I'm leaning towards your theories MolaKule, I was also thinking that winter fuel caused the decrease with GTX, but the increase was instant, not gradual. I never did any straight highway with GTX, but I would average together my 420 mile round trips with the High Mileage and they were between 26-27 mpg highway. Only used High Mileage during warmer months, March through November. Highway trips only took place with High Mileage oil in August, September, and October, which for Georgia was pretty warm, so I doubt the winter gas was in full use.
I installed Amsoil 5w30 and it averaged 25.5 mpg highway at the same speeds, but this was during December and January, so winter gas blend could explain that, plus the temperatures were finally getting into the freezing and below freezing area.
Hadrien, I've heard a few people say that they've gotten the same results from just using High Mileage. And to answer your question, the oil should be safe. How long do you go between changes, 3 months, 6 months, 1 year? I'd say that if you went a year then it may not be safe, but 3-6 months should not be enough time to degrade the oil.