Live Event for Feb 21: Do No-Calorie Sweeteners Affect Health?

What: Virtual Press Briefing on New Study of Low- and No-Calorie Sweeteners and Glycemic Response.

When: Tuesday, February 21 2022 at 1:00 PM EST

Who: Dr. Tauseef Khan, Research Associate in Epidemiology at the University of Toronto

Details:

Public health organizations that are working to reduce intake levels of sugars have suggested that sweetness in the diet be reduced (including from both sugars and low-calorie sweeteners), hypothesizing that consumption of sweet-tasting foods leads to a desire for more sweets. 

This Newswise Live Event will discuss the effects of dietary sweeteners and overall diet quality on metabolic and endocrine health.

Dr. Khan from the University of Toronto will participate in the expert panel and discuss the different aspects of these effects, with questions prepared by Newswise editors and submissions from media attendees.

TRANSCRIPT

Thom: Okay, welcome to today’s Newswise live event. We’re here to talk about no-calorie sweeteners and their effect on health. We have with us today, Dr. Tauseef Khan. He’s a research associate in epidemiology at the University of Toronto. And he’s also affiliated with IAFNS. 

We’ll get started with Dr. Khan and please Dr. Khan, if you would, tell us a little bit about the study that you’re working on and the results here relating to these no-calorie sweeteners. And how is this different from other papers and studies about these sorts of topics? 

Dr. Khan: So, as we know that sugars have emerged as a dominant nutrient of concern and the call for its reduction is presented by all health agencies and nutrition organizations, and dietary guidelines. And the focus has been – so one thing that can replace those excess calories or excess sugars is low-calorie sweeteners. However, low-calorie sweeteners have been –  in the media, there has been a certain amount of information given which might hint at harm. So that attention needs to be addressed. Is there harm with the low-calorie sweeteners? And some proposed mechanisms are that they affect sweet taste receptors, which impair your glucose response, and insulin response, or if you eat them with carbohydrates, then there is another acute response leading to glucose intolerance. So, we wanted to answer these concerns actually. 

First of all, many of these papers or studies did not consider that these low-calorie sweeteners are distinct compounds. So, an effect of one was attributed to all others. Plus, also there are methodological design issues with many of these studies. So how they are taken, what are they taken with, and what are they compared to? So, we want to address that question. 

So, we undertook a systematic review and meta-analysis to compare non-nutritional sweetened beverages to water and also to caloric sweeteners. 

So, recent evidence shows that low-calorie sweeteners can replace those calories. However, the question is there is some concern regarding low-calorie sweeteners – Or I would call them non-nutritive sweeteners over here because that’s the name that we have used, the term we have used in the paper. 

So, eight had been approved by the FDA and the attention has been, as I described, that these non-nutritive sweeteners may affect sweet taste receptors or glucose intolerance, or they might lead to glucose intolerance and then the results are usually given. So, one study is done and it’s attributed to all others. 

So, we want to address those concerns. 

So, what we did was- we did a systematic review and network meta-analysis. So, it’s a kind of a review of all acute studies, all studies which looked at the intake of non-nutritive sweeteners in the beverage form in which the non-nutritive sweetener was either single or blend, compared them to water and sugary beverages. And the outcomes we looked at were glucose, insulin, and all other endocrine responses that are related to sweet taste or weight gain or appetite. 

We looked at three different kinds of studies and one was uncoupling intervention. So where non-nutritive sweetened beverages are consumed without any calories. So, you consume them in water compared to a sugary beverage or compared to water. So, they’re not consumed with any calories. 

Then the second one was coupling interventions with non-nutritive sweetened beverages consumed with calories. And that can answer the specific question that we want to ask. 

And another one was the delayed coupling where intervention with non-nutritive sweetened beverages is taken first and within 15 minutes, or there’s a delay of up to 15 minutes and then a meal is taken afterwards. So this answers the question – so if non-nutritive – do they affect these various responses or outcomes of these endocrine hormonal factors and can they then affect your meal response afterwards? This is a result which is a network meta-analysis. So, the advantage of – I’ll just explain what it is. 

So, these are individual – so this is a big network plot where we have compared the individual sweeteners are here on the axis that is coming down and their individual non-nutritive sweeteners, then blends are here, then water, and these are caloric sweeteners which mean either glucose, sucrose or fructose. 

So, what’s happening is every bar shows you a comparison. So, aspartame over here is compared to glucose or sucralose is compared to ASK and aspartame or saccharin is compared to over here to water. So, network meta-analysis allows us to compare each non-nutritive sweetener to another. So, every comparison can be compared to another, even if in the original studies they haven’t been compared with each other. And what we see is – anything that is bold is significant effect or anything that is blue is in a significant effect that is non-trivial. So, meaning that they are significant and that response actually needs attention. So, what we see is between the individual non-nutritive sweeteners and water, there’s no difference. They’re actually acting similarly. There is slight deviations here but those are non-trivial or unimportant. However, we see a large difference between the sweeteners and the non-nutritive sweeteners and caloric sweeteners. What it shows is compared to caloric sweeteners and non-nutritive sweeteners are acting similar to water and only caloric sweeteners are increasing glucose response. And this was in 14 trials. And if we see a coupling intervention where non-nutritive sweetener was given with calories, there is no difference between the control arm and the non-nutritive sweetener arm. And this is just one for glucose but we have this for all outcomes. I’m just showing you for glucose but we have all these outcomes, more than 11 outcomes that we have compared. 

Delayed coupling where the non-nutritive sweetener is given slightly before the calories and calories are taken afterwards. We see no difference between all these non-nutritive sweeteners and sweetener blends and water. So, they’re very similar to water. They’re inert. They have no effect on the subsequent glucose response at all with meals.

 So, what do we find? 

So, we found that non-nutritive sweetener beverages had no effect on acute glucose, insulin or other endocrine response markers like GLP-1, GIP, PYY, ghrelin, or glucose. These are all appetite or food-related endocrine factors or hormonal factors. 

Non-nutritive sweeteners were similar to water. The findings are similar to previous reviews looking at this topic, ghrelin, Nicole and Tucker. So, these studies looked at either glucose or insulin but we have looked at all the other outcomes too. The results are similar to recently published systematic reviews in which rigorous methods were used. These were from our group also last year, Lee 2022, which was cohort studies and Maglin 2022, which was RCTs. And we show a similar difference of caloric versus non-nutritive sweeteners. 

Non-nutritive sweeteners will be similar to water. 

Our results differ from select narrative reviews, in vitro studies and human studies as they failed to consider key methodological and design issues, which I have described earlier like – a pattern of intake. So, these are three patterns we are looking at, plus the type of non-nutritive sweeteners and the comparator. Are you comparing it to another non-nutritive sweetener? Are you comparing it to blend? Are you comparing it to glucose? Are you comparing it to sucrose? So, all this actually matters. 

This paper actually answers these two very important questions that are raised for acute studies, especially acute responses. One is that there’s uncoupling a sweet taste from caloric content because of non-nutritive sweeteners that disrupt metabolic consequences of sweet taste – through hormonal changes. 

So, what it says is, that when you take non-nutritive sweeteners there are no calories involved. The body actually acts differently, and in that uncoupling, then the body then has to have a different response and it actually eats – there’s a different glucose or hormonal response because of that sweet taste disruption. However, when we looked at non-nutritive sweeteners uncoupled from calories, they did not elicit any different response. It was similar to water and I haven’t shown this but we also had a subset of people with type two diabetes and they showed the same result. 

So, this actually answers this sweet and coupling hypothesis. 

Another hypothesis that is presented in the literature is the non-nutritive sweeteners might alter metabolism when consumed along with carbohydrates. So, on their own they are fine but if you eat them with carbohydrates they have a different response and that is why they might be harmful. However, when we looked at that question – when we looked at the coupled and the delayed coupling studies, delayed coupling was a preload and non-nutritive sweeteners had taken preload. They did not produce any alteration in acute glucose or other metabolic responses and the effect was similar to water. 

So, we answered these two very important questions that are being raised in literature. 

In conclusion, that is my final slide, no differences in acute metabolic and endocrine responses were shown. These metabolic responses were glucose. These are the ones that regulate glucose of food intake. When we compared non-nutritious sweeteners, singles or blends with water – across three patterns of intake. Our study actually supports the use of non-nutritious sweetened beverages and an alternative replacement strategy for sugar-sweetened beverages similar to water. 

That ends my presentation and thank you, and I’m open to questions now. 

Thom: We’ve got a couple of questions from Marlene at Medscape. You addressed some of them already a little bit, but just to recap, if you could, in a few words. Even these sweeteners, these low-calorie sweeteners and things like soft drinks, your study is showing that they do not increase appetite or cause weight gain, and that’s one of Marlene’s questions from Medscape. 

Dr. Khan: Yeah. We can talk about appetite and weight gain related to many of these hormonal factors that we study. These are acute trials, so they’re not looking at your weight gain three months down the line or your appetite changes over a long term. We’ll be looking at acute responses within two hours. Does it affect GLP, GIP, which affect appetite? Your glucose-insulin response might affect how your calories are stored as fat or not or if they are burned up. When we look at those short-term studies, there is no effect of the non-calorie sweeteners. The results are limited to short-term responses. However, these short-term responses can be considered to inform a long-term effect also, because if anything is happening long-term, it should then show something in the short-term also. 

Thom: In light of that, another question from Marlene, that’s a good follow-up to that is, what should then doctors advise patients who want to follow a healthy way of eating and lose weight? The suggestion of substituting these kinds of sweeteners versus others – and as you said, looking at the more long-term patterns versus these acute ones, what would you say in response to that question? 

Dr. Khan: So Long-term cohort studies – there is some literature published which shows that in the long term when you take low-calorie sweeteners or sweetened beverages, there is an increased risk of weight gain, diabetes, or mortality. However, those studies suffer from major methodological issues, and we addressed them in another paper we published recently in Diabetes Care. What those studies do is a lot of people when they’re taking excess calories, so they’re already at high risk of disease. As soon as either the doctor tells them or consciously, they decide to change and then switch to low-calorie sweeteners. When the study is done, actually they are recorded as taking low-calorie sweeteners, but it actually is that risk – so those who switch to low-calorie sweeteners are actually the ones who are at higher risk of disease already because of the excess intake over a lifetime of intake previously, like over decades. That is something, a phenomenon called reverse causality. 

The high risk itself makes them switch to low-calorie sweeteners. When we look at those studies, we see that effect. 

When you actually control for that, and we have done that in the previous paper in Diabetes Care where we looked at people who actually switched from sugar-sweetened beverages to low-calorie sweeteners. Actual switching and adjusting for their weight, and second, those who actually increase their intake of low-calorie sweeteners. In both situations, we found that low-calorie sweeteners actually reduced the risk of type 2 diabetes and mortality, and also was associated with a reduction in weight. Both in the long-term and the acute term, if rigorous methods are used and properly controlled methods are used, then low-calorie sweeteners show that they can be a viable replacement for excess calories.

Thom:  Another question from Kristy Adams relating to oral health and these non-nutritive sweeteners. She references that the World Health Organization has mentioned that dental caries is the single most common health condition globally. Do these low and non-nutritive sweeteners play a role in reducing sugar consumption to support oral health around the world? 

Dr. Khan: Thank you for this question. It’s very interesting. The WHO sugar guidelines for adults and children are actually based on oral health. Excess sugars or sugars that you take actually affect your oral health. So a reduction in sugar intake is recommended because of its benefits to oral health, and oral health then has association with chronic disease also. 

If anything, that can reduce the consistent intake of sugary substances will be beneficial for oral health. So, this is not my area of research, I haven’t seen literature on how low-calorie sweeteners benefit oral health. However, if they are associated with the reduction in replacing those sugar intake, it most likely will affect or benefit oral health also. 

Thom: What, if any, gaps are there still in this research that you’d like further studies to address? 

Dr. Khan: Yeah, there are still some gaps. In acute studies, we had very few studies for blends. The majority of trials looked at single non-nutritive sweeteners. However, in industry, the majority of foods have blends in them. 

More studies or more trials need to be done on blends. That’s one issue. 

Then there has to be consistency between what we see in human studies and what is seen in animal studies. In animal studies, they give very high dosages, and then they show some effect. However, with humans, the amount is so small, it doesn’t. More studies need to be done regarding those specific non-nutritive sweeteners which have shown some effect in animal studies. But in our study, we show that they are also inert in their effect on humans. 

Thom: If we don’t have any others coming in the chat, I wanted to ask Dr. Khan about this sweet uncoupling that you referred to. Could you just summarize that for us as best you can, this separation between the taste of sweetness versus actual calories, and help us make a little bit of sense of that for maybe a takeaway here? 

Dr. Khan: Sweet uncoupling hypothesis is just a hypothesis. It’s not been proven yet. This was presented a few years ago in the literature which says that when there’s uncoupling of sweet taste from calories. When you eat sweet food or caloric sugars, it has sweetness. 

However, non-nutritive sweeteners are sweet, but they have no calories. 

The hypothesis was when there is an uncoupling or separation between that, our body becomes confused and it disrupts the metabolic consequences of sweet taste. When you eat non-nutritive sweeteners, you feel the sweetness, but your gut then is expecting calories, but those calories do not arrive. It then starts responding through some acute hormonal changes. These factors GLP, GIP1, or glucose or insulin response actually then is disrupted. That is the hypothesis. 

Thom: Your feeling is that this study is evidence to disprove that hypothesis? 

Dr. Khan: Yes. Our study is uniquely placed to answer that question because we looked at studies where non-nutritive sweeteners were separated from calories. It did not elicit any acute hormonal response and they were very similar to water. It was both in healthy people and also in people with type 2 diabetes. 

I believe our study actually answers that very well. 

Thom: Fascinating. Thank you so much, Dr. Khan. I think that’s all the questions we have for today. With that, I will say thank you to Steve Gibb from the IAFNS for helping to arrange this and thank you, Dr. Tauseef Khan from the University of Toronto. Really fascinating stuff and good luck with your next studies. Thanks very much. 

Dr. Khan: Thank you. Thanks for having me.