The Frontal Cortex

It’s been recognized for a few years that drinking diet sodas can actually cause weight gain, since the phony sweetness of artificial sweeteners disrupts the “predictive relationship” between a sweet taste and caloric satisfaction. In other words, people drink a diet Coke when they are craving a sweet pick-me-up. However, because the soda doesn’t actually contain any calories, the craving remains unsatisfied. The end result is that rodents (and people) end up consuming more calories later on. The craving returns with a vengeance. Here, for instance, is the abstract for a recent paper in Behavioral Neuroscience:

Animals may use sweet taste to predict the caloric contents of food. Eating sweet noncaloric substances may degrade this predictive relationship, leading to positive energy balance through increased food intake and/or diminished energy expenditure. These experiments were designed to test the hypothesis that experiences that reduce the validity of sweet taste as a predictor of the caloric or nutritive consequences of eating may contribute to deficits in the regulation of energy by reducing the ability of sweet-tasting foods that contain calories to evoke physiological responses that underlie tight regulation. Adult male Sprague-Dawley rats were given differential experience with a sweet taste that either predicted increased caloric content (glucose) or did not predict increased calories (saccharin). We found that reducing the correlation between sweet taste and the caloric content of foods using artificial sweeteners in rats resulted in increased caloric intake, increased body weight, and increased adiposity, as well as diminished caloric compensation and blunted thermic responses to sweet-tasting diets. These results suggest that consumption of products containing artificial sweeteners may lead to increased body weight and obesity by interfering with fundamental homeostatic, physiological processes.

So the sweetness of a food is one way the brain keeps track of its intake. More sugar implies more calories, which is why the hypothalamus gets so annoyed when it’s tricked by Splenda. However, the taste of sugar isn’t the only way the brain monitors calories and cravings. According to a new paper in Neuron, the brain also receives rewarding input from metabolic processes that have nothing to do with the tongue. When you eat a big meal, part of the pleasure of the meal comes from the fact that the food is sustenance, fuel, energy. Even shitty food is a little rewarding.

The Duke scientists came up with a clever paradigm for isolating this more indirect rewarding pathway: they studied mice without a functional TRPM5 channel, which is essential for detecting sweetness. As a result, these mutant mice showed no immediate preference for sugar water.

But here comes the cool part of the experiment. The scientists then allowed the mice to spend some time with the sugar water and normal water. After a few hours, it became clear that the mutant mice greatly preferred the sugar water, even though they couldn’t taste the sugar. (A control experiment with sucralose, an artificial sweetener, demonstrated that the rats were responding to the caloric intake, not the sweet taste.)

Finally, the scientists measured dopamine levels (via in vivo microdialysis) in the nucleus accumbens (a brain area that processes rewards) in the mutant mice and normal mice.* While normal mice exhibited an increase in dopamine in response to both fake sugar and real sugar – the reward was the sweet taste – the mutant mice only demonstrated a dopaminergic spike when consuming genuine sugar water. What they enjoyed were the calories. As the authors conclude:

We showed that dopamine-ventral striatum reward systems, previously associated with the detection and assignment of reward value to palatable compounds, respond to the caloric value of sucros in the absence of taste receptor signaling. Thus, these brain pathways…also perform previously unidentified functions that include the detection of gastro-intestinal and metabolic signals.

Obviously, this research has some implications for the obesity epidemic. If we can somehow disrupt this dopamingeric pathway, it might be possible to erase the subtle pleasure we get from ingesting lots of energy. But I think the data also helps explain why diet sodas so often backfire, at least from a weight loss perspective. When the brain tastes something sweet, it makes a prediction that calories are coming. It waits for that dopamine signal from the stomach. But when no calories arrive – the sweetness is indigestible – that useful and predictive relationship is disrupted. It’s as if the brain can no longer trust the tongue.

Update: Yet another reason to avoid fake sugar:

Splenda is not satisfying–at least according to the brain. A new study found that even when the palate cannot distinguish between the artificial sweetener and sugar, our brain knows the difference.

At the University of California, San Diego, 12 women underwent functional MRI while sipping water sweetened with either real sugar (sucrose) or Splenda (sucralose). Sweeteners, real or artificial, bind to and stimulate receptors on the taste buds, which then signal the brain via the cranial nerve. Although both sugar and Splenda initiate the same taste and pleasure pathways in the brain–and the subjects could not tell the solutions apart–the sugar activated pleasure-related brain regions more extensively than the Splenda did. In particular, “the real thing, the sugar, elicits a much greater response in the insula,” says the study’s lead author, psych ia trist Guido Frank, now at the Univer sity of Colorado at Denver. The insula, involved with taste, also plays a role in enjoyment by connecting regions in the reward system that encode the sens a tion of pleasantness.

Although Splenda elicits less overall activity within the brain, the researchers were surprised to find that the artificial sweetener seems to inspire more communication between these regions. “Looking at the connection between the taste areas, Splenda is stronger,” Frank says. He suggests that when we taste Splenda, the reward system becomes activated but not satiated. “Our hypothesis is that Splenda has less of a feedback mechanism to stop the craving, to get satisfied.”

Comments

  1. #1 OftenWrongTed
    June 5, 2008

    Along the same lines of questioning nutritional value; how does the current epidemic of “energy-drinks”, stack up? These brews contain a large list of ingredients and otherwise smart co-workers are slamming these down several times each day. The outward performance of the workers is enhanced but what is the long-term effect of ingesting these drinks?

  2. #2 MikeD
    June 5, 2008

    This dovetails nicely with this paper by Seth Roberts detailing several experiments he did on his own weight, sleep, mood, etc. He found that consuming either fructose or sucrose dissolved in water at measured amounts during the day (and apart from meals to disconnect the sweetness and calories from a particular taste sensation), he was able to greatly reduce his hunger level and moderate his weight at will.

    http://repositories.cdlib.org/cgi/viewcontent.cgi?article=1315&context=postprints

    Seeing this and the unexpected weight gain from diet soda, I get a feeling that the conventional wisdom of diet and metabolism is about to undergo a dramatic shift.

  3. #3 Luna_the_cat
    June 5, 2008

    One thing I’ve wondered about, though I have no idea if it is related to this or not, is whether the trend in the US (and to a lesser extent, the UK) of sweetening everything more and more has been driven by the growing predominance of artificial sweeteners. I’ve lived in various countries over the last few decades — which don’t have the same diets or dietary trends, thankfully — which means that every time I go back to the US to visit family the increasing sweetness of a horrendously wide variety of foods strikes me all over again. I can barely stomach some of the stuff, now.

    The two things that might be playing into it, as I see it, are the fact that the artificial sweeteners supposedly make all that sugary taste “non-fattening” and “guilt-free” so both manufacturers and consumers indulge it. (Of course, it also doesn’t help that the actual sugar industry managed to get sugar un-blamed for obesity, somehow. How did they manage that?) The other thing this makes me wonder about is, are people unconsciously actually craving more and more snacks to bring up the calorie level to what their brain thinks the stomach is/should be getting, on a national scale? And are people driving the cycle by turning to the artificially-sweetened crap again and again, driving the cycle?

    …As a definitely unrelated side note, I have other concerns about artificial sweeteners, esp. all the ones based on phenylalanine. There was a PKU baby in my family. Normally, as I understand it, the advice is to control phenylalanine in the diet during infancy and possibly as a toddler, but after that a “normal” diet is safe enough without risking brain damage. But a “normal” diet these days contains such elevated levels of phenylalanine in things like aspartame — is it really safe for a PKU adult? Or are they actually risking long-term damage through overload? Has anyone even LOOKED at this? I have not been terribly successful at digging up information on this aspect of things, so if anyone has any, it would be gratefully received.

  4. #4 Julie Stahlhut
    June 5, 2008

    How about diet sodas consumed with meals? Some of us drink the stuff not because we’re craving a sugary snack, but because we like the taste of it with food and prefer not to add 250 calories a glass to the calorie count of whatever else we’re eating. This could be especially important when we drink diet soft drinks in restaurants that keep gigantic refills coming to the table.

  5. #5 Josh Hoisington
    June 5, 2008

    I have to comment on this, because of my relationship with soda pop…

    I think that there are definitely holes in the overarching theory, because like many people and as hinted by Julie, Diet Soda has never convinced me that it’s anything other than a pale imitation of the real stuff. I don’t even think of it as sweet. It tastes “diet-y.” So it’s not fooling my tongue or brain.

    I do drink the stuff though, not for dietary reasons but for dental ones. Sugar rots your teeth, after all.

    I could be an unusual case, but I weigh a pretty constant 125 pounds–but whenever I have a week where I just can’t stand the taste of Diet Soda and splurge on a 12-pack (or two) of Mountain Dew or something, I instantly put on 5 pounds by the end of the week. Like clockwork.

    So I don’t know if that contributes to anything, but I’ve always found the instant effect of regular soda pop on me to be interesting.

    Maybe if they made Diet Soda taste even worse, people would be less tricked into thinking they’re getting sugar? I dunno. It’s never tricked me.

  6. #6 themadlolscientist
    June 5, 2008

    IIRC, low-fat versions of foods can have a similar effect. You may be getting plenty of calories, but your brain thinks you’re not getting what you need.

    I find that most “diet” food doesn’t taste right, has a weird texture (sliminess in place of creaminess, for instance), or both. Add that to the fact that the stuff isn’t satisfying my real hunger, and……. =GAAAAAK= and 24/7 cravings to boot.

    I’m with Julia Child on this one: Eat the real stuff. Just eat less of it.

  7. #7 Blake Stacey
    June 5, 2008

    I switched to diet sodas a while back for basically the reason that Julie Stalhut pointed out (it’s the caffeine and the fizz I want, not so much the sweetness). After a few weeks, I had a regular soda again, and I found that I’d grown to prefer the diet taste. Sign me up for a functional MRI — I want to scope my insula!

  8. #8 Blake Stacey
    June 5, 2008

    I wanna see the actual journal article behind that SciAm piece, as questions spring readily to mind. First, if “the subjects could not tell the solutions apart”, what could cause a difference in their responses? Second, did the sample include people who genuinely prefer the taste of diet soda, like me? :-/

  9. #9 Julie Stahlhut
    June 6, 2008

    Diet Soda has never convinced me that it’s anything other than a pale imitation of the real stuff. I don’t even think of it as sweet. It tastes “diet-y.” So it’s not fooling my tongue or brain.

    Two comments: First: What doesn’t fool our tongues might still be fooling our brains. Second: Blake’s preference for diet soda isn’t unusual. Anecdotally, you’ll find lots of people who started drinking diet sodas and quickly lost their taste for the sugary ones. I used to laugh off the latter until it happened to me within a month of my switching to diet soda. And I’m not a heavy soda drinker — I have maybe two soft drinks a week. I usually satisfy my fizz cravings with mineral water or seltzer, either plain or laced with a little fruit juice. For caffeine, I drink coffee.

    There’s clearly a lot going on here. My comment on the study is that it’s by nature incomplete, since it’s an oversimplified model of how people consume sugar and sugar substitutes. However, in experimental science, it’s best to start with the most controlled situation first and only then add other variables. I do think it would be interesting to follow this up with more detailed simulations of how people actually drink sweet beverages, since some people seem to never be without a soft drink in hand, while others of us drink it only occasionally or only with food.

  10. #10 tara xyz
    June 6, 2008

    In terms of the difference between splenda and actual sugar, artificial sweeteners are a stronger ligand binding to the taste buds(if i remember correctly)…creating a more powerful taste…This I think is crucial to point out, in that not only are we tricking our minds with splenda, but we are fooling it with a more potent version of sweetness.

  11. #11 herbalamanda
    June 6, 2008

    I think its also important to note that artificial sweeteners are thousands of times ‘sweeter’ than sugar which probably confuses out senses even more, which is why some people prefer artificial sweeteners.

    I have also read about the fact that sweeteners like aspartame can actually have a negative effect on your nervous system and in large amounts (drinking diet soda every day for years) has been correlated with seizures and interrupted neural signals.

    Luna: I don’t think the sugar industry had anything to do with the revelation that corn syrup is actually more problem to the obesity problem than sugar. If you read “The Omnivores Dilemma” By Michael Pollan, he explores the idea of how the corn industry has taken over every portion of the food industry in the last 20 years or so, which may be more of a problem than even the artificial sweeteners, when speaking about obesity on the larger scale.

  12. #12 Blake Stacey
    June 8, 2008

    I think its also important to note that artificial sweeteners are thousands of times ‘sweeter’ than sugar which probably confuses out senses even more, which is why some people prefer artificial sweeteners.

    Well, aspartame is only about 180 times as sweet as sugar. You’d think they’d be clever enough to use just 1/180 the weight to get the same effect. . . cost-effectiveness and all. . . .

    I have also read about the fact that sweeteners like aspartame can actually have a negative effect on your nervous system and in large amounts (drinking diet soda every day for years) has been correlated with seizures and interrupted neural signals.

    Sounds like fun!

    http://www.snopes.com/medical/toxins/aspartame.asp

  13. #13 andy
    June 11, 2008

    I can tell the difference between sugared and artificially-sweetened sodas by the ‘calorie feeling’ throughout the day – that’s why I almost always go for the ones with sugar in; It feels like I might as well not be drinking anything when all I’ve got is sugar-free stuff.

    I’m not a particularly health-conscious person and my weight goes up and down according to circumstances but I’ve never been *obese*

    does all this have any bearing on the ‘sugar causes type-II diabetes’ thing? and what’s with ‘sugar-free energy drinks’ you see nowadays? no calories = no energy, right?

  14. #14 natural cynic
    June 12, 2008

    andy: does all this have any bearing on the ‘sugar causes type-II diabetes’ thing?

    Sugar doesn’t cause T2 diabetes. A positive energy balance does. In general, people who eat more sugar tend to eat more calories than they expend, which leads to obesity, which increases the risk of T2D. Another factor is the form of sugar – isocaloric amounts of sucrose and HFCS [high fructose corn syrup, the stuff used in soft drinks and many other foods] effect blood lipids so that HFCS appears to raise lipids more than sucrose, which increases insulin resistance.

    And don’t get the idea that regular soft drinks may somehow suppress appetite. Dietary studies & epidemiology demonstrate an almost perfect correlation between regular soft drinks and obesity. The seemingly paradoxical studies on artificial sweeteners is just a sideshow.

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