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With this in mind, is the real cause "calories in, calories out" or "optimized flavor and marketing strategies"?

The reason a person gains weight is CICO.

The reason a population gains weight is way more complicated and probably best short-handed as “social”. Moving to America typically makes people gain weight. Leaving it leads to weight loss. If you’re trying to fix an overweight population, you need to look at lots and lots of things and, demonstrably (as in: the science is pretty clear), telling people to simply eat less and even very expensive high-touch interventions aimed at diet correction don’t work. Wrong tree to bark up, your solution lies elsewhere—or, probably, several elsewheres.

(But drugs might work!)

Potato, potato. CICO is just physics, but "optimized flavor and marketing strategies" has had impact on the "CI" side of the equation.
It seems very different and critically important. Would we have a current obesity epidemic without "optimized flavor and marketing strategies"? Because if we would not, then that is the true cause and of fundamental public health importance.

If we would have an obesity epidemic even without "optimized flavor and marketing strategies", then it is totally irrelevant.

Yes and no. I think there are two levers on the CI side of the equation and only one of them is hyper-palatability (optimized flavor); the other is simply cost. Food costs have fallen sharply, and that contributes to over-feeding. Hyper-palatability also contributes. It's not irrelevant, but not the only factor.

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