I think you're making some unsupportable assumptions. Read Madison's letter again. In all of the historical record of the debates and discussion during the process of drafting and ratifying the Constitution, preventing the States from using taxes, levies or other contrivances to give themselves a trade advantage over other states is the only purpose for granting the power to regulate commerce among the several states that is discussed or expressed. For the first 150 years, this is how it was used. Our current "substantial effects" doctrine is the product of FDR and the New Deal courts - explicitly derived from a "living document" interpretation of the Constitution.
I am not disagreeing that that is the only reason he stated in his letter. I am simply saying that there "may have been", and still are, more reasons for such regulation. If the feds regulate interstate commerce, than conflicts in trade between states is obviously minimized. Also, since any legislation on that level would have to be passed by representatives of the States, than it makes it not only efficient but a valid form of regulation.