Tricking taste buds but not the brain: Weekly consumption of artificial sweeteners changes the brain’s pleasure response to sweet treats

Originally published at Scientific American.

Do NOT EAT the chemicals. It is the #1 laboratory safety rule young scientists learn to never break and for good reason; it keeps lab citizens alive and unscathed. However, if it hadn’t been for the careless, rule-breaking habits of a few rowdy scientists ingesting their experiments, many artificial sweeteners may never have been discovered.

Perhaps the strangest anecdote for artificial sweetener discovery, among tales of inadvertent finger-licking and smoking, is that of graduate student Shashikant Phadnis who misheard instructions from his advisor to ‘test’ a compound and instead tasted it. Rather than keeling over, he identified the sweet taste of sucralose, the artificial sweetener commonly known today as Splenda.

Artificial sweeteners like Splenda, Sweet’N Low, and Equal provide a sweet taste without the calories.  Around World War II, in response to a sugar shortage and evolving cultural views of beauty, the target consumer group for noncaloric sweetener manufacturers shifted from primarily diabetics to anyone in the general public wishing to reduce sugar intake and lose weight. Foods containing artificial sweeteners changed their labels. Instead of cautioning ‘only for consumption by those who must restrict sugar intake’, they read for those who ‘desire to restrict’ sugar.

Today, the country is in the middle of a massive debate about the health implications of artificial sweeteners and whether they could be linked to obesity, cancer, and Alzheimer disease. It’s a good conversation to have because noncaloric sweeteners are consumed regularly in chewing gums, frozen dinners, yogurts, vitamins, baby food, and particularly in diet sodas.  As research delves deeper into these issues, scientists are gaining a greater understanding of how these sweet synthetic alternatives impact the brain. From engagement mechanisms of the brain’s central taste pathways, to uniquely altering the food reward-system response, we are learning that substituting one sweet taste for another by switching from sugar to artificial sweetener does not fool the brain. This brilliant organ knows the real deal even if your taste buds can’t detect the difference.

Sugar processing in the brain

The moment sugar touches your mouth a complex cascade of events is triggered involving taste, learning, memory, and reward systems in the brain.

The central taste pathway begins with your tongue, which has specialized cells that relay information about taste through cranial nerves to the brain. Taste information is then transmitted through several brain regions before arriving in the primary taste cortex, which is made up of the frontal operculum and the anterior insula. Neurons in the primary taste cortex send projections to areas associated with the brain’s primary reward-pathway located in the dopaminergic midbrain. Neurons within the midbrain then go on to innervate various brain centers that participate in the food reward response (i.e. amygdala, caudate nucleus, and orbitofrontal cortex) and release dopamine, a neurotransmitter commonly associated with reward and pleasure.

The body’s food-reward system plays a critical role in regulating eating behavior and controlling the number of calories you consume. Evolutionary survival mechanisms in the brain place emphasis on the value of high calorie foods and thus we find sugar satisfying so that we will continually seek it out.

The first bite of cupcake is always the best

Say you have a box of cupcakes. The initial bite is bliss. In that first taste, dopamine is released in the brain’s reward pathway and you get a jolt of pleasure. In addition to dopamine, the release of leptin, a hormone that regulates appetite and informs the brain when you are full, reduces activation of dopamine neurons in the midbrain, lowering the reward value of sugar. As a result, the second bite of the cupcake is less rewarding than the first and you begin to feel full with subsequent bites, hopefully stopping you from gorging yourself on the entire box of cupcakes.

What if instead you ate an artificially sweetened cupcake? Does indulging in artificially sweetened food and drink impact the central-taste and reward pathways in the brain? Functional magnetic resonance imaging (fMRI) studies have investigated this question and revealed some interesting findings.

Artificial sweeteners taste sweet but are not as rewarding to the brain as sugar

In a study conducted by Frank et al., 12 healthy women underwent brain scans and were asked to rate the pleasantness and sweetness of several different sugar (sucrose) and artificial sweetener (sucralose) drinks on a scale of 1 (‘did not like the taste’) to 9 (‘extremely enjoyable’).

Researchers found that both sugar and artificial sweetener activate the primary taste pathway in the brain by activating the frontal operculum and the insula, but only real sugar was able to elicit a significant response from several brain regions of the taste-reward system including the midbrain and caudate nucleus. This suggests that the brain’s reward pathway is conditioned to prefer a sugar, or caloric-based, stimulus.

But what happens if you routinely drink diet soda? If sweet taste is no longer a reliable measure of caloric intake because you regularly consume artificial sweeteners, does the brain’s reward response to sweet taste change? Potentially yes, and here’s why:

At the San Diego State University, researchers recruited 24 individuals for an fMRI study to look at brain activation of habitual diet soda drinkers and non-diet soda drinkers. Study participants were grouped as diet soda drinkers if they drank at least one diet beverage a week. On average, diet soda drinkers in the study consumed 8 diet beverages a week.

During the brain scan, subjects were provided with random intermittent sips of sugar (sucrose) water and artificially sweetened (saccharin) water. After each trial taste, they were asked to rate drink pleasantness and given distilled water to cleanse their palate before the next trial.

Green and Murphy found that chronic diet soda drinkers had greater overall activation in several reward processing brain regions to both real sugar and artificial sweetener, compared to the non-diet soda group. Additionally, within diet soda drinkers, the brain’s response to sugar vs. artificial sweetener was nearly identical in the orbitofrontal cortex, dopaminergic midbrain, and amygdala, suggesting regular consumption of diet soda may render particular components of the brain’s reward system incapable of distinguishing between real sugar and artificial sweetener!

Furthermore, while certain components of the reward pathway were numb to sweet taste type, researchers found that the more diet soda an individual consumed, the lower their activation was in the caudate nucleus. Thus, people that drank the most diet soda had the least activity in the caudate head region.

Taste and reward signaling in the brain is immensely complex. Research is only beginning to understand how altered brain activity with prolonged use of artificial sweeteners may impact our health long-term. While previous studies have shown an association between obesity and decreased caudate head activation during food-reward tasks, a link between artificial sweeteners altering brain activity in the caudate head and obesity has not yet been established. Future fMRI studies as well as looking at how appetite hormones, like leptin, alter the brain’s reward pathway after regular use of artificial sweeteners could further piece together this incomplete picture.

Even if you aren’t married to the clean eating fad, the take home message is that real sugar or not, moderation is key for a healthy brain-reward response. Or as Cookie Monster with his new health-motivated outlook might put it: cupcakes are a sometimes food.

Green E. & Murphy C. (2012). Altered processing of sweet taste in the brain of diet soda drinkers, Physiology & Behavior, 107 (4) 560-567. DOI:

Frank G.K.W., Oberndorfer T.A., Simmons A.N., Paulus M.P., Fudge J.L., Yang T.T. & Kaye W.H. (2008). Sucrose activates human taste pathways differently from artificial sweetener, NeuroImage, 39 (4) 1559-1569. DOI:

Image credit: Roadsidepictures (via Flickr)

Being Hangry: The neuroscience behind hunger and a sour mood

Where are our meals? The service at this restaurant is awful. We’ve been waiting for an hour and have yet to even see a glimpse of our appetizers! Those people ordered after us and they just got their food! I’m starving! Don’t tell me to relax; I’m starting to get hangry!

Eek! Sound like an all too familiar scenario? “Hanger”, the portmanteau or mash-up of the words hungry and anger describing a state of rage caused by lack of food, may actually be linked to levels of the neurotransmitter serotonin in the brain.

Be kind, consume some glucose

Photo credit: Carlos Santa Maria

Photo credit: Carlos Santa Maria

What happens to our mood when our body is running low on glucose a.k.a. sugar? Researchers at the University of Kentucky were interested in the link between low glucose levels and aggressive behavior, so they designed a devious study to investigate the sugar-mood association.

In the study, 62 college students were asked to drink lemonade containing either sugar or a sugar substitute. After drinking their randomized beverage, the students participated in a “game” where they were told that they were competing against an opponent to see who could press a button the fastest.

As it turns out, the whole thing was rigged. There was no opponent just a computer. The students were set-up from the beginning to lose about 50% of the time. The loser of each round would receive a blast of white noise in their headphones. Ouch! Additionally, before each new round, the student selected the level and duration of noise their “opponent” would receive following a loss on that round.

As students began receiving white-noise blasts after “losses”, they retaliated, as any frustrated person might do, and tried to return the favor to their opponent by matching the white-noise assault. Interestingly, researchers found that when students were provided with a sugar-substitute lemonade (no glucose) they were more aggressive, providing louder and longer noise blasts, than if they drank the lemonade with sugar. Feeling agitated? Have a glass with glucose and chill out!

How low blood sugar impacts the brain

Your brain needs fuel in order to function properly. Most often this fuel comes in the form of glucose. When you go several hours without eating, your blood sugar drops. Once it falls below a certain point, glucose-sensing neurons in your ventromedial hypothalamus, a brain region involved in feeding, are notified and activated resulting in level fluctuations of several different hormones. Ghrelin, a hormone that increases expression when blood sugar gets low and stimulates appetite through actions of the hypothalamus, has been shown to block the release of the neurotransmitter serotonin. The serotonin system is incredibly complex and contributes to a number of different central nervous system functions. One of the many hats this neurotransmitter wears is modulation of emotional state, including aggression.

Is your mood more difficult to control when serotonin is depleted?

Angry and neutral faces during the task. Brain regions impacted following serotonin depletion: vACC - ventral anterior cingulate cortex; VLPFC - ventrolateral prefronal cortex. (Passamonti et al. 2011)

Angry and neutral faces during the task. Brain regions impacted following serotonin depletion: vACC – ventral anterior cingulate cortex; VLPFC – ventrolateral prefronal cortex. (Passamonti et al. 2011)

Potentially yes, and here’s why. In an functional magnetic resonance imaging (fMRI) study, Passamonti et al. looked at how neuronal networks involved in processing aggression were altered in subjects with low serotonin levels. Nineteen healthy participants underwent brain scans on two separate days: once after consuming a tryptophan-depleting drink and again after drinking a placebo beverage containing tryptophan. Tryptophan is an essential amino acid, found in turkey among other protein sources, that is a building block for serotonin formation.  Your body does not make tryptophan on it’s own and you must get it through your diet. Don’t worry though, there’s plenty of it around! By reducing tryptophan levels, researchers were able to evaluate the effects of low serotonin levels on brain connectivity in individuals viewing angry faces.

After serotonin depletion, participants were scanned to assess brain responses to images of angry, sad, and neutral faces that were presented to them.  Participants were also asked to complete a personality questionnaire to evaluate their individual propensity for aggression.

What did they find? By reducing serotonin through tryptophan depletion, the connectivity between the amygdala and two prefrontal cortex regions, the ventral anterior cingulate cortex and the ventrolateral prefrontal cortex, was altered when processing angry faces but not sad or neutral faces.

Additionally, when looking at individuals that were more prone to aggression based on their personality questionnaires, their brain scans revealed weaker connections between the amygdala and the prefrontal cortex.  Meaning if you have a predisposition to aggression, low serotonin levels circulating in your brain may lead to altered communications between brain regions that wrangle aggressive behavior.

Angry at a restaurant? Stuck in traffic? Late for dinner and feeling a Dr. Jekyll and Mr. Hyde scenario about to unfold? It may be due to serotonin messing with your brain. Grab your emergency turkey sandwich and relax. Life is going to be okay.

DeWall C.N., Deckman T., Gailliot M.T. & Bushman B.J. (2011). Sweetened blood cools hot tempers: physiological self-control and aggression, Aggressive Behavior, 37 (1) 73-80. DOI:

Passamonti L., Crockett M.J., Apergis-Schoute A.M., Clark L., Rowe J.B., Calder A.J. & Robbins T.W. (2011). Effects of acute tryptophan depletion on prefrontal-amygdala connectivity while viewing facial signals of aggression., Biological psychiatry, PMID:

Feeling sluggish? Chew gum for a brain boost

Mona Lisa chomping some gum.

Mona Lisa boosting brain cells while chomping some gum.

Monday mornings. They drag. Getting the ol’ noodle back into work-mode, especially after a fun summer weekend, can be a tall order. Many of us head straight for the classic boost – a cup of Joe – to help combat a case of the Monday’s but some new studies suggest that chewing gum could also provide some relief by enhancing our brain’s arousal, alertness, and attention.

Om, nom, nom. Yes, we feel more alert.

In a recent study published in the British Journal of Psychology, Morgan and colleagues assessed the performance of 40 psychology undergraduate students on an auditory vigilance task while chomping on a wad of gum.

Study participants were split into two groups: (1) no-gum and (2) gum-chewing. They listened in a pair of headphones to a computerized voice reading a series of random numbers and were asked to press a computer spacebar when they identified the target sequence, an odd number followed by an even number and another odd number (i.e. 7-2-1). Reaction time and accuracy to each target-response were recorded over the 30-minute task. Following the task, participants were asked to assess how alert they felt.

Researchers found that, as the task went on, the reaction time and accuracy of identifying the target sequence declined in non-gum chewers. That makes sense. Think of doing a monotonous task, like signing your name on 300 letters, or stuffing 1,000 envelopes. You’re probably not as efficient towards the end of the task as when you started.

Alertness

Mean self-rated alertness pre and post task. Gum-chewer (dark gray); no-gum (light gray). F(1,32) = 14.25, p = .001

Interestingly, in contrast to the no-gum group, gum-chewers had a smaller decrease in performance during the later stages of the task, meaning they performed better overall. Additionally, gum chewers rated themselves as more alert compared to non-gum chewers following the test.

So working out your jaw results in better cognitive performance and a greater feeling of alertness, but how is the brain affected? Well as it turns out, gum chewing increases blood flow to the brain, providing it with more oxygen, and ultimately improving brain power. In another new study, Hirano et al. assessed which brain regions receive more blood flow while chewing gum during an attention task.

Seventeen participants underwent a 30-minute functional magnetic resonance imaging (fMRI) brain scan. fMRI is a brain imaging technique that assesses changes in cerebral blood flow, which is thought to correlate with neural activity. To assess the effect of gum chewing on alertness, subjects were put through two 10-minute periods of a visual attention task, once while chewing gum, and once without. The task required participants to press a button with their right or left thumb corresponding to the direction of an arrow that was presented to them.

Hirano and colleagues identified 8 brain regions that increased activity during performance of the task while chewing. Several of these regions correlated with alertness (premotor cortex), arousal (reticular activating system via the thalamus), and attention (anterior cingulate cortex, left frontal cortex).

fMRIRegions highlighted in yellow indicate areas of increased blood flow
during attention task and gum chewing.
Abbreviations: pm (premotor cortex), aci (anterior cingulate cortex), th (thalamus).

Chewing stimulates the trigeminal nerve, the fifth cranial nerve, which in turn sends information to the brain regions responsible for alertness. Additionally, the trigeminal nerve is known to increase heart rate, which increases blood flow to the brain.

As far as Monday mornings go, it looks like you might need to get yourself going and then chewing a piece of gum will help keep you trucking throughout the work day. Personally, I’m patiently waiting for the launch of Wrigley caffeinated gum – it could be the ultimate one-two punch for the Monday blues!

Morgan K., Johnson A.J. & Miles C. (2013). Chewing gum moderates the vigilance decrement, British Journal of Psychology, n/a-n/a. DOI:

Hirano Y., Obata T., Takahashi H., Tachibana A., Kuroiwa D., Takahashi T., Ikehira H. & Onozuka M. (2013). Effects of chewing on cognitive processing speed., Brain and cognition, PMID: