Afaik this setting only makes civ5 store this mod GUID in the savegame so that:
* If the mod is disabled and you load a savegame created with this mod, civ5 will refuse and will tell you that one mod is missing (let's call that a "unmodding").
* If the mod is enabled and you load a savegame created without this mod, civ5 will silently disable all mods and load this savegame (let's call that a "late modding").
* But this flag could also have another consequence: to allow mods to store data in the savegames. It's just an hypothesis.
Now you have to understand that mods who turn this setting on do so for good reasons.
* CivUp, for example, is not just an UI mod, it changes the gameplay also, it may change things like unit costs, remove some policies, add new ones, etc. So a savegame created with this mod may reference things that only exist in CivUp while a savegame created without it won't store some data civup may need (pretty bad example: imagine if a policy is only available if you were the first one to build a wonder: civ5 does not store that info, so CivUp would have to store it by itself the first time a wonder is built).
* InfoAddict has nice little timelines, which means it had, on every turn, to store those data. While "unmodding" would make sense, the "late modding" would cause InfoAddict to lack the data for the first years.
* However most UI mods do not affect savegames. IGE for example. Those who do typically change the gameplay.
Now, would it be possible to late-mod a savegame? Well, hardly, you would have to edit the file by hand and depending on the mod you could then find yourself with many bugs to deal with.