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 ;-)

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).

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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.