 The approval of aspartame has a controversial history. The FDA commissioner concluded that there was reasonable certainty that human exposure of aspartame would not pose a risk of brain damage, resulting in mental retardation, hormonal dysfunction, or both, and will not cause brain tumors. However, the FDA's own public board of inquiry withdrew their approval over cancer concerns. Furthermore, several FDA scientists advised against the approval, citing the aspartame company's own brain tumor tests. The commissioner approved aspartame anyway, before he left the FDA and enjoyed a $1,000 a day consultancy position with the aspartame company's PR firm. Then the FDA actually prevented the National Toxicology Program from doing further cancer testing, so we were left with people battling over different rodent studies, some of which showed increased cancer risk and some of which that didn't. It reminds me of the whole saccharin story, where it caused bladder cancer in rats, but not mice, leaving us with unanswerable questions like, so are we more like a rat or a mouse? We obviously had to put the aspartame question to the test in people, but the longest human safety study lasted only 18 weeks. We needed better human data. Since the largest rat study highlighted lymphomas and leukemias, the NIH AARP study tracked blood cancer diagnoses, and higher levels of aspartame intake were not associated with the risk of cancer. It's a massive study, but was criticized for only evaluating relatively short-term exposure. People were only studied for five years. Hey, better than 18 weeks, but how about 18 years? All eyes then turned to Harvard, which started following the health and diets of medical professionals since before aspartame even came on the market. In the most comprehensive long-term population study to evaluate the association between aspartame intake and cancer risk in humans, they did find an association between both diet soda and total aspartame intake and the risk of both non-Hodgkin's lymphoma and multiple myeloma in men and leukemia in both men and women. Okay, but why more cancer in men than women? One result was found for pancreatic cancer and diet soda, not soda in general. In fact, the only sugar tied to pancreatic cancer risk was the milk sugar lactose. It was the diet soda. So the male-female discrepancy could have just been a statistical fluke, but they decided to dig a little deeper. Aspartame is broken down into methanol, and the methanol is turned into formaldehyde, a documented human carcinogen by this enzyme here, alcohol dehydrogenase. The same enzyme that detoxifies regular alcohol is the same enzyme that converts methanol to formaldehyde. Is it possible men just have higher levels of this enzyme than women? Yes, that's why women get higher blood alcohol levels drinking the same amount of alcohol. If you look at liver samples from men and women, there's significantly greater enzyme activity in the men. So maybe that explains the increased cancer risk in men, the higher conversion rates from aspartame to formaldehyde. But how do we test it, though? Ethanol-regular alcohol competes with methanol for the same enzyme's attention. In fact, regular alcohol is actually used as an antidote for methanol poisoning. So men who don't drink may have higher formaldehyde conversion rates from aspartame if this whole formaldehyde theory is correct, and indeed consistent with this line of reasoning, it was the men that drank the least alcohol that appeared to have the greatest cancer risk from aspartame. A third cohort study has since been published and found no increased lymphoma risk associated with diet soda during a 10-year follow-up period. So no risk detected in the 18-week study, the 5-year study, or the 10-year study, only in the 18-year study. What should we make of all this? Well, some have called for a re-evaluation of the safety of aspartame. Of course, it's gonna out of the barn at this point with 34 million pounds of the stuff produced annually. But that doesn't mean we have to eat it, especially perhaps pregnant women and children.