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I've been getting into overnight oats recently, and thinking about getting more protein in them. Some recipes (for example, here) suggest just adding protein powder.

But, at least one manufacturer says this:

Q: Will my protein drink lose potency if I pre-mix ahead of time?

A: Not necessary – but, it will spoil if it’s not stored properly or used too long after it’s prepared. For best results, mix-up no more than a day’s worth of protein at a time, store it in the refrigerator (in a covered container), and use within 2 days of preparation.

I usually make a few days to a week's worth of oats at a time, and not knowing what exactly causes protein powder to "spoil," I'm wondering if protein powder will indeed spoil in overnight oats specifically over up to five days.

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The spoilage is not about losing protein content but the same kind of spoilage that any food product will undergo. In this case when you mix the protein powder with water you are doing something similar to making milk from milk powder, and as the guidance from the manufacturer says you should use it up promptly.

There is nothing about mixing it with oats (which just soaks up some of the water in the mixture) that will make it last longer or shorter, so I would apply the same two-day limit to your overnight oats if you make them with protein powder. If you are committed to making your oats further in advance, make them with water or milk or whatever and then just add the protein powder before consumption; you might have to play around with quantity of liquid a little to get the consistency you want since both the oats and the powder 'use up' liquid.

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