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| I just hope that today's SuppVersity article is not going to cause scenes like this, because when it all said and done it may be less likely, but not impossible that it is (for whatever vexed reason) still aspartame that caused the negative effects observed in the study at hand. |
It is one of the recurring motifs here at the
SuppVersisty and at the same time one of the most popular issues of dispute in the health and fitness community:
The Obesogenic Effects of Artificial Sweeteners. Or, in plain English, the question
"Can I use Sucralose, Aspartame and Acesulfam-K without taking the risk of getting fatter - not leaner, as I actually intended?" For all three of the explicitly mentioned agents human studies clearly suggest that the answer is "Yes, you can!" And I will now dare saying that the of the most recent study from the
Oita University in Japan are
not going to change that - as long as you use them
instead of carbs in your diet the said
zero-calorie sweetener are going to help not block weight loss.
So why did the mice in the Mitsutomi study get obese then?By anticipating the most important conclusion, I have made things easy for us, after all the only questions we still have to answer are:
- Why did the mice in the Mitsutomi study get obese?
- Is it possible that this is an erythritol-specific effect?
It would appear as it it could not be all too difficult to answer the first question. It was after all part of the research interests of the Japanese scientists, so that you would expect it to be answered in the discussion of their result. Well, let's see then, ...
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| Exactly what the energy drinks promise, the sugar water got the rats "on sucrose" going: They were >40% more active than their peers - without caffeine as you may notice (Mitsotomi. 2013) |
"Compared with sucrose supplementation, NNS supplementation decreased the serum glucose level. Interestingly, compared with the control treatment, NNS supplementation increased the serum insulin level in mice with DIO. In addition, NNS administration influenced glucose tolerance compared to controls.
These observations suggest that NNS supplementation induced insulin resistance by increase of tissue triglyceride, although some NNSs are used to control hyperglycemia.
NNS supplementation increased the WAT leptin level in DIO mice in the present study.
It is possible that the high leptin level was related to body adiposity. Indeed, NNS administration increased the weight of epididymal fat. Thus, it is possible that the high leptin level was related to the influence on body adiposity." (Mitsotomi. 2013)
No, I don't see an explanation, rather a concise summary of the results, that tells us that the addition of plain sugar (33%) to the drinking water did - as the scientists already expected - lead to a decrease in food intake and an increase in obesity and its nasty unhealthy side effects.
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| Figure 1: Differences in food intake & body composition of mice with 33% sucrose and 4% erythritol + aspartame in the drinking water (left) expressed relative to control w/ plain water, histology of lover (top) and white adipose tissue (WAT, bottom) of mice with regular (control) and sucrose respectively NNS drinking water (Mitsotomi. 2013) |
Much to their own surprise, Mitsotomi et al. did also observe that the group that received the "non-nutritive sweeteners" as a 4% solution (99% of which were erythritol and 1% was aspartame) in their drinking water got exactly as fat (see
Figure 1), had a slightly less pronounced increase in adipocyte size, and experienced a similar fatty acid deposition in the liver (NAFLD). And as if that had not been bad enough, there were also pathological changes in the "fat burning brown adipose tissue" (BAT) of the rodents in the NNS group - a physiological deterioration, Mitsotomi et al. observed exclusively in the erythritol + aspartame goup.
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| Figure 2: Leptin resistance (in WAT) and the major downregulation in UCP-1 (in BAT; both left) are candidates of which the researchers believe that they were responsible for the visible defect (right) in the BAT architecture (Mitsotomi. 2013) |
Let's be honest, if you take another look at the BAT histology in
Figure 2 (right) even you as a non-expert will see that there is a major difference between the meshed BAT in the rodents on the control diet and the messy BAT of the NNS group, compared to which the brown fat cells of the sugar guzzlers still look
very healthy.
Remember: All this mess happened in the absence of an increase in calorie intake Just to make this clear: This is not the first study to show that artificial sweeteners can have obesogenic effects in rodent models. In contrast to Naismith et al. (1995) and Blundell & Hill (1986) who observed a "pradoxical effects" of artificial sweeteners on the appetite of their lab rodents, the rats in the study at hand did
not overeat, though! They also moved about as much as their peers in the control group and still got fat and sick.
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| Want to change your "Fat-o-type"? Work out! | read more |
In other words, the weight gain the Japanese researchers recorded was neither a result of a mismatch between energy intake and expenditure nor the consequence of a promotional effect of artificial sweeteners on the "sweet tooth" of the rodents. Rather than that it was either brought about or accompanied and promoted by the impairment of the thermogenic capacity of the brown adipose tissue, of which you can argue, based on histologies in
Figure 2 that the brown adipose tissue of the furry "subjects" of this study was not just functionally, but also structurally compromised by the ingestion of the non-nutritive sweeteners.
The defective brown adipose tissue (BAT) and the correspondingly reduced UCP 1 expression (UCP increases mitochondrial uncoupling in BAT and burns off energy to increase the body temperature), led to a significant reduction in oxygen consumption. With the latter being a direct marker of fatty acid oxidation the it is difficult to say which came first, the defect in BAT or the onset of obesity. What we can say for sure, though, is that the defective BAT had its share in the rapid weight gain and the corresponding metabolic deterioration.
This could be an erythritol specific effect Despite the fact that Mitsotomi et al. did not address the potential influence the type of artificial sweetener they used, it is not unlikely that the use of erythritol, of which I have seen dozens of toxicity studies, but no long(er) term feeding studies in a potentially obesogenic diet scenario, could explain the unexpected study outcome. So: "Is this an erythritol specific effect?"
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| An advantage of erythritol is that it has almost the same sweetness profile as sugar (sucrose), but is 30-40% less sweet (de Cock. 2012) |
Without further studies, it is obviously not possible to answer this question, it does however not appear to be unlikely that it were the 99% of erythritol in the commercial erythritol + aspartam mixture the researchers used in their study that's to blame for the obesogenic effects. If this was a general NNS effect, a similar impairment of the brown adipose tissue and corresponding increases in body, muscle and liver fat should after all have been observed in previous studies, already. To my knowledge these studies do not exist - specifically not for aspartame. Without speculating about unpredictable interactions within the two we are thus left with erythritol as out only culprit.
While erythritol has only 60% to 70% of the sweetness of sucrose (comparing 10% solutions in water; this means you need much more of it to achieve a similar sweetness) it has an almost identical sweetness profile (no "off" tastes; cf. de Cock. 2012). This is not the only reason both scientists and the food industry are fond of the low-calorie sweetener. It's rather the combination of its gut- and tooth-friendliness that makes it such a valuable addition to everything sweet. So, despite the fact that it does share the the anti-caries effects with sugar alcohols like xylitol, it is so easy on the gut that its use is not restricted to chewing gums and other "food" items that need only marginal amounts of sweeteners to achieve the desired degree of sweetness. If you want to sweeten larger amounts of foods / beverages, erythritol is thus the sugar alcohol of choice
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| There is evidence that suggests aspartame reduces insulin - at least during workouts | learn more |
Why don't you suspect aspartame? The reason that I am scrutinizing erythritol and not aspartame is simple. Despite or rather because of all the hoopla around potential toxic effects of aspartame it is one of the best researched artificial sweeteners and evidence for obesogenic effects in the absence of increases in food intake are simply non-existent. It may thus make this article more popular among the high number of aspartame haters out there, but it would not help us understand the experimental results,if I started lamenting about how Coke and Pepsi are trying to kill us.
If you take a peak at the Wikipedia article and many scientific papers, you will learn that erythritol has been shown to be
mostly (90%) absorbed before the chyme enters the colon (Bernt. 1996). The non-negligible rest of the erythritol (10%), on the other hand, is said to pass through the short and long intestine, where it is generally believed not to fermented by the gut bacteria (Arrigoni. 2005).
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| The cholesterol increase scientists observed in response to a high sucralose diet is another of the many yet not fully understood side effects of artifical sweeteners | learn more |
In view of a more recent study by Beards et al. (2010) it is however more than questionable that this assumption for which researchers usually cite the in vitro results Arrigoni et al. presented in a 2005 paper is accurate.
Beards and her colleagues from the
University of Reading in the UK were after all able to show that erythritol is
not simply excreted undigested. Rather than that it
is fermented and leads to changes in the bacterial composition and a 6.25x increase in acetate production.
In view of the beneficial effects of SFCA (acetate, propionate and butyrate) on the production of satiety hormones this certainly appears to be a good thing. From studies by Patil et al. we do however know that chronically high SCFA levels and decreased relative bacteroides levels are characteristic of features of human obesity (Patil. 2012; see Angelakis
. 2012, as well).
If we include the comparatively short timespan (24h) in the course of which the said changes in the bacterial composition and acetate production in the Beards study occured and assume that this may, after days of constant erythritol exposure have destabilized the previous "ecosystem" in the gut, it does not appear too far fetched to assume that the rodents may have suffered from weight gain and all sorts of metabolic deterioration as a consequence of the potential lactobacilli + Atopobium overgrowth in response to the erythritol in their drinking water.
By now it should no longer appear totally odd to assume that neither artificial sweeteners per se, nor the "bad bad" aspartame are to blame for the "fat effects" the researchers observed in the study at hand, right? I mean, of all the three short chain fatty acids, butyrate, acetate and propionate, acetate is the one with the weakest antiobesogenic effects (Lin. 2012) and in view of the fact that it is preferentially used as a substrate for de novo lipogenesis (=deposition of fat) in colonocytes, hepatocytes and adipocytes (Samuel. 2008), both the fatty liver and the 172% increase in body fat
could be explained by the constant influx of acetate from a dysbiotic gut - right?
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| Suggested Read + Podcast: "he Pro-Insulinogenic Effect of Artificial Sweeteners + Mechanisms & Consequences" | read more |
Reason to be afraid - yes or no?"It could be possible...", these are the four little words that would have to go before each and every of the sentences in this conclusion. It could be possible that the interaction of erythritol with the gut microbiome of the rodents drove the accumulation of lipids in the liver, which would in turn have lead to the development of insulin and leptin resistance and could have compromised the function of the "fat burning brown adipose tissue" of our furry friends. The latter could have sped up the weight gain and may eventually explain why the mice in the "non-nutritive sweetener" group were by no means better off than their similarly obese peers in the sucrose group.
Despite the fact that it
could also be possible that similar negative effects on the accumulation of liver and whole body fat would be observed in humans, the failure of the brown adipose tissue wouldn't be much of a problem for us, a species that has long lost most of its brown fat stores (
learn more). Against that background and in view of the fact that I'd hope that no one of you follows a 60% fat, 20% carbohydrate diet and tries to sooth his / her sweet tooth with 2-3l of erythritol + aspartame sweetened water per day, I'd suggest you refrain from freaking out until we do have more compelling evidence that the stress hormones you will be producing are not more harmful than the few mg of sugar alcohols in your protein bars.
- Angelakis E, Armougom F, Million M, Raoult D. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012 Jan;7(1):91-109.
- Arrigoni E, Brouns F, Amadò R. Human gut microbiota does not ferment erythritol. Br J Nutr. 2005 Nov;94(5):643-6.
- Beards E, Tuohy K, Gibson G. Bacterial, SCFA and gas profiles of a range of food ingredients following in vitro fermentation by human colonic microbiota. Anaerobe. 2010 Aug;16(4):420-5.
- Bernt WO, Borzelleca JF, Flamm G, Munro IC. Erythritol: a review of biological and toxicological studies. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S191-7. Review.
- Blundell JE, Hill AJ. Paradoxical effects of an intense sweetener (aspartame) on appetite. Lancet 1986;1(8489):1092–3.
- de Cock P. Erythritol. In "Sweeteners and Sugar Alternatives in Food Technology". 2nd edition. Ed. O'Donnell & Kearsley. Wiley. 2012.
- Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240.
- Mitsutomi K et al. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism. Oct. 2013 [ahead of print]
- Naismith DJ, Rhodes C. Adjustment in energy intake following the covert removal of sugar from the diet. J Hum Nutr Diet 1995;8:167–75.
- Patil DP, Dhotre DP, Chavan SG, Sultan A, Jain DS, Lanjekar VB, Gangawani J, Shah PS, Todkar JS, Shah S, Ranade DR, Patole MS, Shouche YS. Molecular analysis of gut microbiota in obesity among Indian individuals. J Biosci. 2012 Sep;37(4):647-57.
- Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16767-72.
- Sell H, Deshaies Y, Richard D. The brown adipocyte: update on its metabolic role. Int J Biochem Cell Biol 2004;36: 2098–104.
Adding Fats to Carbs Does not Reduce Insulin
