Sucralose: Sweet Taste / Energy Content Mismatch Offsets Our Nutrient Gauge and May Make us Overeat, but...

Beware: Splenda(R) is not sucralose, but 95% dextrose (D-glucose) and + maltodextrin combined with an undisclosed small amount of mostly indigestible sucralose.
"These findings further reinforce the idea that 'sugar-free' varieties of processed food and drink may not be as inert as we anticipated. Artificial sweeteners can actually change how animals perceive the sweetness of their food, with a discrepancy between sweetness and energy levels prompting an increase in caloric consumption," Professor Herzog said according to the press release the University of Sydney published last week alongside the publication of a study that was co-authored by Herzog in CELL Metabolism - a study with the telling title "Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response" (Wang. 2016).
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The mainstream interpretation of Wang's results says that the researchers show (for the first time] that chronic consumption of the synthetic sweetener sucralose causes increased food intake... what the study doesn't highlight and corresponding media articles try to mention at best in parts the average reader will often skip is the fact that the "subjects" were not humans, not pigs, not even mices, but our close relative *ahm*, the fruit flies.
Figure 1: Food intake in fruit flies that are chronically exposed to high dose sucralose (Wang. 2016).
Only in an extra-experiment in mice the scientists are able to provide at least initial evidence that mammals, in this case wild-type mice that orally consumed sucralose jelly once per day will increase their food intake, as well.
Figure 2: Food intake in rodents who received a jelly with the human equivalent of 3.2g sucralose - that's up to 3.2x sweeter than a full kilogram of sugar (Wang. 2016).
About how much sucralose are we talking? 7.5 mg per day - in mice! With 10-week old female C57BL/6 mice weighing only 15-18g those 7.5mg the rodents received in a jelly on a daily basis would qualify as hardly palatable for human beings for whom the ~500mg/kg (in rodent terms) sucralose would amount to the whopping amount of ca. 3.2 grams of sucralose and should thus have the sweetness of up to 3.2 kg sugar!
This is not only significantly more than the only existing government recommendation of the Canadian Diabetes Association considers safe (namely 9 mg/kg BW/day).
It is also the amount of sucralose in 80 splenda-sweetened diet cokes at 40mg sucralose per can (Franz. 2010), hilarious amounts of SPLENDA®, which contains only relatively small amount of sucralose and is mostly made from dextrose or highly fluffed maltodextrin, "bulking agents" that give SPLENDA® its volume. Even if we combine all sources of sucralose in our diet and assume an "aggressive replacement of sugar" (Grotz. 2009), the predicted daily intake of 1.3 mg/kg body weight/day for the average adult is significantly lower than the 40mg/kg human equivalent of the amount of this sweetener that was used in the rodent experiment of the study at hand.
As the lack of efficacy in NPY-knockout mice shows, probably as a consequence of the same "neuronal starvation pathway" Wang et al. observed in fruit flies. An effect they explain as the re-adjustment of our energy-intake gauge. More specifically, Associate Professor Greg Neely from the University of Sydney's Faculty of Science is quoted in the press release:
"Through systematic investigation of this effect, we found that inside the brain's reward centres, sweet sensation is integrated with energy content. When sweetness versus energy is out of balance for a period of time, the brain recalibrates and increases total calories consumed. In the study, fruit flies that were exposed to a diet laced with artificial sweetener for prolonged periods (more than five days) were found to consume 30 percent more calories when they were then given naturally sweetened food. When we investigated why animals were eating more even though they had enough calories, we found that chronic consumption of this artificial sweetener actually increases the sweet intensity of real nutritive sugar, and this then increases the animal's overall motivation to eat more food" (University of Sidney. 2016)
Eventually, it is thus the mismatch between the sweetness of an ingested substance and its nutritional value, which is at the heart of the problem. Food that contains synthetic sweeteners such as sucralose obviously don't show a correlation between their sweetness and their energy contemt... and that's not news: neither in science, nor here on the SuppVersity where I've previously pointed out that the use of artificial sweeteners may make your sweet tongue even sweeter and thus worsen your ability to stay away from or at leat control the intake of sweets efficiently.

What the press release don't tell you about the practical (in)significance of the results

What is news, however, is that Wang et al. appear to have finally identified the mechanism behind the appetite-stimulating effect of consuming synthetic sweeteners: a conserved neural fasting response, which response integrates pathways that govern feeding, gustatory reward, and energy sensing that together modify how sweet food is perceived. Accordingly, the downstream effects are similar to that of fasting: a compensatory response is activated that alters taste sensitivity and feeding behavior accordingly and we start to eat more. Now this wouldn't be a problem if we stuck to the same artificially sweetened products. Unfortunately, the anti-satiety effects extend whey beyond certain foods and into the realms of everything sweet (probably including starches, as well).
Figure 3: If you compensate the lack of (expected) energy in an artifically sweetened meal with sugar or sugar alcohols, the effect of sucralose on food intake is lost (Wang. 2016). In the real world it should thus only occur in those who use sucralose to starve themselves, not people who drink diet instead of regular coke with their fries ;-)
The consumption of calorie-containing foods however, and that's something I bet you have not read about the study, elsewhere, has been shown to negate the effects. Where? Well, the answer is simple: in Wang's own study, where both, adding sucrose and the sugar-alcohol sorbitol, blunted the hyperphagic (=overeating) effects of sucralose. Unless you're using sucralose to actually starve yourself, the appetite increasing effects of which Wang et al. openly admit that they are induced by fasting should not occur.
Stevia, a proven anti-diabetic, should have similar effects.
How bad is it? Eventually, the study at hand which clearly refutes an involvement of the microbiome or other non-energy-intake-related obesity mechanisms of artificial sweeteners is - as hilarious as this may sound - good news and perfectly in line with both experimental and anecdotal evidence confirming the efficacy of artificially sweetened foods as fat loss aids when they are used in conjunction with an energy-controlled diet, where the increase in AMPK many people seek to induce by taking supplements like curcumin or alpha lipoic acid may have more ad- than disadvantages.

Speaking of fasting, in case you are reading only the head- and bottomline, you may have to be reminded of what I've discussed at the this article: Fasting is necessary for sucralose to have an appetite-increasing effect. Simply adding sugar or the sugar alcohol sorbitol to the fruit flies' food abolished the effects on their food intake completely (see Figure 3).

Moreover, it still needs to be determined (a) if the effect exists in humans, (b) how pronounced its effects (if they exist) are, (c) whether other implications, such as the lack of significance of the microbiome, could be species-specific and thus potentially irrelevant for humans, as well, and, obviously, (d) whether the same effects occur with lower doses of sucralose and/or other sweeteners. So what do you think? Let everyone know!
  • Franz, Mary. "Diabetes Self-Management, Diet Soft Drinks". 2010
  • Grotz, V. Lee, and Ian C. Munro. "An overview of the safety of sucralose." Regulatory toxicology and pharmacology 55.1 (2009): 1-5.
  • University of Sidney. "Why artificial sweeteners can increase appetite." 13 July 2016 < > 
  • Wang, Qiao-Ping, et al. "Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response." Cell Metabolism 24.1 (2016): 75-90.
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