Stefan: You may have heard that a major international health policy group has put in place some new warnings regarding artificial sweeteners and their potential to cause cancer. You may also be dragging your diet soda out to the curb. But before you do that, I'd like to walk you through a little context around this story. Short version: Don't panic. Longer version: This new guidance is based on science, but it's not an open-and-shut case, and some observers say there's a whole 12-pack of issues here.

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On July 14th, the World Health Organization added aspartame to a list of things it considers "possibly cancerous," and included a specific warning for liver cancer. We'll get into what that means in a minute, but let's start with the chemical itself.

Aspartame is an artificial sweetener that was discovered by accident in 1968 and has been on the market since 1981. It's used in many kinds of diet soda and other artificially sweetened beverages and foods. Here in the US, the Food and Drug Administration remains convinced aspartame is safe. That said, research into its safety has continued over the years. So, let's get under the hood of this new decision.

Perhaps the splashiest studies against the use of aspartame came out in 2006. This pair of papers from the same research team found that rats that were given daily doses of aspartame had drastically increased rates of cancers of the blood and the nervous system. But even when these studies were published, other researchers argued that the researchers misdiagnosed what was wrong with the rats.

See, these researchers diagnosed their rats posthumously, conducting necropsies only when the rats died their natural deaths. This isn't the typical way that animal research is done; often, you would raise the animal under the experimental conditions for a set amount of time, and then euthanize them to study. Letting them die of natural causes introduces the possibility that the health issues discovered in the necropsy might have nothing to do with your experiment. And other groups argued that what the team identified as tumors were actually inflammation or signs of bacterial infection in the rats - not cancer.

but even if it was cancer that killed these rats, there's another huge issue with this study, which is just how much aspartame these rats were dosed with every day. Food regulatory agencies like the FDA calculate what a safe daily intake of a given substance might be. The assumption is that the dose makes the poison; even things that could theoretically be dangerous are usually fine in really small doses. So, they define those really small doses and set limits on how much of that thing can be in any food product.

For aspartame, the FDA's safety limit is 50mg/kg of body weight. So, for someone weighting about 68kg (150 lbs) they'd need to consume over 3,400mg of aspartame to exceed that limit. And since a can of diet coke contains a little under 200 mg of aspartame, that means you'd need to drink almost 18 cans per day to exceed that threshold.

Some of the rats in this study were given doses of aspartame equivalent to a human consuming 5,000mg/kg body weight, which is astronomically high. It's literally the equivalent of those rats drinking over 26 sodas a day, and not rat-sized sodas, regular 12-ounce ones. In the entire experiment, only two doses of aspartame that these rats are exposed to are below the FDA's acceptable limit. Another study by that same team looked at aspartame's effects on mice, and found that daily aspartame intake was correlated with increased rates of liver and lung cancers, but only in male mice.

Aside from that, it's important to remember that humans are not rodents. So, the next step in figuring out whether aspartame might be related to health risks in humans is to follow a bunch of humans who consume it and just see what happens. And that's what's called a "longitudinal study," where researchers take a large cohort of people, get their baseline data, and follow them over the course of several years to see what changes occur in their overall health.

So, in response to that rat study, in 2006, a team of researchers at the American Association of Cancer Research published the results of their longitudinal study. It looked at adults who consumed varying amounts of aspartame and the rates at which they developed blood and nervous system cancers. The result? There was no correlation between use of aspartame and cancer. And it's important to remember that the study was looking at people who consumed aspartame in a range of quantities. I mean, I've hear of people who drink a dozen diet Pepsis a day, but that's not most people.

But if these studies came out in 2006, why are we and the World Health Organization talking about this now? Well, it probably has to do with a paper that came out in 2022. Unlike the 2006 cohort study, this one found that consumption of aspartame was correlated to higher risks of breast cancer and cancers related to body weight. And this more recent study found that there was an increased risk of cancers just in general with consumption of artificial sweeteners, which is both interesting and extremely vague. Remember, the new warning is for liver cancer.

And there's one more layer to this artificial sweetener onion; the way that the IARC (International Agency for Research on Cancer) - the WHO's cancer-arm - classifies these risk factors, is not the most intuitive. They have four rankings for how allegedly dangerous something is: carcinogenic, probably carcinogenic, possibly carcinogenic, and not classifiable. But the way that an item gets into any of those categories isn't based on the magnitude of the risk that the thing presents; all that matters is that there's a lot of papers *suggesting* a relationship between cancer and that thing, no matter how small that relationship is.

In fact, in their own words, "The evidence for aspartame causing cancer is limited." And for reference, some things in their "probably cancerous" category include red meat and working the night shift. Like, some of these warnings are simply not practical or feasible to bring into your daily life. Anyone who's ever had a newborn or pulled an all-nighter for school knows that you can't always ensure that a good night's sleep is gonna happen. And those things are in the "probably carcinogenic" pile. Aspartame is going in the one below, the "possibly" group. So, like... eh?

Meanwhile, the WHO also has a food safety committee, and they haven't changed their recommendation on the acceptable limit for aspartame intake; it's still 40mg/kg of body weight, a smidge less than the FDA's. In any case, figuring out the exact relationship between any single factor and cancer is not easy. And while The WHO may be changing their recommendations, the FDA does not look like they will update guidance here in the US anytime soon.

So, should you throw away all your diet beverages? Well, probably not. I have it on good authority that at least one diet cherry Dr Pepper was consumed during the development of this episode. These are decisions that everyone has to make on their own, and bodies like the WHO can only try to provide guidance. So I'll just say it again - don't panic.

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