Years ago I once ran a 29g tank with pool filter sand 2-4" deep. I ran DIY co2 from some yeast, and stuff was great for about a year. I did no root tabs, no fert dosing, and the plants grew okay, but I can't say the sand bed was full of roots. If I remember right, java fern and anubias did okay, but that stuff was attached to driftwood. The plants in the sand did not do well. No real root growth in the sand to speak of. Definitely a low light tank (some kind of flourescent).
Anyway, I began to notice bubbles from the sand. Read up on hydrogen sulfide in sand tanks. One of my otherwise healthy Corydoras died in a rather dramatic fashion (for a few minutes darting about the tank as if terrified, then belly up, stone cold dead). I did more reading over the next few days. I kept seeing bubbles. Something said to prevent it, you stick a pencil or stick in the sand to mix an aerate the sand in lower levels. I did that, and my 8 cories were all dead in the same fashion within 20 minutes.
Don't mix up a deep sand substrate!
I believe that people make deep sand work, but with preconditions. E.g.
http://www.wetwebmedia.com/ca/volume_7/volume_7_1/dsb.html says use plants, MTS, blackworms and even planaria to keep the first inch or so mixed up. And, whatever you do, don't disturb the lower layers -- go as far as cutting off plants at the base instead of pulling them up, etc.