IRA FLATOW: Artificial sweeteners are back in the headlines once again. The WHO recently classified aspartame as a, quote, “possible carcinogen.” Well, what exactly does that mean?

We’re going to dig into the science behind that decision and what the research tells us about the health effects of artificial sweeteners, and we want to hear from you. What are your questions about artificial sweeteners? Our number 844-724-8255, 844-sci-talk, or tweet us @scifri.

Joining me now to talk about all things artificial sweeteners are my guests Marji McCullough, Senior Science Director of Epidemiology Research at the American Cancer Society, based in Atlanta, and Dr. Walter Willett, Professor of Epidemiology and Nutrition at Harvard’s T.H. Chan School of Public Health, based in Cambridge, Massachusetts. Welcome, both of you, to Science Friday.

WALTER WILLETT: Thank you. Good to be with you.

MARJI MCCULLOUGH: Thank you. Thank you. It’s nice to be here.

IRA FLATOW: to have you. Dr. McCullough, there’s a lot of confusion about the term “Possible carcinogen.” Can you explain what that category actually means?

MARJI MCCULLOUGH: OK. Well, yes, it’s understandable that that’s confusing, but “Possible carcinogen” is one of four categories that the International Agency for Research on Cancer’s Monograph program is one of the four classifications that an agent can fall into after being critically reviewed by a team of scientists. So possible carcinogen means that an agent is possibly carcinogenic to humans. This category is generally used when there is limited evidence of carcinogenicity in humans, or there is sufficient evidence of carcinogenicity in experimental animals or strong mechanistic evidence.

But there are established criteria to identify– to classify an agent into one of four categories. and that ranges from Group 1, definite carcinogen, Group 2a is probable carcinogen, 2b is a possible carcinogen, and then and then there’s not classifiable, Group 3. So 2b is one step up from not classifiable.

IRA FLATOW: You were part of the committee that helped determine or decide– weighed the research to make this decision. How do you decide what category to put it in? How did the committee weigh the research to make this decision?

MARJI MCCULLOUGH: Well, yes. I was one of the 25 scientists that reviewed the evidence, and there are four groups that evaluate the science, when it comes to global exposure of humans to aspartame. And then there’s a group that reviews the evidence from human studies and another group that reviews the evidence from animal studies and then mechanistic studies to see whether or not an agent could have plausible mechanisms to cause cancer.

So the four groups review the evidence in detail and then come back together and have a consensus determination of the final conclusion. But there are criteria to follow for whether a study is informative, based on the study size, the study quality, et cetera.

IRA FLATOW: So how should folks understand this research in terms of making their own personal decisions? Should folks consider cutting out diet soda?

MARJI MCCULLOUGH: Well, IARC reviewed– that’s International Agency for Research on Cancer, for short– IARC reviewed the evidence in late June. And then shortly thereafter, another organization called JECFA, which is a Joint Expert Committee on Food Additives, evaluated the safety and the risk associated with aspartame. And they reinstated the acceptable daily intake limit of 40 milligrams per kilogram.

And that, based on their review, that– because it’s on body weight, it depends on what your body size is and how much aspartame is in a particular product– but that could equate to 10 or 15 cans of diet soda and if that’s your only source of aspartame.

So people can take this news, take a look at their diet, come to reflect upon what you’re doing. If you’re only consuming artificially sweetened beverages, or in this case aspartame, occasionally, that’s not likely to be a problem. I think moderation is key. But if you’re drinking diet soda instead of water, or really consuming a lot of these products, you might consider cutting back.

IRA FLATOW: This is Science Friday from WNYC Studios. Dr. Willett, we often lump artificial sweeteners together in a group, but they are not all the same. Right? Can you explain the two broad categories?

WALTER WILLETT: Well, that’s absolutely right. There are dozens of artificial sweeteners that are being used now. And very broadly, there are some like aspartame and that’s the primary sweetener used in diet sodas, which is, until very recently, been the overwhelming source of artificial sweeteners in human diets. And even within this group, they’re very hyper-sweet molecules, and they’re very different molecules. And we, therefore, can’t make any generalizations about possible harms within these highly intense sweeteners.

And then there’s a whole other group called sugar alcohols, and those are basically not too different than sucrose, table sugar, in their sweetness, but they’re not absorbed or digested like sugar is or sucrose is. And so they come with very few usable calories, and most of these pass right through the GI tract without being absorbed. We don’t have the enzymes to absorb them or metabolize them and use them as energy. So they’re going to have a totally different biological effect, and I do have some concerns about those.

I honestly think that, as Dr. McCullough said, up to a dozen or so cans of diet soda, which virtually nobody consumes, is very safe. If there’s– although, I wouldn’t recommend it, but most importantly is to not go back to regular natural sucrose or natural sugar because of being afraid of aspartame. We know that there’s lots of harms, very definite harms we can see in terms of diabetes, cardiovascular disease, and increases in cancer risk with large amounts of regular sugar in our diet. So that’s the worst possible decision somebody could make to go back to that because of fear about aspartame.

But these sugar alcohols that mostly pass through our GI tract, but in quite large amounts, because they have the bulk and body of table sugar, we don’t really have long-term human evidence on their safety. And the fact that they’re entering the colon in substantial amounts, very likely going to change the environment there, change the microbiome in ways that we don’t understand at all, and we don’t understand the implications of those changes. So that gives me pause for concern about consuming those on a regular basis.

IRA FLATOW: And Marji, I understand you wanted to continue talking about the decision for–

MARJI MCCULLOUGH: Oh, right. Right. I realized that I hadn’t noted, the decision to classify aspartame as a Group 2b, or possible carcinogen, was based on what was considered limited evidence on studies in humans for liver cancer. So that was the basis for the determination, along with some limited evidence in animal studies and mechanistic studies. So there was something there for each of those streams of evidence, but it wasn’t conclusive.

IRA FLATOW: OK.

MARJI MCCULLOUGH: Yeah, and but for humans, it was specifically liver cancer.

IRA FLATOW: Thank you an email from Marianne, in Berkeley, wants to know about stevia extract. Is it safe? What is it made out of? Dr. Willett?

WALTER WILLETT: Right. It is an extract from stevia plant, and it is one of these intensely sweet molecules. So it’s natural, but just being natural doesn’t mean that it’s beneficial or even safe when we consume it in unnatural amounts. So again, this is something where we have very little long-term evidence, and that does give me some concern.

And I think it’s better, as Dr. McCullough said, to in general use artificial sweeteners for replacing sugar and helping us get off of, say, diet sodas that are consumed in large amounts. Something like a nicotine patch, which isn’t the best thing to be using on an everyday basis, but if it can replace regular sugar in the amounts that many people are consuming is definitely harmful, then there can be some benefit in doing that. In general our diets are overly sweet, far sweeter than humans consumed until just a few years ago.

IRA FLATOW: Let’s go to the phones, Eva, in Richfield, Minnesota. Hi, Eva. Welcome to Science Friday.

EVA: Hi.

IRA FLATOW: Hi there. Go ahead.

EVA: Hi. Yeah. I was wondering about sucralose as a sweetener. I don’t drink enough water, and I try to do that by putting something called MiO in my water, because it flavors it. But then I read a report that sucralose has negative effects on DNA?

IRA FLATOW: And so you’re worried about it.

EVA: I sure do.

IRA FLATOW: OK. Let me see if I can get an answer. Thanks for calling. Dr. Willett, what is sucralose?

WALTER WILLETT: Well, it’s, again, one of these many different molecules that has intense sweetness. So consuming it in small amounts gives us that sense of sweetness. It activates our sweetness receptors in our mouth, and the animal studies have suggested it’s safe. That’s why it’s been approved by the FDA to use, but again, we really don’t have long-term human studies on this. And I think people just have to realize that you’re taking a little bit of a risk.

IRA FLATOW: Marji, are there new sweeteners coming out all the time? Do you have to keep track and testing them?

MARJI MCCULLOUGH: Well, yes. There’s changes in sweeteners over time, and there’s changes in the trends. People have been, over time, consuming a little bit less aspartame and more stevia and more sucralose, and in fact, their consumption has really increased over time, especially in kids.

But for our studies at the American Cancer Society, we’ve been including questions about specific types of artificial sweeteners that we’ll be able to evaluate in the future in relation to cancer. But as Dr. Willett said, there’s not a lot of evidence on them so far.

IRA FLATOW: Let’s go to–

WALTER WILLETT: Yeah–

IRA FLATOW: Yes, go ahead.

WALTER WILLETT: –if I can just add there a quick word, that of all the sweeteners, really we have the best data on aspartame. In our long-term studies, the Nurses’ Health studies, health professionals follow up study, we’ve been following tens of thousands of people since it was introduced into the food supply, in the early 1980s and updating that information every four years, as we go along.

And after about 30 years, we took a deep look at artificial beverage, diet sodas basically, almost all sweetened with aspartame, and there was no hint of an increase in overall cancer mortality during that time, with many thousands of people who had develop cancer. So that gives me a pretty confident conclusion that there’s no big problem there and, again, much less of an impact than naturally sweetened with sucrose beverages.

IRA FLATOW: And in–

MARJI MCCULLOUGH: And if–

IRA FLATOW: I’m sorry. Go ahead.

MARJI MCCULLOUGH: I’m sorry. If I could just add that the studies that were reviewed for the IARC monographs were mostly the types of studies that Dr. Willett describes, prospective cohort studies in humans. And there were large studies from around the world, and most of them do only have one measure of aspartame at baseline. But they have many years of data and lots of follow up, and that’s the type of data that contributed to the human evidence.

IRA FLATOW: Let me go to the phones, and we’ll get back to another question. Let’s go to Ann, in California. Hi, Ann.

ANN: Hi.

IRA FLATOW: Hi there. Go ahead.

ANN: Well, many years ago, we’re talking the ’80s, I had repeated episodes of severe dizziness, vertigo-like, and this was in Europe. And I had been eating these candies, and not even that much, and it turns out there was this official government warning, like we have on our cigarette packs, that eating so many grams of sorbitol in 24 hours would cause dizziness and other symptoms. But when I stopped, it stopped. And this was like the equivalent of four gumdrops.

And ever since, I’ve noticed that xylitol, sorbitol, all the sugar alcohols cause this insidious vertigo, and I don’t see warnings about that anymore. I can’t find research anymore online, but I keep coming across friends and even family that get this severe vertigo, even hauled away by ambulance. In older woman, it’s a severe symptom. And then there’s no explanation for it, and if they stop the sugar alcohols, which are in a lot of dental products and low-carb foods, it goes away.

IRA FLATOW: Yeah, let me–

ANN: I’m just wondering if your guests know about this and what’s happening.

IRA FLATOW: Well, that’s interesting, because Dr. Willett, you honed in on sugar alcohols here in one of–

WALTER WILLETT: Yes. I’m not familiar with the literature on that specific symptom, but in the amounts that they’re being consumed, people can get gastrointestinal symptoms, so cramping, loose stools, that kind of thing. These are not small amounts, like the amounts of aspartame we would be taking in. In fact, back when I was an intern, in the 1970s, that’s how we cleaned out people’s GI tract was give them a large amount of sugar alcohol, and these will have symptoms. So people should be aware of that. Again, definitely, if somebody is having these kind of symptoms that are being described, and they get better not consuming these sugar alcohols, certainly, avoid them.

IRA FLATOW: So you’re not questioning whether it happens or not. You’re saying, it might happen, and just don’t do that when you do that.

WALTER WILLETT: If that’s your experience, that makes sense.

IRA FLATOW: Let me ask you about the WHO recently saying that artificial sweeteners should not be used in weight loss. What do you make of that?

WALTER WILLETT: Yeah. I have to disagree with that, and they left out, in their review, their meta analysis– it happens to be our study– but it is probably the most detailed long-term study looking at weight change in an observational manner. Again, we followed tens of thousands of people and compared changes in weight among people who started using diet sodas versus people who started using sugar-sweetened beverages or increased their amounts of sugar-sweetened beverages. And there was no increase in weight with the artificial sweeteners and definitely an increase in weight with the regular sugary beverages.

And there are other randomized trials that have looked at replacing sugar-sweetened beverages with artificially-sweetened beverages, and there were some benefits in weight change. Not in every study, not completely consistent, but I think in the best studies, there is some benefit in helping people get off of sugary-sweetened beverages. So that’s the place, if we’re going to use them, they may have some use. Again, like a nicotine patch, helping people who are really having a hard time reducing their sugar-sweetened beverages. I think there is some role, but not as a primary beverage on an everyday basis for the whole of someone’s life.

IRA FLATOW: Could there be a link between artificial sweeteners and the increased risk of heart disease? And I bring that up because there was a study in the British Medical Journal of last year of 103,000 people, and let me quote from the conclusion. “Suggest a potential direct association between higher artificial sweetener consumption, especially aspartame, acesulfame, potassium, and sucralose, and increased cardiovascular disease risk. They remain a controversial topic. They’re currently being re-evaluated by the European Food Safety Authority and the WHO and other health agencies.” Dr. Willett, has your studies showing any connection?

WALTER WILLETT: We, again, you just in that mouthful mentioned a whole bunch of different molecules, and almost for sure, they’re going to have different implications for health. Again, some of those were sugar alcohols, where I do have some concerns. But we have looked at artificially-sweetened beverages, which would be aspartame, and we don’t see an increase in cardiovascular disease or overall mortality.

Maybe a hint in people consuming– just a tiny, little blip and people consuming four or more servings a day. But again, contrast that with regular sugar-sweetened beverages, there’s a huge contrast. There’s definitely increases in diabetes, cardiovascular disease with regular sugar-sweetened beverages.

IRA FLATOW: OK. Let’s go to the phones, to James, in Portland, Oregon. Hi, James.

JAMES: Hi. My question is about the relationship between sucralose and, to a lesser extent, aspartame with SIBO and IBS. And also do you think that there is a correlation between the increase in larger numbers of young people developing colon cancer and the increasing the amount of sucralose use?

IRA FLATOW: Yeah. There has been that uptick.

WALTER WILLETT: I don’t think we have any direct evidence of that. Again, if someone is having– like irritable bowel syndrome that you mentioned, if someone’s having symptoms, there’s no harm in taking some of these artificial sweeteners. There’s no harm in getting off of them and seeing if the symptoms improve. I think you can be your own judge in something like that.

But in terms of the increase in risk of colorectal cancer in younger individuals, basically mostly under 50, I don’t think we have any evidence that that’s due to artificial sweetener use. Definitely, part of it is due to the increasing rates of overweight and obesity. Whether that explains all of this increase of colorectal cancer, it’s not so clear, but a fairly substantial piece is explained by the increase in overweight and obesity.

IRA FLATOW: This is Science Friday from WNYC Studios. Question from Facebook, do artificial sweeteners raise insulin levels, and what are the resulting consequences? Now, I have heard of research way– I can’t remember when– where the body may be tricked into thinking that it’s not an artificial sweetener when you taste it. Could that be happening, Dr. Willett?

WALTER WILLETT: Again, it depends what you’re comparing it to, but there’s definitely not the same increase in blood sugar, very little increase in blood sugar and insulin response to that, as we would get from a regular sugar source. So there has been this hypothesis that they may be a problem, because they keep us conditioned to a high level of sweetness. And therefore, we want to eat a lot of sweet foods and beverages, and there may be something to that. Most of the evidence has not supported that, but I think that’s still a possibility.

And again, that’s an issue of keeping this expectation of high level of sweetness in everything we eat and drink is pushing in a direction of a less healthy diet. It is going to be harder to appreciate the gentle sweetness of a fresh carrot or a fresh apple, if we expect everything to be super sweet.

And the food industry probably could answer many of these questions better than any of us in the scientific community, because they spend vast amounts of money identifying just how much sweetness Americans expect to consume in their foods. And they know, if they go down a little bit, they can lose market share. So they’re keeping us conditioned to this very high level of sweetness in our–

IRA FLATOW: It’s all about the money, again, as we keep– Sam, in South Carolina, welcome to Science Friday. Hi, Sam. Are you there? Hey.

SAM: Yeah. I don’t have a question. It’s just more of an observation. I wait tables, and I’ve been doing it for years. And I’ve noticed that people who drink diet soda want their diet soda refilled at a much higher rate than any other soft drink.

IRA FLATOW: Even the sugary soft drink?

SAM: Even the sugary soft drinks, it’s always the diet sodas that I’m constantly refilling.

IRA FLATOW: Wow. That’s a great observation. Let me get a reaction. Thanks, Sam. I see Marji there smiling or laughing about that one.

MARJI MCCULLOUGH: How do you see me? Yes. That is an interesting observation, and I agree with what Dr. Willett said. I think people can become accustomed to this sweetness in their beverages. And I don’t know in terms of that specific example, but that’s also a reason to be cautious with children, whether they’re giving children artificially-sweetened beverages or other foods.

Because they could develop a taste for sweetness that then tracks into adulthood. So I think it’s something to keep in mind. And generally speaking, people who drink or consume a lot of low-calorie sweeteners or artificial sweeteners don’t necessarily have better diets, better diet quality. Studies have shown that they may have worse diet quality and actually consume more added sugar from other sources too.

IRA FLATOW: Well, so there is the message. The takeaway is, if you have to use artificial sweeteners, go ahead, but it’s better to not be so sweet. Calm down your taste buds for expecting all this sweetness.

I want to thank both of you for taking time to be with us today. Marjorie McCullough, Senior Scientific Director of Epidemiology Research. That’s at the American Cancer Society, based in Atlanta. Dr. Walter Willett, Professor of Epidemiology and Nutrition, at the Harvard T.H. Chan School of Public Health, based in, of course, Cambridge, Massachusetts. Thank you both for taking time to be with us today.

WALTER WILLETT: Thank you.

MARJI MCCULLOUGH: Thank you.

WALTER WILLETT: Have a good weekend.

IRA FLATOW: You too.

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