The entourage effect of kavalactones.

For this kava fact, we will examine the activity of single kavalactones versus the activity of full-spectrum extracts. We will examine the brain concentrations of these kavalactones and how their absorption rates differ when administered alone and together in a full spectrum extract.

Keledjian et al. in 1988 assessed the ability of kavalactones to be taken up into the mouse brain. This study is routinely cited in kava research, and even though it is old, it is still quite important. The information here comes directly from this study.

Individual lactone concentrations in brain matter:

The researchers injected mice with 100 mg/kg (2.5mg of each KL when calculated out for a 25g mouse) of each kavalactone and studied the physical brain material to ascertain the concentration level of kavalactones. Figure 1 shows the results in a graphical format.

They found: (ng = nanogram mg = milligram)

Kavain was observed at a concentration of 29.3 ng/mg in brain tissues.

DHK was observed at 64.7 ng/mg in brain tissues

DMY was observed at 10.4 ng/mg in brain tissues

Yangonin was observed at a concentration of 1.2 ng/mg in brain tissue.

Full-spectrum lactone concentration in brain matter:

The researchers also tested full-spectrum extracts on mice, and a breakdown is listed of each kavalactone in the 120 mg/kg full-spectrum kava extract. The results are shown in Figure 2.

This study suggests that the synergism of pharmacological activity is due to potentiation of penetration into the brain when the kavalactones are administered together instead of separately. Yangonin and DMY were relatively ineffective when taken orally, but when given along with full-spectrum extracts, a marked increase in action was observed. This may also suggest that the absorption of lactones in the intestines increases when all the kavalactones are present together.

I have taken the figures from this study and added them to a spreadsheet to more easily understand the effect of consuming kavalactones together can have. We see that DHK remained approximately the same; however, all the other kavalactones increased in absorption by a rather large amount. Yangonin saw an increase of approximately 20 times that of its application alone. More studies are necessary, but evidence is beginning to support the idea that an entourage effect is strongly at play when considering the physiological actions of kava.

Keledjian, J., P. H. Duffield, D. D. Jamieson, R. O. Lidgard, and A. M. Duffield. 1988. “Uptake into Mouse Brain of Four Compounds Present in the Psychoactive Beverage Kava.” Journal of Pharmaceutical Sciences 77 (12): 1003–6. https://sci-hub.st/10.1002/jps.2600771203