To Spit or to Swallow - That is the Question! Carbohydrate Mouthrinse May Be Better Than Water, Yet Still Not an Option for Performance Oriented Athletes

Image 1: "You need carbs to fuel your workouts!" You know the whole litany... what may be news to you is that scientists are speculating that "intra workout carbs" do not necessarily have to be ingested to do their ergogenic magic.

Those of you, who already "friended" me on Facebook and are following what is going on on the SuppVersity Facebook page (just want to remind you that Facebook has now an option that allows you to be informed, whenever something new is posted), will probably remember the discussion revolving around "carbohydrate mouthrinsing" and whether or not it may be even more beneficial to spit and not to drink your Gatorade... now, all the health benefits of low-carbohydrate (when I am talking "low" I am not talking of Atkins type <80g) diets aside, it does seem pretty counter-intuitive that just swishing one of those carbohydrate-laden electrolyte drinks in between your teeth for a few seconds, to then spit it out again could actually have any merit. Yet, science, or I should say a handful of studies, do suggest otherwise.

As part of their recently published study into the effects of carbohydrate mouthrinsing on exercise capacity in the pre- and postprandial state (Fares. 2011), Elie-J. M. Fares and Bengt Kayser have compiled a list of the 8 hitherto published peer-reviewed papers on that subject. And if you just went by the column "increased perfomance", "yes or no", it appears like it was an established fact that carbohydrate mouthrinsing was highly ergogenic. After all, six out of the eight studies are marked with the tag "increased performance".

Figure 1: Performance increases and standard deviations of the respective measures from studies on the advantage of carbohydrate vs. artificially sweetened or plain water mouthrinse (data calculated based on summary in table 2 of (Fares. 2011)

If we do yet have a look at the quantity of those performance increases and the individual standard deviations (I compiled the respective data for you in figure 1), things begin to look less conclusive. I mean, there is obviously a standard deviation for both arms of each study and there also is a mean improvement (or decrease in performance), but if the "performance increment" is smaller than the standard deviation, for all but one study, this does make me feel uncomfortable with the statement that I would see "scientific evidence", let alone "conclusive scientific evidence" in support of carbohydrate mouth-rinses.

Mouthrinse vs. placebo = minimal (if any advantage), but what about vs. ingestion?

Regardless of what you think about the real world significance of an average performance increase of 1% (calculated based on the data from figure 1), for the small fraction of athletes for whom these minimal performance increases would actually count, i.e. high intensity endurance athletes, like time-trial Tour de France cyclists, the "control", or I should say the "benchmark" should not be plain or sweetened water, but rather one of these crab-, ah... pardon me, carb-loaden sugary electrolyte drinks these athletes are habitually consuming. I was thusly happy to see that Catherine Moss, a student of Sports and Exercise Sciences at the Massey University in Auckland, New Zealand has recently conducted an experiment for her thesis that has much more practical relevance for the high achieving athletes (Moss. 2011).

Table 1: Composition of the placebo and CHO supplement in the Moss study (adopted from Moss. 2011)

In a randomized, counter-balanced, double-blind study, Moss had eight recreationally trained cyclists perform a time trial (with a predetermined amount of work) in the course of which the cyclists ingested or rinsed (swirling 0.33ml/kg body weight of the solution for 8s) with either a placebo solution or a carbohydrate drink, whenever another 12.5% of the total work was done. In that it is worth mentioning that the composition of the CHO solutions differed for the one that was meant to be ingested and the one that was intended to be swished. With the former containing 7.5% and the latter 15% carbs, Moss mimicked solutions that had been used "successfully" previous studies. I do yet no idea, why the placebo did not contain electrolytes, as this could obviously have made a difference at least in the ingestion trials... I guess this is what distinguishes a thesis like this from a study that is worth being published in a peer-reviewed journal ;-)

Figure 2: Mean power output (in Watts) at different time points during time trial (data adapted from Moss. 2011).

As the performance data in figure 2 goes to show, only the ingestion of the carbohydrate led to significant improvements in mean power output, specifically at the later stages of the time trial. This "breakdown" may be explained by the "glycogen reduction exercise protocol" all participants had conducted the day before the time trial. So that after a "low carbohydrate" dinner, the participants were supposed to be glycogen depleted when they performed the time-trial on the subsequent morning.

Figure 3: Total time (in s) during time trial (data adapted from Moss. 2011).

In a way this is an unfair advantage, for the carb ingestion, which accordingly elicited way better time trial times. It does yet not lessen the significance of data on carbohydrate vs. water mouth rinse, which shows pretty conclusively that in a glycogen depleted state both forms of mouthrinsing (plain water or a 15% carbohydrate solution) are equally ineffective, when it comes to actual performance increases.

Figure 4: Pleasure / displeasure feeling during time trial (data adapted from Moss. 2011).

If you do however look at the pleasure/displeasure feeling scale data in figure 4, I would speculate that in a non-glycogen depleted state the carbohydrate-rinsers would have performed significantly better... I mean, without gas in the tank a car won't work even if it "wanted". In view of the fact that the carbohydrate ingestion group did yet pedal at a higher intensity, this would warrant further investigation.

Figure 5: Respiratory exchange ratio (higher values = higher carbohydrate oxidation) during time trial (data adapted from Moss. 2011).

That being said, there was what I consider an interesting effect of carbohydrate rinsing on the respiratory exchange ratio (remember higher values = higher carb oxidation), which would suggest that the theory Fares and Kayser propose (Fares. 2011), according to which the activation of sweetness taste receptors cells (T1R2 and T1R3) in the mouth would explain the previously cited performance "increases" in other studies, may have its merits. What else than the sensation of incoming carbs could explain that the cyclists burned more carbs in the carb mouthrinse compared to the placebo mouthrinse trial (cf. figure 5) - and that in the absence of significant differences in blood glucose or insulin levels?

Spit it or suck it? What's right for you?

While we do not know whether it would make sense to mouthrinse in a glycogen repleted state (yeah, I know +1% ;-), for any athlete interested in maximal performance, simply ingesting his carb + electrolyte drink would certainly be the best option. The (intermittendly) fasting dieter, who wants to maximize his fatty acid oxidation in the course of say his "morning cardio", on the other hand, would be best off with a non-carby electrolyte drink that helps him avoid dehydration and does not compromise (even if the effect is minimal) fatty acid oxidation... what? You want to know who would  benefit from spitting his carbs out? Well, at least based on the current data, mostly the cleaning contractors of your local gym - after all, they would have to work overtime (and be paid overtime) to clean up the mess ;-)

Stevia - So Much More Than Just a Natural Sweetener: Combination "Therapy" With Stevia and Fenugreek as Effective as Common Diabetes Drug!

Image 1: Nature vs. Pharma. Leavs and seeds vs. chemicals - guess who will win!

I have been wondering for quite some time now, why I, as a resident of the European Union, do still have to use my hair-care products to sweeten my tea, my yogurt, or whatever else, if I do want to avoid artificial sweeteners or the good, or I should say, "bad" old table sugar... for those of you who are now wondering how hair-care products relate to my sweet tooth - here in Europe, Stevia rebaudiana Bertoni has still not been approved as a food additive, so that the myriad of health-food shops carrying respective products simply relabel them as "hair-care" or "cosmetic products, not intended for internal application"... and as a obedient citizen I would, of course, never even remotely consider ingesting a product such as stevia that is so utterly natural and genetically unmodified that it must be harmful ;-)

A pros pos harmful: As it turns out, stevia could in fact be pretty harmful - yet not for my or your physiological health, but certainly for the financial health of the big pharma companies. After all, scientists from the Departments of Pharmacology at the Bangladesh Agricultural University and the Faculty of Medicine at the Kagawa University in Japan have recently been able to show that Stevia rebaudiana Bertoni, in combination with Fenugreek aka Methi (Trigonella foenum-graecum), exhibits similarly potent hypoglycemic effects in Streptozotocin treated rats (the reference model for type II diabetes) as Amaryl(R), a commonly used diabetes drug based on the active ingredient Glimepiride (Rafiq. 2011). It thusly stands to reason that big pharma has a vested interest in delaying or even preventing the admission of stevia as an allowable food additive. Think about it: Who would buy all the Amaryls, Metformins & Co if Coca Cola decided to put stevia instead of aspartame into their soft-drinks and - all of a sudden - all those pre-diabetic soft-drink junkies would not develop full-blown type II diabetes, anymore? Ah... I am digressing again. Let's get back to the facts.

For their study Kazi Rafiq and his (I hope that "Kazi" is a male first name ;-) colleagues had collected fresh stevia and methi (=fenugreek) leaves and seeds and prepared them according to the following procedure:

Fresh Stevia leaves that were collected from the garden were oven dried first and then dried leaves were grinded with Grinder machine. Then 1g dried leaves samples were mixed with 10ml distilled water and were allowed to stay for whole night. Everyday fresh extract were prepared by using these techniques. Water extract of methi was made from 100g fresh seed sample by grinding with Grinder machine, and mixed with 2000 ml distilled water. Then the water extract was lyophilized in Central Laboratory, BAU. Finally the herbal drug was collected as powder form by Freeze drying in Central Laboratory, BAU.

The scientists then injected their 30 of their 36 Long Evans rats with Streptozotocin (STZ) to induce insulin resistance (again, STZ-treaded rodents are the most commonly used model of type II diabetes). After two weeks of STZ injection the (then) diabetic rats were divided into 5 groups:

• Group-B: diabetic control (STZ).
• Group-C: STZ + aqueous extract of stevia leaves @ 100 mg/kg,
• Group-D: STZ + aqueous extract of methi leaves @ 500 mg/kg,
• Group-E: STZ + combination of aqueous extract of stevia and methi leaves @ 500 mg/kg
• Group-F: Amaryl @ 800µg/kg

The plant extracts and the drug were administered orally once daily for 60 days. Blood glucose levels were monitored during the treatment period and an oral glucose tolerance test was conducted at the end of the 60-day experiment (results cf. figure 1).

Figure 1: Blood glucose levels (in mg/dl) in response to oral glucose tolerance test in normal and diabetic (STZ) rats after 6 weeks on a combination of stevia and fengreek extracts or the anti-diabetes drug Amaryl - left; change in area under the respective curve (AUC) relative to normal control - right (data adapted from Rafiq. 2011)

As you can see Amaryl and the combination therapy with stevia and fenugreek extracts at 500mg/kg per day (equivalent to 81mg/kg for a human being; or ~6.5g of each for someone weighing about 80kg) were equally effective in ameliorating the blood glucose response (within the statistical margin the AUC was identical).

Figure 2: Elevations in blood sugar levels (compared to healthy control) after STZ treatment and consecutive administration of stevia, fenugreek, a combination of both or Amaryl (data calculated based on Rafiq. 2011)

Moreover, the combination of stevia and fenugreek ameliorated the negative effect the Streptozotocin treatment had on blood glucose concentrations to a similar extend as Amaryl (cf. figure 2), which led the scientists to conclude that...

these findingslend pharmacological support to the suggested folkloric and ethnomedical user of these plants in managing and /or controlling of diabetes mellitus in rural communities of Bangladesh.

While the use of small amounts of stevia to sweeten your beverages and / or food will probably not have the same profound effects on your blood glucose levels as the combination of what would amount to a ~6g equivalent of leaf and seed extracts from stevia and fenugreek used in this study, I would assume that those dubious"hair-care products" still constitutes the most healthy sugar-alternative on the European market - so do your pancreas, ahh.. I mean hair, a favor and get yourself some stevia ;-)

Xylitol, a Low-Calorie Sweetener With Unknown Fat-Burning Side-Effects!? Replacing Cornstarch With the Five-Carbon Sugar, Xylitol, Ramps Up Fat Burning Enzymes in Rodent Model of Diet Induced Obesity.

Image 1: Xylitol christals under the micro-
scope (photo taken by Anders
Østergaard Madsen, Denmark 2001)

From a health perspective, the five-carbon sugar alcohol Xylitol has hitherto principally been known for its beneficial effects on dental health. With a caloric value of 3kcal/g the naturally occurring ingredient of a wide variety of plants, citrus fruits (plums, strawberries, raspberries) and vegetables (cauliflower) does have less calories than sugar, nevertheless, according to the fundamentally flawed, but still widely held paradigm that "a calorie is a calorie, no matter where it comes from", the idea of replacing sugar with xylitol to reduce the overall caloric load would make little sense even on a diet that was relatively high in carbohydrates. So, if it were not for the highly marketable statement "sugar free" on chewing gums and candies, xylitol would probably not even have made it to the consumer market. A cursory glance at the abstract of a study (Ama. 2011) that is about to be published in the July issue of the Journal of Clinical Biochemestry and Nutrition (Vol. 49, No. 1) does yet suggest that these research results could renew the interest in a compound many of you may have considered to be nothing but another marketing scam from the (diet-)food industry - and, before this new data came out, you were 100% spot-on with your assessment ;o)

In the course of an 8-week feeding period, Kikoko Amu and his collegues from the University of Tokoshima Graduate School, the University of Shizuoka and the Food and Science Institute in Kanagawa, Japan, fed a group of 18 male Sprague-Dawley rats (initial body weight 290-310g) a high fat diet containing 312.3 g/kg cornstarch (control group), of which, in the experimental groups, X1 and X2, 16% (X1) or 29% (X2) were replaced with 1.0g/100kcal (X1) and 2.0g/100kcal (X2) of xylitol for group X1 and group X2, respectively. At the end of this period the scientists found that

long-term intake of xylitol supressed the accumulation of visceral fat [cf. figure 1, below] and the increase in plasma insulin and lipids concentrations in rats fed a high-fat diet.

Interestingly, at least part of the effects were mediated by xylitol-stimulated "expression of fatty acid oxidation genes in the liver, and lipid degradation and adiponectin genes in the adipose tissue." Furthermore, Amo et al.

found for the first time that xylitol ingestion lowered postprandial hyperglycemia [if administered at] a none-effective dose in causing diarrhea, and within the limits of orally administered physiological amounts (1-4g/kg body weight daily).

The human equivalent dose for this "non-effective dose in causing diarrhea" (nice, how these Japanese try to paraphrase that the dose they used did not cause "the runs", isn't it?) is 0.16-0.65g/kg per day, which would amount to somewhere between 13g and 52g of xylitol for a man who weighs 80kg. A pretty large dose considering the fact that some low-carbers out survive on hardly more than 40g of carbs a day.

Figure 1: Weight [in g/kg body weight] of retroperitoneal, epididymal and mesenteric part of visceral fat in high-fat (HFD) and high-fat xylitol-substituted (X1, X2) fed rats after 8 weeks of treatment (data adapted from Ama. 2011)

Despite being on a high-fat diet (I hope the readers of this blog have already gotten the message that low carb wont work in the absence of fat) its highly questionable, especially for "low-carbers", whether and to which extent healthy human beings would benefit from xylitol substitution. After all, the "high-fat" chow the rats were fat contained a whopping amount of 362.3g carbohydrates from corn and only 200g of fat from lard (75%) and soybean oil (25%). In view of the dietary 'quality' (I hardly dare to use this word in the context of what those poor critters were fed) of the grub the rats were given, it should not come as a surprise that despite having smaller visceral fat pads, the rats from the experimental groups (X1, X2) were just as overweight (X1: 525.1 +/- 9.6g; X2: 540.4 +/- 9,9g) as their mates (HFD: 543.2 +/- 10.2) who were crammed with what I would like to call a "high-fat corn diet". Furthermore, there were no significant differences in the amount of energie the rats from the different groups consumed and the lean mass of the soleus muscle, the only muscle variable measure in the study, was almost identical. Against that background the improvements in glucose management (cf. figure 2), the scientists observed, could simply be related to the decreased carbohydrate intake. 

Figure 1: Serum markers of glucose and lipid metabolism in high-fat (HFD) and high-fat xylitol-substituted (X1, X2) fed rats after 8 weeks of treatment (data adapted from Ama. 2011)

So, if it were not for the statistically significant increases in adipose gene expression of PPAR-gamma (key regulator of adipocyte differentiation) and the insulin sensitizing hormone adiponectin, as well as the increased lipolytic enzyme-activity (hormone sensitive lipase, HSL; adipose triglyceride lipase, ATGL) within the adipose tissue of the xylitol fed animals, all of you, who have already gotten off the westernized fast-food diet, the scientists were emulating in this study, could easily discard their results as meaningless. Until now, however you will have to wait for future studies on the effects of xylitol on metabolic health and body composition in animals (or humans) who are not fed a diet the detrimental health effects of which cannot be fought off by any supplement or drug on the market. And remember: As always, the SuppVersity is where you will hear about those studies first ;-)

Stevia, the Anti-Diabetic Sweetener: Extract from the Leaves of Stevia rebaudiana Exhibit Anti-Diabetic Effects in Animal Model

Image 1: Stevia rebaudiana foliage
(photo by Ethel Aardvark)

The health-conscious consumer, you, as a SuppVersity reader, are, you will probably have heard of the natural sweetener stevia, which -despite its various advantages over its artificial counterparts- still has not made it to the mass market. While higher costs, certainly are the main culprit here, another factor could be the unfamiliar, for some commercially available products metallic taste. But hey, didn't people initially complain about the taste of aspartame and natrium-cyclamate, as well? And now, the very same people drink one bottle of diet coke after the other?

Well, if not being as toxic as it's artificial counter parts didn't convince people, yet, maybe the findings of a recent study from India will.

On a side note: don't you think it is kind of telling that studies on "alternative" treatments for diabetes never appear to come from the home countries and continents of Big Pharma?

Misra et al. (Misra. 2011) investigated the effect of two different dosages of a medium-polar (polarity determines solubility, with identical polarity of solvent = high solubility) leaf extract of S. rebaudiana at 200 and 400 mg/kg respectively on diabetic (alloxan induced) rats and found:

Medium-polar leaf extract of S. rebaudiana (200 and 400 mg/kg) produced a delayed but significant (P < 0.01) decrease in the blood glucose level, without producing condition of hypoglycemia after treatment, together with lesser loss in the body weight as compared with standard positive control drug glibenclamide.

Sweet and healthy, but not marketable? Well, the real problem is that the lack of financial interest the big beverage and food producers have to replace tried and proven artificial sweeteners, their customers got used (and sometimes addicted) to, with a sugar substitute, the taste of which could potentially harm their sales. Add to that the reluctance of the central organs of the European Union to finally approve "sweetleaves", as stevia is sometimes referred to, as well, for human consumption. Over here in Europe producers and vendors try to circumvent this problem by labeling their stevia products as "cosmetics" and selling them "solely for topical application". Coca Cola, on the other hand, would certainly have a hard time selling a new stevia-based Coca Cola Light as a cosmetic or heaven forbid bath water, which renders the development of a respective product simply unprofitable (let alone the possibility that costumers won't like its taste).

This being said, it is not even sure, whether the same product that would render your future "Stevi-Coke" (I should patent that name ;-) sweet and tasty will also induce the afore-mentioned revitalizing effects on your pancreatic beta-cells. In the end, consumer taste will probably require the extracts to be processed in order to get rid of any annoying flavors (and associated substances) and whether or not what "remains" will still be superior to sulfonylurea drugs such as glibenclamide in ameliorating hyperglycemia is certainly questionable.

Artificial Sweetened Foods Promote, Not Hinder Fat(!) Loss. 1.2kg Body Fat in 70 Days By Eating Artificially Sweetened Products. Lower Hunger, Higher Fat Oxidation vs. Sucrose

Artificial sweeteners - Could they really be less toxic and obesogenic than half of the blogosphere has it? The study at hand suggests so, but its significance is limited..

The recently posted SuppVersity Classic "Sweet, But Not Innocent!? The Fattening Effects of the Non - Nutritive Sweeteners Erythritol & Aspartame Are On Par With Equally Sweet Sugar Water" (read more) has gotten quite some attention on Facebook, against that background I suppose that today's SuppVersity article will, once more inflame passions. The use of artificial sweeteners as dieting aids is after all highly controversial within the health and fitness community.

If you've read my previous reviews of the corresponding papers, you will yet be aware that there is not a single human study to confirm that any of the "classic" artificial sweeteners (sucralose, aspartame & co) would have negative effects on the loss of body and fat mass during dietary restriction - an still you hear and read corresponding claims on almost every virtual corner of the blogosphere.

You can learn more about sweeteners at the SuppVersity

Unsatiating Truth About Sweeteners?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Sweeter Than Your Tongue Allows!

Stevia, Much More Than Sweet?

Sucralose Raises Cholesterol in Diabetics!?

In this respect, the latest paper by Lone B Sørensen, Tatjana H Vasilaras, Arne Astrup, and Anne Raben is no exception. What is extraordinary, though, is that it describes a relatively tightly controlled single-blind 10-week parallel design study that provides convincing evidence that the association between artificial sweetener consumption and obesity that has been observed in epidemiological studies would be a good example to explain the term "reverse causation" [fat people buy diet products vs. diet products make lean people fat].

In the said study, 24 healthy, overweight subjects had to consume a specific minimum amount of either sucrose-sweetened or artificially sweetened foods and drinks daily.

"The subjects were assigned to 3 different levels of supplements according to their initial body weight: level 1, 2, or 3 corresponding to 60–75, 75–90, and.90 kg, respectively. The minimum intake of the experimental diet was regulated by the sucrose intake and corresponded to a sucrose intake of 125 g/d (level 1), 150 g/d (level 2), and 175 g/d (level 3). This corresponded to a total EI from sucrose supplements of 2.74, 3.29, and 3.83 MJ/d, respectively."

The sweetener group received an equivalent amount (by weight) of foods and drinks, which resulted in an average EI of 694, 832, or 971 kJ/d at levels 1, 2, and 3, respectively. The artificial sweetener content of the intervention diet was 54% aspartame, 23% cyclamate, 22% acesulfame K, and 1% saccharin.

No low fat allowed: Some of the artificially sweetened products were low fat, so the subjects in the sweetener group were given additional butter or corn oil to keep the fat intake in the 2 intervention diets as similar as possible.

In the sucrose group, ~70% of the sucrose came from drinks (average: ~1.3 L/d), and ~30% came from solids foods. About 80% by weight of the supplements were beverages, and ~20% by weight were solid foods. The beverages consisted of several soft drinks and fruit juices, and the solid foods consisted of yogurt, marmalade, ice cream, and stewed fruit.

The products were handed to all participants at the University without informing them about the specific content of sucrose and artificial sweeteners in the supplemented products was unknown to the subjects - all thought, they were consuming products with artificial sweeteners. Otherwise, they were advised to to consume their habitual diet ad libitum. And guess what happened!?

Figure 1: Changes in body weight and fat mass (kg) and energy intake (in MJ) during breakfast, lunch and dinner measured on the one day all subjects had to spend in a metabolic ward (Sorensen.2014).

Yep, you already saw it, the sugar victims (sucrose sweetened products) got fat, while the subjects who had been supplied with artificially sweetened products saw small, bus significant improvements in their body composition without deliberately restricting their energy intake (Remember: all subjects thought that they were consuming zero calorie products).

The reason? Well, take a look at the left hand side of Figure 1. The subjects in the sucrose group did what some people claim would happen, if you consume artificially sweetened products: They ate more! Why? Well, because they were hungrier. Significantly hungrier; and that in spite of their 22% higher energy intake.

Figure 2: The satiety response at lunch was (non significantly) less sustained in the sucrose group (full circles) compared to the artificial sweetener group (open circles) during the subjects visit at the metabolic ward (Sorensen. 2014).

Especially after lunch, the satiety effects were significantly less sustained than in the artificial sweetener group (see Figure 2). What is interesting, though, is the fact that unlike its consequences and the perceived fullness and prospective food consumption (not shown in Figure 2), the satiety difference did not reach statistical significance.

Figure 3: 24h fatty acid oxidation after 10 weeks on diets with sucrose or artificially sweetened add-ons (Sorensen. 2014)

The data in Figure 1 did already tell you: The net effect of the satiety differences was a significantly higher energy intake (+22%) that was not fully compensated by the ca. 6% higher total 24h energy expenditure of the subjects in the sucrose group.

In concert with the reduced fatty acid oxidation rates (see Figure 3) the remaining energy surplus of approx. 1,000kcal (that's the mere mathematical difference of total 24h energy expenditure during the stay at the metabolic ward and the corresponding energy intake) was obviously more than enough to fatten the subjects up.

There is one impor- tant reason why I still recommend to be careful with any kind of sweetener (inclu- ding stevia) and that's the fact that they won't help people get rid of their extra-sweet tooth. A "tooth" which is in many cases the reason they ran into weight problems in the first place. And a tooth that is rather going to get more, not less sugar hungry if you are adding stevia, sucralose or aspartame to whatever foods you eat.

Putting the results into perspective: What this study does confirm is that artificially sweetened products can help average healthy non-dieting, non-overweight individuals lose weight. What it does not confirm is that artificially sweetened products will help obese people lose weight or ward off further weight gain in an ad libitum diet scenario such as the one at hand.

If we go one step further and extend our skepticism from a potential subject- to a potential duration-specific effect, we still don't know if the chronic consumption of artificially sweetened products wouldn't have negative effects on what some people call the "energy intake gauge". Or, put differently, whether the constant exposure to no-calorie foods with an extreme sweetness would not - in the long term - reduce the satiety the subjects in the artificial sweetener group obviously felt after consuming their diet products. If that was the case, the "energy deficit" would disappear and the short term benefits would eventually turn against you.

References: 

• Sørensen, Lone B., et al. "Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects." The American journal of clinical nutrition (2014): ajcn-081554.

Fructose Epimer D-Psicose Could Be First Sweetener to Actively Promote Weight Loss: Reduced Weight Gain and Direct Inhibitory Effect on Adipocyte Maturation in Rodent + Reduced Postprandial Glucose & Insulin in Human Trial

Image 1: No, just a few grams of d-psicose won't turn these into a "health food", but it could help ameliorate the "damage"

Good news for everyone with a sweet tooth! Right after stevia has finally made it to the European market, the next 1/2 natural sweetener is at the ready. It's called d-psicose and it is a cousin of fructose that is yet only 70% as sweet as sucrose (fructose is +20% sweeter than sugar) but has only 0.3% of its energy content. In other words on a per calorie base it is 233x sweeter than sugar. That alone would however hardly justify an individual blogpost. What is yet exciting about this molecule is that a recently published rodent study does suggest that it can inhibit adipocyte maturation and thusly exerts direct anti-obesity effects.

The first sweetener that will actively help in weight loss?

In the course of a 12-week trial, a group of Sprague-dawley rats was initially fed up with the standard laboratory "high fat diet" that is essentially an identical twin of the standard American diet with 15.1% of the energy from protein, 38.8% from fats and 47.1% from carbohydrates. After four weeks the rodents were assigned to different groups, which were either switched over to a standard diet (14.7% protein, 9.4% fat, 76.9% carbohydrates) or were maintained on the energy-dense high fat diet. Each of the study arms had another 5 sub-groups the animals in which received, either

• normal (ND) or high fat (HF) diet without supplement (control),
• ND or HF + 5% sucrose (SU-5),
• ND or HF + 5% erythritol (ES-5),
• ND or HF + 2.5% d-psicose (DP-2.5), or
• ND or HF + 5% d-psicose (DP-5)

for another 52 days. The food intake and body weight of the animals was measured three times a week. At the end of the study, serum levels of total cholesterol (TC), triglycerides (TG), LDL-C and HDL-C were measured and biopsies were conducted to evaluate adipose tissue and liver weight.

Figure 1: Change in body weight, total food intake and feed efficiency (right axis) in the 2nd half of the study (data adapted from Chung. 2012)

As you can see in figure 1 there was a dose-dependent decrease in body weight gain, which left the rats in the HFD - ND-DP5 group, i.e. those animals who had been fattened up for 4 weeks and were then switched to a "normal" diet supplemented with 5% of d-psicose (with a food intake of ~20g per day, whit would be 1g per day, or in human terms ~ 0.3g/kg) at a final body weight level that was identical to the animals who had never been fat in the first place - and that despite a slightly higher food intake.

Could d-psicose be an ideal adjunct to your weight loss regimen?

In this context, it is important to note that the previously fattened rodents were already 23% "overweight". In other words, while the rodents on the normal diet kept gaining weight at a rate of 2.4-2.7g per day, the weight gain of the "fat" rodents in the ND-DP5 group was so profoundly ameliorated that they ended up at the same "normal" weight at the end of the study as the intially non-obese rodents on the standard diet. And even without the dietary switch, the addition of 5% d-psicose led to a profound (-50%) reduction in diet induced weight gain in the high fat group.

Figure 2: Total white adipose tissue (right axis, in g), epididymal, perirenal and retroperitoneal visceral fat (in g) in the different groups at the end of the post-fattening 52-day feeding period (data adapted from Chung. 2012)

And while the addition of the C-3 fructose epimer lead to a reduction in body fat in all animals, only the animals who had been switched to the high carb (=normal) diet, achieved body fat levels identical (2.5% d-psicose) and even below (5% d-psicose) those of the rats in the control group (cf. figure 2).

Lose weight, lose fat, but what about your liver?

Yet despite the fact the combined "weight loss effect" of the "normal" (=low fat) diet with supplemental d-psicose is thusly fundamentally different and unquestionably way more desirable than the "Half as Heavy, Twice as Fat" effect of the Atkins diet (cf. news from last Friday), the structural kinship of d-psicose and fructose raises the question if the former did induce similarly detrimental health effect on the liver as its notoriously sweet cousin.

Figure 3: Light image of liver tissue sections from ND, ND-SUS and ND-DP-5 groups (adapted from Chung. 2012)

The light image of liver tissue sections from the ND, the ND-SUS and the ND-DP-5 group does yet show that the dreaded NAFLD fatty deposition did not occur in the DP-5 group. The statistically significant increase in liver weight, on the other hand, is something the researchers attribute to increases in hepatic glycogen stores:

Our results [...] showed that ND-DP group tended to induce liver enlargement suggesting increased glycogen deposition in liver as extra-energy storage of d-psicose. However, HF-DP group did not show any difference compared to HF group. It is possible that HF diets containing relatively low carbohydrates [...] induced lower liver glycogen level masking the effects of d-psicose.

Moreover, previous long-term studies (12-18 months) by Yagi & Matsuo did not reveal any adverse side-effects in relation to the d-psicose induced increase in liver weight (Yagi. 2009).

Figure 4: Lipid profiles (triglycerides, LDL-C and HDL-C) at the end of the study period (data adapted from Chung. 2012)

The totally normal lipid profile (cf. figure 3), with lower triglyceride and cholesterol levels than the control group and identical total cholesterol to HDL-C (control: 1.73; DP5: 1.89) and LDL-C to HDL-C (control: 0.39; DP5: 0.39) ratios also supports the notion that, despite its "frutosian heritage", d-psicose is not promoter of diabesity and metabolic disease.

Bottom line: Promising, but more than one human study would be nice

Image 2: Sponge cakes made without addition, with fructose or with d-psicose (img courtesy of the Kagawa Industry Support Foundation)

If we add to that the results of a previous human trial, in which d-psicose administration reduced the postprandial glucose and insulin response following the ingestion of 75g of maltodextrin with 5g of d-psicose (Lida. 2008), and take into consideration that the incubation of pro-adipocytes with d-psicose led to a dose-dependent inhibition of adipocyte differentiation in the study at hand, the fructose epimer d-piscose could in fact turn out to be way more than just another artificial sweetener. And as you can see in image 2, the first practical applications, or should I say highly marketable "nutritional idiocies" are already on their way: Yummy sponge cakes ;-)

Diet Coke & Liver Damage? Long Term Very High Dose Aspartame Consumption Impairs Antioxidant Defense of Rat Livers.

The ever-growing group of health conscious costumers is rightly very skeptical of artificial sweeteners in general and Aspartame in particular. A recent study (Abhilash. 2011) done by scientists from the Mahatma Gandhi University in Kottayam, Kerala, India, seems to rectify this attitude.

The scientists fed rats drinking water that contained either no, i.e. 0mg, 500mg or 1.000mg aspartame per kg body weight day for a period of 160days. The rats from the 1.000mg/kg group showed...

[...] a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ- glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000mg/kg.b.wt).

The presence of "leukocyte infiltration in aspartame-treated rats (1000mg/kg.b.wt)" further underlines that high dose aspartame consumption over a period of 160 days induced "hepatocellular injury and alterations in liver antioxidant status" by increasing the detoxification burden on the liver to supra-physiological levels.

Yet, what does that mean for the average consumer? Let us put the figures into perspective: 1 liter of diet coke contains about 390mg of aspartame. The rats in the high dose aspartame group in the study (which is the only one where anti-oxidant status fell enough to induce histological side effects) received 1.000mg/kg of aspartame per day. In human equivalent dosages (HED), this is 162mg/kg, which would be 11.35g of aspartame or 29 l diet coke for a 70kg adult. Not that I want to trivialize the possible liver toxicity due to aspartame consumption, but let's be honest: you would probably long have died from hyperhydration before you would notice any of the toxic effects induced by the consumption of an artificial sweetener, which - far from being healthy - is yet not as toxic as some health-fetishists would have it.

In spite of the fact that a diet coke here and there won't kill you, you should still ask yourselves, whether or not you really need this "spawn" of a society where we want all the convenience and (unnaturally sweet) taste of unhealthy foods without the negative consequences for our health? I mean, you obviously chose the "diet" version because you want to avoid sugar; but do you still want the sweet taste, which (at least for some artificial sweeteners, eg. Nakagawa. 2009) has been shown to increase insulin secretion even in the absence of direct beta cell stimulation!? If you are willing to accept this compromise and do not care about the other chemicals your average can of diet coke "nourishes" you with, fine! But do not tell me later on, I had told you that diet coke was good for you ;-)

Stevia Increases Satellite Cell Recruitment and Ameliorates Insulin Resistance by Reducing NF-KappaB Mediated Inflammatory Response to Muscle Damage & High Fat Diet

Image 1: If you take a look at the number of studies on production and processing techniques related to stevia and stevia products, it becomes evident that the production of the traditional South American "sweet leaf" has already been seized by the usual subjects from the "food industry"

"Rats would buy Stevia rebaudiana!" I don't know about you, but personally, I would not advertise my product with this slogan, but if I did, I would at least have valid scientific data to support this claim... well, sort of, because I am not 100% sure where or even that rats even buy any sweeteners. Be that as it may, although Sclafani et al. were able to show that the preference their lab animals showed for stevia over saccharine was related to the activation of the sweet taste receptors (Sclafani. 2010), you could also make a point that the rodents might have "tasted" that there is more to Stevia rebaudiana than its insanely sweet taste (personally, I have been using stevia for ~6months, now, and had to get used to the taste initially), if you take a closer look at some of the more recent data on the potential health benefits of (allegedly large amounts of) steviosids, the major steviol glycosides from the leaves of the stevia plant.

Steviosids work via NF-kappaB by reducing inflammation

Assuming that you have followed the Intermittent Thoughts on Building Muscle series, you will be familiar with the notion that the recruitment of so-called satellite-cells, i.e. muscle-specific stem-cells, is an essential part of the repair process after exercise (or otherwise) induced muscle damage. You will also be aware that inflammation plays an important, albeit hitherto not fully elucidated role in this process and that it is after the initial inflammation is abating, when the macrophages start the actual (re-)construction process (cf. "Inflammation & Hypertrophy"). You will thusly maybe even less surprised than a group of Malayan scientists from the Mahidol University in Bangkok (Bunprajun. 2012), when they found that 10mg/kg of pure steviosids, of which previous studies had already shown that they are able to ameliorate stress-induced NF-kappaB (which is believed to be one of the master regulators of inflammatory responses) expression, did not only lead to the expected amelioration in NF-kappaB expression in cardiotoxin injected tibialis muscles of male rodents, but also increased the post-recovery increase in myo-D positive, i.e. newly recruited satellite cells.

Figure 1: Inflammatory response (left) and satellite cell recruitment (right) after cardiotoxin injection in tibialis muscle in rodents after pre treatment (7 days) and concomitant (7 days after the injury) treatment with vehicle (control) or 10mg/kg steviosids (data adapted from Bunprajun. 2012)

The initial NF-kappaB response, three days after the injection of a cardiotoxin into the tibialis muscles of the rodents was identical (cf. figure 1). After seven days, however, the NF-kappaB levels in the steviosid group, who received their daily dose of stevia 7 days before and in the 7 days after the injury, are significantly lower than in their vehicle (control) treated peers and correspond well with the profoundly increased number of myoD positive (fresh) nuclei in the stained tissue samples of the treatment group.

The same effects on NF-kappaB also help ameliorate diet-induced insulin resistance

With the increased recruitment of satellite cells being only part of a very complex repair process, and given the fact that the scientists did not find any significant difference in tibialis anterior mass, myofibrillar protein content, the number of central located nuclei, it is actually not surprising that the contractile function of the injured legs was still identical 7 days after this profound injury. For an athlete or any active individual this would probably mean a few weeks away from the gym, the court, the green, or the stadium and this in turn could precipitate weight gain, which brings up another nice "side effect" of the NF-kappaB suppressing effects of high dose stevia supplementation that has been recently established by Wang et al. (Wang. 2012).

Figure 2: Body weight gain, fasting blood glucose and insulin levels and glucose infusion response in rats after 4 months on regular or high fat diet (49%fat / 36%carbs / 15% protein) with or without 2x10mg/kg steviosids per day (data calculated  based on Wang. 2012)

As the data in figure 2 goes to show, the oral administration of stevisoids as 2x10mg/kg was able to ameliorate the negative effects 4 months of "high fat" feeding (49% fat / 36% carbs / 15% protein) exerted on body weight and glucose metabolism of previously healthy rats. With a +36% increase in serum insulin and a -19% reduced glucose infusion response (GIR) the rats in the HFD+stevia group were yet still significantly more insulin resistant than their peers on the regular diet - and the results also show that an increase in insulin sensitivity does not translate into a decrease in weight gain. As we are going to see in the course of the current Intermittent Thoughts series on insulin sensitivity, "ideally" the exact opposite should be the case.

Pounding stevia to stay healthy and gain muscle? Probably not the best good idea.

If we get back to my introductory remarks and the not really advertisable slogan "rats would buy stevia rebaudiana", the question that has to be answered now is: Would you buy stevia? I already told you that I do, but certainly not because of the aforementioned effects. I guess, I would probably die from over-sweetening (if there was such a thing), if I took the corresponding one to two "servings" of 1.6mg/kg (human equivalent of 10mg/kg for a rat) of pure steviosids on a daily basis... but all jokes aside, if you are looking for a healthy sweetener, there probably is no better option than stevia.

If you want to ward off insulin resistance, on the other hand, a "clean" diet with a reasonable amounts of carbs (unless you are diabetic ~100g, which as Beth /thx/ rightly pointed out would be way less than 30% of your total energy intake, is something everyone should be able to handle - and what's more, can help you perform better, keep energy levels and metabolism up and contrary to the contemporary anti-carb paradigm, eventually improve weight- and fat-loss), fats and protein in it should be your main concern. This is particularly important, because a combination of the latter with a reasonable workout routine, sufficient time to recover and a decent amount of quality sleep, will also make the use of stevia as a means to increase muscle repair obsolete,... at least as long as you are not attacked by mad Malayan scientist with a syringes full of myotoxins ;-)

Xylitol, A Sweetener W/ Carb Blocker Effect - Up to 33% Reduced Glucose Uptake from Meals, Increased Muscular Glucose Uptake, Improved Glycemia & Pancreatic Health

Who would have thought that something that's good for your teeth could be be good for your pancreas, as well?

In a recent study scientists from the University of KwaZulu-Natal in South Africa investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucos absorption using in vitro, ex vivo and in vivo experimental models.

Xylitol is a 5 carbon sugar alcohol with lower glycemic index (13 vs 65) and calorific value (2.4 vs 4.0 kcal/g) compared to sucrose. A number of previous studies reported that xylitol has many other potential beneficial effects such as control and prevention of obesity, diabetes and related metabolic disorders (Amo. 2011).

You can learn more about sweeteners at the SuppVersity

Unsatiating Truth About Artif. Sweeteners?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Sweeter Than Your Tongue Allows!

Stevia, the Healthy Sweetener?

Sweeteners In- crease Sweet- ness Threshold

In a more recent study, Islam et al. (2011) were able to show that 3 weeks supplementation of 10% dietary xylitol significantly decreased non-fasting blood glucose (NFBG) and serum fructosamine levels, increased serum insulin levels, and improved glucose tolerance ability compared to 10% sucrose in non-diabetic rats.

Figure 1: The significant improvement in glucose clearance (left) and non-fasting blood glucose (right) observed in previous rodent studies (Islam. 2011) raised the question: Is this all a mere results of a reduced GI?

Quite an intriguing result that cannot be explained solely by the reduced glycemic index - specifically in view of the fact that it was repeated in a type II diabetic rats, where it dose-dependently improved the pancreatic island cell morphology, as well (Rahman. 2014). Moreover, ...

[i]n some previous studies, it has been reported that xylitol consumption significantly reduced food intake in normal humans and diabetic rats. Slower gastric emptying and more accelerated intestinal transit were observed in normal human subjected when xylitol was supplied as single oral dose (30 g in 200 ml water) compared to the similar dose of glucose" (Chukwuma. 2015).

Based on these observations, Chukwuma & Islam conclude that xylitol might reduce NFBG levels not only by reducing food intake but also by slowing gastric emptying and accelerating nutrient transit time both in normal and diabetic conditions. Furthermore, the researcher argue that the insulinotropic effect of xylitol in diabetic condition may improve circulating glucose uptake, especially in muscle and fat cells to ameliorate hyperglycemia in diabetics.

What do previous human studies say? You already know that the rodent data is very promising, but what do the human studies say? Well, there only few - here's what we know: (1) As sweetener in a chewing gum xylitol effectively reduces caries in high risk populations (Campus. 2013); (2) xylitol acts as a GLP-1 (learn more) promoter and may thus have beneficial long-term effects on appetite control and glucose management in humans (Vanis. 2011); (3) xylitol increase satiety and acutely reduce the food intake on subsequent meals by up to 25% (Shafer. 1987; King. 2005); and xylitol  has beneficial effects on growth hormone, despite the fact that the serum glucose levels in the corresponding study were not lower than in the glucose control (Spitz. 1970). Overall, the research on the metabolic (long-term) effects is yet scarce - probably also due to the effect that the increased transit times tend to give people the runs so that long-term studies can be a pain in the ass (all puns intended) for every study participant and supplement junkie.

From the above-mentioned studies, however, it is not clear whether xylitol has any additional effects on the absorption of glucose from the different segments of the intestinal tract and on the muscle glucose uptake at the post absorption period. Accordingly the potential effects on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake were the main interests of the study at hand.

Figure 2: Xylitol acts as a "carb blocker" and inhibits the uptake of glucose in the ileum (left) while simultanously increasing the glucose uptake into the muscle (Chukwuma. 2015).

In a combination of in vivo and in-vitro studies, the researchers were eventually able to show that an increase of xylitol concentration in the gut inhibited the 'carbohydrate breakdown enzyme' alpha amylase (IC50 = 1364.04 mM) and alpha glucosidase (IC50 = 1127.52 mM) by up to 85% and 95% at high dosages in vitro. This explains the reduced glucose uptake in the in vivo study (see Figure 2), but it does not necessarily explain the increased muscular glucose uptake, which did not even depend on the presence of insulin (the human data reviewed in the blue box suggests that this may be related to an increase in GLP-1).

The latter effect came as a surprise, because it was not triggered by an increase in insulin production and occurred in the presence of a decreased gastric emptying and increased intestinal digesta transit rate, both in normal and diabetic rats compared to their respective controls.

We do already know that xylitol, just like many other sweeteners, will affect the composition of your gut microbes. We do not know, though that this is going to have ill health effects.

Bottom line: Overall, the data from the study at hand provide intriguing novel insights into the proven anti-diabetic effects of xylitol. Most importantly, it's the first study to confirm that xylitol effectively reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes and increasing the muscle glucose uptake in normal and type 2 diabetic rats.

Based on previous human studies, it is not unlikely that the very same effects occur in humans - including the slow down of gastric emptying and fastening intestinal transit, which would be associated with increased satiety and a decreased energy absorption efficacy | Comment on Facebook!

References:

• Amo, Kikuko, et al. "Effects of xylitol on metabolic parameters and visceral fat accumulation." Journal of clinical biochemistry and nutrition 49.1 (2011): 1.
• Campus, Guglielmo, et al. "Six months of high-dose xylitol in high-risk caries subjects—a 2-year randomised, clinical trial." Clinical oral investigations 17.3 (2013): 785-791.
• Chukwuma, Chika I., and Md S. Islam. "Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: A multi-mode study." Food & Function (2015).
• Islam, Md Shahidul. "Effects of xylitol as a sugar substitute on diabetes-related parameters in nondiabetic rats." Journal of medicinal food 14.5 (2011): 505-511.
• King, Neil A., et al. "Evaluation of the independent and combined effects of xylitol and polydextrose consumed as a snack on hunger and energy intake over 10 d." British journal of nutrition 93.06 (2005): 911-915.
• Rahman, Md, and Md Islam. "Xylitol Improves Pancreatic Islets Morphology to Ameliorate Type 2 Diabetes in Rats: A Dose Response Study." Journal of food science 79.7 (2014): H1436-H1442.
• Spitz, I. M., et al. "The response of growth hormone to xylitol administration in man." The American journal of the medical sciences 260.4 (1970): 224-229.
• Vanis, Lora, et al. "Comparative effects of glucose and xylose on blood pressure, gastric emptying and incretin hormones in healthy older subjects." British Journal of Nutrition 105.11 (2011): 1644-1651.