Any sealing surface that relies on buna orings will have issues when used with CO2. The macro line fittings have those orings.
Ideally, you want a slight tip back on your horizontal CO2 bottle combined with an anti-siphon tube. That will keep liquid out of the valve and still allow you to tip the gun forward in case you have to fire down a hill. When you install the antisiphon tube, it has to be setup for your ASA so that the tube is oriented up when the bottle is screwed in.
Except for the Automag in front, its usually the man behind the equipment that counts.