The Latest on Artificial Sweeteners: #Sucralose Good for the Lean, Bad for the Obese? #Acesulfame-K, the Healthier Alternative? As If! Plus: There's All Wrong w/ the Research

Time to stop discriminating against low-calorie (#LCS) or artificial sweeteners as a category, time to start considering the molecule and subject-dependence of these substances and to get the research back on track. Not sure if this article will achieve the latter but if you realize that generalizations are misplaced when it comes to alleged sugar-alternatives are unwarranted that would be an educational success worth celebrating for the SuppVersity, as well.

Still on schedule! As promised last week, I will continue to do my very best to supply you with at least one in-depth exercise, nutrition, and supplementation article per week again. Worked out last week, worked out this week, will work out next week - promise ;-) -- With that being said, you may look forward to a 2020 research update on the use(fulness) of artificial sweeteners that will hopefully add some color to your perspective on 'artificial sweeteners' as a category and the vast, in many cases dubitable re-search cherry pickers like to cite to pro-vide "evidence" that their #black&white stance towards 'artificial' or, even more generally, 'low-calorie sweeteners' was 'evidence-based', true, and indisputable.

You can learn more about sweeteners at the SuppVersity

Aspartame & Your Microbiome - Not a Problem?

Sucralose 2018 Update #1 - Does it Make Us Fat?

Diet Soda Beats Water as Dieting Aid in RCT

Experiments Don't Support AS<>Obesity link

Stevia, a 2019 research update - #natural=good?

Other Diet Soda Additives May be the Real Problem

• Building a case against #sucralose - Is it especially bad for the obese and beneficial for the normal-weight? based on Nichol 2019 -- A new study seems to suggest that the dreaded artificial sweetener sucralose may differently affect the insulin sensitivity of lean and healthy versus obese individuals.
  

  

  Figure 1: Insulin sensitivity in 10⁻⁵ dl/kg/min/(pmol/L); calculated based on data from OGTT (Nichol 2019)

  In fact, the 48 mg of sucralose the subjects consumed 10 minutes before an oral glucose tolerance test #OGTT in a recent study by scientists from the University of Illinois had opposing effects on normal-weight and obese adults (see Figure 1).

  "Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group" Nichol 2019.

  Even more so, an albeit non-significant decline in insulin sensitivity of -14% was observed in the N=11 subjects with obesity compared to the water condition - pretty much the opposite of what we see in the N=10 normal-weight subjects of this randomized crossover study.
  
  It shouldn't go unmentioned, by the way, that the study also shows that the benefits (and detriments) are at best partially mediated by sweet taste (sensed in the mouth), as the sham-administration where the subjects were not allowed to actually ingest the sucralose had much less pronounced beneficial or detrimental effects.
  
  

  

  #Sweeteners - How much can you use supposedly consume safely? The FDA's ADIs and how to get to those for several artificial sweeteners (MayoClinic.com)

  The mere existence of this (un)tasty side effects of 'super-sweet', on the other hand, these "findings underscore a physiological role for taste perception in postprandial glucose responses, which supports the notion that sweeteners, regardless of their associated caloric contribution, should be consumed in moderation" (Nichol 2019) - by the obese, I should add...
  
  ...ah, and no the study was funded by the National Institutes of Health, not by CocaCola, dear sweetener conspiracy theorists 😗
• Brain = explode!? #InRodents, Acesulfame can boost the release of neurotransmitters - What's the implication? based on Yin 2020. If you've been following the SuppVersity sweetener coverage for some time, you will be aware that Acesulfame-K is by no means harmless... if you check out the limited research, this is not the first but certainly one of the more concerning studies suggesting detrimental effect of this sweetener that has a comparably good reputation compared to sucralose, let alone aspartame (outside of people with phenylalanine issue the latter is largely unwarranted, btw).
  

  

  Figure 2: None of the sweeteners made the rodents overeat (from Yin 2020)

  In their recently published paper, scientists from the Huazhong Agricultural University, describe an experiment with four natural sweeteners (sucrose, stevioside, maltose, and xylitol) and six artificial sweeteners (acesulfame, sucralose, aspartame, cyclamate, saccharin, and neotame) that studied their effects on the behavior and neurotransmitter release of 190 male Kunming mice. With astonishing results:
  • only(!) the consumption of the 10 mM Acesulfame (treatments were standardized for equal sweetness) solution triggered a significant difference in the release of neurotransmitters
  • none of the other bad artificial sweeteners had an effect on brain chemistry; more specifically, the release of neurotransmitters was significantly greater (p < 0.05) than that of the control group (water group), but there was no significant difference in feed intake.
  • no effect on neurotransmitters was observed for any other of the artificial sweeteners - including the dreaded aspartame and sucralose
  • appetite and food intake were not affected by any of the artificial sweeteners, the same goes for the normal body weight gain in all groups
  
  What makes the neurotransmitter-messing effects of Acesulfam particularly 'interesting' is that they are pretty much identical with devil's excrement: simple table sugar (sucrose).
  
  

  

  Figure 3: The contents of neurotransmitters in mice (n = 10). a Dopamine (DA) content; b 5-Hydroxytryptamine (5-HT) content; c Norepinephrine (NE) content; d Epinephrine (EPI) content. The different lower-case letters indicate significant difference (p < 0.05)

  That's bad news: Only acesulfame shares the putatively addictive quality of sugar as it messes w/ dopamine & serotonin.
  
  Why exactly is that bad news? Well, if there is such a thing as sugar-addiction, it will probably be upheld or even triggered with the artificial sweetener Acesul-fame-K that you will find predominantly in products marketed as "aspartame free" and "sucralose free"
  
  ... what a mess. If there's anything you take away from the study at hand (which doesn't disqualify itself by being done in rodents, PubMed warriors), it should be that talking about "artificial sweeteners" as a category is about as accurate as talking about dietary fat as category as if all fats were created equal.
• #BadScience without practical relevance: "Approaches in animal studies, such as very excessive dose loading, may be appropriate for some safety and toxicological research but can have distorting consequences for nutrition-related outcomes." - (Mela 2020) It's a problem I've mentioned in almost every 'sweeteners-are-the-devil' studies discussed on the SuppVersity. In order to confirm their preformed conviction that artificial sweeteners must be inherently dangerous, scientists actively choose to poison their lab animals with amounts of artificial sweeteners - amounts, even the greatest Diet Coke junkie is never going to achieve.
  
  These and a good dozen of other methodological (and reporting) problems all contribute to said "distortion" of the research the authors of a recent paper seek to rectify. In their paper "Perspective: Standards for Research and Reporting on Low-Energy (“Artificial”) Sweeteners" researchers from the Netherlands published a comprehensive list of requirements for future low-calorie-sweetener  (#LCS) research (I quote directly from Mela et al. 2020):

• 

  To talk about "sweeteners" as a category - even if you restrict it to 'artificial' - is absolutely inappropriate if your studies rely on studies w/ only one of them. Saccharin, for example, may well be the black sheep of the family.

  Research hypotheses should be explicit a priori, and the underlying research question(s) reflected in the choice of exposures, comparators and analyses. 
• Primary research studies and their representation in reviews should reflect the stated hypotheses, with particular regard to caloric vs. noncaloric comparators, and potential for extrapolation to LES in general vs. specific LES. 
• Where outcomes are not attributable to energy reduction or perceived sweetness, interpretation relies on the chemical and ADME (absorption, distribution, metabolism, and excretion) properties of specific LES. 
• The selection and citation of existing research should fairly represent (#noCherryPicking) the balance and weight of different types of evidence, particularly where there are data from RCTs with relevant exposures and populations. 
• Animal research and other studies generating evidence related to safety and toxicology should specifically refer to that literature. 
• Reporting of evidence on health associations with LES from observational studies, including prospective cohort studies, should be clear that these are subject to residual confounding, including reverse causality, and may have been designed to answer a different research question. 
• Hypotheses generated by observational and animal data must be interpreted in relation to the specific exposures, plausible causal pathways, and results of any related human intervention trials. 
• If all future research adheres to these principles, the next #sweetener-science-update may well deliver better answers to a question that must, as the authors emphasize, not be answered applying the "precautionary principle" as there's not doubt that there may also be value gained from the use of LES—for example, as a tool for maintaining the acceptability of foods, beverages, and diets reduced in sugar, facilitating progress towards widely advised goals to reduce sugar intakes." (Mela 2020)... and you know that? The SuppVersity is where you'll see this (improved) research being discussed 🤩

This old advertisement for the saccharine-based sweetener T@B is spot on: Since they all use slightly (sometimes profoundly) different sweetener blends, one diet beverage is unlike the other... about time people, including researchers, realize that!

Stay tuned! If you're looking for the ultimate acquittal (or conviction) of artificial sweeteners, you will have to wait for future research updates. What this update taught you is (as usual): you got to be specific. As the Nichol study shows, the effects of #sucralose critically depend on your body fat levels as the same supersweet substance that's making obese individuals' lives more miserable seems to have beneficial (if any) effects in normal-weights. That's in line with the often overlooked specificity of individual artificial sweeteners, of which the Yin study shows you that their effects can differ widely according to the structure of the molecule. In that, it is particularly interesting that with #acesulfam-K which is unwarrantedly considered to be the healthier alternative to sucralose or aspartame and can often be found in protein powders and functional beverages could be among the worst offenders.

And as if that was not enough, there's also Mela's verdict on the laughable (or pathetic) quality of studies that conflate correlation and causality, deliberately overdose to be able to measure any effect, at all, and carelessly ignore the previously highlighted molecule- and subject-specificity ...

...speaking of which, if the authors' advice on how to do sweetener research 'the right way' will be of avail, you can expect more well-conducted quality studies with practical significance to be published in the future - studies, you will obviously see covered here at suppversity.com or in the SuppVersity Facebook News, where you can also leave a comment on this article!

References:

• Mela, David J., John McLaughlin, and Peter J. Rogers. "Perspective: Standards for Research and Reporting on Low-Energy (“Artificial”) Sweeteners." Advances in Nutrition (2020).
• Nichol, Alexander D., et al. "Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial." Nutrients 12.1 (2020): 29.
• Yin, Kai-Jing, et al. "Effects of different sweeteners on behavior and neurotransmitters release in mice." Journal of Food Science and Technology 57.1 (2020): 113-121.