Does 4x8GB RAM run slower than 2x16GB?

Yes, there’s a performance hit. Two sticks beat four sticks almost every time for the same total capacity because four sticks put more electrical load on the memory controller, forcing the CPU to downclock speeds or loosen timings. You often can’t hit the same XMP/DOCP speeds with four sticks. Unless you already own the four sticks, just buy 2x16GB — it’s simpler, faster, and leaves room to upgrade later.