Noncaloric sweeteners might not be the solution either

Aug 25 2009 Published by under Food, Public Health

The American Heart Associations recommendation to cut down on dietary sugar is all over the news. Discussion of this by Isis the Scientist triggered a comment from Callinectes :

Someone reading this may therefore assume diet drinks with Aspartame, Splenda, etc. may be okay because it's 0 calories and added "sugar". Can anyone comment authoritatively on this? The way I see it, it's still just empty calories and not very good for you when consumed regularly on a weekly or (heaven forbid) daily basis.

To which Isis responded:

One might argue that diet drinks still activate the "Hedonistic food pathways" in the brain (centers in the ventral tegmental area and nucleus accumbens) that lead us to associate reward with food intake, causing us to take in more energy-dense food... That said, I don't know of any multi-variate studies comparing risk between sugar drinks, diet drinks,... let's be clear that Aspartame and Splenda are zero calorie sweeteners, meaning they would technically not contribute to the AHA's recommended daily intake.

I am reminded of what I think of as a reasonably provocative series of observation from Susan Swithers and Terry Davidson at Purdue.


One of their more recent takes on this story is found in the following paper:
A role for sweet taste: calorie predictive relations in energy regulation by rats.
Swithers SE, Davidson TL.
Behav Neurosci. 2008 Feb;122(1):161-73. [DOI]
Swithers08-Fig1.jpg
Fig1: Cumulative body weight gain across 5 weeks
exposure to sweet predictive, sweet nonpredictive,
or sweet predictive control diets.
Error bars represent standard error. *p  .05.
The model is reasonably simple to understand. They offer rats the opportunity to consume up to 30 g of plain yoghurt (0.6 kcal/g) in addition to their standardized lab chow, six days per week. On three of these days, the yoghurt is sweetened with either glucose (20% wt/wt; 1.2 kcal/g) or saccharin (0.3% wt/wt). A control group received the three glucose-sweetened yoghurt sessions but not the three unsweetened yoghurt sessions to equate caloric intake with the saccharine group. As we see from the first figure, the rats in the saccharin group (non-predictive) gain more weight than do the rats in the glucose group (predictive) or the control group. They also ended up with increased bodyfat assessed by dual energy x-ray absorptiometry. Yet, the groups did not differ in yoghurt intake, nor total caloric intake (chow + yoghurt).
Nevertheless, the second experiment suggested a disruption of feeding regulation may still be present, you just have to tease it out. In glucose-trained animals a brief pre-meal of palatable Ensure reduced subsequent chow intake relative to when no pre-meal was provided. In the saccharine-trained animals the pre-meal did not suppress later chow feeding. So perhaps the numerical increase in total caloric intake which was not found statistically reliable in the analysis of the long-term training was nevertheless driving part of the observed effect on bodyweight. [This is a reminder to always look at the data and not be driven by the tyranny of the statistical finding.]
The statistically reliable effect shown in the pre-feeding experiment, and the numerical increase in caloric intake during training, both suggest a behavioral disregulation with implications for human dieting. It may be that chronic intake of noncaloric beverages leaves people insensitive to normal compensatory mechanisms involved in eating. To make a long leap from the second experiment, that candybar you eat at 4pm may reduce the amount you eat at dinner at 6pm if you are a sugared soda drinker but not if you consume noncaloric soda.
The group has worked a bit on additional parts of the saccharine effect as well. In this particular paper, they looked at periprandial body temperature, which cited work indicates is triggered by sensory aspects of ingestion rather than caloric absorption. Figure 8 compares body temperature in the hour after yoghurt ingestion for the three sweetened condition days versus the three unsweetened condition days. The addition of glucose to the yoghurt drives a lasting elevation of body temperature that is not seen in the other conditions. Although this is equivocal (being tied to the extra caloric content) additional experiments showed that, for example, when given the same pre-meal detailed above, the non-predictive saccharine trained rats generated a lower body temperature response and less locomotor activity in the first 30 minutes. This would also tend to support their hypothesis of a disruption in the processes triggered by the orosensory properties of consuming palatable foodstuffs. Although I would wish to know a little more, the dumb interpretation is that an attenuation of both higher body temperature and activity following high-calorie food would have an undesirable effect when it comes to weight regulation.
Swithers08-Fig8.jpg
Fig 8. Changes in core body temperature over the first 60 min following yogurt presentation during sweet predictive (A) or sweet nonpredictive (B) training. Error bars represent standard error. *p  .05.

I'll close by noting that another recent paper from the group extends the basic observation to an additional noncaloric sweetener (AceK) and base foodstuff (refried beans; Isis, I swear I am not making that up)
General and persistent effects of high-intensity sweeteners on body weight gain and caloric compensation in rats.
Swithers SE, Baker CR, Davidson TL.
Behav Neurosci. 2009 Aug;123(4):772-80. [DOI]
__
*Discl: I am professionally acquainted with at least one of the authors.
Swithers, S., & Davidson, T. (2008). A role for sweet taste: Calorie predictive relations in energy regulation by rats. Behavioral Neuroscience, 122 (1), 161-173 DOI: 10.1037/0735-7044.122.1.161
Swithers SE, Baker CR, & Davidson TL (2009). General and persistent effects of high-intensity sweeteners on body weight gain and caloric compensation in rats. Behavioral neuroscience, 123 (4), 772-80 PMID: 19634935

38 responses so far

  • And aren't we talking about drinks? Not "yoghurt." What the balls is "yoghurt", btw? Are you British, Monkey?
    So, what is the mechanism here, because I might be missing it. The rats ate the same amount irrespective of the sweetner, but the saccharine group was less active? That led to the body weight increase?

  • dg says:

    "...that candybar you eat at 4pm may reduce the amount you eat at dinner..."
    Or you could simply pay attention to how much you're eating in the first place. Isn't the underlying problem people eating crappy food in whatever the hell amount they feel like, rather than some complicated relationship involving artificial sweetener? Don't humans who drink diet soda have frontal lobes?

  • bikemonkey says:

    Are you British, Monkey?
    Perhaps.
    So, what is the mechanism here, because I might be missing it.
    I don't think they know yet either and for certain I'm not real up on the field. This group has been working on this for a number of years and there are, of course, other players. There was some shit about glucose/sucrose/fructose and the insulin response somewhere in the story I believe. There's lots more to the story.
    The rats ate the same amount irrespective of the sweetner
    Nope. That's the abstract version. The data show a numerical increase in total caloric intake for the training phase but brush it of as not statistically different. The second expt, however, shows a difference in the pre-feeding suppression. So there's a behavioral mech right there to point at.
    the saccharine group was less active? That led to the body weight increase?
    Unfortunately they only present the first 30 min on the temperature and activity. I'd think this could use a little more workup. and if they are going to go this route they need one of them fancy CLAMS type dealios to nail down feeding and metabolism round the clock.

  • bikemonkey says:

    Isn't the underlying problem people eating crappy food in whatever the hell amount they feel like, rather than some complicated relationship involving artificial sweetener? Don't humans who drink diet soda have frontal lobes?
    The notion that humans are magically free of the principles of behavioral biology is quaint, to say the least.
    Humans are just as subject to operant and classical conditioning as any other species. We share mechanisms which regulate feeding with many other species as well.
    Our hypertrophied frontal lobes do not vault us out of these realities.

  • kiwi says:

    Surely an experiment on male scientists who drink diet drinks vs sugared drinks could establish who has frontal lobes. . .
    And we have yoghurt in NZ too - I vote DM as an (honorary) Antipodean.

  • Nope. That's the abstract version...[blah,blah,blah]...I'd think this could use a little more workup. and if they are going to go this route they need one of them fancy CLAMS type dealios to nail down feeding and metabolism round the clock.

    If I am remembering people I've met correctly, I think there are actually data on this in humans....let me have a looksy through my EndNote....

  • Anonymous says:

    I think there are actually data on this in humans....
    Humans aren't a very good rat model.

  • Humans are just as subject to operant and classical conditioning as any other species. We share mechanisms which regulate feeding with many other species as well.
    Our hypertrophied frontal lobes do not vault us out of these realities.

    What a load of fucking horseshit. Our motherfucking huge-ass cortex permits dramatically more behavioral flexibility than rodents.

  • Funky Fresh says:

    Our hypertrophied frontal lobes do not vault us out of these realities.

    Nor do rats dunk an entire bag of Oreos in a bottle of shiraz because they are stressed about the situation with their idiot brother.

  • speedwell says:

    Cue the inevitable whining from my fellow type 2 diabetics that they're cursed to gain weight no matter what they eat. Seriously, until they test this on diabetic rats, I'm bloody just ignoring the study as far as it applies to me.

  • Lindsey says:

    I have been hearing this for years. While I have always avoided sugar substitute (hippie parents who like to scare their kids about cancer a lot), I always thought it odd to watch people down diet coke after diet coke, like it was somehow okay, since it "wasn't really sugar". Also, I'm sure someone out there is testing this on diabetic rats...

  • Roadtripper says:

    Another scientific study to ignore. Yawn.
    Here's another experiment to try, with humans. I did it myself: take a 'regular' soda drinker who's overweight, and drinking up to a six pack of sodas a day. Then switch them to diet soda. In my case, I lost 15 pounds without even trying. All it took was changing from regular to diet soda.
    And I'm supposed to believe this nonsense that 'diet soda causes weight gain?' I'm calling bullshit on this one. My personal experience has been exactly the opposite.
    Rt

  • Jon says:

    "Humans are just as subject to operant and classical conditioning as any other species. We share mechanisms which regulate feeding with many other species as well." I disagree with this statement. I may salivate at the sound of the bell, but unlike all other mammals, I can overcome my conditioning and choose not to eat the food that's placed in front of me.

  • DSKS says:

    "and drinking up to a six pack of sodas a day."
    Struth! To hell with the weight, dude, do you still have any teeth?

  • MattXIV says:

    The problem is that the enviroment the rats are placed in(free access chow but a fixed dose of yogurt with a specific sweetener) doesn't resemble the environment humans are in, where we have cheap access to as much sugar sweetened and artificially sweetened beverages as we want.
    The primary mechanism by which diet soda could result in weight loss in humans would be by substitution for sugar-sweetened beverages. To test that, you'd need to give the rats free access to sweetened and plain options and switch the sweetener to see whether the decreased caloric intake from the sweetener is offset by other behavioral changes. Preferably in the form of a beverage, since adding the sweetener to something with bulk to it limits how much they can consume in a way not analogous to humans and soda.
    Many popular sodas also contain caffeine as well, so there's something that can suppress appetite, increase the metabolic rate, and incentivise habitual consumption in there to further muddy the matter.

  • whimple says:

    To test that, you'd need to give the rats free access to sweetened and plain options and switch the sweetener to see whether the decreased caloric intake from the sweetener is offset by other behavioral changes.
    This is a stupid idea. If you want the human result, do the experiment in humans.

  • bikemonkey says:

    @16,17...sometimes I cry for the sad state of understanding how science works particularly among those that should know better. isolate variables, test, interpret, design up some new studies. wtf is wrong with you people?
    @9, 14: Perhaps I misplaced the word 'just'. I did not mean to imply that behavioral flexibility and response to identical stimuli and cues was *identical* across species. Merely that the general principles apply to humans just as much as to rats. If you deny that assertion, however, you are sadly mistaken.

  • Cashmoney says:

    And I'm supposed to believe this nonsense that 'diet soda causes weight gain?' I'm calling bullshit on this one. My personal experience has been exactly the opposite.
    No offense but you do understand how dumbass this comment is, right? WTF does dropping the caloric load of a 6pk of Coke out of your diet have to do with the studies discussed in this post? You call bullshit on the science?
    Let me refer you to a real expert on complete and utter dumbassness, jump to about 24:00 of the cast. hint, YOU are Beavis dude.

  • MattXIV says:

    bikemonkey,
    WTF is wrong with you,/i>? The study isn't generalizable to any human behavior of interest because the food enviroment doesn't resemble anything humans are likely to encounter because we control the dosing schedule for our sweeteners. It's a simple matter to do it differently in the experiment - give them a sweetened fluid and let them dose ad lib instead of periodic yogurt feedings. The case the study isolates isn't the case of interest.
    And the point about humans being different from rats is important. Feeding related behaviors vary significantly across species. It's not implausible that there are significant differences in the behavioral response to taste and fullness between mammals - hypertrophied frontal lobes aside, I'd be willing to wager if you ran the same experiment with cats or cows, you'd get noticably different results. I don't see why some people can't grasp that even if the rat is the most practical, or even best animal model, for a question it doesn't mean the results are generalizable.

  • bikemonkey says:

    And the point about humans being different from rats is important.
    "may be important" my friend, may be. The plain fact of the matter is that animal models are predictive of the human situation. Imperfectly and sure, there are exceptions. But in a very general sense, unless you have opposing data or an exceptionally good rationale for why a given animal study should not apply (within the usual bounds) then you sound like a knee-jerking idiot. Like PP. If you insist the study simply *must* be wrong based on your anecdote or introspective handwaving anyway. Now if you are advancing a reasonable alternative hypothesis, preferably with some evidence based rationale for not believing a rat model, we'd be talking...

  • whimple says:

    The study isn't wrong, just irrelevant. This study is a great example of an experiment that could and should be done directly in humans without ever involving the rats. Whatever the outcome of the human study is, it's interesting. When you get the result from humans, you don't care what the results is in rats anymore (if indeed you ever did). Doing this study in rats is *lazy*. Try to do research that matters BM. šŸ™‚ *tease*

  • bikemonkey says:

    whimple, please sketch out a study in humans, from your ivory tower armchair, that would elucidate this issue as clearly. make sure to indicate all necessary control groups

  • whimple says:

    No, I'm too busy doing my own human subjects studies. What's your excuse?

  • bikemonkey says:

    What's your excuse?
    FWDAOTI

  • Roadtripper says:

    Cashmoney @19:
    Wow, an irrelevant rant, and a pointless link. Incredibly, you're even less persuasive than a poorly-thought-out study on overweight rats.
    Rt

  • Anonymous Coward says:

    Pure anecdote, but when I was doing diet and weight loss counseling, the clients who went "cold turkey" on sweets had less trouble revamping their eating habits than those who clung to the artificial sweeteners.
    I always thought it kept their "sweet tooth" alive.

  • Theodore says:

    I think the central point is that regular people don't have to use their cortex to regularly balance their calories. That sort of fine hunger vs activity budget really should just be set to a cruise control. The researchers basically challenged whether non-calorie sweeteners would affect that setting. I think the experiment that whimple might be proposing is have four groups of people. Two that want to loose weight and two that do not, then divide those by having two that are on regular soda and two that are on non-calorie sweetener. Have each group keep a food journal and observe weight change over time. If these results are applicable then you would expect both of the non-calorie sweetener groups would weigh more regardless of whether they were trying to actually loose weight or not. The first group would unconsciously trend upward perhaps due to a reward/hunger/satiation pathway triggered by the soda. The other would have a harder time quitting and would feel more hungry and might tend to binge more.
    There are some glaring downsides. For one enrolling patients in a study about weight gain would most likely make the patients more aware of what they eat, especially with a journal, so all groups may very well trend downward. That consciousness might be so bad as to negate the value of trying to look at the cruise settings (the real ideal experiment couldn't be ethically completed). Furthermore, sorting out the pathway would be impossible. You don't know if this is due to metabolic effects or instead due to hedonistic pathways. As mentioned caffeine would play a large role as would sleep schedule, activity, interests, behavior. The journals would also have varying degrees of reliability, portion sizes, etc. Besides, some people just don't like the non-calorie sweeteners so instead of really switching they would simply cut back, or just go straight to bingeing on other sugared items. Finally, the difference here is statistically significant though seems moderately clinically significant ~10-15%. Much more like a tummy that we put on during the holidays and less like patients with morbid obesity. Therefore, the study would have to recruit and then track a lot of people. And if you really wanted to have wide ranging applicability would need to be done in both genders, with several age cohorts, and several socio-economic levels. That would be a cool read if it was ever done though I would sure as hell bet they would need some animal studies like this to justify the necessary funding.

  • lyontamer73 says:

    "My personal experience has been exactly the opposite."
    That's called anecdotal evidence. šŸ˜‰ A better approach would be to conduct a different study, perhaps this time with rats that were first fed sugars until they gained a certain percentage of body fat, to see if these rats then lose weight when switched to the sweeteners.
    This study was done with rats of normal weight, and it does not imply that the sweetener *caused* the weight gain. It only showed a positive correlation. There can always be other things having an influence. For example, eating the sweetener before the meal. Any dieter will tell you that drinking a glass of water, sweetened or not, 30 minutes before eating will fill space so you eat less food. They don't say here that any rats were given water before their meals rather than sweeteners. So there's another experiment possibility. Just like the other comment about diabetic rats. We can make diabetic rats. Go study them.
    Don't just blow a study off you guys. Write your thoughts about it down, and come up with new studies. šŸ™‚

  • Richard Eis says:

    -I can overcome my conditioning and choose not to eat the food that's placed in front of me.-
    Except for when you don't. But then you will have a wonderful excuse for why you didn't because of your incredibly smart brain.

  • Funky Fresh says:

    What's your excuse?
    FWDAOTI

    FWDAOTI FTW!!!

  • Cashmoney says:

    Hey did all you geniuses see that being obese shrinks your brain? Apparently because of cardio-vascular things...

  • Like PP.

    Fuck you, cockknuckle.

  • antipodean says:

    Sorry BikeMonkey but whimple's got a point.
    A rat in your cages is not a human in the real world. If you want to discuss rat physiology then that's fine but this type of information will never be extrapolatable to human public health. There are too many extrapolations.

  • DJ says:

    What does "FWDAOTI" stand for? I'm confused.

  • Ford says:

    For two studies in humans, see refs. 5 & 6 in link.

  • ABradford says:

    If people are insisting on giving anecdotes as evidence, I might as well give mine.
    A few summers ago, I quit soda. Went from drinking a can or bottle (or more) a day to treating it more like the treat it is and drinking water instead. This was the only change to my diet and excercise I made at the time. I didn't switch to diet soda, nor have I ever consumed much of non-calorie sweeteners as I usually can't stand the taste. I lost over 20 pounds that summer and needed a smaller wardrobe. I'm still overweight, but I'm working on it.
    If you're going to commit to losing weight, why take half-measures.

  • grumble says:

    who wants to work with humans anyway.

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