Today, most of the RCTs about things like omega-3 fatty acids show no effect. Why?
My guess at the root cause is a bit of scientific reductionism mixed with overgeneralization. Omega-3 fatty acids are a great example, and often it looks like this:
1. Shockingly healthy population X has a diet rich in foods A, B, and C. What do A, B, and C have in common? Perhaps it's some micronutrient in abundance (like omega-3 in high-fat fish-eating cultures). Logically, the cause might be that micronutrient!
2. Early observational studies that happen to pass publication thresholds show promising connections. People who eat salmon -- high in Omega-3 -- are healthier! They have lower triglycerides, or cholesterol, or whatever.
3. RCTs show no positive effect from supplementing omega-3 fatty acids.
What happens between 2 and 3? Observational studies can't really isolate the effect of a single micronutrient, because there are a ton of interactions happening. Probably one of those other interactions is also necessary, but we don't know what it is -- much like how "plant fats" vs "animal fats" misses a ton of nuance.
I'm not really sure what we can do about this, though, except stop getting excited in phase 2?