Yes, that's a huge message database. I suppose it's running somewhat slow too.
Re: no difference whether I keep 50 or 250 Mails on the phone
I suspect that maybe you've set fairly high "messages to sync" settings -- to avoid the app downloading and then trimming what it downloaded, then doing it over and over again, the app will keep on the device "max(messages to sync, messages to keep)" number of messages, per folder.
Please check, and if it's true, please reduce the "messages to sync" values, and then Menu -> Compact the database again -- you should see the size of Messages.sqldb get smaller immediately after that.