Death by Liquorice

A blog post for the non-expert

The media is reporting a 54-year-old construction worker from Massachusetts has died of liquorice poisoning. Not for the first time when dealing with such issues, the press reports are so similar that they were likely all cloned from the original source, a paper in the New England Journal of Medicine. I thought, therefore, a blog post for the non-expert might put the toxicology of liquorice into perspective.

They make liquorice from the root of the flowering plant Glycyrrhiza glabra, largely native to western Asia. Media reports will tell you a substance called glycyrrhizic acid contained within the root, is responsible for its toxicity. This is correct, to a point. I blogged on the terpene pathway in plants before, pointing out the biochemical connection between turpentine and rubber, and even cannabidiol.  Glycyrrhizic acid is yet another byproduct of this pathway, but in this case it also has two sugar molecules attached. Glycyrrhizic acid itself is not particularly toxic because the sugars inhibit its absorption through the gastrointestinal tract. Bacteria in the digestive system however, remove the sugars to make glycyrrhetinic acid, which is absorbed into the bloodstream and that’s where the trouble starts.

There’s an enzyme with the somewhat complicated name of 11-β-hydroxysteroid dehydrogenase, but those nice biochemists have shortened it to 11β-HSD which is less of a mouthful. 11β-HSD converts a sterol called cortisone into cortisol, which, amongst other things, affects how the kidneys regulate sodium and potassium transport. Messing around with the body’s sodium and potassium levels can lead to a variety of problems. In fact there’s a disease called Cushing’s syndrome, where too much cortisol in the bloodstream leads to a decrease in potassium and a condition known as hypokalemia. Glycyrrhetinic acid is a sterol-like compound* which 11β-HSD mistakes for cortisone, throwing a metaphorical spanner in the biochemical works. This leads to excretion of potassium and sodium retention and in turn causes cardiac arrhythmias and renal failure, which is what seems to have happened to the Massachusetts construction worker. 

Some quarters of the press seem amused there’s such a thing as liquorice poisoning, but we should remember the victim had family and friends who might not see it as a joke. I suspect some will call for a liquorice ban, and warnings have been around for some years. In truth it’s not as simple as that because it’s not only sold widely as a confection, we use glycyrrhetinic acid and its related compounds in a range of foods as a natural sweetener and also in some cosmetics from lipstick to suntan lotion. Some believe liquorice has curative properties for anything from cancer to being an anti-viral –  claims which I believe we should all take with a pinch of salt. The trouble is that anything is toxic if taken in sufficient amounts. This was realised back in the 15th century by a German-Swiss physician, alchemist, astrologer and occultist with the horrendous name of Philippus Aureolus Theophrastus Bombastus von Hohenheim. Perhaps even in his own time, his name may have been a bit of a mouth-full, because he was just known as Paracelsus. Amongst a lot of mumbo-jumbo of his age, he got at least one thing right. He famously said, “what is it that is not poison? All things are poison and nothing is without poison. It is the dose only that makes a thing not a poison.” Over time this became abbreviated to, “the dose makes the poison.”  Anything taken in excess can be toxic, even the most benign of substances, like water for example. Water intoxication, or hyperhydration, is rare but there are occasional cases. In 2007 for example, a Californian woman died after taking part in a water-drinking contest where she drank up to 4 L in an hour. At the other end of the scale, all vegetables contain tiny amounts of more potent toxins. Potatoes, for example, have substances related to glycoalkaloid poisons found in deadly nightshade called solanines. You might believe celery is the most beguine ingredient in a healthy salad but it has a carcinogenic chemical known as psoralen. Cabbage, broccoli and cauliflower all contain a group of chemicals called glucosinolates, which can impair thyroid function. Your body is more than capable of coping with these small of potentially toxic substances in your everyday diet. In fact we have evolved some exquisite detoxification biochemistry to do so with no need for so called detox diets. Talking of detox, grapefruit, so popular with that fad, contains furanocoumarins that inhibit certain enzymes otherwise involved in everyday natural elimination of toxins from the body – biochemical irony!

The Massachusetts construction worker supposedly ate a bag and a half of liquorice a day – that’s around 400-500 grammes. In 2004 a Yorkshire woman in the UK, suffered serious muscle failure requiring hospitalisation after eating less than half that amount of liquorice per day. So the lesson is, everything in moderation and remember Paracelsus, anything in large enough doses can kill you. Now where did I put those Bassetts Liquorice Allsorts?

• – to be more precise it’s a triterpenoid but I’m not getting into that level of detail