In the 70s of last century, a number of studies all supported the anti-flu effects of palmitopylethanolamide (PEA).

This natural compound, available as supplement has effects against flu as good as vaccination! And no side effects!

1972: first proof of anti-flu effects of palmitoylethanolamide

The first trial (Masek 1972a) was a treatment trial; 468 employees of the Skoda car factory were randomized in this trial; of these 444 were completers, available for analysis. The employees had to register the following symptoms: temperature of 37.5°C or higher, headache, sore throat, myalgia, nasal stuffiness or discharge, productive or a dry cough, malaise, and fatigue and had to make a clear impression of being sick. Dosing was 600 mg PEA three times daily during 12 days (total daily dose 1800 mg PEA).

The second trial was a prophylactic trial; 918 volunteers between 18 and 20 years of age from an army unit were included, and 899 completed the trial period. In this trial, medical personnel registered the complaints during a period of 8 weeks. The treatment schedule was 600 mg PEA three times daily for the first 3 weeks, after which a continuation phase started based on a single dose of 600 mg once daily for 6 weeks.

The results from the first trial showed that patients receiving PEA had a lower number of episodes of fever, headache, and sore throat, compared with placebo patients (18 versus 33). PEA had less effect on symptoms such as nasal stuffiness, discharge, and cough. The episodes of fever and pain were significantly reduced by 45.5% in the PEA group compared with the placebo group.

The beneficial effect of PEA was apparent from the second week of the trial. The total number of sick days was also significantly reduced in the PEA group. In the prophylactic trial, Masek 1972b, the incidence of disease in the PEA group was 40% lower at week 6, and 32% lower at week 8 compared to placebo.

In order to verify the conclusions, 3 more trials in soldiers were conducted. Soldiers were selected as they were housed close together. In the period of 1973–1975, these new trials were initiated (Kahlich 1973, 1974, and 1975) and the results were reported in 1979 by Kahlich et al.

Due to the positive effects, it was felt to be unethical to randomize 1:1 and in the last two trials a different randomization schedule was selected, in order to lose the majority of volunteers with PEA (2:1). The authors compared the incidence of clinical endpoints and the titers of influenza viruses between both the PEA and placebo groups. In all three trials, the soldiers in the PEA group had significantly fewer symptoms and were less often diagnosed as flu patients.

The evaluation of results according to morbidity, regardless of etiology, showed a significant reduction in acute respiratory diseases (ARD) after administration of PEA. In the 1973 trial (901 volunteers), 22.7% of ARD cases were found in the PEA group compared to 34.4% in the placebo group. The relevant values in the 1974 trial (610 volunteers) were 19.7% and 40.7% and in the 1975 trial (353 volunteers) 10.6% and 28.8% [14].

In all studies, Kahlich et al. studied serology in order to document the influenza strains. The codes of these strains are described below; however, the nomenclature is outdated. A fourfold increase in the antibody titer was taken as evidence for infection.

Further confirmative studies

In the 1973 study, serum was obtained from 358 persons. 6.9% of the subjects experienced influenza A 2 E in the PEA group and 18.7% of the subjects in the placebo group (). The manifestation rate (MR), expressing the proportion of sick persons out of all sensitive subjects with serologically proved infection, was 15.4% in the PEA group and 44.9% in the placebo group.

In the study of 1974, sera of 108 subjects were analyzed. In the PEA group, 3.8% of the subjects suffered from the influenza B Hong-Kong and 21.4% of the subjects in the placebo group. The MR was 14.3% in the PEA group and 57.1% in the placebo group.

In the study of 1975, with serum gathered from 212 subjects, only 4.3% of the subjects in the PEA group had influenza A Port Chalmers and 7% of the subjects in the placebo group (nonsignificant difference). The incidence rate of influenza A 2 England was 15.4% in the PEA group and 44.9% in the placebo group.

All these clinical trials pointed in the same direction that PEA has clear treatment effects in respiratory infections, can be used as influenza-prophylaxis, and is safe for its use. Side effects were not reported, and Kahlich et al. explicitly stated that

“No side effects were registered after several years of clinical testing of Impulsin in military and civilian communities.”

Kahlich et al. also pointed out that the effects of PEA had a clear advantage over vaccines and antiviral compounds such as amantadine, due to the optimal balance of efficacy and side effects of PEA. They also stated that the ease of application of PEA offers the possibility to have a quick therapeutic answer ready in case of a flu epidemic, especially in cases of a mismatch between circulating strains and the recommendations from WHO.

A last placebo-controlled study with PEA in children aged 11 to 15, examining the incidence of acute respiratory tract infections, was performed in January 1976 [15]. 457 children were included and divided into 2 groups; 64 children dropped out. In the PEA group, 169 children completed the study who received 300 mg PEA 2 times daily with an interval of 6 hours. The placebo group included 224 children receiving 2 placebo tablets following the same regime as the PEA group.

Blood samples were taken before the study and 8 weeks later in 65% of all children. After 8 weeks, children treated with PEA had 15.7% fewer acute respiratory tract infections than the control group. In children from 11 to 13 years of age, the difference was even more pronounced: 25.5%. Due to the short duration of the intake of PEA and the absence of epidemic influenza during the trial period, the differences between both groups were not very large, and thus no significance was reached.

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

PEA protects again flu in more than 3000 patient studies

Taken together, in the period between 1972 and 1977 in total 3627 patients and volunteers completed 6 different placebo-controlled double-blind trials of which 1937 received PEA up to 1800 mg/day. Relevant side effects were not reported and especially the trials conducted during the flu season demonstrated a treatment, as well as a prophylactic effect. The last study in children was not significant due to the fact that during the study period no influenza epidemic occurred.

Primary source of PEA an anti-flu therapy

M. Keppel Hesselink, Tineke de Boer, and Renger F. Witkamp, “Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold,” International Journal of Inflammation, vol. 2013, Article ID 151028, 8 pages, 2013. doi:10.1155/2013/151028

Literature on PEA against flu

R. Bachur, K. Masek, K. L. Melmon, and S. Udenffiend, Fatty acid amides of ethanolamine in mammalian tissues, The Journal of Biological Chemistry, vol. 240, pp. 1019-1024, 1965.

Perlík F, Rasková H, Elis J. Anti-inflammatory properties of N(2-hydroxyethyl) palmitamide. Acta Physiol Acad Sci Hung. 1971;39(4):395-400.

Rasková H, Masek K, Linèt O.

Non-specific resistance induced by palmitoylethanolamide.

Toxicon. 1972 Aug;10(5):485-90.

Sechserová M, Elis J.  The effect of palmitoylethanolamide on the blood level of alcohol in mice. Act Nerv Super (Praha). 1972 Aug;14(3):188.

Perlík F, Krejcí J, Elis J, Pekárek J, Svejcar J. The effect of N-(2-hydroxyethyl)-palmitamide on delayed hypersensitivity in guinea-pig. Experientia. 1973 May 1;29(1):67-8.

Obermajerová H, Masek K, Seifert J, Buchar E, Havlík I. Structural and functional changes in liver mitochondria of mice fed palmitoylethanolamide (PEA).  Biochem Pharmacol. 1973 Oct 15;22(20):2529-36.

Tikal K, Benesová O, Franková S. The effects of centrophenoxine and palmitoylethanolamide on the social behavior of rats malnourished in early postnatal life. Act Nerv Super (Praha). 1973 May;15(2):150-1.

Masek K, Perlík F, Klíma J, Kahlich R. Prophylactic efficacy of N-2-hydroxyethyl palmitamide (impulsin) in acute respiratory tract infections. Eur J Clin Pharmacol. 1974 Oct 4;7(6):415-9.

Tikal K, Benesová O, Hvizdosovă J. Proceedings: Effects of centrophenoxine and palmitoylethanolamide in rats with early protein and calorie malnutrition. I. Neurological tests. Act Nerv Super (Praha). 1974;16(4):253-4.

Hvizdosová J, Benesová O, Tikal K. Proceedings: The effects of centrophenoxine and palmitoylethanolamide in rats with early protein and calorie malnutrition. II. Somatic and biochemical parameters. Act Nerv Super (Praha). 1974;16(4):355-6.

Svec P, Béderová E, Svec J. The influence of N-(2-hydroxyethyl)-palmitamide on virus-induced sarcomas in chickens and Rauscher leukemia in mice. Neoplasma. 1975;22(5):519-24.

Svec P, Béderová E, Svec F. The effect of long-term administration of N-(2-hydroxyethyl)palmitamide on the chemotherapy of RBA rat leukemia. Neoplasma. 1975;22(6):625-30.

Karel Mašek , František Perlík. SLOW ENCEPHALOPATHIES, INFLAMMATORY RESPONSES, AND ARACHIS OIL. The Lancet, Volume 306, Issue 7934, Page 558

Plesník V, Havrlantová M, Jancová J, Januska J, Macková O. Impulsin in the prevention of acute respiratory diseases in school children. Cesk Pediatr. 1977 Jun;32(6):365-9.

Lackovic V, Borecký L, Kresáková J. Effect of impulsin treatment of interferon production and antiviral resistance of mice. Arch Immunol Ther Exp (Warsz). 1977;25(5):655-61.

Wiedermannová D, Wiedermann D, Lokaj J. Prophylactic administration of impulsin to clinically healthy children.–effect on the serum proteins and metabolic activity of granulocytes.  Cas Lek Cesk. 1978 Aug 18;117(33):1030-4.

Lackovic V, Borecký L, Kresáková J, Doskocil J. N[2-hydroxyethyl] palmitamide repeated administration effect on interferon production in mouse organism after phage double-stranded ribonucleic acid [ds-RNA] application.

Cesk Epidemiol Mikrobiol Imunol. 1978 Feb;27(1):38-45.

Wiedermannová D, Lokaj J, Wiedermann D. Prophylactic administration of impulsin to clinically healthy children. The effect on T and B lymphocytes in peripheral blood. Cas Lek Cesk. 1979 Oct 12;118(40-41):1249-51.

Kahlich R, Klíma J, Cihla F, Franková V, Masek K, Rosický M, Matousek F, Bruthans J. Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials. J Hyg Epidemiol Microbiol Immunol. 1979;23(1):11-24.

Hurych J, Holusa R, Effenbergerová E, Mirejovská E. Attempt to influence silicotic fibrosis by means of N-(2-hydroxyethyl) palmitamide (Impulsin). Czech Med. 1980;3(3):218-25.