Use it fasted.
It's half life is about 30 mins so you wanna take it 15 minutes before you're activity.
Any insulin response will prevent its activity so it's best used on empty.
This is what you'll read online (over and over), but it's not really the true picture.
The half-life may be much longer than that (3) and typically bimodal (but not always) - but it's highly variably and possibly dependent upon the genes for a couple of the p450 enzymes. No to mention, the main metabolite 11-0H yohimbine acts the same way (alpha-2 antagonist), and is weaker, but doesn't bind as tightly to plasma proteins leaving more of it to be active... so the effects of this metabolite also come into play.
1. Berlan M, Le Verge R, Galitzky J, Le Corre P. Alpha 2-adrenoceptor antagonist potencies of two hydroxylated metabolites of yohimbine.
Br J Pharmacol. 1993;108(4):927-932.
2. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism.
Clin Pharmacol Ther. 2004;76(2):139-153.
3. Sturgill MG, Grasing KW, Rosen RC, et al. Yohimbine elimination in normal volunteers is characterized by both one- and two-compartment behavior.
J Cardiovasc Pharmacol. 1997;29(6):697-703.
What all that means is that there's a pretty damn variable response to yohimbine - some can handle it and some can't, form what I've seen over the years.
Also, the issue with food is that blocking the alpha-2's impairs the reduction of insulin brought on my sympathetic activation to the pancreas, so you can end up with higher insulin levels when using yohimbine and this could be more of an issue if you've eaten.
https://link.springer.com/article/10.1007/BF00498572 So the issue is raising insulin when using yohimbine (and inhibiting lipolysis), but there's no direct binding the the yohimbine by insulin or something like that. It's just that the effects of insulin are antagonistic to those of yohimbine when it comes to adipose lipolysis.
-S