First up there is just the supplement being toxic. For example vitamin C is water soluble so you can take a fair amount of it and just piss it out, but vitamin A is fat soluble so if you take too much it builds up (e.g. don’t eat polar bear liver).
Further to this is the sketchier supplements. Say for example male sexual performance pills that aren’t complete bunk are going to have some sort of active ingredient that has an effect on blood pressure that has not been well studied.
On to contaminants you could have something as simple as unregulated pesticides on some plant matter mix you are ingesting.
Finally, the big one and probably the main answer to your question, is that a lot of concentration, extraction, refinement, etc. involves industrial chemical processes. Something like you take a giant pot of plant matter and redux it with hydrochloric acid. Then wash with formaldehyde and filter eventually precipitating out crystals of what you want which you extra with acetone that evaporates off leaving you with the final product and hopefully not any adulterants. Maybe mix with a preservative and/or desiccant of sorts to stabilize it. 100% Natural haha.
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