Tuesday, May 1, 2012

Sweeter Than Your Tongue Allows: No-Calorie Sweeteners Disrupt Early Response to Glucose Ingestion, Reduce GLP-1 Expression and Could Thus Promote Overeating

Image 1: Do you remember your first "splendid" experience with saccharine? Disgustingly sweet, right? If that changed over time, this study is for you!
It is one of those never-ending debates: Do artificial sweeteners raise insulin? If you are a regular, here at the SuppVersity you will be aware that none of them exhibits significant satiety effects (cf. "The Unsatieting Truth about Artificial Sweeteners"); still, insulinogenic as some people still believe, they were, is yet none of them. A soon to be published paper by scientists from the Purdue University does yet suggest that saccharine formerly one of the commonest artificial sweeteners (thx. Evelyn for the heads-up, see Evelyn's comment), now most widely used as a preservative adjunct in sweetener blends, which are found, for example in diet soda & co, does still lead to increased weight gain in male Sprague dawley rats that were fed either artificially (0.3% saccharine) or glucose (20%) sweetened yogurt  (Swithers. 2012).

Too sweet to be true... but your tongue doesn't care!

In previous studies, Susan E. Swithers and her colleagues had observed that rodents that were kept on diets with a high artificial sweetener content lost their ability to appropriately control their energy intake - specifically, when subsequent feedings contained caloric sweeteners. As a result of the constant exposure to extreme sweet foods and the subsequent absence of readily available energy the animals had unlearned to appropriately predict the caloric value of their food - something that would not pose a real problem to all the calorie-counters out there who do not eat anything without previously checking its calorie, let alone carbohydrate content on nutritiondata.com, if ... yeah, if this was a mere psychological conditioning process. The results of this follow-up study did yet reveal that
  • preconditioning with saccharine sweetened yoghurt lead to hyperglycemic episodes after the consumption of a glucose sweetened meal
  • the hyperglycemic episodes occur in response to complex test meals and simple glucose solutions and they occur immediately after the ingestion of the test meal / glucose solution
  • the insulin response in preconditioned vs. normal rodents was not different and does thus not provide an adequate explanation of the saccharine induced "glucose intolerance"
Now, if it was not the insulin response, what could possibly explain the inability to cope with the sudden influx of sugar into the blood stream upon pre-exposure to saccharine sweetened yogurt (30g/day on 6 days of the week) for 4 weeks?

It's not just in your brain, neither only in your pancreas... it's in your mouth!

Another series of experiments yielded the answer to this question. Contrary to the oral glucose tolerance test and the consumption of glucose containing complex foods, the same glucose solution, when delivered by gavage, did not elicit differential blood glucose responses in saccharine-naive and saccharine preconditioned animals. Or, as Swithers et al. put it, these...
[...] results indicated that differences in glucose tolerance following exposure to saccharin-sweetened yogurt compared to glucose-sweetened yogurt do not occur when glucose is delivered directly into the stomach, bypassing the oral cavity. This finding is consistent with the idea that saccharin consumption weakens the ability of a sweet taste in the mouth to evoke cephalic phase responses involved with controlling blood glucose levels.
Or put more simply, the constant overstimulation of the sweet taste receptors in the oral cavity "burns them out", or if you like that better, the receptors "lose their credibility".
Note: In a separate experiment in the cause of which the glucose solution was delivered to saccharine-naive animals by gavage either with or without glucose rinsing of the tongue the scientists confirmed their hypothesis that - assuming that the glucose sensing apparatus in the oral cavity is still intact and "credible" - the glucose response, actually starts when the first glucose molecules hit the receptors of your tongue. A study, I had "on short notice" on the SuppVersity Facebook Page, a few days ago, does by the way suggest that the latter is not different in humans. Otherwise you could hardly explain that the associations of increased amylase activity in the oral cavity and better glucose tolerance, Mandel and Breslin observed in group of healthy individuals upon starch exposure (the more amylase the subjects have in their mouths, the more of the starch will be broken down in the mouth already; in other words: more amylase => more glucose => more sweet taste receptor activation upon starch ingestion; cf. Mandel. 2012)
That all this can have detrimental consequences, even if you did "count your calories" (I guess, I don't have to remind you of the fallacy of this undertaking, do I?), was confirmed by the sixth and final experiment in this study.
Figure 1: Weight gain and energy intake of rats maintained on a high-fat, sweetened diet with or without artificial sweetener (left) and glucose, GLP-1 and insulin response over the first 16 min following consumption of 5 ml of a 20% glucose (right); all data expressed relative to saccharine-naive animals (data calculated base on Swithers. 2012).
Although pre-exposure to artificially sweetened yogurt did not influence the insulin response, it did reduce the release of glucagon-like-peptide 1 (GLP1). In view of the far-reaching metabolic effects of the purported "satiety hormone" which reach way beyond the control of energy intake and into the realm of energy expenditure, fatty acid oxidation and glucose homeostasis, as well (cf. "Eat more, burn more and lose fat like on crack with GLP-1"), this effect will have metabolic consequences, no matter how much energy you consume - if those effects are statistically significant will yet have to be determined in future experiments.

So does this mean: No calories are not no calories!?

At least in the study at hand, the increased weight of the rodents was still mainly a result of an increase in food intake. It would thusly be premature to blame the futility of all your past weight loss efforts on the use of reasonable amounts of artificial sweeteners. If you have however been guzzling several liters of diet coke per day and have arrived at a point where you have to pour an additional pint of liquid splenda into your already sweetened protein shake, it is highly indicated to cut back on your sweetener intake, anyways - and, at least in this particular regard, all no-calorie sweeteners, "natural" or artificial, are the same!

Image 2: I am 99.9% sure that this was not the result of artificial or natural sweetener overconsumption. Whether they could make the difference between 8% and 9% body fat, will yet have to be elucidated.
On a side note: In view of the fact that the rodents in the saccharine group also had a statistically higher lean body mass (and "statistically" identical fat mass), the reverse, i.e. "the more artificial sweetener, the better", could be true, when you are not dieting, but bulking... I thought, I'd mention that before I get a call from a flack from Johnson & Johnson or their subsidiary business, McNeil Nutritionals, the company that produces Splenda, accusing me of "not mentioning the body recompositioning effects of their product" - personally I would yet not insist on gaining those 1.4% extra gains (which, by the way, could be increased organ weight, as well; remember: lean mass is not only muscle mass!), if that could hurt my health, derange my natural ability to control my energy intake and set me up for obesity - but hey, everybody is different ;-)