Treating alcohol poisoning… with alcohol?

If you’ve ever had a splitting headache, you know that there are not many immediate pain relieving techniques that you have at your disposal. One peculiar option is to focus on pain elsewhere in the body- say, a stubbed toe or a sore belly, to distract yourself from the real pain. Seems like just another urban myth, right?

It turns out Nature actually employs this trick in biochemistry. Methanol poisoning occurs when someone overconsumes, you guessed it, methanol.  The body breaks down alcohols primarily using alcohol dehydrogenase (ADH), which is a redox-driven enzyme that reduces the alcohol to an aldehyde. Methanol gets converted to formaldehyde, which is consecutively converted to formate by aldehyde dehydrogenase (ALDH). Formate is a dangerous chemical that inhibits Complex IV of ATP synthesis- leading to headaches and CNS depression. You would think a mistake as simple as confusing methanol (or ethylene glycol) with alcohol would be a small one, but many thousands of Americans annually fall victim to methanol poisoning.

toxic_alcohol_metabolism
Alcohol metabolism- note the competitive inhibition of alcohol dehydrogenase (ADH). Source: wikispaces.net

There are two treatment options for methanol poisoning- a) a drug called fomepizole that costs over $1000 per dose, or b) ethanol. Wait, you can’t be serious, right? Consuming more alcohol decreases the effects of methanol poisoning? It turns turns out that ethanol is a strong competitive inhibitor of ADH, which means that the reduction of methanol is dependent on the concentration of ethanol. ADH converts ethanol to acetaldehyde, which is a precursor to the high-energy compound Acetyl-CoA (remember the Kreb’s cycle?) Interestingly enough, fomepizole is also a competitive inhibitor of ADH that seeks to be a true antidote to methanol poisoning by precipitating the intermediates.

What’s even more surprising is that a study comparing the effects of ethanol and fomepizole on methanol poisoning was recently conducted. The results? “Unfortunately, the quality of published data available for our systematic review limits the conclusions which can be drawn.” This shows once again the power of Nature and the need for simplification – a powerful yet astonishingly confusing motif.

Links: Methanol poisoning

Review of ethanol vs. fomepizole

Cost of fomepizole (1990s)

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