If you keep the same speed then yes it'll hurt you by a percent or two.
Usually all you have to do is slow down a little and you'll get much the same burn for the leg. I've flown a 747 for about six hours on a ten hour flight, stuck a good 6,000' - 8,000' low and only lost a tonne or two. Also lost a bit of time but in a ten hour flight not enough to worry about.
FWIW the rule of thumb with a 747 Classic is to keep the TAS to a maximum of 500kts or an IAS of about 320, whichever is lower, that seems to work fairly well down low.