Fungi and statins

Image: Aspergillus terreus

Having passed three score years and ten (playing in extra time as my Grandfather said) I thought it was time to get a bit of an MOT from the doctor. Blood samples revealed that my cholesterol levels were out of kilter and, according to the NHS algorithm, I had a 44.6% chance of a heart attack or stroke in the next 10 years. Dietary and weight considerations aside, the doctor advised a low dose of statins. As he didn’t laugh when I said at least it’s less than 50%, I decided to give them a go.

I vaguely remembered being told that statins were a fungal secondary metabolite so, after taking the first one, decided to find out more.

Statins were discovered by a Japanese biochemist, Akira Endo, who was inspired by Alexander Fleming’s discovery of penicillin to look for other useful fungal compounds. His research had begun in 1966 looking for fungal enzymes for use in the fruit juice industry but then moved on to fungal secondary metabolites.

Akira Endo and Masao Kuroda at Sankyo grew many fungi in culture and extracted fungal secondary metabolites. Their interest was in HMG CoA reductase inhibitors which would inhibit the production of LDL cholesterol in the liver.  Endo had speculated that fungi might produce these compounds to fight off fungal competitors that need cholesterol compounds to survive.

Their first success in 1973 was with a blue green mould from oranges, Penicillium citrinum that produced a compound named mevastatin . Later a similar compound, lovastatin, was produced that was approved for use in the US in 1987. I think this is a good indication of how long it takes from first discovery to a tested drug that is approved for use.

Since then, other statins have been produced either directly from fungi such as Aspergillus terreus or synthetically and have massively reduced cardiovascular disease. The most commonly prescribed statin (which I take!) is Atorvastatin and this is produced synthetically from mevalonate, a secondary fungal metabolite.

Of course there’s a lot more to this story involving other players and companies (which can all be found on the internet) and still things to discover e.g. if it reduces LDL why doesn’t it also reduce HDL (the so called good cholesterol).

There doesn’t seem to be much of a downside to taking statins, there are a few relatively rare side effects and one has to avoid grapefruit juice as this can inhibit the drug. Once you start you have to keep taking it.  

Having said that, Akira Endo died in June this year at the age of 90, which is a pretty good advert in itself, although I don’t know for sure if he ever took the drug that he discovered.