Aspartame: Once more unto the breach

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Look, I get it. Diet Coke tastes sweet because it has aspartame in it. Aspartame is a weird synthetic molecule that’s 200 times sweeter than sucrose. Half of the world’s aspartame is made by Ajinomoto of Tokyo—the same company that first brought us MSG back in 1909. If you look on Wikipedia, you’ll see that aspartame is a methyl ester of the aspartic acid phenylalanine dipeptide, which isn’t, like, comforting. It’s normal to have a prior that aspartame might be bad for you. Certainly, that was my prior. Without looking at any evidence, any reasonable person would think like this: aspartame is… odds …good for you very unlikely …harmless plausible …bad for you plausible This makes the decision theory pretty simple: Consuming aspartame has little upside, but substantial downside. The thing is, we do have evidence. We have a lot of evidence. The FDA calls aspartame “one of the most exhaustively studied substances in the human food supply”. The other thing is, the alternative to aspartame often isn’t no aspartame but rather sugar or corn syrup or even perhaps even alcohol. I don’t want to convince anyone to consume aspartame. But if we’re choosing between aspartame and other risky things, we should evaluate the relative risks. What happens to aspartame after it goes into your body Let’s forget about safety for a second, and just look at the causal chain. Say you drink a Diet Coke. What happens next? Fact 1: Aspartame is quickly broken down in the gut. After you drink a Diet Coke, the aspartame goes to your guts. After that, it’s very quickly broken down into 50% phenylalanine, 40% aspartic acid, and 10% methanol. For example, a can of Diet Coke contains 184 mg of aspartame. This becomes: 92 mg of phenylalanine 73.6 mg aspartic acid 18.4 mg methanol This happens quickly and completely. No aspartame ever enters your bloodstream.

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The rest of your body only ever sees these three other chemicals. (click here or on any paragraph with a triangle for more details) The European Food Safety Authority Report (EFSA) report: Scientific Opinion on the re-evaluation of aspartame as a food additive gives this figure (slightly modified): The same report gives this discussion: Fact 2: Phenylalanine is a standard amino acid you consume all the time. We recently talked about phenylalanine. It is an essential amino acid. If you didn’t consume any of it then when your body tried to make certain proteins those proteins would get truncated, and then they wouldn’t do what they are supposed to do, and then you would die. Fortunately, that’s almost impossible. From 2% to 5% of all protein in food is phenylalanine. The recommended dietary allowance for a 70 kg (154 lb) person is at least 2130 mg. Meat-eating men in the UK average 3500 mg per day, while vegetarians and vegans get slightly less. Here are the amounts of phenylalanine in a few foods: potato 170 mg large egg 340 mg 8 oz (235 ml) glass of milk 430 mg 400g box of tofu 3300 mg The 92 mg of phenylalanine you get from a Diet Coke is much less than what virtually everyone already gets from other sources. MacDonald et al. (2020): RDA guidelines are here. For adults, the recommendation is at least 33 m/kg of phenylalanine (or tyrosine, a metabolite of phenylalanine). For a 70 kg (154 lb) person, that would be 2130 mg. Schmidt et al. (2015): Around 1 in 12,000 babies is born with phenylketonuria, a serious genetic disorder that results in low levels of phenylalanine hydroxylase, making it difficult to metabolize phenylalanine. People with phenylketonuria need to carefully monitor their consumption of phenylalanine (from all sources).

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This is why there’s this scary ALL-BOLD WARNING. If you had phenylketonuria you would know it already. Fact 3: Aspartic acid is a standard amino acid you consume all the time. Here’s a chart from Wikimedia with our friends circled: Aspartic acid is not essential in humans, meaning that if you don’t eat it, your body can make it (usually from oxaloacetic acid). But that’s not likely, since almost everything with protein has aspartic acid including meat, grains, dairy, vegetables, and eggs. Men in the UK average 6600 mg of aspartic acid per day. The 74 mg of aspartic acid you get from a Diet Coke is two orders of magnitude less than what most people get already. Here’s Schmidt et al. (2015) again: Fact 4: Methanol is a simple alcohol you consume all the time. Methanol (CH₃OH) is the simplest alcohol molecule. It’s in lots of food. Here are some foods with larger average amounts. food mg/kg methanol typical serving methanol wine 115.0 150 ml glass 17 mg tomatoes 281.4 medium 125g tomato 35 mg citrus fruit 106.5 medium 140g orange 15 mg This vastly underestimates how much methanol you get. In land plants, the primary component of cells walls is pectin. Once in the body, pectin degrades into methanol. Here are some estimates of the indirect increase in methanol various fruits and vegetables cause in this way. food mg/kg methanol typical serving methanol root vegetables 774 medium 200 g potato 155 mg apples 508.5 medium 170 g apple 132 mg

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oranges 531 medium 140g orange 74 mg bananas 657 120g without skin 79 mg avocados 486 100g (flesh only) 59 mg You get the idea. We eat things that contain methanol or metabolize into methanol all the time. It’s estimated that most people get between 130 and 1030 mg of methanol from food per day, much more than the 18 mg in a Diet Coke. Now isn’t methanol toxic? Sure, if you consume enough of it. The LD₅₀ in rats is around 5600 mg/kg, as compared to 7300 mg/kg for good-old ethanol. One "conspiracy theory" you hear about aspartame is that it becomes formaldehyde once it's in the body. This is absolutely true: When metabolizing methanol, formaldehyde is created. But small amounts of formaldehyde are completely normal. The half-life of formaldehyde in human blood is around 1 minute, meaning it disappears almost immediately. You get more formaldehyde (via methanol) by eating an apple than by drinking a Diet Coke. Formaldehyde itself is also present in lots of foods, like meat, seafood, fruits, vegetables, and coffee. The EFSA report: Also the ESFA report: Dhareshwar and Stella (2008) Also Dhareshwar and Stella (2008): The EFSA report again: Fact 5: This doesn’t prove aspartame is safe. To summarize the above: Aspartame is quickly broken down in the gut into phenylalanine, aspartic acid, and methanol. Aspartame itself never enters your bloodstream or touches any other part of your body. Phenylalanine is normal. Aspartic acid is normal. Methanol is normal. (Incidentally, this same logic does not apply to other artificial sweeteners which mostly aren’t broken down at all.) While informative, this does not prove aspartame is safe.

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Biology is crazy. But it should inform our priors. Speaking for myself, my previous model was that consuming aspartame would result in a crazy unknown synthetic chemical circulating around my body and doing god-knows-what. My updated model is that consuming aspartame results in slightly larger amounts of some totally normal chemicals. This is reassuring. But even if they’re normal, could these chemicals still cause harm? Sure. Fortunately for us, aspartame was invented a long time ago, so we have lots of evidence. The scientific consensus How to think about this situation Aspartame was first made in 1965 and was approved by the FDA in 1981. In the decades since, there have been hundreds of studies. Given so many studies, focusing on individual papers is a mistake. With enough monkeys pounding away at enough typewriters scientists pounding away at enough science, lots of weirdness is expected. The right strategy is to look at the entire pool of evidence. Some tiny number of people have the time and expertise to comb through the entire literature and synthesize everything. For the rest of us, the only sane thing is to read other people who have done that synthesis. The US Food and Drug Administration (FDA) In typical US government fashion, the FDA doesn’t go to great lengths to explain its reasoning to the public. The best you can find is this rather lame page: The history of aspartame and the FDA is contentious and sort of infuriating. For the scientific question of “is aspartame safe?” the main thing to know is that the FDA approved it a long time ago, and continues to stand by those decisions. But it must be said that the history and public communication of the FDA on this issue is kind of a train wreck, and if I wanted to optimize it to serve as conspiracy theory fuel, I could scarcely do any better. The FDA says it continues to monitor new studies and remains confident aspartame is safe. So why doesn't it explain its reasoning to a skeptical public? The newest document the FDA can point people to is from 26 years ago. When a concerned citizen writes in, the FDA does things like respond 12 years later, while acting like that's perfectly normal. The FDA first approved aspartame for dry foods in 1974.

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However, there was a lot of controversy about the studies performed by G.D. Searle, the company that discovered aspartame in 1965 (and that Donald Rumsfeld would become CEO of in 1977). The FDA commissioner agreed with these criticisms and placed a stay on aspartame’s approval. After more debate, the FDA finally approved aspartame in 1981 in a 26-page report with this summary: In 1983 the FDA added approval for carbonated beverages. The report is mostly boring but this part is fun: There was controversy about US Attorney General Samuel Skinner who was involved in the case and then went on to take a job at a law firm that Searle used. This led Senator Metzenbaum to request an investigation by the Government Accountability Office (GAO). They reported in 1987 that the process had been followed correctly. They also got responses from 69 researchers, 43 of whom worked in aspartame research. Finally in 1996, the FDA approved aspartame as a “general sweetener”. Also in 1996, Roger Walton, a psychiatrist at Northeastern Ohio Universities College of Medicine, wrote a survey that claimed that 74 out of 74 industry-funded studies confirmed aspartame’s safety whereas 84 out of 91 independent studies identified health concerns. Walton went appeared in a 60 Minutes special on aspartame. It later turned out that Walton had missed at least 50 peer-reviewed studies and most of the independent “studies” he did cite were really just letters to the editor or similar, many weren’t negative, and some didn’t involve aspartame at all. For example, Walton cites Wurtman (1985). This appeared in the Lancet, which is a very good journal. But it’s just a 5-paragraph letter to the editor that points out that aspartame creates phenylalanine without other amino acids, which might do something in the brain—an idea we’ve looked at recently—and gives some anecdotes about people getting seizures. Real studies do not confirm these anecdotes.