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The Leading Voices in Food

E196: Why do we need zero calorie sweeteners, and are they safe?

Hosted by: Kelly Brownell (Duke)
February 23, 2023

Artificial sweeteners, known more recently as non-nutritive or low-calorie sweeteners, have been a source of great hope. What could be better than enjoying sweetness in foods but without the calories? Sucralose, xylitol, stevia, saccharin, aspartame, there are a lot of them out there. You may add them to food yourself, you may consume them in beverages, and if not, there’s a good chance they’ll show up in foods that you buy. But, do they work and are they safe? Few know this area like Dr. Richard Mattes, distinguished Professor of Nutrition Science at Purdue University.

Richard D. Mattes, MPH, PhD, RD, is a Distinguished Professor of Nutrition Science at Purdue University, Adjunct Associate Professor of Medicine at the Indiana University School of Medicine and Affiliated Scientist at the Monell Chemical Senses Center. His research focuses on the areas of taste function, hunger and satiety, food preferences, regulation of food intake in humans and human cephalic phase responses. At Purdue, Dr. Mattes is the Head of the Ingestive Behavior Research Center.  Outside of Purdue he was a member of the 2020 Dietary Guidelines Advisory Committee; is a past-president of the American Society of Nutrition and Secretary of the Rose Marie Pangborn Sensory Science Scholarship Fund.  He has authored over 300 publications. Dr. Mattes earned an undergraduate degree in biology and a Master’s degree in Public Health from the University of Michigan as well as a doctorate degree in Human Nutrition from Cornell University. He conducted post-doctoral studies at the Memorial Sloan-Kettering Cancer Center and the Monell Chemical Senses Center.


Interview Summary

So Rick, thanks so much for joining us. You’ve done pioneering work on this area and there are a few people better positioned to discuss this topic, so I appreciate you joining us today. So let’s start off with why do we need these sweeteners at all?

Well, I think the primary driver here is concern about the consumption of nutritive sweeteners – sugars. It is the case that often sugars are consumed in foods that provide limited other nutritional value. So they add calories without nutrients. And then given an environment where there’s concern about weight gain and obesity, there is a reasonable assumption that we can reduce sugar intake without compromising nutritional status. So, it’s a good target for interventions to manage body weight. Low-calorie sweeteners, as you pointed out, are one approach that can be taken to reduce sugar intake without compromising the sensory qualities of foods. I think it’s very well accepted that the sensory qualities of foods are really the primary driver of food choice. We as nutritionists would like to believe people make food choices based on nutrition. We recognize the importance of cost and convenience. But the reality is if a product does not have the right sensory properties, people just won’t consume it. We have to pay attention to the sensory properties of foods. Added sugars are presently contributing about 13% of daily energy intake – so that’s a very high percent without contributing a lot of nutrients. To give you a little more perspective, at the 75th percentile in the US population, that translates to about 400 kilocalories a day for males, about 300 kilocalories a day for females. If we use a 2,000 kilocalorie diet as sort of the standard, which is what’s used on food packaging labels, that represents 20% for males and 15% of energy on a daily basis. It’s very, very high. Now, the Dietary Guidelines Advisory Committee from 2020 reviewed sweeteners and their relationship to body weight. In their modeling analyses they concluded that people can really only take in something on the order of 5 to 6% or so of energy from added sugars without going into positive energy balance. That is taking in more energy than we need and as a result, putting ourselves at risk for weight gain. That is based on what it would take to obtain all the necessary nutrients in the diet if we make smart food choices. There’s very little discretionary room for added sugars. As a result, low-calorie sweeteners are a way to reduce total sugar intake, again, without compromising sensory quality.

That makes good sense and those numbers are really quite striking. Can you give us a little bit of a sense of how much these low-calorie sweeteners are consumed and how they show up in the food supply?

Well, the primary source is through sweetened beverages, but there is increasing use in solid foods as well. They are ubiquitous in the food supply, I think that’s safe to say, but low calorie sweetened beverages are the primary source.

There’s been concern that these low-calorie sweeteners can disrupt carbohydrate metabolism and result in greater hunger and food intake. What do you think about that?

Yes, this has been very extensively studied and my interpretation of the literature is that they do not disrupt carbohydrate metabolism. We know that when people consume nutritive sweeteners sugars, that they are absorbed, the blood sugar rises. That elicits the release of insulin as a way to get the sugar out of the blood and into our cells. When blood sugar levels drop and insulin levels are relatively high, that’s viewed as a sort of metabolic signal that we should be hungry and be interested in eating again. However, my reading of the literature shows that low-calorie sweeteners do not elicit a rise in insulin, do not lead to a drop in blood sugar and as a result don’t generate a hunger signal. But even if they did that, the question is, does a rise in blood sugar or a drop in blood sugar or a rise in insulin after a typical meal really serve as the driver, or the primary mechanism for generation of hunger signals? There’s an experimental approach called euglycaemic clamp. We don’t need to go into all of the details, but suffice it to say it’s an approach that allows one to independently manipulate the level of glucose in the blood or the level of insulin in the blood. When those studies have been done, they demonstrate unequivocally that independent changes in glucose do not alter appetitive sensations, hunger, nor do independent manipulations of insulin. They undoubtedly change following a meal, but they are not the cause of the generation of hunger signals.

So this gets right at the heart of a key question. Some people are saying that, when you consume these artificial sweeteners, they rev up the body in a way that makes you want to eat. You’ll then consume as many calories as you might have if you’d been consuming sugar or maybe even overdo it. But you’re saying there’s not a biological basis for that in science.

That’s correct. I think where there is credibility to that scenario lies more in cognitive or psychological dimension. When people use a product or a food that is reduced in energy, and we require products that we purchase to label their energy content and often claims are made about them being low energy when they are, people are overly optimistic about the energy that they save when they consume these products. So they may then may be more inclined to indulge subsequent to that and overestimating the amount of energy they saved, they can indeed offset the benefit of substituting a low-calorie sweetener for a nutritive sweetener and result in higher energy intake. But that is not a biologically-driven phenomenon. It therefore requires more education in terms of how to use low-calorie sweeteners to better effect, rather than it being a biological basis that is kind of out of people’s control.

If people are consuming diet beverages for example, and they’re getting accustomed to a high level of sweetness because they’re consuming these throughout the day, does that generalize to other parts of their diet? Might they then like other things sweeter than they might have otherwise or have sort of a drive for these things?

I think where there is credibility to that scenario lies more in cognitive or psychological dimension. When people use a product or a food that is reduced in energy – and we require products that we purchase to label their energy content and often claims are made about them being low energy when they are – people are overly optimistic about the energy that they save when they consume these products. So, they may be more inclined to indulge subsequent to that and overestimating the amount of energy they saved, they can indeed offset the benefit of substituting a low-calorie sweetener for a nutritive sweetener and result in higher energy intake. But that is not a biologically-driven phenomenon. It therefore requires more education in terms of how to use low-calorie sweeteners to better effect, rather than it being a biological basis that is kind of out of people’s control.

That seems like a really important question to nail down, doesn’t it? Because what you say about salt and fat and the dairy products and things makes all the sense in the world. I know I’ve experienced myself with low fat dairy products compared to when I was a kid and people were drinking high-fat versions of milk and things. So if that’s true and it does apply to sweetness, then you’d think the artificial sweeteners would be counterproductive because they keep people consuming sweet and not getting used to less of it over time. Does that make sense?

That’s a most interesting question and highly relevant right now. So there is a reasonable body of science on the effects of exposure to sensory qualities and the preferred level of that quality in foods for salt and for fat. If one consumes high salt levels, foods with high levels of salt and saltiness, they generally come to like and actually prefer foods that are high in salt. If you’ve gone on a diet that limits sensory exposure, it’s not the amount of sodium actually consumed, it’s the sensory exposure that determines this. If you limit sensory exposure to salt, you can actually come to prefer low salt foods. The same is true for fat. Probably many people have exposed themselves to low fat dairy products, for example, and over time actually come to prefer them to the higher fat versions. But the story for sweeteners is still very much unknown. There is a small amount of evidence based on short-term studies with small sample sizes that would suggest that scenario holds, at least in kids, but the largest and probably best-controlled study to date fails to find an effect of exposure to sweetness on the preference for sweetness of foods. In contrast, they find that it alters the sensory perception (that is the intensity of sweetness) but not the preference or the liking of sweetness. So the jury is still out on that scenario.

Let me ask one of the bottom line question:  Are low-calorie sweeteners associated with lower or higher body weight?

Yes, that’s the logical conclusion. The question is whether sweetness is indeed different from salt and fat and how exposure effects work.

Okay, good to know. We’ve been talking about these sweeteners as a group, but if we start to separate them, do the different ones have different effects on the body?

So there is ammunition for different perspectives on this question. The epidemiologic data, that is the data based on surveys, pretty consistently shows that there is a positive association between consumption of low-calorie sweeteners and indices of adiposity, body fatness, things like body mass index or body weight or waist circumference. However, the evidence also in my opinion quite convincingly and strongly shows from randomized control trials that consumption of low-calorie sweeteners is associated with lower indices of adiposity, BMI, body weight. In the sort of hierarchy of scientific rigor, randomized controlled trials are viewed as stronger than these cohort studies, these survey studies. In my opinion, the strongest science shows that they’re associated with lower body weight rather than higher.

I’m really happy you brought up that study because it’s clearly a landmark study. It’s nice that you’re being modest about it, but boy, it sure opens the door to some very interesting and important questions. I appreciate you doing this study and describing it today. If these compounds are having different effects because they’re different biologically, which would make sense that they wouldn’t all behave the same once they get inside the body. I’m assuming the same thing would probably be true for safety concerns. I know over the years, there have just been lots of things in the press about worries, about safety of these products. What do you think about that? Do you think these concerns are merited?

So this is a very interesting area because we tend to speak about all low-calorie sweeteners as though they were kind of one thing. And it’s true, they all impart sweetness with very little or no energy. But, does that mean that they all have the same effect in the body? We know, again, from other kinds of chemicals that that’s not the case. For example, salt, sodium chloride, tastes salty, but is associated with elevation of blood pressure. Potassium chloride also tastes salty, but the potassium is associated with lower blood pressure. The fact that they share a sensory property doesn’t mean that they have the same physiological effect. Yet we view all these different low-calorie sweeteners that have entirely different chemical structures as though they’re the same thing. I think that the time has come to look at them individually. We conducted a study with Kelly Higgins as the first author, and compared four low-calorie sweeteners and their effects on body weight. People consumed these on a daily basis for 12 weeks. We monitored body weight, as well as things like hunger and appetite and so on, but the most important endpoint was body weight. One of the groups consumed sugar. We expected that if we asked people to consume sugar on a daily basis that they would gain weight and indeed they did. The interesting finding of the study though was when people consumed saccharin, they also gained body weight and at a rate that was comparable to the sugar. In contrast, when they consumed Splenda, they lost body weight. By the end of 12 weeks, there was a significant difference in body weight between those consuming Splenda and those consuming saccharin. So, what this suggests is that there may indeed be substantive differences in how we respond to these different commercially available and widely consumed sweeteners. I want to emphasize that this is the one and only study that has addressed this issue and we should never believe a single study, no matter how well done it is, until it’s replicated. I think this is an intriguing hypothesis. I think there is logic to viewing them as potentially different. Again, they all have different chemical structures, but this requires verification.

I guess because these products are used by so many millions of people, you’d think if there were negative effects, we’d know by now. But on the other hand, there are some of these products relatively new to the market compared to others like Splenda. And if this may not have immediate effects but long-term effects after somebody’s consumed them after many years, we may not know yet, I’m assuming. But it sounds like from your reading of the science, there are no negative effects of these at this moment.

Two levels of response to that. First, I’m not a toxicologist, so you should be cautious in interpreting my perspective on it. But these sweeteners have been highly studied by the regulatory agencies of many, many nations, the European Union, the US, Australia, Canada, Japan, around the world. And uniformly, they have concluded that when used within reasonable amounts, they are safe. And of course, that stipulation, when used in reasonable amounts, may be open to debate among people with different views in this area. But it’s a qualification that would be used for any food or any nutrient. Any nutrient consumed at excessive levels becomes a drug and has effects very different from its role as a nutrient. So it’s not unusual to put that qualification on such a claim. However, yes, they’re different chemicals. They should be evaluated independently. As a particular sweetener is petitioned for approval, regulatory agencies do review the science for its safety independently. So for the commercially available products, I think it’s safe to conclude that they are safe, but as new products are developed, they will have to be evaluated on their own merits as well.



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