While the use of a pair-fed control group is desirable, it should also be noted that they are not a perfect control group. They are required because animals receiving ethanol generally consume less food (and therefore less calories) than control animals (79, 90, 124, 126). However, imposing caloric restriction on naïve animals can also be perceived as introducing a stressor which can be a confounding factor in many studies (69, 124, 137). While ethanol-exposed animals eat less food voluntarily, pair-fed animals are forced to eat less and spend many hours of the day hungry. Another potential problem with this model is that ethanol has inflammatory effects in the stomach [see Ref. (138) for review]. This means that any food that is ingested may not be metabolized as efficiently, and nutrients from the food that is consumed may not be absorbed (139, 140). Unfortunately, this side-effect of ethanol consumption cannot be replicated in pair-fed animals, and therefore it is not possible to be entirely certain that the results observed are not due to a lack of absorption of nutrients. However, in
