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Artificial Sweeteners: A Bitter Truth?

Posted on 25 January 2023

In a world in which sugar has become the main dietary enemy to public health, artificial sweeteners have risen. They’ve made their way into a large swathe of our foods – even foods in which we wouldn’t expect to find them, such as bread. It’s easy to see the appeal of these substitutes for sugar. They taste similar to sugar but contain few to no calories, don’t raise blood sugar, and don’t rot your teeth – or at least, that’s what many of us believed.

Photo by Brett Jordan on Unsplash

However, both the scientific and public view of artificial sweeteners as a guilt-free alternative to sugar is quickly deteriorating. There have been doubts about the safety of these food additives for decades, but many health organisations still maintained that, for diabetics and people seeking to lose weight, artificial sweeteners could be a valuable substitute for sugar. Things took a turn last year (2022) when the WHO put out new draft guidelines on sweetener use. These guidelines paint a darker picture – after reviewing hundreds of studies, the WHO concluded that artificial sweeteners should not be used as a way of preventing long term weight gain or to reduce diabetes risk. On the contrary, they found consistent evidence that these additives raise blood sugar and increase risk of diabetes, heart disease and long term weight gain. But how does something with negligible calories raise your blood sugar? Let’s take a tour of some of the more recent studies that have been done, and what they found.

How bad are artificial sweeteners? Some recent research.

First, let’s look at two studies published last year, both looking at the same study population: the NutriNet-Santé cohort. This is a sample of over 100 000 French adults who were followed up for a median of 7.8 years between 2009–2021. Every 6 months, on 3 random days, researchers made records of participants’ diets over 24 hours. 

The first of these studies, published in March, found that people who consumed more than the median level of artificial sweeteners had a 13% increased risk of developing cancer compared to people who did not consume any sweeteners. When they looked at specific types of cancer, they found that high artificial sweetener consumption was particularly associated with breast cancer (22% increased risk) and to other cancers related to obesity in general (15% increased risk). In other words, artificial sweetener consumption was associated with cancer, and this is probably due in large part to its association with obesity, a risk factor for cancer, rather than any direct carcinogenic effect.

The second study, which was published in September, found a similar trend for cardiovascular diseases: a 9% increase in risk for people consuming more than the median compared to people who consumed none. That risk doubled when looking at diseases affecting blood flow to the brain specifically.

A table showing the hazard ratios for for cardiovascular diseases for people consuming artificial sweeteners above the median intake. The hazard ratio refers to the rate at which people develop a condition relative to the people who consume no artificial sweeteners. Thus a hazard ratio of 1.09 means that people with above median artificial sweetener intake were 9% more likely to develop cardiovascular disease when compared with non-consumers.
Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort

It’s still uncertain exactly how artificial sweeteners could be increasing the risk of these diseases, but researchers in both cases point to the possible metabolic effects of these additives. Previous studies have suggested that artificial sweeteners increase the risk of metabolic syndrome – a deadly combination of high blood sugar, obesity and high blood pressure. This in turn can increase the risk of a whole host of age-related diseases.

Both of these studies were large, powerful studies that took relatively detailed dietary records into account, including participants’ consumption of processed foods. However, they still suffer from the same drawback as any observational study – people who consume more artificial sweeteners by choice also differ in other ways to people who avoid them. For example, they are more likely to be diabetic already (it might be why they’re choosing artificial sweeteners instead of sugar in the first place!). Even though the researchers took this and other factors like diet, exercise, age and education into account, it’s impossible to perfectly control for everything. The only way to remove these confounding factors from the equation is to randomly assign people to consume artificial sweeteners and see what happens. Fortunately, those studies have also been done.

Is it all in the Gut?

In this study, also from September last year, researchers randomised 120 adults into six groups. For two weeks, participants took daily sachets containing either glucose (sugar) alongside one of four artificial sweeteners in varying quantities, glucose by itself, or no supplement. So, when participants are randomly assigned artificial sweeteners, do they fare worse health-wise? 

A graphical summary of the study elements discussed here.
Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance

The answer seems to be yes, at least in the short term – but the specific consequences depended on the type of artificial sweetener consumed. Participants who consumed sucralose or saccharin fared significantly worse in a glucose tolerance test – their blood sugar increased more after consuming sugar when compared to the control groups. As you might remember from earlier, this is a stepping stone on the road to diabetes, metabolic syndrome and many other diseases.

The researchers also looked at how different sweeteners affected the bacteria in the gut and their ability to carry out their different roles within the digestive system. They found that all of the sweeteners were associated with altered function of the gut bacteria, but in different ways, and depending on how much of the sweetener they consumed. For example, saccharin was associated with changes in pathways used by bacteria to break down glucose, while stevia seemed to affect the synthesis of fatty acids.

The study goes into much more detail about these associations, as well as how participants’ individual gut microbiome features correlated with their response to artificial sweeteners. The take-home message is that artificial sweeteners in quantities within the recommended daily intake can alter the function of gut bacteria, which may lead to a reduced ability to control blood sugar. Does this lead to an increased risk of diabetes in the long term? We don’t know for certain, but it’s certainly one mechanism that could explain the associations described in the observational studies discussed earlier.

In the study, participants consumed artificial sweeteners alongside glucose. Some previous research suggests that the reduced ability to control blood sugar only occurs when artificial sweeteners are combined with carbohydrates in this way, and not when sweeteners are consumed alone. We need more, longer-lasting studies to confirm this, but whether it’s a diet drink with your meal or an artificially sweetened sandwich, the sweetener+carb situation is arguably still relevant to most people who regularly consume these sweeteners.

Taste matters

It looks like the effects of artificial sweeteners on the gut bacteria are an important contributor to their suspected health impact. However, there’s another interesting theory about why artificial sweeteners could be bad for you, and it hinges the very thing they are designed to do: taste sweet. 

Artificial sweeteners are very sweet. For a given concentration, aspartame is 200 times sweeter than sucrose (the main component of white sugar), sucralose is 600 times sweeter, and advantame is 20 000 times sweeter. Artificial sweeteners achieve this sweetness by activating the same taste receptors as sugar (surprisingly, many also activate bitter taste receptors). 

Unfortunately, these taste receptors aren’t just responsible for your sense of taste. They are found not just in the mouth, but throughout the digestive system and even outside the digestive system. While you may not be able to taste what’s in your intestines the way you can taste what’s in your mouth (probably for the better), these taste receptors play a role in controlling your gut motility and metabolism according to the foods you eat. Through the release of hormones, they influence your appetite and blood sugar in response to the level of sweetness they are sensing. This means that eating artificial sweeteners can have some of the same metabolic effects as eating sugar, including release of the blood sugar-lowering hormone insulin, even when no sugar has been consumed. Higher levels of insulin in the blood can eventually lead to insulin resistance, making it harder for the body to control real increases in blood sugar.

Still better than sugar?

Photo by Alexander Grey on Unsplash

Based on an increasing pile of evidence, it seems as though artificial sweeteners are far from the guilt-free alternative to sugar once promised. Studies suggest that they contribute to the development of diabetes, cardiovascular disease, obesity-related cancer, disrupt the gut microbiome and promote weight gain – but sugar does all of these things as well. If artificial sweeteners are no angel, are they at least preferable to the devil?

Given that sugar must be consumed in far greater quantities to achieve the same level of sweetness, and carries far more calories than artificial sweeteners, one would think that an artificially sweetened diet would be preferable to a sugar-sweetened one. This does seem to be supported by studies comparing specific foods and drinks. For example, this meta analysis of 34 studies found that sugar- sweetened beverages were associated with a 27% increase in type II diabetes risk, compared with a 13% increase for artificially sweetened beverages. Artificially sweetened beverages were also associated with slightly less cardiovascular disease and mortality – but not by much. However, we are far from having enough data to answer this question definitively. There are many different sweeteners that carry varying risks, and as we already touched on, these risks probably depend on what’s being eaten with the sweeteners.

Now let’s rewind all the way back to the WHO meta-analysis mentioned at the start of this article. Though it warns of the potential dangers of long term consumption, the study did find a case in which artificial sweeteners carry a clear benefit. If people attempted to lose weight by substituting sugar for artificial sweeteners, they were generally more effective at reducing calorie intake and losing weight in the short term than those who were not consuming artificial sweeteners. However, continued consumption of these sweeteners might eventually lead to an increase in weight.

So, while artificial sweeteners could help cure your sugar addiction, it really does seem as though they could be doing almost as much harm as sugar in some circumstances. This story is far from over and more research is needed to figure out exactly how bad they are, and for whom. Observational studies could easily have overestimated the risks, but if no one needs artificial sweeteners in their diet, why take a risk?

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    Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis:

    Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study:

    Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort:

    Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance:

    Intense Sweeteners, Taste Receptors and the Gut Microbiome: A Metabolic Health Perspective:

    Sugar- and Artificially Sweetened Beverages Consumption Linked to Type 2 Diabetes, Cardiovascular Diseases, and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies:

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