Paracelsus' poison

Decaffinated People? Is there an anti-caffeine pill?

Who amongst us hasn’t wished, in the wee small hours when we are staring at the bedroom ceiling wide awake, heart pumping, bitterly regretting that last, late night espresso, that there was an anti-caffeine pill. Well ThinkGeek, that repository of all things cool for us thinking geeks*, is selling pills that are claimed to rapidly remove caffeine from our coffee saturated bodies. Theoretically they should work, but practically they probably don’t.

Which is a good thing.

So how are they supposed to work?

Our livers come equipped with a range of enzymes that break down chemicals foreign to the body. Plants, bacteria and fungi all produce chemicals that are harmful to us, and our bodies have evolved a range of enzymes to deal with them. Some of these foreign chemicals stimulate the body to make more of these enzymes, presumably to deal with an increased toxic threat.

The body can’t differentiate between potentially harmful chemicals and potentially helpful medicinal chemicals. So several herbal medicines increase the amount of breakdown enzymes. The herbal anti-depressant St. John’s Wort is a powerful enzyme inducer for example.

Caffeine, the heart pumping, sleep banishing component of coffee is broken down by the enzyme CYP1A2. Several drugs and chemicals can stimulate the body to make more CYP1A2. So theoretically, if we gave a drug to increase the enzyme levels, caffeine would be broken down faster and we would get to snooze compatible blood levels of caffeine much sooner.

Evodia rutaecarpa. By Philipp Franz von Siebold and Joseph Gerhard Zuccarini [Public domain], via Wikimedia Commons

One such drug is the alkaloid rutaecarpine, from Evodia rutaecarpa, used in herbal medicines. If you give this drug to rats, it will cause them to break down caffeine screamingly fast. Rutaecarpine forms the basis of the anti-caffeine pills sold through ThinkGeek.

But wait, you just said it was unlikely to work.

Yes, I did. For two reasons. Firstly, in all the animal studies I’ve seen, they gave the drug for 3 days before testing the rats ability to break down caffeine. In order to work, the drug must get the body to make more enzyme. This is typically a leisurely affair, with between 24 to 72 hours before you see a substantial increase in enzyme levels in an animal or human. It’s a lot faster if you squirt the drug on cells growing in a dish, but even then I’ve only seen papers that found increased enzyme levels at 18 hours.

Obviously, if you want to get a good nights rest following the double espresso you had at 10 o'clock, you don’t want to wait 18 or more hours to see an effect. The instructions for these tablets say to take them 2-4 hours before going to bed, that’s nowhere near enough time to for the enzyme levels to increase appreciably.

Even if somehow the enzymes levels shot up in 4 hours to double the speed caffeine removal, a normal person takes 6 hours to drop their blood concentration by half. Doubling the rate of removal decreases the time to 3 hours, so it’s still going to be a while before you drift off to the land of nod.

The second reason is if the dose makes the poison, it also makes the drug. The smallest dose I’ve seen used (again over a 3 day period), was 50 milligram per kilogram. The tablets are being sold as 100 milligram per dose. Which, if you are a 70 kilogram person, works out to 1.4 milligrams per kilogram. 20 times less than the rats were getting.

Even if we allow for the fact that dosages don’t scale up up linearly**, you would need to take something like 6 tablets to get the smallest doses used in the rat.

Okay, so the dose is likely too low and the time frame too short. Why is a good thing this drug won’t work as advertised?

As well as taking a while to increase the levels of CYP1A2, once the levels are up, it takes a while for them to come down. Again, this is typically around 24 honours, but can be up to a week.

So you take your anti-caffeine pill, get your caffeine levels down and enjoy some snooze for a blissful 8 hours. Then you leap out of bed, put on your morning coffee, slam back the cup of brew and …. Nothing, because your CYP1A2 is still at high levels chomping away at your caffeine, and will be doing so into late into the afternoon.

Possibly not what you wanted.

Also, if you are on theophylline for your asthma, it’s an analog of caffeine and will be broken down as well, so your asthma control is out the window for around 24 hours. If you are on antidepressants, some anti-cancer drugs, paracetamol, some blood pressure drugs and the anti-clotting drug warfarin (amongst others) these will also be broken down so fast that they will not work properly.

While the drug site does advise you that you should consult your doctor about medication before consuming the pills, most people taking over the counter medications like paracetamol are unlikely to check with their doctor first.

So inducing CYP1A2 is not such a great idea.

No, it takes too long to work, it’s not specific to caffeine, and lasts too long afterwards. We Geeks would do much better to forgo the double espressos late at night.

*My favorite Dr. Who mug comes from thinkGeek.

** typically, you have to multiply the rat dose by 0.16 to get the equivalent human dose for many medications. So the human equivalent of 50 mg/kilogram is 8 mg/kilogram. This means a 70 kilogram human would need 560 mg a day for 3 days to have the same effect, not a single 100 mg tablet.

Hat tip to David Kroll of TerraSigillata.

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