A great number of human studies have been reported on the various uses of PEA in the treatment and prevention of many types of illness and disorder with no major side effects and with good tolerability. Initial tolerance and safety studies were performed in the early seventies of last century.

”Palmitoylethanolamide has an impressive safety and tolerability profile”

A broad PEA evaluation program was conducted in the 70s of last century by the Institute of Pharmacology of the Czechoslovak Academy of Sciences, and its results were documented in a comprehensive, English summary on file by Dr. Karel Masek, M.D., Dr. Sc., Head of the Institute (Masek, 1980, unpublished report).

Science of palmitoylethanolamide

In one early study, 5 hospitalized children were given 50 mg PEA/kg bw/day for 2 weeks, and no side effects were observed. In another, 15 adults were given 100 mg PEA/kg bw/day for 3 weeks, and 12 biochemical parameters were examined before and after exposure to PEA. No adverse effects were found.

Subsequently, two large clinical studies were used to provide documentation for the further analysis of safety and efficacy of PEA in respiratory disorders such as flu. Based on these extensive safety studies, in the 80s PEA became available in different countries under different brandnames, IMPULSIN and PALMIDROL. Impulsin were introduced as tablets and Palmidrol as a suspension. Palmidrol stays available till some years ago. Since early this century PEA became available as a nutraceutical. It is now mainly know as PeaPure, produced in the Netherlands by the company Russell Science.

In two trials (Masek et al., 1974), 1300 subjects were involved, about half receiving 30 mg/kg bw of PEA, and the other half a placebo, for a period of 12 consecutive days. Another study, using the same dose, involved more than 1800 healthy subjects and was divided into three separate subtrials (Kahlich et al., 1979). No adverse side effects were reported in these studies and PEA could clearly reduce the impact of respiratory disorders such as the flu.

From the literature published after the initial flu explorations we identified a great number of clinical studies and a number of case reports and case report collections. [1]

In most clinical trials, PEA was used for periods ranging from 14 to 120 days, and the effective daily doses ranged from 600 mg to 1200 mg. A few studies were published in Italian. Most clinical studies have been summarized and discussed by Keppel Hesselink (2012)in the Open Pain Journal.

For pain relief and for inhibiting inflammation, most patients choose:

  • PEA capsules produced in the Netherlands by Russell
  • PEA tablets produced in Italy by Epitech

Formulations tested: MicroPea

Nearly all formulations tested after the initial period up to the 90s were conducted with either tablets or capsules containing PEA were PEA formulations consisted of a certain amount of small PEA particles, sometimes referred to as micronized, ultramicronized or optimized PEA (Um-PEA, m-PEA or PEA-opt). These patent protected formulations have been developed in order for PEA to enter the bloodstream after intake and gives rise to significant raise in bloodlevels of PEA.

The administration form of MicroPEA was either oral tablets except some occasional use of sachets, or oral capsules, and the commonest form of evaluation was the visual analogue scale (VAS), where the patient makes a subjective assessment of her/his pain level on a 10 cm line where the left side represents no pain, and the right side represents the worst imaginable pain. Almost all available clinical trials reported significantly reduced pain intensity and an almost complete absence of side effects. Early field studies of PEA in healthy individuals were PEA was tested to evaluate its prophylactic effects to confirmed the safety and good tolerability of this fatty compound (Kahlich et al, 1979).

In 2016 an all encompassing review was published on the safety of MicroPea, by Dr Nestmann: Safety of micronized palmitoylethanolamide (microPEA): lack of toxicity and genotoxic potential.
Also all the animal studies supported the extreme safety of the compound, no problems up to the highest doses tested, 1000 mg/kg bw/day. The No Effect Level (NOEL) in 2 animal studies was the highest dose tested!


[1] Clinical randomized trials: Andersen et al., 2016; Assini et al., 2010; Canteri et al., 2010; Conigliaro et al., 2011; Costagliola et al., 2014; Crestani et al., 2013; Dominiguez et al., 2012; Gagliano et al., 2011; Guida et al., 2010; Pescosolido et al., 2011; Strobbe et al., 2013,

Open label or single blind studies: Bacci et al., 2011; Cocito et al., 2014; Del Giorno et al., 2015; Desio et al., 2010, 2011; Gatti et al., 2012; Indraccolo & Barbieri, 2010; Kahlich et al., 1979; Masek, 1980; Masek et al., 1974; Schifilliti et al., 2014; Truini et al., 2011,

Comparative studies: Marini et al., 2012; Cobellis et al., 2011; Giugliano et al., 2013; Marian et al., 2013; Palomba et al.; 2010 Tartaglia et al., 2015.

Case reports and case collections: Calabro et al., 2010; Keppel Hesselink, Hekker, 2012; Keppel Hesselink, 2013; Keppel Hesselink and Kopsky, 2013; Kopsky, Keppel Hesselink 2012; Keppel Hesselink, 2016).