyone? In view of the alleged neg. effects on your gut microbiome, you may feel inclined to increase your prebiotic intake. If that's the case, this top 10 list of food items with prebiotic fiber contents of up to 65% of total weight may help:

1. Chicory root - 65%
2. Jerusalem artichoke - 32%
3. Dandelion greens - 24%
4. Garlic - 18%
5. Leek - 12%
6. Onion - 9% 
7. Cooked Onion - 5% 
8. Asparagus - 5% 
9. Wheat bran - 5% 
10. Banana - 1% 

Remember: These are the "richest" not necessary the "best" sources ;-)

If there is reason to be concerned it's about your gut health and its downstream metabolic effects: In view of the important role of bacteroides for the health of the intestinal eco-system (Lee. 2013) and their persistent reduction even after the 12-week recovery period, the selective antibiotic activity of sucralose is as of now the by far most disconcerting negative health effect discussed in this series.

If the changes Abou-Donia et al. observed in their rodent studies were to be confirmed in human studies, where the subjects consumed a balanced whole foods diet with a high prebiotic content. The profound changes the researchers from the Duke University Medical Center report in their paper from September 2008 would be reason enough to revise my previous conclusions about a potential contribution of sucrose to the diabesity (=obesity + diabetes) epidemic.

In fact, a revision of the potential long(er) term downstream effects of sucralose on your metabolic health could be all the more indicated, if it turns out that the alleged toxic and endocrine-disrupting effects I will discuss in the next installment of this series turn out to be substantiated, as well.

Reference:

• Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health, Part A, 71(21), 1415-1429.
• Bellisle, F., & Drewnowski, A. (2007). Intense sweeteners, energy intake and the control of body weight. European Journal of Clinical Nutrition, 61(6), 691-700.
• De la Hunty, A., Gibson, S., & Ashwell, M. (2006). A review of the effectiveness of aspartame in helping with weight control. Nutrition Bulletin, 31(2), 115-128.
• de Ruyter, J. C., Olthof, M. R., Seidell, J. C., & Katan, M. B. (2012). A trial of sugar-free or sugar-sweetened beverages and body weight in children. New England Journal of Medicine, 367(15), 1397-1406.
• Ebbeling, C. B., Feldman, H. A., Chomitz, V. R., Antonelli, T. A., Gortmaker, S. L., Osganian, S. K., & Ludwig, D. S. (2012). A randomized trial of sugar-sweetened beverages and adolescent body weight. New England Journal of Medicine, 367(15), 1407-1416.
• Liévin-Le Moal, V., & Servin, A. L. (2006). The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota. Clinical Microbiology Reviews, 19(2), 315-337.
• Mattes, R. D. (1996). Dietary compensation by humans for supplemental energy provided as ethanol or carbohydrate in fluids. Physiology & Behavior, 59(1), 179-187.
• Mattes, R. D., & Popkin, B. M. (2009). Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. The American journal of clinical nutrition, 89(1), 1-14.
• Payne, A. N., Chassard, C., & Lacroix, C. (2012). Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity. Obesity Reviews, 13(9), 799-809.
• Porikos, K. P., Hesser, M. F., & Van Itallie, T. B. (1982). Caloric regulation in normal-weight men maintained on a palatable diet of concentional foods. Physiology & behavior, 29(2), 293-300.
• Schiffman, S. S., & Rother, K. I. (2013). Sucralose, A Synthetic Organochlorine Sweetener: Overview Of Biological Issues. Journal of Toxicology and Environmental Health, Part B, 16(7), 399-451. 

Weight Loss Supplements Exposed: Green Tea & Probiotics. Fat Loss, Energy Expenditure, Fat Oxidation, Sex & More

Yesterday at Starbucks: "I just ordered a bottle of probiotics!"

In view of the fact that all the feedback I got in response to the re-installment of the Short News was positive, I guess you won't mind if I use the chance and bundle the two soon-to-be-published weight loss studies from the British Journal of Nutrition into a Weight Loss Supplement Mini-Special of the SuppVersity Short News.

If you were actually sitting next to you, I would probably ask you, whether you'd prefer the good, or the bad news, first!? Well, I guess I'll start with the bad one, then: Green tea sucked - again!

ZERO effect of EGCG supplementation in overweight women

To examine the effects of green tea epigallocatechin-3-gallate (EGCG) on the changes in body composition (! not just weight), energy and substrate metabolism, cardiometabolic risk factors and liver function enzymes after an energy-restricted diet intervention in obese women, a group of researchers from the University of the Basque Country in Spain recruited a group of 83(!) obese (BMI 30-40 kg/m2) pre-menopausal women (Mielgo-Ayuso. 2013).

The women were randomly assigned to consume either 3x100 mg/d of EGCG or placebo (lactose) with each of their three main meals for 12 whole weeks. During those twelve weeks, all women followed a specifically designed low-energy mixed (55 % carbohydrates, 30 % lipids and 15 % proteins) diet that provided ca. 600 kcal/day energy less than the women would need to maintain their body weight. The energy content and macronutrient composition of diets were designed to achieve a weight loss of 0.5 to 1 kg per week, as it was observed by Davis et al. (2006) and Bantle et al. (2008) on very similar regimen. As the scientists point out, the "dietary instructions were reinforced weekly by a dietitian" (Mielgo-Ayuso), to optimise compliance.

Figure 1: Changes in body composition, energy expenditure and fat oxidation, left; changes in glucose, cholesterol metabolism and inflammation, right (Mielgo-Ayuso. 2013)

I am not sure how compliant the participants actually were, but in view of the fact that the women were advised not to change their physical activity habits during the energy restriction program, the relatively meager and statistically non-significant changes in body weight (-0·3 kg, p > 0.05) and fat mass (-0·7 kg, p > 0.05) are probably not really surprising. It is nice to see, though, that the women lost more fat than total mass - muscle loss was thus not an issue for the ladies.

What was not to be expected, though, - at least if you believe a single word of the hype about green tea supplements - were the non-existent effects of the purported weight loss supplement on  energy expenditure, fat metabolism, HOMA-IR (insulin sensitivity), total cholesterol, LDL-cholesterol, or triglycerides. In fact, the only good thing about the whole EGCG intervention was that the recently observed negative effects on the liver did not occur, either.

SIGNIFICANT Effect W/ 16 Million CFU of Nestlé's Lactobacillus rhamnosus strain

Want to check out the patent?

Despite the fact that the overall results are much more exciting than those in the previously discussed green tea study, I'd advise you to keep calm. We are after all dealing with another Nestlé study on a patented strain of Lactobacillus rhamnosus (LPR), i.e. "CGMCC1.3724" (date patented: 2012-05-10; #20120114622), and cannot tell how many never published negative study results the Nestlé guys had to dispose of, before Marina Sanchez et al. finally produced study results that pleased the marketing division of this multinational corporation.

What? Ok, ok... let's get back to the facts: The scientists from the Laval University and the Nestlé Research Center randomized a group of one-hundred fifty-three 18 to 55 year-old obese men and women to receive either a placebo or the said LPR formulation with 1·6 × 10⁸ colony-forming units of LPR and additional oligofructose and inulin per cap for a total of 24 weeks.

In the course of the first 12 weeks (phase 1), each participant received a personalised diet plan that would have him or her consume 500 kcal/d less than he or she'd need for weight maintenance (just as an aside, that's 100kcal more than for the subjects in the green teas study). During phase 2, each participant received a personalised diet plan without energy restriction. The good thing, the resting energy expenditure (REE) was actually measured: after a 12 h overnight fast in subjects having had rested for at least 15 min in a standardised supine position. This procedure was repeated thrice: (1) At baseline, (2) after the weight-loss and (3) after the second phase weight-maintenance periods using indirect calorimetry.

Figure 2: Changes in body composition (all data in kg) in men (left, blue) and women (right, orange) after weight loss (ΔW12) and weight maintenance (ΔW24) phase (Sanchez. 2013)

The data in figure 2 confirms what the abstract says: "The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks, mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered."

Figure 3: Changes in metabolic parameters, i.e. energy intake (kcal/day), resting energy expenditure (REE, kcal/day) and respiratory quotient (RQ, remember: low RQ = high fat, low carb oxidation) after 12 and 24 weeks (Sanchez. 2013)

It does yet also confirm - and that there was a significant treatment × sex interaction, observed with the women in the treatment group losing significantly more weight than those in the placebo group (P= 0·02). More importantly, though...

"[...w]omen in the LPR group continued to lose body weight and fat mass during the weight-maintenance period, whereas opposite changes were observed in the placebo group."

For the unlucky men, on the other hand, the (unquestionably expensive) supplement didn't do sh*t: Their "changes in body weight and fat mass during the weight-maintenance period were similar" irrespective of whether they received the placebo or the active treatment.

Whether this was the reason or a consequence of the fact that the the men didn't show similar significant reductions in circulating leptin, as the women is questionable. Based on the fact that the relative abundance of bacteria of the Lachnospiraceae family in faeces increase only in women, we do yet have to assume that the missing reduction in leptin, as well as the absence of the significant body fat reductions, the researchers observed in their female subjects was simply a results of ...

• under-dosing - the same the 1·6 × 10⁸ colony-forming units of LPR that was sufficient for the average woman (body weight ~89kg) could have been too low for the guys (body weight ~104.3kg) 
• dietary interference - there could have been something in the diets of the guys that ruined the effects of the supplementation (lactobacilli are not exactly friends of meats and we all know that men love their meat ;-)
• different baseline gut microbiome - it goes without saying that you cannot place a group of rabbits in forest full of predators and expect them to survive; similarly the LPR spores may have come off second in the guts of the men, because they have a less "LPR-friendly" baseline colinization
• fundamental sex differences - at the moment I am not sure what the underlying reasons could be, but it's not impossible that hormonal difference could have played a role as well

I am pretty sure that I could come up with a whole host of additional, increasingly bizarre ad-hoc explanations for the null-effect Marina Sanchez and her colleagues from the Laval University and the  Nestlé Research Center in Lausanne observed in their male study but would rather conclude this news-item with the scientists own funky, but not unlikely explanation: Men are simply too good at dieting!

True: Women have a harder time losing weight even with high protein | more

As the authors point out, we know from previous trials (and corresponding SuppVersity posts, read more) that men are generally more prone to respond to a negative-energy balance intervention than women - and that's true irrespective of whether it is an exercise-training programme (Tremblay. 1984), a diet– exercise programme (Doucet. 1999), or a session of exercise and of mental work (Pérusse-Lachance. 2013). Plus, if you look at the data in figure 2, you'll see that this is actualy "concordant with the results of the present study that shows higher weight loss in men in the placebo group than in the women". Sanchez et al. do now believe that the high baseline success "abolished this difference" (Sanchez. 2013).

In view of the fact that there was a difference in a single low-abundance taxonomic group  (Prevotellaceae) between the baseline gut microbiome of the male and female study participants, I would still not exclude that the different baseline gut microbiomes could at least have added to the 'effect abolishing effect' of the sex-specific ease of weight loss in men. I mean, why wouldn't the feces of the men show an increase in lactobacillus spores, if the supplement worked?

Bottom line: Today's installment of the short news is very characteristic of the dilemma with weight loss supplements. We are just realizing that the classic thermogenic 'rodent fat burner' don't really work in humans. Against that background the rise of supplements that target the gut microbiome and exert much more complex body recompositioning effects comes in the nick of time.  Unfortunately, our understanding of the complex interactions between the gut microbiome and our immune system in the context of the emerging science of immunonometabolism is so incomplete (Mathis. 2011) that we are more or less groping in the dark, whenever we supplement subjects, patients or even ourselves with allegedly healthful bacteria.

All alleged benefits aside,  "specificity", the 2nd Principle of Sensible Supplementation, should keep you away from the next best GNC or online supplement store. The two studies at hand do after all not warrant the use of either green tea or lactobacillus supplements as weight loss aids in lean, healthy and active  men or women.

Accordingly, the observation that green tea supplements won't help sedentary over-weight women to lose weight appears to be much more reliable than the allegedly impressive weight loss effects of the probiotic during the "maintenance phase" of the Sanchez study.

We must however not forget the respective constraints of the research design and irresponsibly over-interpret the results of the EGCG study to (a) the potential benefits of regular 'whole' tea consumption in the average, non-obese individual (Wu. 2003) or (b) visceral fat loss in diet + exercise interventions in obese individuals (cf. Maki. 2009). Similarly, the fact that obese women will lose weight on a LPR supplemented maintenance diet is very unlikely going to translate to lean, athletic folks like you and me. According to the 2nd Principle of Sensible Supplementation, which is "specificity" (learn them all), I don't see you or me heading over to the next best online shop to buy LPR or EGCG supplements - irrespective of the promising results of the Sanchez trial.

References: 

• Bantle JP, Wylie-Rosett J, Albright AL,et al.(2008) Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care31, Suppl. 1, S61– S78.
• Davis NJ, Emerenini A & Wylie-Rosett J (2006) Obesity management: physician practice patterns and patient preference. Diabetes Educ32, 557 – 561. 
• Maki, K. C., Reeves, M. S., Farmer, M., Yasunaga, K., Matsuo, N., Katsuragi, Y., ... & Cartwright, Y. (2009). Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. The Journal of nutrition, 139(2), 264-270.
• Mathis, D., & Shoelson, S. E. (2011). Immunometabolism: an emerging frontier. Nature Reviews Immunology, 11(2), 81-83.
• Mielgo-Ayuso J, Barrenechea L, Alcorta P, Larrarte E, Margareto J & Labayen I (2013). Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial. British Journal of Nutrition, available on CJO2013. 
• Tremblay, A., Despres, J. P., Leblanc, C., & Bouchard, C. (1984). Sex dimorphism in fat loss in response to exercise-training. Journal of obesity and weight regulation.
• Wu, C.-H., Lu, F.-H., Chang, C.-S., Chang, T.-C., Wang, R.-H. and Chang, C.-J. (2003), Relationship among Habitual Tea Consumption, Percent Body Fat, and Body Fat Distribution. Obesity Research, 11: 1088–1095.

Natural H. Pylori Treatment and a Brief Overview of its Ill Health Effects & the Scientific Debate About Whether its Eradication Would Necessarily be Good for Us

An H. pylori infection is not exactly a death sentence, but it can still have nasty consequences.

Over the past decade H. pylori has repeatedly been in the focus of scientific research. It has been linked with gastric carcinoma (Parsonnet. 1991; Huang. 1998). The summary of odds-ratio of a 198 meta-analysis by Huang et al. for example shows increases of cancer risk of 92%, 124% and 81% in infected patients for all studies, cohort, and case-control studies, respectively. The meta-analysis also found that "H. pylori–infected younger patients have a higher relative risk for gastric cancer than older patients with odds ratios decreasing from 9.29 at age ≤29 years to 1.05 at age ≥70 years." (Huang. 1998).

But cancer is only the "worst case" scenario, when it comes to the potential (ill) health effects of being infected with H. pylori.

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

The Helicobacter pylori bacterium has also been associated with in cases of chronic gastritis, functional dyspepsia, peptic or duodenal ulcers, and cancer or gastric lymphomas.

"Because it can survive in acidic environments, it remains intact in the stomach and promotes the destruction of the gastric mucosa. This makes the organ sensitive and vulnerable to triggering of ulcerative lesions and blocks the sterilization of food, producing failures in the digestion process." (Bonifácio. 2014)

Atrophic gastritis, which is a common consequence of rampant H. pylori infections, may cause pernicious anemia because it interferes with the absorption of vitamin B12 from food. The symptoms of gastritis in general are burning, abdominal pain, loss of appetite, nausea, vomiting, feeling of satiety and gastrointestinal bleeding.

One question that arises is: How likely is it that you are infected?

With worldwide prevalence estimated at between 50 and 90%, this type of cancer frequently occurs in developing countries. And one of the most comprehensive reviews of the literature confirms, the answer to this question may well depend on where you live.

Table 1: Population-based studies of Helicobacter pylori prevalence according to detection method,
published between April 2008 and March 2009 (Azevedo. 2009).

As a brief glimpse at the data in Table 1 shows, the number of infected individuals is lowest in Japan (in kids) and highest in African immigrants to Australia.

How is H. pylori transmitted? Laboratory studies have yielded evidence in favor of both faecal-oral and oral-oral pathways. However, a role for either waterborne or zoonotic transmission has not been ruled out. Overall, "the failure of investigations to single out a mode of transmission for H. pylori signals the possibility of multiple transmission pathways." (Goodman. 1995)

A classic, pharmacological "H. pylori" eradication scheme that would of which recent studies show that it is more effective if a metronidazole-based therapy is chosen over the standard clarithromycin-based therapy (Nishizawa. 2014), is yet something you should only contemplate if you have actually been diagnosed with the nasty gram-negative, microaerophilic bacterium. If you only suspect being infected or want to reduce your risk of being affected, the following natural H. pylori treatments are certainly preferable to the nitroimidazole antibiotic medication metronidazole:

• 

  Feijoa sellowiana (O.Berg) is one of the natural anti-H. pylori agent (Basile. 2010)

  Feijoa sellowiana fruits have been shown to inhibit the growth of Helicobacter pylori by Basile et al. in 2010.
• Leaves of Strychnos pseudoquina ST. HIL. (Loganiaceae) or rather a methanolic extract from these leaves which have been used traditionally as malaria treatment has been shown to be effective in a rodent study by Silva et al. (2005).
• Chamomille or more specifically an extract from the inflorence of the camomille flower (Cogo. 2010).
• Achiote (Bixa orellana) or rather a tincture that's made from the seeds of this shrub or small tree originating from the tropical region of the Americas (Cogo. 2010).
• Green Yerba mate leaves are another effective H. pylori treatment as Schubert et al. point out in a 2006 paper. Whether drinking mate tea will do the same, has not been established, though.

Maybe H. pylori  is not always bad!? As strange as it may sound, some scientists argue that the contemporary evidence that "with modern life, for probably the first time in human history, there are large numbers of noncolonized persons" and that this decrease in H. pylori infections was associated with an increase in gastroesophageal reflux (GERD), Barrett's esophagus, and adenocarcinomas of the gastric cardia and lower esophagus. These diseases are not directly related to H. pylori, but "colonization with cag+ H. pylori strains appears protective against these diseases." Accordingly, the authors of one of the more recent papers elaborating on this hypothesis conclude: "[I]n the 21st century, the continuing decline in H. pylori may lead to the disappearance of duodenal ulcers and distal gastric cancers and toward a marked increase in GERD, Barrett's esophagus, and esophageal adenocarcinoma." (Blaser. 1999)

• Garlic extracts are another of the better-known H. pylori treatments (Cellini. 1996)
• Pistacios, or rather the mastic gum from Pistacia lentiscus (L.) var. chia (Duham) has been found to inhibit H. pylori growth by Paraschos et al. (2007).
• Malva sylvestris inflorences and leaves have been shown to inhibit the growth of H. pylori by Buffon et al. (2001)
• False rubarb, aka Rheum rhaponticum roots have been reported to be effective H. pylori killers (Cogo. 2010).
• Pomegranate peels exhibit anti-H. pylori activity, as well (Hajimahmoodi. 2011).

Table 2: Anti-Helicobacter pylori activity of essential oils (Bonifácio. 2014)

Next the aforementioned plants, fruit and fruit parts which are usually used as methanolic or aqueous extracts, there is a good dozen of essential oils of which a recent review by Bonifácio et al. (2014) indicates that all of them exert significant inhibitory effects on H. pylori (see Table 2).

As you can see in Table 1 the major problem is that in vivo studies, i.e. studies in which the oil was tested in intact organisms, in the case of the essential oil from Cymbopogon aka lemongrass the anti-H. pylori effects were observed in vivo, as well (in a mouse study by Ohno et al. (2003), to be precise).

Against that background it remains to be seen if any of the previously mentioned oils, fruits, plants and plant extracts are "strong" enough to eradicate a rampant H. pylori infection in a living human being. What appears to be likely, though, is that they could prevent it from becoming "rampant" in the first place.

H. pylori eradication is not the only thing pistachios can do for you - find out more in "The Pistachio Manifesto: Antioxidant, Metal Chelator, DNA Protector, Anti-Cancer Agent, Bug Killer  & More." | read more

Bottom line: While the is conclusive evidence that certain strains, but not all forms of H. pylori increase your risk of developing gastric cancer. There is (a) evidence that some strains may actually protect you from developing other gastrointestinal diseases (see red box) and (b) insufficient data from in vivo studies to recommend any of the previously listed agents as an "effective replacement" for the standard course of antibiotics doctors usually prescribe to eradicate H. pylori.

That being said, it is non unlikely that the regular consumption of garlic and pistacios or the use of essential oils from lemon grass could protect you from being infected or infections from flaring up | Comment on Facebook!

References:

• Azevedo, Nuno F., Janis Huntington, and Karen J. Goodman. "The epidemiology of Helicobacter pylori and public health implications." Helicobacter 14.s1 (2009): 1-7.
• Basile, Adriana, et al. "Antibacterial and antifungal properties of acetonic extract of Feijoa sellowiana fruits and its effect on Helicobacter pylori growth." Journal of medicinal food 13.1 (2010): 189-195.
• Blaser, Martin J. "Hypothesis: the changing relationships of Helicobacter pylori and humans: implications for health and disease." Journal of Infectious Diseases 179.6 (1999): 1523-1530. 
• Bonifácio, Bruna V., et al. "Antimicrobial Activity of Natural Products Against Helicobacter pylori: A Review." Annals of clinical microbiology and antimicrobials 13.1 (2014): 54. 
• Buffon, Marilene da Cruz Magalhães, et al. "Avaliação da eficácia dos extratos de Malva sylvestris, Calendula officinalis, Plantago major e Curcuma zedoarea no controle do crescimento das bactérias da placa dentária. Estudo" in vitro." Revista Visão Acadêmica 2.1 (2001): 31-38. 
• Cellini, Luigina, et al. "Inhibition of Helicobacter pylori by garlic extract (Allium sativum)." FEMS Immunology & Medical Microbiology 13.4 (1996): 273-277.
• Cogo, Laura Lúcia, et al. "Anti-Helicobacter pylori activity of plant extracts traditionally used for the treatment of gastrointestinal disorders." Brazilian Journal of Microbiology 41.2 (2010): 304-309.
• Goodman, Karen J., and Pelayo Correa. "The transmission of Helicobacter pylori. A critical review of the evidence." International Journal of Epidemiology 24.5 (1995): 875-887.
• Hajimahmoodi, M., et al. "In vitro antibacterial activity of some Iranian medicinal plant extracts against Helicobacter pylori." Natural product research 25.11 (2011): 1059-1066.
• Huang, Jia-Qing, et al. "Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer." Gastroenterology 114.6 (1998): 1169-1179. 
• Nishizawa, Toshihiro, et al. "Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan." Journal of clinical gastroenterology (2014).
• Parsonnet, Julie, et al. "Helicobacter pylori infection and the risk of gastric carcinoma." New England Journal of Medicine 325.16 (1991): 1127-1131. 
• Paraschos, Sotirios, et al. "In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori." Antimicrobial agents and chemotherapy 51.2 (2007): 551-559.
• Schubert, Alexandre, et al. "Variação anual de metilxantinas totais em amostras de Ilex paraguariensis A. St.-Hil.(erva-mate) em Ijui e Santa Maria, Estado do Rio Grande do Sul." Quim. Nova 29.6 (2006): 1233-1236.
• Silva, Marcelo Aparecido da, et al. "Evaluation of Strychnos pseudoquina St. Hil. leaves extract on gastrointestinal activity in mice." Chemical and pharmaceutical bulletin 53.8 (2005): 881-885.

Science Round-Up Seconds: How Colostrum Turns the Oxidative Downsides of Endurance Exercise into Benefits and Why Cacao is so Much More Than Just Delicious

Looking for a delicious and more creative way than colostrum powered chocolate milk to combine today's seconds? What about Linda Wagner's Chocolate Cherry Bomb Smoothie with Colostrum, Caco, Maca, Acai, almond milk & more?

By now you will probably have listened to yesterday's installment of the SuppVersity Science Round-Up either via the Super Human Network live stream, or after downloading the podcast (the Round-Up starts in the 2nd hour) that has now been available for ~20h. In case you did not have the chance to listen live or listen to the podcast, but have a vested interest in erectile (dys-)function, optimal testosterone levels, the connection between testosterone, DHT, estrogen, insulin resistance, obesity, the health of your liver and longevity or you are simply eager to learn more about the latest research on high intensity interval training, steady state cardio,  everyday activity and the fallacy of the "exercise just makes you hungry hypothesis" (additional suggested read: "Dr. Oz Was Right: Exercise Does not Just Make You Hungry") and their effects on your metabolic health, conditioning and physique there is no way, you want to miss listening to this show, either before or after you devour this week's installment of the SuppVersity Science Round-Up Seconds.

• Colostrum supplementation blunts exercise induced reduction in endogenous anti-oxidants and potentiates its beneficial effects (Appukutty. 2012) --Published on November 22, this paper by Appukutty et al. is only the latest in a long line of articles on the effectiveness or ineffectiveness of colostrum as an ergogenic aid (suggested read: "Ask Dr. Andro: Are Colostrum and Milk Healthy Muscle Builders?). We will get to these differences in a minute, but let's first take a look at the effects the provision of 50mg/kg body weight (human equivalent: 2.4mg/kg) had on the total antioxidant status, lipid oxidation, xanthine oxidase and super oxide dismutase levels in treadmill exercised (30min per day) mice.

  

  Figure 1: Relative levels of total antioxidants, xanthine oxidase and super oxide dismutase in supplemented (COL), exercised (EX) and exercised + supplemented (EX + COL) mice expressed relative to sedentary non-supplemented control (Appukutty. 2012)

  It's not difficult to see that the effects of the colostrum supplement go beyond the mere amelioration of the exercise induced decrease in total anti-oxidant enzymes and super oxide dismutase levels. The human equivalent of only 2.4mg/kg body weight per day did - after 14 days of supplementation the total antioxidant status in the exercised + supplemented rodents was already 5% greater, after 21 days whopping 11% greater than in the supplement only group.
  
  In view of the previously reported benefits of supplemental colostrum you could certainly argue that the obvious parallels to the difference between "training" and "overtraining", with the former having promotive and the latter having compromising effects on the endogenous anti-oxidant system of your body are no coincidence. In view of the about as many studies which found no or at least no significant factually or potentially ergogenic effects in response to supplemental "beast milk", we still have to answer the question I invoked in the introductory paragraph of this sub/item of today's installment of the SuppVersity Science Round-Up Seconds: "How come it works in some, but by no means all studies?" The answer could actually be way more straight forward than you think and reads "Simply because he scientists used different supplements!"
  
  Even the dairy industry has realized that the way they feed their cows and post-process their colostrum, before they eventually feed it to their offspring, renders almost 60% of the maternal colostrum from US dairy farms "inadequate" so that "a large number of calves are at risk of failure of passive transfer or bacterial infections, or both." (Morrill. 2012)
  
  

  

  Not all colostrum is made the same and the beneficial effects of each and every individual product - specifically with respect to the integrity of the intestinal wall - will necessarily depend on its bacteria content and the latter depends on the feed the cows receive as well as the processing the colostrum undergoes.

  If you do still remember my post on the etiology of exericse-induced increased intestinal permeablity and the beneficial effects 'intact' colostrum has on the integrity of the gut you just have to put two and two together and you have your explanation: Just like the efficacy of any artificial supplement depends on he chemicals the producer puts into it, the effectiveness of a food supplement will vary due do both natural (e.g. seasonal, feed dependent, stress andhealth related...) and 'unnatural' fluctuations in its ingredient profile. Heat treatment, which is applied to almost all commercially available colostrum supplements, for example, may leave most of the IgG content intact, but it will reduce not just the total count, but also the diversity of the microbiota in colostrum (only the heat resistant bacteria, mostly gram-positive, will survive; cf. Hayes. 2012) 

• Study shows, cacao phenols protect your gut from inflammation, but there is much more cacao can do for you (Rodríguez-Ramiro. 2012) -- As a recent paper by scientists from the Ciudad Universitaria in Madrid (Spain) goes to show you, colostrum and bacteria are not the only naturally occuring supplements that are good for your gut health. Cacao has just been shown to do a pretty decent job, as well.
  
  

  

  Table 1: Nutritional content of the experimental diets the rodents were fed for 8 weeks with the carcinogen being injected in week 3 and 4 (Rodríguez-Ramiro. 2012)

  In an in-vivo the Spanish observed that a diet that was enriched with 12% cacao powder had astonishing anti-inflammatory effects in a rat model of azoxymethane (AOM)-induced colon carcinogenesis. The rodents had been fed the 12% cacao diets (composition see table 1 to he right), for 8 weeks. In weeks three and four, the scientists injected the procarcinogenic drug azoyxymethane in order to induce intestinal inflammation that would potentially lead to the development of colon cancer.
  
  Compared to the animals on the regular chow, the rats in the cacao group exhibited highly significant decreases the nuclear levels of  NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase, all of which were profoundly upregulated in response to the AOM injections in their peers on the regular diet.
  
  In a subsequent in-vitro experiment on Caco-2 cells, the scientists were also able to confirm that cocoa the cacao polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation.
  
  Now, it does not really appear feasible to eat a 12% cacao powder diet, right? Well, based on the data from table 1 the average food intake and body weigh of the rodents and some mathematical shenanigan, it's actually not difficult to calculate that the human equivalent dose, which would be 150g of cacao powder per day conains no more than 3g of polyphenols and could theoretically be achieved by supplementing with ~15g of chocamine every day. Ok, that would be hilariously expensive, but I assume you don't inject 3.25mg/kg azoyxymethane on a regular basis, right? Well, I guess this would mean that you won't need 15g of chocamine or 150g of cacoa powder to protect your gut either, right?
  
  Moreover, I suspect that most if not all of you will have heard or read about one of the dozens of epidemiological studies which show associations between very moderate intake of dark chocolate and cardiovascular, neuronal and metabolic health. Apropos "metabolic" did I mention that the animals in the cacao group were also 10% leaner than their peers on the regular - probably not a fair comparison with the differences in the macronutrient make-up but it would still be worth adding another bulletin point to a pretty impressive list of scientifically proven health-benefits of cacao consumption (or supplementation with respective extracts), which comprises among other things

  

  Guess how she got in shape? Right! The EDC Program ! EDC? Yeah: "The Female Weight-Loss EDC: The Fat Burning, Waist Reducing Synergy of Exercise, Diet and Dark Chocolate" - click here to  learn more

  • high antioxidant activity
  • improved insulin sensitivity, beta cell function & carbohydrate metabolism
  • improved HDL/LDL ratios
  • inhibition of detrimental byproducts of the arachidonic acid metabolism
  • induction of NO-mediated, endothelium-dependent relaxations
  • reduced incidence of stroke due to hypotensive effects
  • anti-CVD effects via TGF-β_{1 and} decreased tendency of blood to clotting
  • local and systemic TNF-alpha modulation and VGEF suppression => anti-cancer efects
  • immune effects that can protect you from tooth decay
  • protection against UV radiation and rejuvenating effect if its applied to the skin
  • suppressive effect on fatty acid synthesis
  • increases in mitochondrial respiratio
  • ability to boost serotonine (5-HT), improve mood and lower appetite and cravings
  • [...]
  I am not intending to make an all-encompassing list, here. Instead I will conclude with the astonishing insight from one of the most recent meta analysis that the daily consumption of the polyphenol equivalent of 100g of dark chocolate (at least 60-70% cacao content; 500-1,000mg polyphenols) would prevent 85 cardiovascular events per 10,000 capita every year (Zomer. 2012).
  
  Don't get me wrong I am with you with respect to the absurdity of cost-analyses when we are talking about health, but that's unfortunately the way the health business is operating and therefore I won't simply ignore the 50,000$, which is the saving the scientists estimate for every saved life and the corresponding 40$ of which Zomer et al. suggest that they should be spent "per person per year could be devoted to advertising, educational campaigns, or potentially subsidisation of dark chocolate in this high risk population." (Zomer. 2012)

That's  it for this week - at least as far as the SuppVersity Science Round-Up goes

Since Maxim asked "And what about garlic?", here is an addendum summarizing what I maybe did not get across very well at the end of the show, when I was flabbergast that the show was already over: The researchers took 20 male non-athletes (aged 22-26 years, body fat 16-20% and VO2max 38-42 ml/kg/min) randomized them to 700mg garlic or dextrose control  for 14 days and had them work out at 75% VO2max on the treadmill for 30 minutes at the end of the intervention period. Afterwards they analyzed the blood samples and found that (a)the 14 day supplementation alone reduced the basal triglyceride and increased the high density lipoprotein-cholesterol (HDL) increase (P<0.05) and (b) increased the beneficial effects of the exercise bout on acute reductions in LDL and triglycerides (Zekril. 2012)

I hope you enjoyed listening to the show (click here to download the podcast in case you still haven't done so) and satisfied your cravings for more with this installment of the SuppVersity Science Round-Up Seconds: In case you haven't I suggest you browse over to the SuppVersity Facebook Wall and check out the latest news on

• The connection between MS an impaired blood-brain barrier: A leaky brain and the intrusion of fibrinogen (a coagulation protein from the blood) could be the cause of multiple sclerosis (read more)
• Fishing for Omega-3s in Milk: One cup of fish oil enhanced milk yields 432mg of DHA + EPA... and it does not taste or smell fishy (read  more)
• Heart disease may begin even before you are born: Prenatal stress will turn the "probably" before "develop heart disease" into a "most likely" (read more)

When you are done with that and still hungry for more, you may want to check out my, as well as Patrick Arnold's, Kurtis Frank's (examine.com) and Willem Koert's (ergolog.com) contributions to a round-table discussion on the more or less recent ban of DMAA (aka geranium oil) in Australia - I have been so busy that I totally forgot about having done the respective interview weeks ago. Sorry for letting you know so late ;-)


References:

• Appukutty M, Radhakrishnan AK, Ramasamy K, Ramasamy R, Abdul Majeed AB, Ismail MN, Safii NS, Poh KB, Chinna K, Haleagrahara N. Colostrum supplementation protects against exercise - induced oxidative stress in the skeletal muscle in mice. BMC Res Notes. 2012 Nov 22;5(1):649.
• Hayes MM, Hughes TA, Greene AK. Bacterial diversity in dried colostrum and whey sold as nutraceutical products. J Food Sci. 2012 Jul;77(7):M359-63.
• Morrill KM, Conrad E, Lago A, Campbell J, Quigley J, Tyler H. Nationwide evaluation of quality and composition of colostrum on dairy farms in the United States. J Dairy Sci. 2012 Jul;95(7):3997-4005.  
• Rodríguez-Ramiro I, Ramos S, López-Oliva E, Agis-Torres A, Bravo L, Goya L, Martín MA. Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells. Br J Nutr. 2012 Nov 28:1-10. 
• Zekri1 R, Jafari A, Dehghan G.  The concurrent effect of one bout aerobic exercise and short-term garlic supplementation on the lipids profile in male non-athletes. J Shahrekord Univ Med Sci. 2012; 14 (5) :34-41
• Zomer E, Owen A, Magliano DJ, Liew D, Reid CM. The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model. BMJ. 2012 May 30;344:e3657.

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.