Reconsider the anti-cavity bacteria if you are Asian

Update: further research has led me to believe that people of all races should test themselves for ALDH deficiency before using Lumina. Even if you don’t exhibit AFR symptoms when drinking alcohol, your ALDH activity may still be decreased.

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.

Ethanol Metabolism: Enzymes, Steps, Reactions

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 acetaldehyde levels a day is enough to cause oral cancer—that’s how it works in people with AFR when they drink alcohol!

But perhaps the increase in acetaldehyde is simply too low to cause significant problems, even in the mouth? I think this is possible, but unlikely. The reason Lumina was created at was because of cavities. Most oral bacteria convert sugars to lactic acid as the end product of anaerobic metabolism. This results in cavities when mouth pH is lowered below 5.5. My back-of-envelope calculation say that this implies a 0.01 mol solution of lactic acid, or about 5% by mass. This may well be even higher in practice since saliva acts as a pH buffer. Note that while resting saliva samples rarely measure below 6.3 pH, it can drop down to 4.0 after drinking certain sugary drinks (somehow, this topic is underresearched. Is this why people complain about dental science?). Notably, this is caused by sugar metabolism. Sour milk, sugarless coffee, and light (diet) coke resulted in much higher oral pHs than their sugary counterparts. Again, transient local exposure of oral epithelium to acetaldehyde is exactly what causes the elevated oral cancer risk in the first place, and similar exposure to lactic acid is what causes cavities. Is it possible that acetaldehyde and ethanol behave differently from lactic acid? Maybe. But the weight of evidence is enough to make me concerned.

All considered, I personally consider the negatives of potential cancer risk greater than the positives of cavity prevention for someone with AFR. I would recommend further research on oral acetaldehyde for people with and without ALDH deficiency who have already taken the treatment, advice against the use of Lumina for those known to have the mutation, and urge those of East Asian ancestry to test themselves if they are unsure. As a reminder, ALDH deficiency is a semi-dominant mutation—you may have the phenotype even if you have a low East Asian admixture.

Excerpts from Scott’s FAQ follow:

Conflict of Interest: If you’ve already used Lumina and regularly kiss Asians, this may be a concern. However, my interest in kissing women outweighs my interest in not having cancer, so I recommend no change in behavior.

My recommendations would be:

  1. Measure acetaldehyde levels in the saliva/​oral plaque samples of users of the probiotic who are known to have AFR before, during, and after food, sugary drink, and alcohol consumption.

  2. Ask if a fruity smell has appeared in the breaths of Lumina users, especially those with AFR—acetaldehyde is responsible for the fruity smell associated with drinking alcohol. There is nothing suggesting this on Twitter, which is a good sign.

  3. Don’t use Lumina if you have AFR or aren’t sure. Update: even if you can handle your liquor, you may well still have an ALDH variant that decreases ALDH activity. I would undergo genetic testing, just to be sure. If you have two copies of the mutation, be extra careful. If you already did use Lumina, your risk of cancer may have increased. Consider drinking less alcohol, and take oral hygiene more seriously.

  4. Monitoring oral flora changes and the speed of oral ethanol → acetaldehyde conversion.

  5. Do more research on the interpersonal spread of BCS3-L1 after application.

  6. If the bounty for finding new problems with Lumina is still active, I hope this qualifies for more than $100. I am also more than happy to participate in additional research. I think the additional introduction of bacteria with high ALDH activity might work and also decrease the effect of hangovers, which would be nice and also a potential product. Hey, another reason to hire me!

  7. Update: if you frequently drink alcohol, I would also advise against using Lumina.

  8. Update: check if hangovers get worse over time in Lumina users

Update: I am reminded that ALDH polymorphism isn’t restricted to Asians, and that many variants which don’t heavily disrupt drinking can still result in significant increases in acetaldehyde levels. I would recommend everyone interested in getting Lumina to undergo genetic testing beforehand.