> it seems to me that some of the subtle and/or knock-on effects may not be fully understood

There have probably had hundreds of studies done by people who were actively trying to prove something and wrote that they fully believe that there are bad side effects yet not one states they proved something.

I've found that aspartame gives me really bad insomnia. Almost every time this happens I'll go through what I ate that day and it's always something containing aspartame that was not in my normal diet. This is how I learned that those flavor packets that are mixed into water bottles and some zero-calorie flavorings used at coffee shops contain aspartame.