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Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Reconsider the anti-cavity bacteria if you are Asian, published by Lao Mein on April 15, 2024 on LessWrong.
Many people in the rational sphere have been promoting Lumina/BCS3-L1, a genetically engineered bacterium, as an anti-cavity treatment. However, none have brought up a major negative interaction that may occur with a common genetic mutation.
In short, the treatment works by replacing lactic acid generating bacteria in the mouth with ones that instead convert sugars to ethanol, among other changes. Scott Alexander made a pretty good FAQ about this. Lactic acid results in cavities and teeth demineralization, while ethanol does not. I think this is a really cool idea, and would definitely try it if I didn't think it would significantly increase my chances of getting oral cancer.
Why would that be? Well, I, like around half of East Asians, have a mutation in my acetaldehyde dehydrogenase (ALDH) which results in it being considerably less active. This is known as Asian/Alcohol Flush Reaction (AFR). This results in decreased ability to metabolize acetaldehyde to acetate and consequently a much higher level of acetaldehyde when drinking alcohol.
Although the time ingested ethanol spends in the mouth and stomach are quite short, alcohol dehydrogenase activity by both human and bacterial cells rises rapidly once the presence of ethanol is detected. Some studies have estimated that ~20% of consumed ethanol is converted to acetaldehyde in the mouth and stomach in a process called first pass metabolism. Normally, this is broken down into acetate by the ALDH also present, but it instead builds up in those with AFR.
Acetaldehyde is a serious carcinogen and people with AFR have significantly higher levels of oral and stomach cancer (The odds ratios for Japanese alcoholics with the mutation in relation to various cancers are >10 (!!!) for oral and esophageal cancer).
The Japanese paper also notes that all alcoholics tested only had a single copy of the mutation, since it is very difficult to become an alcoholic with two copies (imagine being on high dosage Antabuse your entire life - that's the same physiological effect).
In addition, there is also the potential for change in oral flora and their resting ADH levels. As oral flora and epithelial cells adapt to a higher resting level of ethanol, they may make the convertion of ethanol to acetaldehyde even faster, resulting in higher peak oral and stomach levels of acetaldehyde during recreational drinking, thereby increasing cancer risk.
There is also the concern of problems further down the digestive track - Japanese alcoholics with AFR also have increased (~3x) colorectal cancer rates, which may well be due to ethanol being fermented from sugars in the large intestines, but my research in that direction is limited and this article is getting too long.
While others have argued that the resulting acetaldehyde levels would be too low to be a full body carcinogen (they make a similar calculation in regards to ethanol in this FAQ), my concern isn't systemic - it's local. AFR increases oral and throat cancer risks most of all, and the first pass metabolism studies imply that oral and gastral acetaldehyde are elevated far above levels found in the blood.
As a thought experiment, consider that a few drops of concentrated sulfuric acid can damage your tongue even though an intraperitoneal (abdominal cavity) injection of the same would be harmless - high local concentrations matter! The same is true for concentration in time - the average pH of your tongue on that day would be quite normal, but a few seconds of contact with high concentrations of acid is enough to do damage.
This is why I'm not convinced by calculations that show only a small overall increase in acetaldehyde levels in the average person. A few minutes of high oral aceta...
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