Well... duh!

This was published yesterday. Just in case you have a "too long, didn't read" moment, here's the story in a nutshell.

Rats were fed normal diet, but some were given sugar (sucrose) in the drinking water, some given high fructose corn syrup (HFCS) in their water. The HFCS group became obese, the sucrose group remained pretty much the same.

HFCS is used extensively in a lot of foods, mainly processed stuff, because it is very cheap to manufacture. A bit like hydrogenated vegetable fats, it creeps into the daily diet of a lot of people, from those who need a microwave meal because it's quick and easy, to those who stuff their faces with crap from McDonalds.

What most people fail to realise is that although the calorific content of the two sugar types is virtually identical, HFCS bypasses the satiety response completely. Ordinarily, sucrose (one molecule of glucose joined up to one of fructose) triggers a negative feedback response: the body senses the high-energy source and eventually does a Mr Creosote ("**** off, I'm full.") This is caused by the metabolism of glucose to glucose-1-phosphate and then to glucose-6 phosphate as part of the glycolysis pathway down to pyruvate.

Fructose misses out this step and joins the pathway further down - the same endpoint, but a different entry point. However, all the metabolic sensors for glycolysis are based at the glucose-6-phosphate step. What this means is that food containing glucose makes the brain and body realise that it's had enough to eat but fructose doesn't.

People who eat this processed junk basically don't realise that they've already eaten enough calories, and as such about an hour after stuffing their faces with a Big Mac they fancy a nice tasty snack. Probably Doritos or some other rubbish. Why? Because they don't actually feel full.

So: one of the many problems with fast food. The trouble is that it's so cheap: so many calories for so little money. Unfortunately buying food that doesn't contain HFCS and other such junk costs more, hence the problems with obesity in the Western world, and until the food lobbyists are rapped on the knuckles this problem is going to continue, much to the detriment of world health.

Which brings me on to a final point: congrats to Obama for getting the USA healthcare bill pushed through, but the wankers that voted against it do have a point: the USA cannot afford the increased cost to the nation simply because the big businesses are still pushing bad diets down the necks of the taxpayers. The fatter they get, the bigger the burden on the tax bill. Obama was right to get the bill pushed through, but needs to tackle the tobacco and food lobbies before any real benefit will ever be seen.

I’ll have the gralefrit please. Followed by the balm carousel.

Obviously the death of Michael Jackson is very sad. For three young children to lose a father is a tragedy, and one must feel for them and the remaining Jackson siblings. It is sad to note that they appear to want to lay blame somewhere (which may or may not be justified, and may or may not lie with his doctor) when I can’t help but feel if Jackson had received help from his family 25 years ago then his might have been avoided.

What I found interesting was a story I found in the Metro this morning, suggesting his grapefruit intake may be responsible in a way. This is not the first instance of such a thing, either. The mechanism of action is interesting, and one that has been of great interest to the pharmaceutical industry for some time: grapefruit juice, or at least one of its components, is a potent cytochrome P450 inhibitor. The P450 enzymes are heavily involved with one of the major pathways of drug metabolism, and make up a substantial part of the screening cascade.

The triazole antifungals were the drug family that first brought the P450 enzymes to people’s attention (if memory serves). Several studies were carried out looking at fluconazole and voriconazole and their breakdown pathway (P450, needless to say) but interestingly voriconazole (Vfend) also activates the P450 pathway, that is to say it contributes to its own clearance. Studies with Vfend and grapefruit juice show that the half life of Vfend is greatly improved.

Antifungals are not the only drug class that are affected. Various HIV drugs, the antiarrhythmic amiodarone, and as is now apparent to the general media, painkillers.

Only a few drugs have this potential interaction highlighted, but surely all prescription only medicines should point out the risks not just of drug-drug interactions but drug-diet as well. Not all drugs would display this, nor would all patients. But if clinical science wants to tailor therapies for the individual then at least the potential risk should be pointed out to everyone given a prescription-only-medicine. It may take the tragic death of one of the most popular entertainers of the late 20th century to bring this about.

And the Gralefrit reference? Fawlty Towers, I'm afraid.