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Can Artificial Sweeteners Make You Hungry?

November 30, 2021 by Dr. Steve Chaney

Why Is There So Much Confusion About Artificial Sweeteners?

Author: Dr. Stephen Chaney

When artificial sweeteners were first introduced over 100 years ago, we were promised they would end obesity. We didn’t have to change our diets. We could just substitute calorie-free artificial sweeteners for sugar in all our favorite foods.

Since then, both consumption of artificial sweeteners and obesity have skyrocketed in this country. For example, in just the past 20 years:

The consumption of artificial sweeteners has increased by 54%, and…

The percentage of obese Americans has increased by 41%.

Today, over 40% of Americans are obese, and almost 10% of Americans are severely obese. That is a 4-fold increase since 1960!

Clearly, something isn’t working. Artificial sweeteners are not the magic solution we once thought they would be.

However, as I have told you before, association does not prove causation. Therefore, two important questions are:

Are we consuming more artificially sweetened foods and drinks because more of us have become obese, or…

2) Do artificial sweeteners cause obesity?

Unfortunately, hundreds of clinical studies on this topic have not provided a definitive answer. For example, when we look at studies on diet sodas:

When the studies are tightly controlled by dietitians so that the people consuming diet sodas don’t add any extra calories to their diet, the results are exactly as expected. People consuming diet sodas lose weight compared to people drinking regular sodas.

However, the results are different in the real world where you don’t have a dietitian looking over your shoulder. In these studies, diet sodas are just as likely to cause weight gain as regular sodas.

As Barry Popkin, a colleague at the University of North Carolina, put it” “The problem is that we [Americans] are using diet sodas to wash down our Big Macs and fries.” In short, people drinking diet sodas tend to increase their caloric intake by adding other foods to their diet. Even worse, the added foods aren’t usually fruits and vegetables. They are highly processed junk foods.

In other words, the suspicion is that artificial sweeteners may cause you to overeat. Various mechanisms for this effect have been proposed. For example, it has been proposed that artificial sweeteners may:

Increase your appetite.
Interfere with blood sugar control.
Increase your cravings for sweets.
Alter your gut bacteria.

Unfortunately, clinical studies designed to test these hypotheses have produced inconsistent results. So, we are left with the question:

3) Why are studies on artificial sweeteners so confusing?

A recent clinical study (AG Yunker et al, JAMA Network Open, 4(9):e2126313, 2021) sheds light on all 3 of these important questions.

How Was This Study Done?

This study was called the “Brain Response to Sugar” study. It was designed to test the hypothesis that previous studies of artificial sweeteners may have provided misleading results because they didn’t account for the sex and BMI (a measure of obesity) of the study participants.

Many previous studies had primarily enrolled male, ideal weight participants. This study hypothesized that the response to artificial sweeteners might be different in female, overweight participants.

This study recruited 76 participants from the Southern California area between July 2016 and March 2020, when recruitment was halted because of the COVID-19 pandemic. The characteristics of the participants were:

18-35 years old.
Weight stable for at least 3 months before the study.
Not taking medications and no history of eating disorders, diabetes, or other diseases.
42% male and 58% female.
37% healthy weight, 32% overweight, and 31% obese.
40% included artificial sweeteners in their diet prior to the study, 60% did not.

The study was what is called a “within-participant randomized crossover trial”. Simply put, this means that each participant served as their own control. Here is how it worked:

Each participant came to the Dornsife Cognitive Neuroimaging Center three times. They arrived at the testing center at 8 AM after an overnight fast.

- They drank either 75 grams of sucrose in 300 mL of water, enough sucralose in 300 mL of water to provide equivalent sweetness, or 300 mL of plain water at the beginning of each visit. The order in which the drinks were administered was randomized.

At 20 minutes after each drink, the participants were placed into an MRI machine shown various food and non-food images.

- Four high-calorie food images (2 sweet and 2 savory), 4 low-calorie food images, and 4 non-food images were shown to the participants in random order.

- As the images were shown, the MRI scanned the medial frontal cortex and orbitofrontal cortex, regions of the brain associated with appetite and hunger. Specifically, these are regions of the brain that affect:

- - Conditioned motivation to eat.

- - The reward value associated with food cues.

- - In addition, greater food cue reactivity in these regions of the brain has been shown to be associated with obesity.

At 125 minutes after each drink, the participants were allowed to select their meal from a buffet table, and the calories consumed was recorded.

Can Artificial Sweeteners Make You Hungry?

Here are the results of the study:

There was no overall difference in brain activity in the regions of the brain associated with appetite, hunger, and desire for high-calorie foods following the sucralose and sucrose drinks. However:

- For participants who were obese, high-calorie savory food images elicited greater brain activity in participants who had consumed sucralose than in participants who had consumed sucrose drinks. This difference was not seen in patients who were normal weight or overweight.

- For female participants, high-calorie sweet and savory food images elicited greater brain activity in participants who had consumed sucralose than in participants who had consumed sucrose drinks. This difference was not seen in male patients.

- These differences were not small. The effect of sucralose on brain activity in regions that control appetite and hunger was several-fold greater than the effect sucrose on brain activity in these regions.

- And as you might expect, the different response to sucralose and sucrose was greatest for women who were obese.

Participants consumed more calories at the buffet table after the sucralose drink than after the sucrose drink.

- There was no significant effect of weight on the differential response to sucralose and sucrose. However:

- The differential response to sucralose and sucrose was larger for female participants than for the whole group.

These results are consistent with previous studies suggesting that appetite responses to food cues might be greater in females and individuals with obesity. However, this was the first study designed to directly test this hypothesis.

The authors concluded, “Our findings indicate that female individuals and those who are obese, and especially female individuals with obesity, might be particularly sensitive to greater neural responsivity elicited by sucralose compared to sucrose consumption. This study highlights the need to consider individual biologic factors in research studies and potentially dietary recommendations regarding the use and efficacy of non-nutritive sweeteners [artificial sweeteners] for body weight management.”

[Note: You may have noticed that the authors extrapolated from their data on sucralose to all artificial sweeteners. Is this extrapolation valid? The short answer is, “We don’t know”. Most of the mechanistic studies have been done with sucralose, but some studies suggest these same effects may be seen with other artificial sweeteners.]

Why Is There So Much Confusion About Artificial Sweeteners?

It seems like a “no brainer” that zero calorie drinks and reduced calorie foods would reduce weight gain and promote weight loss. But that just doesn’t seem to happen in the real world. Why is that?

Is it psychological? Do we feel so virtuous about consuming artificially sweetened foods and drinks that we allow ourselves to splurge on high-calorie junk foods?

Or is it physiological? Do artificial sweeteners increase our appetite for high-calorie junk foods?

Unfortunately, clinical studies have not been much help. Some studies suggest that artificial sweeteners increase our appetite for high-calorie foods, while others suggest they don’t. Clinical studies are supposed to resolve questions like these. Why have they been so confusing?

Part of the problem is that some of the studies on artificial sweeteners have been too small and/or too poorly designed to provide clear-cut answers. However, even well-designed clinical studies have two fundamental flaws:

Clinical studies are based on averages. They assume everyone is the same.

- This study, and others like it, show the flaw in that assumption.

- - It appears that artificial sweeteners affect the appetite for high calorie foods more in individuals who are obese than in individuals who are normal weight or slightly overweight.

- - Artificial sweeteners also affect the appetite for high calorie foods more for females than for males.

- - What about age and ethnicity? Is the effect of artificial sweeteners on the appetite for high calorie foods affected by age or ethnicity? No one knows.

- - What about genetics? Is the effect of artificial sweeteners dependent on our genetic background? No one knows.

- - What about our microbiome? Again, no one knows.

Gold standard clinical studies only change one variable at a time. In studies of artificial sweeteners, the variable is artificial sweetener versus sugar. But we don’t eat just artificial sweeteners or sugar. We eat foods containing artificial sweeteners or sugar. Do the foods we eat alter the effect of the artificial sweeteners on appetite?

- One recent study) suggests they might. It found that consumption of sucralose plus easily digested carbohydrate (such as might be found in artificially sweetened junk foods) may increase the craving for sweets more than consumption of either sucralose or sucrose alone.

What Does This Study Mean For You?

Simply put, the initial promise of artificial sweeteners as a solution to the obesity epidemic and the alarming increase in diabetes has not been borne out by either clinical studies or real-life experience.

And I have not addressed the potential risks of artificial sweeteners in this article. However, in my opinion, something that has potential risks, no matter how small, and no proven benefit is something to avoid.

But don’t take my word for it. As I reported in a previous “Health Tips From the Professor” article, an international consortium of scientists recently reviewed all the pertinent literature and published a position paper on whether artificially sweetened beverages were of value in responding to the global obesity crisis. They concluded:

“In summary, the available evidence…does not consistently demonstrate that artificially-sweetened beverages are effective for weight loss or preventing metabolic abnormalities [pre-diabetes and diabetes]. Evidence on the impact of artificially-sweetened beverages on child health is even more limited and inconclusive than in adults.”

“The absence of evidence to support the role of artificially sweetened beverages in preventing weight gain and the lack of studies on their long-term effects on health strengthen the position that artificially-sweetened beverages should not be promoted as part of a healthy diet.”

The Bottom Line

Since then, both consumption of artificial sweeteners and obesity have skyrocketed in this country. Clearly, something isn’t working. Artificial sweeteners are not the magic solution we once thought they would be.

In recent years some studies have suggested that the reason that artificial sweeteners have failed us is that they stimulate our appetite for high calorie foods. However, this idea has been controversial. Some studies have supported it. Others have not.

Why have the clinical studies been so confusing? The study I describe in this article was designed to test the hypothesis that previous studies of artificial sweeteners may have provided misleading results because they didn’t account for the sex and BMI (a measure of obesity) of the study participants.

Many previous studies had primarily enrolled male, ideal weight participants. This study hypothesized that the response to artificial sweeteners might be different in female, overweight participants. The study found:

There was no overall difference in brain activity in the regions of the brain associated with appetite, hunger, and desire for high-calorie foods following consumption of drinks containing sucralose or sucrose. However:

- For participants who were obese, high-calorie savory food images elicited greater brain activity in participants who had consumed sucralose than in participants who had consumed sucrose drinks.

- For female participants, high-calorie sweet and savory food images elicited greater brain activity in participants who had consumed sucralose than in participants who had consumed sucrose drinks.

- These differences were not small. The effect of sucralose on brain activity in regions that control appetite and hunger was several-fold greater than the effect sucrose on brain activity in those regions.

Participants consumed more calories at the buffet table after the sucralose drink than after the sucrose drink.

- The differential response to sucralose and sucrose was larger for female participants than for the whole group.

These results are consistent with previous studies suggesting that appetite responses to food cues might be greater in females and individuals with obesity. However, this was the first study designed to directly test this hypothesis.

The authors concluded, “Our findings indicate that female individuals and those who are obese, and especially female individuals with obesity, might be particularly sensitive to greater neural responsivity elicited by sucralose compared to sucrose consumption. This study highlights the need to consider individual biologic factors in research studies and potentially dietary recommendations regarding the use and efficacy of non-nutritive sweeteners [eg, artificial sweeteners] for body weight management.”

For more details about this study and what it means for you, read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease.

Why Do Diet Sodas Make You Fat?

March 10, 2020 by Dr. Steve Chaney

Is Mixing Diet Sodas With Carbs Bad For You?

Many people, and many doctors, believe that diet sodas and artificially sweetened foods are a healthy choice. After all:

Cutting calories by drinking diet sodas and eating artificially sweetened foods should help you lose weight.

If sugar is the problem for diabetics, diet sodas and artificially sweetened foods should be a healthier choice.

On the surface, these ideas appear to be self-evident. They seem to be “no-brainers”. The truth, however, is more complicated.

When studies are tightly controlled by dietitians so that the people consuming diet sodas don’t add any extra calories to their diet, the results are exactly as expected. People consuming diet sodas lose weight compared to people drinking regular sodas.

However, as I have described in an earlier issue of “Health Tips From the Professor”, the results are different in the real world where you don’t have a dietitian looking over your shoulder. In those studies, diet sodas are just as likely to cause weight gain as regular sodas.

Why is that? The short answer is that nobody knows (more about that later). However, a recent study (JR Dalenberg et al, Cell Metabolism, 31: 493-502, 2020) suggests an unexpected mechanism for the weight gain associated with diet soda consumption. Let’s look at that study.

How Was The Study Done?

The study recruited 45 healthy young adults (ages 20-45) who habitually consumed less than 3 diet sodas a month. They were randomly assigned to three groups. The participants in each group came into the testing facility seven times over a span of 2 weeks. Each time they were given 12 ounces of one of three equally sweet tasting beverages in a randomized, double-blind fashion.

Group 1 received a sucralose-sweetened drink contained 0.06 grams of sucralose (equivalent to two packets of Splenda).

Group 2 received a sugar-sweetened drink contained 7 teaspoons of sucrose (table sugar).

Group 3 received a combo drink contained 0.06 grams of sucralose plus 7 teaspoons of maltodextrin. Maltodextrin is a water-soluble carbohydrate that does not have a sweet taste.

o Maltodextrin was used because Splenda and most other commercial sucralose products contain it along with sucralose. You need something to fill up those little sucralose-containing packets.

o This drink was included as a control. The expectation was that it would give the same results as the sucralose-sweetened drink.

Three measurements were performed prior to and following the 2-week testing period:

An oral glucose tolerance test in which participants drink a beverage containing a fixed amount of glucose. Then their blood sugar and blood insulin levels are measured over the next two hours.

o This is a measure of how well they were able to control their blood sugar levels.

A test in which they were given samples that had either a sweet, sour, salty, or savory taste. Then:

o They were asked to identify each taste and report how strong the taste was.

o MRI scans of their brains were performed to determine how strongly their brains responded to each of the tastes.

Is Mixing Diet Soda With Carbs Bad For You?

The results were surprising. The first surprise came when the investigators unblinded the results of the oral glucose tolerance test:

Blood sugar and blood insulin responses were unaffected by the 2-week exposure to sugar-sweetened drinks.

o This was expected.

Blood sugar and blood insulin were relatively unaffected by the 2-week exposure to sucralose-sweetened drinks. If anything, the control of blood sugar levels was slightly improved at the end of two weeks.

o This was a disappointment for the investigators. One of the prevailing theories is that artificially sweetened beverages alter the blood sugar response. The investigators found no evidence for that idea.

Following the 2-week exposure to the combo drinks (sucralose plus maltodextrin), blood sugar levels were unaffected, but blood insulin levels were increased. This implies that more insulin was required to control blood sugar levels. In other words, these participants had developed insulin resistance.

o This result was unexpected. Remember the investigators had included this drink as a control.

o The investigators pointed out that the insulin resistance associated with the sucralose-maltodextrin combo could increase the risk of type 2 diabetes and obesity.

Because of this unexpected result, the investigators did a follow-up study in which participants were given a maltodextrin-only drink using the same study protocol. The oral glucose tolerance test was unchanged by the 2-week exposure to maltodextrin-only drinks.

When the investigators conducted taste tests, the ability of participants to taste all four flavors was unchanged by a 2-week exposure to any of the drinks.

However, when the investigators did MRI scans to measure the brain’s response to these flavors:

A two-week exposure to the sucralose plus maltodextrin drinks reduced the brain’s response to sweet but not to any of the other flavors.

o In other words, the subjects could still taste sweet flavors, but their brains were not responding to the sweet taste. Since sweetness activates pleasure centers in the brain this could lead to an increased appetite for sweet-tasting foods.

o This might explain the weight gain that has been observed in many previous studies of diet sodas.

Two-week exposures to the other drinks had no effect on the brain’s response to any of the flavors. Once again, this effect was only seen in the sucralose-maltodextrin combination.

The investigators concluded:

“Consumption of sucralose combined with carbohydrates impairs insulin sensitivity…and…neural responses to sugar.

Insulin sensitivity is not altered by sucralose or carbohydrate consumption alone.

The results suggest that consumption of sucralose in the presence of a carbohydrate dysregulates gut-brain regulation of glucose metabolism.”

The investigators pointed out that this could have several adverse consequences. Again, in the words of the authors:

“Similar exposure combinations (artificial sweeteners plus carbohydrates) almost certainly occur in free-living humans, especially if one considers the consumption of a diet drink along with a meal. This raises the possibility that the combination effect may be a major contributor to the rise in incidence of type 2 diabetes and obesity. If so, addition of artificial sweeteners to increase the sweetness of carbohydrate-containing food and beverages should be discouraged and consumption of diet drinks with meals should be counseled against.”

Why Do Diet Sodas Make You Fat?

As I mentioned at the start of this article, there are a lot of hypotheses as to why diet sodas make us fat. These hypotheses break down into two classifications: psychological and physiological.

The psychological hypothesis is easiest to explain. Essentially, it goes like this: We feel virtuous for choosing a zero-calorie sweetener, so we allow ourselves to eat more of our favorite foods. It is unlikely that this hypothesis holds for all diet soda drinkers. However, it is also hard to exclude it as at least part of the explanation for the food overconsumption associated with diet soda use.

There are multiple physiological hypotheses. Most of them are complicated, but here are simplified explanations of the three most popular hypotheses:

The sweet taste of artificial sweeteners tricks the brain into triggering insulin release by the pancreas. This causes blood sugar levels to plummet, which increases appetite.

The sweet taste of artificial sweeteners is not appropriately recognized by the brain. This diminishes release of hormones that suppress appetite.

Artificial sweeteners interfere with insulin signaling pathways, which leads to insulin resistance.

There is some evidence for and against each of these hypotheses.

However, this study introduces a new physiological hypothesis – namely that it is the combination of artificial sweeteners and carbohydrates that results in a dysregulation of the normal mechanisms controlling appetite and blood sugar.

What Does This Study Mean For You?

Let’s start with the obvious. This is just a hypothesis.

This was a very small study. Until it is confirmed by other, larger studies, we don’t know whether it is true.

This study only tested sucralose. We don’t know whether this applies to other artificial sweeteners.

The study only tested maltodextrin in combination with sucralose. We don’t know whether it applies to other carbohydrates.

Therefore, in discussing how this study applies to you, let’s consider two possibilities – if it is true, and if it is false.

If this hypothesis is true, it is concerning because:

We often consume diet sodas with meals. If, for example, we take the earlier example of a diet soda with a Big Mac and fries, both the hamburger bun and the fries are high carbohydrate foods.

Sucralose and other artificial sweeteners are used in low calorie versions of many carbohydrate rich processed foods.

If this hypothesis is false, it does not change the underlying association of diet soda consumption with weight gain and type 2 diabetes. It is merely an attempt to explain that association. We should still try to eliminate diet sodas and reduce our consumption of artificially sweetened, low calorie foods.

My recommendation is to substitute water and other unsweetened beverages for the diet drinks or sugar sweetened beverages you are currently consuming. If you crave the fizz of sodas, drink carbonated water. If you need more taste, try herbal teas or infuse water with slices of lemon, lime, or your favorite fruit. If you buy commercial brands of flavored water, check the labels carefully. They may contain sugars or artificial sweeteners. Those you want to avoid.

The Bottom Line

Many studies have called into question the assumption that diet sodas and diet foods help us lose weight. In fact, most of these studies show that diet soda consumption is associated with weight gain rather than weight loss.

There are many hypotheses to explain this association, but none of them have been proven at present.

This study introduces a new hypothesis – namely that the combination of artificial sweeteners and carbohydrates results in a dysregulation of the normal mechanisms controlling appetite and blood sugar. In particular, this study suggested that combining sucralose with carbohydrates caused insulin resistance and reduce the ability of the brain to respond appropriately to sweet tastes.

The authors concluded: “Similar exposure combinations (artificial sweeteners plus carbohydrates) almost certainly occur in free-living humans, especially if one considers the consumption of a diet drink along with a meal. This raises the possibility that the combination effect may be a major contributor to the rise in incidence of type 2 diabetes and obesity. If so, addition of artificial sweeteners to increase the sweetness of carbohydrate-containing food and beverages should be discouraged and consumption of diet drinks with meals should be counseled against.”

If this hypothesis is true, it is concerning because:

We often consume diet sodas with meals. If, for example, we take the example of a diet soda with a Big Mac and fries, both the hamburger bun and the fries are high carbohydrate foods.

Artificial sweeteners are used in low calorie versions of many carbohydrate rich processed foods.

If this hypothesis is false, it does not change the underlying association of diet soda consumption with weight gain and type 2 diabetes. It is merely an attempt to explain that association. We should still try to eliminate diet sodas and reduce our consumption of artificially sweetened, low calorie foods.

For more details, read the article above.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.