Zero Calories... But Zero Effect?
Updated: Aug 26
Can something with virtually no calories still influence our biology?
Walk down any supermarket aisle and you'll quickly notice a common theme. Drinks labelled zero sugar, diet or no added sugar (and heavily dicounted may I add!) have become the norm rather than the exception. Whether it's an energy drink before the gym, a diet cola with lunch or a flavoured water on the commute home, many of us choose these products believing they are a healthier alternative because they contain few, if any, calories.
It's understandable that this might be a sensible option. For years, nutrition conversations have revolved around calories. If something contains fewer calories, it is often perceived as the better choice for weight management and overall health. As a result, non-nutritive sweeteners such as sucralose, saccharin, aspartame and stevia have become common ingredients in thousands of products designed to provide sweetness without the energy.
Calories tell us how much energy a food contains, but they don't tell the whole story. They don't explain how that food interacts with the body, how it's digested, or how it might influence processes beyond energy intake. Increasingly, researchers are asking whether ingredients that contribute virtually no calories may still affect our physiology in other ways.
Interesting side note!
Are calories on food labels actually accurate?
Yes, BUT, they're still an estimate. Most people imagine the calories on a food label are measured directly from the food itself. In reality, the food is first analysed for its carbohydrate, protein, fat and alcohol content, and these are then converted into calories using standard values known as the Atwater factors (4 kcal/g for carbohydrate and protein, 9 kcal/g for fat and 7 kcal/g for alcohol). These values were originally developed by measuring how much energy foods release when burned in a device called a bomb calorimeter.
The thing ism humans are not bomb calorimeters.
Our bodies digest, absorb and process food in a much more complex way. The amount of energy we actually obtain can vary depending on the food itself, how it's prepared, how well we digest it and even the microbes living in our gut. For example, whole nuts often provide fewer usable calories than their labels suggest because some of the fat remains trapped within the food's structure and passes through the digestive system. On the other hand, cooking generally makes food easier to digest, meaning we may absorb more energy than we would from the raw version.
So while calorie labelling is an incredibly useful tool, it's still an estimate rather than an exact number. Another reminder that nutrition is rarely as simple as a single figure on a food label. Read this great article about Dave protein bars here)
One area receiving growing attention is the gut microbiome. Home to trillions of microorganisms, the gut microbiome plays an important role in digestion, immune function and metabolism. While we know that dietary fibre and whole foods can shape the composition of our gut bacteria, scientists are now asking whether artificial sweeteners might also influence this complex ecosystem.
A landmark study published in Cell in 2022 explored that question. Rather than asking whether artificial sweeteners are "good" or "bad", the researchers investigated whether commonly used sweeteners could alter the gut microbiome and whether those changes might influence glucose regulation. This is an important distinction because of focusing solely on calories, the researchers were interested in understanding how foods and ingredients interact with the body's biology.
What the research set out to investigate
Artificial sweeteners have been used for decades and are considered safe when consumed within the Acceptable Daily Intake (ADI) established by regulatory authorities (in the UK, Europe and the states) . Previous studies started to suggest that some sweeteners might influence the gut microbiome, however previous evidence had been inconsistent and often limited by the study's design.
The researchers wanted to answer three main questions:
Do commonly consumed artificial sweeteners alter the composition or function of the human gut microbiome?
If changes do occur, do they influence the body's ability to regulate blood glucose?
Finally, are these effects driven by the sweeteners themselves, or are they simply associations with no biological significance?
These questions move beyond the traditional discussion surrounding calorie intake and begin to explore whether ingredients that contribute little or no energy may still have measurable physiological effects.
How was the study conducted?
The study recruited 120 healthy adults who did not routinely consume artificial sweeteners.
Participants were randomly assigned to consume one of four commonly used sweeteners:
Saccharin
Sucralose
Aspartame
Stevia
Each participant consumed their allocated sweetener daily for two weeks, with all doses remaining below the internationally ADI. Throughout the study, researchers collected stool samples to analyse changes within the gut microbiome and performed glucose tolerance tests to assess how effectively participants regulated blood sugar.
What made this study stand out was that rather than simply observing changes in humans, the researchers transplanted gut bacteria from selected participants into germ-free mice. These mice were raised without their own microbiome, allowing scientists to investigate whether any observed metabolic changes could be transferred via the gut bacteria alone. This approach helped move the findings beyond association and closer towards understanding potential cause and effect.
What the researchers found
The results challenged the assumption that all artificial sweeteners behave in the same way. Different sweeteners produced different biological responses. Saccharin and sucralose were associated with measurable changes in the gut microbiome, while aspartame and stevia appeared to have far smaller effects during the study period.
More importantly, some participants consuming saccharin and sucralose demonstrated altered glucose tolerance following the intervention. In other words, their bodies became slightly less effective at regulating blood glucose. The microbiome transplant experiments added another layer to the findings. Germ-free mice that received gut bacteria from some of the human participants who had consumed saccharin or sucralose also developed altered glucose responses. This suggests that, at least in some individuals, changes within the gut microbiome may have contributed to these metabolic effects.
But what I found most fascinating was the considerable variation between individuals. Not everyone responded in the same way. Some participants experienced noticeable microbiome changes, while others showed very little response despite consuming identical amounts of the same sweetener. I've seen this myself in my practice - two clients, the same electrolyte drink with sucralose in it, and one barely moved the levels on her CGM while the other had a real sugar spike. Same drink, two completely different responses.
Strengths and Limitations of the study
This study has several strengths. It was a randomised controlled trial involving healthy human participants, and the researchers used doses of sweeteners that reflected real-world consumption rather than unrealistic laboratory exposures. The inclusion of microbiome transplantation into germ-free mice also strengthened the biological evidence by helping to explore potential mechanisms rather than simple associations.
However, we should interpret these findings carefully. The intervention lasted only two weeks, meaning we cannot determine whether the observed effects persist over months or years. The study also involved healthy adults who rarely consumed artificial sweeteners before the trial, so the findings may not apply to habitual consumers or to individuals with different health conditions.
Finally, the study does not demonstrate that artificial sweeteners are harmful. It demonstrates that some sweeteners may influence the gut microbiome and glucose regulation in certain individuals under specific circumstances. These findings generate important questions, but do not provide definitive answers about long-term health outcomes.
What interested me the most
What I found most interesting wasn't whether artificial sweeteners changed the microbiome. I've said it before and i'll say it forever "nutrition cannot always be reduced to calories". Unfortunately, we've become brainwashed for years to think about food in terms of energy. If something contains fewer calories, we often assume it must have less impact on the body. This study helps challenge that assumption, as a substance can contribute virtually no calories and still interact with our biology.
And thank god, that this highlights one of the principles of functional nutrition: people do not all respond in the same way. Some participants experienced measurable changes, while others did not. The same sweetener, consumed in the same quantity, produced different biological responses in different people. For me, this is where nutrition becomes both fascinating and humbling. Human biology is incredibly complex, and individual differences always matters. Rather than looking for universal answers, research like this encourages us to ask better questions about why one person responds differently from another.
So what does this mean in practice?
This study is not a reason to avoid every product containing artificial sweetener and on the flip-side, nor does it suggest that sugar-sweetened drinks are automatically the better alternative. Instead, it reminds us to think beyond calories alone. Artificial sweeteners remain useful tools for many people, particularly when reducing free sugar intake or supporting weight management. One of the first questions I'd ask with a client is "compared to what?". If replacing a full-sugar fizzy drink with a zero-calorie alternative helps someone reduce their sugar intake, that's an important part of the conversation. However, they should still be viewed as ingredients that interact with the body rather than biologically inactive substances.
For individuals experiencing digestive symptoms or those with particular metabolic concerns, it may be worth considering the overall pattern of sweetener consumption as one part of a much bigger nutritional picture. As always, context matters. The occasional sugar-free drink is unlikely to determine someone's health. Equally, relying heavily on artificially sweetened products while neglecting dietary quality, fibre intake and whole foods is unlikely to support a healthy gut microbiome. Nutrition is rarely about a single ingredient, it's about the overall dietary pattern.
The Empowering Nutrition view
One of the reasons I love reading nutrition research is that it continually reminds me how much more we still have to learn. In fear of sounding like a broken record, good science rarely provides black-and-white answers. It's supposed to it challenges our assumptions and encourage us to always stay curious.
This study didn't convince me that artificial sweeteners are harmful. It did confirm my assumptions that "zero calories" does not necessarily mean "zero biological effect." As the science continues to evolve, I believe our role isn't to chase headlines or label foods as simply good or bad. It's to understand the evidence, recognise its limitations and apply it thoughtfully to the individual sitting in front of us.
Final point before I retire for the day - as someone who works with people wanting to get more from their training, it also reminds me to always take into account those quick to consume, often forgotten about convenience products that are heavily promoted to active individuals. Many of the sports drinks, protein products and on-the-go foods contain artificial sweeteners. That doesn't make them good or bad, it means they're another piece of the puzzle worth considering, particularly when someone is struggling with digestive symptoms or unexplained performance issues. It's never about the one ingredient, it's about stepping back and looking at the bigger picture.
Every person is beautifully unique and that's why there will never be a one-size-fits-all answer. If you'd like support understanding what your own body needs, I'd love to help you navigate the evidence and find an personalised approach that's right for you.
Reference:
Suez J, et al. (2022) Personalised microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.
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