Artificial Sweeteners- A Free Lunch, or an Obesogenic Carcinogen? What 80+ Studies Say.

NOTE - This article first appeared in Science Based Medicine.

Key Takeaways

Artificial sweeteners were created in the late 1800’s and today they can be found in nearly every food product imaginable.
Although they contain 0 calories, some research indicates that artificial sweeteners may pose a serious health risk.
It has been accused that artificial sweeteners cause weight gain and diabetes, disrupt gut bacteria, and even cause cancer.
Weight gain - Observational links between artificial sweetener intake and weight gain are highlighted in the media but can largely be explained by mistaking correlation for causation and the failure to recognize reverse causality. There are ZERO well controlled, experimental studies that show a causal link between artificial sweeteners and weight gain.
Diabetes - Consumption of artificially sweetened beverages are better for acute glycemic response and short-term metabolic health than fully sugar-sweetened beverages. There is no human evidence that shows artificial sweetener consumption increases one’s risk of developing metabolic syndrome or diabetes.
Gut Bacteria - Most of the information regarding the effect of AS consumption on the gut microbiota is speculation derived from observational research and studies performed on rats or in cell cultures. There is a significant need for more well-designed studies to assess this topic and, until that time, it is advised to proceed with caution - consume artificial sweeteners in moderation or not at all if you have concerns about the health of your gut microbiota.
Cancer - Counter to the findings of a study in the 80’s that linked aspartame with bladder cancer in mice, artificial sweeteners do NOT cause cancer.
Artificial sweeteners are not “healthy”, per se, and technically your diet may be better off without them. But for many, myself included, the pros of AS intake - increased adherence to macronutrient/calorie goals, increased enjoyment of food, and overall better physical and emotional health - outweigh the cons - potential increased appetite, decreased sensitivity to sweetness, and negative effects of very high doses on the gut microbiome resulting in decreased glucose tolerance.

Full Story

Many awesome experiences come tethered to inevitable baggage. Take binge drinking, for instance, or eating a dozen chocolate donuts in one sitting. An overflow of dopamine and hedonistic bliss in the moment, but a fiercely unpleasant hangover or stomach ache, along with a strong feeling of self disgust, awaits the next day. But in the case of artificial sweeteners, sugar substitutes that tickle our tastebuds without the massive caloric load that is inherent of “real” sugar, we can have our stevia-sweetened cake and eat it too. Or can we?

On the surface, artificial sweeteners seem too good to be true. Let’s consider the most popular artificially sweetened product – diet soda. Though diet soda has an eerily similar taste to regular soda, the full sugar version contains with an extra 140 calories and 40 grams of sugar per 12oz serving, packing a serious, metabolically damaging punch. Artificial sweeteners deliver a sweet taste sans the calories and sugar but have been very much demonized in the media as a cause of all maladies, from obesity and metabolic syndrome to cancer. As we know, there is no such thing as a free lunch in biology; so, what’s the catch? Are artificial sweeteners the exception to the rule, or are they secretly making us sick and overweight? Let’s find out.

Background

The story of artificial sweeteners begins in 1878 after German researcher Constantin Fahlberg “accidentally” stumbled upon the sweet taste after licking his finger while working in his lab. He went on to break the first rule in every science class and decided to lick every beaker and vial in his lab in a radical yet effective attempt to discover the source. After this severe compromise of hygiene, he identified the sweet substance chemicals and would later produce the first commercially available artificial sweetener, saccharin (1).

Today, the artificial sweetener industry has BOOMED and calorie free sweeteners can be found in nearly every food product imaginable. Sugar-free versions of any sweet fare you can imagine, including barbecue sauce, syrup, and even powdered sugar itself, are readily available on the local supermarket shelf.

As Fahlberg discovered and others would go on to study, artificial sweeteners have a taste practically indistinguishable from sugar because, on a chemical level, the two share a similar molecule shape. The most common artificial sweeteners fall into three categories:

Non-nutritive natural sweeteners, such as stevia or monk fruit.
Non-nutritive artificial sweeteners, such as saccharin, aspartame, ace K, sucralose, etc.
Sugar alcohols, such as erythritol, xylitol, etc. (anything that ends in “ol”).

Despite their molecular similarities, they are processed completely differently than sugar in the body - while most artificial sweeteners are calorie-free and pass through the digestive tract without providing energy, the calories in “real” sugar are converted to fuel or stored for later use as body fat, or as muscle and liver glycogen.

Until recently, most accepted that it was just this simple; artificial sweeteners offer the same sweet taste as sugar without any of the consequences. That was, of course, until studies began to show otherwise. The primary headline about artificial sweeteners was not “Magic substance that will help you lose fat and stave off disease - more scientists need to start licking their lab equipment”, but more along the lines of “Artificial sweeteners cause cancer” and “Artificial sweeteners make you eat more and gain weight.” The 4 most common and alarming accusations against artificial sweeteners include:

1. Artificial sweeteners cause weight gain

2. Artificial sweeteners cause diabetes

3. Artificial sweeteners disrupt gut bacteria

4. Artificial sweeteners cause cancer

These potential side effects sound terrifying, and, if the accusations are true, no self-respecting health nut would be caught dead consuming such a substance. If you have already tossed all of your Splenda in the trash, I wouldn’t blame you. But before you take the can out to the curb and fully swear off on artificial sweeteners, let’s assess each accusation and see if it holds up under the scrutiny of the available body of research.

First, 2 Quick Concepts

To assess the association between artificial sweeteners and weight gain or weight loss, we must first explore the notions of correlation vs. causation and reverse causation. Bear with me, you don’t need a degree in statistics to keep reading - these concepts are simpler than they sound.

Correlation vs. Causation

A correlation is a relationship between two or more things, while causation is the act of causing something. For example, take the incidental fact that both ice cream sales and murder rates increase in the summer. The correlation is the unrelated increase of both ice cream sales and murders in the summer. A causation would be the unfounded claim that ice cream consumption causes one to commit murder -this is obviously not the case, but a textbook example of mistaking correlation for causation. This is the exact mistake most people make when interpreting studies about artificial sweeteners.

2. Reverse Causality

Reverse causality essentially means that instead of X causing Y, Y causes X. In our case, take the example of increased artificial sweetener intake being associated with increased weight gain. Observational studies do not indicate a direction of causality, but this does not prevent people from assuming one. Though it is more than likely that those that are already overweight seek out zero calorie products to try to lose weight, people misinterpret the association to claim that artificial sweeteners cause weight gain.

An understanding of these 2 concepts will help us understand the majority of studies that are cited in the damnation of artificial sweeteners. With the boring definitions out of the way, let’s get to the good stuff.

1. Artificial Sweeteners Cause Weight Gain

If you were to google “artificial sweeteners and obesity”, you would find a ton of websites, news articles, and even research studies that claim artificial sweeteners cause weight gain. As we know, Dr. Google is not a reliable source. This myth has only spread so far and wide because of two factors; misinterpretation of the research and sensationalism in the media. It is a slippery slope:

A researcher finds reports an observational link between obesity and artificial sweeteners.
Then, a journalist misinterprets that claim to believe that artificial sweeteners cause obesity.
Finally, to make matters even more confusing, mainstream media not only misinterprets but sensationalizes the aforementioned studies, with headlines such as “Artificial Sweeteners Linked to Weight Gain and Type 2 Diabetes” and “Your Artificial Sweetener May Be Giving You a Gut” (2, 3).

As you can see, just because headlines on your 5 o’clock news turn a lot of heads does not mean that they are well-substantiated.

The body of research on artificial sweeteners is a mixed bag. Many observational studies, including the first ones to pop up after a quick Google search, link artificial sweeteners to weight gain and unfavorable health outcomes (4, 5, 6, 7, 8). While mis-interpretation of observational studies casts artificial sweeteners in an unfavorable light, to date, there are ZERO well controlled, experimental studies that show a causal link between artificial sweeteners and weight gain. These studies may have some eye popping, clickbait titles, but NOT ONE shows causation in either direction.

Extrapolating from observational studies that “artificial sweeteners cause weight gain” is likened to claiming that ice cream consumption causes murder – just because both ice cream sales and murders increase in the summer does not mean downing a pint of moose tracks will make you kill your neighbor.

The majority of studies, on the other hand, link artificial sweeteners to no change in weight (9, 10, 11, 12) or to weight loss (13, 14, 15, 16, 17, 18, 19, 20, 21, 22). In many cases, the consumption of artificial sweeteners reduces overall sugar and calorie intakes, making it easier to lose or maintain weight. This calorie reducing effect of artificial sweeteners holds up in well designed studies and it appears that AS intake is an effective weight loss strategy for many people. For instance, this 2006 meta-analysis that only considered randomized controlled trials that assessed energy intake for at least 24 hours found that artificial sweetener consumption resulted in a daily average calorie intake reduction of 10% (23). And this 2012 experimental study found that when replacing regular soda in the diet, diet soda had the same weight-loss inducing effects as water (24).

Furthermore, the researchers behind this study had overweight and obese people consume either a quarter gallon of water, milk, regular soda, or diet soda every day for 6 months. By the end of the study, those in the diet soda group weighed 17–21% less, had 24–31% less belly fat, 32% lower cholesterol levels, and 10–15% lower blood pressure, compared with those in the regular soda group (25).

As you can see, the observational links between artificial sweetener intake and weight gain that the media loves to promote can largely be explained by mistaking correlation for causation and the failure to recognize reverse causality. Now that we have explained the faulty link between artificial sweeteners and weight gain or loss, let’s dive a little deeper into the actual mechanisms that may cause artificial sweeteners to impact weight.

To simplify matters, let’s break down the accusation that “artificial sweeteners cause weight gain” into 2 sub-sections:

Artificial sweeteners inherently cause weight gain on a physiological level.

In accordance with the laws of thermodynamics, a food that has 0 calories cannot possibly cause weight gain. If a person consumed only artificial sweeteners and water, he/she would eventually starve to death. Unless they are a substance created by black magic or witchcraft and are able bypass the laws that govern the universe, artificial sweeteners don’t directly cause weight gain in any capacity.

2. Artificial sweeteners cause weight gain through downstream effects, such as by increasing appetite or by decreasing our sensitivity to sweetness and making us crave sugary foods.

This argument is much more interesting and requires that we delve into the research. Because artificial sweeteners taste sweet but do not contain calories, it has been postulated that they “trick” the brain into seeking out high-sugar, calorically dense foods in order to compensate for the lack of energy provided by the sweeteners (26).

It has been demonstrated in multiple studies - some in humans, some in rats - that consumption of artificial sweeteners can increase feeling of hunger (27, 28, 29, 30, 31, 32). For instance, this study showed that after exercise, those that drank either a sugar sweetened beverage or an artificially sweetened beverage consumed more calories at their next meal than those that drank water (33). And this study in rats showed that those that were given artificially sweetened beverages ate more calories compared to a group given sugar sweetened beverages. The authors explain that a possible mechanism may be that consumption of noncaloric sweet beverages either increases food intake or decreases energy expenditure (34).

It makes sense - if you ever want to get hungry quickly (i.e. before a Thanksgiving dinner or going out for ice cream), just consume a sweet such as candy or soda. The hyper-palatability of these foods tend to have an appetite inducing effect, and I suspect that this is the cause for the subsequent increased caloric consumption observed after artificial sweetener intake.

However, multiple studies support that consumption of artificial sweeteners either decrease or have no effect on subsequent energy intake or feelings of hunger (35). This study showed that artificial sweetener consumption did not impact subsequent energy intake or feelings of hunger and this review found that aspartame consumption is not associated with increased food intake (36, 37). Additionally, this 2020 study suggests that consumption of a stevia sweetened beverage, compared to water, before a meal may reduce appetite and energy intake, without affecting blood sugar or other metabolic markers (38).

One of the best explanations of artificial sweetener’s effect on food intake is the following excerpt from researcher Qing Yang:

“Lastly, artificial sweeteners, precisely because they are sweet, encourage sugar craving and sugar dependence. Repeated exposure trains flavor preference. A strong correlation exists between a person’s customary intake of a flavor and his preferred intensity for that flavor. Systematic reduction of dietary salt or fat without any flavorful substitution over the course of several weeks led to a preference for lower levels of those nutrients in the research subjects. In light of these findings, a similar approach might be used to reduce sugar intake. Unsweetening the world’s diet may be the key to reversing the obesity epidemic (39).”

Because repeated exposure does train flavor preference, it certainly follows that consumption of artificial sweeteners could lead to increased sugar consumption (40). This may result in increased consumption of calorically dense foods and lead to excess energy intake.

In short, the effect of artificial sweeteners on appetite and food preference is complicated. Though AS consumption may decrease sensitivity to sweetness and increase sugar cravings for some, it appears that the exact opposite is true for others. At this point, it is unlikely that artificial sweetener intake directly increases appetite or energy intake in healthy humans and one’s behavioral response (i.e. higher or lower appetite, more or less cravings, etc.) seems to be dependent on the context and the individual.

Wrap Up - To Be Continued…

I had intended to cover artificial sweeteners in one post, but my research efforts quickly turned into a meta-analysis-esque project. For an analysis of the next 3 accusations against AS intake (cause diabetes, disrupt gut bacteria, cause cancer), plus my overall recommendation and a breakdown of my personal consumption and, tune in next week for Artificial Sweeteners- A Free Lunch, or an Obesogenic Carcinogen? What 80+ Studies Say. Part TWO. In the meantime, (and SPOILER ALERT) - I don’t think you have much to worry about - enjoy your diet soda and stevia packets in peace.

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