Variations in diet (to an extent) and lifestyle changes (of certain kinds) were common in the ancestral environment, which means that they have been reliably and exhaustively tested on the human race over the course of our entire history as a species.

That is not true with respect to a large part of contemporary Western diet. Things like refined sugar, hydrogenated oils, a wide variety of food preservatives, flavourings and colorings are new and appeared an instant ago on the evolutionary time scale.

To give a basic example, take a look at the ingredients of Coke: high-fructose corn syrup, phosphoric acid, caramel color, caffeine -- I don't think you can make an argument that humans evolved to drink this.

That's not true with respect to lifestyle, too. Sitting pretty motionless on a chair for 10+ hours per day is not something evolution prepared our bodies for.

The issues with the remaining substances is that we don't have enough knowledge about (some of) them to justify what could be existential risk.

My point is precisely that people in the Western world routinely consume large amounts of these "remaining substances" without a second thought. Why eating hydrogenated soybean oil, for example, is not risky?

By the way, do you consider over-the-counter supplements drugs? do your arguments apply to them?