Artificial Sweeteners Myths Debunked

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The history of artificial sweeteners (AS) and debunked the claim that they have been proven to cause weight gain, the most infamous accusation against synthetic sweeteners.
SOURCE SCIENCE BASED MEDICINE
John Solokas on May 21, 2021
  The Glycemic Index of Sweeteners

Artificial sweeteners DO NOT cause weight gain

Artificial Sweeteners:-

  • do not cause Diabetes,
  • do not disrupt gut bacteria, and
  • do not cause Cancer.

If we search PubMed, we’ll find studies that support these claims. We’ll also find studies that contradict them. This makes our job more fun, although significantly more difficult – instead of simply reading titles and abstracts, we have to assess the strength of the evidence to develop an informed opinion. Lucky for you, I’m going to take care of all of it. Additionally, we’ll discuss the acceptable daily intake (ADI) of the most common AS. Sit back, relax, and let’s dive in.

In conclusion: There is no doubt that consumption of artificially sweetened beverages are better for acute glycemic response and short-term metabolic health than fully sugar-sweetened beverages,
and there is no human evidence that shows
Artificial Sweeteners consumption increases one’s risk of developing metabolic syndrome or diabetes.

Now that we know that AS have not been shown to cause fat gain, it’s time to answer another question about its metabolic effects; do AS cause diabetes? Similar to the relationship between AS and obesity, researchers have found an observational link between AS intake and diabetes (1, 2, 3, 4).

Once again, these are observational studies and not well-controlled experimental trials – yet another example of correlation vs. causation and reverse causality leading to a misinterpretation of research. This being the case, the research only conveys that people with metabolic syndrome and diabetes are more likely to consume AS (possibly in an effort to decrease sugar intake) and not that AS cause these diseases. In contrast, high quality studies have found that diet beverage consumption has no effect on metabolic disease risk (5, 6, 7).

To better understand the directionality of the link between AS intake and metabolic disease risk, let’s take a look at the studies on the impact of AS on hormones and blood sugar response. A few studies have found that AS negatively impact satiety hormones and increase blood sugar levels. This study in mice supports that AS consumption may increase energy intake by suppressing GLP-1, a hormone that makes us feel full after a meal and plays an important role in glucose homeostasis (8). And this small study of seventeen obese women found that those who drank an artificially sweetened beverage before consuming a sugary drink had 14% higher blood sugar levels and 20% higher insulin levels, compared with those that drank water before the sugary drink (9). With this study in particular, as these women had not previously consumed artificially sweetened beverages, it is important to note that AS may have different physiological effects depending on one’s age, genes, and history.

If I was trying to demonize AS – as many nutrition “experts” will do – I would end this section here and you would probably be convinced that your weight loss plateau is being caused by the Splenda in your coffee. But, in the interest of painting a comprehensive picture, we must consider the opposing argument. In fact, the majority of human studies have found that AS intake does not increase blood sugar, insulin levels, or other satiety hormones (10-21).

For instance, this randomized controlled trial of 50 people found that an intake of 2 diet sodas/day for twelve weeks had no effect on insulin response, as well as no effect on bodyweight or food intake (23). And in contrast to the previously mentioned rat study on GLP-1, this study of healthy human subjects found that AS had no effect on GLP-1 release (24).

 

In conclusion: The gut microbiota is a complex realm of human physiology. For this reason, it is the effect of Artificial Sweeteners on gut bacteria that gives me greatest pause with my personal Artificial Sweeteners consumption.
Most of the information regarding the effect of
Artificial Sweeteners consumption on the gut microbiota is speculation derived from observational research and studies performed on rodents or petri dishes.
There is a significant need for more well-designed studies in humans 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 (39).

The study of the gut microbiota is a relatively new science with far-reaching implications. It appears likely that the types and number of bacteria that reside in the gut affect many facets of health, from body composition to mood to heart and brain health.

While it is becoming increasingly apparent that the condition of our gut plays an integral part in the maintenance of our health and wellbeing, the impact of AS intake on gut bacteria is not as clear-cut. First, we know that the food we consume does have an impact on the number, structure, and activity of the bacteria in our gut (25, 26). It follows, then, that AS intake would have some effect on the gut microbiota. The question at hand is whether that effect is positive, negative, or inconsequential. Holding strong to the common theme with AS, it’s complicated.

In mouse studies, the effect of AS intake on the gut microbiota looks grim. In general, mice that are given AS experience negative changes to their microbiome, resulting in more fat gain and an impaired metabolic response to glucose, compared to their counterparts given water or sugar sweetened beverages. In some studies, it is suspected that the metabolically damaging effects are due to increased hunger and caloric intake, while in others it is speculated that the negative effects are caused directly by altered gut microbiota resulting in decreased glucose tolerance and insulin sensitivity (27-32).

Fascinatingly enough, some studies even found that AS resulted in adverse metabolic effects despite positive changes in body composition. For instance, a 2014 study found that mice fed artificial sweeteners had increased fasting glucose levels and more insulin resistance than the mice fed sugar, despite having a lower bodyweight and improved body composition (33). For people that consider their physique a reliable indicator of health, this finding is especially concerning – this particular study indicates that artificial sweeteners may have an insignificant effect on our physical appearance but, nevertheless, may cause metabolic damage. As we know from “metabolically obese, normal weight people“, it is certainly possible to look “good” on the outside but be in poor physical health (34).

However, (shocking!) not all of the research is consistent. Another study found that AS intake actually improved glucose tolerance in insulin-resistant mice and yet another study found that Stevia intake had no impact on bodyweight or glucose tolerance (35, 36).

Once again, let’s break down the two sides of the evidence. As we now know, there is a mountain of evidence showing that high intakes of AS in mice wreaks havoc on gut bacteria and results in serious adverse metabolic consequences. On the other hand, humans are not mice and most people do not consume even close to the amount of AS used in these studies. For instance, another rodent study found harmful effects on the gut microbiome, except it was with doses of AS equivalent to humans eating 165 packets of Splenda or 36 cans of diet coke per day, for 6 months! (37).

If you know anyone that consumes 6,500 cans of diet soda over the course of 6 months, he/she may have cause for concern. Otherwise, I am skeptical that AS intake in moderation, i.e. not 36 cans of diet soda a day, as a component of an otherwise well-balanced, primarily whole foods diet, will have significant harmful effects on the gut microbiota (38).

In conclusion: You can rest assured that artificial sweetener intake has NOT been shown to cause cancer. If I haven’t yet convinced you, here are some more resources that explain the history of the relationship between artificial sweeteners and cancer.

Do AS really cause cancer? Despite all of the evidence that supports the contrary, the scary myth that diet soda is a carcinogen can still be heard today at water coolers around the world. After a study was published in 70s that showed saccharin caused increased rates of bladder cancer in rats, it was claimed that AS caused cancer (40). As a result, in the 80s the FDA required that artificial sweeteners come with a warning label and saccharin was even banned in the U.S. until 2000. In Canada, it was banned until just a few years ago! (41, 42)

Not so fast, Canada. The bad news – a lot of innocent rats were killed in that study. The good news – the dosage of AS given to the rats was outrageously high, rats are not humans (in case there’s still confusion), and the carcinogenic effects, as it turns out, do not translate to humans (43). A subsequent study found no association between saccharin intake and bladder cancer in humans (44). Future studies on sucralose and stevia have concluded that they are also not carcinogenic to humans (45, 46).

Artificial sweetener acceptable daily intake

Acceptable daily intake (ADI) is the maximum amount of a compound that can be consumed daily over a lifetime that is deemed to not cause appreciable adverse health effects (50).
The ADI for the most common artificial sweeteners is 
very high. This is important to note because many of the studies I cited, especially those that showed harmful health effects, used doses of artificial sweeteners that were near or at the ADI.

Sweetener ADI

  • Aspartame 50 mg/kg/d     (21 cans of diet soda)
  • Sucralose. 5 mg/kg/d        (31 Splenda packets)
  • ACE-K 15 mg/kg/d             (30 cans of diet soda) (acesulfame K)
  • Saccharin 5 mg/kg/d         (10 Sweet n Low packets)
  • Stevia 40 mg/kg/d              (40 Stevia packets)

From Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States (United States Food and Drug Administration webpage) (51).

Although I’m sure they exist in some dark corner of the universe, nobody I have ever met consumes 20+ cans of diet soda per day. It is not a stretch to believe that while occasional AS intake may be more or less harmless, 20 cans of diet soda daily may have some negative health effects.

  Aspartame is one of the most common artificial sweeteners in use today. It is sold under the brand names NutraSweet® and Equal®. Aspartame is made by joining together the amino acids aspartic acid and phenylalanine. Amino acids are the building blocks of proteins and are found naturally in many foods.
Aspartame
is a minor source of aspartic acid, a naturally-occurring amino acid found in foods that contain protein.
The artificial sweetener aspartame (Equal, NutraSweet), which is added to many medications, diet foods and diet sodas, contains phenylalanine. Federal regulations require that any food that contains aspartame bear this warning:  "Phenylketonurics: Contains phenylalanine."
Milk
contains eight times more phenylalanine than aspartame.  you’d have to consume 97 aspartame packets or more than 17 cans of diet soda in less than 24 hours to reach the aspartame levels deemed unacceptable by the FDA ! source
An Equal sachet contains  dextrose, aspartame(1.7%), acesulfame potassium(1.2%), starch, silicon dioxide(an anti-caking agent), maltodextrin, and unspecified flavoring [2]
A Nutrasweet sachet:- dextrose with maltodextrin , aspartame

SPLENDA® is also the brand name for the ingredient sucralose(GI=0). # Sucralose isn't broken down in the body, so it has zero calories. It's about 600 times sweeter than table sugar and can be used in anything. Splenda contains a relatively small amount of sucralose, virtually all of Splenda's caloric content derives from the dextrose or highly fluffed maltodextrin "bulking agents" that give Splenda its volume. Like other carbohydrates, dextrose and maltodextrin have 3.75 kcal per gram. Sucralose is made through a patented, multi-step process that starts with sugar and converts it to a no calorie, non-carbohydrate sweetener. The process selectively replaces three hydrogen-oxygen groups on the sugar molecule with three chlorine atoms.
2018 STUDY: Sucralose, a widely used artificial sweetener sold under the trade name Splenda, is metabolized in the gut, producing at least two fat-soluble compounds, according to a recent study using rats. The finding differs from the studies used to garner regulatory approval for sucralose, which reported that the substance was not broken down in the body. The new study also found that sucralose itself was found in fatty tissues of the body.

Conclusion:

Human nutrition is complex. Every food decision is influenced by, just to name a few, biological, psychological, physical, societal, and economic cues. The specific choice to consume artificial sweeteners is made even more complicated by mixed research, conflicting expert opinions, headline-grabbing fear mongering, and logical fallacies. It’s not a black and white concept, and there is no correct answer that applies to everyone. That being said, it becomes our responsibility to consider the strength of the available evidence and our individual circumstance to make the best possible decision for our health and wellbeing. After performing a thorough cost benefit analysis, I have made my decision.

For me, the pros of artificial sweeteners:

  • increased adherence to my macronutrient/calorie goals
  • increased enjoyment of my food
  • increased diet satisfaction while limiting my intake of hyper palatable “junk foods” such as donuts, cookies, and ice cream,

outweigh the potential cons:

  • increased appetite
  • decreased sensitivity to sweetness
  • negative effects of very high doses on the gut microbiome resulting in decreased glucose tolerance

Sure, a diet without AS may technically be “healthier”, but if their intake facilitates better overall health through lower caloric intake and decreased stress and feelings of restriction, it may very well be more optimal to include them your diet. Although at this point it does not appear that artificial sweeteners are a 100% risk-free biological free lunch, they are a useful tool that, when used in a reasonable way, can help us achieve our health and body composition goals.

Sources

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Artificial sweeteners DO NOT 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:

  1. A researcher finds reports an observational link between obesity and artificial sweeteners.
  2. Then, a journalist misinterprets that claim to believe that artificial sweeteners cause obesity.
  3. Finally, to make matters even more confusing, the 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 will 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 artificial sweetener 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 (specifically aspartame) 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. In other words, people who are gaining weight or already heavy may be consuming artificial sweeteners in an effort to reduce calorie consumption. 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 DO NOT inherently cause weight gain on a physiological level.

In accordance with the laws of thermodynamics, a food that has zero 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.

Artificial sweeteners DO NOT 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 artificial sweetener 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.

Sources

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PREAMBLE

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 stomach ache or hangover, along with a strong feeling of self disgust, awaits the next day. But in the case of artificial sweeteners, sugar substitutes that tickle our taste buds 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.

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 and lab safety, 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:

  1. Non-nutritive natural sweeteners, such as stevia or monk fruit.
  2. Non-nutritive artificial sweeteners, such as saccharin, aspartame, ace K, sucralose, etc.
  3. 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 glycogen in muscles and the liver.

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.

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