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The Leading Voices in Food

E205: Here’s what sugar and zero-calorie sweeteners do to your body

Hosted by: Kelly Brownell (Duke)
May 17, 2023

Today we speak with an expert on sugar and things meant to replace it. The stakes are high. Very high. Sugar consumption in the population is astronomical and so is the use of sugar replacements. Knowing the impacts of both could help experts provide dietary guidance and help consumers make decisions. Dr. Robert Lustig is Professor Emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco. He specializes on the regulation of energy balance by the central nervous system; body weight regulation, appetite, metabolism, and is very well known for his work on sugar and their substitutes and on policies aimed at improving the diet of the population. A YouTube video on the effects of consuming sugar called “Sugar: The Bitter Truth,” has now been viewed 24 million times.

Robert H. Lustig, M.D., M.S.L. is Emeritus Professor of Pediatrics in the Division of Endocrinology, and Member of the Institute for Health Policy Studies at UCSF. Dr. Lustig is a neuroendocrinologist, with expertise in metabolism, obesity, and nutrition. He is one of the leaders of the current “anti-sugar” movement that is changing the food industry. He has dedicated his retirement from clinical medicine to help to fix the food supply any way he can, to reduce human suffering and to salvage the environment. Dr. Lustig graduated from MIT in 1976, and received his M.D. from Cornell University Medical College in 1980. He also received his Masters of Studies in Law (MSL) degree at University of California, Hastings College of the Law in 2013. He is the author of the popular books Fat Chance (2012), The Hacking of the American Mind (2017), and Metabolical: The Lure and the Lies of Processed Food, Nutrition, and Modern Medicine (2021). He is the Chief Science Officer of the non-profit Eat REAL, he is on the Advisory Boards of the UC Davis Innovation Institute for Food and Health, the Center for Humane Technology, Simplex Health, Levels Health, and ReadOut Health, and he is the Chief Medical Officer of BioLumen Technologies, Foogal, Perfact, and Kalin Health.

Interview Summary

URL for “The Bitter Truth” video.

Let’s start out with this – so the big hope is that sugar replacements, artificial sweeteners, non-nutritive sweeteners, all known as different things, replace sugar and that people can enjoy sweet taste without the calories. But, of course, the picture is way more complicated. Being an endocrinologist, you are in a good position to explain what happens when the sweeteners enter the body. I’d like to get to that in just a moment, but let’s lead off with another question. Why is it so important for people to consume less sugar?

First, let’s talk about what sugar is. The food industry tells you that sugar is just empty calories. I wish that were true. If that were true, then you could basically spend your discretionary calories on sugar with no problem. But it’s not true. There are two molecules in dietary sugar: the sucrose or the high fructose corn syrup or honey maple syrup agave. They are all basically the same. One molecule of something called glucose, one molecule of something called fructose. Glucose is the energy of life. Glucose is metabolizable by every cell on the planet. Glucose is so important that if you don’t consume it, your body makes it. The liver will take fats and turn it into glucose. It will take amino acids and turn it into glucose process called gluconeogenesis. Glucose actually makes your cells work better. It makes your mitochondria function better, the mitochondria being the little energy burning factories inside each of your cells. Glucose, for lack of a better word, we can call good. Fructose, on the other hand, it is completely different, is metabolized completely differently inside the body and inside the liver. What fructose does is it inhibits mitochondrial function. It actually inhibits three separate enzymes necessary for mitochondria to do their job. So, fructose inhibits energy generation. Now, the food industry will tell you fructose is four calories per gram. Fructose is ready energy. That is why they put high fructose corn syrup in the sports drinks, for example. Well, turns out, that fructose may be ready energy for a bomb calorimeter, but it is not ready energy for your mitochondria. You don’t burn in a bomb calorimeter (a laboratory instrument), you burn via your mitochondria. It turns out, mitochondria are actually poisoned by fructose. So in fact, fructose is a chronic, dose-dependent mitochondrial toxin and this is why we have to eat less of it. But the problem is the food industry keeps putting it in anyway despite the fact that it is killing us.

How much more of it are people consuming than what you might suggest?

The American Heart Association years ago came up with a upper limit per day of about 25 grams, which would be about six teaspoons per day. I was actually part of that group that came up with that and I stick to it because that’s what the data show. We are currently consuming 94 grams. We are consuming almost quadruple the amount that is the upper limit. Now, the notion that something could have empty calories but still be bad for you is not a crazy one. We have two things in our diet that we know are calories but are clearly toxic to us. One is alcohol. Alcohol, seven calories per gram, but alcohol is a poison. And then also trans fats. Trans fats are nine calories per gram, but trans fats are a poison. So just because something has calories doesn’t have anything to do with its metabolic impact.

Where are people getting all the sugar from? I’m assuming it’s not from their sugar bowl.

Exactly. It is not the sugar they add. It is the sugar the food industry adds. Now, where is it? Well, the obvious source is soft drinks. That’s number one by far and away. I mean soft drinks are basically, you know, the devil incarnate. Several municipalities have actually figured that out, and it’s one of the reasons we have soda taxes because it’s actually directed at the problem. A lot of it is in other things that we identify as sweet: candy, cakes, ice cream. A lot of it is in other things like breakfast, cereal, yogurt, even cured meats. It is in a whole host of other things. When you add it all up, 65% of the sugar you consume is in ultra-processed foods. It is not in regular food. It is not in sugar you added to your own food. It is in ultra-processed foods. An ultra-processed food is the vehicle by which the payload, that is that fructose, is doing its damage.

Thanks for that background. We’re really here to talk about the artificial sweeteners but it is irresistible talking to you about sugar in general because you described the whole picture in such a compelling way. So thank you for that. So, onto the artificial sweeteners. What are the main ones in the food supply?

Well, there are a whole bunch. The most common ones that the food industry uses the most, obviously aspartame, which is Equal. And also sucralose, which is Splenda. But there are others now out on the market: Neotame, there’s Acesulfame-K, there’s monk fruit, there’s Stevia, and all the Steviol glycoside derivatives. There’s now Allulose, and there’s Tagatose. There’s a whole host of different sweeteners that are considered “non-nutritive” meaning they don’t have calories.

These things show up in ways that people don’t necessarily recognize. I mean Diet Coke, Diet Pepsi, those sort of things, it’s obvious they’re artificially sweetened. But these things are showing up in a lot of places, aren’t they?

Indeed. The food industry now understands that sugar is a problem and people have been calling for less sugar but what they’re not calling for is less sweet. And so the industry has a job. It has to deal with that dichotomy.

I know understanding their impacts is complicated by the fact that there are a lot of these things and they’re all chemically different from one another. I’m imagining they have different metabolic effects. What happens when these things get into the body?

Right, and that is the issue. It has nothing to do with calories. People think calories are the issue. This has nothing to do with calories. That’s one of the reasons, Kelly, that I’m committed to one concept: kill the calorie. Kill the calorie as a unit of measure. It was never appropriate. It was actually subterfuge, and it was actually promoted and promulgated by the food industry because if it is about calories, they can assuage their culpability for what they’ve done to our food supply. This has nothing to do with calories. This has to do with metabolic health.

Now, the World Economic Forum just published a white paper called the, “True Purpose of Nutrition,” and it comes down to two words: metabolic health. That is what is going on inside the cell and that’s where the artificial sweeteners do their damage, inside the cell. That’s what we have to talk about. There are several places in the body where artificial sweeteners can do damage that have absolutely nothing to do with calories. The first, you put something sweet on your tongue. Message goes tongue to brain, “Sugar’s coming.” Brain sends a message to the pancreas, “Sugar’s coming, release the insulin.” Then the sugar never comes because it was a diet sweetener. What does the pancreas do? It turns out it releases the insulin anyway even though it had no calories, even though it wasn’t sugar, just because of the sweet taste. So this is known as the cephalic phase of insulin secretion. That insulin is driving energy storage into fat, number one, and it’s also driving cell proliferation in your coronary arteries, cell proliferation in your breast tissue, in other words, cardiovascular disease and cancer and ultimately leading to burnout of your pancreas, and now you’ve got diabetes too. Even though these artificial sweeteners have no calories, they still generate an insulin response, which is still problematic from a metabolic standpoint.

So because of the sweet taste and the body’s response to that, I’m assuming what you’re saying would be true to all of sweeteners?

Exactly. All of them do that. The next step is the artificial sweetener goes down your gullet, goes into your intestine, and the intestine has these bacteria in it called the microbiome. Most people have now heard of that. Different bacteria lead to different effects in the intestine. But think of your intestine – I mean it’s a sewer. It has a whole lot of S-H-you-know-what in there. The goal of the intestine is to keep the S-H-you-know-what IN the lumen of the intestine and not allow it into the bloodstream. It uses three barriers. It has a physical barrier called the mucin layer. It has a biochemical barrier known as tight junctions or zonulins. It also has an immunological barrier called Th17 cells. Those three barriers have to work right to keep the junk out of your bloodstream because if the junk gets into your bloodstream, you now have systemic inflammation, which drives insulin resistance and drives chronic metabolic disease as well. So keeping your intestine in tiptop shape is really important. Well, it turns out those diet sweeteners alter the microbiome. Some of those bacteria like those sweeteners and utilize them to make toxic byproducts, which damage the mucin layer, damage that biochemical tight junction barrier and allow for things to seep through. This is a process called leaky gut. For reasons that are still unclear, sugar tends to deplete those Th17 cells, rendering the immunologic barrier devoid of function. The sum total of which means all the you-know-what in your intestine ends up in your bloodstream, goes to your liver, generates insulin resistance, and you are off to the chronic metabolic disease races as well, from diet sweeteners having nothing to do with calories.

What an amazing picture your painting of these things.

We’ve got one more mechanism. At the fat cell, now this I really don’t understand and it’s early data but seems to be consistent. Turns out adipocytes, fat cells, have receptors for diet sweeteners. Don’t ask me why. I don’t know why. But it turns out, diet sweeteners can act like insulin right at the fat cell to increase energy deposition into the fat cell. Growing those fat cells all by themselves, due to the diet sweetener rather than due to insulin. Now how dumb is that? As a result, there are a lot of different ways diet sweeteners might end up causing problems as well, having nothing to do with calories, having nothing to do with fructose. There was a paper that came out in the European Journal of Clinical Nutrition. It was a meta-analysis of sugar and also of diet sweeteners in terms of diabetes and heart disease. What I can say in one sentence to sum up what this paper showed is that the toxicity of one Coca-Cola equals the toxicity of two diet Coca-Colas. Half as bad. That doesn’t mean good. It means half as bad.

Boy, I mean, any one of the three major pathways to harm would be of concern. If you add them all together, it is a pretty striking picture, isn’t it? I imagine, even if somebody knew about this, they might say, well, you know, I’m willing to accept those risks. I mean, even though you are making them sound substantial, but I’m willing to accept those risks if these products help me control my weight. Do they?

Well, they don’t. That’s part of the problem. There is not one study, not one study in the entire world’s literature, that shows that switching from sugared beverages to diet beverages actually controls weight. The reason is because even though the diet sweeteners don’t release as much insulin now, when you drink the diet sweetener, the pancreas releases it later. That’s actually been shown in several studies now. You get a delayed insulin response, so that the 24-hour insulin burden is the same whether you consume the sugar or the diet sweetener.

Let’s talk about safety for a minute. What about sort of the typical toxicology concerns that people have had for years about these substances, irrespective of what they’re doing to the pancreas and to the other, the microbiome, et cetera? What about the just kind of pure safety of them?

Right, so the one that has generated the most heat, not too much light, unfortunately, is aspartame, NutraSweet. It turns out that aspartame has a very long and checkered history. Did you know that aspartame was made by Searle, G.D. Searle? And, do you know who the CEO of G.D. Searle was at the time that aspartame was approved by the FDA?

I do not.

His name was Donald Rumsfeld.

An interesting character in history.

Indeed, wouldn’t you think? It turns out that G.D. Searle actually buried most of the toxicology of aspartame in order to get it approved. It is a long complicated and involved story, which we don’t have time for. I’m not even privy to most of the details on that. The bottom line was it ultimately did get approved despite the fact that there was a significant amount of concern about toxicology of this compound. Those questions still remain today. That is one. Another one that is a big issue is sucralose. Sucralose is also called Splenda. Sucralose is a chlorinated poly-fructose and it’s extremely sweet, no question about that. It seems to have some GI side effects that a lot of people don’t like. It also has now been associated with cancer. And most recently, the one that’s gotten the most attention and almost assuredly, Kelly, the reason you called me is the paper that came out about three weeks ago in science about erythritol. So erythritol is a sugar alcohol, and now the meta-analysis of erythritol consumption suggests that it may in fact contribute to heart disease. Now, is that true? Meta-analysis are complicated. People think meta-analysis are the piece de resistance, the highest bar of medical information and analysis. I have four words for meta-analysis: garbage in, garbage out. Meta-analyses are only as good as the studies that they base the data on. If those studies were done by the food industry, which almost all of these are, because that’s who stands to benefit from them. These are almost never NIH studies. These are almost always food industry studies, as you know, the odds are 7.61 times more likely to find in favor of the compound of interest. So all of these are, shall we say, biased. All of these are tainted, and meta-analyses are basically a conglomeration of tainted studies. So what do you expect the result to be?

Thanks for that background. I’m imagining also regarding toxicology and safety, that some of the newer sweeteners like Splenda for example, sucralose, there hasn’t been enough years of use to pick up long-term chronic effects.

Well certainly, if you’re using cardiovascular or cancer events, you’re absolutely right. A lot of these events, you know, take a long time to manifest themselves. Sometimes, a generation or even two generations for that matter, especially for heart disease and cancer. The 15-year-old is drinking 10 diet sodas. When do you expect the heart attack to show up? You know, it’s complicated.

So we use biomarkers to try to answer these questions, but then the biomarker has to actually be a good proxy for those events and often they’re not. Let me give you an example, LDL. Everybody thought LDL was the bad guy. Turns out triglycerides are the way worse guy. LDL has a hazard risk ratio for heart disease of 1.3. Triglycerides have a hazard risk ratio of 1.8. Triglycerides are 50% more important in determining heart disease than LDL is, but we use LDL as the biomarker because it’s more stable. So you have to use the right biomarker and you have to interpret it properly and it actually has to mean something and it has to change relatively acutely. All of which are problematic for all of these biomarkers. It’s hard. It’s hard to do these kinds of analyses. Having said that, my group, a scientific advisory team that I convened to help an offshore ultra-processed food company improve the health of their products. We’ve published this just last month in Frontiers in Nutrition. The company is called Kuwaiti Danish Dairy Company, or KDD. The title of the paper is, “The Metabolic Matrix: Re-Engineering Ultra-processed Foods to Protect the Liver, Feed the Gut, and Support the Brain.” We did a deep dive on diet sweeteners. We looked at all of these diet sweeteners and their proxies, all the biomarkers. The one that actually popped out that looked to be the most beneficial, at least acutely, is a new one that we’re actually kind of interested in and is picking up speed and it’s called allulose. Allulose currently is 12 times the cost of sugar, but that’s coming down. It turns out allulose lowers LDL and raises HDL. So it may have a better cardiovascular profile, but again, all the caveats that we mentioned before.

That’s very interesting. So given your interest in pediatrics, what about children using these sweeteners?

I am totally against children using sugar because they get fatty liver disease and Type 2 diabetes, and I am totally against them using diet sweeteners because, number one, we don’t know what they’re going to do. Number two, they don’t actually lead to weight loss. That data we do have. So as far as I’m concerned, we really only have one option and that is de-sweeten our lives. We have to de-sweeten the food.

Perfect lead in to the next question I was going to ask. So do you think it is possible for people to become accustomed to less sweetness? I mean, let’s say the food industry is required to gradually reduce sugar and sweetness from the sweeteners. What do you think would happen?

Absolutely. It is not only possible, it is eminently doable. And I know why and we have the data for why that is. So there is a very smart lady, neuroscientist at the University of Michigan by the name of Monica Dus, who has done all this work in fruit flies of all places. She has shown the desensitization of the tongue to sugar has to do with changes in receptors and changes in specific substrates in the taste buds of the tongue. When you stop the sugar availability, it takes three weeks for those receptors to increase and repopulate, and for those problematic substrates to go away. You can actually retrain your tongue in three weeks to be much more sensitive to the sugar that is in the food naturally. After a three-week abstinence period or a reduction or a weaning period, a blueberry will taste like a sugar bomb in your mouth. So we know this can happen and we actually have proven this for salt previously. The UK, as you know Kelly, back in 2003, the Blair government convened all the food industry concerns in Great Britain. So Marks & Spencer, and Weight Rose, and Tesco, et cetera, all around the big table, didn’t let media in, and basically said to every single food industry concerned in Great Britain, “Look, we have a hypertension and stroke problem and it’s because of the salt content of the food and we are going to play referee here in the government. And each of you is going to reduce the salt content of your food by 10% per year over a three-year period so that you’ll reduce your salt by 30% at the end of this and everyone’s going to play together, so that there’s no competitive disadvantage and most importantly, we’re not going to tell anybody.” That’s what they did. Sure enough, in 2011, a paper appeared in Burge Medical Journal, demonstrating a 40% reduction in hypertension and stroke because of the public health effort that the Blair government made in terms of reducing the amount of salt in processed food. We can do the same with sugar today.

The salt example is a good one because I think many people have sort of experienced this in their day-to-day lives, even in the United States, where industry hasn’t done exactly what’s happening in Britain. People have tried to reduce salt in their diet, add less salt, and buy products with less salt. And then sometimes they’ll go back and consume something that they had before and find it extremely salty, even unpleasantly salty. It’s interesting to hear on the sugar front that that same experience might be possible and that there’s a biological reason for it. It is not just that you psychologically get accustomed to different levels of sugar, in this case, but there’s a biological change occurring that might help keep that going.

Absolutely. You can change people’s behavior by changing their biochemistry. This is how I got into this field by using a drug that suppressed insulin and getting kids who were 400 pounds due to their brain tumor to actually lose weight and start exercising because we got their insulin down. You can fix the biochemistry and the behavior will follow suit. The food industry could do that and we wouldn’t even notice.

So I’m guessing I know the answer to this question before I even ask it, but let’s go ahead. Would you suggest the food industry be mandated to make gradual reductions in sugar, just like you mentioned with salt in the UK?

Absolutely, I’m working toward that. The only thing that I say is we should not tell anybody.

So it would be sort of a stealth move then. You would not necessarily have to make a big deal of it to the public, because they might assume there’s going to be a change in the desirability and the pleasure of the products when that’s not necessarily the case.

As soon as you do something to their food, someone’s going to scream, “Nanny state!” This is not nanny state. Ultimately, this is a public health problem. We have to deal with it with a public health solution. You know, that means changing things. If the amount of sugar in our food supply went down, say by 3% every six months down, so that we were able to cut our sugar consumption by 25%, which would be the same basically as what a tax would do. We would save so many billions of dollars in healthcare costs, and we would increase productivity so much. We actually published a paper, a microsimulation analysis in BMJ years ago where we quantified the savings to government, to insurers, to the public. If we actually got sugar down and, you know, actually listened to what the USDA told us, it would be amazing. There is data, there’s a pathway forward, there’s precedent for doing it. I absolutely think that is where we need to go.

Rob, you’re making me feel very smart at the moment, because I figured this was going to be a podcast filled with information and helpful bits of knowledge and it sure was. I’m really grateful that you were able to join us and the topic couldn’t be more important. Thank you again for being with us.


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