Palmitoylethanolamine
PEA is a fatty acid amide found to have anti-inflammatory1 and neuroprotective properties with attraction to cannabinoid-like receptors in the body2,3.
The combination of PEA with the natural flavone luteolin at a 10:1 ratio and total dose of 10 microM in isolated brain cells promoted development of oligodendrocytes. Oligodendrocytes are the myelin-producing cells of the CNS, which otherwise have limited ability to repair the damage to themselves or to other nerve cells, as seen in demyelinating diseases like MS4,5.
In a live animal model of MS, the PEA+luteolin combination at a dose of 5 mg/kg resulted in improvements in clinical score (based on weakness, poor balance, and paralysis) as well as decreases in pro-inflammatory molecules and autoimmune cells components in the brain and brainstem6.
During pregnancy, PEA is generated naturally in the body at various levels (Fonseca et al., 2010). Results from a prenatal developmental toxicity study in rats indicated that PEA is well tolerated by and is safe in pregnant rats even at a high dose of 1,000 mg/kg/day, equivalent to a human dose of greater than 9.7 g/day7. Breastmilk content of PEA and related compounds has been linked to healthy regulation of appetite and food intake in children8.
PEA appears to be safe in humans at doses up to 2400 mg/day. It is found naturally in foods such as egg yolks, milk, soy, and peanuts, and can be produced by the human body1.
References
1.Hesselink JMK. Chapter 4. Palmitoylethanolamid and Other Lipid Autacoids Against Neuroinflammation, Pain, and Spasms in Multiple Sclerosis. Nutrition and Lifestyle in Neurological Autoimmune Diseases: Multiple Sclerosis. Academic Press (Elsevier); 2017:29-37.
2.Bottemanne P, Guillemot-Legris O, Paquot A, et al. N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibition, but Not Fatty Acid Amide Hydrolase Inhibition, Prevents the Development of Experimental Autoimmune Encephalomyelitis in Mice. Neurotherapeutics. Jul 2021;18(3):1815-1833. doi:10.1007/s13311-021-01074-x
3.Lambert DM, Vandevoorde S, Jonsson KO, Fowler CJ. The palmitoylethanolamide family: a new class of anti-inflammatory agents? Curr Med Chem. Mar 2002;9(6):663-74. doi:10.2174/0929867023370707
4.Barbierato M, Facci L, Marinelli C, et al. Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells. Sci Rep. Nov 18 2015;5:16676. doi:10.1038/srep16676
5.Skaper SD, Barbierato M, Facci L, et al. Co-Ultramicronized Palmitoylethanolamide/Luteolin Facilitates the Development of Differentiating and Undifferentiated Rat Oligodendrocyte Progenitor Cells. Mol Neurobiol. Jan 2018;55(1):103-114. doi:10.1007/s12035-017-0722-0
6.Contarini G, Franceschini D, Facci L, Barbierato M, Giusti P, Zusso M. A co-ultramicronized palmitoylethanolamide/luteolin composite mitigates clinical score and disease-relevant molecular markers in a mouse model of experimental autoimmune encephalomyelitis. J Neuroinflammation. Jun 20 2019;16(1):126. doi:10.1186/s12974-019-1514-4
7.Deshmukh NS, Gumaste S, Subah S, Bogoda NO. Palmitoylethanolamide: Prenatal Developmental Toxicity Study in Rats. Int J Toxicol. Mar-Apr 2021;40(2):161-170. doi:10.1177/1091581820986073
8.Bruun S, Gouveia-Figueira S, Domellof M, et al. Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother’s Milk Are Strongly Associated with Infant Weight at Four Months of Age-Data from the Odense Child Cohort. Nutrients. Nov 13 2018;10(11)doi:10.3390/nu10111747