The artificial sweetener aspartame, best known as an additive to diet sodas, has been around for more than 50 years. Despite some controversies regarding its approval, aspartame is safe. That fact hasn’t stopped various aspartame hoaxes from regularly circulating, which get signal-boosted by quacks like Dr. Mercola. So I decided to take a look at the molecule, its metabolites, and whether or not there is any veracity to claims of toxicity.
Aspartame is nearly 200 times sweeter than sugar, but there is more than 200 times less aspartame in a can of Diet Coke (180 mg) than there is sugar in a can of Coca Cola (39,000 mg). So already we’re keyed in to the #1 thing ‘natural health experts’ frequently omit – toxicity is related to dose, and the chemicals they make into bogeymen are often quite scarce.
Aspartame binds to receptors on your tongue where it elicits a potently sweet flavor, but the intact molecule never even reaches the bloodstream. Digestive enzymes rapidly break aspartame into 3 molecules – aspartic acid, phenylalanine, and methanol. The first two are amino acids, ubiquitous in your body and your diet—and no Dr. Mercola, the body cannot tell whether these come from natural or synthetic sources. That leaves methanol and its metabolite, formaldehyde.
Formaldehyde has a nasty reputation as a sensitizer, “a chemical that causes a substantial proportion of exposed people or animals to develop an allergic reaction in normal tissue after repeated exposure to the chemical.” At high doses formaldehyde is cytotoxic and carcinogenic. In the cell, formaldehyde reacts with DNA and/or proteins, crosslinking them together. The immune system can recognize these unnatural Frankenstein biomolecules as foreign & elicit an inflammatory response.
But importantly, these phenomena result from inhaling formaldehyde gas, not metabolically-produced formaldehyde. Chronic pulmonary exposure to formaldehyde results in carcinogenesis. Most toxicological studies are related only to inhalation. One 1991 review of formaldehyde oral toxicity concluded that chronic low-level exposure is not toxic or carcinogenic. In fact, the EPA merely points out that it may be present in food, naturally or as a source of contamination.
Formaldehyde also happens to be a fundamental biological building block, an intermediate in the cellular synthesis of amino acids and other biomolecules. In rats, monkeys, and humans, formaldehyde is naturally present in the blood at a concentration of 3 parts per million. Critically, your body rapidly metabolizes excess formaldehyde into formic acid (AKA formate), which is excreted in urine or oxidized to carbon dioxide, which you breathe out. Some formate re-enters the ‘one carbon pool’, a biotic supply of carbon for construction of biomolecules. To reiterate: these are all normal processes in mammals.
How can formaldehyde have such different effects by inhalation versus ingestion? As gaseous formaldehyde passes through the nasal mucus layer, much of it is absorbed and metabolized by local epithelial cells. But acute doses overwhelm these cells’ metabolic capacity, causing the tissue damage and immunogenicity that I mentioned earlier. Nasopharyngeal cancer is the principal malignancy associated with workplace formaldehyde exposure.
I guess we should still talk about methanol, which has exposure concerns of its own. Since it’s a liquid one could ingest an acute toxic dose, like these Russians did when they chugged methanol-tainted ‘scented bath lotion’ because they ran out of vodka (really). Metabolism into formate exceeds cellular metabolic capacity, causing blood serum levels to surge to 30 times higher than normal. These levels of formate disrupt cellular respiration by inhibiting the electron-transport chain in mitochondria, leading to cell death. For somewhat unknown reasons, the optic nerve is particularly sensitive to formate toxicity, such that sublethal methanol doses produce irreversible blindness as a consolation prize. The 74 thirsty Russians were not so lucky.
Aspartame breakdown doesn’t produce enough methanol to elicit acute toxicity—you’d drown in Diet Coke long before you’d get close. Methanol and methyl esters are present naturally in many fruits and vegetables. Natural methyl esters, such as pectin, are responsible for the residual methanol produced during fermentation into spirits. Likewise, fruit juices can contain many times more methanol than results from the breakdown of aspartame in soda. To wit: adults that consumed 40x more aspartame than average daily intake saw their blood methanol concentrations rise all the way to 100x less than the threshold for methanol poisoning, and their formate levels increase…not at all.
So aspartame is present in foods at low concentrations and breaks down completely into benign metabolites our bodies are perfectly capable of handling. But…recent research seems to vindicate Dr. Mercola’s anti-aspartame stance. He may be wrong about all the reasons aspartame is bad, and spread misinformation, but if life was fair there’d be no ‘but’. Endocrinologist and sugarphobe Robert Lustig previously claimed that artificial sweeteners binding to taste receptors triggers insulin release, and experimental evidence supports that theory.
In 2014, a study published in Nature showed that mice consuming sugar and artificial sweeteners (sucralose, saccharin, and aspartame) released higher amounts of insulin, relative to control mice that consumed only sugar. Intriguingly, the effect was ameliorated in sterile mice lacking gut bacteria, or by co-treating with antibiotics. Like most microbiome-related phenomena, an exact mechanism is currently lacking. The effect was observed in humans in a 2013 study, with sucralose in obese subjects. Even more evidence may be coming soon.
Researchers had previously established a link between diet soda consumption and metabolic syndrome, but it’s hard to establish causation from correlation when dealing only with survey data. The experiments in humans and mice are converging on a mechanistic role for artificial sweeteners in the lifestyle diseases that plague Americans and everyone else who consumes a version of our Western diet.
These recent studies indicate that aspartame & artificial sweeteners are chronic rather than acute toxins. The difference is critical because it ends up being prescriptive. A diet soda every now and again isn’t going to have much of an effect at all on your health, but regularly eating sugar-free processed foods contributes to the very diseases we once thought they save us from. Consuming a diet based on whole foods is the best advice I can provide. Avoid aspartame not because it is acutely toxic, avoid it because it is associated with a pattern of eating that portends metabolic syndrome.
So I will begrudingly tip my cap to Dr. Mercola: in this case, 500 wrongs did make a right.
(He’s still a snake oil salesman & B.S. peddler)