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The Leading Voices in Food

E204: The troubling unknowns of non-caloric sweeteners

Hosted by: Kelly Brownell (Duke)
May 4, 2023

As a society, we are eating and drinking low-calorie sweeteners more and more. Researchers are working to understand the long-term impact of such sweeteners for adults and, of course, for children. This interview is part of a series on the impact of sweeteners. Our guest today is Dr. Allison Sylvetsky, Associate Professor in the Department of Exercise and Nutrition Sciences at the George Washington University – Milken Institute School of Public Health.

Dr. Allison Sylvetsky is an Associate Professor in the Department of Exercise and Nutrition Sciences and is Director of the Bachelor of Science in Nutrition program at the George Washington University Milken Institute School of Public Health. Dr. Sylvetsky joined the GW faculty in 2014, prior to which, she was a post-doctoral fellow in the Diabetes, Endocrinology, and Obesity Branch of NIDDK in the Intramural Research Program of the National Institutes of Health (NIH). She received a doctorate in Nutrition and Health Science from Emory University. Dr. Sylvetsky’s research focuses broadly on obesity and diabetes in youth. Her primary research interests are in studying the consumption and health effects of sugar-sweetened beverages and low-calorie (artificial) sweeteners, with a key focus on their consumption during childhood.

Interview Summary

Boy, these sweeteners are in the news all the time, and that’s been the case for many years. And people are really interested in whether they’re safe, whether they help people control their weight and the like. You have a vast knowledge on this, and I’d like to begin with kind of a fundamental question. So, how has the consumption of these sweeteners changed over time? How much are they being used and who is using them?

What’s really interesting is that these sweeteners have been around, at least some of them, for quite a while. But what we’ve seen is that as there’s been more and more emphasis on reducing the consumption of added sugars and sugar sweetened beverages, there’s been a widespread increase in the use of various low-calorie sweeteners in the food supply, which of course has been followed by increases of consumption. So, across all different population subgroups, we’re seeing increases in the intake of low-calorie artificial sweeteners.

So, how much are they used and who are the people who are using them the most?

So, in terms of how much they’re used, that depends to some extent on how we look at this, because it’s very hard to actually quantify the intake given that manufacturers are not required to disclose the amount of different artificial or low-calorie sweeteners in food and beverage products. So, most of the data that we have to rely on either comes from household purchasing data or comes from self-reported dietary intake data from large surveys, for example, the National Health and Nutrition Examination Survey. But, what we’ve seen in these data are that low-calorie sweeteners are being used across the population, though the highest consumption or highest prevalence of consumption is seen in females, in individuals with diabetes and obesity, individuals from higher-income households, and also older adults and older individuals. However, more and more, we are also seeing consumption of low-calorie sweeteners among children, and consumption in products that people wouldn’t necessarily expect would contain these artificial or low-calorie sweeteners.

Let’s talk about that. So, where do the low-calorie sweeteners show up in the food supply? Has this changed over time?

This has definitely changed over time. Several decades ago, you would think of low-calorie sweeteners as being in diet beverages, which of course they still are. Or in sweetener packets that you find on the tabletop. For example, Sweet’n Low that contains saccharin or Equal that contains aspartame. But now we’re seeing these sweeteners showing up across product categories. So, in products including light yogurts, artificially sweetened yogurts, dairy desserts such as ice cream, snack foods such as microwave popcorn, cereals, ready-to-heat oatmeal, all sorts of different products, protein bars, protein shakes, really, you name it. I’ve actually even seen low-calorie sweeteners show up in pickled ginger that usually is used along with sushi. So, again, places where people just wouldn’t expect to find them. We see these sweeteners popping up, and this is more and more the case as there’s been more and more emphasis on reducing the intake of added sugars.

Low-calorie sweeteners in microwave popcorn, who would’ve thought? I mean, that’s just one example and you gave other ones about where these things are showing up. So, big time exposure to these, isn’t there?

Exactly. Also, something like microwave popcorn typically wouldn’t be thought of as a diet food, and that’s part of what is very confusing to consumers. It’s one thing if the product is labeled as “diet” or “no sugar added” even. Not that everybody would recognize that as perhaps being suggestive of having a low-calorie sweetener, but in products like microwave popcorn or certain English muffins, for example, people typically aren’t using these products as a way to manage their weight or as some sort of a diet or reduced calorie food, because they’re not diet or low-calorie foods.

Let’s get right to one of the most fundamental questions of all. What are your thoughts on how these low-calorie sweeteners affect health?

So, that is the big question, and there’s a lot of uncertainty and there’s been more and more research on the topic, which has been exciting and informative. But there still are a lot of questions with regard to how these sweeteners affect health. One thing that is important to clarify right from the start is that, at least the work that I do and the work that a lot of people are focused on to understand their health effects, is different from more of a traditional toxicological safety assessment. So, when I’m talking about their effects on health, I’m really referring to their metabolic and health effects, their role in weight management and chronic disease prevention as opposed to more traditional safety outcomes. Because of course, these low-calorie sweeteners have been reviewed and approved for use in food by the Food and Drug Administration and other regulatory agencies worldwide. But, in terms of weight management and chronic disease prevention, what’s really interesting is, it depends on the type of evidence that you look at. There have been quite a number of randomized control trials primarily in adults that have shown that when added sugars or sugar-sweetened beverages are replaced with low-calorie sweeteners on a one-to-one basis, there typically is either a neutral effect or a modest benefit. Where we do see some modest reductions in energy intake as well as a modest reduction in body weight. But that doesn’t necessarily tell the whole story because that doesn’t necessarily reflect how they’re used, especially given what we’ve just discussed about the use of low-calorie sweeteners in the food supply. What’s interesting is when we look at observational evidence from large perspective cohort studies, typically the vast majority of these studies show positive associations between consumption of diet beverages and low-calorie sweeteners with a variety of adverse health outcomes. This includes higher risk of obesity, higher risk of diabetes, heart disease, and some recent studies also showing an increased risk of certain types of cancer.

So that then leads to the question of: well, what explains this discrepancy? There are several explanations. One is that there are flaws to any type of study, including that a lot of these studies that look at associations may be subject to reverse causality or sort of a chicken and egg situation – which is what’s happening first. But they’re also very plausible biological and behavioral mechanisms that have been put forth to explain how low-calorie sweetener intake may be causally related to some of these outcomes. And that’s really where a lot of the research is focused right now, is trying to understand, what do these low calorie sweeteners actually do metabolically in the body and how does that impact health?

That whole range of metabolic consequences is a very interesting one. You led off this discussion by mentioning toxicology, and I realize that you’re not a toxicologist, nor am I, but I do have a question in that arena. Whatever standards of the FDA uses to assess safety for these things, I’m assuming it’s a range of standard toxicological tests, do you think there’s still a chance that these things, even though they’re considered safe, will have long-term consequences that people don’t know about yet? Just because some of the newer ones, for example, haven’t been on the market long enough for people to have 20 or 30 years of exposure? Is there a reason to be concerned on that front, do you think?

I would say there’s a reason to be concerned in terms of while the levels that they’re consumed are believed to be safe in terms of, as you said, these thresholds that are set forth based on toxicological data – we don’t know what the threshold of exposure is that would be required to have these metabolic effects. When we’re talking about metabolic and health effects, as you’ve alluded to, these are long-term processes, right? We don’t develop diabetes or cancer overnight, but it takes months, years, decades of exposure to see some of these outcomes. So, it is very possible that even though these are safe from a toxicological standpoint, the repeated exposure in the ways that we consume them, in addition to the fact that we don’t consume these in isolation, we consume low-calorie sweeteners in combination with each other, other low-calorie sweeteners, as well as other food additives, other ingredients in various forms. So we don’t fully understand yet what that means for long-term human health.

Thank you for that explanation. Thus far, we’ve been talking about these low-calorie sweeteners as a group, but of course there are different compounds that have different biological effects. What do you think about the different effects of the different versions of low-calorie sweeteners?

That’s become an extremely important question, especially because over time there’s been changes in not just the use of low-calorie sweeteners as a group, but in certain low-calorie sweeteners. As you mentioned, these sweeteners are different compounds. Of course, they’re grouped together because they contain characteristics, such as low-calories that have high potency sweetness and are palatable replacements for added sugars in food. But they are of course, different compounds. And therefore, while they may have some overlapping effects due to their sweetness, they also may have different effects due to their specific chemistry and their way that they are absorbed, metabolized, processed in the body. That’s something that we’re really, as a field, just beginning to understand. In a lot of the research to date, low-calorie sweeteners have been referred to as a group. And that’s in part because, especially in observational studies, it’s very difficult to tease out which ones are being consumed. And that’s in part due to limitations of dietary assessment approaches, and in part due to constantly changing formulations of these products by food and beverage manufacturers.

So, it’s difficult in a lot of the existing research to actually tease apart what specific low-calorie sweeteners we’re talking about. That said, there is more and more of an emphasis on trying to understand these as individual compounds and then hopefully be able to make more tailored and nuanced dietary recommendations for or against their consumption. There’s been some recent studies looking at, for example, comparing different low-calorie sweeteners on outcomes such as body weight over 12 weeks. What that study showed (that was a study out of Purdue University), is that while saccharin consumption actually led to weight gain that was similar to real sugar, sucralose consumption in this particular study led to reductions in body weight. So, while this is just one example, clearly it’s possible and likely that these sweeteners may actually have some different effects, which really reiterates the need to look at them separately and compare their effects on different outcomes.

It’s interesting that you mentioned the research at Purdue, and I’d like to remind our listeners that we reported a podcast with Dr. Richard Mattes, who’s a professor at Purdue, who’s done a good bit of work on this topic. So, let’s turn our attention to children. And I know many parents are very concerned about consumption of these products by their children. So, is their worry warranted? What do you think about use of these things in children?

Yes, I would say their worry is warranted. That said, it’s also not conclusive that these are harmful, but at the same time, it’s not conclusive that these are actually beneficial for their intended benefits of helping to reduce sugar intake and help with weight management. Really when it comes to kids, it’s a question of how you look at the data, because what is obvious is that there is a lack of data in kids. In some cases, kids could be thought of as small adults. But kids also are very different than just being small adults, not just because they’re smaller, but because they’re developing. And we know that early life exposure makes the difference in terms of future dietary patterns. Given that there are many questions about the metabolic and health effects of low-calorie sweeteners in adults that have yet to be answered, to start in a widespread manner, providing these to children is concerning until we have a better handle on how these actually work in the body. As mentioned, there is very limited evidence in children, but at the same time, we’ve seen an explosion of low-calorie sweeteners in products, including products that are directly marketed to children. For example, fruit drinks that have often added sugar in addition to low-calorie sweeteners such as sucralose and acesulfame potassium. We’ve done some work talking to parents as have others, and trying to understand, “Well, what do parents think about this?” And most parents will tell us that they do not want to provide these to their children. Meanwhile, other research has shown that parents cannot identify or recognize products that contain them. What’s happening is that given a lot of different factors, but particularly the fact that more and more of these sweeteners are showing up in children’s products, children are being exposed to low-calorie sweeteners from a very young age. And it’s unclear what that means for their health. There is reason to be concerned, both based on data in adults as well as some of the more mechanistic evidence that’s come out recently related to how these sweeteners may adversely impact glucose homeostasis or insulin resistance, or alter the composition of the gut microbiome. There are a lot of questions when it comes to this topic in general, but particularly for children, it would seem that we may want to take a more cautious approach before widely incorporating these into products that are going to be consumed by youth.

What are some of the key questions that people in this field are addressing now?

So, some of the key questions, and there are many of them, but one is really just to understand the mechanisms through which these sweeteners work, both as a group and individually. That will provide really much needed insight to explain these epidemiologic findings and also to understand some of the discrepancies between the randomized control trial literature and the observational data. That’s one big area of focus. Another is to understand early life exposure. Both exposure among children as well as intergenerational exposure. What happens when a pregnant mother or breastfeeding mother consumes these every day or multiple times a day? We know that they are transferred to the baby. In the case of breastfeeding, for example, we’ve done some work in that area. What we don’t know is what that actually means for the child in terms of their taste preferences, their appetite, their weight trajectory, and their future health. Understanding that early life exposure and intergenerational transmission, as well as focusing on cardiometabolic outcomes beyond body weight. So, we know that when these are used in a certain way, very judiciously, these may… Low-calorie sweeteners, and I’m generalizing the term here, but may be useful for helping with weight management. But we need to study these in a way that better reflects how they’re actually consumed in real life. And then also, as we’ve already discussed, really start to understand the effects of these different compounds as individual sweeteners in addition to as a group of compounds that have some similar sensory property, that being that they’re sweet. I think those are some of the main areas in addition to continuing to translate some of the more mechanistic work that’s been done in rodent models into the context of human consumption.

The whole idea behind these artificial sweeteners in the first place is that people enjoy sweet taste in things. And so, why not go ahead and provide that? And it better to have it in some form that’s not creating the same health problems that sugar has. But what about just changing that assumption and saying that people should get accustomed to less sweetness in things overall, which would then lower intake of both artificial sweeteners and sugar. And I’m wondering if you think that might be possible? Let’s just say that the food industry agreed to or was required to reduce the sweetness in its food by 5% each year for the next 15 years or whatever it would be, so that people wouldn’t notice it from year to year, but generally you would get accustomed to lower levels of sweetness in things. Do you think that would be possible for people to become accustomed to?

I would think it would be possible, certainly that we know that repeated exposure to different levels of sweetness will affect sweetness preference and dietary choices. What you’re describing is very similar to what’s been done with sodium in terms of gradual voluntary reduction of sodium. And I am aware, and as I’m sure you are, of efforts through, for example, the National Salt and Sugar Reduction Initiative (NSSRI), to do exactly that, which is to set targets for lowering the sugar content and therefore lowering the sweetness, assuming that there’s not replacement with low-calorie sweeteners of different products across different product categories. I think there is a lot of promise in that concept, but I do think we would need to obviously see how that actually affects various outcomes before knowing whether it was effective or not. But I think that concept of it’s not just sugar, but also we need to think about the sweetness and how that pertains to other dietary choices and longer term dietary patterns, is really important.


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