Jim Hill: Welcome to “Weight Loss And…”, where we delve into the world of weight loss. I'm Jim Hill.

Holly Wyatt: And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and live your best life while you're doing it.

Jim Hill: Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

Holly Wyatt: Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

Jim Hill: Ready for the “And” factor?

Holly Wyatt: Let's dive in.

Jim Hill: Here we go. Welcome to another episode of Weight Loss And, I'm Jim Hill along with Holly Wyatt. Holly, today we're going to talk about the sweetness of life.

Holly Wyatt: What do you mean by that? The sweetness of life. All right, Jim, you have to tell us more about that.

Jim Hill: I'm talking about the fact that we like sweet things. And here's the deal. We don't learn to like sweet things. I remember when I was in college, I saw this video of babies. You get them something sweet and they smile and they light up. So we're born loving this sweet taste. And again, in my opinion, life wouldn't be as great without sweet things.

Holly Wyatt: I think it's a little of both. And that's a great question. I think we're wired and perhaps we learn a little bit about it too. So yeah, that's that'll be a good question.

Jim Hill: But like anything else, Holly, you can overdo it. So a lot of advice right now is to reduce sugar in your diet. Sugar is a source of sweetness. And I don't know why we can't get nutrition advice to avoid cauliflower.

I mean, man, I could follow that one. But, you know, right now, most of the experts are saying you're eating, you're taking in too much sugar. Those calories are causing problems in weight gain and other negative metabolic effects. So we're asked to reduce something that we like. And that's tough.

Many people trying to lose weight have questions about reducing sugar and finding alternatives. So to help us wade through all this, we have a guest today. One of the fun things, Holly, on this podcast is we can bring in the researchers that we really admire and we really like.

Holly Wyatt: Yes. And the tough questions. I'm like, when is a tough question, let's bring in somebody else to help answer it.

Jim Hill: Yeah, exactly. So our guest today is Dr. John Sievenpiper. He's from our neighboring country up North Canada. He's an associate professor in the Department of Nutrition Sciences at the University of Toronto. I visited him once in Toronto and I think it's the coldest I've ever been in my life.

Toronto is a wonderful city but maybe go in the spring or summer. So John, welcome to Weight Loss And.

John Sievenpiper: Thanks for having me. Happy to be here.

Jim Hill: So before we dive into this issue, tell people about the kind of research that you and your research group at the University of Toronto engage in.

John Sievenpiper: Yeah, thanks for asking. So we're interested. My research program is really focused on using in terms of tools. We use randomized controlled trials and epidemiological tools to analyze large databases. We also review and summarize the available evidence, and analyze data sets like NHANES or large perspective cohorts.

So those are the basic tools we use to answer our questions. The questions are about the importance of carbohydrate quality in relation to sugars and sweeteners, focusing on clinical and public health concerns. And in particular, traditional and therapeutic dietary patterns. So that's kind of the interest in terms of the nutrition. And then the outcomes we're interested in are related to obesity, diabetes, and their downstream. If you like cardiometabolic complications like cardiovascular disease.

Jim Hill: So you're looking at large data sets, what people eat, and sort of health outcomes.

John Sievenpiper: Exactly right.

Jim Hill: Great.

Holly Wyatt: So are we ready to go with the questions, Jim?

Jim Hill: Let's hit him with the hard questions, Holly.

Holly Wyatt: John, it's time to address a common misconception about low calorie sweeteners that many people struggling with their weight face. And I want you at some point to kind of define low-calorie sweeteners versus non-nutritious sweeteners. Make sure we're on the same page there. You know, even I get to get confused. And on one hand, our listeners are being told to avoid sugar. On the other hand, some experts are advising them not to consume products that have low-calorie sweeteners, products that would substitute these low-calorie sweeteners for the sugar. And I think it's especially true with beverages. And on paper, I understand that it looks good to say, you know, drink water.

I mean, that's not a bad thing to say, but let's get real. I would like to be able to have some sweetened beverages sometimes and some foods that have some sweetness. I don't want to go the rest of my life with never tasting something sweet. So what does your research say about these low-calorie sweeteners and body weight regulation, weight loss, et cetera?

John Sievenpiper: Great question, a big question. So I mean, the first thing I think maybe is to talk a little bit about what sweeteners are. So they are alternative sweeteners that are alternatives to sugars.

So in general, these are no or low-calorie options for consumers. The ones that we're most probably familiar with would be ones like Aspartame or Ace-K or Sucralose that would sweeten beverages and some foods. Beverage is the most common format that we find our sweetener

Jim Hill: Splenda, Equal, and Sweet'n Low are the brands.

John Sievenpiper: Yeah, exactly. In terms of brands, what you'd see in terms of packets, but if you were to read the label of a can of your favorite diet beverage, it would probably be Ace-K or Sucralose or Aspartame. These are considered high-intensity sweeteners because they have a much higher sweetness than sugars. So it's a milligrams amounts of these are needed to replace gram amounts. If you take Advantame or Neotame, John Fernstrom would say you need molecular forceps to sweeten your coffee. You need very little amount.

Jim Hill: These things are powerful. They're so sweet.

Holly Wyatt: I like that picture. Just a tiny bit.

John Sievenpiper: And that's important when we talk about how we use them in different food systems and food matrices. But in terms of beverages, which is the most common, this is where we've really looked at the question. This is important to consider because sugar-sweetened beverages have led to the evidence that Jim mentioned about reducing sugars. Our guidelines, recommendations to reduce sugars in the diet and calories from sugars really come from data from sugar-sweetened beverages where they tend to be overconsumed. So if we look at that specific food matrix (and it's important, I think, to look at different matrices), when we look at sugar-sweetened beverages and replacing those with low and no-calorie sweetened beverages or our favorite diet beverages, if you like, we look at that evidence, we look at the randomized controlled trial evidence.

And Jim has certainly contributed to this with the really important trial. When we examine those trials, we consistently see a reduction in weight, body fat, and especially liver fat. When we look at that, what we like to call an intended substitution. That's where the consumer, those listening, you know, we're making our choices. We're looking to reduce sugars, and reduce calories. We're taking the diet option. That intended substitution, we see weight loss.

Jim Hill: So for weight, you're better off doing the non-calorie sweeteners or low-calorie sweeteners than sugar itself.

John Sievenpiper: Exactly right. We synthesized information to update the European guidelines of the European Association for the Study of Diabetes. And we found really what other guidelines had found.

But in particular, when we did our evidence synthesis for that guideline, which we published in JAMA Network Open in early 2022, what we found was that we set it up, we looked at the substitution of low and no calorie for sugar-sweetened beverages. We also wanted to look at water because that's the standard of care. We're being told to drink water. And I think we should be recommending water. So we want to understand what that would look like standard of care and then how it would compare to water. And what we found is that it compares very, very well to water. We found very similar reductions. So our conclusion was really that as an alternative to sugars, it behaves very similarly to water in terms of the weight loss benefit you might expect from displacing those calories.

Holly Wyatt: So I love this. So you could drink water and get the effect, or you could use a non or low-sugar kind of beverage substituted for the sugar and get the same impact in terms of that, your research.

John Sievenpiper: Yeah, exactly. And we looked across actually 20 different intermediate cardio metabolic outcomes, and we found a very similar signal across all of those, in particular, where the benefit seems to be is in terms of displacing calories and then with that displacement of calories, less calories, we see a reduction in weight and adiposity and very similar to what we would see with water. So we were quite confident in our conclusion for those guidelines and others have echoed that in their guidelines that really, yes, the standard of care is water and this is a reasonable alternative to water to get the benefit of displacing those excess calories from sugars.

Jim Hill: You know, Holly, you and I have worked over the years with the National Weight Control Registry, and we ask a lot of questions about sugar and non-caloric sweetener use there, John. One of the things these people tell us is they get no calories from beverages. They're basically saying, I want my calories from food, not beverages.

And they tell us exactly what you said. They said, you know, most of the time we drink water, but we like something sweet sometimes. So we're fine to use the non-caloric sweetener. So what you find in a research study fits with the real life of people who are keeping their weight off.

John Sievenpiper: This is terrific. And believe it's important to mention that clinical practice guidelines development for obesity, diabetes, and cardiovascular disease often overlooks something. And the big push really right now is values, preferences, and treatment goals.

So we have a lot of evidence for different approaches to improve diet, to improve risk factors, but there isn't necessarily one best way of doing it. There are several ways. So then it comes down to values, preferences and treatment goals and meeting people where they're at. So if someone wants sweetness and likes sweetness, then this is a good alternative.

Jim Hill: This is great because we talk a lot about that, John. There is so much in the media, you hear there's one way to do it. You have to do one thing. And what we say over and over is you have options. If water is fine with you, there's no problem. Drink water.

You're great. But if you like something sweet, there are alternatives. And one of the things that we often talk about is if you look at the number of things that probably relate to weight gain, this is not a short list.

This is a long list. And there are different sorts of things you need to worry about. And that's where I love this idea of its preference and its options. And we try to show people options. And this is a great one. You can drink water, or you can use some low-calorie sweetener.

Holly Wyatt: And it's this whole point about the and. This is really what this podcast is weight loss and is that it doesn't have to be one. There are multiple and so it fits nicely. Why are there experts who strongly oppose the use of low-calorie sweeteners?

John Sievenpiper: That's a tough one. It's hard to read minds. I do have a sense of it, as I'm sure both you and Jim do. You know, I think part of it is this sense that they're artificial. I mean, there's a distinction between artificial and natural. And we do have some natural, you know, Stevie or others, somewhat's called natural sweeteners or monk fruit versus the others. But in general, these are considered artificial.

And so there's that whole anti-artificial, anti sort of synthetic compounds bias that I think people have that's natural. It's good. If it's artificial, it's bad. It's not very scientific.

It's just sort of appealing to base emotions. People also, I think, are against things that taste good and worry that they may contribute to overconsumption. So, you know, there's this concern about sweetness. And these, although they don't come with calories , and they do displace calories from sugars, you know, is the sweetness the problem?

Our diet is too sweet and this is contributing to too much sweetness that may lead to overconsumption and may lead to some downstream knock-on adverse effects. So I think there's a there's a lot. And then, I think the main reason is the influence of the big food industry. They manufacture and put additives into packaged foods. It’s also sort of tied into that ultra-processed food concern about ultra processed foods, that these are a marker of that. So I think there are several different ways you can approach why people are concerned. But I think those are a few different ways that think people come to that conclusion.

Jim Hill: One of the things we often tell our listeners, John, is that all research doesn't come up to the same conclusions. There are research studies that come up with different conclusions. And as you know, there are studies out there that show some negative effects of these.

One concern I often have is that many studies use extremely high doses of these things. So can you overdo it? Can you consume too much of this, you think?

John Sievenpiper: So these compounds are regulated as food additives in the U.S. and in most jurisdictions in Canada by Health Canada or in Europe by the European Food Safety Authority. And so as food additives, what's set for them in the case of sweeteners is this acceptable daily intake.

So at what level do we see no harm up to which point? And that's done very well, we could have a whole podcast on how the FDA or Health Canada, these different authorities, and so on, do their assessments and the standards. But needless to say, it's very comprehensive. Sweeteners, in fact, aspartame represents, if not the one of the most studied food ingredients in the history, certainly of the FDA and these different organizations. So very, very well studied from animal up to human studies. And they apply a big safety factor in going from species to species, a tenfold.

And then even with the very variety that we have within species, another 10. So a hundred fold safety factor to set these, what they call ADIs, acceptable daily intakes. So we do have these for sweeteners. To achieve this, you would need to consume an extremely large amount of beverages, around 20 or 30 per day, depending on the sweetener. These quantities are nearly impossible for people to consume. So we are well within the ADIs in terms, certainly of normal intake. Even very large consumers of these products don't come close to the recommended intake. So, yes, you can overdo it. That's why we have an ADI. But the ADI is the bar set so high, they're really within the food supply and the way keep these are consumed. We're not even close to it.

Jim Hill: So my wife consuming two or three diet sodas a day is not a reason for concern.

John Sievenpiper: Absolutely not reason for concern. No.

Jim Hill: She'll be very relieved, John, that I will tell her you said that.

John Sievenpiper: Absolutely. Individual studies can sometimes contradict each other, causing confusion when the media selectively presents the results from only one study. And then the next day or the next week, the results for the next. And then the consumers like, well, what's the answer here? When we review this for guidelines, organizations use it to develop their own guidelines, and we consider all the evidence available. So we synthesize all the available evidence on this question and the highest level of evidence. So when we look at randomized controlled trials, which represent the best evidence that we have, because it gives us the best protection against bias.

This is where we can delve into the answers I've given and discuss the comparison between a low-calorie or no-calorie sweet beverage as a substitute for a sugary beverage or water. When we did that, we were looking at the totality of the evidence. So it wasn't cherry-picking an individual study or looking at one study. It's taking all the studies that have looked at this question and synthesizing them to come to that conclusion.

Jim Hill: What you said is incredibly important. It's crucial because we often come across headlines in newspapers that only highlight the findings of a single study. And you want to say, based on this study, you should go and do this. But that's not how science works. Science works by recognizing that if we do 10 studies, not every result is going to be the same. And we have to sort out the overall gestalt of that. And along those lines, can you tell people what meta-analysis is?

John Sievenpiper: That's a great question. So meta, that term meta, sort of means around. And meta-analysis is a sort of analysis of all of the studies. Meta-analysis combines multiple individual studies to conduct a comprehensive analysis of all available data. It's not just about counting votes and saying whether something is good or bad based on papers' conclusions. It's no, we're going to take all the studies, put them together, and analyze the data, not the conclusions, data, and synthesize it to come to a conclusion where each one is weighted based on how large and important the study is.

Jim Hill: This is precisely why I believe it is crucial for individuals to acknowledge the significance of these guidelines. It involves experts collaborating, diligently examining all the data, and ultimately using that information to formulate accurate translations. The science we know today, and that could change tomorrow, but based on the science we know today, here are some recommendations for you.

Holly Wyatt: It takes it all and uses it all to help come up with a conclusion, which is really what I think we're wanting. We can't take the consumer and our listeners, take these individual studies, we don't know what to do with them, but that's a method to come up with something that uses everything that's out there.

John Sievenpiper: And I think where nutrition is different, let's say, than pharmaceuticals. It seems like each week we come across conflicting pharmaceutical studies regarding a developed medication. These trials involve thousands of patients and should provide clear results, yet contradictions seem to be a common occurrence. So you get a drug that I, I prescriber use, like a PCSK9 inhibitor, that trials almost 28,000 individuals.

So massive trials followed for years. In nutrition, we tend to have much smaller trials. Maybe it's 20 or 30, the larger, some of the larger studies up to 100 or a couple of hundreds, and it's on intermediate biomarkers. But because they're smaller, it means we can get differing results from study to study. There is a power gap in these studies that hinders their ability to reach a definitive conclusion. So in nutrition, in particular, we need meta-analyses because we have all these smaller, we would call sort of underpowered or less powered studies. By combining them, we can increase the information and improve the accuracy of the estimates to get a more accurate estimate of the true effect. So really important in nutrition. It can be confusing with different studies saying different things each week when we're looking at individual studies.

Holly Wyatt: So along those lines, Jim, this is from, I think this fits well, and it's from a listener at this point. So you are kind of putting together all these low-calorie sweeteners. Do you think there is a difference between something like aspartame and monk fruit? And should we be studying those separately? And I think that is some of the confusion too. Of all the low-calorie sweeteners, are there differences? And is there one group that perhaps is better, or I should be considering?

John Sievenpiper: Yeah, this is an important question. So I think, it has to be understood from the safety standpoint. So assessing the safety of these ingredients in the food supply, they're assessed individually. And all of the ones that are approved have an approval based on individual data on the individual sweetener. So in terms of safety, and I think that's important to understand, are these molecules, because they're a very heterogeneous group of very different set of molecules that all have this property of sweet taste and being able to transmit through the sweet taste receptor?

So that's that. When considering the data, assuming that they are safe and knowing that they are safe based on assessments, we can view it from a public health or clinical perspective. This allows us to see it as a tool or a category of components or ingredients that can displace calories. That's their intended use, right? To display sugars and calories.

So now we're looking at them as a class. And here we have much less data on individual sweeteners that we can do head-to-head. Now we've done it on acute studies. These are short-term studies where you give sweeteners individually and use network analysis to create a table. No sweetener is better than another in terms of displacing calories from sugars..

They all seem to do the job as advertised. If we examine the available data from trials and observational studies, we can discuss the sweetener that has been most extensively studied. And I would say most of the studies have been on those sweeteners that are most common in the marketplace.

So it's going to be what you're going to find. The most prevalent sweeteners will be Aspartame and Acesulfame potassium or ACE-K and Sucralose. So most of the research there is on those. The other thing to be said there too is that most sweeteners do not appear alone in food. So you may have it in a pack alone, but when you're having your food, you're blends. So even you could argue that looking at individual sweeteners isn't going to help you to understand what's happening in my diet beverage where it's going to be a blend of Aspartame and ACE-K or maybe all three with sucralose. And they're doing that to get at the sensory properties to elicit a sweet taste that's the most similar to sugars so that the consumer is sort of happiest with the beverage if you like. So a lot of that is being done just from the perspective of achieving the best sensory profile.

Jim Hill: And again, I want to emphasize back to safety. I want to highlight the importance of food regulatory agencies like the FDA and the Canadian regulatory group. These agencies thoroughly examine numerous studies to ensure the safety of food products. Our food supply in the US and Canada is incredibly safe because these organizations go out and look at the totality of the data. So I want to emphasize again, that they all seem to do the job, but they've all been considered safe by the FDA and the Canadian.

John Sievenpiper: Yes, even the European Food Safety Authority and the regulatory group called JAKFA, which operates under the WHO, all have reviewed these and looked at these sweeteners. And so what the FDA approves has been recognized by all of these jurisdictions. So you can be very confident that these are safe.

Holly Wyatt: And I love that they've been studied independently for the safety aspect. Consumers need to understand that they are seen as individual molecules. So that is important. All right, I'm going to switch gears a little bit because here's the other question that came from our listener.

And it's one I get all the time and I can't wait to hear your answer. So maybe, you know, when you have a non-caloric beverage with a non-caloric sweetener in it, what happens to insulin? Is insulin remain flat?

Does it go up? You know, there's the low-carb diet and so much. Lots of talk about insulin and what impact it may have. And with, you know, some of the new medications and everything, there's a big interest in hormones and insulin. If food contains a low-calorie or non-calorie sweetener, but no actual calories, does it still cause an increase in insulin levels?

John Sievenpiper: This is a great question. This is a major concern because the focus is on the mechanism rather than the actual clinical impact. It's like trying to find an effect for a mechanism, rather than the other way around. Trying to understand what's going on.

So the short answer is no. But I want to spend a little time just to so the listeners understand the level of evidence we have here. So we put together something called a network meta-analysis. And that's like a super meta-analysis because it looks at all the pairwise comparisons of where we compared a sweetener to a sugar or a sweetener to water or a sweetener to a sweetener, but then all the indirect as well, where we have a common comparator to increase the information size. We can create a table to see how different sweeteners and water behave. We can also observe how sugars like glucose, sucrose, and fructose behave. When we look at those and we look at not just insulin, but other important metabolic and endocrine responses related to carbohydrate metabolism, handling of glucose, but also food intake regulation because a lot of it's thought is, oh, maybe this uncoupling of sweetness and calories may lead to one consuming more. And we look at that and we look at not just insulin, but we look at other hormones like GLP1 and GIP. These gut hormones are associated with regulating food intake and managing glucose. We look at things like ghrelin and PYY.

So these are the main hormones if you like. We look at also glucose. Does it elicit a glucose response in terms of the metabolic effect? We don't see any effects across any of those for any of the sweeteners.

And so I think we could be confident that no. We looked at it in three different ways, importantly here too, because one is, well, some people say, well, it's the uncoupling of sweetness and calories. Some people say you should drink it as a refreshment, while others say you should have it with a meal. It's when you take it with other carbohydrates or fats or proteins in a mixed meal format. That's where sweeteners have their problem, which we call the coupling hypothesis or uncoupling. Whether it's coupled or uncoupled from food, we see no effect across postprandial glucose. It does not elicit a postprandial glucose-like systemic response does not affect the insulin or any of those hormones.

Jim Hill: Wow, that's the beauty of being able to look at pulling data together and looking at things.

Holly Wyatt: Just to clarify, does your data also demonstrate that it does not lead to an increase in cravings? Because some people say, you know, if I drink something that tastes sweet, even though no calories, it's good that I have no calories then, but then in an hour or two hours later in the day, my cravings come back for a sweeter for sugar or for, you know, wanting more. Is there something, anything in your data that can help with that?

John Sievenpiper: So this question has been looked at too. I don't know that it's been looked at as carefully, but they've certainly put it into trials where you can put it like craving inventories and different things. More importantly than cravings, what matters to me is whether it makes me eat more calories or not. And then beyond that, even more important to me, does it lead to me gaining weight?

Does eating more calories cause weight gain and health problems like diabetes? So when we look at that question, the answer is no. And in fact, they do work as you would expect. Using it to displace sugar can reduce overall energy intake without a complete compensation. It decreases weight, and it decreases some of the risk factors for those downstream. So overall, the answer is no.

Not being aware of how it increases our food cravings and leads to eating more later can result in weight gain and other negative effects of being overweight.

Jim Hill: Okay, Holly, you know what it's time for?

Holly Wyatt: Yes, Jim, go for it. Yes, the vulnerability question, John, you have to get vulnerable. We ask something that maybe you don’t want to share.

Jim Hill: But you have to anyway. So John, do you consume low calorie sweeteners?

John Sievenpiper: Like your wife, Jim, it sounds like enjoy to have a diet beverage. And so she often has it in the fridge and so I'll grab it. My beverage of choice tends to be sparkling water, but I do enjoy a diet beverage. A diet cola usually would be my favorite, a diet beverage of choice. And I would select that over a sugary or caloric beverage because frankly, I don't want the calories. So I make that choice.

Holly Wyatt: Do you have a favorite non-calorie sweetener of all that on the list we've been talking about, do you prefer one?

John Sievenpiper: I can tell you is I know which ones I don't like and it's purely from a sensory standpoint. So although they again, that's why we get a blend. So for some reason, for me, sucralose, I get more metallic and others do too.

And they describe that they can describe that with Stevie and others. With sucralose, I taste that more in yogurt in some beverages. So for me, it's probably aspartame, ace-k, that combination works very well. Purely from a sensory perspective that it, you know, for me gives me the closest sensation to sugar, the sweet taste that I prefer.

Holly Wyatt: So those preferences are coming out.

Jim Hill: Absolutely. You have choices. You have options.

John Sievenpiper: There are lots of sweeteners on the market and lots of options. So yeah, I think you can find the one that works best for you. And they don't all work the same in that cooking property.

The other thing you have to think about is that they're functional properties. So you can't cook with aspartame because it breaks down. You can with Sucralose. So you may like this particular sweetener. It may not have application for all the different foods you might want to consume it.

Jim Hill: But there are many out there. So you have choices.

John Sievenpiper: You have choices.

Holly Wyatt: Last vulnerability question. This is because it's an opinion. A lot of times this question falls under a kind of vulnerability because there's not necessarily a right or wrong. It's kind of your opinion about it. What do you think is the biggest misconception about low-calorie sweeteners that the public or our listeners have?

John Sievenpiper: Yes, there is a common misconception that people believe that consumption in this narrative contributes to weight gain, which I believe has primarily been perpetuated by the media. They may contribute to some of the adverse downstream complications of weight gain.

So they may sabotage our best efforts. We're trying to lose weight. We're trying to reduce sugars and other sources of calories and if these may not be able, it may not behave as advertised. It may be even have an adverse effect in terms of weight gain and some of those things. What I would say to that and that's something I didn't want to get into a bit is a lot of that's driven in nutrition. A lot of guidelines to are driven by epidemiology, large observational studies.

If you like that type of research has particular issues that relates, methodological considerations that relates to sweeteners. And the reason is it's a very high risk of something called reverse causality. So people are taking sweeteners in most cases to displace calories or sugars and they may be doing it because they're overweight or obese or they're at risk for obesity or risk for diabetes or have diabetes. So they're already at a higher risk to begin with and they're taking it as a risk mitigation strategy. Media reports suggesting a link between sweeteners and weight gain, diabetes, or cardiovascular disease might be due to reverse causality. It's not that the sweeteners are causing weight gain or cause diabetes, the cardiovascular disease. It's that because you're at risk for those things, it's causing you to consume the sweeteners. That's the reverse causality.

Jim Hill: That's beautiful, John. And so if you take a group of people, and you say, oh, the heavier people are using more sweeteners, well, duh, right?

John Sievenpiper: Exactly. And I want to say among the very serious epidemiologists, the guidelines, panels, workers, everyone is aware of that. In a study published in Diabetes Care, we used an epidemiology approach to analyze reverse causality, residual confounding, and behavioral clustering in observational studies. We aimed to reconcile the signals for weight benefit seen in trials. It's the epidemiology that's got this disconnect.

Can we find more biologically plausible and reliable signals that align better with randomized trials? And we did as we model change. So a lot of the epidemiology, a lot of observations, they just measure the people at the beginning and then they follow them for decades of years and look at the outcome. They don't sample diet throughout to see if there are changes in diet. They're just assuming the diet stays the same. So if you do change analyses, you see the opposite. You see weight loss and you see improvements, not increased risk.

Substituting sugar with a different sweetener in a drink can be a healthier choice and may even have a positive impact. You see weight loss, you see a reduction in cardiovascular disease, and then really big ones, reductions in cardiovascular mortality and decreases in all-cause mortality. So we're actually seeing signals now that very much support the randomized control trials show on those smaller intermediate outcomes. And we now have good harmonization across these different lines of evidence, if you like. So this is an area where I think the epidemiologists are working on this, and we're trying to improve those signals, trying to sort out their reverse causality. But just know when you have individual studies reporting, again, not pulling them all together.

Depending on the design, there may be methodological issues that we, as researchers, are aware of. However, the public and the media are not always informed or well-informed about these issues. Therefore, these issues are not always expressed or effectively communicated.

Jim Hill: Oh, Holly, I love this episode because we're not out there giving you our opinion. We're sort of telling you what the data says. And John, the thing that amazes me is how consistent the data are once you start looking at large quantities. This is fabulous. So now it's time for pie on the plate. So John, people out there listening, worried about managing weight, thinking about whether should I consume noncaloric sweeteners or not? What's your advice?

John Sievenpiper: My answer would be that based on the data if they choose to, they can. It works very similar to water, behaves very similar to water, and looks at the data, which would be our standard of care, our standard public health advice, or standard clinical practice advice, that it is a viable option.

To help people who enjoy sweetness and want to reduce sugar intake, they can opt for diet or low/no calorie sweetened beverages instead of sugary drinks. This allows them to still enjoy the sensory experience of sweetness while getting the benefits of consuming fewer calories. So yes.

Jim Hill: Fantastic. John, thank you. This has been wonderful. It's great to use science to show people the evidence behind our recommendations. So thank you so much for being part of our episode today. And we will see everybody on the next episode of “Weight Loss And...”.

Holly Wyatt: Yes, thank you so much. This is wonderful.

John Sievenpiper: Thank you.

Jim Hill: And that's a wrap for today's episode of “Weight Loss And…”, we hope you enjoy diving into the world of weight loss with us.

Holly Wyatt: If you want to stay connected and continue exploring the “Ands” of weight loss, be sure to follow our podcast on your favorite platform.

Jim Hill: We'd also love to hear from you. Share your thoughts, questions, or topic suggestions by reaching out at weightlossand.com. Your feedback helps us tailor future episodes to your needs.

Holly Wyatt: And remember, the journey doesn't end here. Keep applying the knowledge and strategies you've learned and embrace the power of the “And” in your own weight loss journey.