The Misrepresented Physiology of Artificial Sweeteners

Calorie free but not metabolically inert

The discovery, mass production and widespread use of calorie-free artificial sweeteners has had a polarising effect on the food and dieting industries. By offering the possibility to enjoy the sensation of sweetness and, simultaneously, evading the direct effects of excessive calorie consumption, diet soda and calorie-free snacks were once considered a promising strategy to address the global obesity epidemic. Yet, after all these years, the numbers don’t seem to add up. If replacing processed sugars with artificial sweeteners actually helped with weight management, we would be able to detect an effect at the population level. Several longitudinal and cross-sectional studies, in contrast to what had been anticipated, found that substituting sugar with sweeteners, particularly in the form of diet soda, is not associated with better health outcomes. To complicate matters further, some studies have found a link between the consumption of diet soda and the prevalence of obesity and other metabolic disorders.

Despite the lack of supporting scientific evidence, artificially sweetened products are often perceived as healthier alternatives to traditional sugar-filled foods. Today, we even have our choice of sweetener. The market is flooded with foods and beverages containing sucralose, aspartame, saccharin, acesulfame potassium, neotame and advantame. And as long as these products continue to sell, profits will be made off our misguided fear of calories. If we are to implement effective weight management strategies with the aid of calorie-free sweeteners, it is critical that we better understand their physiological effects on the body.

Too much sugar is a bad thing, but are we any better off using artificial sweeteners. (Photo Source: feelphotoz via Pixabay)

How Artificial Sweeteners Work

What I find most interesting about artificial sweeteners is that even though they are a chemically diverse group of compounds, they share a common mechanism of action. All sweeteners chemically mimic sugar by binding and activating the subunits that make up our sweet taste receptors. Our brain then decodes this molecular interaction, resulting in the perception of sweetness. When compared by weight, artificial sweeteners are actually hundreds to tens-of-thousands of times sweeter than sugar. The thought alone that we can synthesise food additives that are so much more potent, physiologically, than anything that exists in nature is fascinating. However, it does raise questions about how our body tolerates something that it would never have encountered in our evolutionary past. Various lines of research have looked into the physiological responses of our body to calorie-free sweeteners, each of which can partially explain why their consumption does not necessarily lead to benefits for weight management.

(1) Insulin & Sweet Taste Receptors in the Gut

While our conscious perception of sweetness is derived primarily from taste receptors on the tongue, there are also sweet taste receptors in our digestive tract. These “taste” receptors are responsible for the release of signalling molecules known as incretins, which circulate in the bloodstream and, in turn, stimulate insulin release from the pancreas. The reason behind this is fairly simple. When we consume sugar, insulin is required both to store energy away for later use (as glycogen and fat) and to regulate our blood sugar level. In other words, incretins give your body a head start in preparing for an upcoming sugar spike.

But what happens when you consume artificial sweeteners? Similarly to sugar, artificial sweeteners activate taste receptors in your gut, causing the release of incretins and insulin. So, your body initially responds to artificial sweeteners the same way it would to sugar. However, artificial sweeteners do not actually deliver on their promise of calories because they are, for the most part, not absorbed into the bloodstream. At least in animal studies, the consumption of artificially sweetened diets has been shown to increase adiposity (fat deposition), drive hyperinsulinemia (insulin spikes) and cause insulin resistance during diet-induced obesity. This increase in body fat is in agreement with the well-established association between fat storage and insulin secretion.

(2) What Does Sweetness Mean to the Brain?

Sweet taste receptors in the gut clearly play a major role in determining the post-absorptive outcomes of sugar consumption. But what role does our perception of sweetness play in digestive processes? What happens when our expectations of food are not matched by their nutritional content? According to animal studies, there are notable differences when glucose and calorie-free sweeteners are consumed regularly. Compared to rats that consume a diet sweetened with sugar, those that consume an artificially sweetened diet gain more weight and more body fat, are less able to compensate for pre-meal calorie consumption, and display both hyperglycemia (high blood sugar) and a reduced thermic response when they eat a novel meal. A valid explanation for these differences is that when glucose is consumed regularly, sweetness reliably predicts calorie intake, whereas when artificial sweeteners are consumed, calories can not be predicted through sweetness. In turn, this leads to disruptions in the learned responses elicited by sweet taste reception, rendering the body less efficient in regulating blood sugar.

From a cognitive and behavioural perspective, artificial sweeteners and sugar have different effects on food reward pathways. There are two branches of food reward, the sensory branch and the post-ingestive branch. Eating sugar initially activates the sensory branch, which includes the classic mesolimbic reward pathway (responsible for the hedonic experience of feeding) and the gustatory information pathway (responsible for our taste perception). Following the absorption of sugar across the intestinal wall, a second wave of food reward is mediated by the hypothalamus. The hypothalamus is considered the master regulator of feeding behaviour, taking into consideration all the nutrients in the bloodstream. When artificial sweeteners are consumed, however, this second wave of food reward is lost due to the underwhelming level of circulating nutrients. This is thought to drive an incomplete satisfaction from food that can increase appetite and further promote feeding behaviour.

(3) The Gut Microbiome: Sugar Vs. Artificial Sweeteners

The gut microbiome is no longer considered a passenger in our body, but rather, a metabolically active contributor to physiological processes. As such, our capacity to maintain a healthy gut is a contributing factor to the development of metabolic and lifestyle diseases. Artificial sweeteners cannot be fermented by bacteria and a large body of scientific evidence has highlighted their antibacterial properties. Hence, regular consumption of sweeteners can lead to changes in the composition of our gut microbiome, but not necessarily for the better. While this line of research is still in its infancy, current research suggests that artificial sweetener-induced changes to the gut microbiome can result in poorer glucose sensitivity.

Where Do We Go From Here?

It’s clear that calorie-free artificial sweeteners have not lived up to the hype surrounding them with regard to their potential benefits for weight loss. While more research is still needed to fully understand how they affect the human body, cutting calories through sugar substitutes does not appear to be an effective strategy for achieving better health. At the very least, it appears as if the long-term metabolic and cognitive changes associated with regular consumption of sweeteners will offset any potential benefits of a zero calorie meal today.


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