Absorption studies
Less is known here than most product pages suggest. This summary follows Rankin and Fowler 2020.
What is known
- Unmicronised, micronised and ultra-micronised forms are all absorbed after being taken by mouth.
- After a single 300 mg dose in people, the plasma level roughly doubled at two hours. It returned to normal by four to six hours.
- In rats given a labelled dose by mouth, about 1% was recovered in the brain, mainly in the hypothalamus.
- The molecule is broken down quickly. In rat liver tissue its half-life was about 25 minutes.
What is not known
- Bioavailability. The review found no published figure, and no data on how it varies between people.
- Rate of absorption. Little data, and little on whether formulation improves it.
- Elimination. No published data on the route or rate.
- Interactions. No data beyond trials where it was added to other treatment.
- Micronised against unmicronised. At the time of the review, no head-to-head comparison in people had been published.
One head-to-head absorption study
Briskey 2020 gave 28 healthy volunteers a single 300 mg dose. The dispersion form (Levagen+) gave 1.75 times the plasma exposure of plain powder over 4 hours. The study was funded by the makers, and it did not include a micronised form.
Particle size in rats
Petrosino 2018 gave rats labelled palmitoylethanolamide by mouth. The ultramicronised form gave a peak plasma level 5 times that of plain powder. Several of its authors work for the maker of the ultramicronised form, and the comparison has not been repeated in people.
Why particle size comes up
Palmitoylethanolamide dissolves poorly in water. Making the particles smaller gives more surface area, which is the reason for micronised forms. Dispersion forms such as Levagen+ address the same problem in a different way.
The review’s closing point is that the gaps in the pharmacokinetic data need to be filled.