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Over a long time, say 5 years or more, depending on storage temperature.
What happens is, since the alcohol is continuously evaporating, albeit a molecule at a time though a stopper cork. Over time the whisky will "loose its balance", and quite often tastes a bit flat or stale, for lack of a better term.
Also, the lower your liquid level gets in the bottle the faster this seems to occur. To prevent this, many malt enthusiasts displace the volume of liquid lost with boiled/sterile and properly dried marbles. Thus, leaving less surface area for the alcohol to evaporate, as if the bottle was never opened and not poured. Of course, one reaches a point of more marbles than liquid and one should consider the demise of that magical malt, looking forward to another.
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