Log term flying in unpressurized aircraft affects many folks differently.
I would suggest, at an absoute minimum, that an oxy pulse meter be purchased and used when flying at these higher altitudes.
This device will show the blood oxy saturation level for the respective individual...and different folks respond differently, accordingly.
Usually, and this is a general statement, a blood/oxy saturation level of 92% is required...I use 94%...and I fly my unpressurized private aircraft all the time above 16,000 feet, using an Aerox oxy/saver cannula.
PS:
For best results, especially night flying, use oxygen above 8,000 feet.