I would feel less comfortable carrying something to defend myself. I can't picture myself accessing anything in time to react to someone/thing wanting to do me harm.
I try to run in well populated and well lit areas. I tell DH where I'm going, and he knows approximately when I'll be home. I bring my dog if possible, but that's mostly because he needs the exercise, too. I can't allow myself to live in fear, so I place myself in situations where I feel safe when I am running alone. To me, the knife or bear spray wouldn't make me feel more safe or more confident.
I also live in a family neighbourhood, in a major City, where I know several neighbours and run by their houses on my regular route. I'm not running trails, or country roads, or secluded areas.
When your legs get tired, run with your heart.
Overcome the notion that you must be regular. It robs you of your chance to be extraordinary.