That's might be a sign you don't pay enough attention cryptographic research; compiler optimization side channels are not news.
Of course, the notion that the compiler is a threat here is getting a bit ahead of ourselves, because you don't even know what side channels are in the runtime.
My primary concern is the LLVM bytecode to JS transformation.
Even on the LLVM side certain optimizations may be dangerous in crypto code. I wouldn't play with optimization settings unless I was sure I knew what I was doing. And I'd still think twice.
I completely agree that further analysis is needed on js-nacl, but I hadn't considered that compiler optimizations might lead to vulnerabilities.