It was definitely for sure when A64 was king - the memory controller on the CPU could only cope with running at reduced speed and often only at 2T command rate, whereas with 2 sticks you could easily run at full pelt with 1T. This was because 4 sticks put more of a "strain" on the mem controller.
While technology has moved on (and the mem controller is on the motherboard with Intel), it's still fair to say that running 4 will be more intensive for the memory controller. In addition, twice the amps is required for 4 sticks over 2, thus putting more load requirement on the motherboard's circuitry dedicated to the memory sticks.
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