JOHN YANG: For decades, Americans have been consuming sugar substitutes in their morning coffee, their desserts in their diet drinks, but from the early days of artificial sweeteners questions have been raised about their safety.

Now a new study has found that a popular artificial sweetener called Erythritol has been linked to greater risk of blood clots that could lead to heart attacks or strokes.

Erythritol is used in sugar substitutes like Splenda Naturals and Truvia.

Earlier I spoke with one of the study's authors, Dr. Stanley Hazen of the Cleveland Clinic.

DR. STANLEY HAZEN, Cleveland Clinic: We were looking for new pathways that contribute to cardiac disease risk.

And so we're measuring in patient blood samples, different compounds to see whether or not they predicted the future risk of heart attack stroke or death and what we found is that at the very top of the list turned out to be a compound that once we discovered its structure, it turned out to be Erythritol.

So then we added Erythritol to did mechanistic studies by giving Erythritol to animals, and showing that they developed thrombotic events like a heart attack or stroke.

That's a clot in the vessel that feeds the heart or the brain.

And we also saw when you add Erythritol to blood, it increase the likelihood of clotting.

JOHN YANG: What products that might be on people's shelves or in the refrigerators would have Erythritol.

DR. STANLEY HAZEN: You find it in keto foods, zero sugar foods, many highly processed foods, where it replaces sugar and provides the same sweetness of sugar but zero calories, it has become very common to find it in highly processed foods.

It's also in things like condiments and even, you know, oral care products like cholesterol we make it ourselves and the natural variation and how much a person has in their blood.

Some people have higher levels, other people have lower levels.

But then when you eat Erythritol in like an artificially sweetened pint of keto friendly ice cream, for example, it became, you know, super physiologic outside the normal range, and it took days for it to come down below the threshold of what we think is promoting enhanced clotting risk.

JOHN YANG: Erythritol has been approved by the Food and Drug Administration.

Do you think that approval should be reconsidered in light of this new evidence?

DR. STANLEY HAZEN: I don't know if I would go so far as saying reconsidered, I think that further safety studies are definitely called for.

This was unexpected.

Our studies were done in an agnostic way.

Like is there a compound a chemical in blood that predicts future risk of disease, and it just so happened that Erythritol just showed up at the top of the pile as being a predictor of future events and then it may be that it's only really more important for people who are more vulnerable to experiencing heart attack or stroke, like people who have existing heart disease or diabetes or obesity.

Of course, those are the very people who are reaching for the artificial sweeteners to try to do something that's beneficial for their health, with lower calories and, you know, weight reduction or better control of their diabetes in their blood sugar.

JOHN YANG: Researchers not involved in this study have noted while they agree that it's not proved to be safe, there's not enough research to say if long term use is safe, they do say that the fact that most of your study subjects either had cardiovascular disease or had risk factors for cardiovascular disease might have skewed some of the numbers, but you're saying that those are the very people who would be using these products?

DR. STANLEY HAZEN: Well, if you look at who uses artificial sweeteners, it's more common in people who are obese, or have diabetes, or other conditions where they're trying to limit their calories and limit their blood sugar increases, it is clear that Erythritol when ingested does not make your blood sugar go up.

However, I should point out that beyond our study, there have been a couple of randomized trials looking at artificial sweeteners, including Erythritol for weight reduction or improvement in blood sugar, and many times they have not shown beneficial effects.

So it certainly deserves further attention and further study.

JOHN YANG: What would be your advice to people who are watching and maybe eating and drinking these products should they be concerned?

DR. STANLEY HAZEN: I do think there's reason to try and avoid the use of Erythritol.

I am recommending to my patients that they actually try natural sweeteners and, you know, just watch the calories, watch their blood sugar, if they're diabetic, make sure that they use moderation so that they don't gain weight.

And if they want something to sweeten a beverage, you know use a little bit of honey or a little bit of sugar.

We know that those are actually in moderation, not going to be increasing their risk over the next couple of days for experiencing a heart attack or stroke.

I just hope that people understand that a compound like Erythritol, everything is not all black and white.

There may be shades of gray and it may be actually that it is beneficial in terms of an alternative to sugar and being a low-calorie alternative from a diabetes standpoint, or obesity standpoint.

But I think the exciting thing about this actually is we now recognize this is a pathway just like cholesterol that is linked to causing heart disease that's in every one of us.

And so in the future there may be therapeutic approaches to help modify this pathway and contribute to better treatments for heart disease.

That's where I'm most excited and enthusiastic about this.

JOHN YANG: Dr. Stanley Hazen of the Cleveland Clinic, thank you very much.

DR. STANLEY HAZEN: Oh, thank you for having me.