The cold cure that’s 5000 years old

Could we just remove the front of my face? I think it'd be less painful....

Could we just remove the front of my face? I think it’d be less painful….

A couple of days ago I was struck down with a sinus infection. This is something I thought I’d had before, but it turns out that what I’d actually had before was an uncomfortably stuffy nose. Whereas this, on the other hand, was the sensation that someone had put my forehead in a vice and was inflating my eyeballs with a bicycle pump.

I explained this to the doctor. He nodded sympathetically and suggested a drug that’s been used, in one form or another, for five thousand years.

If you’re new to this blog, you might be wondering at this point whether, when I say ‘doctor’ I actually mean ‘naturopath’ (or some other thing that translates as ‘not a doctor’). But, no, this was a properly qualified member of the medical profession. Well, I hope he is. I mean, I haven’t looked him up on the General Medical Council’s list. I assume my surgery did that. I’m sure they did. Anyway….

207px-(+)-Pseudoephedrin

Pseudoephedrine

What was this mysterious, ancient medicine? It was pseudoephedrine, otherwise known (in the UK anyway) by the brand name Sudafed®.

It’s a drug many of us have probably taken to help with cold symptoms, and not given much thought to, but it’s actually got a pretty interesting story.

Pseudoephedrine falls under the class of amphetamines. The ‘amine’ bit of that word refers to the NH group (or it might be NH2, or even just N) and, being one of the fundamental bits in proteins, it turns up in lots of biologically active molecules. It’s in paracetamol (acetaminophen) for example, and antihistamine drugs used to treat allergies, as well as many molecules that occur naturally in the body, such as dopamine and adrenaline (epinephrine).

It’s also there in methamphetamine (commonly known as ‘crystal meth’ or just ‘meth’). In fact, pseudoephedrine and methamphetamine are chemically similar, and the latter can be synthesised from the former (I’m not recommending any of my readers try this; it’s very much frowned upon from a legal point of view). For this reason, the sale of pseudoephedrine is tightly regulated; in the UK you can only buy it over the counter in a licensed pharmacy, and then only in small blister packs. (Cold medications that you can pick up from the shelf usually contain the far less effective phenylephrine.)

800px-Ephedra_sinica_alexlomas

The Ephedra sinica plant

Where does it come from? These days, pseudoephedrine is made in a three-step process, the first of which involves yeast fermentation, but it was first isolated from plants, in particular Ephedra sinica, also known as Chinese ephedra or Ma Huang.

This is where the five thousand years comes in, because these plants have been used in Chinese medicine for millennia. In fact, Ephedra is one of the oldest known medicines. It’s described in the legendary Chinese pharmacopoeia Pen-tsao Kang-mu, and became a common part of Chinese prescriptions to treat cold symptoms, fevers and asthma.

The first substance in Ephedra plants to be used in western medicine was Ephedrine. It was isolated in 1885 by a Japanese chemist called Nagai Nagayoshi, but it was then rather forgotten about until 1920s, when it was rediscovered and became a popular treatment for asthma.

In those days, steroid inhalers had yet to be developed, and the standard treatment for asthma was adrenaline. This was problematic, because adrenaline isn’t orally stable: it had to be injected. Ephedrine, by contrast, would work if swallowed as a pill, making it much easier to use.

Ephedrine_enantiomers

Ephedrine is made up of a mixture of these two mirror-image molecules

Unfortunately, ephedrine had rather unpleasant side-effects. It caused raised blood pressure, and then there were a number of other potential problems such as dizziness, trembling, headache, irregular heartbeat and even, in some cases, heart attack and stroke. Worth the risk perhaps, if you’re in the middle of a life-threatening asthma attack, but not something you’d want to use routinely.

The story goes (although I haven’t been able to verify this by finding, say, a recorded study) that when the use of the whole Ephedra plant as a treatment was compared to the use of pure ephedrine, people noticed that the side-effects were much less severe, even though the whole plant still appeared to be an effective treatment. This caused researchers to wonder whether there was some other substance in Ephedra that had subtly different effects on the body.

Whether this observation was really made or not, it turned out there was another active molecule in the Ephedra plant. It was first separated from ephedrine in in 1927, and was given the name pseudoephedrine, literally ‘false ephedrine’. Ephedrine and pseudoephedrine are structural isomers: they have the same number and type of atoms, ordered slightly differently. This is a common theme in medicinal chemistry: switching just a couple of atoms around can make big differences to the way the human body reacts to drugs.

Like ephedrine, pseudoephedrine was an effective bronchodilator and vasoconstrictor (causing blood vessels to shrink), but its effects were less dramatic, which made it a lot safer. It doesn’t raise blood pressure nearly as much, and is far less likely to cause something really nasty like a heart attack. That said, it’s not side-effect free, and it should go without saying that anyone with an existing medical condition should speak to their doctor before using it. Likewise, don’t go messing about with Ephedra plants.

Vasoconstriction is why pseudoephedrine such a good decongestant. Less fluid leaves the shrunken blood vessels and therefore less fluid enters the throat, nose and sinus linings. This reduces inflammation mucus production, and the incessant pounding of a sinus headache eases up a bit.

Of course, pseudoephedrine doesn’t somehow know to restrict itself to your nose and lungs. Blood vessels throughout the body are affected. This can be useful – for example, pseudoephedrine can help to treat ear infections – but it can also result in other, less desirable effects. In particular, pseudoephedrine suppresses breast-milk production, and for this reason shouldn’t be used by new mothers trying to establish breastfeeding. It might also interfere with mucus membranes in the vagina, potentially causing a small reduction in fertility and, not surprisingly, a substance which is a vasoconstrictor can also aggravate erectile dysfunction. Basically, if you’re trying to make a baby this might be one to avoid, although if you’re stuffed up with a cold you might not feel like it anyway, so perhaps it doesn’t matter.

Anyway, I know what you’re all desperately wondering: But, Chronicle Flask, did it sort out your sinus infection?!

dara

“Science knows it doesn’t know everything; otherwise, it’d stop.”

Well, actually, I’m relieved to report that after taking three doses of pseudoephedrine twice a day for a couple of days the pain has eased up considerably. Of course, there’s nothing antiviral (or antibacterial) in this medicine, but it would appear that my immune system managed to take care of the infection for me, once the inflammation was reduced and the excess fluid which was causing the pressure was able to (yuck) drain away.

To quote the comedian Dara O’Briain:
“‘Oh, herbal medicine’s been around for thousands of years!’ Indeed it has, and then we tested it all, and the stuff that worked became ‘medicine’.”


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No, ketchup does not cause cancer

ketchup and coke

Do these things really cause breast cancer? (Spoiler: no)

Less than two days into the new year, and I’d already found what might well be one of the silliest health headlines of the year. What is it I hear you ask? Well, it was in a national newspaper on New Years Day, and it was this:

Sugar found in ketchup and Coke linked to breast cancer

This, to borrow a favourite line from an online greetings card company, had me rolling my eyes so hard I could practically see my brain. Why? Because even without reading any further, I knew immediately that it was the equivalent of saying, “too much of thing found in most stuff might cause cancer!”

But let’s not be one of the 70% of users that only read the headline, let’s dig a little further. The newspaper article, which in fairness isn’t too bad – it’s just a bit of a silly headline, alludes to work carried out the University of Texas’ MD Anderson Cancer Centre. If you click on the link I’ve added back there, you’ll see that MD Anderson’s headline was:

“Sugar in Western diets increases risk for breast cancer tumors and metastasis”

Note, they just say ‘sugar’, not sugar in two apparently randomly-selected foodstuffs. The researchers divided mice into four groups, fed some a diet high in sucrose (more commonly called table sugar – in other words, the stuff in the sugar bowl) and compared them to others fed a low-sugar, ‘starch-controlled’ diet. They found that the high-sugar diet lead to increased tumour growth, particularly in mammary glands.

I’ve covered forms of sugar before but still, here’s a quick reminder before we go any further: this is a molecule of sucrose:

Saccharose2

Sucrose

Sucrose is made of two ‘bits’ joined together: one unit of fructose and one unit of glucose.

157px-Alpha-D-Glucopyranose

Glucose

These two molecules are what chemists call isomers. They contain the same number and type of atoms, just joined up differently. They’re both sugars in and of themselves. Glucose is used directly by cells in your body for energy. Fructose, on the other hand, is trickier. It has a lower glycemic index than glucose, in other words, it doesn’t raise your blood sugar as rapidly as glucose, but this doesn’t mean it’s healthier. It’s metabolised almost exclusively in the liver and, long story short, invariably ends up being converted into, and stored as, fat.

179px-Beta-D-Fructofuranose

Fructose

Fruit is high in fructose, and fructose tastes very sweet to us (sweeter than either glucose or sucrose). This is nature’s way of telling us, and other animals that might eat the fruit, that it’s high in nutrients. From the plant’s point of view, it’s an incentive to eat the fruit and, ahem, spread the seeds around.

Humans have, of course messed around with this perfectly sensible survival mechanism by stuffing all kinds of easily-available and not particularly nutrient-rich foods with fructose, and herein lies the problem. Co-author of the paper that started all this, Lorenzo Cohen, Ph.D., professor of Palliative, Rehabilitation, and Integrative Medicine, said “we determined that it was specifically fructose, in table sugar and high-fructose corn syrup […] which was responsible for facilitating lung metastasis and 12-HETE production in breast tumors.” Notice that he mentions fructose in table sugar; this is because, once you eat sucrose, it breaks down into units of glucose and fructose.

The article goes on to suggest that sugar-sweetened beverages are a significant problem, so was the newspaper wrong to pick on Coke? It’s a popular drink after all, and a standard can of Coca-Cola contains approximately 35 grams of sugar (which might come from either sucrose or high fructose corn syrup mainly depending on where you buy it). The guidance for adults is no more than 30 grams of sugar per day, so a single can of regular Coca-Cola would take you over that limit, and it’s very easy to drink two or even three cans without giving it a second thought.

sugar

Soft drinks and fruit juice both contain a lot of sugar

However, the same goes for pretty much any non-diet soft drink.  Pepsi, for example, has a similar amount. Lemonade can be even more sugary, with some drinks hitting 40 grams per 330 ml can. Ginger beer might well be the worst; there are 53 grams per 330 ml in Old Jamaica Ginger beer for example. Fruit juice is no better, with many juices containing 35 g of sugar per 330 ml, although at least fruit juice might contain some other nutrients such as vitamin C.

So really, I’d say it’s a bit unfair to single out Coke in a headline like this.

What about the ketchup (note they didn’t pick a specific brand here, just generic ‘ketchup’)?

Well, ketchup IS high in sugar. It contains about 24 grams of sugar per 100 grams. But hang on, 100 grams of ketchup is quite a lot. A more realistic serving size of a tablespoon is only about 15 grams, which works out at about 3.5 grams of sugar. Still quite a lot, but probably a drop in the ocean compared to all the sugar in cake, bread, drinks, fruit juice, breakfast cereals and the tubs of Roses and Quality Street you scoffed over Christmas. Unless you make a habit of drinking ketchup by the bottle (apparently some people do) this is frankly a ridiculous foodstuff to pick on.

I imagine that someone did a quick search for ‘foods that contain fructose’ and picked Coke because, well, everyone knows that Coke’s bad, right? So that sounds credible. And ketchup because we all sort of suspect it’s probably not that healthy, but it hasn’t been the subject of a health scare recently so that makes it stand out. Great clickbait, bad science.

mouse

Mice are not people

Plus, let’s be absolutely clear, the study was in mice. Mice are not people. While a study that shows an effect in mice is an interesting start, and may well be good reason to conduct more studies, quite possibly in humans, it’s not proof that this mechanism exists in humans. Humans have, after all, evolved to eat a very different diet to mice. There might well be a link, but this doesn’t prove it, and even if a link does exist we certainly can’t say anything about the significance or size of it from this research.

I’m not a dietician, but I’m going to go out on a (fairly sturdy) limb here and say that cutting back on sugar will not do you any harm and is likely to be a jolly good thing. Let’s also be clear that sugar in fruit juice, agave, honey etc is still sugar and is no healthier than table sugar. Eating too much of the sweet stuff is almost definitely bad for your waistline and, as we all learned as children, bad for your teeth too – something which is often overlooked but really shouldn’t be, poor dental health having been linked to other serious health problems including diabetes and heart disease.

ketchup on bread

Maybe cut back on the fried ketchup sandwiches

But, and here’s my big problem with the newspaper’s headline, none of this means that Coke and ketchup directly cause breast cancer which is how, I fear, some people will interpret it. Cut out sugary fizzy drinks by all means, and perhaps ditch the ketchup sandwiches (especially fried ones), but please don’t worry that the occasional dollop of red sauce is going to kill you. I’m pretty certain it won’t.

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A small edit was made on 6th January to clarify that pure fructose isn’t used as an ingredient in Coke, but rather high fructose corn syrup.