Aspartame sweetener linked to vascular disease in mice

Artificial sweeteners have promised to be a guilt-free way to indulge a sweet tooth without the caloric consequences of added sugar. But a research project inspired by a student drinking a can of low-calorie fizzy drink and published this week in Cell Metabolism suggests sweeteners might not be a free lunch after all. Giving mice small - human relevant amounts - of one of the most popular artificial sweeteners, aspartame, led to accelerated rates of arterial disease in the animals. The team think that a high levels of insulin, provoked by the sweet taste, are behind the damaging effect. Yihai Cao is Professor of Vascular Biology at the Karolinska Institute in Sweden…

Yihai - This study was initiated from a can of diet soda. It has been estimated that in the United States, 60% of young people may consume these kinds of beverages. As a scientist, I supervise students. One of the students asked me for projects. He was holding a diet soda can. I said, what are you drinking? He said, I'm drinking a sugar-free beverage. I said, why don't you do a project like that? We have a lot of experimental mouse models, I said, why don't you get these smaller animals to drink this to see what happens to their body? So this is how it started.

Chris - What health impacts specifically were you hoping to probe with your mice drinking fizzy pop?

Yihai - My expertise is in studying blood vessels, cardiovascular disease, stroke, diabetes. So at that time we had a disease model called atherosclerosis. Within the large blood vessel, they form plugs. So I asked the students to let these mice consume artificial sweetener.

Chris - So you have mice that are prone to developing arterial disease like a human does. You feed those animals the same stuff that sweetens a sugar-free beverage. And then you're asking, does this have any impact on the progression of the vascular disease that these animals naturally develop?

Yihai - Exactly. So this is the first experiment we did.

Chris - And what sort of doses of the sweeteners were you administering? Because one criticism of experiments like this is we end up feeding kilogram quantities of things to tiny animals and it's not representative at all. So what was the dosing pattern that you exposed the animals to?

Yihai - So the dosing we used is calculated not based on the weight, how many grams, it's based on the sweetness. For example, aspartame is 200 times more sweet than sucrose. So we converted that formula to make it equivalent to what we consume in the sugar soda, for example.

Chris - And do the rodents like eating this? Will they actually consume this? And will they regularly consume it as though they were consuming with a similar pattern to a human using these sorts of foodstuffs?

Yihai - Mice, they like sweet things very much, even more than people. So if we allow them to drink themselves, they could drink all day long. That's maybe consuming too much. In order to give them a defined dose, we basically drop it on their face, and then they use their front paws to lick.

Chris - Okay, so they don't overdose on the sweetener. What happens though, when you look in the blood vessels, do you see a difference in the animals consuming the artificial sweetener compared to animals eating normal rodent chow?

Yihai - Yes, we saw, very surprisingly, arterial vessel damage is increased when they consume more aspartame.

Chris - When you say increased, is it increased by much, or is it very subtle? Is it a dramatic difference?

Yihai - It is statistically significant. Both the plug numbers and the plug size are increased.

Chris - And what do you think the mechanism is behind this? What's driving that?

Yihai - We think it's related to the sweet taste. So there is in the mouth, in the intestine, sweet taste receptors. So when we eat something sweet, our body can release insulin. Insulin, after consumption of aspartame, is increased in the blood. The first organ in our body that could sense this is the blood vessel. On the vessel wall, the inside cells are called endothelial cells. So what is the insulin impact on these endothelial cells? Very surprisingly, one of the most upregulated genes is the inflammatory protein. This inflammatory protein can cause inflammation in the blood vessels.

Chris - Putting all that together then, if you ingest these chemicals, although there is no sugar there, they fool the body into thinking it's had a massive dose of sugar, which then drives a massive release of insulin, to which blood vessels are highly sensitised. And when the insulin activates them, it produces an inflammatory signal, and you're contending that that inflammation is upstream of forming these deposits in the wall of the arteries that will eventually turn into arterial disease.

Yihai - Correct. What you said is absolutely correct.

Chris - Do we think this is physiologically relevant in humans? Are we as humans, in striving for a healthier lifestyle and drinking these diet beverages then, and eating diet foods and snacks that are full of this stuff, are we actually doing ourselves more harm than if we just ate a sweet cake?

Yihai - In our study, we did not do human studies, but there's no reason we can see that it would not happen in humans in this way. So I would expect that a similar mechanism may exist in humans as well. I would not recommend myself to consume this.

Chris - I was just going to say, has everyone in your group given up drinking artificially sweetened beverages? Do you not have lab meetings where there's no fizzy pop with aspartame in it anymore?

Yihai - One of the students usually consumes many kinds each day, but he stopped completely after doing this project.