NEW YORK (TNS) — There were good reasons to avoid products with the artificial sweetener Aspartame even before the World Health Organization classified it as a “possible carcinogen” last month. But now diet soda drinkers might really want to put down the can.

But first, some perspective: “Possible carcinogen” is the weakest of three bins into which WHO classifies anything that’s been even remotely tied to cancer in any kind of study. The organization labels substances with more serious links to cancer as “probable carcinogens” and if the evidence is really strong, “carcinogenic to humans.” That middle category includes things that many of us consume routinely, including alcoholic beverages and very hot drinks (which have been linked to esophageal cancer).

The evidence behind possible carcinogens is more tenuous. The low-frequency radiation emitted from cell phones is in that category because studies have suggested very weak associations with cancer in animals.

In the case of aspartame, some studies show rats fed high doses of aspartame are more likely to get brain cancer and several other malignancies. Adding to the concern, a large 2022 study followed more than 100,000 people in France and found a possible small increased cancer risk in heavy users of artificial sweeteners.

But studies like this can’t prove that the sweeteners caused cancer. It’s possible that the group consuming more sweeteners also ate more processed food, or were more obese, or there was some other link.

A better way to get information would be to treat the humans more like the lab rats — feeding some people aspartame and comparing them to control groups. And now someone has done that, setting up what’s known as a randomized controlled trial. The study wasn’t set up to find a cancer link, but it did connect artificial sweeteners with the same risks associated with sugar.

Several other studies have linked aspartame, in particular, to spiking blood sugar, and in the longer term, to higher blood sugar and expanded waistlines. Perhaps there’s just no risk-free soda.

The FDA approval of aspartame in 1981 was mired in political controversy. Donald Rumsfeld was chief executive, president and chairman of the company that makes aspartame, G.D. Searle & Co. — and was at the same time part of Ronald Reagan’s transition team. (Rumsfeld had by then already served as defense secretary under President Gerald Ford, a role he reprised for President George W. Bush.)

As soon as he was elected, Reagan appointed a new FDA head who reportedly stacked a scientific panel to push through aspartame’s approval. Today aspartame is in diet drinks, gum, ice creams, puddings, cereals and other packaged foods marketed as sugar-free. Would it have been approved if not for Rumsfeld’s influence? Maybe.

Massive waves of death did not follow the infusion of aspartame into the U.S. diet, but at the same time, there was no improvement in rising rates of obesity or Type 2 diabetes. Fake sugar hasn’t made America healthier. That randomized controlled trial helps explain why.

The study, published in 2022 in the journal Cell, compared six groups, four consuming each of four different artificial sweeteners and two control groups. The sweeteners were Sucralose, Aspartame, Stevia and Saccharine. One control group got no sweetener and the other got a tiny amount of real sugar, the same amount added to artificial sweetener sachets to offset their bitter aftertaste.

The study’s leader, Eran Elinav of the Weizmann Institute of Science in Israel, told me he was interested in exploring the possibility that the artificial sweeteners were interfering with the community of microbes that live in our guts — the microbiome. To start with, he said, he wanted to find volunteers who did not already consume any artificial sweeteners, and after screening more than 1,300 people, he had to narrow it down to 120 subjects whose systems were sufficiently pristine.

The two control groups showed no changes in their microbiome composition or their blood sugar control. The four groups that got artificial sweeteners showed changes in both after just two weeks of consuming an amount similar to what consumers might get drinking a couple of diet sodas a day.

The point, Elinav said, is that these substances aren’t “inert” — they don’t just pass harmlessly through the body. (Inert is the same term many chemists used to describe PFAS, now often called “forever chemicals,” which have also been linked to health problems.)

His results, he said, were interesting because the subjects getting the sweeteners reacted very differently, some showing almost no change and others substantial changes in microbial communities and blood sugar.

Even a low probability of risk might be enough reason for some people to switch to water or unsweetened drinks, given the way recent studies cast doubts on any metabolic benefit.

What should people with a sweet tooth do? Elinav said he absolutely does not want people to interpret his study to say they should switch back to drinks heavily sweetened with regular sugar or corn syrup. These are tied to all sorts of health problems, including cancer.

But it’s impossible to prove beyond doubt that anything, even cell phones, will never cause anyone, anywhere, to get cancer. So we have to weigh the risks and benefits. When I interviewed American Cancer Society head Otis Brawley about cell phones, he acknowledged the possibility of a link, but we were both talking on our cell phones at the time. When I talked to Erinav, he wasn’t drinking a diet soda — and he told me he opts for water.

(F.D. Flam is a Bloomberg Opinion columnist covering science. She is host of the “Follow the Science” podcast.)