Aspartame is in the news again, with the WHO claiming it causes cancer. What does the science say?
Here's the challenge: we can't give a potentially toxic substance to patients, which means the most we can ever do is demonstrate a correlation. A few studies claim to have found one, but confounding factors cannot be ruled out: what other lifestyle factors do people who drink diet soda have that might contribute to cancer?
Let's back up a bit. For aspartame to cause cancer, there are some well-known things it would have to do.
What causes cancer
Cancer is caused by DNA damage. The chemical nature of the toxin determines what type of DNA damage occurs. Reactive molecules can crosslink DNA bases, while oxidants can cause single- or double-strand DNA breakage. A cell with damaged DNA will produce a defective protein. That bad protein may throw the cell into overdrive so it can't stop dividing, or it may prevent the damaged cell from self-destructing (or, as the two-hit theory says, both must occur). If the DNA is really messed up, it can get tangled up when the cell divides and the cell will die in a very messy way. Ultraviolet light, radioactivity, and oxidants such as hydrogen peroxide and ozone typically produce oxidative stress, which can damage DNA.
It's easy enough to measure oxidative stress by looking at oxidized molecules—oxidized lipids or proteins, for instance, or by looking in the urine for evidence of base excision—but the cell has elaborate mechanisms for repairing DNA. Even when these fail, the cell can self-destruct if something goes wrong, and the immune system can often eliminate the bad cell.
No calories or other nutrients of any kind Aspartame is the third largest ingredient in this putatively drinkable commercial liquid, roughly 200 to 300 milligrams for a 12-ounce bottle
But clinical correlations can be misleading. For years it was believed that drinking alcohol caused cancer because it killed cells, which triggered cell division as the body created replacements. If those dividing cells contained mutations, the theory went, cancer could be produced. The effect was small, and people eventually realized that inducing cell division should not be equated with causing cancer.
Ironically, cancer treatment can also cause cancer. Until the advent of immunotherapy, treatment generally consisted of highly toxic drugs or radiation that damaged the DNA, usually with other drugs that blocked DNA repair. The idea was that those cells that divided fastest would have their DNA hopelessly damaged and would self-destruct. Unfortunately, the treatment also produces new DNA damage, and cell death causes a sort of natural selection such that cancer cells become 'resistant.'
Oncologists sometimes erroneously classify anything that promotes cell growth as an ‘oncogene.’ This has done more than any other factor to force researchers in other fields to abandon potentially life-saving treatments. For example, if a drug target is thought to play any role in metastasis, any Alzheimer treatment that touches that target turns into a hot potato.
Aspartame metabolites
So far, there's no evidence that aspartame does any of these things. The challenge is that it's difficult to measure aspartame in patients because it breaks down into phenylalanine, aspartate, and methanol. The first two are harmless amino acids, and while the third can be metabolized to formaldehyde, which is bad for you, it is produced in such small concentrations as to be inconsequential.
Many studies on aspartame have used ridiculously high concentrations, as high as 0.3 mM or 0.05% in drinking water. This means little: the goal is to see an effect, even if it means overwhelming the normal detoxification mechanisms. We also need to be skeptical. Studies purporting to show that a molecule is harmful often mysteriously appear just before a patent is granted for a replacement.
A handful of papers have claimed to find metabolites of aspartame besides the three established ones, such as diketopiperazine (5-benzyl-3,6-dioxo-2-piperazine acetic acid). Another possibility is manufacturing contaminants or racemization caused by heating or chemical synthesis. This could produce small amounts of D-phenylalanine instead of the normal L-phenylalanine.
Typically, a carcinogenic compound needs to be “activated” or metabolized in the liver to something bad before it becomes toxic. That's why the Ames test specified that liver extracts needed to be added. The challenge is not to show that it's produced—that's easy with modern mass spectrometry—but that it's produced in the specific human cells where the disease occurs, at sufficient concentrations and for long enough time to produce the effect, and in living persons, not just in cultured cells or mice.
Your tax dollars screwing up again
Finding a metabolite is only the first step. The oldest joke in molecular biology is that all drugs are specific when they first come out, but over time they become less specific and finally they're abandoned. What does this mean? It means that finding a plausible mechanism—or molecule—does not mean it causes the effect. Indeed, focusing on one single molecule often leads to fanaticism, as we often see with supposed environmental hazards like 5G radio waves, plastics, and “forever chemicals.”
Other fields, such as climate studies, which face insurmountable barriers in establishing causation, tend to ignore this principle, but it's endemic in medicine. We've seen over and over again how scientists can champion a single drug, vitamin, or potential toxin as a cure or as the cause of disease. But proving a single mechanism in an ocean of alternatives is far from easy. Think Linus Pauling with vitamin C or the dozens of failed pharma start-ups that promoted a drug that some entrepreneur believed, in the face of mountains of contradictory evidence, would cure some major disease and make him famous.
The aspartame-cancer story is a perfect example of bad science: so far, it's an effect without a cause. If aspartame is cleared, they'll go after the plastic in the bottle next.
During the Covid panic, many drugs were proposed as potential treatments. The ones that failed all had one thing in common: the lack of a clear mechanism of action at the concentration that is achieved in patients. That's hard enough to demonstrate in the lab. If you can't even measure the blood levels of the toxin, it's worse. And if you have no idea what the toxin is, all you can do is speculate. That's what the WHO seems to be doing.
So guzzle down that Diet Coke if you can stand the taste of it, but I'd worry more about what it does to my teeth than whether it causes cancer.
jul 16 2023, 6:26 am
