September 18, 2019 Tools and tactics for reducing added sugars intake
Over 90% of North Americans exceed the recommended intake level for added sugars in their diet. Diabetes Canada’s position statement emphasizes the urgent need for strategies to reduce the intake of added sugars by Canadians, especially those with or at risk of developing type 2 diabetes. Low Calorie Sweeteners (LCS) are one tool available for sugar intake reduction efforts. Consumers often have questions about LCS and their safe use. The approval process for a new food ingredient will be reviewed along with how regulatory agencies set Acceptable Daily Intake (ADI) values. In this session, speakers will review what is meant by an ADI for food additives and why it provides protection.
Watch this webinar to learn:
- How sweeteners are evaluated to determine their safe use
- Expected risk of sweetener use in different life stages
- How the acceptable daily intake (ADI) value for sweeteners are developed
Marie Latulippe [00:00:00] Welcome, everyone, to today's webinar, which focuses on low calorie sweeteners as one tool for the reduction of added sugars intake. My name is Marie Latulippe and I'm staff with ILSI North America. We're very excited to have you today. We'll start by way of a little background on the topic. We all probably know a long standing nutrition concern across the globe, with very few exceptions, is excessive intake of added sugars. Over 90 percent of North Americans exceed the recommended limit for added sugars in the diet. And as a result, consumers and practitioners really need practical and well accepted tools to reduce the intake of added sugars. And one of these tools is low calorie sweeteners. And although a variety of low calorie sweeteners have been approved as safe by global regulatory authorities, there is continuing confusion around whether or not low calorie sweeteners are a reasonable option for replacement of sugars in the diet. And our objective today is to promote the understanding of how the safety of low calorie sweeteners is evaluated by authoritative groups like the U.S. FDA, how we can apply this knowledge. And then finally, we'd like to provide practitioners with messages that can be used in your practice. This webinar is organized by two groups and you see the logos on that first slide there Diabetes Canada and ILSI North America and we just wanted to spend a couple minutes on each organization in case you are not that familiar.
Marie Latulippe [00:01:48] And ILSI North America to start with is a nonprofit organization that focuses on the understanding and the application of science as related to the nutritional quality and safety of the food supply. And this organization operates under a tripart model. And you see that icon to the left there. The idea is that we bring together scientists from these three sectors to operate cooperatively and with a shared responsibility to provide science that improves the health of the public. And on the next slide here, you see our core values and the idea is that these core values are reflected in all of our meetings as well as in the research that the organization supports. And if you would like to learn more about this organization, you can feel free to visit the website. And that's shown at the bottom of the slide there it is W W W dot ILSI na dot org. Now, Diabetes Canada is a national nonprofit organization that is dedicated to leading the fight against diabetes, and they do this through three primary tactics and those are helping those that are already affected by diabetes to live healthy lives.
Marie Latulippe [00:03:12] They also work to prevent the onset and the consequences of the disease. And then finally, they invest in research towards discovering a cure for diabetes.
Marie Latulippe [00:03:24] Diabetes Canada has actually been helping people affected by diabetes for over 60 years, and in fact, young Canadians now face a 50 50 chance of having diabetes in their lifetime. That's where you can see diabetes has a real sense of urgency about moving forward as an organization to deliver greater impact at the population level. And just to mention, as we get started in the webinar, you should see a chat box in your screen there and you should feel free to type any questions as the webinar proceedes. So no need to wait until the end to let us know what you would like to ask. This webinar has also been approved for one continuing education unit by the Commission on Dietetic Registration and you can also receive a certificate of completion from Diabetes Canada. And we'll let you know at the end of the webinar exactly how you can do that. So here's an outline of what we'd like to talk about today. First, we'll have Dr. Anyangwe tell us a little bit about how food ingredients are evaluated for safety at the US FDA. We'll also hear from Diabetes Canada on their position related to the importance of reducing the use of sugars and how low calorie sweeteners could be a tool. We'll hear about the application of the ADI. That's the acceptable daily intake, a value that will be covered by the first speaker and how that's applied in nutrition research. And then finally, we'll give you some ideas about how to use this information in your nutrition practice. So with that, we will welcome our first speaker, Dr. Anayangwe Njwen. Dr. Anayangwe is a regulatory toxicologist at the US FDA, where she evaluates the safety of direct food ingredients. Dr Anyangwe is a multidisciplinary scientist who has education and experience in many areas of science. And those include biochemistry, nutrition, molecular biology, toxicology and probably other areas as well. Dr. Anyangwe has over 18 years of higher education experience teaching a variety of courses, and those courses include nutrition and health. And with that, I'll hand the platform over to Dr. Anyangwe to tell us a bit about the US FDA.
Anayangwe Njwen [00:05:57] Thank you so much, Marie, for that kind introduction. I want to make sure can you see my slide?
Marie Latulippe [00:06:04] Yeah. We can see them.
Anayangwe Njwen [00:06:05] OK, so I'm going to speak to you this afternoon about the safety evaluation of food additives. Before they go into the market by the US FDA. And these are my views and not necessarily the views of the Food and Drug Administration. So the FDA has its mission to promote and protect public health like ensuring the safety of the nation's drugs, food supply, including dietary supplements, medical devices, cosmetics, biologics and tobacco products. So that's really the mission of the Food and Drug Administration within the FDA there are several centers. One of the center is the Center for Food Safety and Applied Nutrition. Within that center. You have the Office of Food Additive Safety. This is the office that's responsible for ensuring that our ingredients added to food are safe. So the mission of the Office of Food Additive Safety is to protect and enhance consumer health by ensuring the safety of all substances added to food, and, any substance that comes into contact with food. So why does FDA have the ability to regulate food ingredients for the purpose of this presentation I'm going to focus on food additives, but I want you to also understand that this office does regulate a wide variety of food ingredients. And one of them is generally recognized as food substances. However, for this presentation, I'm going to focus on food additives. So there was an amendment in 1958 to the federal Food Drug and Cosmetic Act. Call it food additives amendment of 1958. That amendment defined what you call food additives. And the food additive is defined as any substance, the intended use of which results may reasonably be expected to resolve directly or indirectly it becoming a component or otherwise affecting the characteristics of food. So any substance that's used in the package in preparation, storage, transportation of food is considered food additives, the indirect food additives that food contact substances. Again, for this presentation, my focus is going to be on direct food additives. Yeah, you'll have a list of categories of direct food additives if you have the sweeteners. You have the preservatives, nutrient, substitutes, texturizers, flavouring agents. You might have had a cup of coffee today and maybe you might have added some Splenda in it. So that's something we do regularly to ensure that before it gets to your table, it's safe for your consumption. So Section four or nine of the Federal Food and Drug and Cosmetic Act says that for a food additive to go into the market, there must be data submitted to the FDA to ensure that that food additives is safe and what is really safe? Safe in terms of food additive means that there is reasonable certainty in the minds of competent scientist that the substance is not harmful under the intended conditions of use and the safety standards for food additive is reasonable certainty of no harm. The burden of proof is on the petitioner. The petitioner has to assemble all data, whether favorable or not, about the safety of the ingredient under the intended conditions of use and submit that to the agency for review. And I want to talk about this provision of the amendment called the Delaney clause. The Delaney clause says that the FDA can not approve any food additive if it is found to cause cancer in man or animals. I would have to say that this applies to the food additive, but not to any impurities or components. So how do we do safety evaluation of food additive? Basically, it's the risk assessment process. You have the toxicology assessment. You have the exposure assessment. And you have a risk characterization. So the exposure assessment is typically done by a chemist and they provide us with an estimated daily intake or cumulative estimate, their daily intake. And this is usually based on the ninetieth percentile consumer because that gives us this high chronic dietary exposure for that particular food additive. I am a toxicologist, so I do review the toxicology part of it. So the day that comes in and we review the toxicology of it, determine what we have that is characterized. We have learned that the dose response from that data calculate what you call not acceptable daily intake and compare that acceptable daily intake to the estimated daily intake. And by that, we are characterizing the risk as toxicology. We noted that it does make the poison. So it really is something you have. And even if there is hazard associated with it, there's no exposure. Then there really isn't any risk if the exposure is very low compared to the dose at which you find the hazard, then the risk is very minimal. There isn't any risk. So typically in a petition, the studies that we get would be as sub chronic study that's done for about 90 days to 10 weeks, quality studies done for six months or more. And then we have absorption distribution, metabolism and excretion. So how does that ingredient get absorbed, how is it distributed within the body? How is it metabolized? How is it excreted? And then we also showed, you know, toxicity data, which indicates damage to DNA development to reproductive data, carcinogenic data and sometimes dependance on some of the signals that we get in the studies of the nature of the ingredient. We could also recommend that the petitioner submit neurotoxic data, immuno tampered data, and also if it's a proton, we would expect to see some allergen data and the focus for the toxicologist when we do assess this data is to look at where we have toxicological findings that are adverse you could have a toxicological finding, for example, you could have an increase in liver weight. Is that really adverse? So you have to look at the liver enzymes and look at the histo-pad data and all of that to make a determination whether or not that finding you see is adverse. Sometimes we also do have human studies. Typically, we don't have as many clinical trials as drugs do, but we do see short term clinical studies. We'd call them tolerance studies where they're typically looking at the absorption distribution, metabolism and its excretion. You can find this protocol or the guidance in the FDA Red Book on how to conduct some of these studies. So from the toxicological study, we determine what we call a point of departure. That point of departure is a point on a Toxicological dose response curve established on experimental data are observation lab data generally corresponding to an estimated low effect or no effect. This really marks the beginning of extrapolation to a toxicological fifth level. So that's what point of departure typically we use did no observe a no adverse effect level. So this is the dose at which the highest dose at which there is no observable adverse effect. So let's say you have four doses in this study and let's say at the highest dose we'll see if that thing changes in the liver weight enzymes and all of that. The dose next to that will be considered the dose where you do not see any adverse effects and that's been more of a adverse effect level. There's also a point of departure called the benchmark dose, both lower bound be empty and this takes into consideration the whole dose response curve. So we use that point of departure output, which could be in NOAEL or BMDL and divided by an uncertainty factor. So what that factor does is to extrapolate the animal data you get from animal studies to humans. The inter species differences between animals and humans. The inter species differences between one human and the other. And sometimes, if that NOAEL comes from a shorter term study, in light of this study, instead of a one year study, we could include an additional uncertainty factor for food additives. We typically use 100 because with the most of it that would come from chronic studies. So we divide that point of departure, which could be in NOAEL or by the uncertainty factor, which is 100 and we get what we call an acceptable daily intake. So that's one definition of the acceptable daily intake that I found online from the European Food Safety Authority. The first definition of an acceptable daily intake is an estimate of the amount of the substance in food or drink in water that can be consumed over a lifetime without presenting an appreciable risk to health. And this is expressed in mg per kilogram body weight per day. The definition from science directive is the maximum amount of a chemical that can be ingested daily over a lifetime with not appreciable risk. And this is based on the highest intake that doesn't give rise to any observable adverse effects so now we are talking about that low observe adverse effect level. So far, nutrition is in the audience. An acceptable daily intake is a safe level and it's kind of comparable to what you have for nutrients with tolerable upper intake level. So at the end now you have the CEDI or the EDI. And you also have come on the chemical exposure assessment. And you also have an ADI comming from the toxicological assessment. So you have to characterize the risk. One way to characterize what the risk is to compare the EDI or the CEDI to the ADI. It's the exposure, the estimated daily intake is less than the acceptable daily intake that is considered safe when you see the rebirth. If the EDI is greater than the ADI, then there is a problem. Another way to characterize risk is usually what we call the margin of exposure. The margin of exposure. You've been NOAEL or by the EDI or the BMDI over the EDI. The higher the margin of exposure, the lower there is the default is one hundred. And sometimes we conclude that the totality of the evidence. What does the distribution, what does the metabolism say? Do you have the same metabolites that are active that you find in animals, in humans? Is a mode of action the same? One example I'll give you is like the protein , you'll find a male rats involving a protein called the Alpha two new globulin. You do not have that protien in humans. So when you see a renal tumor in male rats, it's definitely not relevant to humans. So I just want to give you a table. Yes, sort of the focus for this webinar is on sweeteners. This is just a table that shows you the EDI compared to the ADI of several approved sweeteners. I'm just for the sake of time, I want to point to you to Aspartame. Aspartame, also known as Neutra-sweet or Equal. The FDA established an ADI of 50 for aspartame and the ADA is eight point seven. So based on what I just said, if the EDI is less than the ADA, eight point seven is less than 50 therefore is concerned safe. And you see the same thing for you for Acesulfame K also known as Sunett and same as you see for Advantame and you see. One thing I want to point out here too is a number of table top sweetener packets equivalent to the ADA. So let's take sucralose. So the ADI for sucrose established by the FDA is five and six per kilogram body weight and that's equivalent to 23 packets of the tabletop sweetener. So you have to consume twenty three for you to get to the ADI. So I want to use Advantame as a case study very quickly, So Advantame if a non-nutritive sweetener that was approved by the FDA in 2014, it's also been approved in Canada, Europe and Australia and New Zealand. So this is just to tell you how much data comes in the petition for Advantame. There were 37 clinical studies done in different animal models, rat, mouse, rabit dog. And the studies range from cancer studies to neuro tox to immuno tox to admin data. And its pivotal studies were all done under good laboratory practices and there were four clinical studies done in therapy and type 2 diabetics. So for Advantame even though there were several clinical studies and four human studies of these, four of these studies were found to be critical studies in that petition. A rat reproductive study, a dog 2 week study, mouse two year and they run to about. I think they're roughly about say it was the study that was used to determine the ADI Cancer Assessment Committee of the FDA. It concluded that Advantame treatment did not result in any increased incidence of tumors in rats in this two year. And the one portion of that article was used to calculate the ADI to determine what in the NOAEL was that was used to calculate the ADI for several reasons. It was 52 weeks long. There was a survival group and there was no cancer in the two year bio acid. So the highest goals in that study, though, were four doses in 0 2, PPM, 10000 PPM and 50000 PPM. And the highest dose of fifty thousand fifty and was found to be the NOAEL. Well, that was converted to a mg per kilogram body weight to be three thousand two hundred and seventy nine. And when you divide that a 100, the ADI for Advantame was found to be thirty two point eight mg per person per day the EDI was estimated to be zero point 1 6 7. So again, you see here that the EDA is less than the ADI and therefore considered safe. And if we convert that to per person per day by multiplying by 60, it still comes to that phase. So, based on the data that was submitted in that petition, concluded that there is reasonable certainty that the substance is not harmful under the conditions of use and therefore approved Avantame. So in conclusion, I want consumers to know that the FDA is food additive review process is a rigorous science based process. It is found process mapped by scientific rigor and high integrity and before a food additive gets to that consumer table. It has gone through a thorough scientific investigation and ADIs are safe levels to give consumers the confidence as new data becomes available might have to go back and reevaluate the safety of the food additives. Thank you.
Marie Latulippe [00:20:48] Great. Thank you, Dr Anyangwe. In our next talk. We'll hear from Diabetes Canada about their position on added sugars intake, as well as how they incorporate some of this low calorie sweeteners, safety evaluation information into their materials and messaging. So our next presenter is Joanne Lewis. Joanne is a registered dietitian, as well as the director of Knowledge Management, at Diabetes Canada. And she has worked there for over six years. She's involved in developing position statements and advising on policies related to diabetes, care and management, as well as the dissemination of the clinical practice guidelines. Joanne has several years of experience practicing in clinical settings as well as in the development of diabetes, education, material and programing. So we will now hand the platform over to you. Joanne.
Joanne Lewis [00:21:39] Thank you, Marie, for the introduction and for the opportunity to be a part of this panel presentation today. It's a real pleasure for Diabetes Canada to be able to partner with ILSI to bring this webinar to you. And I want to acknowledge also my colleague Erin Krusky, who's responsible for working closely with ILSI and for ensuring that we have a great turnout for today's presentation. And the response was actually really positive. So that means that this is a topic that many people are really interested in learning more about. So thank you, everyone, for being here. And also a huge thank you to Lindsay Clark from TimedRight for making sure that everyone got logged in and the technology works. So it's no surprise that to anyone that diabetes has a serious impact on on on the health and quality of life in Canada. A diagnosis of diabetes or pre diabetes is made every three minutes. Understanding what causes type 2 diabetes is more important now than ever.
Joanne Lewis [00:22:42] And I'm just trying to advance my screen, which I am not having any luck. So let me do that.
Joanne Lewis [00:22:51] Apologies for that. So understanding what causes Type 2 diabetes is more important now than ever. And if we can prevent the onset of diabetes and pre diabetes, we stand a better chance at improving the health and and lives of Canadians. So I won't take up too much time as there are other speakers who have a lot of very interesting information to share with you today. But essentially, these are the key takeaway messages from Diabetes Canada. Recently sugar and especially sugar sweetened beverages have grabbed the media's attention and the attention of health organizations such as Diabetes Canada, Heart and Stroke and the World Health Organization. There's more evidence today that there are health implications of sugar consumption beyond dental care. Recent research has evolved to demonstrate that there is a link between the consumption of sugar sweetened beverages and an increased risk of heart disease, type 2 diabetes and gestational diabetes. There is no one solution to reduce the amount of sugar Canadians consume. Rather, there are a number of different strategies that can play a role in today's discussion. In today's discussion, we are mostly focusing on one possible solution and that is the substitution of sugar with low calorie sweeteners. What we've learned is that individuals who consume more than or equal to 10 percent, but less than 25 percent of total energy from added sugar have a 30 percent higher risk of death from heart disease or stroke when compared to those who consume less than 10 percent. And for those who consume 25 percent or more of calories from added sugar, the risk is nearly tripled. You may or may not be surprised to know that the single largest contributor of sugar in our diet is sugar sweetened beverages and individuals consuming more than one sugar sweetened beverage per day have a higher risk of developing diabetes. And as added sugar consumption increases, the risk of death from heart disease and stroke also increases. And so in response to these findings, Diabetes Canada felt it was important to publish a position statements. The Diabetes Canada position statement on sugar was published in 2015, around the same time that the World Health Organization published its recommendation on the intake of free sugar. If you'd like to get a copy of the full position statement, please contact us at Diabetes Canada or check our website at Diabetes.ca The World Health Organization published three main recommendations in 2015. Two of them are considered strong recommendations. And these are one a recommendation for reduced intake of free sugars throughout the life course. And number two, in both adults and children, intake of free sugars not exceed 10 percent of total energy, Which is in line with the recommendations in Diabetes Canada's clinical practice guidelines. The World Health Organization also made a conditional recommendation to further reduce the intake of free sugars to 5 percent of total energy. But the evidence for this recommendation was low quality and it was related to dental caries only. 10 percent of total daily energy intake is about 50 grams of sugar or 12 to 13 teaspoons of sugar a day. So how do average Canadians measure up to these recommendations? It's estimated that 15 percent of Canadians daily caloric intake comes from sugars, which is about seventy five grams of sugar a day, which is equal to about two cans of regular soda per day. And as Marie had mentioned earlier, that about approximately over 90 percent of people worldwide exceed the intake or the acceptable intake or recommended intake of added sugar per day. Diabetes Canada, along with other health organizations, is advocating for alternative and healthier hydration strategy and the reduced intake of sugar sweetened beverages. Some of the recommendations made in the position statement include a call to the government to implement a tax on sugar sweetened beverages and use the revenues generated to promote the health of Canadians. To have clear nutrition labels on packaged food, and include the amount of free sugars on these labels to restrict and prevent marketing of foods to children and beverages to children to support an improved access and affordability to nutrition foods in all regions. To label free sugars on menus in restaurants. To help consumers make more informed choices on what they eat. And for recreational events, schools, workplaces, facilities, government spaces not to offer sugar sweetened beverages for purchase and instead provide free water for consumption. A couple of years ago, the University of Waterloo looked at the sales data for soft drinks, fruit drinks and 100 percent juice. Over the course of eleven years, sales in all three of these categories decreased. During this time period, however, sales of other popular sugar sweetened beverages increased. These include energy drinks, sweetened coffee, sugar sweetened flavored water, sugar sweetened, drinkable yogurt, sweetened tea flavored milk and sports drink. And so it's important in our message to the public to emphasize that sugar sweetened beverages do not just include soft drinks. On this slide are a few examples of the type of communication that can be effective in educating the public about the amount of sugar in some common beverages. There are many examples of these online. This is an example of one that was created by Diabetes Canada. At Diabetes Canada we no longer serve sugar sweetened beverages at any events or meetings. We also have committed to serving healthier food options at events. And of course, we're asking and encouraging other organizations, particularly health organizations, to do the same. So a very common question that we hear from the public. Is, is diet soda better than regular soda? And as we were just seeing on the other slide, we're really not really limiting this discussion to just regular soda as there's so many other sweetened beverages, sugar sweetened beverages to choose from. However, this is a very common question. So we may not have all the answers about diet soda, but what we do know is that there are no nutritional benefits drinking diet soda. So when we say better than regular soda, what we really mean is that diet soda do not have the same harmful effects as sodas that contain sugar. But what we just heard in the previous talk was that acceptable daily intakes are considered safe. And that is definitely the message of Diabetes Canada that when it comes to low calorie sweeteners themselves, their position is that sweeteners used in our foods and drinks are regulated and safe to consume. That the ADI should be referred to when talking with the public. That it's a good idea to use information about the different types of sweeteners and how they're differently digested and the make up of the various sweeteners. So that when you're counseling people about the amount that they're consuming in one day, that there are ways to not actually accumulate too much of any one sweetener over the course of a day by switching it up or using soft drinks that are sweetened with one type of sweetener, but then using a different sweetener in their coffee. Let's say we definitely need more high quality studies that look at long term effects and we should feel confident that artificial sweeteners do not cause harm and are safe to consume. On the right of your screen is an image of one of the education resources that Diabetes Canada has created to help educate the public about the use of low calorie sweeteners. This is available for free at the free download on our website. So I'm going to end here so you can continue with the rest of the program and I'd be happy to answer any questions later.
Marie Latulippe [00:31:25] Great. Thank you, Joanne. Our next talk will take a look at how a metric for safety here are the ADI, which was described by both of our previous speakers. How the ADI is applied in scientific research. And as Joanne noted, this research often forms the basis of professional practice guidelines, so it's important to understand its use. I would like to introduce Dr. Danielle Wikoff, who is a health sciences practice leader for Tox Strategies, which is based in Asheville, North Carolina. She specializes in using evidence based methods to evaluate health hazards and risks that are associated with exposures to a wide variety of consumer products. And that includes food, ingredients and industrial chemicals. And Dr. Wikoff, area of focus is on the use of systematic methods in support of risk assessment applications, including the development of health based toxicity values. So with that, I will turn it over to you, Dr. Wykoff.
Danielle Wikoff [00:32:25] Thank you, Marie. And again, thank you for the opportunity to be part of this presentation today. It's a very interesting set of talks and I think that as we have heard that the the process for developing ADI is very robust, yet the communication of how to use ADIs continues to be somewhat complex. So that is what our focus of of this research is, to help build tools to bridge that gap before saying more important to disclose that this work that we'll be presenting on was commissioned by ILSI North America. And then a number of other disclosures from coauthors are provided in our protocol, though most are related to our various expertise with low calorie sweeteners and no conflicts were noted. So as I was mentioning, the the overall objective of this project is really to create a resource for practitioners and public health professionals to help bridge and provide clarity on ADIs and the use of the safe use of low calorie sweeteners as it relates to safety goals. To do this, we felt like that baseline, a baseline needed to be established based looking at how ADIs and daily intake levels are being addressed in the context of ADIs in the peer reviewed literature. So our overall approach is was to look at what is available in the literature to chart the types of types of publications and the ways that ADIs are being used. And then to think about that in context of the overall research question in terms of is the ADI being used appropriately? What types of communication or what types of tools are needed to better help public health professionals and practitioners to better use and better understand ADI and how to compare to EDI etc.? This work is carried out by a multidisciplinary team on the left, as it is a table of authors, all from Tox Strategies with a variety of backgrounds, including Ms. Seneca Fitch, who is also on the line today, who has been responsible for a large portion of this work. She is an information specialist and evidence analyst at Tox Strategies. And important to this work, as well as we have a number of advisory panel members, one of whom you've you heard at the beginning and also the fourth speaker in this presentation who provided a high level of expertise as it relates to the toxicology of low calorie sweetness as well as nutritional aspects. All of this work is being held to very high transparency standards based on transparency, transparency and openness promotions are top guidelines. And this entire project, including our protocol, are posted on the open science framework. And this is freely available to to visit the website here on is provided on the slide and find out information about this project. The systematic map that we are conducting is based on the Joanna Briggs Institute framework for scoping reviews. Those terms are commonly used as synonyms, scoping or scoping reviews and systematic maps. The steps are shown on this slide. They're very linear in that you start with defining the objective in the question a priority. You make sure that that fits with overall research methods. Excuse me. Overall research objectives. You describe a plan for for conducting and resubmit essentially addressing the question and again, you do that a priority. The protocol you then moving into to the middle of the of the figure. Once you have established a priority your methods, you go and conduct those methods which generally involve extracting the evidence is from from what you've selected and then charting it based on characteristics that you've extracted and then summarizing the evidence in relation to this. So the research question followed by reporting and really where we're at in this project now is we have searched, extracted evidence and where we've been charting and synthesizing it relative to the findings. Again, I want to mention that the protocol is also available on the open science framework. All of this work was carried out in accordance with the protocol which which outlines these specific search syntax, the databases, the inclusion exclusion criteria, the methods for extracting, etc. in this protocol. So the review question that we tailor the actual mapping exercise around is in nutrition research studies, how our daily intake levels of low calorie sweeteners in human populations assessed in the context of acceptable daily intake drive by authoritative bodies. This was addressed specifically using the PCC structure or the population concept and context. So we defined each of these elements as shown on this slide. And based on each of these elements, we also derived inclusion and exclusion criteria for each component. So for example, the concept being comparison of the ADI values to a daily intake of low calorie sweeteners we require the studies reported the quantitative intake estimate of low calorie specific low calorie sweeteners included. However, we would exclude studies the estimated exposure via for example, blood or serum or urine concentration. So again, we required it and a measure of intake and similar inclusion exclusion criteria were developed for each. Following review sorry, implementation of our search strategy using multiple databases Pub med and em base. We came up with a fair number of articles that were screened at the title, and abstract level for those that made it through based on the title and abstract, we obtain full text through these exercises we also implemented a duplication process. We also looked at studies and included additional studies based on hand searching and reference chasing. Throughout this process, we did exclude a fair number of the studies. Common reasons for exclusion were, for example, that there was not a quantitative intake of estimated or measured. It was not a population of interest, but where it was a low calorie sweetener wasn't adressed that might have just been mentioned in a study. In the as we applied the criteria through the multiple phases we ultimately charted or included one hundred and twenty one studies. Now, for these 121 studies that compared an intake to an ADI in some capacity, we had to further refine these or categorize these based on their relevance. And this was a refinement to our protocol, those implemented at the stage of review calibration. this was needed because we were observing that within our evidence base, which was incredibly heterogeneous. The study designs and objectives really varied. We were finding not only primary versus research, but secondary research that reviews that we're addressing this topic, but in different ways, also unique to this study. The type of information that we were looking for would commonly be reported in the discussion, for example. So unlike looking for studies that met very specific research objectives in terms of an experimental design, we were looking more for how data were being interpreted relative to the ADI, which makes the evidence slightly could be difficult to to look for or essentially also required that we looked at full text for many more publications. We use two categories for this included evidence directly relevant as well contextual. So for the directly relevant category, study had to make a comparison of an intake or controlled exposure to an ADI, whereas for the contextual these studies were important to have for informing the question, but weren't direct evaluations. These were often reviewed in etc.. By taking this approach, we were able to prevent collection of duplicate data. In many of the reviews, the primary studies were were a fact. We also collected different volumes of information from from these types of studies. So getting a little bit here into the into the findings, the study characteristics by the level of relevance. So so here on the left you see the the actual sweetener, the individual sweeteners, including the first year of publication where there was a comparison. Aspartame was the first year of what was a publication excuse me, with a sweetener that was first published on in context of comparison to ADI. I'd also had one of the. It was one of the sweeteners with the most directly relevant publications. So this next chart shows the publication frequency for each of the low calorie sweeteners of interest by year. Now, clearly, you can see that the publications comparing have certainly increased over time. In fact, over half of the identified studies were published in the final eight years of our mapping exercise compared to the to the approximately 20 years prior to that. To give you a minute to study this, but you can see that consistent with the slide before several of the sweeteners, perhaps more commonly used or more commonly evaluated, sucralose, saccharine, aspartame tended to have the most publications within a year and across time. Also of interest was the geographical distribution of of the studies that we were finding here, we've shown the darker the shading, the higher the number of studies in the populations for this area.
Danielle Wikoff [00:43:24] There were several.
Danielle Wikoff [00:43:28] There were several characteristics of interest in here, for example. Ireland was one of the countries with the most publication. However, a number of those publications come out of the same laboratory. So as we go forward to map and chart and interpret these results, we'll provide breakdowns of of the evidence in such such a manner. Also of interest, when you think about the geographical distribution, is the content is the context of the ADIs used. So as we heard that the ADIs undergo a rigorous process, but there are also multiple authoritative bodies, established values, ADI values or similar. And so when you think about the geographical distribution, we have also categorized the ADIs being used. The majority of the studies use the ADIs developed by ASIO. Those are primarily the studies conducted in Europe, followed by those from JAXA and then FDA. So as we continue to work through the charting, the element and the element of trust is really to see how the ADI was used. And this is as we as we collected information. It was certainly very complex because of the heterogeneity of the evidence base. And so the way that we are approaching this is for the studies that were were categorized as direct. So they had a direct measurement of low calorie sweetener in some capacity. We combined four elements of the given study. The goal of the study, the population and health status, age and in the context that the comparison was being made. And so over to the right, there's a figure that shows or a map that shows some of these relationships. And as you can see, there really is quite a span. So we're looking at many different populations. There were many different objectives. And the number of studies which is shown by is emphasized by the thickness of the line also varies across the evidence base. Overall, we had a you know, there's pretty. There was good coverage for a number of areas of interest. Most for example, if there was a study in a diabetic population, there was more than one or so shown. Here are some of the scenes that we are going to be able to gather in terms of characterization of this evidence base. So drilling down a little bit more on these comparisons of how the ADI is used in the evidence base. There were generally a limited number of categories of how ADIs were used. The majority of studies in the evidence base where we're EDI to ADI comparisons. So these were studies that looked at dietary intake, whether that was measured or modeled in a given population. They often looked at multiple sweeteners and then compared the output or the EDI to ADI. And so that was shown in the blue here on this wheel. We also found a number of studies that looked at me that discussed the ADI in context of safety or adverse effects. And these studies, for example, use the ADI as a way to determine the type of dose to use in an experimental animal study, for example. Perhaps they were looking at specific safety endpoints and they wanted to mimic what human exposure may be. Conversely, the ADI was also discussed in safety studies where if in effect in a study was seen, the exposure levels associated with that effect were compared to the ADI. There were also there were also a handful of studies looking at ADI and context of metabolism and thinking about how the ADI level could be used or interpreted in context of metabolic differences, etc.. So as we continue to work through this synthesis and interpretation, we'll be working with our advisory panel to go through more of the details with particular focus on the ADI to EDI portion of the evidence base. Overall, we had found that as reported by the study authors, the ADI is generally used in an appropriate manner and only very few of these studies reported concerns or thoughts in context. The potential exceeds that of the ADI or how the ADI is used. But by and large we were seeing comparisons that were consistent with the definitions of the API. We will also do additional breakdowns by populations, health status, age, etc. and then combine this with our expert advisory panels expert knowledge in this area to help identify possible needs for additional tools for it or approaches for education and communication for practitioners and health professionals. This work is also currently being drafted in the form of a publication and will be submitted to appear in the journal. And with that, I thank you very much again for your attention and the opportunity to present these findings.
Marie Latulippe [00:49:11] Awesome, thank you, Danielle. We've covered a lot of information today, which we realize may be new to many of you that typically focus on nutrition and less on safety. So how is this information applicable to nutrition practitioners? This brings us to a presentation by Dr. Deepa Handu Dr. Handu serves as a senior scientific director for the Academy of Nutrition and Dietetics Evidence Analysis Library. She has methodological expertise in conducting systematic reviews and quantitative analysis in the field of nutrition and in her position at the Academy. She has led the development of a number of systematic reviews in clinical practice guidelines, and she's conducted research to actually improve evidence based methods for the library. So I will hand it over to you, Dr. Handu.
Deepa Handu [00:50:06] Thank you so much, Marie, and I hope my slides, everybody can see my slides. Just confirming that. And thank you to everyone who's been so patient and listening to our speakers. Ten more minutes. So stay with me. And just a disclosure that this presentation as presented by me, develped by me, and it reflects my experience and my knowledge in the field and not the academy's position, or policy or anything.
Deepa Handu [00:50:32] So moving on.
Deepa Handu [00:50:39] When I started thinking for this presentation and thinking, what would the practitioners want to think about? Do you know when it comes to low calorie sweeteners, the parts in my mind, where safety first. ADIs that you have heard a lot for everyone, I'm going a little bit. Talk about it. Not in details as others did. Then comes to mind is the effect on health outcomes. Is there any scientific evidence that clarifies that issue? And then finally, what do I tell my clients? So let's talk about safety a little bit. As you have heard from previous speakers, a lot about ADI, so I'm not gonna go into details. But you know, what I wanted to say mainly is that low calorie sweeteners, thoroughly tested and carefully regulated by FDA and U.S. and Health Canada and Canada for approval using foods and beverages. As mentioned before, the ADI is the amount of an ingredient that a person can safely consume every day over a lifetime without risk. It's an extremely conservative number to make sure that there's no chance of harm. The slide states unless the FDA and Health Canada approve low calorie sweetness. I'm not gonna read each of them. So what foods typically have low calorie sweeteners? Nowadays low calorie sweetness are widely present in foods, medication for personal care products like your toothpaste might have it. If you go and look at the ingredient list and in many other foods and beverages but are not marketed specifically for make management. So talking to your clients, think about telling them to read ingredient list because we are really familiar with some of the ones over here, like diet sodas, some energy drinks, sports drinks, but people never think about yogurts. The flavoured yogurts might have these. So thinking about, you know, other foods and non-food products that can be out there which might have these sweet now low calorie sweeteners present. The next question that always comes to mind is safety. So at present, based on evidence, low calorie sweeteners are safe and approved by the regulatory bodies. They are some of the most researched and studied food ingredients. However, at this point, we still keep on debating about the long term effects on human health. So there is still that issue hanging on. But based on all the organizations that are regulating the quality of these things, we should feel confident and safe. This slide states the current evidence on low calorie sweetness. And as you can see, it is a little conflicting. So evidence from cross-sectional and prospective cohort studies suggests that the use of low calorie sweeteners is associated with increased body weight, whereas evidence from randomised controlled trials suggests that the use of low calorie sweeteners for weight lose, you know, is beneficial. So that's where the whole confusion comes in between. And then comes the other types of study designs like systematic reviews and meta analysis. The findings from these studies is a little bit mixed. So most of the discordance that we see in these findings, they could be to a number of factors like study design limitations and sometimes its challenges in interpreting the findings. Sometimes that's what population is being studied. So when we talk about cross sectional or prospective studies for most of these studies, we do see a lot of self reported data. So that might be beat. And one of the issues. The other issue in those kind of studies, which has popped up a lot, is called something called effect modification. That means the existing unhealthy diet could be influencing this insulin relationship. Also, sometimes the association between sweetener consumption and weight gain, maybe because individuals, you know, they're already predisposed to obesity and they consume more sweeteners in their attempt to prevent weight gain. Usually you'll see it written up as a reverse causality that they're assuming something and they're doing to, you know, to fight that they're doing this action of consuming way more. There can be a lot of other unmeasured, unexplained factors that could influence this relationship between the sweetner consumption and weight related metabolic outcomes. It's like in most of the food related studies and nutrition related studies. There's so many co-factors that can influence that relationship. And one of them could be that when people consume non nutritional sweeteners, they also consuming some sugary foods. They do not change the full diet. So there's a lot of debate right now about out, you know, this conflict between evidence and and hence the systematic reviews and meta analysis, which at a top level study design. They are mixed, too. And the reason being there based on the original research study. So when you watch those studies and you're still getting confused and conflicting results. There are many organizations out there that have to have developed these guidelines in regards to low calorie sweeteners. They all have a little different take on the message as they're addressing different populations. Also, you know, the approach of developing these guidelines a little different. Some of them are based on systematic review, some of them are based on comprehensive reviews. So a little bit of difference in the angle could change the language a little bit. Overall message, most likely from all of them is kind of a standard message, but you'll see a little different take by them if you start reviewing them. There are references, but all of these at the end of the presentation. The academy, on the other hand, has two guidelines in this area and one of them is in the pregnant diabetic women. It was published in 2016. The I'm not going to read the full thing, but the bottom line of this guideline was that if they choose to use if pregnant women with gestational diabetes choose to use a non-nutritive sweetener, they can. But remember, you should select the FDA approved once and you should limit your dietary intake to ADI within the ADI. So within the safe range, the ones that are recognized safe, if they consume those, they should be OK.
Deepa Handu [00:56:53] There is no evidence that.
[00:56:58] It now just so any adverse effects that the. The cavie also has another guideline on the diabetics, people, people who have diabetes. This was published in 2015 and the message is mainly saying that it's safe to be consumed within the recommended ADI. However, you should educate your clients and remind them, you know, the big thing is that they should know that other sources of calories and carbohydrates in these foods are also present and they need to be taken into consideration. Use of non nutritive sweeteners has the potential to reduce overall calorie and carbohydrate intake. If substituted for calorie sweeteners without compensation by intake of additional calories from other sources. So again, emphasizing a moderation of intake of all other food groups as well as a full diet becomes very important. So what are the major practice implications for like and from the dietitians perspective, what should you know? You should be familiar, with the science behind non-nutritive sweetness for sure. Because that's how you prepare yourself and be ready to answer the questions of the client. But you also need to understand how each sweetener works. Their function and how they taste feels a little different. Non-nutritive sweeteners, non nutritive sweeteners can trigger a slightly different taste receptors and they have different properties when they are used in different applications like acid foods or heated foods. So being a little familiar about that and also to work with your clients to understand their needs and interests, you might realize if you work with one right now that some of them have preferences, a certain non-nutritive sweetness compared to others. And this brings their personal preference in to talking to them. In that respect is very important. Understanding the science brings the whole question about how do you look at this evidence when you know that it's so much of conflict going on. The key thing to keep in mind would be please do not base your opinions on one single study in today's day and age when everything gets published so fast. As online medium, what you see is a study popping up here. Or a newspaper covering just one study and talking about it? But beware of the single study syndrome. There's something called that because people base their opinions just on one study. So when you are reviewing literature, make sure that you evaluate the study of the day for the methodological issues. Look at whether the studies are animal versus human based, who is the population of this study, whether they're healthy people or overweight people, people with diabetes, etc.. So the condition of the population they are studying is very important. Whether the epidemiological studies work in clinical trials. We did talk about them a little bit. Remember, clinical trials provide excellent results, but are they applicable in free living people? Whereas epidemiological studies have the whole issues of confounding factors. So do those studies control for some of the known confounding factors? That other big thing is the dose dose of the LCS as is very important. Some of the studies that have shown historically, some of the studies have shown that that have shown adverse effects. They were giving way about way above the ADI doses. So keeping in mind what is an appropriate ADI? What kind of doses and what are these studies talking about? Also making sure that these studies are doing some comparisons between treatment group and a control group comparison and reporting those not just, you know, focusing on one area of their feeding health. This what happens. We're trying to make comparisons within that population base. So these are some important things to keep in mind when reviewing studies of some other things which a lot of you might be familiar with. But when you consider using LCS and working with your clients, make sure the key things are blood glucose, responsive to values, sweetness. How are they going to be use ADI? FDA approved and then also take into consideration some special considerations, certain conditions that your clients might have. So if someone has an increased desire for sweet intake do you replace basically it or here I'm trying to tell you what to do. You might be still feeling confused. So what do you do with your client? Are you going to save a comment or not recommend using LCS? So it just tells you work with an individual client. Some of them would have increased desire for sweet intake. And in those scenarios, replacing some of high sugar foods that LCS would be very helpful because it does help put down your caloric intake. Keeping in mind they are paying attention to other things that they are eating. Makes sure that it's FDA approved. And the other thing to remember when you're educating or discussing LCS with your client is that although many products in the marketplace use artificial sweeteners, it doesn't mean that the product is completely carbohydrate or calorie free to use the artificial sweeteners. You know, they might be still high in fat, saturated fat. So these products that are out there and they are kind of saying we use artificial sweeteners, look out for the fat content, the saturated fat or salt content. It's still essential that people read nutrition labels before they buy a particular product. So based on the current evidence that we have right now, there is no reason not to to recommend if somebody wants to use it and incorporate in their diet. The key thing to remember is that the potential benefits from low calorie sweetened beverages or foods as a replacement for sugar sweetened beverages. If their use is accompanied by a compensatory increase in energy intake from other sources. So again, bringing in the concept of overall helpful dietary pattern is advised. Yes, you can substitute some things in your diet, but that's not a magic bullet. There are other things that you still need to take into consideration and think about it. I imparted. That's all keeping time and everything in mind and going quickly, I think that's all I had. Any questions? I'd welcome. Thank you.
Marie Latulippe [01:03:16] Thank you very much, Dr. Handu, that brings us to our wrap up in Q and A. So if anyone has questions, please type those in the chat box. Again, if we can't get to them today, we will still be able to answer those and post on the Diabetes 365 Forum just to let you know if you would like a record of your participation. It would be helpful, for it's kind of required to fill out that post webinar survey and that will be available, as you can see here on the event page where you registered after the webinar concludes. You can just go back there after this is over. And the survey should be posted with a couple of questions that will answer. One is, of course, everyone wants to know if the slides will be available after the presentation. We actually won't have the slides necessarily, but we'll have this entire recording available. And I believe we'll be able to provide everyone who registered with a link to that recording. We'll do that shortly. So one question is, I think for Joanne or anyone in Canada. But the question is, do you know of a couple of current examples of products in Canada that actually contain Advantame?
Joanne Lewis [01:04:33] OK. Joanne here. So currently Advantame is is accepted as a as a sweetener in Canada. It's not currently in any products. I think it just this past couple of weeks ago, I think there was approval for it to be used in certain beverage and food products. So I think it's to be seen in the near future what where that will end up on the shelf.
Marie Latulippe [01:05:07] OK. Thank you, Joanne.
Marie Latulippe [01:05:08] And in the interest of time, I think we're actually a little bit over. If you have more questions. There is an opportunity in the survey to type questions. So that's another way we can answer anything.
Marie Latulippe [01:05:20] So we just want to thank everyone for participating today. We really appreciate it. We would love to have your feedback on the survey on this. And it also asks if you'd like to learn about any other topic. So thanks again to everyone and have a great rest of day.
Moderator: Marie Latulippe, MS, RD, ILSI North America
Presented by: Joanne Lewis, RD, Diabetes Canada
Njwen Anyangwe, PhD, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, U.S. Food and Drug Administration
Daniele Wikoff, PhD, ToxStrategies
Deepa Handu, PhD, RD, Academy of Nutrition and Dietetics