How bad could it be if piperine, in pepper is also an MAO-B inhibitor?
Piperine is a relatively weak inhibitor of the MAOs. In order to get 50% inhibition of MAO A or B would require a plasma concentration of piperine of 49.3 and 91.3 micromolar, respectively, in the rat. Achieving these concentrations in (human) plasma would require an IV injection of 71 or 130 mg of piperine, respectively, assuming a 5 L plasma volume. Determining the amount that would be needed orally is harder, but needless to say it is more, as the drug is not fully absorbed and it is constantly metabolized in the liver. Various forms of pepper could contain as little as 1% or as much as 9% piperine, according to Wikipedia. Depending on the absorption of piperine, the total fluid volume of the person, possible active transport, and metabolism of the piperine, in addition to likely differences in inhibitory potency of piperine for human vs. rat MAOs, it might be possible to get enough piperine for significant MAO inhibition with a non-crazy amount of a high-piperine pepper. For example, if piperine has really great bioavailability such that the necessary oral dose is only a factor of two greater than the IV dose (unlikely), and you had a 9% piperine pepper, you would only need about a gram and a half of pepper. Probably it's at least several times higher than this, though. The piperine is tied up in a resinous matrix in the pepper, and would leach out slowly. I suspect that most pepper that we consume is toward the lower end of the piperine spectrum. One paper I saw found green peppercorns to be highest in piperine, and red lowest. Realistically, I doubt this is a significant effect, (and the analysis is rife with assumptions) but if you were really nuts about pepper consumption...
J Ethnopharmacol. 2004 Apr;91(2-3):351-5.
Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones.
Kong LD, Cheng CH, Tan RX.
A total of seventeen phytochemicals including seven alkaloids (piperine, strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine), four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial. Among these compounds, piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine on MAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the K(i) and K(I) were determined to be 35.8 and 25.7microM, respectively. For paeonol, the K(i) was estimated to be 51.1 microM. The inhibition of piperine and paeonol on MAO B was of competitive type with K(i) values of 79.9 and 38.2 microM, respectively. The inhibition of emodin on MAO B was of mixed type with the K(i) and K(I) data of 15.1 and 22.9 microM, respectively. The present investigation showed that the phytochemicals piperine, paeonol and emodin are potent MAO inhibitors whereas other compounds were inactive against any type of MAO at 100 microM in the present assay.
PMID: 15120460