The common-sense wisdom about the most widespread artificial sweetener on the market, aspartame, is that it's perfectly safe. The substance laces more than 6,000 products and is added to diet versions of Coke, Pepsi, Sprite, and Dr. Pepper. It is also sold under the brand names NutraSweet and Equal. It represents a multi-billion-dollar industry.
Popular pieces across the internet in recent years have declared that concerns about aspartame are just a bunch of hype. A pediatrician and writer for The New York Times defends aspartame and says he regularly gives it to his kids. Vox dismisses concerns about the sweetener and includes a video about how safe the stuff is.
These are reputable news outlets. Yet unlike what their headlines suggest (see, among many others: The Evidence Supports Artificial Sweeteners Over Sugar or Sugar-Free Soda is Safe), the scientists I spoke to for this story are not comfortable making such bold statements. They say there truly is no definitive data to show that aspartame is safe. "I certainly would not be saying it is safe," says Robert Lustig, a pediatric neuroendocrinologist at the University of California, San Francisco, who has written extensively on the subject. "We just don't have the data."
There's no question that scare tactics are sometimes used by health alarmists who overstate the case or misstate the science, but the rush to defend a billion-dollar industrial product—that at the very least has proven to have little benefit—is also curious. Before we get to the actual health concerns of aspartame, though, let's take a look at the telling history of its controversial approval by the FDA.
Aspartame was discovered at GD Searle, a Chicago drug company, in the 1960s. The FDA first approved it in 1974, but an FDA scientist at the time, Adrian Gross, discovered that there were serious shortcomings in all 15 long-term studies that Searle submitted for review. For example, some rats in the studies died but were not autopsied after to discern the cause; in other cases, the aspartame was not mixed well enough into the feed and the rats were eating around it. There was also evidence of brain tumors in the rats in several studies.
Gross's findings, along with pressure from other scientists, resulted in a public board of inquiry in early 1980 consisting of three independent scientists who reviewed the data and voted to withhold approval because they "did not believe Searle's studies conclusively showed aspartame did not cause brain tumors."
At the time, Donald Rumsfeld was the CEO of Searle. He was also on the transition team for Ronald Reagan, who was inaugurated in 1981. After the inauguration, Searle re-applied to the FDA for approval, at which point Reagan fired the FDA commissioner and replaced him with Arthur Hayes Hull, Jr., who re-approved aspartame for dry products.
Aspartame quickly flooded the market, and two years later was also approved for use in liquids. Soon after, Hull left the FDA and took a job with Burson Marsteller, the PR firm for Searle. Meanwhile, Searle (which Monsanto purchased in 1985) made billions and Rumsfeld, of course, later became the Secretary of Defense under George W. Bush. (For more on this history, check out the 60 Minutes segment from 1996 and the Times article from 2006.)
Many of those Searle studies that Gross questioned are now lumped into the data that says aspartame is safe. And though the question of aspartame causing brain tumors has largely been dismissed over the years, there hasn't been much new data on the subject. In fact, a 1987 General Accounting Office report states that 28 out of 69 scientists said more research was needed in the areas of "neurological functions, brain tumors, seizures, headaches, and adverse effects on children and pregnant women." Nonetheless, the report added, research was ongoing in all areas except brain tumors. What's more, the FDA dissuaded the National Toxicology Program (NTP) from doing further cancer research on aspartame. As the founder of the NTP, David Rall, put it, "It's a wonderful way to ensure that it isn't tested—discourage the testing group from testing it and then say it's safe."
A longterm study in humans found a positive association between aspartame intake and risks for non-Hodgkin lymphomas and multiple myeloma in men, and leukemia in both men and women.
In 1996, John Olney, a professor of pathology and immunology at Washington University Medical School, claimed to have found epidemiological evidence that the introduction of aspartame in the US was connected to an increase in an aggressive form of brain tumor called glioblastomas. But this was criticized for just being a correlation and dismissed by the FDA.
Then, from 2006 to 2010, the Ramazzini Institute in Italy published three papers with evidence of cancers in laboratory animals exposed to aspartame. In the longest and largest study, which went on for seven years in 1,900 rats, researchers found surprisingly high rates of lymphomas, leukemias, and other tumors, including kidney tumors. A follow-up study in 2007, which exposed mice to aspartame in the womb and through the entire lifespan, found the same kinds of cancers in addition to breast cancer. A third study in 2010 found cancer of the liver and lung in male mice. These findings provoked controversy as well, with questions swirling about the laboratory itself. Industry quickly criticized the findings for alleged flaws in the research.
The Center for Science in the Public Interest (CSPI) conducted a detailed investigation into the findings reported by the Ramazzini Institute, filing FOIA requests for further information. Lisa Lefferts, senior scientist at CSPI, said they found the criticisms to be entirely without merit, and characterized the findings this way: "There is consistent evidence from well-designed, independent studies that aspartame causes cancer in animals and therefore, it may also cause cancers in humans. It is pretty compelling evidence and we recommend that consumers avoid it."
Lefferts adds that the Ramazzini findings were enough for the International Agency for Research on Cancer (IARC), which is a branch of the World Health Organization, to "sit up and take notice. These are the kinds of findings that meet the criteria for concern," she says. CSPI submitted data to IARC for review in 2014; at the time the agency agreed that it should be a priority for review, Lefferts says.
Erik Millstone, professor of science policy research at the University of Sussex, who has been studying aspartame since 1984, says that the Ramazzini studies provide "sufficient grounds to ban aspartame. We know it caused cancer in several varieties of several species of laboratory animals in dose-related ways, and at diverse sites."
Then, in 2012, Harvard published findings on the longest epidemiological study in humans, which looked at aspartame consumption over an 18-year period. The researchers found a positive association between diet soda and total aspartame intake and risks for non-Hodgkin lymphomas and multiple myeloma in men and leukemia in both men and women (why men appear to be more at risk is interesting, see this video for more).
These findings were controversial as well, and just prior to the paper's publication, senior scientists at Brigham and Women's Hospital (at Harvard) sent memos to the press that said they felt the data were weak. But Walter Willett, professor of epidemiology and nutrition at Harvard and a co-author on the study, told NPR at the time that the findings were strong enough to "justify further research on aspartame and cancer risk."
"Am I concerned? Absolutely," Lustig says. "Would I drink the stuff? No way in hell."
The checkered history and scientific findings on the sweetener raise a lot of concern—but these aren't the only factors to consider. What about its stated purpose: to reduce calorie consumption, aid in weight loss, and perhaps lower diabetes risk?
It's well established that there is a correlation between being overweight and diet soda consumption, but the question is which way the association works. Do people who are overweight tend to drink diet soda, or is something about the diet soda contributing to weight gain? A 2015 study found that long-term consumption was associated with increased waist circumference. And a 2016 study found that mothers who consumed diet soda while pregnant had babies with a two-fold higher risk of being overweight at age one.
While the question of whether the sweetener causes weight gain, diabetes, or other metabolic disease is unsettled, there are some remarkable correlations. A 2013 Purdue review over 40 years found that people who regularly consume artificial sweeteners are at increased risk for obesity, type 2 diabetes, metabolic syndrome, and cardiovascular disease. A 2013 analysis of more than 66,000 women showed that consumption of both sugar-sweetened beverages and artificially-sweetened beverages was associated with increased risk for type 2 diabetes. And another major finding came when researchers from Harvard Medical School analyzed data from the Nurse's Health Study and found that women who drank more than two artificially sweetened sodas per day had a twofold increased risk for kidney function decline over two decades.
But the latest research is working on models of causality, not just association. At the Weizmann Institute in Israel, researchers found that feeding mice artificial sweeteners caused glucose intolerance, one of the key markers in diagnosing diabetes. Through a series of experiments, the researchers concluded that the sweeteners were making changes to the bacteria in the gut (called the microbiota), inducing glucose intolerance. The researchers did a small follow-up study in humans and got the same result.
Another concern, Lustig says, is that artificial sweeteners may make you more likely to overeat. Two recent studies show that artificial sweeteners result in an increase in insulin levels in response to other foods consumed. That is, drinking artificial sweeteners has a metabolic effect that changes the way your body reacts to other foods.
M. Yanina Pepino, the author of one of these studies at Washington University in St. Louis, said of her research, "Our results indicate that this artificial sweetener is not inert—it does have an effect. And we need to do more studies to determine whether this observation means long-term use could be harmful."
There is yet another issue: Since our bodies have been primed to detect sweetness, we have receptors on our tongue that send messages throughout our systems when something sweet lands there. First, a message goes to the brain telling it to expect a flood of sugar, then the message goes to the pancreas, which prepares to release insulin. But in the case of an artificial sweetener, the sugar never comes, so the pancreas sends a signal to seek out more glucose, which results in you feeling hungry, potentially causing you to overeat.
David Ludwig, an endocrinologist and professor of nutrition at Harvard Medical School, writes in a comment for JAMA that "artificial sweeteners have the potential to interact with our evolutionarily ancient sensorineural pathways at remarkably high affinity." In other words, the body does not know how to respond to artificially sweetened products; it gets confused and things can go haywire.
"Artificial sweeteners bind the sweet taste receptor hundreds to thousands of times more potently than sugar itself," Ludwig says. "What effect might that have on our taste preferences and metabolism over the long term? Unfortunately, we just don't yet know from available research, but preliminary findings provide cause for concern." One thing is clear at this point, Lustig adds: "Diet sweeteners are certainly not doing what the companies say they are in terms of a method for promoting weight loss."
Keep in mind that since the substance has only been in the food supply since the 1980s, long-term effects are only beginning to be understood, including aspartame's effects on the microbiota as well as the potential for cancer over the course of decades of consuming it.
For its part, the FDA stands by its ruling on aspartame. In an email to Tonic, a spokesperson wrote, "Aspartame is one of the most exhaustively studied substances in the human food supply, with more than 100 studies supporting its safety. FDA scientists have reviewed scientific data regarding aspartame in determining that aspartame is safe for the general population under certain conditions."
I asked Lustig how concerned he was about the pervasive diet sweetener. "Am I concerned? Absolutely," he says. "Would I drink the stuff? No way in hell."